WO2024227051A1

WO2024227051A1 - Irak inhibitor free base, salts, and polymorphic forms thereof

Info

Publication number: WO2024227051A1
Application number: PCT/US2024/026606
Authority: WO
Inventors: Mark SORENSON; Richard Varsolona
Original assignee: Kurome Therapeutics, Inc.
Priority date: 2023-04-28
Filing date: 2024-04-26
Publication date: 2024-10-31

Abstract

The present disclosure provides crystalline free base and salts of an imidazo[1,2- b]pyridazine compound. In some embodiments, the crystalline imidazo[1,2-b]pyridazine compound is a single crystal. The present disclosure also provides methods of using the crystal forms to treat certain diseases or disorders. Some embodiments include methods of using the crystal forms to treat hematopoietic cancers, myelodysplastic syndromes (MDS), or acute myeloid leukemia (AML). Additional embodiments provide disease treatment using the crystal forms in combination with other therapies, such as cancer therapies.

Description

IRAK INHIBITOR FREE BASE, SALTS, AND POLYMORPHIC FORMS THEREOF FIELD OF THE DISCLOSURE [0001] The present disclosure generally relates to crystal forms which are kinase inhibitors and the use of the same in treating diseases and disorders, including cancers. CROSS-REFERENCE TO RELATED APPLICATIONS [0002] The present application claims priority to U.S. Provisional Patent Application No. 63/499,042, filed April 28, 2023, and U.S. Provisional Patent Application No.63/590,940, filed October 17, 2023, each of which is incorporated by reference herein in its entirety. BACKGROUND [0003] Myelodysplastic syndromes (MDS) are malignant, potentially fatal blood diseases that arise from a defective hematopoietic stem/progenitor cell, confer a predisposition to acute myeloid leukemia (AML) (Corey et al., 2007; Nimer, 2008), and often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). A majority of patients having MDS die of marrow failure, immune dysfunction, and/or transformation to overt leukemia. [0004] MDS are heterogeneous diseases with few treatment options, as there is a lack of effective medicines capable of providing a durable response. Current treatment options for MDS are limited but include allogeneic HSC transplantation, demethylating agents, and immunomodulatory therapies (Ebert, 2010). While hemopoeitic stem cell (HSC) transplantation can be used as a curative treatment for MDS, this option is unavailable to many older patients, who instead receive supportive care and transfusions to ameliorate disease complications. Unfortunately, MDS clones can persist in the marrow even after HSC transplantation, and the disease invariably advances (Tehranchi et al., 2010). For advanced disease or high-risk MDS, patients may also receive immunosuppressive therapy, epigenetic modifying drugs, and/or chemotherapy (Greenberg, 2010). Despite recent progress, most MDS patients exhibit treatment-related toxicities or relapse (Sekeres, 2010a). Overall, the efficacy of these treatments is variable, and generally life expectancies are only slightly improved as compared to supportive care. The complexity and heterogeneity of MDS, and the lack of human xenograft models are obstacles which are challenging for identifying and evaluating novel molecular targets for this disease. [0005] Approximately 30% of MDS patients also develop aggressive AML due to acquisition of additional mutations in the defective hematopoietic stem/progenitor cell (HSPC) (Greenberg et al., 1997). AML is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare disease, accounting for approximately 1.2% of cancer deaths in the United States, its incidence is expected to increase as the population ages. Several risk factors and chromosomal abnormalities have been identified, but the specific cause is not clear. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated. The prognosis for AML that arises from MDS is worse as compared to other types of AML. [0006] Several compounds are known to treat blood disorders and cancers (e.g. MDS, AML), but do so inadequately. While some known compounds, such as Quizartinib, Gilteritinib, and Crenolanib, can be used to treat AML, some of these treatments do not result in complete remission or partial remission. In some instances, for example, treatment can result in adaptive resistance or selecting mutations that are resistant to inhibitors, as with Quizartinib, in particular, where repeated administration can lead to desensitization in tumor cell suppression of proliferation (Melgar et al., 2019). [0007] In treating MDS and/or AML, there is a need to develop therapies capable of inhibiting the adaptive resistance mechanism, to improve survival in the context of AML and MDS. There is also an unmet need in AML for drugs that increase overall survival, decrease the length of hospital stay as well as hospital readmission rates, overcome acquired resistance to other treatments, and increase the success rate for hematopoietic stem cell transplant. There is additionally a need for drugs for treating MDS which can slow the conversion rate to AML, and decrease transfusion dependence. [0008] It is therefore necessary to develop treatments and methods of effectively treating MDS and/or AML, and/or other conditions or disorders characterized by dysregulated (e.g., hyperactive) IRAK (e.g., IRAK 1 and/or 4). Additionally, in doing so, it will be important to determine whether a patient is likely to be responsive to a particular treatment or method of treatment. Certain embodiments of the disclosure can address one or more of these issues. SUMMARY OF THE DISCLOSURE [0009] In one aspect, the present disclosure provides a crystal form of a free base of a compound of Formula (1):

characterized by an X-ray powder diffraction pattern comprising one or more peaks at 8.5102 ± 0.2°, 13.4583 ± 0.2°, 16.3830 ± 0.2°, 20.0082 ± 0.2°, and 24.6817 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 11.2514 ± 0.2°, 16.8018 ± 0.2°, 20.9239 ± 0.2°, 22.2447 ± 0.2°, 28.6101 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X- ray powder diffraction pattern further comprising one or more peaks at 10.2265 ± 0.2°, 17.1029 ± 0.2°, 18.3658 ± 0.2°, 22.6040 ± 0.2°, and 23.6583 ± 0.2° 2θ. In one embodiment, the crystal form is futher characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 12.4152 ± 0.2°, 15.6546 ± 0.2°, 18.5476 ± 0.2°, 19.1056 ± 0.2°, 19.3265 ± 0.2°, 20.4980 ± 0.2°, 21.3232 ± 0.2°, 23.2420 ± 0.2°, 24.2705 ± 0.2°, 25.8013 ± 0.2°, 26.1668 ± 0.2°, 27.1774 ± 0.2°, 27.5557 ± 0.2°, 28.1259 ± 0.2°, 30.1759 ± 0.2°, 31.5240 ± 0.2°, 31.8408 ± 0.2°, 32.3075 ± 0.2°, 32.8563 ± 0.2°, 33.7388 ± 0.2°, 36.0412 ± 0.2°, 36.7705 ± 0.2°, 37.7457 ± 0.2°, and 39.0376 ± 0.2° 2θ. In one embodiment, the crystal form comprises a single crystal characterized by one or more of: i) a monoclinic Space group P2₁; ii) lattice parameters a = 9.5817(11) Å, b = 20.916(2) Å, c = 10.8470(12) Å, α = 90º, β = 114.836(4)°, and γ = 90º; iii) a volume of about 1972.8(4) Å³; and/or iv) a crystal density dc = 1.348 g/cm³. [0010] In another aspect, the present disclosure provides a crystal form of a salt of a compound of Formula (1):

wherein the salt comprises a p-toluenesulfonic acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 5.1743 ± 0.2°, 8.1663 ± 0.2°, 10.3704 ± 0.2°, 14.4880 ± 0.2°, and 16.8942 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 7.0186 ± 0.2°, 11.7589 ± 0.2°, 14.0747 ± 0.2°, 14.2385 ± 0.2°, and 21.1626 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 12.5062 ± 0.2°, 13.2636 ± 0.2°, 17.6050 ± 0.2°, 25.1678 ± 0.2°, and 26.2810 ± 0.2° 2θ. [0011] In yet another aspect, the present disclosure provides a crystal form of a salt of a compound of Formula (1):

wherein the salt comprises a tartaric acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 7.7633 ± 0.2°, 8.2996 ± 0.2°, 12.4661 ± 0.2°, 15.5489 ± 0.2°, and 24.7464 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 4.1463 ± 0.2°, 11.3791 ± 0.2°, 17.4289 ± 0.2°, 20.4382 ± 0.2°, and 25.1566 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 14.1011 ± 0.2°, 18.6536 ± 0.2°, 19.1095 ± 0.2°, 22.5011 ± 0.2°, and 25.4454 ± 0.2° 2θ. [0012] In yet another aspect, the present disclosure provides a crystal form of a salt of a compound of Formula (1): wherein the salt comprises a meth n and the crystal form is

characterized by an X-ray powder diffraction pattern comprising one or more peaks at 13.8951 ± 0.2°, 15.8697 ± 0.2°, 18.4951 ± 0.2°, 19.5773 ± 0.2°, and 21.5492 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 10.7336 ± 0.2°, 16.2453 ± 0.2°, 21.7550 ± 0.2°, 22.5396 ± 0.2°, and 23.8137 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 9.4332 ± 0.2°, 15.3077 ± 0.2°, 25.6827 ± 0.2°, 27.3636 ± 0.2°, and 28.4083 ± 0.2° 2θ. [0013] In yet another aspect, the present disclosure provides a crystal form of a salt of a compound of Formula (1): wherein the salt comprises a benz

and the crystal form is characterized by an X-ray powder diffraction pattern comprising peaks at 13.3296 ± 0.2°, 14.2875 ± 0.2°, 14.6072 ± 0.2°, 17.6593 ± 0.2°, and 20.4010 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 8.8966 ± 0.2°, 11.2206 ± 0.2°, 12.2073 ± 0.2°, 25.5863 ± 0.2°, and 27.1334 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 6.0882 ± 0.2°, 14.1225 ± 0.2°, 16.6160 ± 0.2°, 21.5845 ± 0.2°, and 21.9720 ± 0.2° 2θ. [0014] In yet another aspect, crystal form of a salt of a compound of Formula (1): wherein the salt comprises a mon rion and the crystal form is

characterized by an X-ray powder diffraction pattern comprising peaks at 6.8619 ± 0.2°, 11.3373 ± 0.2°, 14.5399 ± 0.2°, 17.1417 ± 0.2°, and 23.6521 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 14.7217 ± 0.2°, 16.2725 ± 0.2°, 22.4223 ± 0.2°, 23.3316 ± 0.2°, and 28.8331 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 2.0916 ± 0.2°, 11.1062 ± 0.2°, 20.9023 ± 0.2°, 21.9400 ± 0.2°, and 27.5840 ± 0.2° 2θ. In one embodiment, the crystal form is further characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 11.6132 ± 0.2°, 13.7106 ± 0.2°, 14.3405 ± 0.2°, 15.3177 ± 0.2°, 17.5260 ± 0.2°, 17.6282 ± 0.2°, 18.8337 ± 0.2°, 20.0236 ± 0.2°, 20.8136 ± 0.2°, 21.0463 ± 0.2°, 22.9619 ± 0.2°, 24.4120 ± 0.2°, 24.9258 ± 0.2°, 26.0850 ± 0.2°, 26.7151 ± 0.2°, 26.9745 ± 0.2°, 27.2880 ± 0.2°, 27.8954 ± 0.2°, 28.1817 ± 0.2°, 28.3383 ± 0.2°, 29.2852 ± 0.2°, 29.8645 ± 0.2°, 32.2115 ± 0.2°, 33.1644 ± 0.2°, 33.5088 ± 0.2°, 33.8427 ± 0.2°, 34.6622 ± 0.2°, 35.6915 ± 0.2°, 36.3485 ± 0.2°, 37.3533 ± 0.2°, and 38.0511 ± 0.2° 2θ. In one embodiment, the crystal form has a Formula (2):

. comprises a bis-hydrochloric acid counterion and the crystal form is described herein. [0015] In one embodiment, the present disclosure provides a crystal form described herein wherein the compound is an inhibitor of at least one of IRAK1, IRAK4, and FLT3 and/or wherein the compound is an inhibitor of IRAK1 and IRAK4 and is not an inhibitor of FLT3. In one embodiment, the present disclosure provides a crystal form described herein wherein: the water content of the crystal form is less than or equal to about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %; the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer; the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer; and/or the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, the present disclosure provides a crystal form described herein upon storage for 6 months at about 25 °C and about 60% relative humidity or 6 months at about 40 °C and about 75% relative humidity: the water content of the crystal form is less than or equal to about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %; the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)- enantiomer; the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer; and/or the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [0016] In yet another aspect, the present disclosure provides a pharmaceutical composition comprising a crystal form described herein and a formulary ingredient, an adjuvant, or a carrier. In one embodiment, the pharmaceutical composition comprises between about 0.1 mg to 10,000 mg, about 1.0 mg to about 9,000 mg, about 1.0 mg to about 8,000 mg, about 1.0 mg to about 7,000 mg, about 1.0 mg to about 6,000 mg, about 1.0 mg to about 5,000 mg, about 1.0 mg to about 4,000 mg, about 1.0 mg to about 3,000 mg, about 1.0 mg to about 2,000 mg, about 1.0 mg to about 1,500 mg, about 1about 1.0 mg to about 1,000 mg, about 1.0 mg to about 750 mg, about 1.0 mg to about 700 mg, about 1.0 mg to about 650 mg, about 1.0 mg to about 600 mg, about 1.0 mg to about 550 mg, about 1.0 mg to about 500 mg, about 1.0 mg to about 450 mg, about 1.0 mg to about 400 mg, about 1.0 mg to about 350 mg, about 1.0 mg to about 300 mg, about 1.0 mg to about 250 mg, about 1.0 mg to about 200 mg, about 1.0 mg to about 150 mg, or about 1.0 mg to about 100 mg of the crystal form. In one embodiment, the pharmaceutical composition comprises an amount of crystal form equivalent to between about 0.1 mg to 10,000 mg, about 1.0 mg to about 9,000 mg, about 1.0 mg to about 8,000 mg, about 1.0 mg to about 7,000 mg, about 1.0 mg to about 6,000 mg, about 1.0 mg to about 5,000 mg, about 1.0 mg to about 4,000 mg, about 1.0 mg to about 3,000 mg, about 1.0 mg to about 2,000 mg, about 1.0 mg to about 1,500 mg, about 1about 1.0 mg to about 1,000 mg, about 1.0 mg to about 750 mg, about 1.0 mg to about 700 mg, about 1.0 mg to about 650 mg, about 1.0 mg to about 600 mg, about 1.0 mg to about 550 mg, about 1.0 mg to about 500 mg, about 1.0 mg to about 450 mg, about 1.0 mg to about 400 mg, about 1.0 mg to about 350 mg, about 1.0 mg to about 300 mg, about 1.0 mg to about 250 mg, about 1.0 mg to about 200 mg, about 1.0 mg to about 150 mg, or about 1.0 mg to about 100 mg of free base. In one embodiment, the pharmaceutical composition is a solid dosage form. In one embodiment, the pharmaceutical composition is a capsule. In one embodiment, the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.0 wt. %, about 1.0 wt. %, about 0.5 wt. %, or about 0.25 wt. %; the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer crystal form; the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer crystal form; and/or the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, upon storage for 3 months at about 25 °C and about 60% relative humidity or 3 months at about 40 °C and about 75% relative humidity: the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.0 wt. %, about 1.0 wt. %, about 0.5 wt. %, or about 0.25 wt. %; the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer crystal form; the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)- enantiomer crystal form; and/or the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [0017] In yet another aspect, the present disclosure provides a method of treating a disease or disorder in a subject, the method comprising administering to the subject a crystal form described herein or the pharmaceutical composition described herein, comprising a therapeutically effective amount of the compound. In one embodiment, the administration comprises parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. In one embodiment, the therapeutically effective amount of the compound is from about 0.005 mg/kg subject body weight to about 1,000 mg/kg subject body weight. In one embodiment, the pharmaceutical composition disintegrates in the subject’s gastrointestinal tract in about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. In one embodiment, the disease or disorder comprises a hematopoietic cancer. In one embodiment, the disease or disorder comprises myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). In one embodiment, the MDS comprises MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2; the AML comprises relapsed AML, refractory AML, relapsed/refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML; or the AML comprises AML with a splicing factor mutation, AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the AML is not driven by FLT3 mutations but expresses IRAK4-Long. In one embodiment, the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2; or the AML splicing factor mutation comprises AML with a splicing factor mutation in U2AF1 or SF3B1. In one embodiment, the disease or disorder comprises lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL with MYD88 mutation, follicular lymphoma, or marginal zone lymphoma. In one embodiment, the disease or disorder comprises at least one cancer selected from glioblastoma multiforme, myelofibrosis, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer. In one embodiment, the disease or disorder comprises one or more inflammatory diseases or autoimmune disease selected from chronic inflammation, sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, colitis, and atopic dermatitis. In one embodiment, the disease or disorder comprises diffuse large B-cell lymphoma (DLBCL), and wherein the DLBCL comprises a L265P MYD88 mutant (ABC) subtype of DLBCL or a S219C MYD88 mutant (GCB) subtype of DLBCL. In one embodiment, the disease or disorder is a FLT3 inhibitor resistant disease or disorder. In one embodiment, the disease or disorder is FLT3 inhibitor resistant acute myeloid leukemia (AML), FLT3 inhibitor resistant refractory acute myeloid leukemia (AML), or FLT3 inhibitor resistant relapsed acute myeloid leukemia (AML). In one embodiment, the method further comprises administering to the subject one or more additional therapies selected from: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor/hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, an antibody-drug conjugate, an mAbs/immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2/MAPK1 or ERK1/MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase/Leukotriene A4 hydrolase inhibitor, a FLT3/Axl/ALK inhibitor, a FLT3/KIT/PDGFR, PKC, and/or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB/C/VEGFR1/2/3/FLT3/CSF-1R/Kit/PDGFRA/B inhibitor, an AKT 1, 2, and/or 3 inhibitor, a ABL1/2/SRC/EPHA2/LCK/YES1/KIT/PDGFRB/FYN inhibitor, a farnesyltransferase inhibitor, a BRAF/MAP2K1/MAP2K2 inhibitor, a Menin-KMT2A/MLL inhibitor, and a multikinase inhibitor. In one embodiment, the additional therapy is at least one of a BCL2 inhibitor, a BTK inhibitor, a gluococorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. In one embodiment, the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof, the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof, the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone, or a pharmaceutically acceptable salt of any one thereof, the CDK inhibitor is selected from CDK4/6 inhibitor palbociclib, CDK7 inhibitor THZ1, and/or CDK9 inhibitors BAY1251152 and atuveciclib, or a pharmaceutically acceptable salt of any one thereof, or the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. In one embodiment, the disease or disorder is: a BCL2 inhibitor resistant disease or disorder, a venetoclax resistant disease or disorder, a BTK inhibitor resistant disease or disorder, an ibrutinib resistant disease or disorder, sensitive to anti-inflammatory glucocorticoids, a dexamethasone, methylprednisolone, or prednisolone resistant disease or disorder, a CDK inhibitor resistant disease or disorder, a palbociclib, THZ1, BAY 12511152, or atuveciclib resistant disease or disorder, a DNA methyltransferase inhibitor resistant disease or disorder, an azacitidine resistant disease or disorder, a BCL2 inhibitor and DNA methyltransferase inhibitor resistant disease or disorder, or a venetoclax and azacitidine resistant disease or disorder. In one embodiment, the disease or disorder is BCL2 inhibitor resistant acute myeloid leukemia (AML), venetoclax resistant AML, BCL2 inhibitor resistant refractory AML, venetoclax resistant refractory AML, BCL2 inhibitor resistant relapsed AML, or venetoclax resistant relapsed AML. In one embodiment, the crystal form described herein or the composition described herein and the one or more additional therapies are administered together in one administration or composition. In one embodiment, the crystal form described herein or the composition described herein and the one or more additional therapies are administered separately in more than one administration or more than one composition. In one embodiment, the disease or disorder is alleviated by inhibiting at least one of IRAK1, IRAK4, and FLT3 in the subject. BRIEF DESCRIPTION OF THE DRAWINGS [0018] FIGS.1A-1H are the characterization of starting material. FIG.1A: PLM image of the starting material with ~82% purity. FIG.1B: PLM image of the starting material with ~98% purity. FIG.1C: PXRD patterns of ~98% purity starting material (top) and ~82% purity starting material (bottom). FIG.1D: TGA and DSC spectra of the ~82% purity starting material. FIG.1E: TGA and DSC spectra of the ~98% purity starting material. FIG.1F: ¹HNMR spectrum of the ~82% purity starting material. FIG.1G: ¹HNMR spectrum of the ~98% purity starting material. FIG.1H: HPLC-UV chromatogram of the ~82% purity starting material (top) and the ~98% purity starting material (bottom). [0019] FIGS.2A-2E are the characterization of the free base (FB) obtained from ~82% purity starting material. FIG.2A: ¹HNMR of the FB in MeOD-d6 before vacuum drying (VD). FIG.2B: ¹HNMR of the FB in DMSO-d₆ before vacuum drying. FIG.2C: ¹HNMR of the FB in MeOD-d₆ after vacuum drying. FIG.2D: ¹HNMR of the FB in DMSO-d₆ after vacuum drying (at step 19 of Table 1). FIG.2E: HPLC of the FB after vacuum drying (VD). [0020] FIGS.3A-3E are the characterization of the FB (Lot 1011-59-1) after vacuum drying. FIG.3A: Image of the FB. FIG.3B: PLM image of the FB. FIG.3C: PXRD pattern of the FB. FIG.3D: ¹HNMR overlay of a) SM, b) FB (Lot 1011-59-1) before VD, and c) FB (Lot 1011-59-1) after VD. FIG.3E: TGA-DSC thermograms of FB (Lot 1011-62-4) after VD. [0021] FIG.4 is an HPLC-UV chromatogram of the starting material (initial intermediate method, 81.6%). [0022] FIGS.5A-5C are the UV, TIC, and MS characterization of the starting material (developed method, 81.8%). FIG.5A: UV & TIC chromatograms of the starting material. FIG. 5B: UV spectra of the starting material. FIG.5C: MS spectra of the starting material. [0023] FIGS.6A-6C are the UV, TIC, and MS characterization of the FB (Lot 1011-62- 4). FIG.6A: UV & TIC chromatograms of the FB (Lot 1011-62-4). FIG.6B: UV spectra of the FB (Lot 1011-62-4). FIG.6C: MS spectra of the FB (Lot 1011-62-4). [0024] FIGS.7A-7F are LCMS and MS characterization of the starting material. FIG. 7A-7B: LCMS spectra of the starting material. FIGS.7C-7D: MS of the starting material at different retention times. FIGS.7E-7F: MS of the two major LCMS starting material peaks. [0025] FIGS.8A-8F are LCMS and MS characterization of the FB (Lot 1011-62-4). FIG.8A-8B: LCMS spectra of the FB. FIGS.8C-8D: MS of the FB at different retention times. FIGS.8E-8F: MS of the two major LCMS FB peaks. [0026] FIG.9 is a HPLC calibration curve with the FB (Lot 1011-74-1) as the reference standard. [0027] FIGS.10A-10C are characterization of the FB after vacuum drying (Lot 1011-70- 2) and FB purification attempts using TLC. FIG.10A: Image of the recovered FB after vacuum drying. FIG.10B: Image of TLC result (Exp 1011-65-6). FIG.10C: TGA-DSC overlay of the recovered FB. [0028] FIGS.11A-11C are characterization of the recovered FB (Lot 1011-70-2). FIG. 11A: ¹HNMR spectrum of of the recovered FB before vacuum drying in deuterated dichloromethane. FIG.11B: ¹HNMR spectrum of the recovered FB after vacuum drying. FIG. 11C: HPLC-UV chromatogram of the recovered FB after vacuum drying. [0029] FIGS.12A-12C are characterization of the FB from the TSA-1 salt break (Lot 1011-74-1). FIG.12A: ¹HNMR spectrum of the FB. FIG.12B: HPLC spectrum of the FB. FIG.12C: TGA-DSC overlay of the FB. [0030] FIGS.13A-13F are HPLC-UV chromatograms associated with the stability experiment of Table 6. FIG.13A: Starting material HPLC-UV chromatogram (top) and FB (Lot 1011-62-4) HPLC-UV chromatogram (bottom). FIG.13B: FB (Lot 1011-63-4) HPLC-UV chromatogram (top) and FB (Lot 1011-63-1) HPLC-UV chromatogram (bottom). FIG.13C: FB (Lot 1011-63-2) HPLC-UV chromatogram. FIG.13D: HPLC-UV chromatogram of the buffer with an initial pH of 3.0 (pH of 7.83 over the weekend). FIG.13E: FB (Lot 1011-63-3) HPLC- UV chromatogram. FIG.13GF: HPLC-UV chromatogram of the buffer with an initial pH of 4.0 (pH of 7.88 over the weekend). [0031] FIG.14 is a PXRD pattern overlay of resulted solids from the experiment of Table 7. [0032] FIGS.15A-15B are characterization of the FB (Lot 1011-84-1) obtained from ~98% purity starting material. FIG.15A: ¹HNMR of the FB after vacuum drying. FIG.15B: TGA-DSC overlay of the FB after vacuum drying. [0033] FIG.16 is a PXRD pattern overlay of a) amorphous FB (Lot 1011-84-1), b) product post TGA, and c) product in Exp 1011-85-5. [0034] FIGS.17A-17G are the characterization of FB-1 (Lot 1011-85-5). FIG.17A: PLM of FB-1. FIG.17B: PXRD pattern of FB-1. FIG.17C: ¹HNMR spectrum of FB-1 after TGA. FIG.17D: HPLC-UV chromatogram of FB-1 (98.88% purity). FIG.17E: TGA-DSC of FB-1. TGA: 0.334% weight loss up to 100 °C, decomposition 200 °C. DSC: 1st endo 157.54 °C. FIG.17F: DVS of FB-1 (2.238% weight gain at 80% relative humidity (RH), hygroscopic). FIG.17G: PXRD pattern of FB-1 post DVS. [0035] FIG.18 is a PXRD overlay of a) FB-1, b) 1011-94-1, c) 1011-94-2, d) 1011-94-3, e) 1011-94-4, f) 1011-94-5, g) 1011-94-6, h) 1011-94-7, i) 1011-94-8, j) 1011-94-9, k) 1011-94- 10, l) 1011-94-11, m) 1011-94-12, n) 1011-94-13, o) 1011-94-14, and p) ACE-1: 1011-94-15 (from the experiment in Table 10). [0036] FIGS.19A-19C are characterization of ACE-1 (Lot 1011-94-15). FIG.19A: ¹HNMR spectrum of ACE-1 after overnight vacuum drying. FIG.19B: PXRD pattern of ACE- 1. FIG.19C: TGA-DSC overlay of ACE-1. TGA: 0.864% weight loss up to 100 °C, decomposition 100 °C. DSC: 1^st endo 110.70 °C, 2^nd endo 146.29 °C. [0037] FIGS.20A-20C are characterization of ACE-2 (Lot 1011-99-16). FIG.20A: PXRD pattern of ACE-2. FIG.20B: ¹HNMR of ACE-2. FIG.20C: TGA-DSC overlay of ACE- 2. TGA: 0.746% weight loss up to 100 °C, decomposition 100 °C. DSC: 1^st endo 143.16 °C. [0038] FIG.21 is a PXRD overlay of a) FB-1, b) 1011-91-1, c) 1011-91-2, d) 1011-91-3, and d) 1011-91-4 (from the experiment in Table 13). [0039] FIGS.22A-22F are the stability assessment of FB-1 controls at the t₀ timepoint. FIG.22A: FB-1 control stored at 25 °C / 60% RH in an open dish. FIG.22B: FB-1 control stored at 40 °C / 75% RH in an open dish. FIG.22C: FB-1control stored at 60 °C in an open dish. FIG.22D: FB-1 control stored at 25 °C / 60% RH in a closed dish. FIG.22E: FB-1 control stored at 40 °C / 75% RH in a closed dish. FIG.22F: FB-1 control stored at 60 °C in a closed dish. [0040] FIGS.23A-23F are the stability assessment of FB-1 controls at the 1 week timepoint. FIG.23A: FB-1 control stored at 25 °C / 60% RH in an open dish. FIG.23B: FB-1 control stored at 40 °C / 75% RH in an open dish. FIG.23C: FB-1 control stored at 60 °C in an open dish. FIG.23D: FB-1 control stored at 25 °C / 60% RH in a closed dish. FIG.23E: FB-1 control stored at 40 °C / 75% RH in a closed dish. FIG.23F: FB-1 control stored at 60 °C in a closed dish. [0041] FIGS.24A-24F are the stability assessment of FB-1 controls at the 2 week timepoint. FIG.24A: FB-1 control stored at 25 °C / 60% RH in an open dish. FIG.24B: FB-1 control stored at 40 °C / 75% RH in an open dish. FIG.24C: FB-1 control stored at 60 °C in an open dish. FIG.24D: FB-1 control stored at 25 °C / 60% RH in a closed dish. FIG.24E: FB-1 control stored at 40 °C / 75% RH in a closed dish. FIG.24F: FB-1 control stored at 60 °C in a closed dish. [0042] FIGS.25A-25F are the stability assessment of FB-1 at the 1 week timepoint. FIG.25A: FB-1 stored at 25 °C / 60% RH in an open dish. FIG.25B: FB-1 stored at 40 °C / 75% RH in an open dish. FIG.25C: FB-1 stored at 60 °C in an open dish. FIG.25D: FB-1 stored at 25 °C / 60% RH in a closed dish. FIG.25E: FB-1 stored at 40 °C / 75% RH in a closed dish. FIG.25F: FB-1 stored at 60 °C in a closed dish. [0043] FIGS.26A-26F are the stability assessment of FB-1 at the 2 week timepoint. FIG.26A: FB-1 stored at 25 °C / 60% RH in an open dish. FIG.26B: FB-1 stored at 40 °C / 75% RH in an open dish. FIG.26C: FB-1 stored at 60 °C in an open dish. FIG.26D: FB-1 stored at 25 °C / 60% RH in a closed dish. FIG.26E: FB-1 stored at 40 °C / 75% RH in a closed dish. FIG.26F: FB-1 stored at 60 °C in a closed dish. [0044] FIGS.27A-27B are PXRD overlays of FB-1 from the stability assessment. FIG. 27A: PXRD patterns of FB-1 and the 1 week pulls (a) FB-1, b) 1011-90-1A-1w, c) 1011-90-1B- 1w, d) 1011-90-1C-1w, e) 1011-90-1D-1w, f) 1011-90-1E-1w, and g) 1011-90-1F-1w). FIG. 27B: PXRD patterns of FB-1 and the 2 week pulls (a) FB-1, b) 1011-90-1A-2w, c) 1011-90-1B- 2w, d) 1011-90-1C-2w, e) 1011-90-1D-2w, f) 1011-90-1E-2w, and g) 1011-90-1F-2w). [0045] FIG.28: Compound 106 with atom labeling for the pKa prediction. [0046] FIGS.29A-29B are PLM images of salt screen #1 (from the experiment in Table 16). FIG.29A: PLM images of the first 18 slurries after stirring overnight. FIG.29B: images of another four slurries after stirring over the weekend. [0047] FIGS.30A-30D are PXRD patterns of four salts from the experiment in Table 16. FIG.30A: PXRD overlay of a) fumaric acid and b) the residual fumaric acid obtained from MeCN (1011-66-6B_wc). FIG.30B: PXRD overlay of a) citric acid and b) the residual citric acid obtained from MeCN (1011-66-7B_wc). FIG.30C: PXRD overlay of a) pTSA, b) the pTSA salt obtained from EtOAc (TSA-1: 1011-66-3D_wc), and c) the pTSA salt obtained from 9:1 actone:water (TSA-1: 1011-66-3E_wc). FIG.30D: PXRD overlay of a) tartaric acid and b) the tartaric acid salt obtained from 9:1 acetone:water (TAR-1: 1011-66-5E_wc). [0048] FIGS.31A-31F are the characterization of TSA-1 (Lot 1011-89-1). FIG.31A: PLM of TSA-1. FiG.31B: DVS of TSA-1 (weight gain at 80% RH: 3.954%, non-hygroscopic). FIG.31C: PXRD pattern of TSA-1. FIG.31D: TGA-DSC overlay of TSA-1. TGA: 3.165% weight loss up to 100 °C, decomposition 250 °C. DSC: 1^st endo 64.14 °C, 2^nd endo (mp) 122.17 °C. FIG.31E: ¹HNMR spectrum of TSA-1. FIG.31F: HPLC-UV chromatogram of TSA-1. [0049] FIGS.32A-32E are the characterization of TAR-1 (Lot 1011-89-2). FIG.32A: PLM of TAR-1. FIG.32B: DVS of TAR-1 (weight gain at 80% RH: 8.046%). FIG.32C: PXRD pattern of TAR-1. FIG.32D: TGA-DSC overlay of TAR-1. TGA: 5.426% weight loss up to 100 °C, decomposition 200 °C. DSC: 1^st endo: 60.69 °C, 2^nd endo: 125.62 °C, 3^rd endo: 177.08 °C. FIG.32E: ¹HNMR spectrum of TAR-1. [0050] FIG.33 is a PXRD overlay of 1011-71-3 to 1011-71-10 (from the experiment in Table 20). [0051] FIGS.34A-34I are HPLC-UV chromatograms from the polymorph screening of TSA-1 described in Table 20. FIG.34A: HPLC-UV chromatogram of TSA-1 (Lot 1011-68-1). FIG.34B: HPLC-UV chromatogram of TSA-1 polymorph from iPAc. FIG.34C: HPLC-UV chromatogram of the TSA-1 polymorph from EtOAc. FIG.34D: HPLC-UV chromatogram of the TSA-1 polymorph from MeCN. FIG.34E: HPLC-UV chromatogram of the TSA-1 polymorph from MEK. FIG.34F: HPLC-UV chromatogram of the TSA-1 polymorph from MTBE. FIG.34G: HPLC-UV chromatogram of the TSA-1 polymorph from THF. FIG.34H: HPLC-UV chromatogram of the TSA-1 polymorph from water. FIG.34I: HPLC-UV chromatogram of the TSA-1 polymorph from acetone. [0052] FIGS.35A-35F are the characterization of TSA-2 (Lot 1011-75-2). FIG.35A: PLM of TSA-2. FIG.35B: DVS of TSA-2 (weight gain at 80% RH: 3.193%, hydrate). FIG. 35C: PXRD pattern of TSA-2. FIG.35D: TGA-DSC overlay of TSA-2. TGA: 3.334% weight loss (RT – 100 °C), decomposition 250 °C. DSC: 1^st endo 54.27 °C, 2^nd endo (mp of TSA-1) 124.83 °C, 3^rd endo (mp of TSA-2) 175.23 °C. FIG.35E: ¹HNMR spectrum of TSA-2. FIG. 35F: HPLC-UV chromatogram of TSA-2. [0053] FIGS.36A-36B are PXRD patterns of TSA salts. FIG.36A: PXRD overlay of TSA-1 and TSA-2. FIG.36B: PXRD overlay of a) TSA-1, b) TSA-2, c) 1011-91-5, d) 1011-91- 6, e) 1011-91-7, f) 1011-91-8, g) FB-1, and h) pTSA (from the experiment in Table 23). [0054] FIGS.37A-37B are the characterization of TSA-3 (Lot 1011-91-8). FIG.37A: PXRD pattern of TSA-3. FIG.37B: ¹HNMR spectrum of TSA-3. [0055] FIGS.38A-38C are data from a two-week stability study of TSA-2 (Lot 1011-88- 3) and TAR-1 (Lot 1011-88-5). FIG.38A: Stability assessment summary of TSA-2 and TAR-1. FIG.38B: PXRD overlay of TSA-2 and the 1 week pulls (a) TSA-2, b) 1011-90-2A-1w, c) 1011- 90-2B-1w, d) 1011-90-2C-1w, e) 1011-90-2D-1w, f) 1011-90-2E-1w, and g) 1011-90-2F-1w). FIG.38C: PXRD overlay of TSA-2 and the 2 week pulls (a) TSA-2, b) 1011-90-2A-2w, c) 1011- 90-2B-2w, d) 1011-90-2C-2w, e) 1011-90-2D-2w, f) 1011-90-2E-2w, and g) 1011-90-2F-2w). [0056] FIGS.39A-39F are the stability assessment of TSA-2 controls at the t₀ timepoint. FIG.39A: TSA-2 control stored at 25 °C / 60% RH in an open dish. FIG.39B: TSA-2 control stored at 40 °C / 75% RH in an open dish. FIG.39C: TSA-2 control stored at 60 °C in an open dish. FIG.39D: TSA-2 control stored at 25 °C / 60% RH in a closed dish. FIG.39E: TSA-2 control stored at 40 °C / 75% RH in a closed dish. FIG.39F: TSA-2 control stored at 60 °C in a closed dish. [0057] FIGS.40A-40F are the stability assessment of TSA-2 controls at the 1 week timepoint. FIG.40A: TSA-2 control stored at 25 °C / 60% RH in an open dish. FIG.40B: TSA- 2 controls stored at 40 °C / 75% RH in an open dish. FIG.40C: TSA-2 control stored at 60 °C in an open dish. FIG.40D: TSA-2 control stored at 25 °C / 60% RH in a closed dish. FIG.40E: TSA-2 control stored at 40 °C / 75% RH in a closed dish. FIG.40F: TSA-2 control stored at 60 °C in a closed dish. [0058] FIGS.41A-41F are the stability assessment of TSA-2 controls at the 2 week timepoint. FIG.41A: TSA-2 control stored at 25 °C / 60% RH in an open dish. FIG.41B: TSA- 2 control stored at 40 °C / 75% RH in an open dish. FIG.41C: TSA-2 control stored at 60 °C in an open dish. FIG.41D: TSA-2 control stored at 25 °C / 60% RH in a closed dish. FIG.41E: TSA-2 control stored at 40 °C / 75% RH in a closed dish. FIG.41F: TSA-2 control stored at 60 °C in a closed dish. [0059] FIGS.42A-42F are the stability assessment of TSA-2 (Lot 1011-88-3) at the 1 week timepoint. FIG.42A: TSA-2 stored at 25 °C / 60% RH in an open dish. FIG.42B: TSA-2 stored at 40 °C / 75% RH in an open dish. FIG.42C: TSA-2 stored at 60 °C in an open dish. FIG.42D: TSA-2 stored at 25 °C / 60% RH in a closed dish. FIG.42E: TSA-2 stored at 40 °C / 75% RH in a closed dish. FIG.42F: TSA-2 stored at 60 °C in a closed dish. [0060] FIGS.43A-43F are the stability assessment of TSA-2 (Lot 1011-88-3) at the 2 week timepoint. FIG.43A: TSA-2 stored at 25 °C / 60% RH in an open dish. FIG.43B: TSA-2 stored at 40 °C / 75% RH in an open dish. FIG.43C: TSA-2 stored at 60 °C in an open dish. FIG.43D: TSA-2 stored at 25 °C / 60% RH in a closed dish. FIG.43E: TSA-2 stored at 40 °C / 75% RH in a closed dish. FIG.43F: TSA-2 stored at 60 °C in a closed dish. [0061] FIGS.44A-44B are PXRD overlays of the TAR-1 stability assessment. FIG. 44A: PXRD overlay of TAR-1 and the 1 week pulls (a) TAR-1, b) 1011-90-3A-1w, c) 1011-90- 3B-1w, d) 1011-90-3C-1w, e) 1011-90-3D-1w, f) 1011-90-3E-1w, and g) 1011-90-3F-1w). FIG. 44B: PXRD overlay of TAR-1 and the 2 week pulls (a) TAR-1, b) 1011-90-3A-2w, c) 1011-90- 3B-2w, d) 1011-90-3C-2w, e) 1011-90-3D-2w, f) 1011-90-3E-2w, and g) 1011-90-3F-2w). [0062] FIGS.45A-45F are the stability assessment of TAR-1 controls at the t0 timepoint. FIG.45A: TAR-1 control stored at 25 °C / 60% RH in an open dish. FIG.45B: TAR-1 control stored at 40 °C / 75% RH in an open dish. FIG.45C: TAR-1 control stored at 60 °C in an open dish. FIG.45D: TAR-1 control stored at 25 °C / 60% RH in a closed dish. FIG.45E: TAR-1 control stored at 40 °C / 75% RH in a closed dish. FIG.45F: TAR-1 control stored at 60 °C in a closed dish. [0063] FIGS.46A-46F are the stability assessment of TAR-1 controls at the 1 week timepoint. FIG.46A: TAR-1 control stored at 25 °C / 60% RH in an open dish. FIG.46B: TAR-1 control stored at 40 °C / 75% RH in an open dish. FIG.46C: TAR-1 control stored at 60 °C in an open dish. FIG.46D: TAR-1 control stored at 25 °C / 60% RH in a closed dish. FIG. 46E: TAR-1 control stored at 40 °C / 75% RH in a closed dish. FIG.46F: TAR-1 control stored at 60 °C in a closed dish. [0064] FIGS.47A-47F are the stability assessment of TAR-1 controls at the 2 week timepoint. FIG.47A: TAR-1 control stored at 25 °C / 60% RH in an open dish. FIG.47B: TAR-1 control stored at 40 °C / 75% RH in an open dish. FIG.47C: TAR-1 control stored at 60 °C in an open dish. FIG.47D: TAR-1 control stored at 25 °C / 60% RH in a closed dish. FIG. 47E: TAR-1 control stored at 40 °C / 75% RH in a closed dish. FIG.47F: TAR-1 control stored at 60 °C in a closed dish. [0065] FIGS.48A-48F are the stability assessment of TAR-1 (Lot 1011-88-5) at the 1 week timepoint. FIG.48A: TAR-1 stored at 25 °C / 60% RH in an open dish. FIG.48B: TAR-1 stored at 40 °C / 75% RH in an open dish. FIG.48C: TAR-1 stored at 60 °C in an open dish. FIG.48D: TAR-1 stored at 25 °C / 60% RH in a closed dish. FIG.48E: TAR-1 stored at 40 °C / 75% RH in a closed dish. FIG.48F: TAR-1 stored at 60 °C in a closed dish. [0066] FIGS.49A-49F are the stability assessment of TAR-1 (Lot 1011-88-5) at the 2 week timepoint. FIG.49A: TAR-1 stored at 25 °C / 60% RH in an open dish. FIG.49B: TAR-1 stored at 40 °C / 75% RH in an open dish. FIG.49C: TAR-1 stored at 60 °C in an open dish. FIG.49D: TAR-1 stored at 25 °C / 60% RH in a closed dish. FIG.49E: TAR-1 stored at 40 °C / 75% RH in a closed dish. FIG.49F: TAR-1 stored at 60 °C in a closed dish. [0067] FIG.50 provides PLM images of the obtained slurries from the experiment in Table 27. [0068] FIGS.51A-51E are PXRD patterns and DSC-TGA overlays of BSA-1 (Lot 1011- 79-1). FIG.51A: PXRD overlay of a) BSA, b) the BSA salt (wet cake) obtained from THF (1011-79-1C_wc), c) the BSA salt obtained from THF after vacuum drying (1011-79-1C_pw), d) the BSA salt (wet cake) obtained from EtOAc (1011-79-1D_wc), e) the BSA salt obtained from EtOAc after vacuum drying (1011-79-1C_pw), f) the BSA salt (wet cake) obtained from MeCN (1011-79-1B_wc), and g) the BSA salt obtained from MeCN after vacuum drying (1011-79- 1B_pw). FIG.51B: PXRD pattern of BSA-1. FIG.51C: DSC-TGA overlay of BSA-1 obtained from MeCN. FIG.51D: DSC-TGA overlay of BSA-1 obtained from THF. FIG.51E: DSC- TGA overlay of BSA-1 obtained from EtOAc. [0069] FIGS.52A-52B are PXRD patterns of the ESA salts obtained from the experiment in Table 27. FIG.52A: PXRD overlay of a) the ESA salt (wet cake) obtained from EtOAc (ESA-1, Lot 1101-79-2) (1011-79-2D_wc) and b) the ESA salt obtained from EtOAc after vacuum drying (1011-79-2D_pw). FIG.52B: PXRD pattern of ESA-1. [0070] FIG.53 is a PXRD overlay of a) L-aspartic acid, b) FB-1, c) the mixture of L- aspartic acid salt and FB-1 (wet cake) obtained from MeCN (1011-79-4B_wc), d) the mixture of L-aspartic acid salt and FB-1 obtained from MeCN after vacuum drying (1011-79-4B_pw), e) the residual L-aspartic acid obtained from EtOH (1011-79-4A_wc), f) the residual L-aspartic acid obtained from THF (1011-79-4C_wc), and g) the residual L-aspartic acid obtained from EtOAc (1011-79-4D_wc). [0071] FIG.54 is a PXRD overlay of the glutamic acid solids collected from the experiment in Table 27: a) glutamic acid, b) the residual glutamic acid obtained from MeCN (1011-79-6B), c) the residual glutamic acid obtained from EtOAc (1011-79-6D), d) the residual glutamic acid obtained from EtOH (1011-79-6A), and e) the residual glutamic acid obtained from THF (1011-79-6C). [0072] FIG.55 is a PXRD overlay of the glycolic acid solids collected from the experiment in Table 27: a) glycolic acid, b) FB-1, c) the glycolic acid and FB-1 mixture (wet cake) obtained from EtOAc (1011-79-7D_wc), d) the glycolic acid and FB-1 mixture obtained from EtOAc after vacuum drying (1011-79-7D_pw), e) the glycolic acid and FB-1 mixture (wet cake) obtained from MeCN (1011-79-7B_wc), and f) the glycolic acid and FB-1 mixture obtained from MeCN after vacuum drying (1011-79-7B_pw). [0073] FIGS.56A-56C are PXRD patterns and DSC-TGA overlays of the maleic acid salts obtained from the experiment in Table 27. FIG.56A: PXRD overlay of a) maleic acid, b) the maleic acid salt (wet cake) obtained from MeCN, and c) the maleic acid salt obtained from MeCN after vacuum drying (1011-79-5B_pw). FIG.56B: PXRD pattern of MAL-1. FIG.56C: DSC-TGA overlay of MAL-1 obtained from MeCN. [0074] FIGS.57A-57D are PXRD patterns and DSC-TGA overlays of the methanesulfonic acid salts obtained from the experiment in Table 27. FIG.57A: is a PXRD overlay of the MSA-1 salt (a) the methanesulfonic acid salt (wet cake) obtained from MeCN (1011-79-3B_wc), b) the methanesulfonic acid salt obtained from MeCN after vacuum drying (1011-79-3B_pw), c) the methanesulfonic acid salt (wet cake) obtained from THF (1011-79- 3C_wc), d) the methanesulfonic acid salt obtained from THF after vacuum drying (1011-79- 3C_pw), e) the methanesulfonic acid salt (wet cake) obtained from EtOAc (1011-79-3D_wc), and f) the methanesulfonic acid salt obtained from EtOAc after vacuum drying (1011-79- 3D_pw)). FIG.57B: DSC-TGA overlay of MSA-1 obtained from MeCN. FIG.57C: DSC-TGA overlay of MSA-1 obtained from THF. FIG.57D: DSC-TGA overlay of MSA-1 obtained from EtOAc. [0075] FIGS.58A-58E are the characterization of MSA-1 (Lot 1011-85-3). FIG.58A: PLM of MSA-1. FIG.58B: DVS of MSA-1 (weight gain at 80% RH: 9.53%, hygroscopic). FIG.58C: PXRD pattern of MSA-1. FIG.58D: TGA-DSC of MSA-1. TGA: 0.805% weight loss up to 100 °C, decomposition 250 °C. DSC: 1^st endo 207.94 °C. FIG.58E: ¹HNMR spectrum of MSA-1. [0076] FIGS.59A-59C are the results of a two-week solid-state stability study with MSA-1 (Lot 1011-88-6). FIG.59A: Stability assessment summary. FIG.59B: PXRD overlay of MSA-1 and the 1 week pulls (a) MSA-1, b) 1011-90-4A-1w, c) 1011-90-4B-1w, d) 1011-90-4C- 1w, e) 1011-90-4D-1w, f) 1011-90-4E-1w, and g) 1011-90-4F-1w). FIG.59C: PXRD overlay of MSA-1 and the 2 week pulls (a) MSA-1, b) 1011-90-4A-2w, c) 1011-90-4B-2w, d) 1011-90-4C- 2w, e) 1011-90-4D-2w, f) 1011-90-4E-2w, and g) 1011-90-4F-2w). [0077] FIGS.60A-60F are the stability assessment of MSA-1 controls at the t0 timepoint. FIG.60A: MSA-1 control stored at 25 °C / 60% RH in an open dish. FIG.60B: MSA-1 control stored at 40 °C / 75% RH in an open dish. FIG.60C: MSA-1 control stored at 60 °C in an open dish. FIG.60D: MSA-1 control stored at 25 °C / 60% RH in a closed dish. FIG.60E: MSA-1 control stored at 40 °C / 75% RH in a closed dish. FIG.60F: MSA-1 control stored at 60 °C in a closed dish. [0078] FIGS.61A-61F are the stability assessment of MSA-1 controls at the 1 week timepoint. FIG.61A: MSA-1 control stored at 25 °C / 60% RH in an open dish. FIG.61B: MSA-1 control stored at 40 °C / 75% RH in an open dish. FIG.61C: MSA-1 control stored at 60 °C in an open dish. FIG.61D: MSA-1 control stored at 25 °C / 60% RH in a closed dish. FIG. 61E: MSA-1 control stored at 40 °C / 75% RH in a closed dish. FIG.61F: MSA-1 control stored at 60 °C in a closed dish. [0079] FIGS.62A-62F are the stability assessment of MSA-1 controls at the 2 week timepoint. FIG.62A: MSA-1 control stored at 25 °C / 60% RH in an open dish. FIG.62B: MSA-1 control stored at 40 °C / 75% RH in an open dish. FIG.62C: MSA-1 control stored at 60 °C in an open dish. FIG.62D: MSA-1 control stored at 25 °C / 60% RH in a closed dish. FIG. 62E: MSA-1 control stored at 40 °C / 75% RH in a closed dish. FIG.62F: MSA-1 control stored at 60 °C in a closed dish. [0080] FIGS.63A-63F are the stability assessment of MSA-1 (Lot 1011-88-6) at the 1 week timepoint. FIG.63A: MSA-1 stored at 25 °C / 60% RH in an open dish. FIG.63B: MSA- 1 stored at 40 °C / 75% RH in an open dish. FIG.63C: MSA-1 stored at 60 °C in an open dish. FIG.63D: MSA-1 stored at 25 °C / 60% RH in a closed dish. FIG.63E: MSA-1 stored at 40 °C / 75% RH in a closed dish. FIG.63F: MSA-1 stored at 60 °C in a closed dish. [0081] FIGS.64A-64F are the stability assessment of MSA-1 (Lot 1011-88-6) at the 2 week timepoint. FIG.64A: MSA-1 stored at 25 °C / 60% RH in an open dish. FIG.64B: MSA- 1 stored at 40 °C / 75% RH in an open dish. FIG.64C: MSA-1 stored at 60 °C in an open dish. FIG.64D: MSA-1 stored at 25 °C / 60% RH in a closed dish. FIG.64E: MSA-1 stored at 40 °C / 75% RH in a closed dish. FIG.64F: MSA-1 stored at 60 °C in a closed dish. [0082] FIG.65 is a PXRD overlay of a) L-ascorbic acid and b) the residual L-ascorbic acid obtained from EtOAc (1011-79-9D_wc). [0083] FIGS.66A-66E are a DVS analysis of TSA-2 (Lot 1011-75-2) and characterization of TSA-2 post DVS. FIG.66A: DVS of TSA-2. TSA-2 was non-hygroscopic with a moisture uptake of 3.193% at 80% RH and the isotherm suggested a monohydrate when RH >10%. FIG.66B: PXRD pattern overlay of a) TSA-2 and b) TSA-2 post DVS. FIG.66C: ¹HNMR spectrum of TSA-2 post DVS. FIG.66D: ¹HNMR overlay of a) TSA-2 post DVS, b) TSA-2, and c) TSA-1. FIG.66E: HPLC-UV chromatogram of TSA-2 post DVS. [0084] FIGS.67A-67G are a TGA-PXRD-DSC analysis of TSA-2 (Lot 1011-75-2). FIG.67A: HPLC-UV chromatogram of TSA-2 post TGA. FIG.67B: TGA thermogram of TSA- 2. FIG.67C: PXRD overlay of a) TSA-2 and b) TSA-2 post TGA. FIG.67D: ¹HNMR spectrum of TSA-2 post TGA. FIG.67E: ¹HNMR overlay of a) TSA-2 post TGA, b) TSA-2, and c) TSA- 1. FIG.67F: DSC thermogram of TSA-2 post TGA. FIG.67G: DSC heat-cool-heat data of TSA-2. [0085] FIGS.68A-68B are a DVS analysis of TAR-1 and characterization of TAR-1 post DVS. FIG.68A: DVS of TAR-1 (Lot 1011-76-5) with a weight gain of 8.046% at 80% RH. TAR-1 was inconclusively determined to be hygroscopic. FIG.68B: PXRD pattern overlay of a) TAR-1 and b) TAR-1 post DVS. [0086] FIGS.69A-69B are PXRD and DSC-TGA characterization of L-aspartic acid salts from the experiment in Table 27. FIG.69A: PXRD overlay of a) L-aspartic acid, b) the L- aspartic acid salt (wet cake) obtained from MeCN (1011-79-4B_WC), c) the L-aspartic acid salt obtained from MeCN after vacuum drying (1011-79-4B_PW), d) the L-aspartic acid salt (wet cake) obtained from EtOH (1011-79-4A_WC), e) the L-aspartic acid salt (wet cake) obtained from THF (1011-79-4C_WC), and f) the L-aspartic acid salt (wet cake) obtained from EtOAc (1011-79-4D_WC). FIG.69B: DSC-TGA overlay of ASP-1 obtained from MeCN. [0087] FIGS.70A-70C are PXRD and DSC-TGA characterization of glycolic salts from the experiment in Table 27. FIG.70A: PXRD overlay of a) glycolic acid, b) the glycolic acid salt (wet cake) obtained from EtOAc (GLY-1) (1011-79-7D_WC), c) the glycolic acid salt obtained from EtOAc after vacuum drying (1011-79-7D_PW), d) the glycolic acid salt (wet cake) obtained from MeCN (1011-79-7B_WC), and e) the glycolic acid salt obtained from MeCN after vacuum drying (GLY-2) (1011-79-7B_PW). FIG.70B: DSC-TGA overlay of GLY- 1 obtained from EtOAc. FIG.70C: DSC-TGA overlay of GLY-2 obtained from MeCN. [0088] FIGS.71A-71J are HPLC-UV chromatograms of the salts obtained from the experiment in Table 27. FIG.71A: HPLC-UV chromatogram of the BSA salt obtained from THF. FIG.71B: HPLC-UV chromatogram of the BSA salt obtained from EtOAc. FIG.71C: HPLC-UV chromatogram of the BSA salt obtained from MeCN. FIG.71D: HPLC-UV chromatogram of the ESA salt obtained from EtOAc. FIG.71E: HPLC-UV chromatogram of the MSA salt obtained from MeCN. FIG.71F: HPLC-UV chromatogram of the MSA salt obtained from THF. FIG.71G: HPLC-UV chromatogram of the L-aspartic acid salt obtained from MeCN. FIG.71H: HPLC-UV chromatogram of the maleic acid salt obtained from MeCN. FIG.71I: HPLC-UV chromatogram of the glycolic salt obtained from MeCN. FIG.71J: HPLC- UV chromatogram of the glycolic acid salt obtained from EtOAc. [0089] FIGS.72A-72K are ¹HNMR spectra of the salts obtained from the experiment in Table 27. FIG.72A: ¹HNMR spectrum of the BSA salt obtained from MeCN. FIG.72B: ¹HNMR spectrum of the BSA salt obtained from THF. FIG.72C: ¹HNMR spectrum of the BSA salt obtained from EtOAc. FIG.72D: ¹HNMR spectrum of the ESA salt obtained from EtOAc. FIG.72E: ¹HNMR spectrum of the MSA salt obtained from MeCN. FIG.72F: ¹HNMR spectrum of the MSA salt obtained from THF. FIG.72G: ¹HNMR spectrum of the MSA salt obtained from EtOAc. FIG.72H: ¹HNMR spectrum of the L-aspartic acid salt obtained from MeCN. FIG.72I: ¹HNMR spectrum of the maleic acid salt obtained from MeCN. FIG.72J: ¹HNMR spectrum of the glycolic salt obtained from MeCN. FIG.72K: ¹HNMR spectrum of the glycolic acid salt obtained from EtOAc. [0090] FIGS.73A-73B are PXRD spectra of the Compound 106 mono-HCl salt SM. [0091] FIGS.74A-74D are the characterization of the Compound 106 mono-HCl salt SM (Lot# 1050-19-2). FIG.74A: ¹HNMR spectrum. FIG.74B: HPLC spectrum. FIG.74C: PLM characterization. FIG.74D: DSC-TGA characterization. [0092] FIGS.75A-75D are the characterization of the Compound 106 mono-HCl salt SM (Lot# 1036-84-8). FIG.75A: ¹HNMR spectrum. FIG.75B: HPLC spectrum. FIG.75C: PLM characterization. FIG.75D: DSC-TGA characterization. [0093] FIG.76 is an ¹HNMR overlay of the two lots of the Compound 106 mono-HCl salt SM (Lot# 1036-84-8 (bottom) and Lot# 1050-19-2 (top)). [0094] FIG.77 is the DVS of the Compound 106 mono-HCl salt SM (Lot# 1050-19-2). [0095] FIG.78 is a PXRD overlay of the Compound 106 mono-HCl salt SM (ID: 1050- 19-2) a) before and b) post DVS. [0096] FIG.79 provides PLM images of crystals in the starting material (left: Lot 966- 195) and from recrystallization of the starting material in THF/methyl tert-butyl ether (MTBE) (right: ZW-1109-07-A6). [0097] FIG.80 is a unit cell of the Compound 106 free base neat form, containing four molecules (Z’ = 2). [0098] FIG.81 is an ORTEP drawing of two crystallographically independent molecules of Compound 106 (i.e., two conformers) in the free base neat form, with non-hydrogen atoms in ellipsoids drawn at 45% probability and hydrogen atoms in small circles. Carbon and hydrogen atoms are not labelled. [0099] FIG.82 is an image of the crystal packing in the Compound 106 free base neat form, showing infinite hydrogen bonding interactions along the crystallographic a-axis, involving three amines (N2_1-H…N4_1, N2_2-H…N4_2, N1_1-H…N1_2). [00100] FIG.83 is a PXRD overlay of the Compound 106 FB-1 reference (top), bulk solids of ZW-1109-07-A6 (middle), and Compound 106 simulated from the crystal structure (bottom). [00101] FIG.84 is an XRPD overlay of Compound 106 free form SM (ID: ZW-1109-01- A) from Example 2 and FB-1 from an earlier project (Q3864). [00102] FIG.85 is a PLM image of Compound 106 free form SM (ID: ZW-1109-01-A). [00103] FIG.86 is a DSC-TGA spectrum of Compound 106 free form SM (ID: ZW-1109- 01-A). [00104] FIG.87 is an ¹HNMR spectrum of Compound 106 free form SM (ID: ZW-1109- 01-A). [00105] FIG.88 is an XRPD pattern overlay of Compound 106 FB-1 (ZW-1109-01-A), FB-2 (ZW-1109-07-A4), FB-3 (ZW-1109-09-A7), and the simulated pattern of FB-1. [00106] FIG.89 is an inter-conversion diagram of Compound 106 crystal free forms. [00107] FIG.90 is an ¹HNMR spectrum of Compound 106 FB-3 (ZW-1109-09-A7) in DMSO-d6. [00108] FIG.91 is a DSC-TGA spectrum of Compound 106 FB-2. [00109] FIG.92 is a DSC-TGA spectrum of Compound 106 FB-3. [00110] FIG.93 is a PLM image of Compound 106 FB-3. [00111] FIG.94 provides DSC heat-cool-heat curves of Compound 106 free form SM (ZW-1109-01-A). [00112] FIG.95 is an XRPD pattern overlay of Compound 106 FB-1 Ref. (ZW-1109-01- A), FB-2 Ref. (ZW-1109-07-A4), and re-prepared FB-2 (ZW-1109-07-A6 and ZW-1109-17- A7). [00113] FIG.96 is an XRPD pattern overlay of Compound 106 FB-1 Ref. (ZW-1109-01- A), re-prepared FB-3 (ZW-1109-09-A7), and a mixture of FB-1 and FB-3 from the polymorph screening (ZW-1109-09-A5). [00114] FIG.97 is an XRPD overlay of the Compound 106 HCl salt: a) 1036-072-FS-MP (ref), b) mono-hydrochloride neat form simulated pattern, and c) SM (ID: 1050-19-2). [00115] FIG.98 provides PLM images of Compound 106 mono-HCl salt SM (ID: 1050- 19-2). [00116] FIG.99 is a DSC-TGA spectrum of Compound 106 HCl salt SM (ID: 1050-19-2). [00117] FIG.100 is an ¹HNMR spectrum of Compound 106 mono-HCl salt SM (top figure, ID: 1050-19-2). [00118] FIG.101 is an overlay of the ¹HNMR spectrum of Compound 106 mono-HCl salt SM (top) with FB #966-195 (bottom), where a chemical shift was observed. [00119] FIG.102 is an XRPD of overlay of Compound 106 HCl salt: a) 1036-072-FS-MP (ref), b) mono-hydrochloride neat form simulated pattern, and c) SM (ID: 1036-84-FS). [00120] FIG.103 provides PLM images of Compound 106 mono-HCl salt SM (ID: 1036- 84-FS). [00121] FIG.104 is a DSC-TGA spectrum of Compound 106 HCl salt SM (ID: 1036-84- FS). [00122] FIG.105 is an ¹HNMR spectrum of Compound 106 HCl salt SM (ID: 1036-84- FS). [00123] FIG.106 is an overlay of the ¹HNMR spectrum of Lot# 1036-84-FS (bottom) and the ¹HNMR spectrum of Lot# 1050-19-2 (top). [00124] FIG.107 is an HPLC chromatogram of FB (Lot# 966-195) w/ 99.9 A%. [00125] FIG.108 is an overlay of Compound 106 mono-HCl #1036-84-FS w/ blank (A% < 0.05 rejection). [00126] FIG.109 is an HPLC calibration curve with FB (Lot# 966-195). [00127] FIG.110 is an HPLC chromatogram of Compound 106 FB (#966-195). [00128] FIG.111 is an HPLC chromatogram of Compound 106 mono-HCl (#1036-84- FS). [00129] FIG.112 provides dynamic vapor sorption (DVS) data of Compound 106 HCl salt SM (ID: 1050-19-2), weight gain at 80% RH: 0.24%, slightly hygroscopic. [00130] FIG.113 is an XRPD overlay of Compound 106 SM (ID: 1050-19-2): a) before and b) post DVS. [00131] FIG.114 is a polymorph screen of HCl-1 (Compound 106 #1036-84-FS) XRPD overlay at RT/1d: a) HCl-1 ref, b) Chloroform, c) EtOH, d) nPA, e) DMF, and f) DMSO. [00132] FIG.115 is a polymorph screen of HCl-1 (Compound 106 #1036-84-FS) XRPD overlay at 50 °C/3d: a) HCl-1 ref, b-l) slurry in solvents. [00133] FIG.116 is a polymorph screen of HCl-1 (Compound 106 #1036-84-FS) XRPD overlay at 50 °C/3d: a) HCl-1 ref, b-p) slurry in solvents. [00134] FIG.117 is a polymorph screen of HCl-1 (Compound 106 #1036-84-FS) XRPD overlay at 50 °C/3d: a) HCl-1 ref, b) Compound 106 HCl in isopropanol (IPA) w/ extra peaks. [00135] FIG.118 is a polymorph screen of HCl-1 (Compound 106 #1036-84-FS) XRPD overlay at 50 °C/3d: a) HCl-1 ref, b) Compound 106 HCl in 2-butanol w/ extra peaks. [00136] FIG.119 is an attempt to reproduce the polymorph screen at 50 °C/2d: a) HCl-1 ref, b) IPA, and c) 2-Butanol. [00137] FIG.120 is a repeat of the polymorph screen at 50 °C: a) HCl-1 ref, b) 1^st polymorph screen in IPA, and c) attempt to reproduce in IPA 50 °C/5d. [00138] FIG.121 is a repeat of the polymorph screen at 50 °C: a) HCl-1 ref and b) attempt in 2-Butanol 50°C/5d. [00139] FIG.122 is a repeat of the polymorph screen at 50 °C: a) HCl-1 ref, b) IPA 50 °C/5 days, c) IPA 50 °C/10 days, d) 2-butanol 50 °C/5 days, and e) 2-butanol 50 °C/10 days. [00140] FIG.123 is a repeat of the polymorph screen at 50 °C: a) HCl-1 ref, b) IPA 50 °C/13 days, and c) 2-butanol 50 °C/13 day. [00141] FIG.124 is a polymorph screening of Compound 106 mono-HCl (Lot# 1036-84- FS) in 2 vol% water in organic solvents of at 50 °C/1d: a) HCl-1 ref, and b)-l) 2 vol% water in organic solvents. [00142] FIG.125 is a polymorph screening of Compound 106 mono-HCl (Lot# 1036-84- FS) in 2 vol% water in organic solvents at 50 °C/4d: a) HCl-1 ref, and b)-j) 2 vol% water in organic solvents. [00143] FIG.126 is a polymorph screening by liquid assist grinding of Compound 106 mono-HCl (Lot# 1036-84-FS) at RT: a) HCl-1 ref, and b)-k) organic solvents. [00144] FIG.127 is a polymorph screening by solid vapor diffusion of Compound 106 mono-HCl (Lot# 1036-84-FS) at RT: a) HCl-1 ref, and b)-i) organic solvents. [00145] FIG.128 is a polymorph screening by liquid vapor diffusion of Compound 106 mono-HCl (Lot# 1036-84-FS) at RT: a) HCl-1 ref, and b)-c) organic solvents. [00146] FIG.129 is a solubility profile of Compound 106 mono-HCl (#1036-84-FS) in an aqueous 2-butanol system tested with three compositions ((1, 2, and 3 vol% water) at 4 temperatures (50 °C, 40 °C, 30 °C, and 20 °C). [00147] FIG.130 is an example of a solvent rejection of impurities overlay of SM #1036- 84-FS vs. w/ 3% H₂O in 2-butanol at 30˚C. [00148] FIGS.131A-131B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 50 °C for 18h in 1 vol% H2O in 2-butanol. FIG.131A: PLM image. FIG.131B: HPLC chromatogram. [00149] FIGS.132A-132B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 50 °C for 18h in 2 vol% H2O in 2-butanol. FIG.132A: PLM image. FIG.132B: HPLC chromatogram. [00150] FIGS.133A-133B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 50 °C for 18h in 3 vol% H₂O in 2-butanol. FIG.133A: PLM image. FIG.133B: HPLC chromatogram. [00151] FIGS.134A-134B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 40 °C for 2h in 1 vol% H₂O in 2-butanol. FIG.134A: PLM image. FIG.134B: HPLC chromatogram. [00152] FIGS.135A-135B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 40 °C for 2h in 2 vol% H₂O in 2-butanol. FIG.135A: PLM image. FIG.135B: HPLC chromatogram. [00153] FIGS.136A-136B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 40 °C for 2h in 3 vol% H₂O in 2-butanol. FIG.136A: PLM image. FIG.136B: HPLC chromatogram. [00154] FIGS.137A-137B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 30 °C for 2h in 1 vol% H₂O in 2-butanol. FIG.137A: PLM image. FIG.137B: HPLC chromatogram. [00155] FIGS.138A-138B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 30 °C for 2h in 2 vol% H2O in 2-butanol. FIG.138A: PLM image. FIG.138B: HPLC chromatogram. [00156] FIGS.139A-139B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 30 °C for 2h in 3 vol% H2O in 2-butanol. FIG.139A: PLM image. FIG.139B: HPLC chromatogram. [00157] FIGS.140A-140B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 20 °C for 18h in 1 vol% H2O in 2-butanol. FIG.140A: PLM image. FIG.140B: HPLC chromatogram. [00158] FIGS.141A-141B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 20 °C for 18h in 2 vol% H2O in 2-butanol. FIG.141A: PLM image. FIG.141B: HPLC chromatogram. [00159] FIGS.142A-142B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 20 °C for 18h in 3 vol% H2O in 2-butanol. FIG.142A: PLM image. FIG.142B: HPLC chromatogram. [00160] FIG.143 is an XRPD analysis of the solubility of Compound 106 mono-HCl (#1036-84-FS) end solids at 50 ˚C: a) HCl-1 ref, b) 1 vol% water in 2-butanol, c) 2 vol% water in 2-butanol, and d) 3 vol% water in 2-butanol. [00161] FIG.144 is an XRPD analysis of the solubility of Compound 106 mono-HCl (#1036-84-FS) end solids at 40 ˚C: a) HCl-1 ref, b) 1 vol% water in 2-butanol, c) 2 vol% water in 2-butanol, and d) 3 vol% water in 2-butanol. [00162] FIG.145 is an XRPD analysis of the solubility of Compound 106 mono-HCl (#1036-84-FS) end solids at 30 ˚C: a) HCl-1 ref, b) 1 vol% water in 2-butanol, c) 2 vol% water in 2-butanol, and d) 3 vol% water in 2-butanol. [00163] FIG.146 is an XRPD analysis of the solubility of Compound 106 mono-HCl (#1036-84-FS) end solids at 20 ˚C: a) HCl-1 ref, b) 1 vol% water in 2-butanol, c) 2 vol% water in 2-butanol, and d) 3 vol% water in 2-butanol. [00164] FIGS.147A-147B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 20 °C for 1-3 days in 1 vol% H₂O in acetone. FIG.147A: PLM image. FIG.147B: HPLC chromatogram. [00165] FIGS.148A-148B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 35 °C for 1-3 days in 1 vol% H2O in acetone. FIG.148A: PLM image. FIG.148B: HPLC chromatogram. [00166] FIGS.149A-149B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 40 °C for 1-3 days in 1 vol% H2O in acetone. FIG.149A: PLM image. FIG.149B: HPLC chromatogram. [00167] FIGS.150A-150B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 50 °C for 1-3 days in 1 vol% H2O in acetone. FIG.150A: PLM image. FIG.150B: HPLC chromatogram. [00168] FIGS.151A-151B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 25 °C for 1-3 days in 1 vol% H2O in IPA. FIG.151A: PLM image. FIG.151B: HPLC chromatogram. [00169] FIGS.152A-152B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 35 °C for 1-3 days in 1 vol% H2O in IPA. FIG.152A: PLM image. FIG.152B: HPLC chromatogram. [00170] FIGS.153A-153B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 40 °C for 1-3 days in 1 vol% H₂O in IPA. FIG.153A: PLM image. FIG.153B: HPLC chromatogram. [00171] FIGS.154A-154B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 50 °C for 1-3 days in 1 vol% H₂O in IPA. FIG.154A: PLM image. FIG.154B: HPLC chromatogram. [00172] FIGS.155A-155B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 60 °C for 1-3 days in 1 vol% H₂O in IPA. FIG.155A: PLM image. FIG.155B: HPLC chromatogram. [00173] FIGS.156A-156B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 70 °C for 1-3 days in 1 vol% H₂O in IPA. FIG.156A: PLM image. FIG.156B: HPLC chromatogram. [00174] FIGS.157A-157B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 20 °C for 1-3 days in 1 vol% H₂O in acetonitrile (ACN). FIG.157A: PLM image. FIG.157B: HPLC chromatogram.

[00175] FIGS.158A-158B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 35 °C for 1-3 days in 1 vol% H2O in ACN. FIG.158A: PLM image. FIG.158B: HPLC chromatogram. [00176] FIGS.159A-159B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 40 °C for 1-3 days in 1 vol% H2O in ACN. FIG.159A: PLM image. FIG.159B: HPLC chromatogram. [00177] FIGS.160A-160B provide purity studies of resulting solids separated from mono- HCl (Lot# 1036-84-FS) agitated at 50 °C for 1-3 days in 1 vol% H2O in ACN. FIG.160A: PLM image. FIG.160B: HPLC chromatogram. [00178] FIG.161 is a solubility profile of Compound 106 mono-HCl (#1036-84-FS) in 1 vol% aqueous-organic solvent systems tested at different temperatures. [00179] FIG.162 is an overlay of XRPD patterns of Compound 106 mono-HCl (#1036- 84-FS) solubility in 1 vol% water in acetone: a) HCl-1 ref, b) 20 ˚C, c) 35 ˚C, d) 40 ˚C, and e) 50 ˚C. [00180] FIG.163 is an overlay of XRPD patterns of Compound 106 mono-HCl (#1036- 84-FS) solubility in 1 vol% water in IPA: a) HCl-1 ref, b) 25 ˚C, c) 35 ˚C, d) 40 ˚C, e) 50 ˚C, f) 60 ˚C, and g) 70 ˚C. [00181] FIG.164 is an overlay of XRPD patterns of Compound 106 mono-HCl (#1036- 84-FS) solubility in 1 vol% water in ACN: a) HCl-1 ref, b) 20 ˚C, c) 35 ˚C, d) 40 ˚C, and e) 50 ˚C. [00182] FIG.165 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 8 vol% water in IPA at 25 ˚C. [00183] FIG.166 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 8 vol% water in IPA at 42 ˚C. [00184] FIG.167 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 8 vol% water in IPA at 60 ˚C. [00185] FIG.168 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 8 vol% water in IPA at 70 ˚C. [00186] FIG.169 is the solubility profile of Compound 106 mono-HCl (#1036-84-FS) in 8 vol% aqueous-IPA tested at different temperatures. [00187] FIG.170 is an overlay of XRPD patterns of Compound 106 mono-HCl (#1036- 84-FS) solubility in 8 vol% water in IPA: a) HCl-1 ref, b) 25 ˚C, c) 42 ˚C, d) 60 ˚C, and e) 70 ˚C. [00188] FIG.171 is the solubility profile of Compound 106 mono-HCl (#1036-84-FS) in pure IPA at different temperatures (between 5-80 ˚C). [00189] FIG.172 provides solubility measurements of Compound 106 mono-HCl (#1036- 84-FS) in pure IPA vs.1 vol% water in IPA and 8 vol% water in IPA at different temperatures. [00190] FIG.173 is an overlay of XRPD patterns of Compund 106 mono-HCl (#1036-84- FS) solubility in IPA by XRPD: a) HCl-1 ref, b) 5 ˚C, c) 25 ˚C, d) 50 ˚C, e) 65 ˚C, and f) 80 ˚C. [00191] FIG.174 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 20 wt. % acetone antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00192] FIG.175 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 40 wt. % acetone antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00193] FIG.176 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 60 wt. % acetone antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00194] FIG.177 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 80 wt. % acetone antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00195] FIG.178 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 20 wt. % MTBE antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00196] FIG.179 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 40 wt. % MTBE antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00197] FIG.180 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 60 wt. % MTBE antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00198] FIG.181 is an HPLC chromatogram from impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 80 wt. % MTBE antisolvent with 8 wt. % aqueous-IPA at 25 °C. [00199] FIG.182 is a solubility profile of Compound 106 mono-HCl (#1036-84-FS) in 8 wt. % aqueous-IPA with antisolvents tested at 25 ˚C (acetone and MTBE). [00200] FIG.183 is an overlay of XRPD patterns of Compound 106 mono-HCl (#1036- 84-FS) in 8 wt. % water in IPA with acetone at 25 ˚C: a) HCl-1 ref, b) 20 wt. % acetone, c) 40 wt. % acetone, d) 60 wt. % acetone, and e) 80 wt. % acetone. [00201] FIG.184 is an overlay of XRPD patterns of Compound 106 mono-HCl (#1036- 84-FS) in 8 wt. % water in IPA with MTBE at 25 ˚C: a) HCl-1 ref, b) 20 wt. % MTBE, c) 40 wt. % MTBE, d) 60 wt. % MTBE, and e) 80 wt. % MTBE. [00202] FIG.185 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in DCM. [00203] FIG.186 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in MTBE. [00204] FIG.187 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in acetone. . [00205] FIG.188 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in THF. [00206] FIG.189 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in hexane. [00207] FIG.190 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in diisopropyl ether (DIPE). [00208] FIG.191 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in EtOAc. [00209] FIG.192 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in EtOH. [00210] FIG.193 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in MEK. [00211] FIG.194 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 2-MeTHF. [00212] FIG.195 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in cyclohexane. [00213] FIG.196 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in ACN. [00214] FIG.197 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in IPA. [00215] FIG.198 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 1,2-Dimethoxyethane (DME). [00216] FIG.199 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in isopropyl acetate (iPAc). [00217] FIG.200 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in n-propanol (nPA). [00218] FIG.201 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in heptane. [00219] FIG.202 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 2-butanol. [00220] FIG.203 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in 1,4-dioxane. [00221] FIG.204 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in CPME. [00222] FIG.205 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in toluene. [00223] FIG.206 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in methyl isobutyl ketone (MIBK). [00224] FIG.207 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in n-butanol. [00225] FIG.208 is an HPLC chromatogram from the impurity rejection studies of Compound 106 mono-HCl (Lot# 1036-84-FS) in DMSO. [00226] FIG.209 is a ¹HNMR spectrum of Compound 106. [00227] FIG.210 is a gradiant COSY spectrum of Compound 106. [00228] FIG.211 is a ROESY2D spectrum of Compound 106. [00229] FIG.212 is a ¹⁹FNMR spectrum of Compound 106. [00230] FIG.213 is a ¹³CNMR spectrum of Compound 106. [00231] FIG.214 is an HSQC spectrum of Compound 106. [00232] FIG.215 is a gradiant HMBC spectrum of Compound 106. [00233] FIG.216 is a ¹HNMR spectrum of the Compound 106 HCl salt. [00234] FIG.217 is a ¹³CNMR spectrum of the Compound 106 HCl salt. [00235] FIG.218 is a gradiant COSY spectrum of the Compound 106 HCl salt. [00236] FIG.219 is a ROESY2D spectrum of the Compound 106 HCl salt. [00237] FIG.220 is an HSQC spectrum of the Compound 106 HCl salt. [00238] FIG.221 is a gradiant HMBC spectrum of the Compound 106 HCl salt. [00239] FIG.222 is a ¹⁹FNMR spectrum of the Compound 106 HCl salt. [00240] FIG.223 is a typical working standard chromatogram for UPLC testing of Compound 106 capsules. [00241] FIG.224 is a typical working standard chromatogram for HPLC testing of the level of the S-enantiomer content in Compound 106 capsules. [00242] FIG.225 is a chart of API stability results after storage for 6 months at 25°C ± 2°C and 60% room humidity ± 5%. [00243] FIG.226 is a chart of API stability results after storage for 6 months at 40°C ± 2°C and 75% room humidity ± 5%. [00244] FIG.227 is a chart of DP stability results for a 10 mg dose after storage for 3 months at 25°C ± 2°C and 60% room humidity ± 5%. ND = not detected or <0.10%, CFU = colony forming unit, RRT = relative retention time, NT = not tested, TGA = thermogravimetric analysis, PXRD = powder X˗ray diffraction, ¹ Refer to COA˗1585˗001.0, ² Listed RRTs reflect current time point. Previous RRTs may vary, ³ Testing outsourced. [00245] FIG.228 is a chart of DP stability results for a 10 mg dose after storage for 3 months at 40°C ± 2°C and 75% room humidity ± 5%. ND = not detected or <0.10%, CFU = colony forming unit, RRT = relative retention time, NT = not tested, TGA = thermogravimetric analysis, PXRD = powder X˗ray diffraction, ¹ Refer to COA˗1585˗001.0, ² Listed RRTs reflect current time point. Previous RRTs may vary, ³ Testing outsourced. [00246] FIG.229 is a chart of DP stability results for a 50 mg dose after storage for 3 months at 25°C ± 2°C and 60% room humidity ± 5%. ND = not detected or <0.10%, CFU = colony forming unit, RRT = relative retention time, NT = not tested, TGA = thermogravimetric analysis, PXRD = powder X˗ray diffraction, ¹ Refer to COA˗1585˗001.0, ² Listed RRTs reflect current time point. Previous RRTs may vary, ³ Testing outsourced. DETAILED DESCRIPTION OF THE DISCLOSURE [00247] The following related applications are incorporated by reference herein in their entirety, and for all purposes: International Publication No. WO 2018081738, TREATMENT OF DISEASES ASSOCIATED WITH ACTIVATED IRAK, filed October 30, 2017; U.S. Publication No.2021/0292843, TREATMENT OF DISEASES ASSOCIATED WITH ACTIVATED IRAK, filed April 4, 2019; International Publication No. WO 2014190163, Combination Therapy for MDS, filed May 22, 2014; U.S. Patent No.9,168,257, Combination Therapy for MDS, issued October 27, 2015; U.S. Patent No.9,504,706, Combination Therapy for MDS, issued November 29, 2016; U.S. Patent No.9,855,273, Combination Therapy for MDS, issued January 2, 2018; International Publication No. WO 2018038988, Compounds, Compositions, Methods for Treating Diseases, and Methods for Preparing Compounds, filed August 16, 2017; U.S. Patent No.11,254,667, Substituted imidazo[1,2-a]pyridines as IRAK 1/4 and FLT3 inhibitors, issued February 2, 2022; U.S. Publication No.2022/0213094, Substituted Imidazo[l,2-a]-pyridines as IRAK 1/4 and FLT3 Inhibitors, filed January 4, 2022; U.S. Publication No.2020/0199123, Substituted imidazo[1,2-a]pyridines as IRAK 1/4 and FLT3 inhibitors, filed February 28, 2020; U.S. Publication No.2022/0235042, Substituted Imidazo[l,2- a]-pyridines as IRAK 1/4 and FLT3 Inhibitors, filed January 28, 2022; International Publication No. WO 2020252487, Rational therapeutic targeting of oncogenic immune signaling states in myeloid malignancies via the ubiquitin conjugating enzyme UBE2N, filed June 15, 2020; International Publication No. WO 2022026935, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed July 31, 2021; International Publication No. WO 2022140647, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed December 23, 2021; International Publication No. WO 2023009833, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed July 29, 2022; International Patent Application No. PCT/US2023/068520, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed June 15, 2023; International Patent Application No. PCT/US2023/068897, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed June 22, 2023; International Patent Application No. PCT/US2023/071435, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed August 1, 2023; International Patent Application No. PCT/US2023/034438, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed October 4, 2023; U.S. Patent Application No.18/293,109, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed January 29, 2024; and International Patent Application No. PCT/US2024/014038, Multi-Cyclic IRAK and FLT3 Inhibiting Compounds and Uses Thereof, filed February 1, 2024. [00248] While embodiments encompassing the general inventive concepts may take diverse forms, various embodiments will be described herein, with the understanding that the present disclosure is to be considered merely exemplary, and the general inventive concepts are not intended to be limited to the disclosed embodiments. [00249] Some embodiments of the invention include a crystal form of Compound 106 and/or a polymorph crystal form of Compound 106. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising a crystal form of Compound 106 described herein. Still other embodiments of the invention include compositions for treating, for example, certain diseases using a crystal form of Compound 106 described herein. Some embodiments include methods of using a crystal form of Compound 106 described herein (e.g., in compositions or in pharmaceutical compositions) for administering and treating. Further embodiments include methods for making the crystal forms disclosed herein. Yet further embodiments include methods for determining whether a particular patient is likely to be responsive to such treatment with the inventive compounds and compositions. [00250] Unless otherwise noted, terms are to be understood according to conventional usage by those of ordinary skill in the relevant art. [00251] The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts. [00252] The term “about” used in the context of a numeric value indicates a range of +/- 10% of the numeric value, unless expressly indicated otherwise. [00253] Some compounds of the invention can have one or more chiral centers and can exist in and be isolated in optically active and racemic forms, for any of the one or more chiral centers. Some compounds can exhibit polymorphism. The compound of the present invention encompasses any optically active, racemate, stereoisomer form, polymorphism, or mixtures thereof. If a chiral center does not provide an indication of its configuration (i.e., R or S) in a chemical structure, it should be considered to represent R, S or a racemate. [00254] As used herein, the term “assessing” includes any form of measurement, and includes determining if an element is present or not. The terms “determining,” “measuring,” “evaluating,” “assessing,” “analyzing,” and “assaying” can be used interchangeably and can include quantitative and/or qualitative determinations. [00255] As used herein, the term “monitoring” with reference to a type of cancer refers to a method or process of determining the severity or degree of the type of cancer or stratifying the type of cancer based on risk and/or probability of mortality. In some embodiments, monitoring relates to a method or process of determining the therapeutic efficacy of a treatment being administered to a patient. [00256] As used herein, “outcome” can refer to an outcome studied. In some embodiments, “outcome” can refer to survival / mortality over a given time horizon. For example, “outcome” can refer to survival / mortality over 1 month, 3 months, 6 months, 1 year, 5 years, or 10 years or longer. In some embodiments, an increased risk for a poor outcome indicates that a therapy has had a poor efficacy, and a reduced risk for a poor outcome indicates that a therapy has had a good efficacy. [00257] As used herein, the term “high risk clinical trial” refers to one in which the test agent has “more than minimal risk” (as defined by the terminology used by institutional review boards, or IRBs). In some embodiments, a high risk clinical trial is a drug trial. [00258] As used herein, the term “low risk clinical trial” refers to one in which the test agent has “minimal risk” (as defined by the terminology used by IRBs). In some embodiments, a low risk clinical trial is one that is not a drug trial. In some embodiments, a low risk clinical trial is one that that involves the use of a monitor or clinical practice process. In some embodiments, a low risk clinical trial is an observational clinical trial. [00259] As used herein, the terms “modulated” or “modulation,” or “regulated” or “regulation” and “differentially regulated” can refer to both up regulation (i.e., activation or stimulation, e.g., by agonizing or potentiating) and down regulation (i.e., inhibition or suppression, e.g., by antagonizing, decreasing or inhibiting), unless otherwise specified or clear from the context of a specific usage. [00260] As used herein, the term “subject” refers to any suitable (e.g., treatable) member of the animal kingdom. In the methods, the subject is preferably a mammal. In the methods, the subject is preferably a human patient. In the methods, the subject may be a mammalian pediatric patient. In the methods, the pediatric patient is a mammalian (e.g., preferably human) patient under 18 years of age, while an adult patient is 18 or older. [00261] As used herein, the term “treating” (and its variations, such as “treatment” “treating,” “treat,” and the like) is, unless stated otherwise, to be considered in its broadest context and refers to obtaining a desired pharmacologic and/or physiologic effect. In particular, for example, the term “treating” may not necessarily imply or require that an animal is treated until total recovery. Accordingly, “treating” includes amelioration of the symptoms, relief from the symptoms or effects associated with a condition, decrease in severity of a condition, or preventing, preventively ameliorating symptoms, or otherwise reducing the risk of developing a particular condition. In some aspects, “treating” may not require or include prevention. As used herein, reference to “treating” an animal includes but is not limited to prophylactic treatment and therapeutic treatment. The effect can be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or can be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease. “Treatment,” as used herein, covers any treatment of a disease in a subject, preferably in a mammal (e.g., in a human), and may include one or more of: (a) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression or elimination of the disease and/or relieving one or more disease symptoms. In particular aspects of the methods, such as conditions or disorders characterized by dysregulated IRAK expression or dysregulated (e.g., hyperactive) IRAK-mediated signaling pathway(s), treatment may be or include reducing such expression or signaling. “Treatment” can also encompass delivery of an agent or administration of a therapy in order to provide for a pharmacologic effect, even in the absence of a disease or condition. Any of the compositions (e.g., pharmaceutical compositions) described herein can be used to treat a suitable subject. [00262] “Therapeutically effective amount” means an amount effective to achieve a desired and/or beneficial effect. An effective amount can be administered in one or more administrations. In the methods, a therapeutically effective amount is an amount appropriate to treat an indication. By treating an indication is meant achieving any desirable effect, such as one or more of palliate, ameliorate, stabilize, reverse, slow, or delay disease progression, increase the quality of life, or to prolong life. Such achievement can be measured by any suitable method, such as measurement of tumor size or blood cell count, or any other suitable measurement. [00263] As used herein, the term “marker” or “biomarker” refers to a biological molecule, such as, for example, a nucleic acid, peptide, protein, hormone, and the like, whose presence or concentration can be detected and correlated with a known condition, such as a disease state. It can also be used to refer to a differentially expressed gene whose expression pattern can be utilized as part of a predictive, prognostic or diagnostic process in healthy conditions or a disease state, or which, alternatively, can be used in methods for identifying a useful treatment or prevention therapy. [00264] As used herein, an mRNA “isoform” is an alternative transcript for a specific mRNA or gene. This term includes pre-mRNA, immature mRNA, mature mRNA, cleaved or otherwise truncated, shortened, or aberrant mRNA, modified mRNA (e.g. containing any residue modifications, capping variants, polyadenylation variants, etc.), and the like. [00265] “Antibody” or “antibody peptide(s)” refer to an intact antibody, or a binding fragment thereof that competes with the intact antibody for specific binding; this definition also encompasses monoclonal and polyclonal antibodies. Binding fragments are produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact antibodies. Binding fragments include Fab, Fab′, F(ab′)₂, Fv, and single-chain antibodies. An antibody other than a “bispecific” or “bifunctional” antibody is understood to have each of its binding sites identical. An antibody, for example, substantially inhibits adhesion of a receptor to a counterreceptor when an excess of antibody reduces the quantity of receptor bound to counterreceptor by at least about 20%, 40%, 60% or 80%, and more usually greater than about 85% (as measured in an in vitro competitive binding assay). [00266] Compositions of the invention also include crystalline forms of Compound 106 including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), and conformational polymorphs, as well as mixtures thereof. “Crystalline form”, “form,” and “polymorph” are intended to include all crystalline forms of the compound, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), and conformational polymorphs, as well as mixtures thereof, unless a particular crystalline form is referred to. [00267] “Solvate” refers to a crystalline phase of a compound in physical association with one or more molecules of a solvent. The crystalline phase of a compound in physical association with one or more molecules of water is referred to as a “hydrate.” [00268] “Amorphous form” refers to a form of a compound, or a salt or molecular complex of a compound, that lacks long range crystalline order. [00269] Embodiments of the invention set forth herein include crystal forms of Compound 106 and/or polymorph crystal forms of Compound 106 described herein. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising a crystal form and/or a polymorph crystal form of Compound 106. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using a crystal form and/or a polymorph crystal form of Compound 106. Some embodiments include methods of using a crystal form and/or a polymorph crystal form of Compound 106 (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer or blood disorders). Some embodiments include methods of determining whether a patient is suitable for, or likely to respond favorably to, a particular treatment. Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein. Compounds and Compositions, Including Pharmaceutical Compositions [00270] In one aspect, the present disclosure relates to Compound 106: a salt, ester, solvate, optical isomer, geometric isomer, or salt of

diment, the present disclosure relates to crystal forms and/or polymorph crystal forms of Compound 106. In one embodiment, the present disclosure relates to single crystal forms of Compound 106. In an embodiment, the disclosure provides a single crystal of a salt of Compound 106. In an embodiment, the disclosure provides a crystalline solid form of the free base of Compound 106. In an embodiment, the disclosure provides a crystalline solid form of a salt of Compound 106. The disclosure provides polymorphs, for example, crystal forms of Compound 106. In some embodiments, the polymorphs include the free base of Compound 106. In some embodiments, the polymorphs include salts of Compound 106 including a counterion corresponding to an acid selected from benzenesulfonic acid, ethanesulfonic acid, hydrochloric acid, methanesulfonic acid, p-toluenesulfonic acid, L-aspartic acid, maleic acid, acetic acid, furmaric acid, citric acid, tartaric acid, glutamic acid, glycolic acid, and L-ascorbic acid, and the like. In some embodiments, the disclosure provides an acetate salt of Compound 106. In one embodiment, the disclosure provides a single crystal of the free base of Compound 106. [00271] In one embodiment, the compounds disclosed herein (i.e., Compound 106 or a salt, ester, solvate, optical isomer, geometric isomer, salt of an isomer, a crystal form and/or a polymorph crystal form thereof) is an IRAK1, IRAK4, IRAK1/4, and/or FLT3 inhibitor. In one embodiment, the compounds disclosed herein are IRAK1/4, panFLT3 inhibitors. [00272] In some embodiments, the compounds can be in the form of salts, optical and geometric isomers, and salts of isomers. In other embodiments, the compounds can be in various forms, such as uncharged molecules, components of molecular complexes, or non-irritating pharmacologically acceptable salts, including but not limited to hydrochloride, bis-hydrochloride (bis-HCl), hydrobromide, sulphate, phosphate, nitrate, borate, acetate, maleate, tartrate, and salicylate. In some instances, for acidic compounds, salts can include metals, amines, or organic cations (e.g. quaternary ammonium). In yet other embodiments, simple derivatives of the compound (e.g., ethers, esters, or amides) which have desirable retention and release characteristics but which are easily hydrolyzed by body pH, enzymes, or other suitable means, can be employed. [00273] In some embodiments, the compounds of the disclosure have a chiral center and can exist in and be isolated in optically active and racemic forms. In other embodiments, the compounds may exhibit polymorphism. Some embodiments of the present disclosure encompass any racemic, optically active, polymorphic, or stereoisomeric form, or mixtures thereof, of a compound described herein, including isotopically-labeled and radio-labeled compounds. See e.g., Goding, 1986, Monoclonal Antibodies Principles and Practice; Academic Press, p.104. Such isomers can be isolated by standard resolution techniques, including e.g., fractional crystallization, chiral chromatography, and the like. See e.g., Eliel, E. L. & Wilen S. H., 1993, Stereochemistry in Organic Compounds; John Wiley & Sons, New York. The preparation of optically active forms can be accomplished by any suitable method, including but not limited to, resolution of the racemic form by recrystallization techniques, synthesis from optically-active starting materials, chiral synthesis, or chromatographic separation using a chiral stationary phase. [00274] In some embodiments, the compounds disclosed herein have one or more asymmetric centers and can occur as racemates, racemic mixtures, and as individual enantiomers or diastereoisomers, with all isomeric forms as well as mixtures thereof being contemplated for use in the compounds and methods described herein. The compounds contemplated herein do not include those that are known in the art to be too unstable to synthesize and/or isolate. [00275] The compounds disclosed herein can also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds can be radiolabeled with radioactive isotopes, such as for example tritium (³H), iodine-125 (¹²⁵I), or carbon-14 (¹⁴C). All isotopic variations of the compounds disclosed herein, whether radioactive or not, are encompassed within the contemplated scope. [00276] In some embodiments, metabolites of the compounds disclosed herein are useful for the methods disclosed herein. [00277] In some embodiments, compounds contemplated herein may be provided in the form of a prodrug. The term “prodrug” refers to a compound that can be converted into a compound (e.g., a biologically active compound) described herein in vivo. Prodrugs can be useful for a variety of reason known in the art, including e.g., ease of administration due e.g., to enhanced bioavailability in oral administration, and the like. The prodrug can also have improved solubility in pharmaceutical compositions over the biologically active compounds. An example, without limitation, of a prodrug is a compound which is administered as an ester (i.e., the "prodrug") to facilitate transmittal across a cell membrane where water solubility is detrimental to mobility but which then is metabolically hydrolyzed to the carboxylic acid, the active entity, once inside the cell where water solubility is beneficial. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in Design of Prodrugs, (ed. H. Bundgaard, Elsevier, 1985), which is hereby incorporated herein by reference for the limited purpose describing procedures and preparation of suitable prodrug derivatives. [00278] Certain compounds disclosed herein can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of contemplated compounds. Certain compounds of the present disclosure can exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the compounds and methods contemplated herein and are intended to be within the scope disclosed herein. [00279] In certain embodiments, one or more compounds of the disclosure (e.g., Compound 106, a crystal form of Compound 106, and/or a polymorph crystal form of Compound 106) can be part of a composition and can be in an amount (by weight of the total composition) of at least about 0.0001%, at least about 0.001%, at least about 0.10%, at least about 0.15%, at least about 0.20%, at least about 0.25%, at least about 0.50%, at least about 0.75%, at least about 1%, at least about 10%, at least about 25%, at least about 50%, at least about 75%, at least about 90%, at least about 95%, at least about 99%, at least about 99.99%, no more than about 75%, no more than about 90%, no more than about 95%, no more than about 99%, or no more than about 99.99%, from about 0.0001% to about 99%, from about 0.0001% to about 50%, from about 0.01% to about 95%, from about 1% to about 95%, from about 10% to about 90%, or from about 25% to about 75%. [00280] In some embodiments, one or more compounds of the disclosure (e.g., Compound 106, a crystal form of Compound 106, and/or a polymorph crystal form of Compound 106) can be purified or isolated in an amount (by weight of the total composition) of at least about 0.0001%, at least about 0.001%, at least about 0.10%, at least about 0.15%, at least about 0.20%, at least about 0.25%, at least about 0.50%, at least about 0.75%, at least about 1%, at least about 10%, at least about 25%, at least about 50%, at least about 75%, at least about 90%, at least about 95%, at least about 99%, at least about 99.99%, no more than about 75%, no more than about 90%, no more than about 95%, no more than about 99%, no more than about 99.99%, from about 0.0001% to about 99%, from about 0.0001% to about 50%, from about 0.01% to about 95%, from about 1% to about 95%, from about 10% to about 90%, or from about 25% to about 75%. Crystalline Forms [00281] In an embodiment, the disclosure provides a crystalline solid form of Compound 106, or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. In an embodiment, the disclosure provides a single crystal of Compound 106. In an embodiment, the disclosure provides a single crystal of a salt of Compound 106. In an embodiment, the disclosure provides a crystalline solid form of the free base of Compound 106. In an embodiment, the disclosure provides a crystalline solid form of a salt of Compound 106. The disclosure provides polymorphs, for example, crystal forms of Compound 106. In some embodiments, the polymorphs include the free base of Compound 106. In some embodiments, the polymorphs include salts of Compound 106 including a counterion corresponding to an acid selected from benzenesulfonic acid, ethanesulfonic acid, hydrochloric acid, methanesulfonic acid, p- toluenesulfonic acid, L-aspartic acid, maleic acid, acetic acid, furmaric acid, citric acid, tartaric acid, glutamic acid, glycolic acid, and L-ascorbic acid, and the like. In some embodiments, the disclosure provides an acetate salt of Compound 106. In one embodiment, the disclosure provides a single crystal of the free base of Compound 106. [00282] Any crystalline form described herein can be characterized by X-ray diffraction. In some embodiments, X-ray diffraction refers to X-ray powder diffraction. In some embodiments, X-ray diffraction may be measured using transmission mode or reflection mode. In an embodiment, the X-ray diffraction pattern of any embodiments herein is measured in transmission mode. In an embodiment, the X-ray diffraction pattern of any embodiments herein is measured in reflection mode. It is known in the art that an X-ray powder diffraction pattern may be obtained which has one or more measurement errors depending on measurement conditions (such as equipment, sample preparation, or instrument used). In particular, it is generally known that intensities in an X-ray powder diffraction pattern may vary depending on measurement conditions and sample preparation. For example, persons skilled in the art of X- ray powder diffraction will realize that the relative intensities of peaks may vary according to the orientation of the sample under test and based on the type and settings of the instrument used. The skilled person will also realize that the position of reflections can be affected by the precise height at which the sample sits in the diffractometer, the sample’s surface planarity, and the zero calibration of the diffractometer. Hence a person skilled in the art will appreciate that the diffraction pattern data presented herein is not to be construed as absolute and any crystalline form that provides a power diffraction pattern substantially the same as those disclosed herein fall within the scope of the present disclosure. For further information, see Jenkins and Snyder, Introduction to X-Ray Powder Diffractometry, John Wiley & Sons, 1996. [00283] Different crystalline form may provide surprising advantages compared to non- crystalline forms, including improved thermodynamic stability, faster dissolution rate, improved performance in the stomach and gastric environment (including the avoidance of, or reduced, precipitation from solution upon a change to higher pH), improved exposure in mammals, and superior processability for formulation of drug into finished products suitable for patients. [00284] In one aspect, the present disclosure provides a crystal form of Compound 106 free base and/or a polymorph crystal form of Compound 106 free base (FB-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts]

9 17.1029 362.63 10 18.3658 373.30 In some embodiments, e on of ± 0.1°, ± 0.2°, or ±

0.3°. [00285] In another aspect, the present disclosure provides a crystal form of an acetic acid salt of Compound 106 and/or a polymorph crystal form of an acetic acid salt of Compound 106 (ACE-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts]

6 12.4889 661.63 7 13.0149 198.69 In some embodiments, e on of ± 0.1°, ± 0.2°, or ±

0.3°. [00286] In another aspect, the present disclosure provides a crystal form of an acetic acid salt of Compound 106 and/or a polymorph crystal form of an acetic acid salt of Compound 106 (ACE-2), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts]

6 14.9697 15.88 7 16.2453 8.02 In some embodiments, ea ion of ± 0.1°, ± 0.2°, or ± 0.3°.

[00287] In yet another aspect, the present disclosure provides a crystal form of a p- toluenesulfonic acid salt of Compound 106 and/or a polymorph crystal form of a p- toluenesulfonic acid salt of Compound 106 (TSA-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts] 1 51743 187949

21 20.5140 132.26 22 21.1626 260.87 In some embodiments of ± 0.1°, ± 0.2°, or ± 0.3°.

[00288] In yet another aspect, the present disclosure provides a crystal form of a p- toluenesulfonic acid salt of Compound 106 and/or a polymorph crystal form of a p- toluenesulfonic acid salt of Compound 106 (TSA-2), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts] 1 59392 96734

20 19.0089 318.58 21 19.7271 125.92 In some embodiments of ± 0.1°, ± 0.2°, or ±

0.3°. [00289] In yet another aspect, the present disclosure provides a crystal form of a p- toluenesulfonic acid salt of Compound 106 and/or a polymorph crystal form of a p- toluenesulfonic acid salt of Compound 106 (TSA-3), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts]

9 13.5800 462.40 10 14.7963 622.61

54 35.6577 35.98 55 36.2798 71.10 In some embodiments of ± 0.1°, ± 0.2°, or ± 0.3°.

[00290] In yet another aspect, the present disclosure provides a crystal form of a tartaric acid salt of Compound 106 and/or a polymorph crystal form of a tartaric acid salt of Compound 106 (TAR-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts] 1 4.1463 292.13

30 28.1883 75.69 31 29.5023 29.96 In some embodiments of ± 0.1°, ± 0.2°, or ± 0.3°.

[00291] In yet another aspect, the present disclosure provides a crystal form of a benzenesulfonic acid salt of Compound 106 and/or a polymorph crystal form of a benzenesulfonic acid salt of Compound 106 (BSA-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts] 1 6.0882 171.45

31 25.1031 21.26 32 25.5863 387.01 In some embodiments of ± 0.1°, ± 0.2°, or ± 0.3°.

[00292] In yet another aspect, the present disclosure provides a crystal form of an ethanesulfonic acid salt of Compound 106 and/or a polymorph crystal form of an ethanesulfonic acid salt of Compound 106 (ESA-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts] 1 2.1456 362.07

In some embodiments, each peak independently may include a variation of ± 0.1°, ± 0.2°, or ± 0.3°. [00293] In yet another aspect, the present disclosure provides a crystal form of a maleic acid salt of Compound 106 and/or a polymorph crystal form of a maleic acid salt of Compound 106 (MAL-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts] 1 7.6183 153.33 In some embodiments f ± 0.1°, ± 0.2°, or ±

0.3°. [00294] In yet another aspect, the present disclosure provides a crystal form of a methanesulfonic acid salt of Compound 106 and/or a polymorph crystal form of a methanesulfonic acid salt of Compound 106 (MSA-1), characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts]

8 18.4951 565.77 9 19.5773 1743.95 In some embodiment of ± 0.1°, ± 0.2°, or ±

0.3°. 295] In yet another aspect, the present disclosure provides a crystal form of a mono hydrochloric acid salt of Compound 106 and/or a polymorph crystal form of a mono hydrochloric acid salt of Compound 106, characterized by an X-ray powder diffraction pattern including one or more peaks selected from: Peak # Pos. [°2θ] Height [cts]

10 15.3177 261.07 11 16.2725 461.28 In some embodiments, n of ± 0.1°, ± 0.2°, or ±

0.3°. 296] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 8.5102 ± 0.2°, 10.2265 ± 0.2°, 11.2514 ± 0.2°, 12.4152 ± 0.2°, 13.4583 ± 0.2°, 15.6546 ± 0.2°, 16.3830 ± 0.2°, 16.8018 ± 0.2°, 17.1029 ± 0.2°, 18.3658 ± 0.2°, 18.5476 ± 0.2°, 19.1056 ± 0.2°, 19.3265 ± 0.2°, 20.0082 ± 0.2°, 20.4980 ± 0.2°, 20.9239 ± 0.2°, 21.3232 ± 0.2°, 22.2447 ± 0.2°, 22.6040 ± 0.2°, 23.2420 ± 0.2°, 23.6583 ± 0.2°, 24.2705 ± 0.2°, 24.6817 ± 0.2°, 25.8013 ± 0.2°, 26.1668 ± 0.2°, 27.1774 ± 0.2°, 27.5557 ± 0.2°, 28.1259 ± 0.2°, 28.6101 ± 0.2°, 30.1759 ± 0.2°, 31.5240 ± 0.2°, 31.8408 ± 0.2°, 32.3075 ± 0.2°, 32.8563 ± 0.2°, 33.7388 ± 0.2°, 36.0412 ± 0.2°, 36.7705 ± 0.2°, 37.7457 ± 0.2°, and 39.0376 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a free base of Compound 106. In some embodiments, the crystal form includes a neat free base form of Compound 106. [00297] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 6.5000 ± 0.2°, 6.7290 ± 0.2°, 7.5260 ± 0.2°, 10.5847 ± 0.2°, 11.0130 ± 0.2°, 12.4889 ± 0.2°, 13.0149 ± 0.2°, 16.3929 ± 0.2°, 16.8800 ± 0.2°, 17.1858 ± 0.2°, 18.4708 ± 0.2°, 18.8843 ± 0.2°, 19.5304 ± 0.2°, 20.0616 ± 0.2°, 21.3454 ± 0.2°, 21.7009 ± 0.2°, 22.3172 ± 0.2°, 22.5705 ± 0.2°, 22.9289 ± 0.2°, 23.9165 ± 0.2°, 24.7744 ± 0.2°, 25.0876 ± 0.2°, 25.5671 ± 0.2°, 26.1732 ± 0.2°, 26.5912 ± 0.2°, 27.0355 ± 0.2°, 27.2423 ± 0.2°, 27.6728 ± 0.2°, 28.3256 ± 0.2°, 29.0800 ± 0.2°, 31.1977 ± 0.2°, 32.9851 ± 0.2°, 34.0111 ± 0.2°, 34.7003 ± 0.2°, 35.6768 ± 0.2°, and 38.0226 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes an acetic acid salt of Compound 106. In some embodiments, the crystal form includes a solvated acetic acid salt of Compound 106. [00298] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 6.2182 ± 0.2°, 9.4463 ± 0.2°, 10.3025 ± 0.2°, 12.4148 ± 0.2°, 14.3135 ± 0.2°, 14.9697 ± 0.2°, 16.2453 ± 0.2°, 16.8470 ± 0.2°, 17.9204 ± 0.2°, 18.9193 ± 0.2°, 19.4893 ± 0.2°, 20.0171 ± 0.2°, 21.6036 ± 0.2°, 22.4177± 0.2°, 23.5670 ± 0.2°, 24.4393 ± 0.2°, 25.0411 ± 0.2°, 26.0228 ± 0.2°, 26.6839 ± 0.2°, 27.3926 ± 0.2°, and 33.2748 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes an acetic acid salt of Compound 106. In some embodiments, the crystal form includes a desolvated acetic acid salt of Compound 106. [00299] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 5.1743 ± 0.2°, 7.0186 ± 0.2°, 8.1663 ± 0.2°, 9.1859 ± 0.2°, 10.3704 ± 0.2°, 11.7589 ± 0.2°, 12.5062 ± 0.2°, 13.2636 ± 0.2°, 14.0747 ± 0.2°, 14.2385 ± 0.2°, 14.4880 ± 0.2°, 14.7418 ± 0.2°, 15.1588 ± 0.2°, 15.6231 ± 0.2°, 16.2702 ± 0.2°, 16.8942 ± 0.2°, 17.6050 ± 0.2°, 17.9401 ± 0.2°, 19.0641 ± 0.2°, 19.8933 ± 0.2°, 20.5140 ± 0.2°, 21.1626 ± 0.2°, 21.7948 ± 0.2°, 22.4148 ± 0.2°, 23.0891 ± 0.2°, 23.8417 ± 0.2°, 24.6896 ± 0.2°, 24.8272 ± 0.2°, 25.1678 ± 0.2°, 26.2810 ± 0.2°, 26.7775 ± 0.2°, 27.4170 ± 0.2°, 28.1822 ± 0.2°, 29.0287 ± 0.2°, 29.9521 ± 0.2°, 31.4883 ± 0.2°, and 33.1844 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a p- toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a hydrated p-toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a p-toluenesulfonic acid monohydrate salt of Compound 106. [00300] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 5.9392 ± 0.2°, 7.0763 ± 0.2°, 8.7637 ± 0.2°, 10.9989 ± 0.2°, 11.8931 ± 0.2°, 12.8975 ± 0.2°, 13.2326 ± 0.2°, 13.5257 ± 0.2°, 14.0442 ± 0.2°, 14.2012 ± 0.2°, 14.3568 ± 0.2°, ± 0.2°, 15.2718 ± 0.2°, 15.6918 ± 0.2°, 16.2197 ± 0.2°, 16.6651 ± 0.2°, 17.2545 ± 0.2°, 17.5695 ± 0.2°, 17.8762 ± 0.2°, 18.4091 ± 0.2°, 19.0089 ± 0.2°, 19.7271 ± 0.2°, 20.0891 ± 0.2°, 20.2884 ± 0.2°, 21.3708 ± 0.2°, 21.6008 ± 0.2°, 21.8351 ± 0.2°, 22.0956 ± 0.2°, 22.8019 ± 0.2°, 23.3518 ± 0.2°, 24.5049 ± 0.2°, 25.0766 ± 0.2°, 25.2479 ± 0.2°, 25.4378 ± 0.2°, 26.1134 ± 0.2°, 26.6147 ± 0.2°, 27.2503 ± 0.2°, 27.4629 ± 0.2°, 27.7389 ± 0.2°, 28.6339 ± 0.2°, 30.0194 ± 0.2°, 30.7184 ± 0.2°, 31.6744 ± 0.2°, 32.6249 ± 0.2°, 33.1826 ± 0.2°, 33.7315 ± 0.2°, 35.6161 ± 0.2°, and 36.1791 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a p-toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a hydrated p- toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a p-toluenesulfonic acid monohydrate salt of Compound 106. [00301] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 7.7311 ± 0.2°, 8.6730 ± 0.2°, 9.1020 ± 0.2°, 10.0547 ± 0.2°, 10.4519 ± 0.2°, 11.4067 ± 0.2°, 11.7315 ± 0.2°, 12.4876 ± 0.2°, 13.5800 ± 0.2°, 14.7963 ± 0.2°, 15.4790 ± 0.2°, 16.5562 ± 0.2°, 16.7117 ± 0.2°, 17.2255 ± 0.2°, 17.9216 ± 0.2°, 18.2518 ± 0.2°, 18.7057 ± 0.2°, 18.9171 ± 0.2°, 19.7204 ± 0.2°, 20.1315 ± 0.2°, 21.0767 ± 0.2°, 21.5198 ± 0.2°, 22.0848 ± 0.2°, 22.3841 ± 0.2°, 22.7469 ± 0.2°, 22.9067 ± 0.2°, 23.0532 ± 0.2°, 23.3139 ± 0.2°, 23.5901 ± 0.2°, 24.0642 ± 0.2°, 24.4832 ± 0.2°, 25.1100 ± 0.2°, 25.4147 ± 0.2°, 26.2214 ± 0.2°, 26.4958 ± 0.2°, 26.8376 ± 0.2°, 27.2203 ± 0.2°, 27.5068 ± 0.2°, 27.9358 ± 0.2°, 28.3874 ± 0.2°, 29.5122 ± 0.2°, 29.9189 ± 0.2°, 30.2906 ± 0.2°, 30.8246 ± 0.2°, 31.3301 ± 0.2°, 31.7008 ± 0.2°, 32.9084 ± 0.2°, 32.9880 ± 0.2°, 33.7702 ± 0.2°, 34.0199 ± 0.2°, 34.3192 ± 0.2°, 34.7098 ± 0.2°, 35.4529 ± 0.2°, 35.6577 ± 0.2°, 36.2798 ± 0.2°, 36.7875 ± 0.2°, 37.2640 ± 0.2°, 37.8389 ± 0.2°, 38.7782 ± 0.2°, and 39.4366 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a p- toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a hydrated p-toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes an anhydrous p-toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a solvated p-toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a desolvated p-toluenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes an amorphous p-toluenesulfonic acid salt of Compound 106. [00302] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 4.1463 ± 0.2°, 7.7633 ± 0.2°, 8.2996 ± 0.2°, 10.1216 ± 0.2°, 11.3791 ± 0.2°, 12.4661 ± 0.2°, 13.7867 ± 0.2°, 14.1011 ± 0.2°, 15.5489 ± 0.2°, 16.6578 ± 0.2°, 17.4289 ± 0.2°, 18.6536 ± 0.2°, 19.1095 ± 0.2°, 19.3112 ± 0.2°, 19.6662 ± 0.2°, 20.4382 ± 0.2°, 20.8586 ± 0.2°, 21.3540 ± 0.2°, 22.5011 ± 0.2°, 22.8792 ± 0.2°, 23.4372 ± 0.2°, 23.7287 ± 0.2°, 24.7464 ± 0.2°, 25.1566 ± 0.2°, 25.4454 ± 0.2°, 25.9362 ± 0.2°, 26.4885 ± 0.2°, 26.7874 ± 0.2°, 27.7072 ± 0.2°, 28.1883 ± 0.2°, 29.5023 ± 0.2°, 31.4659 ± 0.2°, 33.1605 ± 0.2°, 35.2961 ± 0.2°, and 36.2252 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a (+)-L-tartaric acid salt of Compound 106. In some embodiments, the crystal form includes a (+)-L-tartaric acid hydrate salt of Compound 106. [00303] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 6.0882 ± 0.2°, 7.1501 ± 0.2°, 8.8966 ± 0.2°, 11.2206 ± 0.2°, 12.2073 ± 0.2°, 12.9781 ± 0.2°, 13.3296 ± 0.2°, 14.1225 ± 0.2°, 14.2875 ± 0.2°, 14.6072 ± 0.2°, 15.5340 ± 0.2°, 15.8947 ± 0.2°, 16.6160 ± 0.2°, 16.9428 ± 0.2°, 17.6593 ± 0.2°, 17.8182 ± 0.2°, 18.1970 ± 0.2°, 19.2161 ± 0.2°, 19.4884 ± 0.2°, 19.9886 ± 0.2°, 20.1070 ± 0.2°, 20.4010 ± 0.2°, 20.9762 ± 0.2°, 21.5845 ± 0.2°, 21.9720 ± 0.2°, 22.5384 ± 0.2°, 23.3474 ± 0.2°, 23.5613 ± 0.2°, 23.8492 ± 0.2°, 24.8742 ± 0.2°, 25.1031 ± 0.2°, 25.5863 ± 0.2°, 25.9489 ± 0.2°, 26.2968 ± 0.2°, 26.5983 ± 0.2°, 27.1334 ± 0.2°, 28.4875 ± 0.2°, 29.1808 ± 0.2°, 29.8640 ± 0.2°, 30.6238 ± 0.2°, 31.5579 ± 0.2°, 32.7200 ± 0.2°, and 33.4281 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a hydrated benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes an anhydrous benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a solvated benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a desolvated benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes an amorphous benzenesulfonic acid salt of Compound 106. [00304] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 2.1456 ± 0.2°, 9.4378 ± 0.2°, 10.5830 ± 0.2°, 13.5242 ± 0.2°, 15.6498 ± 0.2°, 16.1666 ± 0.2°, 18.2082 ± 0.2°, 19.1561 ± 0.2°, 19.5803 ± 0.2°, 21.4651 ± 0.2°, 22.5054 ± 0.2°, 23.1563 ± 0.2°, 24.4272 ± 0.2°, 24.9066 ± 0.2°, 26.2932 ± 0.2°, 26.6850 ± 0.2°, 27.1646 ± 0.2°, 27.6300 ± 0.2°, 28.0821 ± 0.2°, 29.1008 ± 0.2°, 29.7364 ± 0.2°, 30.1128 ± 0.2°, 31.0951 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes an ethanesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a hydrated ethanesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes an anhydrous benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a solvated benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a desolvated benzenesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes an amorphous benzenesulfonic acid salt of Compound 106. [00305] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 7.6183 ± 0.2°, 8.8782 ± 0.2°, 10.1164 ± 0.2°, 10.4550 ± 0.2°, 11.3945 ± 0.2°, 12.6363 ± 0.2°, 14.9782 ± 0.2°, 16.0301 ± 0.2°, 16.5998 ± 0.2°, 17.8112 ± 0.2°, 19.2988 ± 0.2°, 20.7943 ± 0.2°, 22.5892 ± 0.2°, 24.0658 ± 0.2°, 25.1163 ± 0.2°, 25.8815 ± 0.2°, 27.5537 ± 0.2°, and 30.8678 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a maleic acid salt of Compound 106. In some embodiments, the crystal form includes a hydrated maleic acid salt of Compound 106. In some embodiments, the crystal form includes an anhydrous maleic acid salt of Compound 106. In some embodiments, the crystal form includes a solvated maleic acid salt of Compound 106. In some embodiments, the crystal form includes a desolvated maleic acid salt of Compound 106. In some embodiments, the crystal form includes an amorphous maleic acid salt of Compound 106. [00306] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 9.4332 ± 0.2°, 10.7336 ± 0.2°, 13.1847 ± 0.2°, 13.8951 ± 0.2°, 15.3077 ± 0.2°, 15.8697 ± 0.2°, 16.2453 ± 0.2°, 18.4951 ± 0.2°, 19.5773 ± 0.2°, 20.4125 ± 0.2°, 21.5492 ± 0.2°, 21.7550 ± 0.2°, 22.5396 ± 0.2°, 23.1636 ± 0.2°, 23.8137 ± 0.2°, 24.4222 ± 0.2°, 24.9633 ± 0.2°, 25.6827 ± 0.2°, 26.2564 ± 0.2°, 26.5213 ± 0.2°, 26.7162 ± 0.2°, 27.3636 ± 0.2°, 28.0011 ± 0.2°, 28.4083 ± 0.2°, 30.0138 ± 0.2°, 30.6070 ± 0.2°, 32.0467 ± 0.2°, 33.2600 ± 0.2°, 34.7889 ± 0.2°, 36.4246 ± 0.2°, 37.0117 ± 0.2°, 37.5445 ± 0.2°, 38.3512 ± 0.2°, and 39.4875 ± 0.2° 2θ. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a methanesulfonic acid salt of Compound 106. In some embodiments, the crystal form includes a neat methanesulfonic acid salt of Compound 106. [00307] In one embodiment, the present disclosure provides a crystal form of Compound 106 characterized by an X-ray powder diffraction pattern including one or more peaks selected from 2.0916 , 6.8619 , 11.1062 , 11.3373 , 11.6132 , 13.7106 , 14.3405 , 14.5399 , 14.7217 , 15.3177 , 16.2725 , 17.1417 , 17.5260 , 17.6282 , 18.8337 , 20.0236 , 20.8136 , 20.9023 , 21.0463 , 21.9400 , 22.4223 , 22.9619 , 23.3316 , 23.6521 , 24.4120 , 24.9258 , 26.0850 , 26.4484 , 26.7151 , 26.9745 , 27.2880 , 27.5840 , 27.8954 , 28.1817 , 28.3383 , 28.8331 , 29.2852 , 29.8645 , 32.2115 , 33.1644 , 33.5088 , 33.8427 , 34.6622 , 35.6915 , 36.3485 , 37.3533 , and 38.0511. In some embodiments, the X-ray diffraction pattern includes at least one peak, at least two peaks, at least three peaks, at least four peaks, at least five peaks, or the like, selected from the above group of peaks. In some embodiments, the crystal form includes a mono hydrochloric acid salt of Compound 106. In some embodiments, the crystal form includes a hydrated mono hydrochloric acid salt of Compound 106. In some embodiments, the crystal form includes an anhydrous mono hydrochloric acid salt of Compound 106. In some embodiments, the crystal form includes a solvated mono hydrochloric acid salt of Compound 106. In some embodiments, the crystal form includes a desolvated monohydrochloric acid salt of Compound 106. In some embodiments, the crystal form includes an amorphous mono hydrochloric acid salt of Compound 106. [00308] In one embodiment, upon formation, the water content of the crystal form is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %. In one embodiment, the water content of the crystal form is measured by Karl Fischer titration. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00309] In one embodiment, upon formation, the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer. In one embodiment, upon formation, the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00310] In one embodiment, upon formation, the crystal form comprises less than or equal to about 10%, about 9.0%, about 8.0%, about 7.0%, about 6.0%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, the impurities comprise soluble impurities. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00311] In one embodiment, upon storage for 6 months at about 25 °C and about 60% relative humidity, the water content of the crystal form is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00312] In one embodiment, upon storage for 6 months at about 25 °C and about 60% relative humidity, the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer. In one embodiment, upon storage for 6 months at about 25 °C and about 60% relative humidity, the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00313] In one embodiment, upon storage for 6 months at about 25 °C and about 60% relative humidity, the crystal form comprises less than or equal to about 10%, about 9.0%, about 8.0%, about 7.0%, about 6.0%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, the impurities comprise soluble impurities. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00314] In one embodiment, upon storage for 6 months at about 40 °C and about 75% relative humidity, the water content of the crystal form is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00315] In one embodiment, upon storage for 6 months at about 40 °C and about 75% relative humidity, the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer. In one embodiment, upon storage for 6 months at about 40 °C and about 75% relative humidity, the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00316] In one embodiment, upon storage for 6 months at about 40 °C and about 75% relative humidity, the crystal form comprises less than or equal to about 10%, about 9.0%, about 8.0%, about 7.0%, about 6.0%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, the impurities comprise soluble impurities. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00317] In one embodiment, the water content of the crystal form upon formation is measured by Karl Fischer titration. In one embodiment, the water content of the crystal form upon storage for 6 months at about 25 °C and about 60% relative humidity is measured by Karl Fischer titration. In one embodiment, the water content of the crystal form upon storage for 6 months at about 40 °C and about 75% relative humidity is measured by Karl Fischer titration. [00318] In one embodiment, the chiral purity of the crystal form upon formation is measured by high performance liquid chromatography (HPLC). In one embodiment, the chiral purity of the crystal form upon storage for 6 months at about 25 °C and about 60% relative humidity is measured by HPLC. In one embodiment, the chiral purity of the crystal form upon storage for 6 months at about 40 °C and about 75% relative humidity is measured by HPLC. In one embodiment, the percentage of each enantiomer in the crystal form upon formation and upon storage is measured as a percent area of an HPLC chromatogram. In an embodiment, the chiral purity of the crystal form upon formation and upon storage is measured by HPLC as described in the “Chiral Purity by High Performance Liquid Chromatography” section of Example 6 in the present disclosure. [00319] In one embodiment, the impurities present in the crystal form upon formation are measured by ultra performance liquid chromatography (UPLC). In one embodiment, the impurities present in the crystal form upon storage for 6 months at about 25 °C and about 60% relative humidity are measured by UPLC. In one embodiment, the impurities present in the crystal form upon storage for 6 months at about 40 °C and about 75% relative humidity are measured by UPLC. In one embodiment, the percentage of each impurity in the crystal form upon formation and upon storage is measured as a percent area of an UPLC chromatogram. In an embodiment, the amount of impurities present in the crystal form upon formation and upon storage are measured by UPLC as described in the “Identification, Assay and Related Substances by Ultra Performance Liquid Chromatography” section of Example 6 in the present disclosure. [00320] In one embodiment, the present disclosure provides a single crystal of Compound 106 free base. In one embodiment, the single crystal of Compound 106 free base comprises a lattice parameter a of about 9.0 Å to about 10.0 Å, about 9.1 Å to about 9.9 Å, about 9.2 Å to about 9.8 Å, about 9.3 Å to about 9.7 Å, about 9.4 Å to about 9.7 Å, about 9.5 Å to about 9.7 Å, or about 9.58 Å. In one embodiment, the single crystal of Compound 106 free base comprises a lattice parameter b of about 15.0 Å to about 25.0 Å, about 16.0 Å to about 24.0 Å, about 17.0 Å to about 23.0 Å, about 18.0 Å to about 22.0 Å, about 19.0 Å to about 22.0 Å, about 20.0 Å to about 22.0 Å, or about 20.9 Å. In one embodiment, the single crystal of Compound 106 free base comprises a lattice parameter c of about 5.0 Å to about 15.0 Å, about 6.0 Å to about 14.0 Å, about 7.0 Å to about 13.0 Å, about 8.0 Å to about 12.0 Å, about 9.0 Å to about 12.0 Å, about 10.0 Å to about 12.0 Å, or about 10.8 Å. In one embodiment, the single crystal of Compound 106 free base comprises an α of about 85º to about 95°, about 86º to about 94°, about 87º to about 93°, about 88º to about 92°, about 89º to about 91°, or about 90°. In one embodiment, the single crystal of Compound 106 free base comprises a β of about 110° to about 120°, about 111° to about 119°, about 112° to about 118°, about 113° to about 117°, about 114° to about 116°, or about 114.8°. In one embodiment, the single crystal of Compound 106 free base comprises a γ of about 85º to about 95°, about 86º to about 94°, about 87º to about 93°, about 88º to about 92°, about 89º to about 91°, or about 90°. In one embodiment, the single crystal of Compound 106 free base comprises a volume of about 1950 Å³ to about 2000 Å³, about 1955 Å³ to about 1995 Å3, about 1960 Å³ to about 1990 Å³, about 1965 Å³ to about 1985 Å³, about 1965 Å³ to about 1980 Å³, about 1970 Å³ to about 1975 Å³, or about 1972 Å³ _. In one embodiment, the single crystal of Compound 106 free base comprises crystal density d_c of about 0.9 g/cm³ to about 1.9 g/cm³, about 0.9 g/cm³ to about 1.8 g/cm³, about 0.9 g/cm³ to about 1.7 g/cm³, about 0.9 g/cm³ to about 1.6 g/cm³, about 1.0 g/cm³ to about 1.5 g/cm³, about 1.1 g/cm³ to about 1.4 g/cm³, about 1.2 g/cm³ to about 1.4 g/cm³, or about 1.35 g/cm³. [00321] In another aspect, the present disclosure provides a pharmaceutical composition comprising a crystal form of Compound 106 and a formulary ingredient, an adjuvant, or a carrier. In one embodiment, the crystal form of Compound 106 is described elsewhere herein. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. In one embodiment, the pharmaceutical composition comprises between about 1 mg and about 100 mg, between about 10 mg and about 100 mg, between about 10 mg and about 90 mg, between about 20 mg and about 90 mg, between about 20 mg and about 80 mg, between about 30 mg and about 80 mg, between about 30 mg and about 70 mg, between about 40 mg and about 70 mg, between about 40 mg and about 60 mg, between about 45 mg and about 55 mg, or about 50 mg of the crystal form of Compound 106. In another embodiment, the pharmaceutical composition comprises between about 1 mg and about 100 mg, between about 1 mg and about 90 mg, between about 1 mg and about 80 mg, between about 1 mg and about 70 mg, between about 1 mg and about 60 mg, between about 1 mg and about 50 mg, between about 1 mg and about 40 mg, between about 1 mg and about 30 mg, between about 1 mg and about 20 mg, between about 5 mg and about 15 mg, or about 10 mg of the crystal form of Compound 106. [00322] In one embodiment, upon formation, the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %. In one embodiment, the water content of the pharmaceutical composition is measured by Karl Fischer titration. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00323] In one embodiment, upon formation, the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)- enantiomer. In one embodiment, upon formation, the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00324] In one embodiment, upon formation, the pharmaceutical composition comprises less than or equal to about 10%, about 9.0%, about 8.0%, about 7.0%, about 6.0%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, the impurities comprise soluble impurities. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00325] In one embodiment, upon storage for 1 month or 3 months at about 25 °C and about 60% relative humidity, the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00326] In one embodiment, upon storage for 1 month or 3 months at about 25 °C and about 60% relative humidity, the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer. In one embodiment, upon storage for 1 month or 3 months at about 25 °C and about 60% relative humidity, the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00327] In one embodiment, upon storage for 1 month or 3 months at about 25 °C and about 60% relative humidity, the pharmaceutical composition comprises less than or equal to about 10%, about 9.0%, about 8.0%, about 7.0%, about 6.0%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, the impurities comprise soluble impurities. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00328] In one embodiment, upon storage for 1 month or 3 months at about 40 °C and about 75% relative humidity, the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00329] In one embodiment, upon storage for 1 month or 3 months at about 40 °C and about 75% relative humidity, the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer. In one embodiment, upon storage for 1 month or 3 months at about 40 °C and about 75% relative humidity, the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00330] In one embodiment, upon storage for 1 month or 3 months at about 40 °C and about 75% relative humidity, the pharmaceutical composition comprises less than or equal to about 10%, about 9.0%, about 8.0%, about 7.0%, about 6.0%, about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. In one embodiment, the impurities comprise soluble impurities. In one embodiment, the crystal form comprises Compound 106 free base. In one embodiment, the crystal form comprises a mono hydrochloric acid salt of Compound 106. [00331] In one embodiment, the water content of the pharmaceutical composition upon formation is measured by thermogravimetric analysis (TGA). In one embodiment, the water content of the pharmaceutical composition upon storage for 1 month or 3 months at about 25 °C and about 60% relative humidity is measured by TGA. In one embodiment, the water content of the pharmaceutical composition upon storage for 1 month or 3 months at about 40 °C and about 75% relative humidity is measured by TGA. [00332] In one embodiment, the chiral purity of the crystal form in the upon formation of the pharmaceutical composition is measured by high performance liquid chromatography (HPLC). In one embodiment, the chiral purity of the crystal form upon storage of the pharmaceutical composition for 1 month or 3 months at about 25 °C and about 60% relative humidity is measured by HPLC. In one embodiment, the chiral purity of the crystal form upon storage of the pharmaceutical composition for 1 month or 3 months at about 40 °C and about 75% relative humidity is measured by HPLC. In one embodiment, the percentage of each enantiomer in the crystal form upon formation and upon storage is measured as a percent area of an HPLC chromatogram. In an embodiment, the chiral purity of the crystal form upon formation and upon storage of the pharmaceutical composition is measured by HPLC as described in the “Chiral Purity by High Performance Liquid Chromatography” section of Example 6 in the present disclosure. [00333] In one embodiment, the impurities present in the pharmaceutical composition upon formation are measured by ultra performance liquid chromatography (UPLC). In one embodiment, the impurities present in the pharmaceutical composition upon storage for 1 month or 3 months at about 25 °C and about 60% relative humidity are measured by UPLC. In one embodiment, the impurities present in the pharmaceutical composition upon storage for 1 month or 3 months at about 40 °C and about 75% relative humidity are measured by UPLC. In one embodiment, the percentage of each impurity in the pharmaceutical composition upon formation and upon storage is measured as a percent area of an UPLC chromatogram. In an embodiment, the amount of impurities present in the pharmaceutical composition upon formation and upon storage are measured by UPLC as described in the “Identification, Assay and Related Substances by Ultra Performance Liquid Chromatography” section of Example 6 in the present disclosure. [00334] In one embodiment, the pharmaceutical composition is a solid dosage form. In one embodiment, the solid dosage form is a capsule or tablet. In one embodiment, the solid dosage form comprises a cellulose capsule that is filled with Compound 106 or a salt, ester, solvate, optical isomer, geometric isomer, or salt of an isomer thereof. In one embodiment, the cellulose capsule comprises a hypromellose capsule. In one embodiment, the hypromellose capsule is a hard hypromellose capsule. In one embodiment, the capsule is filled with the mono˗HCl form of Compound 106 described elsewhere herein. In one embodiment, the solid dosage form is orally administered to a subject in need thereof. In one embodiment, upon oral administration of the solid dosage form, the solid dosage form disintegrates in the subject’s gastrointestinal tract in about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. In one embodiment, upon oral administration of the solid dosage form, the solid dosage form disintegrates in the subject’s stomach in about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. Combination Therapies [00335] In one embodiment, the crystalline form of the Compound 106 free base is administered with one or more therapeutic agents. In another embodiment, the crystalline form of a salt of Compound 106 is administered with one or more therapeutic agents. Exemplary therapeutic agents include, but are not limited to, a CDK inhibitor, a BCL2 inhibitor, a PTEFb inhibitor, a DNA polymerase inhibitor, a cytidine deaminase inhibitor, a DNA methyltransferase (DNMT) inhibitor, an immunomodulatory imide, a cereblon modulator, a purine nucleoside antimetabolite, a Type II topoisomerase inhibitor, a DNA intercalator, a hedgehog antagonist, an IDH2 inhibitor, an IDH1 inhibitor, a ribonucleotide reductase inhibitor, an adenosine deaminase inhibitor, a Mek 1/2 inhibitor, an ERK 1/2 inhibitor, an AKT inhibitor, a PTPN11 inhibitor, an SHP2 inhibitor, a glucocorticoid steroid, a menin inhibitor, an MDM2 inhibitor, a BTK inhibitor, and a mutant/inactivated p53 reactivator. [00336] In one embodiment, the therapeutic agent comprises a BCL2 inhibitor. In one embodiment, the BCL2 inhibitor is venetoclax or a salt thereof. In one embodiment, the therapeutic agent comprises a DNA polymerase inhibitor. In one embodiment, the DNA polymerase inhibitor is cytidine. In one embodiment, the therapeutic agent comprises a cytidine deaminase inhibitor. In one embodiment, the cytidine deaminase inhibitor is zebularine. In one embodiment, the therapeutic agent comprises a DNMT inhibitor. In one embodiment, the DNMT inhibitor is zebularine, decitabine, or azacitidine. In one embodiment, the therapeutic agent comprises an immunomodulatory imide (cereblon modulator). In one embodiment, the immunomodulatory imide (cereblon modulator) is lenalidomide. In one embodiment, the therapeutic agent comprises a purine nucleoside antimetabolite. In one embodiment, the purine nucleoside antimetabolite is clofarabine. In one embodiment, the therapeutic agent comprises a Type II topoisomerase inhibitor/ DNA intercalator. In one embodiment, the Type II topoisomerase inhibitor/ DNA intercalator is vosaroxin. In one embodiment, the therapeutic agent comprises a hedgehog antagonist. In one embodiment, the hedgehog antagonist is glasdegib. In one embodiment, the therapeutic agent comprises an IDH1 inhibitor. In one embodiment, the IDH1 inhibitor is ivosidenib. In one embodiment, the therapeutic agent comprises an IDH2 inhibitor. In one embodiment, the IDH2 inhibitor is enasidenib. In one embodiment, the therapeutic agent comprises a ribonucleotide reductase inhibitor. In one embodiment, the ribonucleotide reductase inhibitor is gemcitabine. In one embodiment, the therapeutic agent comprises an adenosine deaminase inhibitor. In one embodiment, the adenosine deaminase inhibitor is cladribine. In one embodiment, the therapeutic agent comprises a Mek 1/2 inhibitor. In one embodiment, the Mek 1/2 inhibitor is trametinib. In one embodiment, the therapeutic agent comprises an ERK 1/2 inhibitor. In one embodiment, the ERK 1/2 inhibitor is ulixertinib. In one embodiment, the therapeutic agent comprises an AKT inhibitor. In one embodiment, the AKT inhibitor is capivasertib (AZD5363). In one embodiment, the therapeutic agent comprises a PTPN11/SHP2 inhibitor. In one embodiment, the PTPN11/SHP2 inhibitor is TNO-155. In one embodiment, the therapeutic agent comprises a glucocorticoid steroid. In one embodiment, the glucocorticoid steroid is prednisolone. In one embodiment, the therapeutic agent comprises a menin inhibitor. In one embodiment, the menin inhibitor is SNDX-5613. In one embodiment, the therapeutic agent comprises an MDM2 inhibitor. In one embodiment, the MDM2 inhibitor is navtemadlin (AMG 232, KRT-232). In one embodiment, the therapeutic agent comprises a BTK inhibitor. In one embodiment, the BTK inhibitor is selected from ibrutinib, acalabrutinib, and zanubrutinib. In one embodiment, the therapeutic agent comprises a mutant/inactivated p53 reactivator. In one embodiment, the mutant/inactivated p53 reactivator is Eprenetapopt (APR-246). [00337] In one embodiment, the therapeutic agent comprises a CDK inhibitor. The CDK inhibitor can be any CDK inhibitor known to a person of ordinary skill in the art. In one embodiment, the CDK inhibitor is a CKD1, CKD2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, or CDK13 inhibitor or a combination thereof. [00338] In one embodiment, the CDK inhibitor comprises an inhibitor described in one of the following patents or patent applications: US 20210332071, US 20210330653, WO 2021214253, WO 2021178595, WO 2021207632, US 8685660, US 20200361906, US 10695346, US 11142507, WO 2021198439, WO 2021201170, US 8153632, US 11013743, US 11135198, US 20210299111, WO 2021190637, WO 2021188855, WO 2021188849, US 20210292299, US 11124836, US 10961527, US 20210284629, US 20210283265, WO 2021183994, WO 2021181233, US 11116755, WO 2021176045, WO 2021177816, WO 2021176049, WO 2021176349, US 20210275522, US 20210275491, US 20210277037, US 11111250, WO 2021142448, WO 2021172359, WO 2021174195, US 20210260209, US 20210261609, US 20210261636, US 20210261546, WO 2021168341, US 11014911, US 9932344, US 8415355, US 11091485, US 11091490, US 20210246422, US 20210246138, US 20210244715, US 11083722, US 11083728, US 20210238226, US 20190142835, WO 2021155006, WO 2021152107, WO 2021155192, US 10294234, US 11077156, WO 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6420345, WO 2002051849, US 6413974, US 6414013, US 6407103, WO 2001083716, US 5672508, US 6291504, WO 2001038532, WO 2001027080, US 6303618, US 6290951, WO 2001055148, WO 2001053293, US 6001868, US 6197804, WO 1999066055, US 6013646, WO 1999043676, US 5767258, US 5733920, and any INPADOC family member of each of the above references, each of which is incorporated herein by reference in its entirety. In another embodiment, the CDK inhibitor comprises an inhibitor described in: Alsfouk, A., Journal of Enzyme Inhibition and Medicinal Chemistry, 2021, 36(1):693-706; Goel, B. et al., Curr. Top. Med. Chem., 2020, 20(17):1535-1563; Heptinstall, A. B. et al., Future Med. Chem., 2018, 10(11):1369-1388; Sánchez-Martínez, C. et al., Bioorganic & Medicinal Chemistry Letters, 2019, 29:126637; Di Sante, G. et al., Expert Review of Anticancer Therapy, 2019, 19(7): 569-587; Whittaker, S. R. et al., Pharmacology & Therapeutics, 2017, 173:83-105; Chou, J. et al., Cancer Discovery, 2020, 10:351-370; Galbraith, M. D. et al., Transcription, 2019, 10(2):118-136; Goel, B. et al., Current Topics in Medicinal Chemistry, 2020, 20:1535-1563; Heptinstall, A. B. et al., Future Medicinal Chemistry, 2018, 10(11): 1369-1388; each of which is incorporated herein by reference in its entirety. [00339] In one embodiment, the CDK inhibitor is a CDK9 inhibitor. In one embodiment, the CDK9 inhibitor is Atuveciclib (BAY-1143572) or BAY-1251152 (VIP152). In one embodiment, BAY-1251152 (VIP152) is a selective CDK9 inhibitor while Atuveciclib (BAY- 1143572) is a CDK9/PTEFb inhibitor. In one embodiment, the CDK inhibitor is a CDK4/6 inhibitor. In one embodiment, the CDK4/6 inhibitor is Palbociclib. In one embodiment, the CDK inhibitor is a CDK7 inhibitor. In one embodiment, the CDK7 inhibitor is THZ1. [00340] Exemplary CDK inhibitors include, but are not limited to: Compound 21 (PMID 27326333) CYC065; YKL-1-116; i-CDK9; JH-VII-49; JH-XI-10-02; SEL120-34A; MM-D37K; PF-06873600; BEY-1007; BEY-1107; birociclib (XZP-3297); FCN-437; TP-1287; BEBT-209; TQB-3616; AMG-925 (FLX-925); CS3002; HS-10342; terameprocol (EM-1421); NU-6102; CGP-60474; BMS-265246; NU-6027; Purvalanol A; Purvalanol B; RGB-286147; Indirubin; 7- Hydroxystaurosporine; BS-194; PHA-690509; Cdk4/6 Inhibitor IV; FCN437c; Dinaciclib (SCH 727965); 7);

flavopiridol (alvocidib); dinaciclib;

lib, 9,

Verzenio); Palbociclib (PD-0332991, Ibrance);

lib A-

b 19; );

Y-

Z1;

59- b;

95;

22; H roxyl-zhc-

84; abemaciclib; vorinostat;

tin

orafenib;

32;

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;

;

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;

; ;

;

;

;

r R H₃

_, wherein R is t-butyl carboxyl and n is 1 or R is H and n is 2; wherein X is NH or O;

w eren s - 3 an s - 3 or s an s cyclopropyl;

wherein R is 3-fluoroailin-lyl and R’ is F or R is phenyl and

R’ is -CH3; H3; R is

-1-1- yl, X is F and n is 1, or oxatan-3-yl, X is -CH3, and n is 1; yl;

y p p y; wherein R is H, CH₃, 2-aminoethyan-1yl, 3-aminopropan-1yl, or

2,3-dihydroxpropan-1yl; H₃; l; hylphenyl, 3- f

luorophenyl, 4-methylphenyl, 2-ethylphenyl, or 3-pyridyl and R is H, cyclopropyl, cylcopentyl, or cycloheptyl; wherein R is 2-phenylethan-1yl or (furan-2-yl)methyl;

H; ’ is -CH3 or

wherein R is 2,6-dichlorophenyl, 2,3,4,5,6-tetrafluorophenyl, or 3-

fluorophenyl; H; CH₃)₂, 4-carboxylic acid-

, R’ is H or F, and R” is H or -CH2CH3; wherein R1 is -OH, R2 is H, R3 is H, and R4 is H (meridianin A), R1 is

, , ₃ , nd R₄ is H (meridianin B), R₁ is H, R₂ is Br, R₃ is H, and R₄ is H (meridianin C), R₁ is H, R₂ is H, R₃ is Br, and R₄ is H (meridianin D), or R₁ is -OH, R₂ is H, R₃ is H, and R4 is Br (meridianin E); and wherein R is piperidin-3yl, pyrrolodin-3yl, or morpholin-2yl. [

one embodiment, the therapeutic agent comprises a BCL2 inhibitor and a DNMT inhibitor. In one embodiment, the therapeutic agent comprises venetoclax, or a salt therof, and azacitidine, or a salt thereof. [00342] In some embodiments, the one or more therapeutic agents can be in the form of salts, optical and geometric isomers, and salts of isomers. In other embodiments, the therapeutic agent can be in various forms, such as uncharged molecules, components of molecular complexes, or non-irritating pharmacologically acceptable salts, including but not limited to hydrochloride, hydrobromide, sulphate, phosphate, nitrate, borate, acetate, maleate, tartrate, and salicylate. In some instances, for acidic compounds, salts can include metals, amines, or organic cations (e.g. quaternary ammonium). In yet other embodiments, simple derivatives of the therapeutic agents (e.g., ethers, esters, or amides) which have desirable retention and release characteristics but which are easily hydrolyzed by body pH, enzymes, or other suitable means, can be employed. [00343] In some embodiments, the therapeutic agent has a chiral center and can exist in and be isolated in optically active and racemic forms. In other embodiments, the therapeutic agent may exhibit polymorphism. Some embodiments of the present disclosure encompass any racemic, optically active, polymorphic, or stereoisomeric form, or mixtures thereof, of a compound described herein, including isotopically-labeled and radio-labeled compounds. See e.g., Goding, 1986, Monoclonal Antibodies Principles and Practice; Academic Press, p. 104. Such isomers can be isolated by standard resolution techniques, including e.g., fractional crystallization, chiral chromatography, and the like. See e.g., Eliel, E. L. & Wilen S. H., 1993, Stereochemistry in Organic Compounds; John Wiley & Sons, New York. The preparation of optically active forms can be accomplished by any suitable method, including but not limited to, resolution of the racemic form by recrystallization techniques, synthesis from optically-active starting materials, chiral synthesis, or chromatographic separation using a chiral stationary phase. [00344] In some embodiments, the therapeutic agent has asymmetric centers and can occur as racemates, racemic mixtures, and as individual enantiomers or diastereoisomers, with all isomeric forms as well as mixtures thereof being contemplated for use in the compounds and methods described herein. The compounds contemplated for use in the compounds and methods described herein do not include those that are known in the art to be too unstable to synthesize and/or isolate. [00345] The therapeutic agents disclosed herein can also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds can be radiolabeled with radioactive isotopes, such as for example tritium (³H), iodine-125 (¹²⁵I), or carbon-14 (¹⁴C). All isotopic variations of the compounds disclosed herein, whether radioactive or not, are encompassed within the contemplated scope. [00346] In some embodiments, metabolites of the the therapeutic agents disclosed herein are useful for the methods disclosed herein. [00347] In some embodiments, the therapeutic agents contemplated herein may be provided in the form of a prodrug. The term “prodrug” refers to a compound that can be converted into a compound (e.g., a biologically active compound) described herein in vivo. Prodrugs can be useful for a variety of reason known in the art, including e.g., ease of administration due e.g., to enhanced bioavailability in oral administration, and the like. The prodrug can also have improved solubility in pharmaceutical compositions over the biologically active compounds. An example, without limitation, of a prodrug is a compound which is administered as an ester (i.e., the "prodrug") to facilitate transmittal across a cell membrane where water solubility is detrimental to mobility but which then is metabolically hydrolyzed to the carboxylic acid, the active entity, once inside the cell where water solubility is beneficial. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in Design of Prodrugs, (ed. H. Bundgaard, Elsevier, 1985), which is hereby incorporated herein by reference for the limited purpose describing procedures and preparation of suitable prodrug derivatives. [00348] Certain the therapeutic agent disclosed herein can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of contemplated compounds. Certain the therapeutic agents of the present disclosure can exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the compounds and methods contemplated herein and are intended to be within the scope disclosed herein. Pharmaceutical Compositions and Formulations [00349] In one embodiment, the present disclosure further relates to a composition comprising a crystalline form of a free base or a salt of Compound 106 and a composition comprising a therapeutic agent. Exemplary therapeutic agents are described elsewhere herein. In another embodiment, the crystalline form of a free base or a salt of Compound 106 and the therapeutic agent are co-formulated into a single composition. In one embodiment, the crystalline form of a free base or a salt of Compound 106 and the therapeutic agent are administered together in one administration or composition. In another embodiment, the crystalline form of a free base or a salt of Compound 106 and the therapeutic agent are administered separately in more than one administration or more than one composition. In one embodiment, the composition comprising crystalline form of a free base or a salt of Compound 106 and the composition comprising the therapeutic agent are administered to a subject at the same time. In another embodiment, the composition comprising the crystalline form of a free base or a salt of Compound 106 and the composition comprising the therapeutic agent are administered to a subject sequentially. In one embodiment, the composition comprising the crystalline form of a free base or a salt of Compound 106 and the composition comprising the therapeutic agent are co-administered (or administered within a defined time period) such that the subject is exposed to both inhibitors over a period of time in which they can act synergistically. [00350] Some embodiments of the present disclosure include compositions comprising one or more compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106). In one embodiment, the composition comprising a compound of the disclosure further comprises one or more therapeutic agents described elsewhere herein. In one embodiment, the present disclosure includes a separate composition comprising one or more of the therapeutic agents described elsewhere herein. In certain embodiments, the composition is a pharmaceutical composition, such as compositions that are suitable for administration to animals (e.g., mammals, primates, monkeys, humans, canine, feline, porcine, mice, rabbits, rats, etc.). In some embodiments, there is provided a pharmaceutical composition comprising a crystalline form disclosed herein and a pharmaceutically acceptable excipient. The crystalline form can be a free base or a salt of Compound 106, or a pharmaceutically acceptable salt, ester, solvate, optical isomer, geometric isomer, salt of an isomer, prodrug, or derivative thereof. [00351] Further embodiments of the disclosure relate to compositions including a compound as described above. In some embodiments, the amount of the compound can be from about 0.0001% (by weight total composition) to about 99%. In some embodiments, the composition can further include a formulary ingredient, an adjuvant, or a carrier. In some embodiments, the composition can further include a BCL2 inhibitor. In some embodiments, the composition can be used in combination with a second composition including a BCL2 inhibitor. In some embodiments, the BCL2 can be venetoclax, or a salt, isomer, derivative or analog thereof. [00352] The term “pharmaceutically acceptable salts” is meant to include salts of the active compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds disclosed herein contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds disclosed herein contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, oxalic, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galacturonic acids and the like (see, for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain specific compounds disclosed herein contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. [00353] Compounds disclosed herein can exist as salts, such as with pharmaceutically acceptable acids. Accordingly, the compounds contemplated herein include such salts. Examples of such salts include hydrochlorides, hydrobromides, sulfates, methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, tartrates (e.g., (+)-tartrates, (-)-tartrates, or mixtures thereof including racemic mixtures), succinates, benzoates, and salts with amino acids such as glutamic acid. These salts can be prepared by methods known to those skilled in the art. [00354] The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents. [00355] Pharmaceutically acceptable salts of the compounds above, where a basic or acidic group is present in the structure, are also included within the scope of compounds contemplated herein. When an acidic substituent is present, such as -NHSO₃H, -COOH and -P(O)(OH)2, there can be formed the ammonium, sodium, potassium, calcium salt, and the like, for use as the dosage form. Basic groups, such as amino or basic heteroaryl radicals, or pyridyl and acidic salts, such as hydrochloride, hydrobromide, acetate, maleate, palmoate, methanesulfonate, p-toluenesulfonate, and the like, can be used as the dosage form. [00356] Also, in the embodiments in which R-COOH is present, pharmaceutically acceptable esters can be employed, e. g., methyl, ethyl, tert-butyl, pivaloyloxymethyl, and the like, and those esters known in the art for modifying solubility or hydrolysis characteristics for use as sustained release or prodrug formulations. [00357] In some instances, the pharmaceutical composition is non-toxic, does not cause side effects, or both. In some embodiments, there may be inherent side effects (e.g., it may harm the patient or may be toxic or harmful to some degree in some patients). [00358] In some embodiments, one or more compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) can be part of a pharmaceutical composition and can be in an amount of at least about 0.0001%, at least about 0.001%, at least about 0.10%, at least about 0.15%, at least about 0.20%, at least about 0.25%, at least about 0.50%, at least about 0.75%, at least about 1%, at least about 10%, at least about 25%, at least about 50%, at least about 75%, at least about 90%, at least about 95%, at least about 99%, at least about 99.99%, no more than about 75%, no more than about 90%, no more than about 95%, no more than about 99%, no more than about 99.99%, from about 0.001% to about 99%, from about 0.001% to about 50%, from about 0.1% to about 99%, from about 1% to about 95%, from about 10% to about 90%, or from about 25% to about 75%. In some embodiments, the pharmaceutical composition can be presented in a dosage form which is suitable for the topical, subcutaneous, intrathecal, intraperitoneal, oral, parenteral, rectal, cutaneous, nasal, vaginal, or ocular administration route. In other embodiments, the pharmaceutical composition can be presented in a dosage form which is suitable for parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. The pharmaceutical composition can be in the form of, for example, tablets, capsules, pills, powders granulates, suspensions, emulsions, solutions, gels (including hydrogels), pastes, ointments, creams, plasters, drenches, delivery devices, suppositories, enemas, injectables, implants, sprays, aerosols or other suitable forms. [00359] In some embodiments, the compounds disclosed herein can be administered orally as tablets, aqueous or oily suspensions, lozenges, troches, powders, granules, emulsions, capsules, syrups or elixirs. The composition for oral use can contain one or more agents selected from the group of sweetening agents, flavoring agents, coloring agents and preserving agents in order to produce pharmaceutically elegant and palatable preparations. Accordingly, there are also provided pharmaceutical compositions comprising a pharmaceutically acceptable carrier or excipient and one or more compounds disclosed herein. [00360] In some embodiments, tablets contain the acting ingredient in admixture with non-toxic pharmaceutically acceptable excipients that are suitable for the manufacture of tablets. These excipients can be, for example, (1) inert diluents, such as calcium carbonate, lactose, mannitol, calcium phosphate, carboxymethylcellulose, microcrystalline cellulose, or sodium phosphate; (2) granulating and disintegrating agents, such as copovidone, corn starch, croscarmellose sodium, or alginic acid; (3) binding agents, such as starch, gelatin, or acacia; and (4) lubricating agents, such as magnesium stearate, sodium stearyl fumarate, stearic acid, or talc. These tablets can be uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate can be employed. [00361] For preparing pharmaceutical compositions from the compounds disclosed herein, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substance that can also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material. [00362] A compound disclosed herein, in the form of a free compound or a pharmaceutically acceptable pro-drug, metabolite, analogue, derivative, solvate or salt, can be administered, for in vivo application, parenterally by injection or by gradual perfusion over time. Administration can be intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavity, or transdermally. For in vitro studies the compounds can be added or dissolved in an appropriate biologically acceptable buffer and added to a cell or tissue. [00363] In powders, the carrier is a finely divided solid in a mixture with the finely divided active component. In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired. [00364] The powders and tablets preferably contain from 5% to 70% of the active compound. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term “preparation” is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration. [00365] For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify. [00366] Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water/propylene glycol solutions. For parenteral injection, liquid preparations can be formulated in solution in aqueous polyethylene glycol solution. [00367] When parenteral application is needed or desired, particularly suitable admixtures for the compounds disclosed herein are injectable, sterile solutions, preferably oily or aqueous solutions, as well as suspensions, emulsions, or implants, including suppositories. This suspension can be formulated according to known methods using those suitable dispersing or wetting agents and suspending agents that have been mentioned above. The sterile injectable preparation can also a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles, carriers, and solvents that can be employed are water, Ringer’s solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono-or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. In particular, carriers for parenteral administration include aqueous solutions of dextrose, saline, pure water, ethanol, glycerol, propylene glycol, peanut oil, sesame oil, polyoxyethylene-block polymers, and the like. Ampoules are convenient unit dosages. The compounds disclosed herein can also be incorporated into liposomes or administered via transdermal pumps or patches. Pharmaceutical admixtures suitable for use in the pharmaceuticals compositions and methods disclosed herein include those described, for example, in PHARMACEUTICAL SCIENCES (17th Ed., Mack Pub. Co., Easton, PA) and WO 96/05309, the teachings of both of which are hereby incorporated by reference. [00368] In some embodiments, preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Frequently used carriers or auxiliaries include magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatin, starch, vitamins, cellulose and its derivatives, animal and vegetable oils, polyethylene glycols and solvents, such as sterile water, alcohols, glycerol and polyhydric alcohols. Intravenous vehicles include fluid and nutrient replenishers. Parenteral vehicles include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer’s dextrose), and the like. Preservatives and other additives can also be present such as, for example, antimicrobials, antioxidants, chelating agents, growth factors and inert gases and the like. [00369] Preservatives include antimicrobial, antioxidants, chelating agents and inert gases. Other pharmaceutically acceptable carriers include aqueous solutions, non-toxic excipients, including salts, preservatives, buffers and the like, as described, for instance, in Remington’s Pharmaceutical Sciences, 15th ed. Easton: Mack Publishing Co. , 1405-1412, 1461-1487 (1975) and The National Formulary XIV., 14th ed. Washington: American Pharmaceutical Association (1975), the contents of which are hereby incorporated by reference. The pH and exact concentration of the various components of the pharmaceutical composition are adjusted according to routine skills in the art. See e.g., Goodman and Gilman (eds.), 1990, THE PHARMACOLOGICAL BASIS FOR THERAPEUTICS (7th ed.). [00370] Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizers, and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, me thylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents. Aqueous suspensions normally contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspension. Such excipients can be (1) suspending agent such as sodium carboxymethyl cellulose, methyl cellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; (2) dispersing or wetting agents which can be (a) naturally occurring phosphatide such as lecithin; (b) a condensation product of an alkylene oxide with a fatty acid, for example, polyoxyethylene stearate ; (c) a condensation product of ethylene oxide with a long chain aliphatic alcohol, for example, heptadecaethylenoxycetanol; (d) a condensation product of ethylene oxide with a partial ester derived from a fatty acid and hexitol such as polyoxyethylene sorbitol monooleate, or (e) a condensation product of ethylene oxide with a partial ester derived from fatty acids and hexitol anhydrides, for example polyoxyethylene sorbitan monooleate [00371] Also included are solid form preparations that are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations can contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like. [00372] The pharmaceutical preparation is preferably in unit dosage form. In such form the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form. [00373] In some embodiments, the pharmaceutical composition can include one or more formulary ingredients. A “formulary ingredient” can be any suitable ingredient (e.g., suitable for the drug(s), for the dosage of the drug(s), for the timing of release of the drugs(s), for the disease, for the disease state, or for the delivery route) including, but not limited to, water (e.g., boiled water, distilled water, filtered water, pyrogen-free water, or water with chloroform), sugar (e.g., sucrose, glucose, mannitol, sorbitol, xylitol, or syrups made therefrom), ethanol, glycerol, glycols (e.g., propylene glycol), acetone, ethers, DMSO, surfactants (e.g., anionic surfactants, cationic surfactants, zwitterionic surfactants, or nonionic surfactants (e.g., polysorbates)), oils (e.g., animal oils, plant oils (e.g., coconut oil or arachis oil), or mineral oils), oil derivatives (e.g., ethyl oleate , glyceryl monostearate, or hydrogenated glycerides), excipients, preservatives (e.g., cysteine, methionine, antioxidants (e.g., vitamins (e.g., A, E, or C), selenium, retinyl palmitate, sodium citrate, citric acid, chloroform, or parabens, (e.g., methyl paraben or propyl paraben)), or combinations thereof. [00374] In certain embodiments, pharmaceutical compositions can be formulated to release the active ingredient (e.g., a crystalline form of a free base or a salt of Compound 106) substantially immediately upon the administration or any substantially predetermined time or time after administration. Such formulations can include, for example, controlled release formulations such as various controlled release compositions and coatings. [00375] Other formulations (e.g., formulations of a pharmaceutical composition) can, in certain embodiments, include those incorporating the drug (or control release formulation) into food, food stuffs, feed, or drink. [00376] Some compounds can have limited solubility in water and therefore can require a surfactant or other appropriate co-solvent in the composition. Such co-solvents include: Polysorbate 20, 60, and 80; Pluronic F-68, F-84, and P-103; cyclodextrin; and polyoxyl 35 castor oil. Such co-solvents are typically employed at a level between about 0.01 % and about 2% by weight. [00377] Viscosity greater than that of simple aqueous solutions can be desirable to decrease variability in dispensing the formulations, to decrease physical separation of components of a suspension or emulsion of formulation, and/or otherwise to improve the formulation. Such viscosity building agents include, for example, polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxy propyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxy propyl cellulose, chondroitin sulfate and salts thereof, hyaluronic acid and salts thereof, and combinations of the foregoing. Such agents are typically employed at a level between about 0.01% and about 2% by weight. [00378] The compositions disclosed herein can additionally include components to provide sustained release and/or comfort. Such components include high molecular weight, anionic mucomimetic polymers, gelling polysaccharides, and finely divided drug carrier substrates. These components are discussed in greater detail in U.S. Pat. Nos.4,911,920; 5,403,841; 5,212,162; and 4,861,760. The entire contents of these patents are incorporated herein by reference in their entirety for all purposes. [00379] There are provided various pharmaceutical compositions useful for ameliorating certain diseases and disorders. The pharmaceutical compositions according to one embodiment are prepared by formulating a compound disclosed herein in the form of a free compound or a pharmaceutically-acceptable pro-drug, metabolite, analogue, derivative, solvate or salt, either alone or together with other pharmaceutical agents, suitable for administration to a subject using carriers, excipients and additives or auxiliaries. Frequently used carriers or auxiliaries include magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatin, starch, vitamins, cellulose and its derivatives, animal and vegetable oils, polyethylene glycols and solvents, such as sterile water, alcohols, glycerol and polyhydric alcohols. Intravenous vehicles include fluid and nutrient replenishers. [00380] There are provided various pharmaceutical compositions useful for ameliorating certain diseases and disorders. The pharmaceutical compositions according to one embodiment are prepared by formulating a compound disclosed herein in the form of a free compound or a pharmaceutically acceptable pro-drug, metabolite, analogue, derivative, solvate or salt, either alone or together with other pharmaceutical agents, suitable for administration to a subject using carriers, excipients and additives or auxiliaries. Frequently used carriers or auxiliaries include magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatin, starch, vitamins, cellulose and its derivatives, animal and vegetable oils, polyethylene glycols and solvents, such as sterile water, alcohols, glycerol and polyhydric alcohols. Intravenous vehicles include fluid and nutrient replenishers. Methods of Treating and Preventing Disease [00381] Further embodiments of the disclosure relate to methods for providing a subject with a compound including one or more administrations of one or more compositions including a crystalline form of a free base or a salt of Compound 106 as described above, the compositions may be the same or different if there is more than one administration. In some embodiments, at least one of the one or more compositions further includes a formulary ingredient. In some embodiments, at least one of the one or more compositions includes a composition including a compound as described above. In some embodiments, at least one of the one or more administrations includes parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. In some embodiments, if there is more than one administration at least one composition used for at least one administration is different from the composition of at least one other administration. In some embodiments, the compound of at least one of the one or more compositions can be administered to the subject in an amount of from about 0.005 mg/kg subject body weight to about 50 mg /kg subject body weight. In some embodiments, the subject is a mammal, preferably a human, a rodent, or a primate. [00382] Further embodiments of the disclosure relate to methods for treating a disease or disorder, where the method includes one or more administrations to a subject of one or more compositions including a compound as described above, where the compositions may be the same or different if there is more than one administration. In some embodiments, the disease or disorder can be responsive to at least one of interleukin-1 receptor-associated kinase (IRAK) inhibition or fms-like tyrosine kinase 3 (FLT3) inhibition. In some embodiments, at least one of the one or more compositions further includes a formulary ingredient. In some embodiments, at least one of the one or more compositions includes a composition as described above. [00383] In some embodiments, at least one of the one or more administrations includes parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, transdermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. In some embodiments, at least one of the one or more administrations includes an oral administration. In some embodiments, if there is more than one administration at least one composition used for at least one administration is different from the composition of at least one other administration. In some embodiments, the compound of at least one of the one or more compositions is administered to the subject in an amount of from about 0.005 mg/kg subject body weight to about 50 mg /kg subject body weight. In some embodiments, the subject can be a mammal, preferably a human, a rodent, or a primate. In some embodiments, the subject is in need of the treatment. [00384] In some embodiments, the method is for treating a hematopoietic cancer. In some embodiments, the method is for treating a myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). In some embodiments, the method is for treating at least one of lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL with MYD88 mutation, follicular lymphoma, or marginal zone lymphoma. In some embodiments, the method is for treating at least one cancer selected from glioblastoma multiforme, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer, or one or more inflammatory diseases or autoimmune disease characterized by overactive IRAK1 and/or IRAK4, or combinations thereof. In some embodiments, the method is for treating one or more inflammatory diseases or autoimmune disease selected from chronic inflammation (i.e., associated with viral and bacterial infection), sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, colitis, Crohn’s disease, atopic dermatitis, or combinations thereof. In some embodiments, the method is for treating myelofibrosis. In some embodiments, the method is for treating colitis. In some embodiments, the method is for treating Crohn’s disease. In some embodiments, the method is for treating MDS, MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2, or the method is for treating AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or where the AML is not driven by FLT3 mutations but expresses IRAK4-Long. In some embodiments, the method is for treating DLBCL, and the DLBCL includes a L265P MYD88 mutant (ABC) subtype of DLBCL. [00385] In some embodiments, the method further includes administration of a composition including a BTK inhibitor. In some embodiments, the BTK inhibitor includes ibrutinib. [00386] In some embodiments, the subject is susceptible to AML and/or MDS, and/or the method prevents or ameliorates future AML and/or MDS. In some embodiments, the method occurs after one or more of having myelodysplastic syndrome, having myeloproliferative disease, an occurrence of chemical exposure, an exposure to ionizing radiation, or a treatment for cancer. [00387] In some embodiments, the method further includes administration of a composition including a BCL2 inhibitor, or at least one of said compositions including a compound as described above further includes a BCL2 inhibitor. In some embodiments, the compound as described above and the BCL2 inhibitor may be administered together or separately, in one or more administrations of one or more compositions. In some embodiments, the BCL2 inhibitor includes venetoclax, or a salt, isomer, derivative or analog thereof. [00388] In some embodiments, the method further includes administration of one or more additional therapy selected from one or more chemotherapy, DNA methyltransferase inhibitor/hypomethylating agent, anthracycline, histone deacetylase (HDAC) inhibitor, purine nucleoside analogue (antimetabolite), isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, antibody-drug conjugate, mAbs/immunotherapy, CAR-T cell therapy, Plk inhibitor, MEK inhibitor, CDK9 inhibitor, CDK8 inhibitor, retinoic acid receptor agonist, TP53 activator, smoothened receptor antagonist, ERK inhibitor, PI3K inhibitor, mTOR inhibitor, glucocorticoid receptor modulator, or EZH2 inhibitor, or one or more combinations thereof. In some embodiments, the DNA methyltransferase inhibitor/hypomethylating agent includes azacytidine, decitabine, cytarabine, and/or guadecitabine; the anthracycline includes daunorubicin, idarubicin, doxorubicin, mitoxantrone, epirubicin, and/or CPX-351 (a combination cytarabine and daunorubicin in a fixed 5:1 molar ratio); the histone deacetylase (HDAC) inhibitor includes vorinostat, panobinostat, valproic acid, and/or pracinostat; the purine nucleoside analogue (antimetabolite) includes fludarabine, cladribine, and/or clofarabine; the isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor includes ivosidenib and/or enasidenib; the antibody-drug conjugate includes Anti-CD33 (e.g. Ac225-lintuzumab, vadastuximab, or gemtuzumab- ozogamicin) and/or Anti-CD45 (e.g. I¹³¹-apamistamab); the mAbs/Immunotherapy includes Anti-CD70 (e.g. ARGX-110, cusatuzumab), a bispecific antibody (e.g. floteuzumab (CD123 x CD3)), Anti-CTLA4 (e.g. ipilimumab), Anti-PD1/PDL1 (e.g. nivolumab, pembrolizumab, atezolizumab, avelumab, PDR001, MBG453), and/or Anti-CD47 (e.g.5F9 (Magrolimab)); the Plk inhibitor includes volasertib and/or rigosertib; the MEK inhibitor includes trametinib, cobimetinib, selumetinib, pimasertib, and/or refametinib; the CDK9 inhibitor includes alvocidib and/or voruciclib; the CDK8 inhibitor includes SEL120; the retinoic acid receptor agonist includes ATRA (all-trans retinoic acid) and/or SY-1425 (a selective RARα agonist); the TP53 activator includes APR-246 (Eprenetapopt); the smoothened receptor antagonist includes glasdegib; the ERK inhibitor includes an ERK2/MAPK1 or ERK1/MAPK3 inhibitor including ulixertinib, SCH772984, ravoxertinib, MK-8353, and/or VTX-11e; the PI3K inhibitor includes fimepinostat (CUDC-907), alpelisib, leniolisib (CDZ-173), pilaralisib (XL147, SAR245408), and/or bimiralisib (PQR-309); the mTOR inhibitor includes bimiralisib (PQR-309), sapanisertib (TAK-228, INK-128), ridaforolimus (MK-8669, AP-23573), everolimus, and/or vistusertib (AZD2014); the glucocorticoid receptor modulator includes an agonist including prednisolone, beclometasone, methylprednisolone, prednisone, fluticasone, budesonide, dexamethasone, and/or cortisol, and/or an antagonist including mifepristone, miricorilant, and/or onapristone, and/or another binding ligand including vamorolone (VBP15); and/or the EZH2 inhibitor includes tazemetostat. [00389] Further embodiments of the disclosure relate to crystalline forms as described above, for use in a method for treating a disease or disorder, the method including inhibiting at least one of IRAK and FLT3 by administering one or more compositions including the compound, where the compositions may be the same or different if there is more than one administration. In some embodiments, disease or disorder can be responsive to at least one of interleukin-1 receptor-associated kinase (IRAK) inhibition or fms-like tyrosine kinase 3 (FLT3) inhibition. In some embodiments, at least one of the one or more compositions further includes a formulary ingredient. In some embodiments, at least one of the one or more compositions includes the composition as described above. In some embodiments, at least one of the one or more administrations includes parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, transdermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. In some embodiments, at least one of the one or more administrations includes an oral administration. In some embodiments, if there is more than one administration at least one composition used for at least one administration is different from the composition of at least one other administration. [00390] In some embodiments, the compound of at least one of the one or more compositions can be administered to the subject in an amount of from about 0.005 mg/kg subject body weight to about 50 mg /kg subject body weight. In some embodiments, the subject is a mammal, preferably a human, a rodent, or a primate. In some embodiments, the subject is in need of the treatment. [00391] In some embodiments, the method is for treating a hematopoietic cancer. In some embodiments, the method is for treating MDS and/or AML. In some embodiments, the method is for treating at least one of lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non- Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL with MYD88 mutation, follicular lymphoma, or marginal zone lymphoma. In some embodiments, the method is for treating at least one cancer selected from glioblastoma multiforme, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer, or one or more inflammatory diseases or autoimmune disease characterized by overactive IRAK1 and/or IRAK4, or combinations thereof. In some embodiments, the method is for treating one or more inflammatory diseases or autoimmune disease selected from chronic inflammation (i.e., associated with viral and bacterial infection), sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, or combinations thereof. In some embodiments, the method is for treating MDS, MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2, or the method is for treating AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or the AML is not driven by FLT3 mutations but expresses IRAK4-Long. In some embodiments, the method is for treating DLBCL, and the DLBCL includes a L265P MYD88 mutant (ABC) subtype of DLBCL. [00392] In some embodiments, the method further includes administration of a composition including a BTK inhibitor. In some embodiments, the BTK inhibitor includes ibrutinib. [00393] In some embodiments, the subject is susceptible to AML and/or MDS, and/or the method prevents or ameliorates future AML and/or MDS. In some embodiments, the method occurs after one or more of having myelodysplastic syndrome, having myeloproliferative disease, an occurrence of chemical exposure, an exposure to ionizing radiation, or a treatment for cancer. In some embodiments, method further includes administration of a composition including a BCL2 inhibitor, or at least one of said compositions including the crystalline form of a free base or a salt of Compound 106 further includes a BCL2 inhibitor. In some embodiments, the crystalline form of a free base or a salt of Compound 106 and the BCL2 inhibitor can be administered together or separately, in one or more administrations of one or more compositions. In some embodiments, the BCL2 inhibitor includes venetoclax, or a salt, isomer, derivative or analog thereof. [00394] In some embodiments, the method further includes administration of one or more additional therapy selected from one or more chemotherapy, DNA methyltransferase inhibitor/hypomethylating agent, anthracycline, histone deacetylase (HDAC) inhibitor, purine nucleoside analogue (antimetabolite), isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, antibody-drug conjugate, mAbs/immunotherapy, CAR-T cell therapy, Plk inhibitor, MEK inhibitor, CDK9 inhibitor, CDK8 inhibitor, retinoic acid receptor agonist, TP53 activator, smoothened receptor antagonist, ERK inhibitor, PI3K inhibitor, mTOR inhibitor, glucocorticoid receptor modulator, or EZH2 inhibitor, or one or more combinations thereof. In some embodiments, the DNA methyltransferase inhibitor/hypomethylating agent includes azacytidine, decitabine, cytarabine, and/or guadecitabine; the anthracycline includes daunorubicin, idarubicin, doxorubicin, mitoxantrone, epirubicin, and/or CPX-351 (a combination cytarabine and daunorubicin in a fixed 5:1 molar ratio); the histone deacetylase (HDAC) inhibitor includes vorinostat, panobinostat, valproic acid, and/or pracinostat; the purine nucleoside analogue (antimetabolite) includes fludarabine, cladribine, and/or clofarabine; the isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor includes ivosidenib and/or enasidenib; the antibody-drug conjugate includes Anti-CD33 (e.g. Ac225-lintuzumab, vadastuximab, or gemtuzumab- ozogamicin) and/or Anti-CD45 (e.g. I¹³¹-apamistamab); the mAbs/Immunotherapy includes Anti-CD70 (e.g. ARGX-110, cusatuzumab), a bispecific antibody (e.g. floteuzumab (CD123 x CD3)), Anti-CTLA4 (e.g. ipilimumab), Anti-PD1/PDL1 (e.g. nivolumab, pembrolizumab, atezolizumab, avelumab, PDR001, MBG453), and/or Anti-CD47 (e.g.5F9 (Magrolimab)); the Plk inhibitor includes volasertib and/or rigosertib; the MEK inhibitor includes trametinib, cobimetinib, selumetinib, pimasertib, and/or refametinib; the CDK9 inhibitor includes alvocidib and/or voruciclib; the CDK8 inhibitor includes SEL120; the retinoic acid receptor agonist includes ATRA (all-trans retinoic acid) and/or SY-1425 (a selective RARα agonist); the TP53 activator includes APR-246 (Eprenetapopt); the smoothened receptor antagonist includes glasdegib; the ERK inhibitor includes an ERK2/MAPK1 or ERK1/MAPK3 inhibitor including ulixertinib, SCH772984, ravoxertinib, MK-8353, and/or VTX-11e; wherein the PI3K inhibitor includes fimepinostat (CUDC-907), alpelisib, leniolisib (CDZ-173), pilaralisib (XL147, SAR245408), and/or bimiralisib (PQR-309); the mTOR inhibitor includes bimiralisib (PQR- 309), sapanisertib (TAK-228, INK-128), ridaforolimus (MK-8669, AP-23573), everolimus, and/or vistusertib (AZD2014); the glucocorticoid receptor modulator includes an agonist including prednisolone, beclometasone, methylprednisolone, prednisone, fluticasone, budesonide, dexamethasone, and/or cortisol, and/or an antagonist including mifepristone, miricorilant, and/or onapristone, and/or another binding ligand including vamorolone (VBP15); and/or the EZH2 inhibitor includes tazemetostat. [00395] In one aspect, the present disclosure relates to a method of treating and/or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a crystalline form of a free base or a salt of Compound 106 and a therapeutically effective amount of a CDK inhibitor. In one embodiment, a composition comprising a therapeutically effective amount of a crystalline form of a free base or a salt of Compound 106 is administered to the subject. In one embodiment, a composition comprising a therapeutically effective amount of the CDK inhibitor is administered to the subject. In one embodiment, the crystalline form of a free base or a salt of Compound 106 treats and/or prevents the disease or disorder by inhibiting FLT3 (wild type FLT3 and/or mutant FLT3) as well as IRAK4, IRAK1, or both IRAK4 and IRAK1 in the subject in need thereof. In one embodiment, the CDK inhibitor treats and/or prevents the disease or disorder by inhibiting one or more of CKD1, CKD2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, or CDK13 in the subject in need thereof. [00396] In addition to their ability to inhibit IRAK, IRAK inhibitors have been demonstrated to have selectivity for multiple kinases. In some embodiments, compounds described herein, such as the crystalline form of a free base or a salt of Compound 106, exhibit have inhibitory action against one or more kinase, such as interleukin-1 receptor-associated kinase (IRAK) and FMS-like tyrosine kinase 3 (FLT3). The inhibitory action against one or more kinase, such as IRAK and FLT3, can allow for treatment and/or prevention of diseases in an animal (e.g., mammals, porcine, canine, avian (e.g., chicken), bovine, feline, primates, rodents, monkeys, rabbits, mice, rats, and humans) using a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) including, but not limited to hematopoietic cancers (e.g., disorders of hematopoietic stem cells in the bone marrow or disorders related to myeloid lineage), MDS, AML, myeloproliferative disease, and diseases (e.g., hematopoietic cancers) related to mutations in IRAK1, IRAK4, and/or FLT3 (e.g., mutations in the juxtamembrane region of FLT3, mutations in the kinase domain of FLT3, FLT3 point mutations, FLT3 internal tandem duplication mutations, the FLT3-ITD mutation, the D835Y FLT3 mutation, the D835V FLT3 mutation, the F691L FLT3 mutation, or the R834Q FLT3 mutation). [00397] In some embodiments, the compounds of the disclosure can inhibit the activity of one or more of FLT3, mutations of FLT3 (e.g., mutations in the juxtamembrane region of FLT3, mutations in the kinase domain of FLT3, FLT3 point mutations, FLT3 internal tandem duplication mutations, the FLT3-ITD mutation, the D835Y FLT3 mutation, the D835V FLT3 mutation, the F691L FLT3 mutation, or the R834Q FLT3 mutation), IRAK4 (interleukin-1 receptor associated kinase 4), isoforms of IRAK4, mutations of IRAK4, IRAK1 (interleukin-1 receptor associated kinase 1), isoforms of IRAK1, and/or mutations of IRAK1. In some embodiments, the compounds of the disclosure can inhibit the activity of one or both of FLT3 and mutations of FLT3 (e.g., mutations in the juxtamembrane region of FLT3, mutations in the kinase domain of FLT3, FLT3 point mutations, FLT3 internal tandem duplication mutations, the FLT3-ITD mutation, the D835Y FLT3 mutation, the D835V FLT3 mutation, the F691L FLT3 mutation, or the R834Q FLT3 mutation) and optionally inhibits one or more of IRAK4, isoforms of IRAK4, mutations of IRAK4, IRAK1, isoforms of IRAK1, or mutations of IRAK1. In some embodiments, the compounds of the disclosure can inhibit the activity of one or both of FLT3 and mutations of FLT3 (e.g., mutations in the juxtamembrane region of FLT3, mutations in the kinase domain of FLT3, FLT3 point mutations, FLT3 internal tandem duplication mutations, the FLT3-ITD mutation, the D835Y FLT3 mutation, the D835V FLT3 mutation, the F691L FLT3 mutation, or the R834Q FLT3 mutation) and optionally inhibits one or both of IRAK4 and IRAK1, or an isoform or mutation thereof. In some embodiments, the compounds of the disclosure can inhibit FLT3 in combination with IRAK4, IRAK1, or with IRAK4 and IRAK1. [00398] In some embodiments, compounds exhibit inhibitory activity against IRAK and/or FLT-3 with activities ≥ 1 µM, e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 nM, or even greater. In some embodiments, the compounds exhibit inhibitory activity against IRAK and/or FLT-3 with activities between 0.1 nM and 1 nM, e.g., about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 or 1.0 nM. In some embodiments, compounds described herein exhibit inhibitory activity against IRAK and/or FLT-3 with activities ≤ 0.1 µM, e.g., about 1, 2, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 nM. Ranges of values using a combination of any of the values recited herein as upper and/or lower limits are also contemplated, for example, but not limited to, 1-10 nM, 10- 100 nM, 1-100 nM, 0.1-1 nM, 0.1-100 nM, 0.1-200 nM, 1-200 nM, 10-200 nM, 100-200 nM, 200-500 nM, 0.1-500 nM, 1-500 nM, 10-500 nM, 500-1000 nM, 0.1-1000 nM, 1-1000 nM, 10- 1000 nM, or 100-1000 nM. In some embodiments, the inhibitory activity is less than 0.1 nM, less than 1 nM, less than 10 nM, less than 100 nM, or less than 1000 nM. In some embodiments, the inhibitory activity is in the range of about 1-10 nM, 10-100 nM, 0.1-1 µM, 1-10 µM, 10-100 µM, 100-200 µM, 200-500 µM, or even 500-1000 µM. It is understood that for purposes of quantification, the terms “activity,” “inhibitory activity,” “biological activity,” “IRAK activity,” “IRAK1 activity,” “IRAK4 activity,” “FLT-3 activity,” and the like in the context of an inhibitory compound disclosed herein can be quantified in a variety of ways known in the art. Unless indicated otherwise, as used herein such terms refer to IC₅₀ in the customary sense (i.e., concentration to achieve half-maximal inhibition. [00399] In some embodiments, hematopoietic cancers that can be treated in an animal (e.g., mammals, porcine, canine, avian (e.g., chicken), bovine, feline, primates, rodents, monkeys, rabbits, mice, rats, and humans) using a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) include, but are not limited to hematopoietic cancers and cancers of the myeloid line of blood cells, cancers with an increased risk of occurrence due to other blood disorders, cancers with an increased risk of occurrence due to chemical exposure (e.g., anti-cancer therapies or occupational chemical exposure), cancers with an increased risk of occurrence due to ionizing radiation (e.g., anti-cancer therapies), cancers evolving from myelodysplastic syndromes, cancers evolving from myeloproliferative disease, and cancers of the B cells. [00400] In some embodiments, hematopoietic cancers that can be treated include, but are not limited to, MDS, AML, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non- Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL) (e.g. ABC DLBCL with MYD88 mutation (e.g., L265P)), follicular lymphoma, or marginal zone lymphoma, or combinations thereof. [00401] In some embodiments, cancers characterized by dysregulated IRAK expression (IRAK1 and/or IRAK4) and/or IRAK-meidated intracellular signaling, can be treated, and include, but are not limited to, glioblastoma multiforme, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer, and the like, and combinations thereof. [00402] In some embodiments, compounds of the present disclosure can be used to inhibit targets in the context of additional conditions characterized by overactive IRAK1 and/or IRAK4. According to particular aspects of the disclosure, compounds of the present disclosure can be used to inhibit overactive IRAK1 and/or IRAK4 in conditions such as inflammatory diseases and autoimmune disease, wherein said inflammatory diseaess and autoimmune diseases are characterized by overactive IRAK1 and/or IRAK4. In some embodiments, inflammatory and autoimmune diseases characterized by dysregulated (e.g., hyperactive) IRAK expression (IRAK1 and/or IRAK4) and/or IRAK-mediated intracellular signaling, can be treated, and include, but are not limited to, chronic inflammation (i.e., associated with viral and bacterial infection), sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, and the like, and combinations thereof. [00403] In certain embodiments, MDS that can be treated in a subject (e.g., mammals, porcine, canine, avian (e.g., chicken), bovine, feline, primates, rodents, monkeys, rabbits, mice, rats, and humans) using a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) include but are not limited to MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2, refractory cytopenia with unilineage dysplasia (e.g., refractory anemia, refractory neutropenia, and refractory thrombocytopenia), refractory anemia with ring sideroblasts, refractory cytopenia with multilineage dysplasia (e.g., refractory cytopenia with multilineage dysplasia and ring sideroblasts and animals/humans with pathological changes not restricted to red cells such as prominent white cell precursor and platelet precursor (megakaryocyte) dysplasia), refractory anemias with excess blasts I and II, 5q-syndrome, megakaryocyte dysplasia with fibrosis, and refractory cytopenia of childhood. In some embodiments, MDS that can be treated include, but are not limited to, MDS that is inherited, MDS with an increased risk of occurrence due to an inherited predisposition, MDS with an increased risk of occurrence due to other blood disorders, MDS with an increased risk of occurrence due to chemical exposure, MDS with an increased risk of occurrence due to ionizing radiation, MDS with an increased risk of occurrence due to cancer treatment (e.g., a combination of radiation and the radiomimetic alkylating agents such as busulfan, nitrosourea, or procarbazine (with a latent period of 5 to 7 years) or DNA topoisomerase inhibitors), MDS evolving from acquired aplastic anemia following immunosuppressive treatment and Fanconi's anemia, MDS with an increased risk due to an mutation in splicing factors, MDS with an increased risk due to a mutation in isocitrate dehydrogenase 1, and MDS with an increased risk due to a mutation in isocitrate dehydrogenase 2. Animals that can be treated include but are not limited to mammals, rodents, primates, monkeys (e.g., macaque, rhesus macaque, pig tail macaque), humans, canine, feline, porcine, avian (e.g., chicken), bovine, mice, rabbits, and rats. In the methods, the term “subject” may refer to both human and non-human subjects. In some instances, the subject is in need of the treatment (e.g., by showing signs of disease, e.g. MDS, AML, cancer, autoimmune disease, inflammatory condition, etc., or by having a low blood cell count). [00404] In some embodiments, MDS that can be treated in a subject (e.g., mammals, porcine, canine, avian (e.g., chicken), bovine, feline, primates, rodents, monkeys, rabbits, mice, rats, and humans) using a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) include, but are not limited to MDS that can be treated by inhibiting one or more of FLT3 (e.g., using FLT3 inhibitors), mutations of FLT3 (e.g., using inhibitors of FLT3 mutants), IRAK4 (e.g., using IRAK4 inhibitors), mutations of IRAK4 (e.g., using inhibitors of IRAK4 mutants), IRAK1 (e.g., using IRAK 1 inhibitors), and/or mutations of IRAK1 (e.g., using inhibitors of IRAK1 mutant). In certain embodiments, MDS that can be treated include, but are not limited to MDS that can be treated by inhibiting IRAK4 (or its mutations), MDS that can be treated by inhibiting and IRAK1 (or its mutations), or MDS that can be treated by inhibiting IRAK4 (or its mutations) and IRAK1 (or its mutations). In some embodiments, MDS that can be treated include, but are not limited to MDS that can be treated by inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1. In some embodiments, inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1 provides for treating tumors with FLT3 mutations, which can be or become resistant to FLT3 inhibitors due to adaptive resistance mechanism(s), e.g., driven by IRAK. In some embodiments, MDS that can be treated is characterized by MDS having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the MDS is not driven by FLT3 mutations but expresses IRAK4- Long, based on the use of IRAK4L and the ratio of IRAK4L to IRAK4S (e.g., as described in U.S. Patent Application No.16/339,692; and Smith, M. A., et al. (2019). “U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies.” Nat Cell Biol 21(5): 640-650. DOI: 10.1038/s41556-019-0314-5, both incorporated by reference herein in their entirety). [00405] In some embodiments, AML that can be treated in a subject (e.g., mammals, porcine, canine, avian (e.g., chicken), bovine, feline, primates, rodents, monkeys, rabbits, mice, rats, and humans) using a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) include, but are not limited to AML that is inherited, AML with an increased risk of occurrence due to an inherited predisposition, AML with one or more recurrent genetic abnormality (e.g., with inversions or translocations, such as MLLT3/MLL which is a translocation between chromosome 9 and 11 (“MLL”) AML with translocation between chromosomes 8 and 21, AML with translocation or inversion in chromosome 16, AML with translocation between chromosomes 9 and 11, APL (M3) with translocation between chromosomes 15 and 17, AML with translocation between chromosomes 6 and 9, AML with translocation or inversion in chromosome 3, and the like), AML (megakaryoblastic) with a translocation between chromosomes 1 and 22, AML with myelodysplasia-related changes, AML related to previous chemotherapy or radiation (such as, for example, alkylating agent-related AML, topoisomerase II inhibitor-related AML, and the like), AML not otherwise categorized (does not fall into above categories - similar to FAB classification; such as, for example, AML minimally differentiated (M0), AML with minimal maturation (M1), AML with maturation (M2), acute myelomonocytic leukemia (M4), acute monocytic leukemia (M5), acute erythroid leukemia (M6), acute megakaryoblastic leukemia (M7), acute basophilic leukemia, acute panmyelosis with fibrosis, and the like), myeloid sarcoma (also known as granulocytic sarcoma, chloroma or extramedullary myeloblastoma), undifferentiated and biphenotypic acute leukemias (also known as mixed phenotype acute leukemias), AML with an increased risk of occurrence due to other blood disorders, AML with an increased risk of occurrence due to chemical exposure, AML with an increased risk of occurrence due to ionizing radiation, AML evolving from myelodysplastic syndromes, AML evolving from myeloproliferative disease, AML with an increased risk due to an FLT3 mutation, AML with an increased risk due to an FLT3 mutation in the juxtamembrane region of FLT3, AML with an increased risk due to an FLT3 mutation of an internal tandem duplication in the juxtamembrane region of FLT3, AML with an increased risk due to an FLT3 mutation in the kinase domain of FLT3, AML with an increased risk due to the FLT3 mutation D835Y, AML with an increased risk due to the FLT3 mutation D835V, AML with an increased risk due to the FLT3 mutation F691L, and AML with an increased risk due to the FLT3 mutation R834Q, and the like. In some embodiments, AML that can be treated include AML that by inhibiting one or more of FLT3 (e.g., using FLT3 inhibitors), mutations of FLT3 (e.g., using inhibitors of FLT3 mutants), IRAK4 (e.g., using IRAK4 inhibitors), mutations of IRAK4 (e.g., using inhibitors of IRAK4 mutants), IRAK1 (e.g., using IRAK 1 inhibitors), and/or mutations of IRAK1 (e.g., using inhibitors of IRAK1 mutant). In certain embodiments, AML that can be treated include, but are not limited to AML that can be treated by inhibiting IRAK4 (or its mutations), MDS that can be treated by inhibiting and IRAK1 (or its mutations), or AML that can be treated by inhibiting IRAK4 (or its mutations) and IRAK1 (or its mutations). In some embodiments, AML that can be treated include, but are not limited to AML that can be treated by inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1. In some embodiments, inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1 provides for treating tumors with FLT3 mutations which can be or become resistant to FLT3 inhibitors due to adaptive resistance mechanism(s), e.g., driven by IRAK. In some embodiments, AML that can be treated is characterized by AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the AML is not driven by FLT3 mutations but expresses IRAK4-Long, based on the use of IRAK4L and the ratio of IRAK4L to IRAK4S (e.g., as described in U.S. Patent Application No.16/339,692; and Smith, M. A., et al. (2019). “U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies.” Nat Cell Biol 21(5): 640-650. DOI: 10.1038/s41556-019- 0314-5, both incorporated by reference herein in their entirety). [00406] In some embodiments, hematopoietic cancers that can be treated in a subject (e.g., mammals, porcine, canine, avian (e.g., chicken), bovine, feline, primates, rodents, monkeys, rabbits, mice, rats, and humans) using a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) include, but are not limited to hematopoietic cancers (e.g. MDS, AML, DLBCL, and the like, as described previously) that can be treated by inhibiting (e.g., reducing the activity or expression of) one or more of FLT3 (e.g., using FLT3 inhibitors), mutations of FLT3 (e.g., using inhibitors of FLT3 mutants), IRAK4 (e.g., using IRAK4 inhibitors), isoforms of IRAK4, mutations of IRAK4 (e.g., using inhibitors of IRAK4 mutants), IRAK1 (e.g., using IRAK 1 inhibitors), isoforms of IRAK1, or mutations of IRAK1 (e.g., using inhibitors of IRAK1 mutants). In certain embodiments, hematopoietic cancers that can be treated include, but are not limited to cancers that can be treated by inhibiting (e.g., reducing the activity or expression of) FLT3 (or its mutations) and IRAK4 (or its mutations), hematopoietic cancers that can be treated by inhibiting (e.g., reducing the activity or expression of) FLT3 (or its mutations) and IRAK1 (or its mutations), or hematopoietic cancers that can be treated by inhibiting (e.g., reducing the activity or expression of) FLT3 (or its mutations), IRAK4 (or its isoforms or mutations), and IRAK1 (or its isoforms or mutations). In some embodiments, hematopoietic cancer that can be treated include, but are not limited to hematopoietic cancer that can be treated by inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1. In some embodiments, inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1 provides for treating tumors with FLT3 mutations which can be or become resistant to FLT3 inhibitors due to adaptive resistance mechanism(s), e.g., driven by IRAK. In some embodiments, hematopoietic cancer that can be treated is characterized by hematopoietic cancer having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the hematopoietic cancer is not driven by FLT3 mutations but expresses IRAK4-Long, based on the use of IRAK4L and the ratio of IRAK4L to IRAK4S (e.g., as described in U.S. Patent Application No.16/339,692; and Smith, M. A., et al. (2019). “U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies.” Nat Cell Biol 21(5): 640-650. DOI: 10.1038/s41556-019-0314-5, both incorporated by reference herein in their entirety). [00407] In some embodiments, cancers that can be treated include, but are not limited to, glioblastoma multiforme, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer, and the like, and combinations thereof, that can be treated by inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1. In some embodiments, inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1 provides for treating tumors with FLT3 mutations which can be or become resistant to FLT3 inhibitors due to adaptive resistance mechanism(s), e.g., driven by IRAK. In some embodiments, cancer that can be treated is characterized by cancer having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the cancer is not driven by FLT3 mutations but expresses IRAK4- Long, based on the use of IRAK4L and the ratio of IRAK4L to IRAK4S (e.g., as described in U.S. Patent Application No.16/339,692; and Smith, M. A., et al. (2019). “U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies.” Nat Cell Biol 21(5): 640-650. DOI: 10.1038/s41556-019-0314-5, both incorporated by reference herein in their entirety). [00408] In some embodiments, inflammatory and autoimmune diseases characterized by dysregulated (e.g., hyperactive) IRAK expression (IRAK1 and/or IRAK4) and/or IRAK- meidated intracellular signaling, that can be treated include, but are not limited to, chronic inflammation (i.e., associated with viral and bacterial infection), sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, colitis, Crohn’s disease, atopic dermatitis, and the like, and combinations thereof, that can be treated by inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1. In some embodiments, inhibiting FLT3 in combination with IRAK4, IRAK1, or both IRAK4 and IRAK1 provides for treating inflammatory and autoimmune diseases with FLT3 mutations which can be or become resistant to FLT3 inhibitors due to adaptive resistance mechanism(s), e.g., driven by IRAK. In some embodiments, inflammatory and autoimmune disease that can be treated is characterized by inflammatory and autoimmune disease having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the inflammatory and autoimmune disease is not driven by FLT3 mutations but expresses IRAK4-Long, based on the use of IRAK4L and the ratio of IRAK4L to IRAK4S (e.g. as described in U.S. Patent Application No.16/339,692; and Smith, M. A., et al. (2019). “U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies.” Nat Cell Biol 21(5): 640-650. DOI: 10.1038/s41556-019-0314-5, both incorporated by reference herein in their entirety). [00409] As related to treating MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2), treating can include but is not limited to prophylactic treatment and therapeutic treatment. As such, treatment can include, but is not limited to: preventing MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); reducing the risk of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); ameliorating or relieving symptoms of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); eliciting a bodily response against MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); inhibiting the development or progression of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); inhibiting or preventing the onset of symptoms associated with MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); reducing the severity of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); causing a regression of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2) or one or more of the symptoms associated with MDS (e.g., an increase in blood cell count); causing remission of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); causing remission of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2) by preventing or minimizing FLT3 mutations (e.g., internal tandem duplication mutations or the D835Y mutation); preventing relapse of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); or preventing relapse of MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2) in animals/humans that have intrinsic or acquired resistance to other MDS treatments. In some embodiments, treating does not include prophylactic treatment of MDS (e.g., preventing or ameliorating future MDS). [00410] As related to treating hematopoietic cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, or Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation (e.g., ABC DLBCL with MYD88 mutation L265P), follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like), treating can include but is not limited to prophylactic treatment and therapeutic treatment. As such, treatment can include, but is not limited to: preventing cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, or Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); reducing the risk of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, or Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); ameliorating or relieving symptoms of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, or Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); eliciting a bodily response against cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, or Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); inhibiting the development or progression of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, or Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); inhibiting or preventing the onset of symptoms associated with cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, or Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); reducing the severity of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); causing a regression of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like) or one or more of the symptoms associated with cancer (e.g., a decrease in tumor size); causing remission of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); causing remission of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like) by preventing or minimizing FLT3 mutations (e.g., internal tandem duplication mutations or the D835Y mutation); causing remission of acute myeloid leukemia by preventing or minimizing FLT3 mutations (e.g., internal tandem duplication mutations or the D835Y mutation); preventing relapse of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like); preventing relapse of cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like) in animals/humans that have intrinsic or acquired resistance to other cancer treatments (e.g., from some FLT3 inhibitors or from MLL); or preventing relapse of acute myeloid leukemia in animals/humans that have intrinsic or acquired resistance to other cancer treatments (e.g., from some FLT3 inhibitors or from MLL). In some embodiments, treating does not include prophylactic treatment of cancer (e.g., preventing or ameliorating future cancer). [00411] Treatment of a subject can occur using any suitable administration method (such as those disclosed herein) and using any suitable amount of a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106). In some embodiments, methods of treatment comprise treating an animal or human for MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2). In some embodiments, methods of treatment comprise treating an animal or human for a hematopoietic cancer (e.g., acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like). Other embodiments include treatment after one or more of having a blood disorder, having myelodysplastic syndrome, having myeloproliferative disease, an occurrence of chemical exposure, an exposure to ionizing radiation, or a treatment for a hematopoietic cancer (e.g., with chemotherapy, ionizing radiation, or both). Some embodiments of the disclosure include a method for treating a subject (e.g., an animal such as a human or primate) with a composition comprising a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) (e.g., a pharmaceutical composition) which comprises one or more administrations of one or more such compositions; the compositions may be the same or different if there is more than one administration. [00412] In some embodiments, the method of treatment includes administering to a subject an effective amount of a composition comprising a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106). As used herein, the term “effective amount” refers to a dosage or a series of dosages sufficient to affect treatment (e.g., to treat MDS such as but not limited to MDS (e.g., MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, or MDS with a mutation in isocitrate dehydrogenase 2); or to treat a hematopoietic cancer, such as but not limited to acute myeloid leukemia, lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL MYD88 mutation, follicular lymphoma, or marginal zone lymphoma, and combinations thereof, and the like) in a subject. In some embodiments, an effective amount can encompass a therapeutically effective amount, as disclosed herein. In certain embodiments, an effective amount can vary depending on the subject and the particular treatment being affected. The exact amount that is required can, for example, vary from subject to subject, depending on the age and general condition of the subject, the particular adjuvant being used (if applicable), administration protocol, and the like. As such, the effective amount can, for example, vary based on the particular circumstances, and an appropriate effective amount can be determined in a particular case. An effective amount can, for example, include any dosage or composition amount disclosed herein. In some embodiments, an effective amount of at least one compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) (which can be administered to a subject such as mammals, primates, monkeys or humans) can be an amount of about 0.005 to about 50 mg/kg body weight, about 0.01 to about 15 mg/kg body weight, about 0.1 to about 10 mg/kg body weight, about 0.5 to about 7 mg/kg body weight, about 0.005 mg/kg, about 0.01 mg/kg, about 0.05 mg/kg, about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, about 3 mg/kg, about 5 mg/kg, about 5.5 mg/kg, about 6 mg/kg, about 6.5 mg/kg, about 7 mg/kg, about 7.5 mg/kg, about 8 mg/kg, about 10 mg/kg, about 12 mg/kg, or about 15 mg/kg. In regard to some embodiments, the dosage can be about 0.5 mg/kg body weight or about 6.5 mg/kg body weight. In some instances, an effective amount of at least one compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) (which can be administered to a subject such as mammals, rodents, mice, rabbits, feline, porcine, or canine) can be an amount of about 0.005 to about 50 mg/kg body weight, about 0.01 to about 15 mg/kg body weight, about 0.1 to about 10 mg/kg body weight, about 0.5 to about 7 mg/kg body weight, about 0.005 mg/kg, about 0.01 mg/kg, about 0.05 mg/kg, about 0.1 mg/kg, about 1 mg/kg, about 5 mg/kg, about 10 mg/kg, about 20 mg/kg, about 30 mg/kg, about 40 mg/kg, about 50 mg/kg, about 80 mg/kg, about 100 mg/kg, or about 150 mg/kg. In some embodiments, an effective amount of at least one compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) (which can be administered to an animal such as mammals, primates, monkeys or humans) can be an amount of about 1 to about 1000 mg/kg body weight, about 5 to about 500 mg/kg body weight, about 10 to about 200 mg/kg body weight, about 25 to about 100 mg/kg body weight, about 1 mg/kg, about 2 mg/kg, about 5 mg/kg, about 10 mg/kg, about 25 mg/kg, about 50 mg/kg, about 100 mg/kg, about 150 mg/kg, about 200 mg/kg, about 300 mg/kg, about 400 mg/kg, about 500 mg/kg, about 600 mg/kg, about 700 mg/kg, about 800 mg/kg, about 900 mg/kg, or about 1000 mg/kg. In regard to some conditions, the dosage can be about 20 mg/kg human body weight or about 100 mg/kg human body weight. In some instances, an effective amount of at least one compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) (which can be administered to an animal such as mammals, rodents, mice, rabbits, feline, porcine, or canine) can be an amount of about 1 to about 1000 mg/kg body weight, about 5 to about 500 mg/kg body weight, about 10 to about 200 mg/kg body weight, about 25 to about 100 mg/kg body weight, about 1 mg/kg, about 2 mg/kg, about 5 mg/kg, about 10 mg/kg, about 25 mg/kg, about 50 mg/kg, about 100 mg/kg, about 150 mg/kg, about 200 mg/kg, about 300 mg/kg, about 400 mg/kg, about 500 mg/kg, about 600 mg/kg, about 700 mg/kg, about 800 mg/kg, about 900 mg/kg, or about 1000 mg/kg. [00413] In some embodiments, the treatments can also include one or more of surgical intervention, chemotherapy, radiation therapy, hormone therapies, immunotherapy, and adjuvant systematic therapies. Adjuvants may include but are not limited to chemotherapy (e.g., temozolomide), radiation therapy, antiangiogenic therapy (e.g., bevacizumab), and hormone therapies, such as administration of LHRH agonists; anti-estrogens, such as tamoxifen; high-dose progestogens; aromatase inhibitors; and/or adrenalectomy. Chemotherapy can be used as a single-agent or as a combination with known or new therapies. [00414] In some embodiments, the administration to a subject of at least one compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) is an adjuvant cancer therapy or part of an adjuvant cancer therapy. Adjuvant treatments include treatments by the mechanisms disclosed herein and of cancers as disclosed herein, including, but not limited to tumors. Corresponding primary therapies can include, but are not limited to, surgery, chemotherapy, or radiation therapy. In some instances, the adjuvant treatment can be a combination of chemokine receptor antagonists with traditional chemotoxic agents or with immunotherapy that increases the specificity of treatment to the cancer and potentially limits additional systemic side effects. In still other embodiments, a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) can be used as adjuvant with other chemotherapeutic agents. The use of a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) may, in some instances, reduce the duration of the dose of both drugs and drug combinations reducing the side effects. [00415] In some embodiments, the administration to a subject may decrease the incidence of one or more symptoms associated with MDS / AML / a type of hematopoietic cancer. In some embodiments, the administration may decrease marrow failure, immune dysfunction, transformation to overt leukemia, or combinations thereof in said subject, as compared to a subject not receiving said composition. [00416] In some embodiments, the method may decrease a marker of viability of MDS cells AML cells, or cancer cells in a subject. In one aspect, the method may decrease a marker of viability of MDS, AML, and/or cancer cells. The marker may be selected from survival over time, proliferation, growth, migration, formation of colonies, chromatic assembly, DNA binding, RNA metabolism, cell migration, cell adhesion, inflammation, or a combination thereof. [00417] In one embodiment, the crystalline forms described herein and/or the compositions comprising the crystalline forms described herein are used in one or more administrations, together with or in combination with a CDK inhibitor. Various CDK isoforms play key roles in regulating cell cycle progression in a variety of cell types and these pathways become dysregulated in hematopoietic cancers and solid tumors. Nonselective CDK inhibitors have shown efficacy in various hematological cancer models (Whittaker S.R. et al., Pharmacology & Therapeutics (2017) 173:83-105). In one embodiment, the CDK inhibitor is a CDK9 inhibitor. [00418] The cyclin-dependent kinase 9 (CDK9) pathway is dysregulated in AML and therefore targeting this pathway is an attractive approach to treat AML. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As first generation CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety. In one embodiment, the CDK9 inhibitor is alvocidib, a multi-serine threonine cyclin-dependent kinase inhibitor with demonstrable in vitro and clinical activity in AML when combined in a timed sequential chemotherapy regimen. In another embodiment, the CDK9 inhibitor is BAY1143752 (atuveciclib) which has demonstrated antiproliferative activity against HeLa and MOLM-12 AML cells in vitro. BAY1143752 also significantly reduced the growth of MOLM-13 and MV4-11 tumor xenografts in nude mice and rats, respectively, and was well-tolerated in both models. In another embodiment, the CDK9 inhibitor is NVP-2, which displays anti-proliferative activity against multiple leukemia cell lines and induces MCL-1 loss and apoptosis within four hours in MOLT4 ALL cells. In yet another embodiment, the CDK inhibitor is THAL-SNS-032, which has been shown to selectively induce CDK9 degradation with little effect on the protein levels of other CDKs, despite retaining its ability to block their kinase activity. Combination Therapies [00419] In some embodiments, the treatments disclosed herein can include use of other drugs (e.g., antibiotics) or therapies for treating disease, e.g., MDS / AML / a type of hematopoietic cancer. For example, antibiotics can be used to treat infections and can be combined with a compound of the disclosure to treat disease (e.g., infections). In other embodiments, intravenous immunoglobulin (IVIG) therapy can be used as part of the treatment regime (i.e., in addition to administration of the compound(s) of the disclosure). For example, treatment regimens for various types of cancers can involve one or more elements selected from chemotherapy, targeted therapy, alternative therapy, immunotherapy, and the like. [00420] Accordingly, in some embodiments, the compounds and/or compositions described herein can be used in one or more administrations to a subject, in combination with one or more BCL2 inhibitor, BTK inhibitor, chemotherapy, targeted therapy, alternative therapy, immunotherapy, DNA methyltransferase inhibitor/hypomethylating agent, anthracycline, histone deacetylase (HDAC) inhibitor, purine nucleoside analogue (antimetabolite), isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, antibody-drug conjugate, mAbs/immunotherapy, CAR-T cell therapy, Plk inhibitor, MEK inhibitor, CDK9 inhibitor, CDK8 inhibitor, retinoic acid receptor agonist, TP53 activator, smoothened receptor antagonist, ERK inhibitor, PI3K inhibitor, mTOR inhibitor, glucocorticoid receptor modulator, or EZH2 inhibitor, and the like, or one or more combinations thereof, where the compositions may be the same or different if there is more than one administration. In some embodiments, if there is more than one administration at least one composition used for at least one administration is different from the composition of at least one other administration. [00421] In particular, IRAK inhibitors have been demonstrated to have synergistic effects when administered in combination with an apoptosis modulator/inhibitor, such as a BCL2 inhibitor. As described in U.S. Patent Application No.16/804,518 (incorporated herein by reference in its entirety), an exemplary apoptosis/BCL2 inhibitor has been shown to have a synergistic effect when used in combination with an exemplary IRAK inhibitor in multiple AML cell lines. Venetoclax was used as a representative apoptosis/BCL2 inhibitor. [00422] When a concentration of an exemplary IRAK inhibitor was combined with venetoclax, the potency of venetoclax was increased by an unexpectedly high ~50-fold. According to particular aspects of the disclosure, this synergistic combination allows for increased efficacy of venetoclax at lower doses, to provide for avoiding at least some of the toxicity observed in the clinic. According to particular aspects, the degree of interaction is dependent on the dose ratio combination that is used, with lower concentrations of the exemplary IRAK inhibitor providing larger shifts in the venetoclax IC50. This unexpected and dramatic shift in the venetoclax IC50 is substantially more than an additive response and demonstrates the unexpected synergistic interaction of the two drugs even in cell lines that do not express activated FLT3 mutants. [00423] Accordingly, the present disclosure encompasses methods for treating a disease or disorder which is responsive to inhibition of IRAK, comprising administration to a subject of a composition comprising an IRAK inhibiting compound, wherein some embodiments of the method can further involve administration of an apoptotic modulator. The apoptotic modulator may comprise a BTK and/or a BCL2 inhibitor. BTK and BCL2 inhibitors may be, for example, those known in the art. In some embodiments, the method may comprise the step of administering to the subject an apoptotic modulator. In some embodiments, the apoptotic modulator may comprise a BCL2 inhibitor selected from ABT-263 (Navitoclax), ABT-737, ABT-199 (venetoclax), GDC-0199, GX15-070 (Obatoclax) (all available from Abbott Laboratories), HA14-1, S1, 2-methoxy antimycin A3, gossypol, AT-101, apogossypol, WEHI- 539, A-1155463, BXI-61, BXI-72, TW37, MIM1, UMI-77, and the like, and combinations thereof. One skilled in the art would appreciate that there are many known BCL2 inhibitors which can be used in accordance with the present disclosure. In some embodiments, the BCL2 inhibitor comprises venetoclax. [00424] In some embodiments, the administration step comprises administration to a subject of a composition comprising an IRAK inhibiting compound and a BCL2 inhibitor. In some embodiments, the administration step comprises administration of a composition comprising an IRAK inhibiting compound in combination with a composition comprising a BCL2 inhibitor. [00425] In some embodiments, the IRAK inhibiting compound is a compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) or an isomer, derivative or analog thereof, and the BCL2 inhibitor is venetoclax, or a a salt, isomer, derivative or analog thereof. [00426] In some embodiments, the method can further involve administration to a subject of an immune modulator. The immune modulator can include, for example, Lenalidomide (Revlamid; Celgene Corporation). In some embodiments, the method can involve administration of an epigenetic modulator. The epigenetic modulator can include, for example, a hypomethylating agent such as azacitidine, decitabine, or a combination thereof. [00427] In some embodiments, the compounds and/or compositions described herein can be used in one or more administrations to a subject, together with or in combination with one or more BTK inhibitor, such as, for example, ibrutinib, or a salt, isomer, derivative or analog thereof. [00428] For example, the compounds and/or compositions described herein can be used in one or more administrations, together with or in combination with a DNA methyltransferase inhibitor/hypomethylating agent, such as, for example, azacytidine, decitabine, cytarabine, and/or guadecitabine; an anthracycline, such as, for example, daunorubicin, idarubicin, doxorubicin, mitoxantrone, epirubicin, and/or CPX-351 (a combination cytarabine and daunorubicin in a fixed 5:1 molar ratio), and the like; a histone deacetylase (HDAC) inhibitor, such as, for example, vorinostat, panobinostat, valproic acid, and/or pracinostat, and the like; a purine nucleoside analogue (antimetabolite), such as, for example, fludarabine, cladribine, and/or clofarabine, and the like; an isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, such as, for example, ivosidenib and/or enasidenib, and the like; an antibody-drug conjugate, such as, for example, Anti-CD33 (e.g. Ac225-lintuzumab, vadastuximab, or gemtuzumab-ozogamicin) and/or Anti-CD45 (e.g. I¹³¹-apamistamab), and the like; an mAbs/Immunotherapy, such as, for example, Anti-CD70 (e.g. ARGX-110, cusatuzumab), a bispecific antibody (e.g. floteuzumab (CD123 x CD3)), Anti-CTLA4 (e.g. ipilimumab), Anti-PD1/PDL1 (e.g. nivolumab, pembrolizumab, atezolizumab, avelumab, PDR001, MBG453), and/or Anti-CD47 (e.g.5F9 (Magrolimab)), and the like; a Plk inhibitor, such as, for example, volasertib and/or rigosertib, and the like; a MEK inhibitor, such as, for example, trametinib, cobimetinib, selumetinib, pimasertib, and/or refametinib, and the like; a CDK9 inhibitor, such as, for example, alvocidib and/or voruciclib, and the like; a CDK8 inhibitor, such as, for example, SEL120, and the like; a retinoic acid receptor agonist, such as, for example, ATRA (all-trans retinoic acid) and/or SY- 1425 (a selective RARα agonist), and the like; a TP53 activator, such as, for example, APR-246 (Eprenetapopt), and the like; a smoothened receptor antagonist, such as, for example, glasdegib, and the like; an ERK inhibitor, such as, for example, an ERK2/MAPK1 or ERK1/MAPK3 inhibitor, such as, for example, ulixertinib, SCH772984, ravoxertinib, MK-8353, and/or VTX- 11e, and the like; a PI3K inhibitor, such as, for example, fimepinostat (CUDC-907), alpelisib, leniolisib (CDZ-173), pilaralisib (XL147, SAR245408), and/or bimiralisib (PQR-309), and the like; an mTOR inhibitor, such as, for example, bimiralisib (PQR-309), sapanisertib (TAK-228, INK-128), ridaforolimus (MK-8669, AP-23573), everolimus, and/or vistusertib (AZD2014), and the like; a glucocorticoid receptor modulator, such as, for example, an agonist comprising prednisolone, beclometasone, methylprednisolone, prednisone, fluticasone, budesonide, dexamethasone, and/or cortisol, and/or an antagonist comprising mifepristone, miricorilant, and/or onapristone, and/or another binding ligand comprising vamorolone (VBP15), and the like; and/or an EZH2 inhibitor, such as, for example, tazemetostat, and the like. In some embodiments, compounds and pharmaceutical compositions including the same can be used in prevention of secondary malignancies when used in combination with an EZH2 inhibitor. Further therapies are described below and are contemplated in combination therapies in the context of the present disclosure. Chemotherapy / Targeted Therapy / Alternative Therapy [00429] Cancers are commonly treated with chemotherapy and/or targeted therapy and/or alternative therapy. Chemotherapies act by indiscriminately targeting rapidly dividing cells, including healthy cells as well as tumor cells, whereas targeted cancer therapies rather act by interfering with specific molecules, or molecular targets, which are involved in cancer growth and progression. Targeted therapy generally targets cancer cells exclusively, having minimal damage to normal cells. Chemotherapies and targeted therapies which are approved and/or in the clinical trial stage are known to those skilled in the art. Any such compound can be utilized in the practice of the present disclosure. [00430] For example, approved chemotherapies include abitrexate (Methotrexate Injection), abraxane (Paclitaxel Injection), adcetris (Brentuximab Vedotin Injection), adriamycin (Doxorubicin), adrucil Injection (5-FU (fluorouracil)), afinitor (Everolimus), afinitor Disperz (Everolimus), alimta (PEMETREXED), alkeran Injection (Melphalan Injection), alkeran Tablets (Melphalan), aredia (Pamidronate), arimidex (Anastrozole), aromasin (Exemestane), arranon (Nelarabine), arzerra (Ofatumumab Injection), avastin (Bevacizumab), beleodaq (Belinostat Injection), bexxar (Tositumomab), BiCNU (Carmustine), blenoxane (Bleomycin), blincyto (Blinatumoma b Injection), bosulif (Bosutinib), busulfex Injection (Busulfan Injection), campath (Alemtuzumab), camptosar (Irinotecan), caprelsa (Vandetanib), casodex (Bicalutamide), CeeNU (Lomustine), CeeNU Dose Pack (Lomustine), cerubidine (Daunorubicin), clolar (Clofarabine Injection), cometriq (Cabozantinib), cosmegen (Dactinomycin), cotellic (Cobimetinib), cyramza (Ramucirumab Injection), cytosarU (Cytarabine), cytoxan (Cytoxan), cytoxan Injection (Cyclophosphamide Injection), dacogen (Decitabine), daunoXome (Daunorubicin Lipid Complex Injection), decadron (Dexamethasone), depoCyt (Cytarabine Lipid Complex Injection), dexamethasone Intensol (Dexamethasone), dexpak Taperpak (Dexamethasone), docefrez (Docetaxel), doxil (Doxorubicin Lipid Complex Injection), droxia (Hydroxyurea), DTIC (Decarbazine), eligard (Leuprolide), ellence (Ellence (epirubicin)), eloxatin (Eloxatin (oxaliplatin)), elspar (Asparaginase), emcyt (Estramustine), erbitux (Cetuximab), erivedge (Vismodegib), erwinaze (Asparaginase Erwinia chrysanthemi), ethyol (Amifostine), etopophos (Etoposide Injection), eulexin (Flutamide), fareston (Toremifene), farydak (Panobinostat), faslodex (Fulvestrant), femara (Letrozole), firmagon (Degarelix Injection), fludara (Fludarabine), folex (Methotrexate Injection), folotyn (Pralatrexate Injection), FUDR (FUDR (floxuridine)), gazyva (Obinutuzumab Injection), gemzar (Gemcitabine), gilotrif (Afatinib), gleevec (Imatinib Mesylate), Gliadel Wafer (Carmustine wafer), Halaven (Eribulin Injection), Herceptin (Trastuzumab), Hexalen (Altretamine), Hycamtin (Topotecan), Hycamtin (Topotecan), Hydrea (Hydroxyurea), Ibrance (Palbociclib), Iclusig (Ponatinib), Idamycin PFS (Idarubicin), Ifex (Ifosfamide), Imbruvica (Ibrutinib), Inlyta (Axitinib), Intron A alfab (Interferon alfa-2a), Iressa (Gefitinib), Istodax (Romidepsin Injection), Ixempra (Ixabepilone Injection), Jakafi (Ruxolitinib), Jevtana (Cabazitaxel Injection), Kadcyla (Ado-trastuzumab Emtansine), Keytruda (Pembrolizumab Injection), Kyprolis (Carfilzomib), Lanvima (Lenvatinib), Leukeran (Chlorambucil), Leukine (Sargramostim), Leustatin (Cladribine), Lonsurf (Trifluridine and Tipiracil), Lupron (Leuprolide), Lupron Depot (Leuprolide), Lupron DepotPED (Leuprolide), Lynparza (Olaparib), Lysodren (Mitotane), Marqibo Kit (Vincristine Lipid Complex Injection), Matulane (Procarbazine), Megace (Megestrol), Mekinist (Trametinib), Mesnex (Mesna), Mesnex (Mesna Injection), Metastron (Strontium-89 Chloride), Mexate (Methotrexate Injection), Mustargen (Mechlorethamine), Mutamycin (Mitomycin), Myleran (Busulfan), Mylotarg (Gemtuzumab Ozogamicin), Navelbine (Vinorelbine), Neosar Injection (Cyclophosphamide Injection), Neulasta (filgrastim), Neulasta (pegfilgrastim), Neupogen (filgrastim), Nexavar (Sorafenib), Nilandron (Nilandron (nilutamide)), Nipent (Pentostatin), Nolvadex (Tamoxifen), Novantrone (Mitoxantrone), Odomzo (Sonidegib), Oncaspar (Pegaspargase), Oncovin (Vincristine), Ontak (Denileukin Diftitox), onxol (Paclitaxel Injection), opdivo (Nivolumab Injection), panretin (Alitretinoin), paraplatin (Carboplatin), perjeta (Pertuzumab Injection), platinol (Cisplatin), platinol (Cisplatin Injection), platinolAQ (Cisplatin), platinolAQ (Cisplatin Injection), pomalyst (Pomalidomide), prednisone Intensol (Prednisone), proleukin (Aldesleukin), purinethol (Mercaptopurine), reclast (Zoledronic acid), revlimid (Lenalidomide), rheumatrex (Methotrexate), rituxan (Rituximab), roferonA alfaa (Interferon alfa-2a), rubex (Doxorubicin), sandostatin (Octreotide), sandostatin LAR Depot (Octreotide), soltamox (Tamoxifen), sprycel (Dasatinib), sterapred (Prednisone), sterapred DS (Prednisone), stivarga (Regorafenib), supprelin LA (Histrelin Implant), sutent (Sunitinib), sylatron (Peginterferon Alfa-2b Injection (Sylatron)), sylvant (Siltuximab Injection), synribo (Omacetaxine Injection), tabloid (Thioguanine), taflinar (Dabrafenib), tarceva (Erlotinib), targretin Capsules (Bexarotene), tasigna (Decarbazine), taxol (Paclitaxel Injection), taxotere (Docetaxel), temodar (Temozolomide), temodar (Temozolomide Injection), tepadina (Thiotepa), thalomid (Thalidomide), theraCys BCG (BCG), thioplex (Thiotepa), TICE BCG (BCG), toposar (Etoposide Injection), torisel (Temsirolimus), treanda (Bendamustine hydrochloride), trelstar (Triptorelin Injection), trexall (Methotrexate), trisenox (Arsenic trioxide), tykerb (lapatinib), unituxin (Dinutuximab Injection), valstar (Valrubicin Intravesical), vantas (Histrelin Implant), vectibix (Panitumumab), velban (Vinblastine), velcade (Bortezomib), vepesid (Etoposide), vepesid (Etoposide Injection), vesanoid (Tretinoin), vidaza (Azacitidine), vincasar PFS (Vincristine), vincrex (Vincristine), votrient (Pazopanib), vumon (Teniposide), wellcovorin IV (Leucovorin Injection), xalkori (Crizotinib), xeloda (Capecitabine), xtandi (Enzalutamide), yervoy (Ipilimumab Injection), yondelis (Trabectedin Injection), zaltrap (Ziv-aflibercept Injection), zanosar (Streptozocin), zelboraf (Vemurafenib), zevalin (Ibritumomab Tiuxetan), zoladex (Goserelin), zolinza (Vorinostat), zometa (Zoledronic acid), zortress (Everolimus), zydelig (Idelalisib), zykadia (Ceritinib), zytiga (Abiraterone), and the like, in addition to analogs and derivatives thereof. For example, approved targeted therapies include ado-trastuzumab emtansine (Kadcyla), afatinib (Gilotrif), aldesleukin (Proleukin), alectinib (Alecensa), alemtuzumab (Campath), axitinib (Inlyta), belimumab (Benlysta), belinostat (Beleodaq), bevacizumab (Avastin), bortezomib (Velcade), bosutinib (Bosulif), brentuximab vedotin (Adcetris), cabozantinib (Cabometyx [tablet], Cometriq [capsule]), canakinumab (Ilaris), carfilzomib (Kyprolis), ceritinib (Zykadia), cetuximab (Erbitux), cobimetinib (Cotellic), crizotinib (Xalkori), dabrafenib (Tafinlar), daratumumab (Darzalex), dasatinib (Sprycel), denosumab (Xgeva), dinutuximab (Unituxin), elotuzumab (Empliciti), erlotinib (Tarceva), everolimus (Afinitor), gefitinib (Iressa), ibritumomab tiuxetan (Zevalin), ibrutinib (Imbruvica), idelalisib (Zydelig), imatinib (Gleevec), ipilimumab (Yervoy), ixazomib (Ninlaro), lapatinib (Tykerb), lenvatinib (Lenvima), necitumumab (Portrazza), nilotinib (Tasigna), nivolumab (Opdivo), obinutuzumab (Gazyva), ofatumumab (Arzerra, HuMax-CD20), olaparib (Lynparza),osimertinib (Tagrisso), palbociclib (Ibrance), panitumumab (Vectibix), panobinostat (Farydak), pazopanib (Votrient), pembrolizumab (Keytruda), pertuzumab (Perjeta), ponatinib (Iclusig), ramucirumab (Cyramza), rapamycin, regorafenib (Stivarga), rituximab (Rituxan, Mabthera), romidepsin (Istodax), ruxolitinib (Jakafi), siltuximab (Sylvant), sipuleucel-T (Provenge), sirolimus, sonidegib (Odomzo), sorafenib (Nexavar), sunitinib, tamoxifen, temsirolimus (Torisel), tocilizumab (Actemra), tofacitinib (Xeljanz), tositumomab (Bexxar), trametinib (Mekinist), trastuzumab (Herceptin), vandetanib (Caprelsa), vemurafenib (Zelboraf), venetoclax (Venclexta), vismodegib (Erivedge), vorinostat (Zolinza), ziv-aflibercept (Zaltrap), and the like, in addition to analogs and derivatives thereof. [00431] Those skilled in the art can determine appropriate chemotherapy and/or targeted therapy and/or alternative therapy options, including treatments that have been approved and those that in clinical trials or otherwise under development. Some targeted therapies are also immunotherapies. Any relevant chemotherapy, target therapy, and alternative therapy treatment strategies can be utilized, alone or in combination with one or more additional cancer therapy, in the practice of the present disclosure. Immunotherapy [00432] In some embodiments, immunotherapies include cell-based immunotherapies, such as those involving cells which effect an immune response (such as, for example, lymphocytes, macrophages, natural killer (NK) cells, dendritic cells, cytotoxic T lymphocytes (CTL), antibodies and antibody derivatives (such as, for example, monoclonal antibodies, conjugated monoclonal antibodies, polyclonal antibodies, antibody fragments, radiolabeled antibodies, chemolabeled antibodies, etc.), immune checkpoint inhibitors, vaccines (such as, for example, cancer vaccines (e.g. tumor cell vaccines, antigen vaccines, dendritic cell vaccines, vector-based vaccines, etc.), e.g. oncophage, sipuleucel-T, and the like), immunomodulators (such as, for example, interleukins, cytokines, chemokines, etc.), topical immunotherapies (such as, for example, imiquimod, and the like), injection immunotherapies, adoptive cell transfer, oncolytic virus therapies (such as, for example, talimogene laherparepvec (T-VEC), and the like), immunosuppressive drugs, helminthic therapies, other non-specific immunotherapies, and the like. Immune checkpoint inhibitor immunotherapies are those that target one or more specific proteins or receptors, such as PD-1, PD-L1, CTLA-4, and the like. Immune checkpoint inhibitor immunotherapies include ipilimumab (Yervoy), nivolumab (Opdivo), pembrolizumab (Keytruda), and the like. Non-specific immunotherpaies include cytokines, interleukins, interferons, and the like. In some embodiments, an immunotherapy assigned or administered to a subject can include an interleukin, and/or interferon (IFN), and/or one or more suitable antibody-based reagent, such as denileukin diftitox and/or administration of an antibody-based reagent selected from the group consisting of ado-trastuzumab emtansine, alemtuzumab, atezolizumab, bevacizumab, blinatumomab, brentuximab vedotin, cetuximab, catumaxomab, gemtuzumab, ibritumomab tiuxetan, ilipimumab, natalizumab, nimotuzumab, nivolumab, ofatumumab, panitumumab, pembrolizumab, rituximab, tositumomab, trastuzumab, vivatuxin, and the like. In some embodiments, an immunotherapy assigned or administered to a subject can include an indoleamine 2,3-dioxygenase (IDO) inhibitor, adoptive T-cell therapy, virotherapy (T-VEC), and/or any other immunotherapy whose efficacy extensively depends on anti-tumor immunity. [00433] Those skilled in the art can determine appropriate immunotherapy options, including treatments that have been approved and those that in clinical trials or otherwise under development. Any relevant immunotherapy treatment strategies, alone or in combination with one or more additional cancer therapy, can be utilized in the practice of the present disclosure. Other Cancer Treatments [00434] In addition to chemotherapies, targeted therapies, alternative therapies, and immunotherapies, cancer can additionally be treated by other strategies. These include surgery, radiation therapy, hormone therapy, stem cell transplant, precision medicine, and the like; such treatments and the compounds and compositions utilized therein are known to those skilled in the art. Any such treatment strategies can be utilized in the practice of the present disclosure. [00435] Alternative treatment strategies have also been used with various types of cancers. Such treatment can be used alone or in combination with any other treatment modality. These include exercise, massage, relaxation techniques, yoga, acupuncture, aromatherapy, hypnosis, music therapy, dietary changes, nutritional and dietary supplements, and the like; such treatments are known to those skilled in the art. Any such treatment strategies can be utilized, alone or in combination with one or more additional cancer therapy, in the practice of the present disclosure. Dosage and Administration Routes [00436] Other embodiments of the disclosure can include methods of administering or treating an animal/human, which can involve treatment with an amount of at least one compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) that is effective to treat the disease, condition, or disorder that the organism has, or is suspected of having, or is susceptible to, or to bring about a desired physiological effect. In some embodiments, the composition or pharmaceutical composition comprises at least one compound of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) which can be administered to an animal (e.g., mammals, primates, monkeys, or humans) in an amount of about 0.005 to about 50 mg/kg body weight, about 0.01 to about 15 mg/kg body weight, about 0.1 to about 10 mg/kg body weight, about 0.5 to about 7 mg/kg body weight, about 0.005 mg/kg, about 0.01 mg/kg, about 0.05 mg/kg, about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, about 3 mg/kg, about 5 mg/kg, about 5.5 mg/kg, about 6 mg/kg, about 6.5 mg/kg, about 7 mg/kg, about 7.5 mg/kg, about 8 mg/kg, about 10 mg/kg, about 12 mg/kg, or about 15 mg/kg. In regard to some conditions, the dosage can be about 0.5 mg/kg human body weight or about 6.5 mg/kg human body weight. In some instances, some subjects (e.g., mammals, mice, rabbits, feline, porcine, or canine) can be administered a dosage of about 0.005 to about 50 mg/kg body weight, about 0.01 to about 15 mg/kg body weight, about 0.1 to about 10 mg/kg body weight, about 0.5 to about 7 mg/kg body weight, about 0.005 mg/kg, about 0.01 mg/kg, about 0.05 mg/kg, about 0.1 mg/kg, about 1 mg/kg, about 5 mg/kg, about 10 mg/kg, about 20 mg/kg, about 30 mg/kg, about 40 mg/kg, about 50 mg/kg, about 80 mg/kg, about 100 mg/kg, or about 150 mg/kg. Of course, those skilled in the art will appreciate that it is possible to employ many concentrations in the methods of the present disclosure, and using, in part, the guidance provided herein, will be able to adjust and test any number of concentrations in order to find one that achieves the desired result in a given circumstance. In some embodiments, a dose or a therapeutically effective dose of a compound disclosed herein will be that which is sufficient to achieve a plasma concentration of the compound or its active metabolite(s) within a range set forth herein, e.g., 1-10 nM, 10-100 nM, 1-100 nM, 0.1-1 nM, 0.1-100 nM, 0.1-200 nM, 1-200 nM, 10-200 nM, 100-200 nM, 200- 500 nM, 0.1-500 nM, 1-500 nM, 10-500 nM, 500-1000 nM, 0.1-1000 nM, 1-1000 nM, 10-1000 nM, or 100-1000 nM. In some embodiments, the inhibitory activity is less than 0.1 nM, less than 1 nM, less than 10 nM, less than 100 nM, or less than 1000 nM, 0.1-1 µM, 1-10 µM, 10-100 µM, 100-200 µM, 200-500 µM, or even 500-1000 µM, preferably about 1-10 nM, 10-100 nM, or 0.1- 1 µM. Without wishing to be bound by any theory, it is believe that such compounds are indicated in the treatment or management of hematopoietic cancers, such as, for example, MDS and/or AML and/or DLBCL, etc., other types of cancers, inflammatory conditions, and/or autoimmune diseases, as described herein. [00437] In other embodiments, the compounds and/or pharmaceutical compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106 and pharmaceutical compositions including the same) can be administered in combination with one or more other therapeutic agents for a given disease, condition, or disorder. [00438] The compounds and pharmaceutical compositions are preferably prepared and administered in dose units. Solid dose units are tablets, capsules and suppositories. For treatment of a subject, depending on activity of the compound, manner of administration, nature and severity of the disease or disorder, age and body weight of the subject, different daily doses can be used. [00439] Under certain circumstances, however, higher or lower daily doses can be appropriate. The administration of the daily dose can be carried out both by single administration in the form of an individual dose unit or else several smaller dose units and also by multiple administrations of subdivided doses at specific intervals. [00440] The compounds and pharmaceutical compositions contemplated herein can be administered locally or systemically in a therapeutically effective dose. Amounts effective for this use will, of course, depend on the severity of the disease or disorder and the weight and general state of the subject. Typically, dosages used in vitro can provide useful guidance in the amounts useful for in situ administration of the pharmaceutical composition, and animal models can be used to determine effective dosages for treatment of particular disorders. [00441] Various considerations are described, e. g. , in Langer, 1990, Science, 249: 1527; Goodman and Gilman's (eds.), 1990, Id., each of which is herein incorporated by reference and for all purposes. Dosages for parenteral administration of active pharmaceutical agents can be converted into corresponding dosages for oral administration by multiplying parenteral dosages by appropriate conversion factors. As to general applications, the parenteral dosage in mg/mL times 1.8 = the corresponding oral dosage in milligrams (“mg”). As to oncology applications, the parenteral dosage in mg/mL times 1.6 = the corresponding oral dosage in mg. An average adult weighs about 70 kg. See e.g., Miller-Keane, 1992, Encyclopedia & Dictionary of Medicine, Nursing & Allied Health, 5th Ed., (W. B. Saunders Co.), pp.1708 and 1651. [00442] It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the particular disease undergoing therapy. [00443] In some embodiments, the compounds and/or pharmaceutical compositions can include a unit dose of one or more compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106 and pharmaceutical compositions including the same) in combination with a pharmaceutically acceptable carrier and, in addition, can include other medicinal agents, pharmaceutical agents, carriers, adjuvants, diluents, and excipients. In certain embodiments, the carrier, vehicle or excipient can facilitate administration, delivery and/or improve preservation of the composition. In other embodiments, the one or more carriers, include but are not limited to, saline solutions such as normal saline, Ringer's solution, PBS (phosphate-buffered saline), and generally mixtures of various salts including potassium and phosphate salts with or without sugar additives such as glucose. Carriers can include aqueous and non-aqueous sterile injection solutions that can contain antioxidants, buffers, bacteriostats, bactericidal antibiotics, and solutes that render the formulation isotonic with the bodily fluids of the intended recipient; and aqueous and non-aqueous sterile suspensions, which can include suspending agents and thickening agents. In other embodiments, the one or more excipients can include, but are not limited to water, saline, dextrose, glycerol, ethanol, or the like, and combinations thereof. Nontoxic auxiliary substances, such as wetting agents, buffers, or emulsifiers may also be added to the composition. Oral formulations can include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, and magnesium carbonate. [00444] The quantity of active component in a unit dose preparation can be varied or adjusted from 0.1 mg to 10000 mg, more typically 1.0 mg to 1000 mg, most typically 10 mg to 500 mg, according to the particular application and the potency of the active component. The composition can, if desired, also contain other compatible therapeutic agents. [00445] The compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) can be administered to subjects by any number of suitable administration routes or formulations. The compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) of the disclosure can also be used to treat subjects for a variety of diseases. Subjects include but are not limited to mammals, primates, monkeys (e.g., macaque, rhesus macaque, or pig tail macaque), humans, canine, feline, bovine, porcine, avian (e.g., chicken), mice, rabbits, and rats. As used herein, the term “subject”, unless stated otherwise, encompasses both human and non-human subjects. [00446] The route of administration of the compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) can be of any suitable route. Administration routes can be, but are not limited to the oral route, the parenteral route, the cutaneous route, the nasal route, the rectal route, the vaginal route, and the ocular route. In other embodiments, administration routes can be parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. The choice of administration route can depend on the compound identity (e.g., the physical and chemical properties of the compound) as well as the age and weight of the animal/human, the particular disease (e.g., cancer or MDS), and the severity of the disease (e.g., stage or severity of cancer or MDS). Of course, combinations of administration routes can be administered, as desired.

[ 00447 ] Some embodiments of the disclosure include a method for providing a subject with a composition comprising one or more compounds of the disclosure (e.g., a crystalline form of a free base or a salt of Compound 106) described herein (e.g., a pharmaceutical composition) which comprises one or more administrations of one or more such compositions; the compositions may be the same or different if there is more than one administration.

Toxicity

[ 00448 ] The ratio between toxicity and therapeutic effect for a particular compound is its therapeutic index and can be expressed as the ratio between LD50 (the amount of compound lethal in 50% of the population) and ED50 (the amount of compound effective in 50% of the population). Compounds that exhibit high therapeutic indices are preferred. Therapeutic index data obtained from in vitro assays, cell culture assays and/or animal studies can be used in formulating a range of dosages for use in humans. The dosage of such compounds preferably lies within a range of plasma concentrations that include the ED50 with little or no toxicity. The dosage can vary within this range depending upon the dosage form employed and the route of administration utilized. See, e.g. Fingl et al., In: THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, Ch. l, p.l, 1975. The exact formulation, route of administration, and dosage can be chosen by the individual practitioner in view of the patient’s condition and the particular method in which the compound is used. For in vitro formulations, the exact formulation and dosage can be chosen by the individual practitioner in view of the patient’s condition and the particular method in which the compound is used.

[ 00449 ] Having described the disclosure in detail, it will be apparent that modifications, variations, and equivalent embodiments are possible without departing from the scope of the disclosure defined in the appended claims. Furthermore, it should be appreciated that all examples in the present disclosure are provided as non-limiting examples.

[00450] ERK2/MAPK1 or ERK1/MAPK3 inhibitor comprising ulixertinib, SCH772984, ravoxertinib, MK-8353, and/or VTX-1 le; wherein the PI3K inhibitor comprises fimepinostat (CUDC-907), alpelisib, leniolisib (CDZ-173), pilaralisib (XL147, SAR245408), and/or bimiralisib (PQR-309); wherein the mTOR inhibitor comprises bimiralisib (PQR-309), sapanisertib (TAK-228, INK-128), ridaforolimus (MK-8669, AP -23573), everolimus, and/or vistusertib (AZD2014); wherein the glucocorticoid receptor modulator comprises an agonist comprising prednisolone, beclometasone, methylprednisolone, prednisone, fluticasone, budesonide, dexamethasone, and/or cortisol, and/or an antagonist comprising mifepristone, miricorilant, and/or onapristone, and/or another binding ligand comprising vamorolone (VBP15); and/or wherein the EZH2 inhibitor comprises tazemetostat. [00451] The following clauses describe certain embodiments of the disclosure. [00452] Clause 1. A crystal form of a free base of a compound of Formula (1):

characterized by an X-ray powder diffraction pattern comprising one or more peaks at 8.5102 ± 0.2°, 13.4583 ± 0.2°, 16.3830 ± 0.2°, 20.0082 ± 0.2°, and 24.6817 ± 0.2° 2θ. [00453] Clause 2. The crystal form of clause 1, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 11.2514 ± 0.2°, 16.8018 ± 0.2°, 20.9239 ± 0.2°, 22.2447 ± 0.2°, 28.6101 ± 0.2° 2θ. [00454] Clause 3. The crystal form of clause 1 or 2, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 10.2265 ± 0.2°, 17.1029 ± 0.2°, 18.3658 ± 0.2°, 22.6040 ± 0.2°, and 23.6583 ± 0.2° 2θ. [00455] Clause 4. A crystal form of a salt of a compound of Formula (1): wherein the salt comprises a p-tol

on and the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 5.1743 ± 0.2°, 8.1663 ± 0.2°, 10.3704 ± 0.2°, 14.4880 ± 0.2°, and 16.8942 ± 0.2° 2θ. [00456] Clause 5. The crystal form of clause 4, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 7.0186 ± 0.2°, 11.7589 ± 0.2°, 14.0747 ± 0.2°, 14.2385 ± 0.2°, and 21.1626 ± 0.2° 2θ. [00457] Clause 6. The crystal form of clause 4 or 5, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 12.5062 ± 0.2°, 13.2636 ± 0.2°, 17.6050 ± 0.2°, 25.1678 ± 0.2°, and 26.2810 ± 0.2° 2θ. [00458] Clause 7. A crystal form of a salt of a compound of Formula (1):

wherein the salt comprises a tartaric acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 7.7633 ± 0.2°, 8.2996 ± 0.2°, 12.4661 ± 0.2°, 15.5489 ± 0.2°, and 24.7464 ± 0.2° 2θ. [00459] Clause 8. The crystal form of clause 7, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 4.1463 ± 0.2°, 11.3791 ± 0.2°, 17.4289 ± 0.2°, 20.4382 ± 0.2°, and 25.1566 ± 0.2° 2θ. [00460] Clause 9. The crystal form of clause 7 or 8, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 14.1011 ± 0.2°, 18.6536 ± 0.2°, 19.1095 ± 0.2°, 22.5011 ± 0.2°, and 25.4454 ± 0.2° 2θ. [00461] Clause 10. A crystal form of a salt of a compound of Formula (1):

, wherein the salt comprises a methanesulfonic acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 13.8951 ± 0.2°, 15.8697 ± 0.2°, 18.4951 ± 0.2°, 19.5773 ± 0.2°, and 21.5492 ± 0.2° 2θ. [00462] Clause 11. The crystal form of clause 10, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 10.7336 ± 0.2°, 16.2453 ± 0.2°, 21.7550 ± 0.2°, 22.5396 ± 0.2°, and 23.8137 ± 0.2° 2θ. [00463] Clause 12. The crystal form of clause 10 or 11, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 9.4332 ± 0.2°, 15.3077 ± 0.2°, 25.6827 ± 0.2°, 27.3636 ± 0.2°, and 28.4083 ± 0.2° 2θ. [00464] Clause 13. A crystal form of a salt of a compound of Formula (1): wherein the salt comprises a benz

and the crystal form is characterized by an X-ray powder diffraction pattern comprising peaks at 13.3296 ± 0.2°, 14.2875 ± 0.2°, 14.6072 ± 0.2°, 17.6593 ± 0.2°, and 20.4010 ± 0.2° 2θ. [00465] Clause 14. The crystal form of clause 13, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 8.8966 ± 0.2°, 11.2206 ± 0.2°, 12.2073 ± 0.2°, 25.5863 ± 0.2°, and 27.1334 ± 0.2° 2θ. [00466] Clause 15. The crystal form of clause 13 or 14, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 6.0882 ± 0.2°, 14.1225 ± 0.2°, 16.6160 ± 0.2°, 21.5845 ± 0.2°, and 21.9720 ± 0.2° 2θ. [00467] Clause 16. A crystal form of a salt of a compound of Formula (1):

Formula (1), wherein the salt comprises a bis-hydrochloric acid counterion and the crystal form is described herein. [00468] Clause 17. A crystal form of a salt of a compound of Formula (1):

wherein the salt comprises a mono-hydrochloric acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising peaks at 6.8619 ± 0.2°, 11.3373 ± 0.2°, 14.5399 ± 0.2°, 17.1417 ± 0.2°, and 23.6521 ± 0.2° 2θ. [00469] Clause 18. The crystal form of clause 17, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 14.7217 ± 0.2°, 16.2725 ± 0.2°, 22.4223 ± 0.2°, 23.3316 ± 0.2°, and 28.8331 ± 0.2° 2θ. [00470] Clause 19. The crystal form of clause 17 or 18, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 2.0916 ± 0.2°, 11.1062 ± 0.2°, 20.9023 ± 0.2°, 21.9400 ± 0.2°, and 27.5840 ± 0.2° 2θ. [00471] Clause 20. The crystal form of any one of clauses 1-19, wherein the crystal form is an inhibitor of at least one of IRAK1, IRAK4, and FLT3. [00472] Clause 21. The crystal form of any one of clauses 1-20, wherein the crystal form is an inhibitor of at least two of IRAK1, IRAK4, and FLT3. [00473] Clause 22. The crystal form of any one of clauses 1-21, wherein the crystal form is an inhibitor of IRAK1 and IRAK4. [00474] Clause 23. The crystal form of any one of clauses 1-21, wherein the crystal form is an inhibitor of IRAK1, IRAK4, and FLT3. [00475] Clause 24. The crystal form of any one of clauses 20, 21, or 23, wherein FLT3 is selected from WT FLT3, activated FLT3, and mutated FLT3. [00476] Clause 25. The crystal form of clause 24, wherein the mutated FLT3 is D835Y mutated FLT3 or F691L mutated FLT3. [00477] Clause 26. A composition comprising a crystal form of any one of clauses 1-19, wherein the composition further comprises a formulary ingredient, an adjuvant, or a carrier. [00478] Clause 27. The composition of clause 26, wherein the composition is used in combination with one or more of: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor/hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, an antibody- drug conjugate, an mAbs/immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2/MAPK1 or ERK1/MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase/Leukotriene A4 hydrolase inhibitor, a FLT3/Axl/ALK inhibitor, a FLT3/KIT/PDGFR, PKC, and/or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB/C/VEGFR1/2/3/FLT3/CSF-1R/Kit/PDGFRA/B inhibitor, an AKT 1, 2, and/or 3 inhibitor, a ABL1/2/SRC/EPHA2/LCK/YES1/KIT/PDGFRB/FYN inhibitor, a farnesyltransferase inhibitor, a BRAF/MAP2K1/MAP2K2 inhibitor, a Menin-KMT2A/MLL inhibitor, and a multikinase inhibitor. [00479] Clause 28. The composition of clause 27, wherein the composition is used in combination with at least one of a BCL2 inhibitor, a BTK inhibitor, a gluococorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. [00480] Clause 29. The composition of clause 28, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof. [00481] Clause 30. The composition of clause 28, wherein the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof. [00482] Clause 31. The composition of clause 28, wherein the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone or a pharmaceutically acceptable salt of any one thereof. [00483] Clause 32. The composition of clause 28, wherein the CDK inhibitor is a CDK4 inhibitor, a CDK6 inhibitor, a CDK7 inhibitor, and/or a CDK9 inhibitor. [00484] Clause 33. The composition of clause 32, wherein the CDK inhibitor is selected from CDK4/6 inhibitor Palbociclib, CDK7 inhibitor THZ1, and/or CDK9 inhibitors BAY1251152 and Atuveciclib, or a pharmaceutically acceptable salt of any one thereof. [00485] Clause 34. The composition of clause 28, wherein the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. [00486] Clause 35. A method of treating a disease or disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of a crystal form of any one of clauses 1-19 or a composition of any one of clauses 20-34. [00487] Clause 36. The method of clause 35, wherein the disease or disorder is responsive to at least one of interleukin-1 receptor-associated kinase (IRAK) inhibition and fms-like tyrosine kinase 3 (FLT3) inhibition. [00488] Clause 37. The method of clause 35 or 36, wherein the administration comprises parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. [00489] Clause 38. The method of any one of clauses 35-37, wherein the crystal form is administered to the subject in an amount of from about 0.005 mg/kg subject body weight to about 1,000 mg /kg subject body weight. [00490] Clause 39. The method of any one of clauses 35-38, wherein the disease or disorder comprises a hematopoietic cancer. [00491] Clause 40. The method of any one of clauses 35-38, wherein the disease or disorder comprises myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). [00492] Clause 41. The method of any one of clauses 35-38, wherein the disease or disorder comprises lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL with MYD88 mutation, follicular lymphoma, or marginal zone lymphoma. [00493] Clause 42. The method of any one of clauses 35-38, wherein the disease or disorder comprises at least one cancer selected from glioblastoma multiforme, myelofibrosis, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer, or one or more inflammatory diseases or autoimmune disease characterized by overactive IRAK1 and/or IRAK4, or combinations thereof. [00494] Clause 43. The method of any one of clauses 35-38, wherein the disease or disorder comprises one or more inflammatory diseases or autoimmune disease selected from chronic inflammation, sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, colitis, or combinations thereof. [00495] Clause 44. The method of any one of clauses 35-38, wherein the disease or disorder comprises: (i) MDS, MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2; or (ii) AML with a splicing factor mutation, AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the AML is not driven by FLT3 mutations but expresses IRAK4-Long. [00496] Clause 45. The method of clause 44, wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1 or SF3B1 and the AML splicing factor mutation comprises AML with a splicing factor mutation in U2AF1 or SF3B1. [00497] Clause 46. The method of any one of clauses 35-38, wherein the disease or disorder comprises diffuse large B-cell lymphoma (DLBCL), and wherein the DLBCL comprises a L265P MYD88 mutant (ABC) subtype of DLBCL or a S219C MYD88 mutant (GCB) subtype of DLBCL. [00498] Clause 47. The method of any one of clauses 35-46, further comprising administering to the subject one or more additional therapies selected from: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor/hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, an antibody-drug conjugate, an mAbs/immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2/MAPK1 or ERK1/MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase/Leukotriene A4 hydrolase inhibitor, a FLT3/Axl/ALK inhibitor, a FLT3/KIT/PDGFR, PKC, and/or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB/C/VEGFR1/2/3/FLT3/CSF-1R/Kit/PDGFRA/B inhibitor, an AKT 1, 2, and/or 3 inhibitor, a ABL1/2/SRC/EPHA2/LCK/YES1/KIT/PDGFRB/FYN inhibitor, a farnesyltransferase inhibitor, a BRAF/MAP2K1/MAP2K2 inhibitor, a Menin-KMT2A/MLL inhibitor, and a multikinase inhibitor. [00499] Clause 48. The method of any one of clauses 35-47, wherein the disease or disorder is responsive to at least one of BCL2 inhibition, BTK inhibition, CDK inhibition, and DNA methyltransferase inhibition; or wherein the disease or disorder is sensitive to anti- inflammatory glucocorticoids. [00500] Clause 49. The method of clause 48, wherein the additional therapy is at least one of a BCL2 inhibitor, a BTK inhibitor, a gluococorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. [00501] Clause 50. The method of clause 49, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof. [00502] Clause 51. The method of any one of clauses 35-49, wherein the disease or disorder is a BCL2 inhibitor resistant disease or disorder. [00503] Clause 52. The method of any one of clauses 35-49, wherein the disease or disorder is a venetoclax resistant disease or disorder. [00504] Clause 53. The method of any one of clauses 35-49, wherein the disease or disorder is BCL2 inhibitor resistant acute myeloid leukemia (AML). [00505] Clause 54. The method of any one of clauses 35-49, wherein the disease or disorder is venetoclax resistant acute myeloid leukemia (AML). [00506] Clause 55. The method of any one of clauses 35-49, wherein the disease or disorder is BCL2 inhibitor resistant refractory acute myeloid leukemia (AML). [00507] Clause 56. The method of any one of clauses 35-49, wherein the disease or disorder is venetoclax resistant refractory acute myeloid leukemia (AML). [00508] Clause 57. The method of any one of clauses 35-49, wherein the disease or disorder is BCL2 inhibitor resistant relapsed acute myeloid leukemia (AML). [00509] Clause 58. The method of any one of clauses 35-49, wherein the disease or disorder is venetoclax resistant relapsed acute myeloid leukemia (AML). [00510] Clause 59. The method of clause 49, wherein the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof. [00511] Clause 60. The method of any one of clauses 35-49, wherein the disease or disorder is a BTK inhibitor resistant disease or disorder. [00512] Clause 61. The method of any one of clauses 35-49, wherein the disease or disorder is an ibrutinib resistant disease or disorder. [00513] Clause 62. The method of clause 49, wherein the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone, or a pharmaceutically acceptable salt of any one thereof. [00514] Clause 63. The method of any one of clauses 35-49, wherein the disease or disorder is sensitive to anti-inflammatory glucocorticoids. [00515] Clause 64. The method of any one of clauses 35-49, wherein the disease or disorder is a dexamethasone, methylprednisolone, or prednisolone resistant disease or disorder. [00516] Clause 65. The method of clause 49, wherein the CDK inhibitor is selected from CDK4/6 inhibitor palbociclib, CDK7 inhibitor THZ1, and/or CDK9 inhibitors BAY1251152 and atuveciclib, or a pharmaceutically acceptable salt of any one thereof. [00517] Clause 66. The method of any one of clauses 35-49, wherein the disease or disorder is a CDK inhibitor resistant disease or disorder. [00518] Clause 67. The method of any one of clauses 35-49, wherein the disease or disorder is a palbociclib, THZ1, BAY 12511152, or atuveciclib resistant disease or disorder. [00519] Clause 68. The method of clause 49, wherein the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. [00520] Clause 69. The method of any one of clauses 35-49, wherein the disease or disorder is a DNA methyltransferase inhibitor resistant disease or disorder. [00521] Clause 70. The method of any one of clauses 35-49, wherein the disease or disorder is an azacitidine resistant disease or disorder. [00522] Clause 71. The method of any one of clauses 35-49, wherein the disease or disorder is a BCL2 inhibitor and DNA methyltransferase inhibitor resistant disease or disorder. [00523] Clause 72. The method of any one of clauses 35-49, wherein the disease or disorder is a venetoclax and azacitidine resistant disease or disorder. [00524] Clause 73. The method of clause 49, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof and the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. [00525] Clause 74. The method of any one of clauses 35-49, wherein the disease or disorder is a FLT3 inhibitor resistant disease or disorder. [00526] Clause 75. The method of any one of clauses 35-49, wherein the disease or disorder is FLT3 inhibitor resistant acute myeloid leukemia (AML). [00527] Clause 76. The method of any one of clauses 35-49, wherein the disease or disorder is FLT3 inhibitor resistant refractory acute my98eloid leukemia (AML). [00528] Clause 77. The method of any one of clauses 35-49, wherein the disease or disorder is FLT3 inhibitor resistant relapsed acute myeloid leukemia (AML). [00529] Clause 78. The method of clause 49, wherein the crystal form of any one of clauses 1-19 or the composition of any one of clauses 20-34 and the one or more additional therapies are administered together in one administration or composition. [00530] Clause 79. The method of clause 49, wherein the crystal form of any one of clauses 1-19 or the composition any one of clauses 20-34 and the one or more additional therapies are administered separately in more than one administration or more than one composition. [00531] Clause 80. The method of any one of clauses 35-79, wherein the disease or disorder is alleviated by inhibiting at least one of IRAK1, IRAK4, and FLT3 in the subject. [00532] Clause 81. The method of any one of clauses 35-80, wherein the disease or disorder is alleviated by inhibiting at least two of IRAK1, IRAK4, and FLT3 in the subject. [00533] Clause 82. The method of any one of clauses 35-81, wherein the disease or disorder is alleviated by inhibiting IRAK1 and IRAK4 in the subject. [00534] Clause 83. The method of any one of clauses 35-81, wherein the disease or disorder is alleviated by inhibiting IRAK1, IRAK4, and FLT3 in the subject. [00535] Clause 84. The method of any one of clauses 80, 81, or 83, wherein FLT3 is selected from WT FLT3, activated FLT3, and mutated FLT3. [00536] Clause 85. The method of clause 84, wherein the mutated FLT3 is D835Y mutated FLT3 or F691L mutated FLT3. [00537] Clause 101. A crystal form of a mono-HCl salt of a compound of Formula (1):

[00538] Clause 102. The crystal form of clause 101, having Formula (2):

[00539] Clause 103. The crystal form of clause 101 or 102, characterized by an X-ray powder diffraction pattern comprising peaks at 6.8619 ± 0.2°, 11.3373 ± 0.2°, 14.5399 ± 0.2°, 17.1417 ± 0.2°, and 23.6521 ± 0.2° 2θ. [00540] Clause 104. The crystal form of clause 103, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 14.7217 ± 0.2°, 16.2725 ± 0.2°, 22.4223 ± 0.2°, 23.3316 ± 0.2°, and 28.8331 ± 0.2° 2θ. [00541] Clause 105. The crystal form of clause 103 or 104, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 2.0916 ± 0.2°, 11.1062 ± 0.2°, 20.9023 ± 0.2°, 21.9400 ± 0.2°, and 27.5840 ± 0.2° 2θ. [00542] Clause 106. A crystal form of a free base of a compound of Formula (1):

[00543] Clause 107. The crystal form of clause 106, characterized by an X-ray powder diffraction pattern comprising one or more peaks at 8.5102 ± 0.2°, 13.4583 ± 0.2°, 16.3830 ± 0.2°, 20.0082 ± 0.2°, and 24.6817 ± 0.2° 2θ. [00544] Clause 108. The crystal form of clause 107, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 11.2514 ± 0.2°, 16.8018 ± 0.2°, 20.9239 ± 0.2°, 22.2447 ± 0.2°, 28.6101 ± 0.2° 2θ. [00545] Clause 109. The crystal form of clause 107 or 108, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 10.2265 ± 0.2°, 17.1029 ± 0.2°, 18.3658 ± 0.2°, 22.6040 ± 0.2°, and 23.6583 ± 0.2° 2θ. [00546] Clause 110. The crystal form of any one of clauses 106-109, wherein the crystal form comprises a single crystal characterized by one or more of: i) a monoclinic Space group P21; ii) lattice parameters a = 9.5817(11) Å, b = 20.916(2) Å, c = 10.8470(12) Å, α = 90º, β = 114.836(4)°, and γ = 90º; iii) a volume of about 1972.8(4) Å³; and/or iv) a crystal density d_c = 1.348 g/cm³. [00547] Clause 111. The crystal form of any one of clauses 101-110, wherein the compound is an inhibitor of at least one of IRAK1, IRAK4, and FLT3. [00548] Clause 112. The crystal form of any one of clauses 101-111, wherein the compound is an inhibitor of at least two of IRAK1, IRAK4, and FLT3. [00549] Clause 113. The crystal form of any one of clauses 101-112, wherein the compound is an inhibitor of IRAK1 and IRAK4. [00550] Clause 114. The crystal form of any one of clauses 101-112, wherein the compound is an inhibitor of IRAK1, IRAK4, and FLT3. [00551] Clause 115. The crystal form of any one of clauses 111, 112, or 114, wherein FLT3 is selected from WT FLT3, activated FLT3, and mutated FLT3. [00552] Clause 116. The crystal form of clause 113, wherein the mutated FLT3 is D835Y mutated FLT3 or F691L mutated FLT3. [00553] Clause 117. A composition comprising the crystal form of any one of clauses 101-116, wherein the composition further comprises a formulary ingredient, an adjuvant, or a carrier. [00554] Clause 118. A method of treating a disease or disorder in a subject, the method comprising administering to the subject a crystal form of any one of clauses 101-116 or a composition of clause 117, comprising a therapeutically effective amount of the compound. [00555] Clause 119. The method of clause 118, wherein the disease or disorder is responsive to at least one of interleukin-1 receptor-associated kinase (IRAK) inhibition and fms- like tyrosine kinase 3 (FLT3) inhibition. [00556] Clause 120. The method of clause 118 or 119, wherein the administration comprises parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. [00557] Clause 121. The method of any one of clauses 118-120, wherein the therapeutically effective amount of the compound is from about 0.005 mg/kg subject body weight to about 1,000 mg/kg subject body weight. [00558] Clause 122. The method of any one of clauses 118-121, wherein the disease or disorder comprises a hematopoietic cancer. [00559] Clause 123. The method of any one of clauses 118-122, wherein the disease or disorder comprises myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). [00560] Clause 124. The method of clause 123, wherein MDS comprises MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2. [00561] Clause 125. The method of clause 124, wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2. [00562] Clause 126. The method of clause 123, wherein AML comprises relapsed AML, refractory AML, relapsed/refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML. [00563] Clause 127. The method of clause 123, wherein AML comprises AML with a splicing factor mutation, AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the AML is not driven by FLT3 mutations but expresses IRAK4-Long. [00564] Clause 128. The method of clause 127, wherein the AML splicing factor mutation comprises AML with a splicing factor mutation in U2AF1 or SF3B1. [00565] Clause 129. The method of any one of clauses 118-122, wherein the disease or disorder comprises lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL with MYD88 mutation, follicular lymphoma, or marginal zone lymphoma. [00566] Clause 130. The method of any one of clauses 118-121, wherein the disease or disorder comprises at least one cancer selected from glioblastoma multiforme, myelofibrosis, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, uterine cancer, or combinations thereof. [00567] Clause 131. The method of any one of clauses 118-121, wherein the disease or disorder comprises one or more inflammatory diseases or autoimmune disease selected from chronic inflammation, sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, colitis, or combinations thereof. [00568] Clause 132. The method of any one of clauses 118-122, wherein the disease or disorder comprises diffuse large B-cell lymphoma (DLBCL), and wherein the DLBCL comprises a L265P MYD88 mutant (ABC) subtype of DLBCL or a S219C MYD88 mutant (GCB) subtype of DLBCL. [00569] Clause 133. The method of any one of clauses 118-132, further comprising administering to the subject one or more additional therapies selected from: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor/hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, an antibody-drug conjugate, an mAbs/immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2/MAPK1 or ERK1/MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase/Leukotriene A4 hydrolase inhibitor, a FLT3/Axl/ALK inhibitor, a FLT3/KIT/PDGFR, PKC, and/or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB/C/VEGFR1/2/3/FLT3/CSF-1R/Kit/PDGFRA/B inhibitor, an AKT 1, 2, and/or 3 inhibitor, a ABL1/2/SRC/EPHA2/LCK/YES1/KIT/PDGFRB/FYN inhibitor, a farnesyltransferase inhibitor, a BRAF/MAP2K1/MAP2K2 inhibitor, a Menin-KMT2A/MLL inhibitor, and a multikinase inhibitor. [00570] Clause 134. The method of any one of clauses 118-133, wherein the disease or disorder is responsive to at least one of BCL2 inhibition, BTK inhibition, CDK inhibition, and DNA methyltransferase inhibition; or wherein the disease or disorder is sensitive to anti- inflammatory glucocorticoids. [00571] Clause 135. The method of clause 134, wherein the additional therapy is at least one of a BCL2 inhibitor, a BTK inhibitor, a gluococorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. [00572] Clause 136. The method of clause 135, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof. [00573] Clause 137. The method of any one of clauses 134-136, wherein the disease or disorder is a BCL2 inhibitor resistant disease or disorder. [00574] Clause 138. The method of any one of clauses 134-137, wherein the disease or disorder is a venetoclax resistant disease or disorder. [00575] Clause 139. The method of any one of clauses 134-138, wherein the disease or disorder is BCL2 inhibitor resistant acute myeloid leukemia (AML). [00576] Clause 140. The method of any one of clauses 134-139, wherein the disease or disorder is venetoclax resistant acute myeloid leukemia (AML). [00577] Clause 141. The method of any one of clauses 134-139, wherein the disease or disorder is BCL2 inhibitor resistant refractory acute myeloid leukemia (AML). [00578] Clause 142. The method of any one of clauses 134-139, wherein the disease or disorder is venetoclax resistant refractory acute myeloid leukemia (AML). [00579] Clause 143. The method of any one of clauses 134-139, wherein the disease or disorder is BCL2 inhibitor resistant relapsed acute myeloid leukemia (AML). [00580] Clause 144. The method of any one of clauses 134-139, wherein the disease or disorder is venetoclax resistant relapsed acute myeloid leukemia (AML). [00581] Clause 145. The method of clause 134, wherein the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof. [00582] Clause 146. The method of clause 134 or 145, wherein the disease or disorder is a BTK inhibitor resistant disease or disorder. [00583] Clause 147. The method of any one of clauses 134, 145, or 146, wherein the disease or disorder is an ibrutinib resistant disease or disorder. [00584] Clause 148. The method of clause 134, wherein the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone, or a pharmaceutically acceptable salt of any one thereof. [00585] Clause 149. The method of clause 134 or 148, wherein the disease or disorder is sensitive to anti-inflammatory glucocorticoids. [00586] Clause 150. The method of any one of clauses 134, 148, or 149, wherein the disease or disorder is a dexamethasone, methylprednisolone, or prednisolone resistant disease or disorder. [00587] Clause 151. The method of clause 134, wherein the CDK inhibitor is selected from CDK4/6 inhibitor palbociclib, CDK7 inhibitor THZ1, and/or CDK9 inhibitors BAY1251152 and atuveciclib, or a pharmaceutically acceptable salt of any one thereof. [00588] Clause 152. The method of clause 134 or 151, wherein the disease or disorder is a CDK inhibitor resistant disease or disorder. [00589] Clause 153. The method of any one of clauses 134, 151, or 152, wherein the disease or disorder is a palbociclib, THZ1, BAY 12511152, or atuveciclib resistant disease or disorder. [00590] Clause 154. The method of clause 134, wherein the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. [00591] Clause 155. The method of clause 134 or 154, wherein the disease or disorder is a DNA methyltransferase inhibitor resistant disease or disorder. [00592] Clause 156. The method of any one of clauses 134, 154, or 155, wherein the disease or disorder is an azacitidine resistant disease or disorder. [00593] Clause 157. The method of any one of clauses 134 or 154-156, wherein the disease or disorder is a BCL2 inhibitor and DNA methyltransferase inhibitor resistant disease or disorder. [00594] Clause 158. The method of any one of clauses 134 or 154-157, wherein the disease or disorder is a venetoclax and azacitidine resistant disease or disorder. [00595] Clause 159. The method of clause 158, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof and the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. [00596] Clause 160. The method of any one of clauses 134-144, wherein the disease or disorder is a FLT3 inhibitor resistant disease or disorder. [00597] Clause 161. The method of clause 160, wherein the disease or disorder is FLT3 inhibitor resistant acute myeloid leukemia (AML). [00598] Clause 162. The method of clause 160 or 161, wherein the disease or disorder is FLT3 inhibitor resistant refractory acute myeloid leukemia (AML). [00599] Clause 163. The method of clause 160 or 161, wherein the disease or disorder is FLT3 inhibitor resistant relapsed acute myeloid leukemia (AML). [00600] Clause 164. The method of clause 133, wherein the crystal form of any one of clauses 101-116 or the composition of clause 117 and the one or more additional therapies are administered together in one administration or composition. [00601] Clause 165. The method of clause 133, wherein the crystal form of any one of clauses 101-116 or the composition of clause 117 and the one or more additional therapies are administered separately in more than one administration or more than one composition. [00602] Clause 166. The method of any one of clauses 118-165, wherein the disease or disorder is alleviated by inhibiting at least one of IRAK1, IRAK4, and FLT3 in the subject. [00603] Clause 167. The method of any one of clauses 118-166, wherein the disease or disorder is alleviated by inhibiting at least two of IRAK1, IRAK4, and FLT3 in the subject. [00604] Clause 168. The method of any one of clauses 118-167, wherein the disease or disorder is alleviated by inhibiting IRAK1 and IRAK4 in the subject. [00605] Clause 169. The method of any one of clauses 118-167, wherein the disease or disorder is alleviated by inhibiting IRAK1, IRAK4, and FLT3 in the subject. [00606] Clause 170. The method of any one of clauses 166, 167, or 169, wherein FLT3 is selected from WT FLT3, activated FLT3, and mutated FLT3. [00607] Clause 171. The method of clause 170, wherein the mutated FLT3 is D835Y mutated FLT3 or F691L mutated FLT3. [00608] Clause 201. A crystal form of a free base of a compound of Formula (1):

characterized by an X-ray powder diffraction pattern comprising one or more peaks at 8.5102 ± 0.2°, 13.4583 ± 0.2°, 16.3830 ± 0.2°, 20.0082 ± 0.2°, and 24.6817 ± 0.2° 2θ. [00609] Clause 202. The crystal form of clause 201, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 11.2514 ± 0.2°, 16.8018 ± 0.2°, 20.9239 ± 0.2°, 22.2447 ± 0.2°, and 28.6101 ± 0.2° 2θ. [00610] Clause 203. The crystal form of clause 201 or 202, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 10.2265 ± 0.2°, 17.1029 ± 0.2°, 18.3658 ± 0.2°, 22.6040 ± 0.2°, and 23.6583 ± 0.2° 2θ. [00611] Clause 203a. The crystal form of any one of clauses 201-203, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 12.4152 ± 0.2°, 15.6546 ± 0.2°, 18.5476 ± 0.2°, 19.1056 ± 0.2°, 19.3265 ± 0.2°, 20.4980 ± 0.2°, 21.3232 ± 0.2°, 23.2420 ± 0.2°, 24.2705 ± 0.2°, 25.8013 ± 0.2°, 26.1668 ± 0.2°, 27.1774 ± 0.2°, 27.5557 ± 0.2°, 28.1259 ± 0.2°, 30.1759 ± 0.2°, 31.5240 ± 0.2°, 31.8408 ± 0.2°, 32.3075 ± 0.2°, 32.8563 ± 0.2°, 33.7388 ± 0.2°, 36.0412 ± 0.2°, 36.7705 ± 0.2°, 37.7457 ± 0.2°, and 39.0376 ± 0.2° 2θ. [00612] Clause 204. A crystal form of the free base of a compound of Formula (1):

, wherein the crystal form comprises a single crystal characterized by one or more of: i) a monoclinic Space group P2₁; ii) lattice parameters a = 9.5817(11) Å, b = 20.916(2) Å, c = 10.8470(12) Å, α = 90º, β = 114.836(4)°, and γ = 90º; iii) a volume of about 1972.8(4) Å³; and/or iv) a crystal density dc = 1.348 g/cm³. [00613] Clause 205. A crystal form of a salt of a compound of Formula (1): wherein the salt comprises a p-tol n and the crystal form is

characterized by an X-ray powder diffraction pattern comprising one or more peaks at 5.1743 ± 0.2°, 8.1663 ± 0.2°, 10.3704 ± 0.2°, 14.4880 ± 0.2°, and 16.8942 ± 0.2° 2θ. [00614] Clause 206. The crystal form of clause 205, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 7.0186 ± 0.2°, 11.7589 ± 0.2°, 14.0747 ± 0.2°, 14.2385 ± 0.2°, and 21.1626 ± 0.2° 2θ. [00615] Clause 207. The crystal form of clause 205 or 206, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 12.5062 ± 0.2°, 13.2636 ± 0.2°, 17.6050 ± 0.2°, 25.1678 ± 0.2°, and 26.2810 ± 0.2° 2θ. [00616] Clause 208. A crystal form of a salt of a compound of Formula (1): wherein the salt comprises a tarta

crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 7.7633 ± 0.2°, 8.2996 ± 0.2°, 12.4661 ± 0.2°, 15.5489 ± 0.2°, and 24.7464 ± 0.2° 2θ. [00617] Clause 209. The crystal form of clause 208, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 4.1463 ± 0.2°, 11.3791 ± 0.2°, 17.4289 ± 0.2°, 20.4382 ± 0.2°, and 25.1566 ± 0.2° 2θ. [00618] Clause 210. The crystal form of clause 208 or 209, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 14.1011 ± 0.2°, 18.6536 ± 0.2°, 19.1095 ± 0.2°, 22.5011 ± 0.2°, and 25.4454 ± 0.2° 2θ. [00619] Clause 211. A crystal form of a salt of a compound of Formula (1):

wherein the salt comprises a methanesulfonic acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 13.8951 ± 0.2°, 15.8697 ± 0.2°, 18.4951 ± 0.2°, 19.5773 ± 0.2°, and 21.5492 ± 0.2° 2θ. [00620] Clause 212. The crystal form of clause 211, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 10.7336 ± 0.2°, 16.2453 ± 0.2°, 21.7550 ± 0.2°, 22.5396 ± 0.2°, and 23.8137 ± 0.2° 2θ. [00621] Clause 213. The crystal form of clause 211 or 212, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 9.4332 ± 0.2°, 15.3077 ± 0.2°, 25.6827 ± 0.2°, 27.3636 ± 0.2°, and 28.4083 ± 0.2° 2θ. [00622] Clause 214. A crystal form of a salt of a compound of Formula (1):

, wherein the salt comprises a benzenesulfonic acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising peaks at 13.3296 ± 0.2°, 14.2875 ± 0.2°, 14.6072 ± 0.2°, 17.6593 ± 0.2°, and 20.4010 ± 0.2° 2θ. [00623] Clause 215. The crystal form of clause 214, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 8.8966 ± 0.2°, 11.2206 ± 0.2°, 12.2073 ± 0.2°, 25.5863 ± 0.2°, and 27.1334 ± 0.2° 2θ. [00624] Clause 216. The crystal form of clause 214 or 215, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 6.0882 ± 0.2°, 14.1225 ± 0.2°, 16.6160 ± 0.2°, 21.5845 ± 0.2°, and 21.9720 ± 0.2° 2θ. [00625] Clause 217. A crystal form of a salt of a compound of Formula (1):

wherein the salt comprises a mono-hydrochloric acid counterion and the crystal form is characterized by an X-ray powder diffraction pattern comprising peaks at 6.8619 ± 0.2°, 11.3373 ± 0.2°, 14.5399 ± 0.2°, 17.1417 ± 0.2°, and 23.6521 ± 0.2° 2θ. [00626] Clause 218. The crystal form of clause 217, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 14.7217 ± 0.2°, 16.2725 ± 0.2°, 22.4223 ± 0.2°, 23.3316 ± 0.2°, and 28.8331 ± 0.2° 2θ. [00627] Clause 219. The crystal form of clause 217 or 218, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 2.0916 ± 0.2°, 11.1062 ± 0.2°, 20.9023 ± 0.2°, 21.9400 ± 0.2°, and 27.5840 ± 0.2° 2θ. Clause 219a. The crystal form of any one of clauses 217-219, characterized by an X-ray powder diffraction pattern further comprising one or more peaks at 11.6132 ± 0.2°, 13.7106 ± 0.2°, 14.3405 ± 0.2°, 15.3177 ± 0.2°, 17.5260 ± 0.2°, 17.6282 ± 0.2°, 18.8337 ± 0.2°, 20.0236 ± 0.2°, 20.8136 ± 0.2°, 21.0463 ± 0.2°, 22.9619 ± 0.2°, 24.4120 ± 0.2°, 24.9258 ± 0.2°, 26.0850 ± 0.2°, 26.7151 ± 0.2°, 26.9745 ± 0.2°, 27.2880 ± 0.2°, 27.8954 ± 0.2°, 28.1817 ± 0.2°, 28.3383 ± 0.2°, 29.2852 ± 0.2°, 29.8645 ± 0.2°, 32.2115 ± 0.2°, 33.1644 ± 0.2°, 33.5088 ± 0.2°, 33.8427 ± 0.2°, 34.6622 ± 0.2°, 35.6915 ± 0.2°, 36.3485 ± 0.2°, 37.3533 ± 0.2°, and 38.0511 ± 0.2° 2θ. [00628] Clause 220. The crystal form of any one of clauses 217-219a, having Formula (2):

[00629] Clause 221. A crystal form of a salt of a compound of Formula (1):

wherein the salt comprises a bis-hydrochloric acid counterion and the crystal form is described herein. [00630] Clause 222. The crystal form of any one of clauses 201-221, wherein the compound is an inhibitor of at least one of IRAK1, IRAK4, and FLT3. [00631] Clause 223. The crystal form of any one of clauses 201-222, wherein the compound is an inhibitor of at least two of IRAK1, IRAK4, and FLT3. [00632] Clause 224. The crystal form of any one of clauses 201-223, wherein the compound is an inhibitor of IRAK1 and IRAK4. [00633] Clause 225. The crystal form of any one of clauses 201-223, wherein the compound is an inhibitor of IRAK1, IRAK4, and FLT3. [00634] Clause 226. The crystal form of any one of clauses 201-223, wherein the compound is an inhibitor of IRAK1 and IRAK4 and is not an inhibitor of FLT3. [00635] Clause 227. The crystal form of any one of clauses 222, 223, or 225, wherein FLT3 is selected from WT FLT3, activated FLT3, and mutated FLT3. [00636] Clause 228. The crystal form of clause 227, wherein the mutated FLT3 is D835Y mutated FLT3 or F691L mutated FLT3. [00637] Clause 229. The crystal form of any one of clauses 201-228, wherein: the water content of the crystal form is less than or equal to about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %; the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer; the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer; and/or the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [00638] Clause 230. The crystal form of any one of clauses 201-229, wherein: upon storage for 6 months at about 25 °C and about 60% relative humidity, the water content of the crystal form is less than or equal to about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %; upon storage for 6 months at about 25 °C and about 60% relative humidity, the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer; upon storage for 6 months at about 25 °C and about 60% relative humidity, the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)- enantiomer; and/or upon storage for 6 months at about 25 °C and about 60% relative humidity, the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [00639] Clause 231. The crystal form of any one of clauses 201-230, wherein: upon storage for 6 months at about 40 °C and about 75% relative humidity, the water content of the crystal form is less than or equal to about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %; upon storage for 6 months at about 40 °C and about 75% relative humidity, the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer; upon storage for 6 months at about 40 °C and about 75% relative humidity, the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)- enantiomer; and/or upon storage for 6 months at about 40 °C and about 75% relative humidity, the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [00640] Clause 232. A pharmaceutical composition comprising the crystal form of any one of clauses 201-231, and a formulary ingredient, an adjuvant, or a carrier. [00641] Clause 233. The pharmaceutical composition of clause 232, comprising between about 0.1 mg to 10,000 mg, about 1.0 mg to about 9,000 mg, about 1.0 mg to about 8,000 mg, about 1.0 mg to about 7,000 mg, about 1.0 mg to about 6,000 mg, about 1.0 mg to about 5,000 mg, about 1.0 mg to about 4,000 mg, about 1.0 mg to about 3,000 mg, about 1.0 mg to about 2,000 mg, about 1.0 mg to about 1,500 mg, about 1about 1.0 mg to about 1,000 mg, about 1.0 mg to about 750 mg, about 1.0 mg to about 700 mg, about 1.0 mg to about 650 mg, about 1.0 mg to about 600 mg, about 1.0 mg to about 550 mg, about 1.0 mg to about 500 mg, about 1.0 mg to about 450 mg, about 1.0 mg to about 400 mg, about 1.0 mg to about 350 mg, about 1.0 mg to about 300 mg, about 1.0 mg to about 250 mg, about 1.0 mg to about 200 mg, about 1.0 mg to about 150 mg, or about 1.0 mg to about 100 mg of the crystal form. [00642] Clause 233a. The pharmaceutical composition of claim 232, comprising an amount of crystal form equivalent to between about 0.1 mg to 10,000 mg, about 1.0 mg to about 9,000 mg, about 1.0 mg to about 8,000 mg, about 1.0 mg to about 7,000 mg, about 1.0 mg to about 6,000 mg, about 1.0 mg to about 5,000 mg, about 1.0 mg to about 4,000 mg, about 1.0 mg to about 3,000 mg, about 1.0 mg to about 2,000 mg, about 1.0 mg to about 1,500 mg, about 1about 1.0 mg to about 1,000 mg, about 1.0 mg to about 750 mg, about 1.0 mg to about 700 mg, about 1.0 mg to about 650 mg, about 1.0 mg to about 600 mg, about 1.0 mg to about 550 mg, about 1.0 mg to about 500 mg, about 1.0 mg to about 450 mg, about 1.0 mg to about 400 mg, about 1.0 mg to about 350 mg, about 1.0 mg to about 300 mg, about 1.0 mg to about 250 mg, about 1.0 mg to about 200 mg, about 1.0 mg to about 150 mg, or about 1.0 mg to about 100 mg of free base. [00643] Clause 234. The pharmaceutical composition of clause 232 or 233a, wherein the pharmaceutical composition is a solid dosage form. [00644] Clause 235. The pharmaceutical composition of any one of clauses 232-234, wherein the pharmaceutical composition is a capsule. [00645] Clause 236. The pharmaceutical composition of any one of clauses 232-235, wherein: the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.0 wt. %, about 1.0 wt. %, about 0.5 wt. %, or about 0.25 wt. %; the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer crystal form; the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer crystal form; and/or the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [00646] Clause 237. The pharmaceutical composition of any one of clauses 232-236, wherein: upon storage for 3 months at about 25 °C and about 60% relative humidity, the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.0 wt. %, about 1.0 wt. %, about 0.5 wt. %, or about 0.25 wt. %; upon storage for 3 months at about 25 °C and about 60% relative humidity, the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer crystal form; upon storage for 3 months at about 25 °C and about 60% relative humidity, the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer crystal form; and/or upon storage for 3 months at about 25 °C and about 60% relative humidity, the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [00647] Clause 238. The pharmaceutical composition of any one of clauses 232-237, wherein: upon storage for 3 months at about 40 °C and about 75% relative humidity, the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.0 wt. %, about 1.0 wt. %, about 0.5 wt. %, or about 0.25 wt. %; upon storage for 3 months at about 40 °C and about 75% relative humidity, the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer crystal form; upon storage for 3 months at about 40 °C and about 75% relative humidity, the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer crystal form; and/or upon storage for 3 months at about 40 °C and about 75% relative humidity, the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. [00648] Clause 239. A method of treating a disease or disorder in a subject, the method comprising administering to the subject a crystal form of any one of clauses 201-231 or the pharmaceutical composition of any one of clauses 232-238, comprising a therapeutically effective amount of the compound. [00649] Clause 240. The method of clause 239, wherein the disease or disorder is responsive to at least one of interleukin-1 receptor-associated kinase (IRAK) inhibition and fms- like tyrosine kinase 3 (FLT3) inhibition. [00650] Clause 241. The method of clause 239 or 240, wherein the administration comprises parenteral administration, a mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration. [00651] Clause 242. The method of any one of clauses 239-241, wherein the therapeutically effective amount of the compound is from about 0.005 mg/kg subject body weight to about 1,000 mg/kg subject body weight. [00652] Clause 243. The method of any one of clauses 239-242, wherein the pharmaceutical composition disintegrates in the subject’s gastrointestinal tract in about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. [00653] Clause 244. The method of any one of clauses 239-243, wherein the disease or disorder comprises a hematopoietic cancer. [00654] Clause 245. The method of any one of clauses 239-243, wherein the disease or disorder comprises myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). [00655] Clause 246. The method of clause 245, wherein MDS comprises MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2. [00656] Clause 247. The method of clause 246, wherein the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2. [00657] Clause 248. The method of clause 245, wherein AML comprises relapsed AML, refractory AML, relapsed/refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML. [00658] Clause 249. The method of clause 245, wherein AML comprises AML with a splicing factor mutation, AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the AML is not driven by FLT3 mutations but expresses IRAK4-Long. [00659] Clause 250. The method of clause 249, wherein the AML splicing factor mutation comprises AML with a splicing factor mutation in U2AF1 or SF3B1. [00660] Clause 251. The method of any one of clauses 239-243, wherein the disease or disorder comprises lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL with MYD88 mutation, follicular lymphoma, or marginal zone lymphoma. [00661] Clause 252. The method of any one of clauses 239-243, wherein the disease or disorder comprises at least one cancer selected from glioblastoma multiforme, myelofibrosis, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer. [00662] Clause 253. The method of any one of clauses 239-243, wherein the disease or disorder comprises one or more inflammatory diseases or autoimmune disease selected from chronic inflammation, sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, colitis, and atopic dermatitis. [00663] Clause 254. The method of any one of clauses 239-243, wherein the disease or disorder comprises diffuse large B-cell lymphoma (DLBCL), and wherein the DLBCL comprises a L265P MYD88 mutant (ABC) subtype of DLBCL or a S219C MYD88 mutant (GCB) subtype of DLBCL. [00664] Clause 255. The method of any one of clauses 239-243, wherein the disease or disorder is a FLT3 inhibitor resistant disease or disorder. [00665] Clause 256. The method of any one of clauses 239-243, wherein the disease or disorder is FLT3 inhibitor resistant acute myeloid leukemia (AML). [00666] Clause 257. The method of any one of clauses 239-243, wherein the disease or disorder is FLT3 inhibitor resistant refractory acute myeloid leukemia (AML). [00667] Clause 258. The method of any one of clauses 239-243, wherein the disease or disorder is FLT3 inhibitor resistant relapsed acute myeloid leukemia (AML). [00668] Clause 259. The method of any one of clauses 239-258, further comprising administering to the subject one or more additional therapies selected from: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor/hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, an antibody-drug conjugate, an mAbs/immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2/MAPK1 or ERK1/MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase/Leukotriene A4 hydrolase inhibitor, a FLT3/Axl/ALK inhibitor, a FLT3/KIT/PDGFR, PKC, and/or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB/C/VEGFR1/2/3/FLT3/CSF-1R/Kit/PDGFRA/B inhibitor, an AKT 1, 2, and/or 3 inhibitor, a ABL1/2/SRC/EPHA2/LCK/YES1/KIT/PDGFRB/FYN inhibitor, a farnesyltransferase inhibitor, a BRAF/MAP2K1/MAP2K2 inhibitor, a Menin-KMT2A/MLL inhibitor, and a multikinase inhibitor. [00669] Clause 260. The method of any one of clauses 239-259, wherein the disease or disorder is responsive to at least one of BCL2 inhibition, BTK inhibition, CDK inhibition, and DNA methyltransferase inhibition; or wherein the disease or disorder is sensitive to anti- inflammatory glucocorticoids. [00670] Clause 261. The method of clause 239 or 240, wherein the additional therapy is at least one of a BCL2 inhibitor, a BTK inhibitor, a glucocorticoid, a CDK inhibitor, and a DNA methyltransferase inhibitor. [00671] Clause 262. The method of any one of clauses 259-261, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof. [00672] Clause 263. The method of any one of clauses 259-261, wherein the disease or disorder is a BCL2 inhibitor resistant disease or disorder. [00673] Clause 264. The method of any one of clauses 259-261, wherein the disease or disorder is a venetoclax resistant disease or disorder. [00674] Clause 265. The method of any one of clauses 259-261, wherein the disease or disorder is BCL2 inhibitor resistant acute myeloid leukemia (AML). [00675] Clause 266. The method of any one of clauses 259-261, wherein the disease or disorder is venetoclax resistant acute myeloid leukemia (AML). [00676] Clause 267. The method of any one of clauses 259-261, wherein the disease or disorder is BCL2 inhibitor resistant refractory acute myeloid leukemia (AML). [00677] Clause 268. The method of any one of clauses 259-261, wherein the disease or disorder is venetoclax resistant refractory acute myeloid leukemia (AML). [00678] Clause 269. The method of any one of clauses 259-261, wherein the disease or disorder is BCL2 inhibitor resistant relapsed acute myeloid leukemia (AML). [00679] Clause 270. The method of any one of clauses 259-261, wherein the disease or disorder is venetoclax resistant relapsed acute myeloid leukemia (AML). [00680] Clause 271. The method of any one of clauses 259-261, wherein the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof. [00681] Clause 272. The method of any one of clauses 259-261, wherein the disease or disorder is a BTK inhibitor resistant disease or disorder. [00682] Clause 273. The method of any one of clauses 259-261, wherein the disease or disorder is an ibrutinib resistant disease or disorder. [00683] Clause 274. The method of any one of clauses 259-261, wherein the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone, or a pharmaceutically acceptable salt of any one thereof. [00684] Clause 275. The method of any one of clauses 259-261, wherein the disease or disorder is sensitive to anti-inflammatory glucocorticoids. [00685] Clause 276. The method of any one of clauses 259-261, wherein the disease or disorder is a dexamethasone, methylprednisolone, or prednisolone resistant disease or disorder. [00686] Clause 277. The method of any one of clauses 259-261, wherein the CDK inhibitor is selected from CDK4/6 inhibitor palbociclib, CDK7 inhibitor THZ1, and/or CDK9 inhibitors BAY1251152 and atuveciclib, or a pharmaceutically acceptable salt of any one thereof. [00687] Clause 278. The method of any one of clauses 259-261, wherein the disease or disorder is a CDK inhibitor resistant disease or disorder. [00688] Clause 279. The method of any one of clauses 259-261, wherein the disease or disorder is a palbociclib, THZ1, BAY 12511152, or atuveciclib resistant disease or disorder. [00689] Clause 280. The method of any one of clauses 259-261, wherein the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. [00690] Clause 281. The method of any one of clauses 259-261, wherein the disease or disorder is a DNA methyltransferase inhibitor resistant disease or disorder. [00691] Clause 282. The method of any one of clauses 259-261, wherein the disease or disorder is an azacitidine resistant disease or disorder. [00692] Clause 283. The method of any one of clauses 259-261, wherein the disease or disorder is a BCL2 inhibitor and DNA methyltransferase inhibitor resistant disease or disorder. [00693] Clause 284. The method of any one of clauses 259-261, wherein the disease or disorder is a venetoclax and azacitidine resistant disease or disorder. [00694] Clause 285. The method of any one of clauses 249-251, wherein the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof and the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. [00695] Clause 286. The method of clause 259, wherein the crystal form of any one of clauses 201-231 or the composition of any one of clauses 232-238 and the one or more additional therapies are administered together in one administration or composition. [00696] Clause 287. The method of clause 259, wherein the crystal form of any one of clauses 201-231 or the composition of any one of clauses 232-238 and the one or more additional therapies are administered separately in more than one administration or more than one composition. [00697] Clause 288. The method of any one of clauses 239-287, wherein the disease or disorder is alleviated by inhibiting at least one of IRAK1, IRAK4, and FLT3 in the subject. [00698] Clause 289. The method of any one of clauses 239-288, wherein the disease or disorder is alleviated by inhibiting at least two of IRAK1, IRAK4, and FLT3 in the subject. [00699] Clause 290. The method of any one of clauses 239-289, wherein the disease or disorder is alleviated by inhibiting IRAK1 and IRAK4 in the subject. [00700] Clause 291. The method of any one of clauses 239-289, wherein the disease or disorder is alleviated by inhibiting IRAK1, IRAK4, and FLT3 in the subject. [00701] Clause 292. The method of any one of clauses 288, 289, or 291, wherein FLT3 is selected from WT FLT3, activated FLT3, and mutated FLT3. [00702] Clause 293. The method of clause 292, wherein the mutated FLT3 is D835Y mutated FLT3 or F691L mutated FLT3. EXAMPLES [00703] The following non-limiting examples are provided to further illustrate embodiments of the disclosure disclosed herein. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent approaches that have been found to function well in the practice of the disclosure, and thus can be considered to constitute examples of modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments that are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure. Example 1: Salt & Polymorph Screen of Compound 106 Instruments and Methods [00704] Powder X-Ray Diffraction (PXRD) Instrument: Panalytical Empyrean Parameters: X-Ray tube Cu (Kα radiation); tube voltage 45 kV; tube current 40 mA Scanning range [°2θ]: 2 to 40 Step size [°2θ]: 0.013 degree Scan type: Continuous [00705] Proton Nuclear Magnetic Resonance (¹HNMR) Instrument: Bruker 400 Ultrashield Solvent: DMSO-d6 [00706] Differential Scanning Calorimetry (DSC) Instrument: TA Instruments DSC 2500 Parameters: Ramp 0.5/10 °C per minute, up to 250/300 °C [00707] Thermo-Gravimetric Analysis (TGA) Instrument: TA Instruments TGA 5500 Parameters: 25 to 300 °C, 10 °C/min, 50 mL/min N2 sweep Attorney Docket No.: 130364-5014-WO [00708] Polarized Light Microscopy (PLM) Instrument: Nikon Eclipse Ci Pol Software: Nikon NIS Elements [00709] Dynamic Vapor Sorption (DVS) Instrument: DVS Intrinsic, Surface Measurement Systems Parameters: 25 °C, 30-90-0-90-0% RH for 2 cycles [00710] High-Performance Liquid Chromatography (HPLC) Instrument: Agilent 1260 Infinity II Column: SB-Aq 3.5 μm, 150 x 4.6 mm, PN: 863953-914 (purchased) Column temperature: 25 °C Flow rate: 1.0 mL/min Mobile phase A: 0.1% v/v TFA in DI H2O Mobile phase B: 0.1% v/v TFA in MeCN Diluent: 20:80 MeCN/water Injection volume: 10 µL Concentration: 0.25 mg/mL [00711] Liquid Chromatography–Mass Spectrometry (LC-MS) LC conditions are the same as the original HPLC method Instrument: CY-LCMS-01 (Agilent 1290 Infinity LC system with 6140 Quadrupole MS system) Ionization Mode: API-ES Polarity: Positive Frag mentor: 125 Mass Range:100-1000 Gas Temperature: 350 °C Nebulizer pressure: 35 psig Drying Gas: 12 L/min Characterization of Starting Material (SM, Compound 106 bis-HCl salt) [00712] Two kinds of SM were received: 8 grams of SM with a liquid chromatography area % (LCAP) purity of 82% and 55 grams of SM with a LCAP purity of 98%. Both were yellow powders with poor crystallinity and highly hygroscopic under ambient conditions. The SM was characterized by powder X-ray diffraction (PXRD), polarized light microscopy (PLM), differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), HPLC, and ¹HNMR. The results are depicted in FIGS.1A-1H. Preparation and Characterization of Free Base (FB) from SM (LCAP purity ~82%) [00713] Salt Break Procedure Table 1. Salt break of SM (LCAP ~84%) procedure Step Procedure Comment 1 Add 5 g of SM (LCAP ~84%) to a 500 mL glass bottle Off White solids

HNMR: FB only C^{haracterize solid by 1}HNMR (DMSO-d₆: FIG.2C; HPLC: Purity ~92.5% p

d from the lower purity starting material. [00715] HPLC Method Development and Calibration/Linearity Curve for FB Table 2. HPLC and MS method details HPLC conditions Column Temperature: 25ºC Injection Volume: 10 μL

[00716] FIG.4 is an HPLC-UV chromatogram of the SM (initial intermediate method, 81.6%). FIGS.5A-5C are UV, TIC, and MS characterization of the SM (developed method, 81.8%). FIGS.6A-6C UV, TIC, and MS characterization of the FB (Lot 1011-62-4). FIGS.7A- 7F are LCMS spectra of the SM and FIGS.8A-8F are LCMS spectra of the FB (Lot 1011-62-4). A calibration/linearity curve was constructed, which gave R² of 0.9998 with Lot 1011-74-1 as the reference standard (FIG.9). [00717] Recovery of FB from Salt Screening Experiments At [00718] A recovery experiment (Exp 1011-70-2) of FB from 25 salt screen experiments was conducted to generate more FB using the procedure in Table 3. FIG.10A is an image of the recovered FB and FIG.10C is a TGA-DSC overlay of the recovered FB (Lot 1011-70-2). Table 3. The procedure for recovery of FB Step Procedure Comment 1 Add DCM to 25 vials and combine them in a beaker Yellow hazy solution 4

[00719] Purification of FB [00720] Purification of the FB (Lot 1011-62-4) was attempted via TLC. Six eluents were used, and none were able to separate the FB and the impurities (Table 4 and FIG.10B). Table 4. TLC details E_{luent V/V} ^Elution t_{imes Result}

y y break. The purity of the FB was upgraded from 84% to 97%. [00722] Preparation and characterization of TSA-1 are shown in Table 5 and FIGS.12A- 12C. Preparation of the FB from TSA-1 salt break was conducted through the following procedure shown in Table 5. Table 5. Procedure for the preparation of FB from TSA-1 salt break Step Procedure Comment A^{dd DCM to 100 m TSA (Lot 1011-72-1) in a 20} 4

₁₂ ^{Add 50 mL water to the separatory funnel containing} t_{he DCM phase} nt

[ 7 ] a y o e c c o o s [00724] FB (Lot 1011-62-4) stability was evaluated in 3 pH buffers: pH = 1, 3, and 4 with the results summarized in Table 6. No degradation was found in all three solutions for up to three days at RT. Experimental: 1) 10 mg of FB (Lot 1011-62-4) was added in 400 µL of media targetting to get slurry. 2) The slurry was agitated with a stir bar at 25 °C over the weekend. 3) The mother liquour (ML) and solids in the slurry were separated via centrifuge. 4) The purity of the ML was tested by HPLC. 5) The post-media pH was measured. 6) The HPLC data was compared with the SM (ID: NCGC00841450-05; Vial Barcode: S000001VA) and two batches of FB: Lot 1011-62-4 and Lot 1011-63-4 (FIGS.13A-13F). Table 6. Stability experiment results and HPLC details HPLC SM FB FB FB FB FB 3)

0.42 0 0 0 0 57.7286* 71.248* 0.62 0.1604 0.2161 0 0.1995 0 0

[00726] The approximate solubility of the FB (Lot 1011-84-1) was estimated in 20 solvents at RT. Crystallization screening in 11 solvents yielded 10 crystalline FB (FB-1) and one grease (FIG.14). The results are summarized in Table 7. Experimental: 1) Weighed ~ 5 mg of FB (Lot 1011-84-1) into a 4.0 mL vial. Added 25 µL (0.025 mL) of solvent using a micropipette at RT. 2) The solution was shoke and stirred. If no clear solution was obtained, another 25 µL was added and repeated until 4 mL solvent was added. 3) More FB was added into the vials to make a slurry (t₀). 4) The solution was stirred overnight. 5) PXRD was run for the resulting solids. Table 7. Approximate solubility of FB and crystallization screening b.p Added Solubil Crystallization S_l ^Solvent l ity i D 1 1 1 1 1 1

17 1,4-Dioxane 2 101 0.025 >>200 TS HS FB-1 18 2-MeTHF* 2 80.2 0.025 >>200 CL - - 1 1 1

Preparation and Characterization of FB from SM (LCAP purity ~98%) [00727] Salt Break Procedure Table 8. Salt break of SM procedure Step Procedure Comment A^{dd 15 g of SM (ID: NCGC00841450-06; Vial}

₁₆ ^{Foam oil under vacuum using a rotavap with RT and at} 2_{5 mBara for 3 hours Slightly yellow solids} s , p

y [00729] A Tg of 44.19 °C and crystallization onset temperature of 120.32 °C were observed from the DSC thermogram. Crystalline FB (FB-1) was obtained by heating FB (5 mg, Lot 1011-84-1) in a TGA pan up to 125 °C, holding 125 °C for 10 min, and cooling down to RT. [00730] To obtain more FB-1, crystallization of FB (200 mg, Lot 1011-84-1) was conducted by heating 200 mg FB (Lot 1011-84-1) in a 20 mL vial up to 125 °C with a hotplate and holding 125 °C for 10 min (Exp 1011-85-5). 190 mg of FB-1 was obtained from 200 mg of amorphous FB (Lot 1011-84-1). FIG.16 shows the PXRD pattern overlay of a) amorphous FB (Lot 1011-84-1), b) product post TGA, and c) product in Exp 1011-85-5. FIGS.17A-17H provide characterization of FB-1 (Lot 1011-85-5) by PLM (FIG.17A), PXRD (FIG.17B), ¹HNMR (FIG.17C), HPLC (FIG.17D, 98.88% purity), TGA-DSC (FIG.17E), dynamic vapor sorption (DVS, FIGS.17F and 17G), and PXRD post DVS (FIG.17H). Table 9. PXRD data of FB-1 (Lot 1011-85-5) Peak # Pos. [°2θ] Height [cts]

13 19.3265 194.07 14 20.0082 1520.77

[00731] Solubility Estimation of FB-1 and Polymorph Screening [00732] The approximate solubility of FB-1 (Lot 1011-93-2) was estimated in 15 solvents at RT. Polymorph screening in 15 solvents yielded 14 FB-1 and one new salt, designated as ACE-1. The results are summarized in Table 10. Experimental: 1) Weighed 5 mg of FB-1 (Lot 1011-93-2) into a 4.0 mL vial. Added 25 µL (0.025 mL) of solvent using a micropipette at RT. 2) The solution was shoke and stirred. If no clear solution was obtained, another 25 µL was added and repeated until 4 mL solvent was added. 3) More FB was added into the vials to make a slurry (t₀). 4) The slurry was stirred over the weekend at RT (t_2d). 5) PXRD was run for the resulting solids to determine form change. Table 10. Solubility measurements of FB-1 and polymorph screening Added Approxim Polymorph 1_{011-94 Solvent} ^Solvent b.p ate sol screening C_l (°C) vent solubility D 1

. y , , , -3, e) 1011-94-4, f) 1011-94-5, g) 1011-94-6, h) 1011-94-7, i) 1011-94-8, j) 1011-94-9, k) 1011-94- 10, l) 1011-94-11, m) 1011-94-12, n) 1011-94-13, o) 1011-94-14, and p) ACE-1: 1011-94-15. ACE-1 (Lot 1011-94-15) was characterized by PXRD (FIG.19A, Table 11), ¹HNMR (FIG. 19B), TGA, and DSC (TGA-DS: FIG.19C). [00734] Heating ACE-1 to 130 ºC afforded a desolvated form, designated as ACE-2. Lot1011-99-16 of ACE-2 was characterized by PXRD (FIG.20A, Table 12), ¹HNMR (FIG.20B), TGA, and DSC (TGA-DSC: FIG.20C). Table 11. PXRD peaks of ACE-1. Peak # Pos. [°2θ] Height [cts]

11 18.4708 375.26 12 18.8843 52.20

Table 12. PXRD peaks of ACE-2. Peak # Pos. [°2θ] Height [cts] 1 62182 6234

16 24.4393 10.16 17 25.0411 12.24 [00735] Kinetic Solu

[00736] Kinetic solubility measurements of FB-1 (Lot 1011-88-2) were measured in water and three biorelevant media and the results are summarized in Table 13. Biorelevant media were prepared as per the instruction provided. The solubility is in the range of 3.7 to 26.1 mg/mL. No form changes were obtained. Experimental: 1) 30 mg of FB-1 was added to 300 µL of media to get a slurry. 2) The slurry was agitated with a stir bar at 37 °C. 3) The pH was checked and HPLC was run at 1h, 4h, and 24 h time points. 4) PXRD of the residue solids was run at 24h time point (FIG.21). Table 13. Kinetic solubility measurements Sample Concent 1011-91 Sample added _Media ^Initial ration (_mg/mL) ^pH _PXRD 1 1 1 1

[00737] Two-Week Stability Study of FB-1 [00738] The two-week solid-state stability started with FB-1 (Lot 1011-88-2) under three conditions (25 ºC/60% RH, 40 ºC/75% RH, and 60 °C) with open and closed dish (Tables 14 and 15, FIGS.22A-22F (FB-1 control, t₀ timepoint), FIGS.23A-23F (FB-1 control, 1w timepoint), FIGS.24A-24F (FB-1 control, 2w timepoint), FIGS.25A-25F (FB-1, 1w timepoint), and FIGS. 26A-26F (FB-1, 2w timepoint)). FB-1 remained with high crystallinity after the one-week and two-week pull. Slight liquid chromatography area % (LCAP) (based on FB) fluctuations were found. Table 14. Stability assessment summary Form Standard 25 °C/60% RH 40 °C/75% RH 60 °C

t0 1w 2w open closed open closed open closed 1w 2w 1w 2w 1w 2w 1w 2w 1w 2w 1w 2w FB-1 99.06 98.80 98.91 98.71 98.90 98.83 98.81 98.90 98.29 98.82 98.45 98.52 98.53 98.60 98.25

1^{-90-1 Sto} Timepoint 1^{01 rage} C_onditions ^Analysis FB-1 FB-1 FB-1 1w 2w 1 % 0 1 % 9 1 % 3 1 % 1

PXRD FB-1 FB-1 FB-1 FB-1 FB-1 HPLC (RRT) Area% Area% Area% Area% Area% 2 5 1 % 5

[00739] G. 7 s a overay o a) - , b) 0 -90- - w, c) 0 -90- - w, d) 1011-90-1C-1w, e) 1011-90-1D-1w, f) 1011-90-1E-1w, and g) 1011-90-1F-1w. FIG.27B is a PXRD overlay of a) FB-1, b) 1011-90-1A-2w, c) 1011-90-1B-2w, d) 1011-90-1C-2w, e) 1011- 90-1D-2w, f) 1011-90-1E-2w, and g) 1011-90-1F-2w. Salt Screen [00740] pKa Prediction of FB [00741] No acid pK_a was predicted. The strongest pK_a (Base) was predicted to be 9.3 + - 0.1 (at atom number 21, FIG.28). [00742] Salt Screen #1 [00743] 50 salt screen experiments were conducted using 10 acids and 5 solvents. Five crystalline hits were obtained and two of them exhibited noval patterns. Slow evaporation for clear solutions at RT over 7 days yielded no crystalline hits. Grease was obtained from the other 21 experiments. Results are demonstrated in Table 16. Experimental: 1) ~ 30 mg of FB (Lot 1011-63-4, purity ~92.5%) was added into a 4.0 mL vial. 2) 1.0 equiv. counterion was added into the vial. 3) 0.3 mL of selected solvent was added. 4) The vial was agitated at RT with a stir bar overnight and over the weekend. 5) PLM, PXRD, HPLC, and ¹HNMR analysis were conducted for the crystalline products obtained. Table 16. Salt screen (10 acids × 5 solvents, loading: 1.0 equiv. acid, FB 100 mg/mL) Solvent EtOH MeCN THF EtOAc Acetone: ) d R R R * R _* S R R R R

shown in FIGS.29A-29B. PXRD spectra of the products are shown in FIGS.30A-30D. [00745] Scale-up and Characterization [00746] A scale-up of TSA-1 to 100 mg (Lot 1011-71-1), 300 mg (Lot 1011-68-1), 400 mg (Lot 1011-76-3), 500 mg (Lot 1011-71-1, 1011-72-1, 1011-85-1, 1011-88-4), 2 g (Lot 1011- 89-1), and 2.2 g (Lot 1011-76-4) of FB as well as a scale-up of TAR-1 to 50 mg (Lot 1011-76-5), 500 mg (Lot 1011-85-2), 800 mg (Lot 1011-88-5), and 2 g (Lot 1011-89-2) were performed to afford material for full characterization and further studies. Details of the preparation procedure for TSA-1 (1011-89-1) and TAR-1 (1011-89-2) are given in Table 17. The scaled-up TSA-1 was analyzed by PLM (FIG.31A), DVS (FIG.31B), PXRD (FIG.31C), DSC, TGA (DSC-TGA: FIG.31D), and ¹HNMR (FIG.31E). The PXRD peaks of TSA-1 (possibly in monohydrate form) are provided in Table 18. The scaled-up TAR-1 was analyzed by PLM (FIG.32A), DVS (FIG. 32B), PXRD (FIG.32C), DSC, TGA (DSC-TGA: FIG.32D), and ¹HNMR (FIG.32E). The PXRD peaks of TAR-1 (possibly in hydrate form) are provided in Table 19 respectively. Table 17. Preparation of TSA-1 (1011-89-1) and TAR-1 (1011-89-2) Starting Materials COMP FB (Lot 1011-88-1) FB (Lot 1011-88-1)

abe 8. pea s o S - ( ot 0 -89-) Peak # Pos. [°2θ] Height [cts] 1 5.1743 1879.49

Table 19. PXRD peaks of TAR-1 (1011-89-2)

28 26.7874 88.49 29 27.7072 85.98 [00747] Solubility E

[00748] A solubility estimation of TSA-1 (Lot 1011-68-1) was conducted in 12 solvents at RT (Table 20). A polymorph screening of the tosylate in 8 solvents at RT for 4 days confirmed no polymorph was found. TSA-1 in MeCN, MEK, THF, water, and acetone exhibited improved purity. TSA-1 in water exhibited the highest purity of 99.4%. Experimental: 1) Weighed ~ 5 mg of TSA-1 (Lot 1011-68-1) into a 4.0 mL vial. Added 25 µL of solvent using a micropipette at RT. 2) The solution was stirred and shoke. If no clear solution was obtained, another 25 µL of solvent was added and repeated until 4 mL solvent was added. 3) More TSA-1 (Lot 1011-68-1) was added into the vials containing the clear solution to make a slurry (t₀). 4) The slurry was stirred for 3 days (t3d). 5) The slurry was checked for solids via PXRD (FIG.33) and HPLC (Table 21 and FIGS.34A- 34I). Table 20. Approximate solubility of TSA-1 and polymorph screening S^olvent Added Polymorph screening Solubility i^t ) ₃ 2 8 1 3

8 THF 2 4 <1.25 TS TS TSA-1 98.72 9 Water - 2.5 2-2.5 TS TS TSA-1 99.39 10 A t 3 4 <125 TS TS TSA 1 9880

Table 21. HPLC details of polymorph screening of TSA-1 Exp ^1011- 1011-71- 1011- 1011- 1011- 1011- 1011- 1011- 1011- 6_8-1 3 71-4 71-5 71-6 71-7 71-8 71-9 71-10 8 0 1

[00749] A new crystalline tosylate salt, designated as TSA-2, was obtained by agitation of TSA-1 in water at RT/50 °C overnight. A scale-up of TSA-1 to 80 mg (Lot 1011-75-2) and 500 mg (Lot 1011-88-3) of TSA-1 was performed to afford material for full characterization and further studies. TSA-1 and TSA-2 were compared by PLM, ¹HNMR, HPLC-UV, DSC, TGA, PXRD, and DVS, with the data for TSA-1 shown in FIGS.31A-31F. TSA-2 was characterized with PLM (FIG.35A), DVS (FIG.35B), PXRD (FIG.35C), DSC, TGA (TGA-DSC: FIG.35D), ¹HNMR (FIG.35E) and HPLC-UV (FIG.35F). The PXRD peaks of TSA-2 (possibly in monohydrate form) are provided in Table 22. Table 22. PXRD peaks of TSA-2 (Lot 1011-75-2) Peak # Pos. [°2θ] Height [cts]

8 13.5257 360.74 9 14.0442 247.16

[00750] Kinetic Solubility Measurements of TSA-2 and TAR-1 at 37 °C [00751] FIGS.36A-36B are PXRD patterns of TSA salts. [00752] Kinetic solubility measurements of TSA-2 (Lot 1011-88-3) and TAR-1 (Lot 1011-88-5) were taken in water and three biorelevant media and the results are summarized in Table 23. Biorelevant media were prepared as per the instruction provided. For TSA-2, the solubility was in the range of 2.8-18.7 mg/mL and no form changes were obtained in water at 24 h. A mixture of TSA-2 and a new form, designated as TSA-3, was obtained in SGF and FaSSIF at 24 h and TSA-3 was obtained in FeSSIF at 24 h. The PXRD of TSA-3 is shown in FIG.37A, the PXRD peaks are listed in Table 24, and the ¹HNMR spectrum is provided in FIG.37B. For TAR-1, instant dissolution was found, and the solubility was greater than 400 mg/mL. Experimental: 1) At most 120 mg of sample (TSA-2 and TAR-1) were added to 300 µL of media to get a slurry. 2) The slurry was agitated with a stir bar at 37 °C. 3) The pH and HPLC of the mother liquor was checked at the 1h, 4h, and 24 h time points. 4) PXRD of the residue solids was run at 24h time point. 5) If no solids were obtained, the concentration is > 400 mg/mL. HPLC and PXRD were not measured. Table 23. Kinetic solubility measurements Sample Concentration 1011-91 Sam le added _Media ^Initial _{(m /mL)} ^pH _PXRD f d f d

Table 24. Peak table of TSA-3 PXRD pattern Pos. [°2θ] Height [cts]

7.7311 878.06 8.6730 470.34

31.7008 105.42 32.9084 248.96 [00753] Two-wee

a y u y o - a - [00754] A two-week solid-state stability was run, starting with TSA-2 (Lot 1011-88-3) and TAR-1 (Lot 1011-88-5) under three conditions 25 ºC/60% RH, 40 ºC/75% RH, and 60 °C with open and closed dish. All four samples remained with good crystallinity after a one-week and two-week pull. Slight LCAP (based on FB) fluctuations were found. The stability assessment summary of TSA-2 and TAR-1 is provided in FIG.38A with the individual stability assessments provided in Table 25 (TSA-2) and Table 26 (TAR-1). The PXRD spectra of TSA-2 are provided in FIGS.38B-38C. The stability assessment of TSA-2 is provided in FIGS.39A- 39F (TSA-2 control, t₀ timepoint), FIGS.40A-40F (TSA-2 control, 1w timepoint), FIGS.41A- 41F (TSA-2 control, 2w timepoint), FIGS.42A-42F (TSA-2, 1w timepoint), and FIGS.43A-43F (TSA-2, 2w timepoint). The PXRD spectra of TAR-1 are provided in FIGS.44A-44B. The stability assessment of TAR-1 is provided in FIGS.45A-45F (TAR-1 control, t₀ timepoint), FIGS.46A-46F (TAR-1 control, 1w timepoint), FIGS.47A-47F (TAR-1 control, 2w timepoint), FIGS.48A-48F (TAR-1, 1w timepoint), and FIGS.49A-49F (TAR-1, 2w timepoint). Table 25. Stability assessment of TSA-2 (Lot 1011-88-3) S_torage Timepoint 2 %

1.14 0 0 0 0.24 0 40 °C / PXRD TSA-2 TSA-2 TSA-2 TSA-2 TSA-2 % 2 % 2 % 2 % 2 %

Table 26. Stability assessment of TAR-1 (Lot 1011-88-5) S^torage Timepoint A^nalysis TAR-1 TAR-1 TAR-1

1.00 98.94 99.22 98.22 98.68 98.63 1.07-1.08 1.06 0.78 1.02 0.52 0.82

[00755] Salt Screen #2 [00756] 50 new salt screen experiments were conducted using 10 acids and 5 solvents. 19 crystalline hits were obtained and 7 exhibited novel patterns. The results of the salt screen are provided in Table 27. Experimental: 1) Added ~30 mg of FB (Lot 1011-78-1, purity ~96.2%) into a 4.0 mL vial. 2) Added 1.0 equiv. counterion into the vial. 3) Added 0.3 mL of selected solvent. 4) Agitated at RT with a stir bar for 4 days (t). 5) Observed resulting slurries with PLM (FIG.50) to obtain crystalline solids. 6) Conducted PXRD analysis for crystalline solids obtained to obtain crystalline salts. 7) Dried crystalline salts in a vacuum oven at RT overnight. 8) Conducted PXRD, HPLC, HNMR, TGA, and DSC analysis for dried crystalline products. 9) Slow evaporation for clear solutions is ongoing. Table 27. Salt screen (10 acids × 5 solvents, loading: 1.0 equiv. acid, FB 100 mg/mL) Solvent 1011-79 Acid Class pKa EtOH MeCN THF EtOAc Acetone:water R^R ^R ^R ^R ^R ^R ^R ^R ^R

Acid pattern [00757] 19 crystalline solids were observed by PLM in 19 experiments that afforded solids. 11 crystalline salts obtained with benzenesulfonic acid, ethane sulfonic acid, methane sulfonic acid, L-aspartic acid, maleic acid, and glycolic acid (named as BSA-1, ESA-1, MSA-1, ESP-1, MAL-1, GLY-1, and GLY-2). PXRD patterns remained after vacuum drying at RT overnight. The purity was in the range of 95.2% -96.9%, which is similar to the FB used with LCAP of 96.2%. [00758] FIG.51A is a PXRD overlay of a) benzenesulfonic acid (BSA), and the benzenesulfonic acid salts obtained from the experiment in Table 27. FIG.51B is the PXRD pattern of BSA-1, with the peaks provided in Table 28. FIGS.51C-51E are DSC-TGA overlays of benzenesulfonic acid salts obtained from the experiment in Table 27. FIG.52A is PXRD overlay of salts obtained from ESA from the experiment in Table 27. FIG.52B is the PXRD pattern of ESA-1, with the peaks provided in Table 29. Table 28. Peak table of BSA-1 PXRD pattern Peak # Pos. [°2θ] Height [cts]

4 11.2206 257.48 5 12.2073 272.12

Table 29. Peak table of ESA-1 PXRD pattern Peak # Pos. [°2θ] Height [cts]

2 9.4378 185.71 3 10.5830 85.72

[00759] PXRD overlays of the L-aspartic acid solids collected from the experiment in Table 27 are shown in FIG.53, PXRD overlays of the L-ascorbic acid solids collected from the experiment in Table 27 are shown in FIG.65, PXRD overlays of the glutamic acid solids collected from the experiment in Table 27 are shown in FIG.54, and PXRD overlays of the glycolic acid solids collected from the experiment in Table 27 are shown in FIG.55. [00760] FIG.56A is a PXRD overlay of maleic acid and maleic acid salts obtained from MeCN (see experiment in Table 27). FIG.56B is the PXRD pattern of MAL-1, with the peaks provided in Table 30. FIG.56C is a DSC-TGA overlay of MAL-1. Table 30. Peak table of MAL-1 PXRD pattern Peak # Pos. [°2θ] Height [cts]

9 16.5998 133.91 10 17.8112 151.49

. SA salts obtained from the experiment in Table 27. FIGS.57B-57D are DSC-TGA overlays of the MSA salts obtained from the experiment in Table 27. [00762] FIG.69A is a PXRD overlay of L-aspartic acid and the L-aspartic acid salts obtained from the experiment in Table 27. FIG.69B is a DSC-TGA overlay of ASP-1. [00763] FIGS.70A-70B are DSC-TGA overlays of the glycolic acid salts obtained from the experiment in Table 27. [00764] FIGS.70A-70C are PXRD and DSC-TGA characterization of glycolic salts from the experiment in Table 27. [00765] FIGS.71A-71J are HPLC-UV chromatograms and FIGS.72A-72K are ¹HNMR spectra of the salts obtained from the experiment in Table 27. [00766] Scale-up and Characterization [00767] A scale-up of MSA-1 to 300 mg (Lot 1011-85-3), 800 mg (Lot 1011-88-6), and 2 g (Lot 1011-89-3) of FB were performed to afford material for full characterization and further studies. Details of the preparation procedure for MSA-1 (1011-85-3) are given in Table 31. The MSA-1 salt (possibly in a neat form) was analyzed by PLM (FIG.58A), DVS (FIG.58B), PXRD (FIG.58C, peaks in Table 32), DSC, TGA (DSC-TGA: FIG.58D), and ¹HNMR (FIG. 58E). Table 31. Preparation of MSA-1 (Lot # 1011-85-3) Starting Materials

Exp ID 1011-85-3 1. Weighed 300 mg of FB (Lot 1011-84-1) into a 40 mL vial. .

Peak # Pos. [°2θ] Height [cts] 1 9.4332 240.48

33 38.3512 34.52 34 39.4875 28.64 [00768] Kineti

[00769] Kinetic solubility measurements of MSA-1 (Lot 1011-88-6) were measured in water and three biorelevant media and the results are summarized in Table 33. Biorelevant media were prepared as per the instruction provided. Instant dissolution was found, and solubility is greater than 400 mg/mL. Experimental: 1) 120 mg of MSA-1 was added to 300 µL of media to get a slurry. 2) The slurry was agitated with a stir bar at 37 °C. 3) The pH and HPLC of the mother liquor were checked at 1h, 4h, and 24 h time points. 4) PXRD of the residue solids was run at 24h time point. 5) If no solids were obtained, the concentration is > 400 mg/mL. HPLC and PXRD were not measured. Table 33. Kinetic solubility measurements 1011- Sample Concentration S^ample added _Media ^Initial _(mg/mL) ^pH _PXRD

[00770] Two-week Stability Study MSA-1 [00771] A two-week solid-state stability study was run with MSA-1 (Lot 1011-88-6) under three conditions 25 ºC/60% RH, 40 ºC/75% RH, and 60 °C with open and closed dish. All four samples remained with good crystallinity after a one-week and two-week pull. Slight LCAP (based on FB) fluctuations were found. A summary of the stability study is provided in FIG. 59A with the PXRD patterns from the one week pull in FIG.59B and those from the two week pull in FIG.59C. The stability assessment is shown in Table 34 and FIGS.60A-60F (MSA-1 control, t₀ timepoint), FIGS.61A-61F (MSA-1 control, 1w timepoint), FIGS.62A-62F (MSA-1 control, 2w timepoint), FIGS.63A-63F (MSA-1, 1w timepoint), and FIGS.64A-64F (MSA-1, 2w timepoint). The PXRD spectra of TAR-1 are provided in FIGS.44A-44B. Table 34. Stability assessment of MSA-1 (Lot 1011-88-6) 1011- Storage Timepoint 90-4 _Conditions ^Analysis MSA-1 MSA-1 MSA-1 ^{1w 2w} 1 1 1 1

1.32 0 0.12 0 0 0 1.43 0 0 0.10 0 0 1 1

[00772] DVS of TSA-2 [00773] DVS analysis was conducted on TSA-2 (Lot 1011-75-2) (FIG.66A). TSA-2 was non-hygroscopic with a moisture uptake of 3.193% at 80% RH and the isotherm suggested a monohydrate when RH >10%. A PXRD pattern of the solids post DVS (FIG.66B) matched TSA-2 with a few extra peaks after ¹HNMR (FIGS.66C and 66D) and HPLC (FIG.66E) analysis. [00774] TGA-PXRD-DSC analysis of TSA-2 [00775] TGA-PXRD-DSC analysis of TSA-2 (Lot 1011-75-2) was conducted and confirmed that TSA-2 is a reversible hydrate. TGA showed 3.101 % weight loss (67B). The PXRD pattern of solids post TGA (FIG.67C) matched TSA-2 with extra peaks confirmed by ¹HNMR and (FIGS.67D and 67E) HPLC (FIG.67A) analysis. DSC showed a 1^st endotherm at 61.57 °C, 2^nd endotherm (mp of TSA-1) at 123.93 °C, and 3^rd endotherm (mp of TSA-2) at 175.83 °C (FIG.67F). [00776] Experimental: 1) Run TGA for TSA-2 (Lot 1011-75-2) with temp range of RT to 100 °C. 2) Run PXRD for products after TGA. 3) Run DSC, HPLC, and ¹HNMR for products after TGA. [00777] DSC heat-cool-heat analysis of TSA-2 (Lot 1011-75-2) was conducted (FIG. 67G). Only the 1^st endotherm (water) was displayed in the 1^st heating and only the 2^nd endotherm (m.p.) was displayed in the 2^nd heating. Water molecules in TSA-1 were eliminated in the 2^nd heating with the crystallinity of structure. [00778] DVS analysis of TAR-1 [00779] TAR-1 was possibly hygroscopic with a moisture uptake of 8.046% @ 80% RH (FIG.68A). The PXRD pattern of the solids remaining post DVS demonstrated high crystallinity (FIG.68B). Mono-HCl Salt of Compound 106 [00780] Two different lots of starting material (SM) were received for the preparation of the mono-HCl salt of Compound 106 (Lot# 1050-19-2 and Lot# 1036-84-8). Lot# 1050-19-2 was characterized by ¹HNMR (FIG.74A), HPLC (FIG.74B), PLM (FIG.74C), and DSC-TGA (FIG.74D). Lot# 1036-84-8 was also characterized by ¹HNMR (FIG.75A), HPLC (FIG.75B), PLM (FIG.75C), and DSC-TGA (FIG.75D). The results of both lots are summarized in Table 35. Table 35. Characterization of Compound 106 mono-HCl salt SM (Lot# 1050-19-2 and 1036-84- 8) Characterization of Compound 106 mono-HCl salt SM L t ID C m nd 106 HCl lt SM C m nd 106 HCl lt SM

[00781] The PXRD spectra of the Compound 106 mono-HCl salt SM are depicted in FIGS.73A-73B with the peaks listed in Table 36. An ¹HNMR overlay of Lot# 1036-84-8 (bottom) and Lot# 1050-19-2 (top) is in FIG.76. Table 36. PXRD peaks of the mono-HCl salt SM of Compound 106. Peak # Pos. [°2θ] Height [cts]

1 2.0916 351.93 2 6.8619 1456.89

46 37.3533 38.93 47 38.0511 25.62 [00782] The Compoun

0-19-2) was analyzed by DVS (0-90-0-90-0% RH at 25 °C) (FIG.77). Based on the moisture uptake of the sorption isotherm at 80% RH showing 0.24%, the material was classified as slightly hygroscopic and the post DVS sample showed no change in PXRD (FIG.78). [00783] Kinetic solubility measurements of the mono-HCl salt (Lot# 1050-19-2) are summarized in Table 37. Biorelevant media were prepared. Approximately 50 mg of SM was added to 0.5 mL of the media in an attempt to obtain a slurry. The experiments were conducted at a temperature of 37 °C. At all of the time points, the solutions in all four media were clear, and no solids were obtained for PXRD measurement. The concentration was concluded to be > 100 mg/mL in all media at all time points. The pH of the media was measured 24 hours after the experiment. [00784] Experimental: 1) 50 mg of mono-HCl (Lot# 1050-19-2) was added to 500 μL of media in an attempt to obtain a slurry. 2) The slurry was agitated with a stir bar at 37 °C. 3) If a slurry was obtained, the concentration was checked by HPLC at 1h, 4h, and 24 h time points. 4) PXRD of the residue solids (if any) was run and the pH of the mother liquour was checked at 24h time point. Table 37. Mono-HCl (Lot# 1050-19-2) solubility data in water and biorelevant media Exp ID Conce 9_{9 58} ^M ntration 1₀ ^edia _{/ L} ^24h

Conclusions [00785] Compound 106 is a basic molecule with a pKa of 9.3. A salt screen with 20 acids in 5 solvents afforded seven crystalline salts, including tosylate, besylate, esylate, mesylate, L- tartarate, L-aspartate, and maleate. One additional crystalline salt, an acetate, was found during crystallization screening of the free base. The free base was successfully crystallized from heating amorphous solids at ~125 °C. The free base and three salt forms (mesylate, tartrate, and tosylate) were scaled up to gram scale and further characterized and evaluated against salt form selection criteria, e.g., hygroscopicity, kinetic solubility and 2-week stability under 25 °C/60 % RH, 40 °C/75 % RH, and 60 °C in open and close conditions. Example 2: Single Crystal X-ray Diffraction Analysis of Compound 106 Free Base Experimental Methods [00786] Bruker D8 QUEST Single-crystal X-ray Diffractometer, equipped with high brightness IµS 3.0 microfocus (50kV x 1 mA) for Cu radiation (λ = 1.54178 Å) and with PHOTON II Charge-Integrating Pixel Array Detector of superior speed, sensitivity, and accuracy, was used for screening/evaluation of crystals and for diffraction data collection. Bruker APEX3 software suite was used for diffraction experiments including data collection and integration, and for solving, refining, displaying, and publishing of structural results. [00787] A clear colourless, plate-like specimen of C20H22F2N6O, approximate dimensions 0.050 mm x 0.250 mm x 0.360 mm, was used for the X-ray crystallographic analysis. The X-ray intensity data were measured (λ = 1.54178 Å) at RT. A total of 2634 frames were collected. The total exposure time was 9.56 hours. The frames were integrated with the Bruker SAINT software package using a narrow-frame algorithm. The integration of the data using a monoclinic unit cell yielded a total of 46172 reflections to a maximum θ angle of 69.27° (0.82 Å resolution), of which 6137 were independent (average redundancy 7.524, completeness = 85.4%, Rint = 3.75%, Rsig = 2.33%) and 5249 (85.53%) were greater than 2σ(F²). The final cell constants of a = 9.5817(11) Å, b = 20.916(2) Å, c = 10.8470(12) Å, β = 114.836(4)°, volume = 1972.8(4) Å³, are based upon the refinement of the XYZ-centroids of 9658 reflections above 20 σ(I) with 8.455° < 2θ < 136.8°. Data were corrected for absorption effects using the Multi- Scan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.857. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.7520 and 0.9590. [00788] The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group P 1211, with Z = 4 for the formula unit, C20H22F2N6O. The final anisotropic full-matrix least-squares refinement on F² with 534 variables converged at R1 = 4.38%, for the observed data and wR2 = 10.66% for all data. The goodness-of-fit was 1.123. The largest peak in the final difference electron density synthesis was 0.190 e-/Å³ and the largest hole was -0.177 e-/Å³ with an RMS deviation of 0.037 e-/Å³. On the basis of the final model, the calculated density was 1.348 g/cm³ and F(000), 840 e-. Results and Discussion [00789] Recrystallization of the starting material was performed to prepare crystals of suitable dimension and quality for structure determination. Well-formed plates obtained from recrystallization of the starting material in THF/MTBE (FIG.79) were used for single crystal X- ray diffraction data collection at RT. The crystal structure of a Compound 106 free base neat form was solved (FIG.80) in monoclinic Space group P2₁ with lattice parameters a = 9.5817(11) Å, b = 20.916(2) Å, c = 10.8470(12) Å, α = 90º, β = 114.836(4)°, γ = 90º, volume = 1972.8(4) Å³, Z = 4 and calculated crystal density dc = 1.348 g/cm³. The R absolute configuration of Compouund 106 was confirmed based on anomalous scattering effects, with a Flack parameter of 0.10(6). Two crystallographically independent molecules were present in the crystal and differ in conformation (FIG.81). Infinite hydrogen bonding interactions involving three amines were observed along the crystallographic a-axis, (FIG.82). [00790] PXRD simulated from the crystal structure matched the bulk pattern of FB-1 (FIG.83), confirming FB-1 and the single crystal are the same crystalline phase. Table 38. Sample and crystal data Identification code Compound 106_1109_07_A6_RT_033023

_{c = 10.8470(12) Å γ = 90°} _{Volume 1972.8(4) Å} ³

Theta range for data collection 4.23 to 69.27° Index ran es -11<=h<=11 -25<=k<=25 -12<=l<=12

Table 40. Atomic coordinates and equivalent isotropic atomic displacement parameters (Å²) U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. _{x/a y/b z/c U(eq)} F1 1 0.0816(4) 0.5145(2) 0.3553(4) 0.0625(11) 1) 3) 5) 2) 4) 3) 2) 9) 9) 7) 5) 6) 6) 5) 5) 4) 7) 5) 6) 7) 6) 9) 2) 1) 2) 7)

_{x/a y/b z/c U(eq)} N3 2 0.8499(5) 0.4382(3) 0.0308(6) 0.0432(12) 4) 2) 4) 7) 6) 5) 5) 6) 5) 5) 7) 6) 6) 6) 6)

Table 41. Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å²) U(eq) is defined as one third of the trace of the orthogonalized U_ij tensor. x/a y/b z/c U(eq)

x/a y/b z/c U(eq) H3A 1 1.2821 0.8050 0.6810 0.129000

x/a y/b z/c U(eq) H18 2 0.5013 0.7135 0.1899 0.094000

. D_{onor-H Acceptor-H Donor-Acceptor Angle} N1 1 H1 1 N1 2#5 095515 2452 339511 172 7

#1 x-1, y, z

Example 3: Polymorph Screen of Compound 106 Free Base and Mono Hydrochloride (Project Q-4062) Summary [00791] 10 g of the starting material (SM) of the Compound 106 free base (FB) was provided. The material was confirmed to be crystalline form FB-1 and characterized by polarized light microscopy (PLM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and nuclear magnetic resonance (¹H-NMR). [00792] A polymorph screen of 66 experimental conditions was performed on the FB, using various screening methods including slow evaporation, slow cooling, (reverse) anti-solvent addition, slurry at RT/50°C, solid/liquid vapor diffusion, and heat-cool-heat, etc. A total of three crystal forms of the FB were observed, including the anhydrous FB-1 and two solvates, FB-2 and FB-3. FB-3 was reproduced but appeared to be a DMF solvate based on characterizations; however, efforts to reproduce FB-2 were not successful. [00793] In the course of determination of crystal structure of FB-1, an anhydrous form of mono hydrochloride was found by X-ray Crystallography from large rod-like crystals in a slurry sample which was prepared earlier (project Q-3864) and had sat at RT for months. It should be mentioned that an earlier salt screening conducted (project Q-3864) did not afford a crystalline hydrochloride hit. It was then learnt from process chemistry that mono hydrochloride had been isolated in bulk. Thus, the project was redirected to characterization of the new form. Process isolates of ~99.0 LCAP were used for studies, which were highly crystalline, designated as HCl- 1, and matched the simulated pattern of the crystal structure of the anhydrous form. HCl-1 displayed a high melting point. [00794] Dynamic Vapor Sorption (DVS) conducted using a representative process lot showed that HCl-1 exhibited 0.24% moisture uptake at 80% RH and was categorized as slightly hygroscopic according to the hygroscopicity classifications. There was no form change post DVS analysis. HCl-1 displayed high solubility of > 100 mg/mL in water and biorelevant media (SGF, FaSSIF, and FeSSIF). [00795] Desired properties of HCl-1 led to polymorph screening of the salt form. The approximate solubility of crystalline HCl-1 was first measured in 30 solvents. The material exhibited high solubility in MeOH and H₂O, good solubility in TFA and DMSO, moderate solubility in CHCl₃, EtOH, and DMF, and low solubility in other organic solvents tested. Polymorph screening was subsequently conducted in these single solvents at RT and 50°C. A total of 119 polymorph screening experiments were carried out starting with HCl-1. Six techniques were employed, including slurry in single solvents at RT and 50 °C, slurry in binary solvents at 50 °C, liquid-assisted grinding, solid vapor diffusion, and liquid vapor diffusion. XRPD analysis of solids or slurries obtained from the experimental conditions showed HCl-1 in most samples and gel or amorphous material in others. An interesting observation was made in two slurry samples at 50 °C, in IPA and 2-butanol respectively, which exhibited HCl-1 with extra peaks. The experimental conditions were repeated but gave no extra peaks after two days. With continuously stirring at 50 °C for an additional three days, the extra peaks were detected by XRPD. To investigate further, both slurry experiments were stirred at 50 °C for a total of 10 days and 13 days and were monitored by XRPD. The extra peaks disappeared when checked on day 10 and day 13. To date, no new polymorphs have been found. [00796] Additional studies related to physical stability of HCl-1 came from experiments that were conducted to support process development for impurity rejection. No form change was observed when HCl-1 was suspended in 25 individual solvents selected based on the approximate solubility and pervious polymorph screening. Experiments were also conducted using binary solvent systems at RT, below RT and elevated temperatures in aqueous 2-Butanol system (1, 2, and 3 vol% water), 1 vol% aqueous organic system (acetone, IPA, and ACN), IPA, 8 vol% water in IPA, and 8 wt. % aqueous IPA system with antisolvent (acetone and MTBE), etc. [00797] No form change was observed in all the experiments. [00798] In summary, polymorph screening was performed on the Compound 106 free base and mono-hydrochloride and did not discover any crystalline form thermodynamically more stable than FB-1 and HCl-1. Both free base and hydrochloride showed low risk of polymorphism. HCl-1 has exhibited excellent aqueous solubility, together with low moisture uptake, and satisfactory solid-state chemical and physical stability, and appears easy to prepare and scalable. Instruments and Methods [00799] Powder X-Ray Diffraction (PXRD) Instrument: Panalytical Empyrean Parameters: X-Ray tube Cu (Kα radiation); tube voltage 45 kV; tube current 40 mA Scanning range [°2θ]: 2 to 40 Step size [°2θ]: 6.33 [°2θ]/min Scan type: Continuous [00800] Proton Nuclear Magnetic Resonance (¹H NMR) Instrument: Bruker 400 Ultrashield

Solvent: DMSO-d₆ [00801] Differential Scanning Calorimetry (DSC) Instrument: TA Instruments DSC 2500 Parameters: Ramp 10 °C per minute, up to 300 °C [00802] Thermo-Gravimetric Analysis (TGA) Instrument: TA Instruments TGA 5500 Parameters: 25 to 300 °C, 10 °C/min, N₂ sweep [00803] Polarized Light Microscopy (PLM) Instrument: Nikon Eclipse Ci Pol Software: Nikon NIS Elements [00804] Dynamic Vapor Sorption (DVS) Instrument: DVS Intrinsic, Surface Measurement Systems Parameters: 25 °C, 0-90-0% RH for 2 cycles [00805] Karl Fischer Titration (KF) The instrument of V20S volumetric KF Titrator from Mettler Toledo was used. [00806] High Performance Liquid Chromatography (HPLC) Instrument: Agilent 1260 Infinity II Column: Agilent poroshell 120 EC-C18, 100 x 4.6 mm, 2.7 µm, Part#695975-902T

Characterization of Free Form (FB) Starting Material [00807] The starting material (SM) for Compound 106 free form Lot# 966-195 was received and labeled as ZW-1109-01-A. The starting material was characterized by XRPD (FIG. 84), PLM (FIG.85), TGA-DSC (FIG.86), and ¹HNMR (FIG.87). Results are summarized in Table 43. Table 43. Characterization of Compound 106 free form SM (ZW-1109-01-A) Sample Technique Results

Solubility Estimation of Compound 106 FB SM [00808] The approximate solubility of crystalline Compound 106 FB SM was estimated in various solvents and the corresponding results are presented in Table 44. [00809] Procedure: [00810] ~ 2 mg solids were weighed into each 4 mL glass vial, the corresponding solvent was added step wise and the vial was shook or sonicated to see if solids dissolved completely. Solvent addition was stopped when the total volume reached 1 mL. The approximate solubility was calculated. Table 44. Approximate solubility of Compound 106 FB S_olvent ^Solubility Solubility (_{mg/mL) Solvent} (mg/mL)

Polymorph Screening Experiments of Compound 106 FB [00811] Polymorph screening of Compound 106 was performed under 66 experimental conditions, using different screening methods, including evaporation, slow cooling, (reverse) anti-solvent addition, slurry at RT/50°C, solid/liquid vapor diffusion, and heat-cool-heat. The results of polymorph screening were summarized in Table 45. Table 45. Summary result of polymorph screening for Compound 106 M^{ethod No. of Result}

^{Method No. of} E_xperiments ^Result

FB-2, FB-3) were obtained. FB-1 is considered anhydrate, FB-2 and FB-3 are speculated to be solvates based on the characterization. An inter-conversion diagram was illustrated in FIG.89. Experimental details are included in the section below. The characterization of crystal forms is summarized in Table 46. The characterizations of crystal forms (FB-2 and FB-3) are shown in FIGS.90-93. Table 46. Characterization results of Compound 106 crystal free forms Crystal Experimental ¹ condition ^Endotherm HNMR in Form F to ^{Weight Loss (%)} _º DM I ifi ion

Polymorph Screen Design and Results of Compoud 106 FB [00813] Procedure: [00814] 1. Solid vapor diffusion – (ID: ZW-1109-02) [00815] ~ 15 mg free base was kept in 4 mL vials which were placed in 20 mL glass vials containing different solvents. The solids were characterized by XRPD after 7 days. [00816] 2. Anti-solvent addition – (ID: ZW-1109-03) [00817] ~ 20 mg free base was dissolved in different solvents to obtain saturated solutions and anti-solvents were added up to 15 mL. The obtained solids were characterized by XRPD. [00818] 3. Slow cooling – (ID: ZW-1109-04) [00819] ~ 20 mg solid into each 4-mL glass vial, add in 1 mL of corresponding solvent to get a suspension, and transfer the suspension to slurry at 50 °C with magnetic stirring. Filter each sample after equilibrating at 50 °C for 2h, and cooling the filtrate in each 4-mL glass vial, from 50 °C to 5 °C. The sample was stored at 5 °C before solids were isolated and analyzed using XRPD. [00820] 4. Slurry at RT – (ID: ZW-1109-05) [00821] ~ 20 mg free base was suspended and stirred in different solvents in 4 mL vials at RT. The solids in the slurry were characterized by XRPD after 7-days. [00822] 5. Slurry at 50 °C – (ID: ZW-1109-06) [00823] ~ 20 mg free base was suspended and stirred in different solvents in 4 mL vials at 50 °C. The solids in the slurry were characterized by XRPD after 3 days. [00824] 6. Liquid vapor diffusion – (ID: ZW-1109-07) [00825] ~ 20 mg free base was dissolved in different solvents to obtain saturated solutions in 4 mL vials which were placed in 20 mL glass vials containing anti-solvents. The obtained solids were characterized by XRPD after 7 days. [00826] 7. Slow evaporation at RT – (ID: ZW-1109-08) [00827] ~ 15 mg free base was dissolved in different solvents to obtain saturated solutions in 4 mL vials. The vials were covered with parafilm with 3 holes and placed at RT for evaporation. The obtained solids were characterized by XRPD. [00828] 8. Reverse anti-solvent addition – (ID: ZW-1109-09) [00829] ~ 20 mg free base was dissolved in different solvents to obtain saturated solutions which were then added dropwise to anti-solvents. The obtained solids were characterized by XRPD. [00830] 9. Heat-cool-heat [00831] DSC cycle was performed on starting material via heat-cool-heat process, RT- 190°C-25°C-250°C, at rate of 10°C/min. The DSC heat-cool-heat curves are shown in FIG.94. [00832] The results of the polymorph screenings are shown in Tables 47-55. Table 47. Results of polymorph screening experiments of Compound 106 FB by solid vapor diffusion Exp. ID Solvent Solid Form

ZW-1109-02-A2 MeOH Gel ZW-1109-02-A3 IPA FB-1

. p y p g p p y addition Exp. ID Solvent Anti-solvent Solid Form Z^{W-1109-03-A1 H2O FB-1}

Table 49. Results of polymorph screening experiments of Compound 106 FB by slow cooling Exp. ID Solvent (v/v) Solid Form ZW110904A1 ACN FB1

Table 50. Results of polymorph screening experiments of Compound 106 FB by slurry at RT Exp. ID Solvent (v/v) Temperature ^Solid

ZW-1109-05-A7 ACN FB-1 ZW-1109-05-A8 2-MeTHF FB-1

°C Exp.ID Solvent Temperature Solid Form ZW-1109-06-A1 H2O FB-1 T

able 52. Results of polymorph screening experiments of Compound 106 FB by liquid vapor diffusion Exp. ID Solvent Anti-solvent Solid Form ZW-1109-07-A1* 14-Dioxane n-he tane Gel

Table 53. Results of polymorph screening experiments of Compound 106 FB by slow evaporation Exp. ID Solvent Solid Form

_{ZW-1109-08-A7 IPA} ^FB-1

solvent addition Exp. ID Solvent Anti-solvent Solid Form Z^{W-1109-09-A1#} E_tOH ^{n-Heptane FB-1} 3

&: Solid was obtained via evaporation at RT Table 55. Results of polymorph screening experiments of Compound 106 FB DSC based (heat- cool-heat) Starting material DSC method Solid Form ZW-1109-01-A RT-190 ºC -25 ºC-250 ºC 10 ºC/min Amorphous w/ Tg ~at 58.8 ºC

Re-preparation of Compound 106 Free Form FB-2 and FB-3 [00833] Re-preparation of novel free forms FB-2 and FB-3 was performed for further evaluation of the form, with detailed information shown in Table 56. FB-2 could not be reproduced, and FB-1 was obtained as shown in FIG.95. Pure FB-3 was obtained from re- preparation compared with the form obtained from screening, which was mixture of FB-1 and FB-3 (FIG.96). Table 56. Re-preparation of Compound 106 free form FB-2 and FB-3 E_{xp.ID Method} ^Solid

*: No precipitation was obtained, transfer solution to slow evaporation at RT Preparation of Compound 106 Amorphous FB [00834] The preparation of an amorphous free form of Compound 106 was attempted with plans to use it as a starting material for the polymorph screening. No pure amorphous form was obtained. The methods and results of the amorphous preparation are shown in Table 57. Table 57. Preparation of Compound 106 amorphous FB Exp. ID Procedure Solid Form Z_W-1109-01-B1 ^{Dissolve FB-1 (ZW-1109-01-A) into THF, dry out} _FB-1

Characterization of Mono-HCl Starting Material [00835] The starting materials (SM) for Compound 106 mono-HCl were denoted as Lot# 1050-19-2 and Lot# 1036-84-FS. Both materials were characterized by XRPD, PLM, DSC, TGA, and ¹HNMR. The characterization of Lot# 1050-19-2 can be found in FIG.97 (XRPD), FIG.98 (PLM), FIG.99 (DSC-TGA), FIG.100 (¹HNMR), and FIG.101 (¹HNMR). The characterization of Lot# 1036-84-FS can be found in FIG.102 (XRPD), FIG.103 (PLM), FIG. 104 (DSC-TGA), FIG.105 (¹HNMR), and FIG.106 (¹HNMR). Results of both lots are summarized in Table 58. Table 58. Characterization of Compound 106 mono-HCl salt SM (ID: 1050-19-2 and 1036-84- FS) Characterization of Compound 106 mono-HCl salt SM

PLM Crystalline Crystalline X_RPD ^{Highly crystalline, matched w/ simulated pattern of Compound 106 mono-}

[00837] The starting material Compound 106 FB (Lot# 966-195) was analyzed by HPLC following the method MR-739 (Table 59). The HPLC method provided was successfully transferred. The experimental results of FB Lot# 966-195 are presented in FIG.107 with a purity of 99.9%. The purity of mono-HCl Lot# 1036-84-FS was tested as 99.0% LCAP, as shown in Table 60 and FIG.108. The linearity curve was also constructed using this method, which gave R² >0.999 (FIG.109). The calibration curve was used to evaluate solubility studies of mono-HCl and concentration calculation. Table 59. HPLC method MR-739 Column: Agilent poroshell 120 EC-C18, 100 x 4.6 mm, 2.7 µm, Part#695975-902T Mobile Phase A: H2O / 0.1% TFA Mobile Phase B: MeCN / 0.1% TFA

Table 60. Purity of Compound 106 FB #966-195 and mono-HCl #1036-84-FS S_{ample ID} ^{Compound 106 FB} Compound 106 mono-HCl

Hygroscopicity Assessment of Compound 106 Mono-HCl (Lot# 1050-19-2) by DVS [00838] The Compound 106 HCl salt (Lot# 1050-19-2) was analyzed by DVS (0-90-0-90- 0% RH at 25 °C). Based on the moisture uptake of the sorption isotherm at 80% RH showing 0.24%, the material was classified as slightly hygroscopic, as shown in FIG.112. The post DVS sample showed no change in by XRPD (FIG.113). Kinetic Solubility Measurements of Mono-HCl salt at 37 °C [00839] The experimental set-up and the results of the kinetic solubility measurements of the mono-HCl (Lot# 1050-19-2) are summarized in Table 61. Biorelevant media were prepared according to the instructions provided by the manufacturer. Approximately 50 mg of SM was added to 0.5 mL of the media targeting to obtain a slurry. The experiments were conducted at a temperature of 37 °C. At all the time points, the solutions in all four media were clear, and no solids were obtained for XRPD measurement. The concentration was concluded to be > 100 mg/mL in all media at all time points. The pH of the media was measured 24 hours after the experiment. [00840] Experimental: 1) 50 mg of mono-HCl (Lot# 1050-19-2) was added to 500 μL of media targeting to get a slurry. 2) The slurry was agitated with a stir bar at 37 °C. 3) The concentration was checked by HPLC at the 1h, 4h, and 24 h time points (if slurry). 4) An XRPD of the residue solids (if any) was run and the pH of the mother liquor was checked at the 24h time point. Table 61. Mono-HCl (Lot# 1050-19-2) solubility data in water and biorelevant media M^{edia Concentration (mg/mL) 24h} E ID I i i l 1h 4h 24h H ±01 XRPD

Solubility Estimation and Polymorph Screening of Compound 106 Mono-HCl [00841] The approximate solubility of crystalline Compound 106 mono-HCl (designated as HCl-1) was estimated in 30 solvents; the corresponding results are presented in Table 62 and categorized results are shown in Table 63. Additional materials were then added to make a slurry for polymorph screening. Samples that exhibited significant or moderate solubility were subjected to XRPD analysis after stirring at room temperature for one day. All samples were subsequently transferred to 50 °C for three days before being analyzed via XRPD. HCl-1 remained in all solvents, except IPA and 2-butanol, which exhibited additional peaks. After attempts to reproduce the two slurries, consistent results could not be obtained in the two solvents after 2 days. Both vials were continuously stirred at 50 °C for an additional 3 days, and the presence of extra peaks were then again detected by XRPD. All XRPD results from this set of experiments are displayed in FIGS.114-118. [00842] Procedure: 1) Weighed ~5 mg of starting material (Lot# 1036-84-FS) into a 4.0 mL vial. Added 50 µL of solvent at RT. 2) Shook and stirred the solution. If no clear solution was obtained, another 50 µL was added and repeated until 2.0 mL of solvent was added. 3) Additional SM was added, targeting to make a slurry (enough for polymorph screening XRPD characterization). 4) The slurries were stirred overnight at RT/350 rpm/1d and solids were analyzed by XRPD. 5) All vials were moved to 50 °C/350 rpm/3d and solids were analyzed by XRPD. Table 62. Approximate solubility and polymorph screening w/ single solvent of Compound 106 mono-HCl (Lot# 1036-84-FS) Exp ID ^Solv Solvent b.p Solubility XRPD results 1_{099 59} ^ents Cl °C / L RT/1d 50°C/3d

Exp ID ^Sol Solvent b.p Solubility XRPD results 1_099-59 ^vents Class (°C) (mg/mL) RT/1d 50°C/3d

Table 63. Categorized approximate solubility table Sr. Solvent capacity N _{t RT} ^Solvents

Reproducing HCl-1 w/ Extra Peaks from IPA and 2-Butanol [00843] The samples for polymorph screening in IPA and 2-Butanol showed additional peaks after being stirred at 50 °C for 3 days, as observed via XRPD. Upon attempting to reproduce the two slurries, the extra peaks were again obtained from both solvents after stirring at 50 °C for 5 days. To investigate further, both vials were left continuously stirring at 50 °C for an additional 5 days (total of 10 days) while monitoring any changes in growth or formation via XRPD. Interestingly, the extra peaks disappeared as analyzed at day 10. Samples are left for another additional 3 days (total of 13 days), and it was confirmed that the extra peaks disappeared and remained as pure HCl-1. Results are summarized in Table 64. XRPD results of different time points are displayed in FIGS.119-123. [00844] Procedure: 1) Added starting material (# 1036-84-FS) into a 4.0 mL vial. Added 0.4 mL of solvent to make a slurry. 2) Shook and stirred the solution. 3) Stirred slurries at 50 °C/350 rpm/2d and the solids were analyzed by XRPD. 4) The vials were stirred at 50 °C for additional 3 days: total 5 days. 5) The vials were kept stirring at 50 °C for 10 days and the solids were analzyed by XRPD. 6) The vials were kept stirring at 50 °C for 13 days and the solids were analyzed by XRPD. Table 64. XRPD results of attempting to reproduce extra peaks from IPA and 2-butanol E^{xp.ID Solvent XRPD} XRPD XRPD XRPD 5_0°C/2d 50°C/5d 50 °C/10d 50 °C/13d

Additional Polymorph Screening Studies of Mono-HCl Compound 106 [00845] Slurry in Binary Solvent Systems (2 vol% Water in Organic Solvents) [00846] Based on the approximate solubility of the starting material (Lot# 1036-84-FS, designated as HCl-1) and the miscibility of the solvent with water, polymorph screening experiments were carried out to find potential crystalline forms slurring at 50 °C using binary solvent systems (2 vol% water in organic solvents). The corresponding results are presented in Table 65. Samples were subjected to XRPD analysis after stirring at 50 °C for one day. XRPD analysis for samples with no form change or that did not become amorphous are shown in FIG. 124. All samples were subsequently stirred at 50 °C for another three days for form analysis via XRPD (presented in FIG.125) which resulted in no new forms. [00847] Procedure: 1) Added 0.5-1 mL of 2 vol% water w/ solvent mixtures at RT into a 4.0 mL vial. 2) Added starting material (# 1036-84-FS) targeting to make a slurry (enough for polymorph screening XRPD characterization). 3) The slurries were stirred overnight at 50 °C/350 rpm/1d and the solids were analyzed by XRPD. 4) The vials were kept stirring at 50 °C/350 rpm/4d and the solids were analyzed by XRPD. Table 65. Results/status of polymorph screening in 2 vol% water w/organic solvents Exp ID 1_099-72 ^{Solvents Water Content 50 °C/1d 50 °C/4d}

[00848] Liquid Assist Grinding (ID: 1099-76) [00849] Procedure: 1) ~30 mg of the mono-HCl salt was ground with different solvents using a mortar and pestle. The obtained solids/slurry were characterized by XRPD (FIG.126) with the results summarized in Table 66. Table 66. Results/status of polymorph screening experiments by liquid assist grinding (# 1099- 76) Exp. ID ^{Solvent Observation Crystal Form}

3 Chloroform solids HCl-1 4 nPA solids HCl-1

[00851] Procedure: 1) ~20 mg of the mono-HCl salt was kept in 4 mL vials which were placed in 20 mL glass vials containing different solvents. The solids were characterized by XRPD after 14 days (FIG.127) with the results summarized in Table 67. Table 67. Results/status of polymorph screening experiments by solid vapor diffusion: (# 1099- 77) Exp. ID 1_099-77 ^{Solvent Observation Crystal Form}

[00852] Liquid Vapor Diffusion (ID: 1099-78) [00853] Procedure: 1) ~30 mg of the mono-HCl salt was dissolved in different solvents to obtain saturated solutions in 4 mL vials which were placed in 20 mL glass vials containing anti-solvents. The obtained solids were characterized by XRPD after 14 days (FIG.128) with the results summarized in Table 68. Table 68. Results/status of polymorph screening experiments by liquid vapor diffusion: (# 1099-78) Exp. ID Solvent Antisolvent Observation Crystal Form

1099-78 1 DCM Clear NA

ono- o u y easu emen s an mpu y ejec on [00854] Aqueous 2-Butanol System Tested with Three Compositions (1, 2, and 3 vol% Water) at 4 Temperatures (20, 30, 40, and 50 °C) [00855] Solubility measurements and impurity rejection of mono-HCl (Lot# 1036-84-FS, 99.0%, LCAP) in an aqueous/2-butanol system was tested with three compositions (1, 2, and 3 vol% water) at 4 temperatures (50°C/18h → 40/2h → 30/2h →20°C/18h). PLM, solubility, solid form, and solid purity results are shown in Table 32. FIG.129 displays the solubility profile. [00856] The results of the purity analysis demonstrated that the percentage of water plays a crucial role in eliminating impurities (an example overlay of SM vs.3% H₂O in 2-butanol at 30˚C, shown in FIG.130. An RRT table for comparison is provided in Table 70 showing specifically that a higher water content led to better removal of impurities. However, the solubility remained too high with 2-butanol as an anti-solvent at RT, which would ultimately result in lower yield. No form change was observed post measurement by XRPD (FIGS.143- 146). [00857] Consequently, further experiments were conducted using different solvents in combination with water to find a more optimal purification process. Solvent selection was based on solvent class and miscibility with water. All results were tested at 4 temperatures (20, 30, 40, and 50 °C) (FIGS.131A-142B) and summarized in Table 69. The experimental design is shown below. [00858] Experimental: 1) Added enough mono-HCl (Lot# 1036-84-FS) into 4.0 mL vial containing > 1.0 mL of the selected solvents to make a slurry. 2) Agitated the solution starting at 50 °C for 18 hours. 3) Separated the mother liquor and the solids via centrifuge with a PTFE filter. 4) PLM and XRPD were run for the resulting solids. 5) HLPC was run for the mother liquor to determine equilibrium solubility and impurity rejection. 6) The vials were moved to 40 °C/2 hours; 30 °C/2 hours; 20 °C/18 hours and steps 3)-5) were repeated. Table 69. Solubility measurements and impurity rejection of mono-HCl (Lot# 1036-84-FS) in H2O/2-butanol Solvent vol% Results 1099- Tem erature of

99- Temperature Solv Results 10 ent vol% of HO in XRPD

a e . o mpur y pro e suy o vs. n aqueous -uano sysem ese w compositions at 20 ˚C Purity (%) RRT SM #1036- 1 vol% H2O in 2- 2 vol% H2O in 2- 3 vol% H2O in 2-

[00859] Solubility of 1 vol% Aqueous - Acetone, IPA, and ACN and Impurity Rejection at Different Temperatures [00860] Solubility measurements and impurity rejection of mono-HCl (Lot# 1036-84-FS, 99.0%, LCAP) in 1 vol% aqueous/organic system tested with three solvents (acetone, IPA, and ACN) at different temperatures. PLM, solubility, solid form, and solid purity results are shown in Table 71 and FIGS.147A-160B. The solubility profile was established and is shown in FIG. 161. [00861] The analysis of solubility and purity for 1 vol% water in acetone and ACN revealed that these solvents act as antisolvents, exhibiting low solubility even at high temperatures. On the other hand, for 1 vol% water in IPA, temperature plays a crucial role in eliminating impurities, an RRT comparison table is shown in Table 72. Higher temperatures were found to be more effective in removing impurities. However, at room temperature, the solubility with IPA as an anti-solvent remained too high, which ultimately led to lower yield. No form change was observed post measurement by XRPD (FIGS.162-164). [00862] Experimental: 1) Enough mono-HCl (Lot# 1036-84-FS) was added into a 4.0 mL vial containing > 1.0 mL of the selected solvents to make a slurry. 2) The solution was agitated at the different selected temperatures for 1-3 days. 3) The mother liquor and the solids were separated via centrifuge with a PTFE filter. 4) PLM and XRPD were run to check for resulting solids. 6) HLPC of the mother liquor was run to determine equilibrium solubility and impurity rejection. Table 71. Solubility measurements and impurity rejection of mono-HCl (Lot# 1036-84-FS) in 1 vol% aqueous-acetone, IPA, and ACN Exp ID XRPD S^{olvents Temp} Solubility (mg/mL) Solid Purity

Exp ID XRPD 1₀₉₉ ^{Solvents Temp} Solubility (mg/mL) Solid Purity

Table 72. Solid impurity profile study of SM and in 1 vol% aqueous-organic system tested at RT Purity (%) RRT SM #1036 1 l% H O in t n 1 l% H O in IPA 1 l% H O in ACN

[00863] Solubility of 8 vol% Aqueous - IPA and Impurity Rejection at Different Temperatures [00864] The solubility and purity for 8 vol% water in IPA was also studied. The results displayed in Table 73 and FIGS.165-168 showed high solubility even at RT. A solubility profile was established and is shown in FIG.169. No form change was observed post measurement by XRPD (FIG.170). This solvent system exhibited a great enhancement in purity, with a greater increase observed as the temperature rises. Table 73. Solubility measurements and impurity rejection of mono-HCl (Lot# 1036-84-FS) in 8 vol% water in IPA Exp ID XRPD 1_{099 69} ^{Solvents Temp} Solubility (mg/mL)

[00865] Solubility in IPA at Different Temperatures [00866] Solubility in pure IPA at 5 °C, 25 °C, 50 °C, 65 °C, and 80 °C were also measured (FIG.171) and the end solids were also analyzed by XRPD. As anticipated, the solubility profile displayed a lower solubility trend when compared to the solvent containing 1 and 8 vol% water (FIG.172). There were no observable XRPD changes in form after the measurement was taken (FIG.173). [00867] 8 wt. % Aqueous-IPA System with Addition of wt. % (20, 40, 60, and 80) of Antisolvents Tested at 25 °C [00868] Solubility measurements and impurity rejection of mono-HCl (Lot# 1036-84-FS, 99.0%, LCAP) in an 8 wt. % aqueous/IPA system was tested with two antisolvents (acetone and MTBE) with 20, 40, 60, and 80, wt. % at 25 °C. Solubility, solid form, and solid purity results are shown in Table 74 and FIGS.174-181. [00869] An analysis conducted on the solubility and purity of two solutions containing 8 wt. % water in IPA with acetone and MTBE revealed that acetone demonstrated higher solubility compared to MTBE. The solubility profile and results are displayed in FIG.182. As anticipated, the solubility profile indicated that higher solubility resulted in greater improvements in purity. Consequently, acetone proved to be more effective than MTBE in terms of its ability to purify the solution. Furthermore, it was observed that decreasing the quantity of antisolvent led to even greater enhancements in purity (RRT table shown in Table 75). No form change was observed post measurement by XRPD (FIGS.183 and 184). [00870] Experimental: 1) Enough mono-HCl (Lot# 1036-84-FS) was added into a 4.0 mL vial containing > 1.0 mL of the selected solvents to make a slurry. 2) The solution was agitated at 50 °C overnight and moved to 25 °C for 6.hours. 3) The mother liquor and solids were separated via centrifuge with a PTFE filter. 4) XRPD was run to check for resulting solids. 5) An HLPC of the mother liquor was run to determine equilibrium solubility and solids for impurity rejection. Table 74. Solubility measurements and impurity rejection of mono-HCl (Lot# 1036-84-FS) in antisolvents with 8 wt. % aqueous-IPA at 25 °C Exp ID XRPD

Table 75. Solid impurity profile study of SM vs. antisolvents w/ 8 wt. % aqueous-IPA at 25 ˚C RRT Purity (%)

_SM ^{wt. % acetone in 8 wt. % aqueous-} wt. % MTBE in 8 wt. % aqueous- I_PA IPA

[00871] Single Solvent Screening for Impurity Rejection [00872] Table 76 shows the 25 individual solvents selected based on the approximate solubility data and good slurry observations from single solvent polymorph screening experiments. The resulting slurries were agitated at 50 °C overnight, and the solid purity was determined by HPLC analysis after cooling to RT (FIGS.185-208). A notable improvement in solvent purity was demonstrated for DCM/EtOH/IPA/nPA/2-Butanol/n-Butanol/DMSO (purity > 99.3% by area). [00873] Experimental: 1) Enough mono-HCl (Lot# 1036-84-FS) was added into a 4.0 mL vial containing > 1.0 mL of the selected solvent to make a slurry. 2) The solution was agitated at 50 °C overnight and let cool to RT. 3) The mother liquor and solids were separated via centrifuge with a PTFE filter. 4) HLPC was run on the solids to determine impurity rejection. Table 76. Single solvent screening for impurity rejection. Exp ID ^Solvent b.p Approx.

Exp ID ^Sol b.p Approx. 1099- _Solvents ^vent C_lass (°C) solubility Purity (%)

Conclusions [00874] The primary objective of this project was to conduct a polymorph screen of the Compound 106 FB, aiming to discover new crystalline forms, characterize their relationships, and identify a thermodynamically more stable form for development. A total of 66 experimental conditions were performed, using various screening methods, and led to observation of three distinct crystal forms, namely FB-1, FB-2, and FB-3. Among these forms, FB-1 was previously known and is an anhydrous form, while FB-2 and FB-3 were found to be solvates. FB-1 remains the leading candidate of the free base. [00875] The project scope was redefined to focus on mono hydrochloride upon discovery and characterization of an anhydrous form HCl-1. HCl-1 not only displayed superior properties, especially its excellent aqueous solubility and low moisture uptake, but also provided an effective way to purge impurities, and thus prompted a decision to switch the API from the free base to mono-hydrochloride salt. [00876] A polymorph screen of 119 experimental conditions were conducted on mono hydrochloride, and no new crystalline form was found. Polymorphism of mono hydrochloride was also assessed during studies aimed to assist the process team in evaluating crystallization solvents for HCl-1 to optimize impurity rejection. Various solvent systems and compositions were tested at different temperatures. While the data helped purity upgrade, they also showed no crystalline form other than HCl-1 appeared. Example 4: Compound 106 NMR Structure Elucidation Report [00877] Detailed NMR studies were carried out on Compound 106 (#966-195) (¹HNMR: FIG.209; ¹³CNMR: FIG.213). Gradient COSY (FIG.210), ROESY (FIG.211), HSQC (FIG. 214), and HMBC (FIG.215) 2-D experiments were used to assign the H-1 and C-13 spectral data presented in Table 77. An assigned F-19 NMR spectrum is included in FIG.212. All spectra were fully consistent with the structure shown below.

₅ ⁵ ₂ O ^W-⁴ ₁ ⁰ ₅-₄ ⁶ ₃ ⁰ ₃ ¹ _: ^. _o ^N _t ^e _k ^c _o ^D ^y _e ⁿ _r ^o _tt A

₆ ⁵ ₂

Example 5: Compound 106 HCl NMR Structure Elucidation Report [00878] Detailed NMR studies were carried out on Compound 106 HCl (#935-167) (¹HNMR: FIG.216; ¹³CNMR: FIG.217). Gradient COSY (FIG.218), ROESY (FIG.219), HSQC (FIG.220), and HMBC (FIG.221) 2-D experiments were used to assign the H-1 and C- 13 spectral data presented in Table 78. An assigned F-19 NMR spectrum is included in FIG. 222. All spectra were fully consistent with the structure shown below.

₈ ⁵ ₂

₉ ⁵ ₂ O ^W-⁴ ₁ ⁰ ₅-₄ ⁶ ₃ ⁰ ₃ ¹ _: ^. _o ^N _t ^e _k ^c _o ^D ^y _e ⁿ _r ^o _tt A

₀ ⁶ ₂ O ^W-⁴ ₁ ⁰ ₅-₄ ⁶ ₃ ⁰ ₃ ¹ _: ^. _o ^N _t ^e _k ^c _o ^D ^y _e ⁿ _r ^o _tt A

Example 6: Compound 106 Stability Studies Experimental Procedures [00879] Description of the Dosage Form: [00880] The Compound 106 oral drug product was manufactured in strengths of 10 mg and 50 mg. The mono˗HCl form of Compound 106 was filled into hard hypromellose capsules as decribed in Table 79. This Compound 106 oral drug product is supplied in a 60-cc high- density polyethylene bottle with 30 capsules per bottle. Table 79. Description of Compound 106 capsules Strength Description 10 mg Capsule Size 3 hard hypromellose, opaque orange capsule, containing a white o

[0088 ] ompos on: [00882] The composition of the 10 mg and 50 mg Compound 106 capsules is presented in Table 80. Table 80. Unit composition, pharmaceutical function quality standards and ingredients Ingredients 10 mg 50 mg

y roc or e con en , wa er con en , an res ua so vens conen [00883] Analytical Procedures: [00884] The analytical procedures used to release the Compound 106 capsules were a combination of compendial & non-compendial methods. The compendial analytical procedures used to test the Compound 106 capsules are summarized in Table 81. All compendial analytical procedures used are performed to their respective compendial standards. Table 81. Compendial analytical procedures used to test Compound 106 capsules Test Method Use Disintegration USP <701> Release, Stability

capsules are provided in Table 82. A description of the non-compendial analytical procedures used to test the Compound 106 capsules is provided below. Table 82. Non-compendial analytical procedures used to test Compound 106 capsules Test Method Use Appearance Visual Release, Stability

[00886] Appearance: [00887] The appearance test was to assess the drug product for color, shape and for the presence of any visual defects. The appearance test was performed by visual inspection. [00888] Identification, Assay and Related Substances by Ultra Performance Liquid Chromatography: [00889] The ultra-performance liquid chromatography (UPLC) test method for testing the Compound 106 capsules is summarized in Tables 83 and 84. The Compound 106 capsules identity was determined by comparing the retention time and UV spectrum of the Compound 106 main peak to that of the standard solution. Assay of the Compound 106 capsules was calculated on a weight/weight basis against a reference standard. Impurities in the Compound 106 capsules were reported based on percent area. Table 83. Chromatographic conditions Column Agilent Infinity Poroshell 120 EC-C182.7 µm, 4.6 mm x 100 mm

Mobile Phase A: 0.1% Trifluoroacetic acid in water Mobile Phase B: 0.1% Trifluoroacetic acid in acetonitrile

Time (min) Flow (mL/min) % Solvent A % Solvent B Curve 0.0 1.0 93 7 NA

g p p ed. [00891] Sample Solution Preparation: A solution of approximately 0.5 mg/mL capsule contents in diluent was prepared. [00892] Working Standard Preparation: A solution of approximately 0.5 mg/mL drug substance reference standard in diluent was prepared. [00893] Sensitivity Solution Preparation: A solution of approximately 0.0005 mg/mL drug substance reference standard (0.1% of nominal) was prepared by diluting 100 µL of working standard to 100 mL with diluent. [00894] System Suitability Criteria: The diluent was injected to obtain a blank chromatogram to confirm that there were no interfering peaks at the retention time of Compound 106. An injection of the sensitivity solution was made to verify that the signal to noise ratio is ≥ 10. Five replicate injections of the Compound 106 standard solution must have an RSD of ≤ 2.0% for the peak area of drug substance and the retention time for the drug substance peak. The mean drug substance USP tailing factor and plate count was reported. The recovery of the check standard was 98.0 – 102.0%. [00895] Chromatograms: A typical working standard chromatogram is provided in FIG. 223. [00896] Calculations: [00897] Identification n time comparison (%) = ^ோ் [00898] Retentio ^{ೄು^} ோ_்ೄ^ವ , [00899] Where: [00900] RTSPL = Retention time of main peak in the first SPL chromatogram. [00901] RTSTD = Average retention time of main peak in the 5 standard injections. [00902] The identity is confirmed if the ratio of RTSPL/ RTSTD is within 0.98-1.02. [00903] % Assay (w/w) [00904] Assay (wt.% as is) = × PF [00905] Where:

[00906] AS = peak area of Compound 106 in sample chromatogram [00907] C_S = concentration of sample solution in mg/mL [00908] CRS = concentration of standard solution in mg/mL [00909] ARS = average peak area of Compound 106 in standard chromatograms [00910] PF = purity factor (in %) of the Compound 106 reference standard [00911] Area % of Impurities by RRT [00912] Impurity (area %) = [00913] RRT

[00914] [00915]

Imp pea a ea o epo tab e pu ty sample chromatogram [00916] A_Total = sum of areas of all reportable peaks in sample chromatogram [00917] Chiral Purity by High Performance Liquid Chromatography: [00918] The high-performance liquid chromatography (HPLC) test method used to determine the level of the S-enantiomer content in the Compound 106 capsules is summarized in Table 85. The quantity of the S-enantiomer in the Compound 106 capsules was reported based on percent area. Table 85. Chromatographic conditions Column Daicel Chiralpak IG, 5 µm, 4.6 x 150 mm

Run Time 30 minutes

epared. [00920] Sample Solution Preparation: A solution of approximately 0.6 mg/mL capsule contents in diluent was prepared. [00921] Working Standard Preparation: A solution of reference standard in diluent was prepared, containing approximately 0.6 mg/mL R-enantiomer and 0.006 mg/mL S-enantiomer. [00922] Sensitivity Solution Preparation: Asolution of approximately 0.0006 mg/mL S- enantiomer in diluent was prepared. [00923] System Suitability Criteria: The diluent was injected to obtain a blank chromatogram to confirm that there were no interfering peaks at the retention time of the Compound 106 S-enantiomer. An injection of the sensitivity solution was made to verify that the signal to noise ratio of the S-enantiomer peak was ≥ 10. Five replicate injections of standard solution must have an RSD of ≤ 2.0% for the peak area of drug substance and the retention time for the R-enantiomer peak. The mean drug substance USP tailing factor and plate count for the R-enantiomer was reported. The recovery of the check standard is 95 – 105% for the enantiomer. [00924] Chromatograms: A typical working standard chromatogram is provided in FIG. 224. [00925] Calculations: [00926] Enantiomer Impurity Content [00927] Enantiomer Content (area %) = AEnantiomer/(ATOTAL) [00928] Where: [00929] A_Enantiomer = peak area of S-enantiomer in sample chromatogram [00930] ATOTAL = Sum of peak areas of Compound 106 R-enantiomer and S- enantiomer in sample chromatogram Results [00931] Active pharmaceutical ingredient (API) and drug product (DP) stability protocols were run under two conditions: standard at 25°C ± 2°C and 60% room humidity ± 5% with timepoints collected over 36 months and accelerated at 40°C ± 2°C and 75% room humidity ± 5% with timepoints collected over 6 months. [00932] Stability results for the API were obtained after 6 months of storage at 25°C ± 2°C and 60% room humidity ± 5% (FIG.225) and after 6 months of storage at 40°C ± 2°C and 75% room humidity ± 5% (FIG.226). [00933] Stability results for the DP at a 10 mg dose were obtained after 3 months of storage at 25°C ± 2°C and 60% room humidity ± 5% (FIG.227) and after 3 months of storage at 40°C ± 2°C and 75% room humidity ± 5% (FIG.228). Stability results for the DP at a 50 mg dose were obtained after 3 months of storage at 25°C ± 2°C and 60% room humidity ± 5% (FIG. 229). [00934] All patents, patent applications, publications of patent applications, and other material, such as articles, books, specifications, publications, documents, things, and/or the like, referenced herein are hereby incorporated herein by this reference in their entirety for all purposes, excepting any prosecution file history associated with same, any of same that is inconsistent with or in conflict with the present document, or any of same that may have a limiting affect as to the broadest scope of the claims now or later associated with the present document. By way of example, should there be any inconsistency or conflict between the description, definition, and/or the use of a term associated with any of the incorporated material and that associated with the present document, the description, definition, and/or the use of the term in the present document shall prevail. [00935] In closing, it is to be understood that the embodiments of the application disclosed herein are illustrative of the principles of the embodiments of the disclosure. Other modifications that can be employed can be within the scope of the application. Thus, by way of example, but not of limitation, alternative configurations of the embodiments of the application can be utilized in accordance with the teachings herein. Accordingly, embodiments of the present application are not limited to that precisely as shown and described.

Claims

CLAIMS What is claimed is: 1. A crystal form of a mono-HCl salt of a compound of Formula (1): wherein the crystal form is charac r diffraction pattern comprising

peaks at 6.8619 ± 0.2°, 11.3373 ± 0.2°, 14.5399 ± 0.2°, 17.1417 ± 0.2°, and 23.6521 ± 0.2° 2θ. 2. The crystal form of claim 1, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 14.7217 ± 0.2°, 16.2725 ± 0.2°, 22.4223 ± 0.2°, 23.3316 ± 0.2°, and 28.8331 ± 0.2° 2θ. 3. The crystal form of claim 1 or 2, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 2.0916 ± 0.2°, 11.1062 ± 0.2°, 20.9023 ± 0.2°, 21.9400 ± 0.2°, and 27.5840 ± 0.2° 2θ. 4. The crystal form of any one of claims 1-3, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 11.6132 ± 0.2°, 13.7106 ± 0.2°, 14.3405 ± 0.2°, 15.3177 ± 0.2°, 17.5260 ± 0.2°, 17.6282 ± 0.2°, 18.8337 ± 0.2°, 20.0236 ± 0.2°, 20.8136 ± 0.2°, 21.0463 ± 0.2°, 22.9619 ± 0.2°, 24.4120 ± 0.2°, 24.9258 ± 0.2°, 26.0850 ± 0.2°, 26.4484 ± 0.2°, 26.7151 ± 0.2°, 26.9745 ± 0.2°, 27.2880 ± 0.2°, 27.8954 ± 0.2°, 28.1817 ± 0.2°, 28.3383 ± 0.2°, 29.2852 ± 0.2°, 29.8645 ± 0.2°, 32.2115 ± 0.2°, 33.1644 ± 0.2°, 33.5088 ± 0.2°, 33.8427 ± 0.2°, 34.6622 ± 0.2°, 35.6915 ± 0.2°, 36.3485 ± 0.2°, 37.3533 ± 0.2°, and 38.0511 ± 0.2° 2θ. 5. The crystal form of any one of claims 1-4, the mono-HCl salt having Formula (2):

6. A crystal form of the free base of a compound of Formula (1): characterized by an X-ray powde sing one or more peaks at 8.5102 ±

0.2°, 13.4583 ± 0.2°, 16.3830 ± 0.2°, 20.0082 ± 0.2°, and 24.6817 ± 0.2° 2θ. 7. The crystal form of claim 6, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 11.2514 ± 0.2°, 16.8018 ± 0.2°, 20.9239 ± 0.2°, 22.2447 ± 0.2°, and 28.6101 ± 0.2° 2θ. 8. The crystal form of claim 6 or 7, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 10.2265 ± 0.2°, 17.1029 ± 0.2°, 18.3658 ± 0.2°, 22.6040 ± 0.2°, and 23.6583 ± 0.2° 2θ. 9. The crystal form of any one of claims 6-8, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 12.4152 ± 0.2°, 15.6546 ± 0.2°, 18.5476 ± 0.2°, 19.1056 ± 0.2°, 19.3265 ± 0.2°, 20.4980 ± 0.2°, 21.3232 ± 0.2°, 23.2420 ± 0.2°, 24.2705 ± 0.2°, 25.8013 ± 0.2°, 26.1668 ± 0.2°, 27.1774 ± 0.2°, 27.5557 ± 0.2°, 28.1259 ± 0.2°, 30.1759 ± 0.2°, 31.5240 ± 0.2°, 31.8408 ± 0.2°, 32.3075 ± 0.2°, 32.8563 ± 0.2°, 33.7388 ± 0.2°, 36.0412 ± 0.2°, 36.7705 ± 0.2°, 37.7457 ± 0.2°, and 39.0376 ± 0.2° 2θ. 10. A crystal form of the free base of a compound of Formula (1): wherein the crystal form compris ized by one or more of:

i) a monoclinic Space group P21; ii) lattice parameters a = 9.5817(11) Å, b = 20.916(2) Å, c = 10.8470(12) Å, α = 90º, β = 114.836(4)°, and γ = 90º; iii) a volume of about 1972.8(4) Å³; and/or iv) a crystal density dc = 1.348 g/cm³. 11. A crystal form of a p-toluenesulfonic acid salt of a compound of Formula (1):

wherein the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 5.1743 ± 0.2°, 8.1663 ± 0.2°, 10.3704 ± 0.2°, 14.4880 ± 0.2°, and 16.8942 ± 0.2° 2θ. 12. The crystal form of claim 11, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 7.0186 ± 0.2°, 11.7589 ± 0.2°, 12.5062 ± 0.2°, 13.2636 ± 0.2°, 14.0747 ± 0.2°, 14.2385 ± 0.2°, 17.6050 ± 0.2°, 21.1626 ± 0.2°, 25.1678 ± 0.2°, and 26.2810 ± 0.2° 2θ.

13. The crystal form of claim 11 or 12, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 9.1859 ± 0.2°, 14.7418 ± 0.2°, 15.1588 ± 0.2°, 15.6231 ± 0.2°, 16.2702 ± 0.2°, 17.9401 ± 0.2°, 19.0641 ± 0.2°, 19.8933 ± 0.2°, 20.5140 ± 0.2°, 21.1626 ± 0.2°, 21.7948 ± 0.2°, 22.4148 ± 0.2°, 23.0891 ± 0.2°, 23.8417 ± 0.2°, 24.6896 ± 0.2°, 24.8272 ± 0.2°, 26.7775 ± 0.2°, 27.4170 ± 0.2°, 28.1822 ± 0.2°, 29.0287 ± 0.2°, 29.9521 ± 0.2°, 31.4883 ± 0.2°, and 33.1844 ± 0.2° 2θ. 14. A crystal form of a tartaric acid salt of a compound of Formula (1): wherein the crystal form is chara r diffraction pattern comprising one

or more peaks at 7.7633 ± 0.2°, 8.2996 ± 0.2°, 12.4661 ± 0.2°, 15.5489 ± 0.2°, and 24.7464 ± 0.2° 2θ. 15. The crystal form of claim 14, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 4.1463 ± 0.2°, 11.3791 ± 0.2°, 14.1011 ± 0.2°, 17.4289 ± 0.2°, 18.6536 ± 0.2°, 19.1095 ± 0.2°, 20.4382 ± 0.2°, 22.5011 ± 0.2°, 25.1566 ± 0.2°, and 25.4454 ± 0.2° 2θ. 16. The crystal form of claim 14 or 15, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 10.1216 ± 0.2°, 13.7867 ± 0.2°, 16.6578 ± 0.2°, 19.3112 ± 0.2°, 19.6662 ± 0.2°, 20.8586 ± 0.2°, 21.3540 ± 0.2°, 22.8792 ± 0.2°, 23.4372 ± 0.2°, 23.7287 ± 0.2°, 25.9362 ± 0.2°, 26.4885 ± 0.2°, 26.7874 ± 0.2°, 27.7072 ± 0.2°, 28.1883 ± 0.2°, 29.5023 ± 0.2°, 31.4659 ± 0.2°, 33.1605 ± 0.2°, 35.2961 ± 0.2°, and 36.2252 ± 0.2° 2θ. 17. A crystal form of a methanesulfonic acid salt of a compound of Formula (1):

wherein the crystal form is characterized by an X-ray powder diffraction pattern comprising one or more peaks at 13.8951 ± 0.2°, 15.8697 ± 0.2°, 18.4951 ± 0.2°, 19.5773 ± 0.2°, and 21.5492 ± 0.2° 2θ. 18. The crystal form of claim 17, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 9.4332 ± 0.2°, 10.7336 ± 0.2°, 15.3077 ± 0.2°, 16.2453 ± 0.2°, 21.7550 ± 0.2°, 22.5396 ± 0.2°, 23.8137 ± 0.2°, 25.6827 ± 0.2°, 27.3636 ± 0.2°, and 28.4083 ± 0.2° 2θ. 19. The crystal form of claim 17 or 18, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 13.1847 ± 0.2°, 20.4125 ± 0.2°, 23.1636 ± 0.2°, 24.4222 ± 0.2°, 24.9633 ± 0.2°, 26.2564 ± 0.2°, 26.5213 ± 0.2°, 26.7162 ± 0.2°, 28.0011 ± 0.2°, 30.0138 ± 0.2°, 30.6070 ± 0.2°, 32.0467 ± 0.2°, 33.2600 ± 0.2°, 34.7889 ± 0.2°, 36.4246 ± 0.2°, 37.0117 ± 0.2°, 37.5445 ± 0.2°, 38.3512 ± 0.2°, and 39.4875 ± 0.2° 2θ. 20. A crystal form of a benzenesulfonic acid salt of a compound of Formula (1):

, wherein the crystal form is characterized by an X-ray powder diffraction pattern comprising peaks at 13.3296 ± 0.2°, 14.2875 ± 0.2°, 14.6072 ± 0.2°, 17.6593 ± 0.2°, and 20.4010 ± 0.2° 2θ.

21. The crystal form of claim 20, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 6.0882 ± 0.2°, 8.8966 ± 0.2°, 11.2206 ± 0.2°, 12.2073 ± 0.2°, 14.1225 ± 0.2°, 16.6160 ± 0.2°, 21.5845 ± 0.2°, and 21.9720 ± 0.2°, 25.5863 ± 0.2°, and 27.1334 ± 0.2° 2θ. 22. The crystal form of claim 20 or 21, wherein the X-ray powder diffraction pattern further comprises one or more peaks at 7.1501 ± 0.2°, 12.9781 , 15.5340 ± 0.2°, 15.8947 ± 0.2°, 16.9428 ± 0.2°, 17.8182 ± 0.2°, 18.1970 ± 0.2°, 19.2161 ± 0.2°, 19.4884 ± 0.2°, 19.9886 ± 0.2°, 20.1070 ± 0.2°, 20.9762 ± 0.2°, 22.5384 ± 0.2°, 23.3474 ± 0.2°, 23.5613 ± 0.2°, 23.8492 ± 0.2°, 24.8742 ± 0.2°, 25.1031 ± 0.2°, 25.9489 ± 0.2°, 26.2968 ± 0.2°, 26.5983 ± 0.2°, 28.4875 ± 0.2°, 29.1808 ± 0.2°, 29.8640 ± 0.2°, 30.6238 ± 0.2°, 31.5579 ± 0.2°, 32.7200 ± 0.2°, and 33.4281 ± 0.2° 2θ. 23. The crystal form of any one of claims 1-22 wherein the compound is an inhibitor of at least one of IRAK1, IRAK4, and FLT3. 24. The crystal form of any one of claims 1-23, wherein the compound is an inhibitor of IRAK1 and IRAK4 and is not an inhibitor of FLT3. 25. The crystal form of claim 23 or 24, wherein FLT3 is selected from WT FLT3, activated FLT3, and mutated FLT3. 26. The crystal form of claim 25, wherein the mutated FLT3 is D835Y mutated FLT3 or F691L mutated FLT3. 27. The crystal form of any one of claims 1-26, wherein: the water content of the crystal form is less than or equal to about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %; and/or the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer; and/or the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer; and/or the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. 28. The crystal form of any one of claims 1-27, wherein upon storage for 6 months at about 25 °C and about 60% relative humidity or 6 months at about 40 °C and about 75% relative humidity: the water content of the crystal form is less than or equal to about 3.0 wt. %, about 2.8 wt. %, about 2.6 wt. %, about 2.4 wt. %, about 2.2 wt. %, about 2.0 wt. %, about 1.8 wt. %, about 1.6 wt. %, about 1.4 wt. %, about 1.2 wt. %, about 1.0 wt. %, about 0.8 wt.%, about 0.6 wt. %, about 0.4 wt. %, or about 0.2 wt. %; and/or the crystal form comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer; and/or the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer; and/or the crystal form comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. 29. A pharmaceutical composition comprising the crystal form of any one of claims 1-28, and a formulary ingredient, an adjuvant, or a carrier. 30. The pharmaceutical composition of claim 29, comprising between about 0.1 mg to 10,000 mg, about 1.0 mg to about 9,000 mg, about 1.0 mg to about 8,000 mg, about 1.0 mg to about 7,000 mg, about 1.0 mg to about 6,000 mg, about 1.0 mg to about 5,000 mg, about 1.0 mg to about 4,000 mg, about 1.0 mg to about 3,000 mg, about 1.0 mg to about 2,000 mg, about 1.0 mg to about 1,500 mg, about 1about 1.0 mg to about 1,000 mg, about 1.0 mg to about 750 mg, about 1.0 mg to about 700 mg, about 1.0 mg to about 650 mg, about 1.0 mg to about 600 mg, about 1.0 mg to about 550 mg, about 1.0 mg to about 500 mg, about 1.0 mg to about 450 mg, about 1.0 mg to about 400 mg, about 1.0 mg to about 350 mg, about 1.0 mg to about 300 mg, about 1.0 mg to about 250 mg, about 1.0 mg to about 200 mg, about 1.0 mg to about 150 mg, or about 1.0 mg to about 100 mg of the crystal form. 31. The pharmaceutical composition of claim 29, comprising an amount of crystal form of a salt equivalent to between about 0.1 mg to 10,000 mg, about 1.0 mg to about 9,000 mg, about 1.0 mg to about 8,000 mg, about 1.0 mg to about 7,000 mg, about 1.0 mg to about 6,000 mg, about 1.0 mg to about 5,000 mg, about 1.0 mg to about 4,000 mg, about 1.0 mg to about 3,000 mg, about 1.0 mg to about 2,000 mg, about 1.0 mg to about 1,500 mg, about 1about 1.0 mg to about 1,000 mg, about 1.0 mg to about 750 mg, about 1.0 mg to about 700 mg, about 1.0 mg to about 650 mg, about 1.0 mg to about 600 mg, about 1.0 mg to about 550 mg, about 1.0 mg to about 500 mg, about 1.0 mg to about 450 mg, about 1.0 mg to about 400 mg, about 1.0 mg to about 350 mg, about 1.0 mg to about 300 mg, about 1.0 mg to about 250 mg, about 1.0 mg to about 200 mg, about 1.0 mg to about 150 mg, or about 1.0 mg to about 100 mg of free base. 32. The pharmaceutical composition of any one of claims 29-31, wherein: the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.0 wt. %, about 1.0 wt. %, about 0.5 wt. %, or about 0.25 wt. %; and/or the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer crystal form; and/or the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer crystal form; and/or the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities.

33. The pharmaceutical composition of any one of claims 29-32, wherein upon storage for 3 months at about 25 °C and about 60% relative humidity or 3 months at about 40 °C and about 75% relative humidity: the water content of the pharmaceutical composition is less than or equal to about 10.0 wt. %, about 9.0 wt. %, about 8.0 wt. %, about 7.0 wt. %, about 6.0 wt. %, about 5.0 wt. %, about 4.0 wt. %, about 3.0 wt. %, about 2.0 wt. %, about 1.0 wt. %, about 0.5 wt. %, or about 0.25 wt. %; and/or the pharmaceutical composition comprises greater than or equal to about 95%, about 95.5%, about 96.0%, about 96.5%, about 97.0%, about 97.5%, about 98.0%, about 98.5%, about 99.0%, or about 99.5% of the Formula (1) (R)-enantiomer crystal form; and/or the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, or about 0.5% of the Formula (1) (S)-enantiomer crystal form; and/or the pharmaceutical composition comprises less than or equal to about 5.0%, about 4.5%, about 4.0%, about 3.5%, about 3.0%, about 2.5%, about 2.0%, about 1.5%, about 1.0%, about 0.5%, or about 0.25% impurities. 34. A dosage form comprising the pharmaceutical composition of any one of claims 29-33. 35. The dosage form of claim 34, wherein the dosage form is a tablet or a capsule. 36. A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject the crystal form of any one of claims 1-28 comprising a therapeutically effective amount of the free base or any salt of the compound of Formula (1), the pharmaceutical composition of any one of claims 29-33, or the dosage form of any one of claims 34-35. 37. The method of claim 36, wherein the administration comprises parenteral administration, mucosal administration, intravenous administration, subcutaneous administration, topical administration, intradermal administration, oral administration, sublingual administration, intranasal administration, or intramuscular administration.

38. The method of claim 36 or 37, wherein the therapeutically effective amount is from about 0.005 mg/kg subject body weight to about 1,000 mg/kg subject body weight. 39. The method of any one of claims 36-38, wherein the crystal form, the pharmaceutical composition, or the dosage form disintegrates in the subject’s gastrointestinal tract in about 10 minutes, about 9 minutes, about 8 minutes, about 7 minutes, about 6 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, or about 1 minute. 40. The method of any one of claims 36-39, wherein the disease or disorder comprises a hematopoietic cancer. 41. The method of any one of claims 36-39, wherein the disease or disorder comprises myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). 42. The method of claim 41, wherein: the MDS comprises MDS with a splicing factor mutation, MDS with a mutation in isocitrate dehydrogenase 1, MDS with a mutation in isocitrate dehydrogenase 2; the AML comprises relapsed AML, refractory AML, relapsed/refractory AML, AML with resistance to hypomethylating agents, AML with resistance to venetoclax, AML with resistance to hypomethylating agents and venetoclax, monocytic AML, or monocytic-like AML; or the AML comprises AML with a splicing factor mutation, AML having enhanced IRAK4-Long expression and/or activity relative to IRAK4-Short, and/or wherein the AML is not driven by FLT3 mutations but expresses IRAK4-Long. 43. The method of claim 42, wherein: the MDS with a splicing factor mutation comprises MDS with a splicing factor mutation in U2AF1, SRSF2, SF3B1, or ZRSR2; or the AML splicing factor mutation comprises AML with a splicing factor mutation in U2AF1 or SF3B1.

44. The method of any one of claims 36-39, wherein the disease or disorder comprises lymphoma, leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), bone marrow cancer, non-Hodgkin lymphoma, Waldenstrom’s macroglobulinemia, B cell lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL with MYD88 mutation, follicular lymphoma, or marginal zone lymphoma. 45. The method of any one of claims 36-39, wherein the disease or disorder comprises at least one cancer selected from glioblastoma multiforme, myelofibrosis, endometrial cancer, melanoma, prostate cancer, lung cancer, breast cancer, kidney cancer, bladder cancer, basal cell carcinoma, thyroid cancer, squamous cell carcinoma, neuroblastoma, ovarian cancer, renal cell carcinoma, hepatocellular carcinoma, colon cancer, pancreatic cancer, rhabdomyosarcoma, meningioma, gastric cancer, Glioma, oral cancer, nasopharyngeal carcinoma, rectal cancer, stomach cancer, and uterine cancer. 46. The method of any one of claims 36-39, wherein the disease or disorder comprises one or more inflammatory diseases or autoimmune disease selected from chronic inflammation, sepsis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, psoriasis, Sjögren’s syndrome, Ankylosing spondylitis, systemic sclerosis, Type 1 diabetes mellitus, Crohn’s disease, colitis, and atopic dermatitis. 47. The method of any one of claims 36-39, wherein the disease or disorder comprises diffuse large B-cell lymphoma (DLBCL), and wherein the DLBCL comprises a L265P MYD88 mutant (ABC) subtype of DLBCL or a S219C MYD88 mutant (GCB) subtype of DLBCL. 48. The method of any one of claims 36-39, wherein the disease or disorder is a FLT3 inhibitor resistant disease or disorder. 49. The method of any one of claims 36-39, wherein the disease or disorder is FLT3 inhibitor resistant acute myeloid leukemia (AML), FLT3 inhibitor resistant refractory acute myeloid leukemia (AML), or FLT3 inhibitor resistant relapsed acute myeloid leukemia (AML).

50. The method of any one of claims 36-49, further comprising administering to the subject one or more additional therapies selected from: a chemotherapy agent, a BCL2 inhibitor, an immune modulator, a BTK inhibitor, a DNA methyltransferase inhibitor/hypomethylating agent, an anthracycline, a histone deacetylase (HDAC) inhibitor, a purine nucleoside analogue (antimetabolite), an isocitrate dehydrogenase 1 or 2 (IDH1 and/or IDH2) inhibitor, an antibody- drug conjugate, an mAbs/immunotherapy, a Plk inhibitor, a MEK inhibitor, a CDK inhibitor, a CDK9 inhibitor, a CDK8 inhibitor, a retinoic acid receptor agonist, a TP53 activator, a CELMoD, a smoothened receptor antagonist, an ERK inhibitor including an ERK2/MAPK1 or ERK1/MAPK3 inhibitor, a PI3K inhibitor, an mTOR inhibitor, a steroid or glucocorticoid, a steroid or glucocorticoid receptor modulator, an EZH2 inhibitor, a hedgehog (Hh) inhibitor, a Topoisomerase I inhibitor, a Topoisomerase II inhibitor, an aminopeptidase/Leukotriene A4 hydrolase inhibitor, a FLT3/Axl/ALK inhibitor, a FLT3/KIT/PDGFR, PKC, and/or KDR inhibitor, a Syk inhibitor, an E-selectin inhibitor, an NEDD8-activator, an MDM2 inhibitor, a PLK1 inhibitor, an Aura A inhibitor, an aurora kinase inhibitor, an EGFR inhibitor, an AuroraB/C/VEGFR1/2/3/FLT3/CSF-1R/Kit/PDGFRA/B inhibitor, an AKT 1, 2, and/or 3 inhibitor, a ABL1/2/SRC/EPHA2/LCK/YES1/KIT/PDGFRB/FYN inhibitor, a farnesyltransferase inhibitor, a BRAF/MAP2K1/MAP2K2 inhibitor, a Menin-KMT2A/MLL inhibitor, an immune checkpoint inhibitor, and a multikinase inhibitor. 51. The method of claim 50, wherein the additional therapy is at least one of a BCL2 inhibitor, a BTK inhibitor, a gluococorticoid, a CDK inhibitor, an immune checkpoint inhibitor, and a DNA methyltransferase inhibitor. 52. The method of claim 50 or 51, wherein: the BCL2 inhibitor is venetoclax or a pharmaceutically acceptable salt thereof, the BTK inhibitor is ibrutinib or a pharmaceutically acceptable salt thereof, the glucocorticoid is selected from dexamethasone, methylprednisolone, prednisolone, or a pharmaceutically acceptable salt of any one thereof, the CDK inhibitor is selected from CDK4/6 inhibitor palbociclib, CDK7 inhibitor THZ1, and/or CDK9 inhibitors BAY1251152 and atuveciclib, or a pharmaceutically acceptable salt of any one thereof, the immune checkpoint inhibitor is selected from ipilimumab, nivolumab, pembrolizumab, or a pharmaceutically acceptable salt of any one thereof, or the DNA methyltransferase inhibitor is azacitidine or a pharmaceutically acceptable salt thereof. 53. The method of any one of claims 50-52, wherein the disease or disorder is: a BCL2 inhibitor resistant disease or disorder, a venetoclax resistant disease or disorder, a BTK inhibitor resistant disease or disorder, an ibrutinib resistant disease or disorder, a disease or disorder that is sensitive to anti-inflammatory glucocorticoids, a dexamethasone, methylprednisolone, or prednisolone resistant disease or disorder, a CDK inhibitor resistant disease or disorder, a palbociclib, THZ1, BAY 12511152, or atuveciclib resistant disease or disorder, a DNA methyltransferase inhibitor resistant disease or disorder, an azacitidine resistant disease or disorder, an immune checkpoint inhibitor resistant disease or disorder, an ipilimumab, nivolumab, or pembrolizumab resistant disease or disorder, a BCL2 inhibitor and DNA methyltransferase inhibitor resistant disease or disorder, or a venetoclax and azacitidine resistant disease or disorder. 54. The method of any one of claims 50-53, wherein the disease or disorder is BCL2 inhibitor resistant acute myeloid leukemia (AML), venetoclax resistant AML, BCL2 inhibitor resistant refractory AML, venetoclax resistant refractory AML, BCL2 inhibitor resistant relapsed AML, or venetoclax resistant relapsed AML. 55. The method of claim 50, wherein the crystal form of any one of claims 1-28, the composition of any one of claims 29-33, or the dosage for of any one of claims 34-35, and the one or more additional therapies are administered together in one administration or composition. 56. The method of claim 50, wherein the crystal form of any one of claims 1-28, the composition of any one of claims 29-33, or the dosage form of any one of claims 34-35, and the one or more additional therapies are administered separately in more than one administration or more than one composition. 57. The method of any one of claims 36-56, wherein the disease or disorder is alleviated by inhibiting at least one of IRAK1, IRAK4, and FLT3 in the subject.