WO2025137508A1

WO2025137508A1 - Solid forms of cyclohexyl thiazolyl phenyl carbamate and methods of use thereof

Info

Publication number: WO2025137508A1
Application number: PCT/US2024/061374
Authority: WO
Inventors: Amir Joorab DOOZHA; Jean-Marc Lapierre; Lauren MACEACHERN; R. Alex MAYO; Bernhard Josef PAUL
Original assignee: Cyteir Therapeutics Inc
Current assignee: Cyteir Therapeutics Inc
Priority date: 2023-12-22
Filing date: 2024-12-20
Publication date: 2025-06-26
Anticipated expiration: 2026-06-22

Abstract

The present disclosure relates to a Form of Compound A: (Compound A) and to their pharmaceutically acceptable prodrugs or solvates, pharmaceutical compositions, methods of use, and methods for their preparation. The Forms of Compound A disclosed herein are useful for the treatment of disorders such as a cancer or a neurodegenerative disease.

Description

SOLID FORMS OF CYCLOHEXYL THIAZOLYL PHENYL CARBAMATE AND

METHODS OF USE THEREOF

CROSS-REFERENCE TO RELATED APPLICATION

[001] This application claims priority to, and the benefit of, U.S. Provisional .Application No. 63/613,978, filed on December 22, 2023, the entire contents of which are incorporated herein by reference.

BACKGROUND

[002] Monocarboxylate transporters (MCTs) mediate influx and efflux of monocarboxylates such as lactate, pyruvate, ketone bodies (acetoacetate and betahydroxybutyrate) across cell membranes. These monocarboxylates play an essential role in carbohydrate, amino acid, and fat metabolism in mammalian cells. MCTs catalyze the transport of solutes via a facilitative diffusion mechanism that requires co-transport of protons. Monocarboxylates such as lactate, pyruvate, and ketone bodies play a central role in cellular metabolism and metabolic communications among tissues. Lactate is the end product of aerobic glycolysis. Lactate has recently emerged as a critical regulator of cancer development, invasion, and metastasis. Tumor lactate levels correlate well with metastasis, tumor recurrence, and poor prognosis.

[003] Malignant tumors contain well oxygenated and hypoxic regions, and this hypoxia is associated with increased risk of cancer invasion and metastasis. Tumor hypoxia is associated with treatment failure, relapse, and patient mortality, as these hypoxic cells are generally resistant to standard chemotherapy and radiation therapy. In tumors, cancer cells often prefer to utilize glycolysis rather than oxidative phosphorylation to generate energy by metabolizing glucose into lactate, and are thus referred to as glycolytic tumors. In order to avoid lactate- induced cytotoxicity, glycolytic cancer cells upregulate the expression of MCTs to increase their export capacity and avoid reaching toxic intracellular levels of lactate.

[004] The disclosure arises from a need to provide further compounds for the modulation of monocarboxylate transporters (MCTs). In particular, compounds with improved physicochemical, pharmacological and pharmaceutical properties to existing compounds are desirable. The present disclosure addresses such needs. SUMMARY

[005] The present disclosure provides solid forms of Compound A:

(Compound A), or a hydrate or solvate thereof, and methods of preparing and using the same.

[006] In one aspect, the present disclosure provides a solid form of Compound A:

(Compound A), wherein the solid form is selected from:

Form G: characterized by having X-ray powder diffraction signals at approximately

6.3, 8.6, and 12.6 °29 using Cu Ka radiation,

Form B: characterized by having X-ray powder diffraction signals at approximately

5.3, 7.2, and 15.8 °29 using Cu Ka radiation,

Form I: characterized by having X-ray powder diffraction signals at approximately

11.5 and 14.9 and at least one of 12.9 and 17.4 °29 using Cu Ka radiation,

Form Y: characterized by having X-ray powder diffraction signals at approximately

6.4, 9.0, and 12.5 °29 using Cu Ka radiation,

Form Uu: characterized by having X-ray powder diffraction signals at approximately

8.2, 12.5, and 15.7 °29 using Cu Ka radiation, and

Form Tt: characterized by having X-ray powder diffraction signals at approximately

8.8 and 17.8 and at least one of 19.7 and 20.8 °29 using Cu Ka radiation.

[007] In one aspect, the present disclosure provides a solid form of a hydrate of Compound A:

Compound A), wherein the solid form is Form HD: characterized by having X-ray powder diffraction signals at approximately 5.1 and at least two of 14.9, 17.4, and 20.5 °29 using Cu Ka radiation.

[008] In one aspect, the present disclosure provides a solid form of a 2-MeTHF solvate of Compound A:

Compound A), wherein the solid form is selected from:

Form SV1 : characterized by having X-ray powder diffraction signals at approximately

4.7, 8.1, and 9.3 °29 using Cu Ka radiation, and

Form SV2: characterized by having X-ray powder diffraction signals at approximately

8.3, 12.4, and 19.2 °20 using Cu Ka radiation.

[009] In one aspect, the present disclosure provides a solid form of a 2-DMF solvate of Compound A:

Compound A), wherein the solid form is Form SV3: characterized by having X-ray powder diffraction signals at approximately 9.2, 11.3, and 19.7 °29 using Cu Ka radiation.

[010] The present disclosure also provides a pharmaceutical composition comprising a solid form, e.g., Form G, B, I, Y, Uu, Tt, HD, SV1, SV2, or SV3, disclosed herein and pharmaceutically acceptable carriers or excipients. [Oi l] The present disclosure further provides methods of treating or preventing a disease or disorder, comprising administering to a subject in need thereof a solid form, e.g., Form G, B, I, Y, Uu, Tt, HD, SV1, SV2, or SV3, or a pharmaceutical composition comprising the solid form disclosed herein.

[012] In some aspects, the present disclosure provides a solid form obtainable by, or obtained by, a method for preparing a solid form as described herein.

[013] In some aspects, the present disclosure provides a method of modulating MCT (e.g., MCT1) activity (e.g., in vitro or in vivo), comprising contacting a cell with an effective amount of a solid form as described herein.

[014] In some aspects, the present disclosure provides a solid form as described herein for use in modulating MCT (e.g., MCT1) activity (e.g., in vitro or in vivo).

[015] In some aspects, the present disclosure provides a solid form as described herein for use in treating or preventing a disease or disorder disclosed herein.

[016] In some aspects, the present disclosure provides use of a solid form as described herein in the manufacture of a medicament for modulating MCT (e.g., MCT1) activity (e.g., in vitro or in vivo).

[017] In some aspects, the present disclosure provides use of a solid form as described herein in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein.

[018] In some aspects, the present disclosure provides a method of preparing a solid form as described herein.

[019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. In the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures will control. [020] Other features and advantages of the disclosure will be apparent from the following detailed description and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[021] Fig. 1 depicts the XRPD pattern of Form G.

[022] Fig. 2 depicts the DSC/TGA thermograms of Form G.

[023] Fig. 3 depicts the DSC thermogram of Form G.

[024] Fig. 4 depicts the NMR spectrum of Form G.

[025] Fig. 5 depicts the XRPD pattern of Form B.

[026] Fig. 6 depicts the NMR spectrum of the scaled-up Form B in DMSO-de.

[027] Fig. 7 depicts the DSC thermogram of Form B.

[028] Fig. 8 depicts the DSC/TGA-IR thermograms of Form B. (Top) Coupled TGA/DSC thermograms; (Middle) IR spectrum of Form B at 20.7 min; (Bottom) Gram-Schmidt plot at 2972 cm’¹ indicating the possible evolution of water as a function of time.

[029] Fig. 9 depicts the XRPD pattern of Form I.

[030] Fig. 10 depicts the NMR spectrum of the scaled-up Form I in DMSO-de.

[031] Fig. 11 depicts the DSC thermogram of Form I.

[032] Fig. 12 depicts the DSC/TGA thermograms of Form I.

[033] Fig. 13 depicts the DVS isotherm of Form I.

[034] Fig. 14 depicts the XRPD diffractograms of Form I, before (bottom) and after (top) DVS analysis.

[035] Fig. 15 depicts the XRPD pattern of Form Y.

[036] Fig. 16 depicts the DSC thermogram of Form Y.

[037] Fig. 17 depicts the DSC/TGA thermograms of Form Y.

[038] Fig. 18 depicts the NMR spectrum of the scaled-up Form Y in DMSO-de.

[039] Fig. 19 depicts the XRPD pattern of Form Uu.

[040] Fig. 20 depicts the DSC thermogram of Form Uu.

[041] Fig. 21 depicts the NMR spectrum of the scaled-up Form Uu in DMSO-de.

[042] Fig. 22 depicts the DSC/TGA-IR thermograms of Form Uu. (Top) Coupled TGA/DSC thermograms; (Middle) IR spectrum of Form Uu at 6.2 min; (Bottom) Gram- Schmidt plot at 1105 cm’¹ indicating the possible evolution of chlorobenzene as a function of time.

[043] Fig. 23 depicts the XRPD patterns obtained from the scale-up of Form SV2. (1) Form SV2; (2) Form SV2 (EtOAc); (3) Form Tt. [044] Fig. 24 depicts the XRPD diffractograms of (1) Forms Tt and (2) Uu.

[045] Fig. 25 depicts the XRPD diffractograms of Form SV2 (trace 1, marked by arrow).

[046] Fig. 26 depicts the XRPD pattern of Form Tt.

[047] Fig. 27 depicts the DVS isotherm of Form Tt.

[048] Fig. 28 depicts the XRPD diffractograms of Form Tt, before (bottom) and after (top) DVS analysis.

[049] Fig. 29 depicts the DSC/TGA thermograms of Form Tt.

[050] Fig. 30 depicts the DSC/TGA-IR of Form SV2 obtained from evaporative crystallization in 2-MeTHF. (Top) Coupled TGA/DSC thermograms; (Middle) IR spectrum of Form SV2 at 9.0 min; (Bottom) Gram-Schmidt plot at 2975 cm'¹ indicating the evolution of 2-MeTHF as a function of time.

[051] Fig. 31 depicts the XRPD pattern of Form HD.

[052] Fig. 32 depicts the NMR spectrum of the scaled-up Form HD in DMSO-de.

[053] Fig. 33 depicts the DSC thermogram of Form HD immediately after drying.

[054] Fig. 34 depicts the DSC/TGA thermograms of Form HD immediately after drying.

[055] Fig. 35A depicts the DSC thermogram of Form HD after sitting on the bench. Fig. 35B depicts the DSC/TGA thermograms of Form HD after sitting on the bench.

[056] Fig. 36 depicts the DVS isotherm of Form HD.

[057] Fig. 37 depicts the XRPD diffractograms of Form HD before (bottom) and after (top) DVS analysis.

[058] Fig. 38 depicts the XRPD diffractograms of Forms HD (trace 1, bottom) and Tt (trace 2, top).

[059] Fig. 39 depicts the XRPD pattern of crystalline Form SV2.

[060] Fig. 40 depicts the XRPD pattern of crystalline Form SV3.

[061] Fig. 41 depicts the XRPD patterns obtained from evaporative crystallization (undersaturated experiments). (1) Form G; (2) Form SV3 (DMF:ACN (2:8 vol.)).

[062] Fig. 42 depicts the DSC/TGA-IR of Form SV3 obtained from long-term slurry crystallization in DMF:ACN (2:8 vol.) (Top) Coupled TGA/DSC thermograms; (Middle) IR spectrum of Form SV3 at 15.7 min; (Bottom) Gram-Schmidt plot at 1720 cm'¹ indicating the evolution of DMF as a function of time.

[063] Fig. 43 depicts the XRPD patterns of crystalline Form SV1.

[064] Fig. 44 depicts the DSC/TGA-IR of Form SV1 obtained from evaporative crystallization in 2-MeTHF. (Top) Coupled TGA/DSC thermograms; (Middle) IR spectrum of Form SV1 at 8.2 min; (Bottom) Gram-Schmidt plot at 2980 cm'¹ indicating the evolution of 2-MeTHF as a function of time.

[065] Fig. 45 depicts the solubility of Form G in simulated fluids as a function of time (h).

(1) FaSSGF, (2) FeSSIF, (3) FaSSIF, and (4) Water.

[066] Fig. 46 depicts the solubility of Form G in different buffers.

[067] Fig. 47 depicts the XRPD patterns of the solids crashed out from 0.2 M potassium (bottom) and 1 M sodium (top) phosphate after dissolving in 2% SLS.

[068] Fig. 48 depicts the solubility of Form G in different SLS % loadings.

[069] Fig. 49 depicts the XRPD results for solubility experiment in phosphate buffer and SLS loadings. (1) Form G; (2) Form HD, wet; (3) SLS.

DETAILED DESCRIPTION

[070] The present disclosure relates to solid forms of Compound A or a hydrate or solvate thereof, useful for the specific modulation of MCT-dependent cellular processes and treatment of various disorders. In particular, solid forms of Compound A or a hydrate or solvate thereof with improved physicochemical, pharmacological and pharmaceutical properties are disclosed herein.

Solid Forms

[071] The present disclosure provides solid forms of Compound A:

Compound A), or a hydrate or solvate thereof.

[072] In certain embodiments, the solid form is a solid form of anhydrous Compound A. In certain embodiments, the solid form is Form G. In certain embodiments, the solid form is Form B. In certain embodiments, the solid form is Form I. In certain embodiments, the solid form is Form Y. In certain embodiments, the solid form is Form Uu. In certain embodiments, the solid form is Form Tt.

[073] In certain embodiments, the solid form is a solid form of a hydrate of Compound A. In certain embodiments, the solid form is Form HD. [074] In certain embodiments, the solid form is a solid form of a solvate of Compound A. In certain embodiments, the solid form is a solid form of a 2-MeTHF solvate of Compound A. In certain embodiments, the solid form is Form SV1. In certain embodiments, the solid form is Form SV2. In certain embodiments, the solid form is a solid form of a 2-DMF solvate of Compound A. In certain embodiments, the solid form is Form SV3.

Form G

[075] In one aspect, the present disclosure provides Form G, characterized by having X-ray powder diffraction (“XRPD”) signals at approximately 6.3, 8.6, and 12.6 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at approximately 6.3, 8.3, 8.6, 12.6, and 18.0 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at approximately 6.3, 8.3, 8.6, 12.6, 14.2, 18.0, and 18.6 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at approximately 6.3, 8.3, 8.6, 12.6, 14.2, 18.0, 18.6, and 22.0 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at approximately 6.3, 8.3, 8.6, 12.6, 14.2, 18.0, 18.6, 20.2, 20.7, and 22.0 °29 using Cu Ka radiation.

[076] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.2, 8.6 ± 0.2, and 12.6 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.2, 8.3 ± 0.2, 8.6 ± 0.2, 12.6 ± 0.2, and 18.0 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.2, 8.3 ± 0.2, 8.6 ± 0.2, 12.6 ± 0.2, 14.2 ± 0.2, 18.0 ± 0.2, and 18.6 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.2, 8.3 ± 0.2, 8.6 ± 0.2, 12.6 ± 0.2, 14.2 ± 0.2, 18.0 ± 0.2, 18.6 ± 0.2, and 22.0 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.2, 8.3 ± 0.2, 8.6 ± 0.2, 12.6 ± 0.2, 14.2 ± 0.2, 18.0 ± 0.2, 18.6 ± 0.2, 20.2 ± 0.2, 20.7 ± 0.2, and 22.0 ± 0.2 °29 using Cu Ka radiation. [077] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.1, 8.6 ± 0.1, and 12.6 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.1, 8.3 ± 0.1, 8.6 ± 0.1, 12.6 ± 0.1, and 18.0 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.1, 8.3 ± 0.1, 8.6 ± 0.1, 12.6 ± 0.1, 14.2 ± 0.1, 18.0 ± 0.1, and 18.6 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form G is characterized by having XRPD signals at 6.3 ± 0.1, 8.3 ± 0.1, 8.6 ± 0.1, 12.6 ± 0.1, 14.2 ± 0.1, 18.0 ± 0.1, 18.6 ± 0.1, 20.2 ± 0.1, 20.7 ± 0.1, and 22.0 ± 0.1 °29 using Cu Ka radiation.

[078] In some embodiments, Form G is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 1.

[079] In some embodiments, Form G is characterized by an endothermic event with an onset temperature at approximately 152 °C as measured by DSC. In some embodiments, Form G is characterized by an endothermic event with a peak temperature at approximately 161 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form G is characterized by an endothermic event with an onset temperature at 152 ± 2 °C as measured by DSC. In some embodiments, Form G is characterized by an endothermic event with a peak temperature at 161 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form G is characterized by an endothermic event with an onset temperature at 152 ± 1 °C as measured by DSC. In some embodiments, Form G is characterized by an endothermic event with a peak temperature at 161 ± 1 °C as measured by DSC.

[080] In some embodiments, Form G is characterized by a DSC thermogram substantially the same as that set forth in Fig. 2.

[081] In some embodiments, Form G is characterized by a DSC thermogram substantially the same as that set forth in Fig. 3.

[082] In some embodiments, Form G is characterized by an NMR spectrum substantially the same as that set forth in Fig. 4.

[083] In some embodiments, Form G is characterized by a weight loss of approximately 0% as measured by TGA between approximately 30 °C and approximately 250 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form G is characterized by a weight loss of approximately 0% as measured by TGA between 30 ± 2 °C and 250 ± 2 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form G is characterized by a weight loss of approximately 0% as measured by TGA between 30 ± 1 °C and 250 ± 1 °C as measured by TGA.

[084] In some embodiments, Form G is characterized by a weight loss of residual acetonitrile of between approximately 30 °C and approximately 250 °C as measured by TGA. [085] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form G is characterized by a weight loss of residual acetonitrile of between 30 ± 2 °C and 250 ± 2 °C as measured by TGA.

[086] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form G is characterized by a weight loss of residual acetonitrile of between 30 ± 1 °C and 250 ± 1 °C as measured by TGA.

[087] In some embodiments, Form G has at least one of the characteristics listed in the table below:

[088] In some embodiments, Form G is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table A.

Table A. XRPD signal table for Form G

[089] In some embodiments, Form G is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty XRPD signals selected from those set forth in Table A, as measured with Cu Ka radiation.

[090] In some embodiments, Form G is prepared by a method comprising: combining Compound A with a solvent comprising acetonitrile to form a mixture; heating the mixture to form a solution, and cooling the solution; and optionally isolating Form G. In some embodiments, the solvent is acetonitrile. In some embodiments, the solution is heated to a temperature of approximately 90 °C. In some embodiments, the solution is heated to a temperature of approximately 85 °C. In some embodiments, the solution is heated to a temperature of approximately 80 °C. In some embodiments, the solution is heated to a temperature of approximately 75 °C. In some embodiments, the solution is heated to a temperature of approximately 70 °C. In some embodiments, the solution is heated to a temperature of approximately 65 °C. In some embodiments, the solution is heated to a temperature of greater than 60 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 55 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 50 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 45 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 40 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 35 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 30 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 25 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 20 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 15 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 10 °C. In some embodiments, the solution is cooled to a temperature of approximately or below 5 °C. In some embodiments, the cooling comprises multiple steps of cooling. In some embodiments, the cooling comprises cooling to a first temperature, followed by cooling to a second temperature.

Form B

[091] In one aspect, the present disclosure provides Form B, characterized by having XRPD signals at approximately 5.3, 7.2, and 15.8 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at approximately 5.3, 7.2, 15.8, 17.5, and at least one of 13.4, 14.4, and 21.0 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at approximately 5.3, 7.2, 13.4, 15.8, and 17.5 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at approximately 5.3, 7.2, 14.4, 15.8, and 17.5 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at approximately 5.3, 7.2, 15.8, 17.5, and 21.0 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at approximately 5.3, 7.2, 13.4, 14.4, 15.8, 17.5, and 21.0 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at approximately 5.3, 7.2, 13.4, 14.4, 15.8, 17.5, 18.4, and 21.0 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at approximately 5.3, 7.2, 13.4, 14.4, 15.8, 17.4, 17.5, 18.4, 21.0, and 24.0 °29 using Cu Ka radiation.

[092] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, and 15.8 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, 15.8 ± 0.2, 17.5 ± 0.2, and at least one of 13.4 ± 0.2, 14.4 ± 0.2, and 21.0 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, 13.4 ± 0.2, 15.8 ± 0.2, and 17.5 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, 14.4 ± 0.2, 15.8 ± 0.2, and 17.5 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, 15.8 ± 0.2, 17.5 ± 0.2, and 21.0 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, 13.4 ± 0.2, 14.4 ± 0.2, 15.8 ± 0.2, 17.5 ± 0.2, and 21.0 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, 13.4 ± 0.2, 14.4 ± 0.2, 15.8 ± 0.2, 17.5 ± 0.2, 18.4 ± 0.2, and 21.0 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.2, 7.2 ± 0.2, 13.4 ± 0.2, 14.4 ± 0.2, 15.8 ± 0.2, 17.4 ± 0.2, 17.5 ± 0.2, 18.4 ± 0.2, 21.0 ± 0.2, and 24.0 ± 0.2 °29 using Cu Ka radiation.

[093] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, and 15.8 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, 15.8 ± 0.1, 17.5 ± 0.1, and at least one of 13.4 ± 0.1, 14.4 ± 0.1, and 21.0 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, 13.4 ± 0.1, 15.8 ± 0.1, and 17.5 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, 14.4 ± 0.1, 15.8 ± 0.1, and 17.5 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, 15.8 ± 0.1, 17.5 ± 0.1, and 21.0 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, 13.4 ± 0.1, 14.4 ± 0.1, 15.8 ± 0.1, 17.5 ± 0.1, and 21.0 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, 13.4 ± 0.1, 14.4 ± 0.1, 15.8 ± 0.1, 17.5 ± 0.1, 18.4 ± 0.1, and 21.0 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form B is characterized by having XRPD signals at 5.3 ± 0.1, 7.2 ± 0.1, 13.4 ± 0.1, 14.4 ± 0.1, 15.8 ± 0.1, 17.4 ± 0.1, 17.5 ± 0.1, 18.4 ± 0.1, 21.0 ± 0.1, and 24.0 ± 0.1 °29 using Cu Ka radiation.

[094] In some embodiments, Form B is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 5.

[095] In some embodiments, Form B is characterized by an endothermic event with an onset temperature at approximately 136 °C as measured by DSC. In some embodiments, Form B is characterized by an endothermic event with a peak temperature at approximately 147 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form B is characterized by an endothermic event with an onset temperature at 136 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form B is characterized by an endothermic event with a peak temperature at 147 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form B is characterized by an endothermic event with an onset temperature at 136 ± 1 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form B is characterized by an endothermic event with a peak temperature at 147 ± 1 °C as measured by DSC.

[096] In some embodiments, Form B is characterized by a DSC thermogram substantially the same as that set forth in Fig. 7.

[097] In some embodiments, Form B is characterized by a weight loss of methanol of approximately 1.7% between approximately 46 °C and approximately 165 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form B is characterized by a weight loss of methanol of approximately 1.7% between 46 ± 2 °C and 165 ± 2 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form B is characterized by a weight loss of methanol of approximately 1.7% between approximately 46 ± 1 °C and 165 ± 1 °C as measured by TGA. [098] In some embodiments, Form B is characterized by a weight loss of methanol of between approximately 46 °C and approximately 165 °C as measured by TGA.

[099] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form B is characterized by a weight loss of methanol of between 46 °C ± 2 and 165 ± 2 °C as measured by TGA.

[0100] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form B is characterized by a weight loss of methanol of approximately 1.7% between 46 °C ± 1 and 165 ± 1 °C as measured by TGA.

[0101] In some embodiments, Form B has at least one of the characteristics listed in the table below:

[0102] In some embodiments, Form B is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table B.

Table B. XRPD signal table for Form B

[0103] In some embodiments, Form B is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, and eighteen XRPD signals selected from those set forth in Table B, as measured with Cu Ka radiation.

[0104] In some embodiments, Form B is prepared by a method comprising: combining Compound A (e.g., Form G) with a solvent comprising methanol to form a mixture; stirring the mixture to form a solution, and evaporating the solvent; and optionally isolating Form B. In some embodiments, the solvent is methanol. In some embodiments, the solution is stirred for about 6 hours. In some embodiments, the solution is stirred for about 5 hours. In some embodiments, the solution is stirred for about 4 hours. In some embodiments, the solution is stirred for about 3 hours. In some embodiments, the solution is stirred for about 2 hours. In some embodiments, the solution is stirred for about 1 hour.

[0105] In some embodiments, the solution is stirred at a temperature of approximately or below 40 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 35 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 30 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 25 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 20 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 15 °C.

Form I

[0106] In one aspect, the present disclosure provides Form I, characterized by having XRPD signals at approximately 11.5 and 14.9 and at least one of 12.9 and 17.4 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at approximately 11.5, 12.9, and 14.9 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at approximately 11.5, 14.9, and 17.4 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at approximately 11.3, 11.5, 12.9, 14.9, and 17.4 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at approximately 10.6, 11.3,

11.5, 12.9, 14.6, 14.9, and 17.4 °29 using Cu Ka radiation. In some embodiments, Form I is In some embodiments, Form I is characterized by having XRPD signals at approximately 9.9,

10.6, 11.3, 11.5, 12.9, 14.6, 14.9, and 17.4 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at approximately 9.9, 10.6, 11.3, 11.5, 12.9,

14.6, 14.9, 16.6, 17.4, and 22.1 °29 using Cu Ka radiation.

[0107] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In some embodiments, Form I is characterized by having XRPD signals at 11.5 ± 0.2 and 14.9 ± 0.2 and at least one of 12.9 ± 0.2 and 17.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 11.5 ± 0.2, 12.9 ± 0.2, and 14.9 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 11.5 ± 0.2, 14.9 ± 0.2, and 17.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 11.3 ± 0.2, 11.5 ± 0.2, 12.9 ± 0.2, 14.9 ± 0.2, and 17.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 10.6 ± 0.2, 11.3 ± 0.2, 11.5 ± 0.2, 12.9 ± 0.2, 14.6 ± 0.2, 14.9 ± 0.2, and 17.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form I is In some embodiments, Form I is characterized by having XRPD signals at 9.9 ± 0.2, 10.6 ± 0.2, 11.3 ± 0.2, 11.5 ± 0.2, 12.9 ± 0.2, 14.6 ± 0.2, 14.9 ± 0.2, and

17.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 9.9 ± 0.2, 10.6 ± 0.2, 11.3 ± 0.2, 11.5 ± 0.2, 12.9 ± 0.2, 14.6 ± 0.2, 14.9 ± 0.2, 16.6 ± 0.2, 17.4 ± 0.2, and 22.1 ± 0.2 °29 using Cu Ka radiation.

[0108] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In some embodiments, Form I is characterized by having XRPD signals at

11.5 ± 0.1 and 14.9 ± 0.1 and at least one of 12.9 ± 0.1 and 17.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 11.5 ± 0.1, 12.9 ± 0.1, and 14.9 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 11.5 ± 0.1, 14.9 ± 0.1, and 17.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 11.3 ± 0.1, 11.5 ± 0.1, 12.9 ± 0.1, 14.9 ± 0.1, and 17.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 10.6 ± 0.1, 11.3 ± 0.1, 11.5 ± 0.1, 12.9 ± 0.1, 14.6 ± 0.1, 14.9 ± 0.1, and 17.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form I is In some embodiments, Form I is characterized by having XRPD signals at 9.9 ± 0.1, 10.6 ± 0.1, 11.3 ± 0.1, 11.5 ± 0.1, 12.9 ± 0.1, 14.6 ± 0.1, 14.9 ± 0.1, and 17.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form I is characterized by having XRPD signals at 9.9 ± 0.1, 10.6 ± 0.1, 11.3 ± 0.1, 11.5 ± 0.1, 12.9 ± 0.1, 14.6 ± 0.1, 14.9 ± 0.1, 16.6 ± 0.1, 17.4 ± 0.1, and 22.1 ± 0.1 °29 using Cu Ka radiation.

[0109] In some embodiments, Form I is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 9.

[0110] In some embodiments, Form I is characterized by endothermic events with onset temperatures at approximately 135 °C and/or 189 °C as measured by DSC. In some embodiments, Form I is characterized by endothermic events with peak temperatures at approximately 141 °C and/or 191 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form I is characterized by endothermic events with onset temperatures at 135 ± 2 °C and/or 189 ± 2 °C as measured by DSC. In some embodiments, Form I is characterized by endothermic events with peak temperatures at 141 ± 2 °C and/or 191 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form I is characterized by endothermic events with onset temperatures at 135 ± 1 °C and/or 189 ± 1 °C as measured by DSC. In some embodiments, Form I is characterized by endothermic events with peak temperatures at 141 ± 1 °C and/or 191 ± 1 °C as measured by DSC.

[0111] In some embodiments, Form I is characterized by a DSC thermogram substantially the same as that set forth in Fig. 11.

[0112] In some embodiments, Form I is characterized by a weight loss of ethanol/water of approximately 0.03% between approximately 58 °C and approximately 120 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form I is characterized by a weight loss of ethanol/water of approximately 0.03% between 58 ± 2 °C and 120 ± 2 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form I is characterized by a weight loss of ethanol/water of approximately 0.03% between 58 ± 1 °C and 120 ± 1 °C as measured by TGA.

[0113] In some embodiments, Form I is characterized by a weight loss of ethanol/water of between approximately 58 °C and approximately 120 °C as measured by TGA.

[0114] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form I is characterized by a weight loss of ethanol/water of between 58 ± 2 °C and 120 ± 2 °C as measured by TGA.

[0115] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form I is characterized by a weight loss of ethanol/water of between 58 ± 1 °C and 120 ± 1 °C as measured by TGA.

[0116] In some embodiments, Form I has at least one of the characteristics listed in the table below:

[0117] In some embodiments, Form I is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown Table C. Table C. XRPD signal table for Form I

[0118] In some embodiments, Form I is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty one, twenty two, twenty three, twenty four, twenty five or twenty six XRPD signals selected from those set forth in Table C, as measured with Cu Ka radiation. [0119] In some embodiments, Form I is prepared by a method comprising: combining Compound A (e.g., Form G) with a solvent comprising ethanol to form a mixture; heating the mixture to form a solution, and evaporating the solvent; and optionally isolating Form I. In some embodiments, the solvent is a mixture of ethanol and water. In some embodiments, the solution is heated to a temperature of approximately 65 °C. In some embodiments, the solution is heated to a temperature of approximately 60 °C. In some embodiments, the solution is heated to a temperature of approximately 55 °C. In some embodiments, the solution is heated to a temperature of approximately 50 °C. In some embodiments, the solution is heated to a temperature of approximately 45 °C. In some embodiments, the solution is heated to a temperature of approximately 40 °C. In some embodiments, the solution is heated to a temperature of greater than 35 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 60 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 55 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 50 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 45 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 40 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 35 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 30 °C.

Form Y

[0120] In one aspect, the present disclosure provides Form Y, characterized by having XRPD signals at approximately 6.4, 9.0, and 12.5 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 9.0, 11.1, 11.5, and 12.5 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 9.0, 10.4, 11.1, 11.5, and 12.5, and at least one of 12.9, and 15.7 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 9.0, 10.4, 11.1, 11.5, 12.5, and 12.9 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 9.0, 10.4, 11.1, 11.5, 12.5, and 15.7 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 9.0, 10.4, 11.1, 11.5, 12.5, 12.9, and 15.7 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 9.0, 10.4, 11.1, 11.5, 12.5, 12.9, and 15.7 and at least two of 8.2, 11.3, and 20.7 °20 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 8.2, 9.0, 10.4, 11.1, 11.3, 11.5, 12.5, 12.9, and 15.7 °20 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 9.0, 10.4, 11.1, 11.3, 11.5, 12.5, 12.9, 15.7, and 20.7 °20 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at approximately 6.4, 8.2, 9.0, 10.4, 11.1, 11.5, 12.5, 12.9, 15.7, and 20.7 °20 using Cu Ka radiation.

[0121] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, and 12.5 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, 11.1 ± 0.2, 11.5 ± 0.2, and 12.5 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.5 ± 0.2, and 12.5 ± 0.2, and at least one of 12.9 ± 0.2, and 15.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.5 ± 0.2, 12.5 ± 0.2, and 12.9 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.5 ± 0.2, 12.5 ± 0.2, and 15.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.5 ± 0.2, 12.5 ± 0.2, 12.9 ± 0.2, and 15.7 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.5 ± 0.2, 12.5 ± 0.2, 12.9 ± 0.2, and 15.7 ± 0.2 and at least two of 8.2 ± 0.2, 11.3 ± 0.2, and 20.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.3 ± 0.2, 11.5 ± 0.2, 12.5 ± 0.2, 12.9 ± 0.2, and 15.7 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.3 ± 0.2, 11.5 ± 0.2, 12.5 ± 0.2, 12.9 ± 0.2, 15.7 ± 0.2, and 20.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 9.0 ± 0.2, 10.4 ± 0.2, 11.1 ± 0.2, 11.5 ± 0.2, 12.5 ± 0.2, 12.9 ± 0.2, 15.7 ± 0.2, and 20.7 ± 0.2 °29 using Cu Ka radiation.

[0122] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, and 12.5 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, 11.1 ± 0.1, 11.5 ± 0.1, and 12.5 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.5 ± 0.1, and 12.5 ± 0.1, and at least one of 12.9 ± 0.1, and 15.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.5 ± 0.1, 12.5 ± 0.1, and 12.9 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.5 ± 0.1, 12.5 ± 0.1, and 15.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.5 ± 0.1, 12.5 ± 0.1, 12.9 ± 0.1, and 15.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.5 ± 0.1, 12.5 ± 0.1, 12.9 ± 0.1, and 15.7 ± 0.1 and at least two of 8.2 ± 0.1, 11.3 ± 0.1, and 20.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.3 ± 0.1, 11.5 ± 0.1, 12.5 ± 0.1, 12.9 ± 0.1, and 15.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.3 ± 0.1, 11.5 ± 0.1, 12.5 ± 0.1, 12.9 ± 0.1, 15.7 ± 0.1, and 20.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Y is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 9.0 ± 0.1, 10.4 ± 0.1, 11.1 ± 0.1, 11.5 ± 0.1, 12.5 ± 0.1, 12.9 ± 0.1, 15.7 ± 0.1, and 20.7 ± 0.1 °29 using Cu Ka radiation.

[0123] In some embodiments, Form Y is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 15.

[0124] In some embodiments, Form Y is characterized by endothermic events with onset temperatures at approximately 103 °C and/or 173 °C as measured by DSC. In some embodiments, Form Y is characterized by endothermic events with peak temperatures at approximately 116 °C and/or 177 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Y is characterized by endothermic events with onset temperatures at 103 ± 2 °C and/or 173 ± 2 °C as measured by DSC. In some embodiments, Form Y is characterized by endothermic events with peak temperatures at 116 ± 2 °C and/or 177 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Y is characterized by endothermic events with onset temperatures at 103 ± 1 °C and/or 173 ± 1 °C as measured by DSC. In some embodiments, Form Y is characterized by endothermic events with peak temperatures at 116 ± 1 °C and/or 177 ± 1 °C as measured by DSC.

[0125] In some embodiments, Form Y is characterized by a DSC thermogram substantially the same as that set forth in Fig. 16.

[0126] In some embodiments, Form Y is characterized by a weight loss of toluene of approximately 0.9% between approximately 45 °C and approximately 172 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Y is characterized by a weight loss of toluene of approximately 0.9% between 45 ± 2 °C and 172 ± 2 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Y is characterized by a weight loss of toluene of approximately 0.9% between 45 ± 1 °C and 172 ± 1 °C as measured by TGA.

[0127] In some embodiments, Form Y is characterized by a weight loss of toluene of between approximately 45 °C and approximately 172 °C as measured by TGA.

[0128] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Y is characterized by a weight loss of toluene of between 45 ± 2 °C and 172 ± 2 °C as measured by TGA.

[0129] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Y is characterized by a weight loss of toluene of between 45 ± 1 °C and 172 ± 1 °C as measured by TGA.

[0130] In some embodiments, Form Y has at least one of the characteristics listed in the table below:

[0131] In some embodiments, Form Y is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table D. Table D. XRPD signal table for Form Y

[0132] In some embodiments, Form Y is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, thirty-two, thirty-three, thirty- four, or thirty-five XRPD signals selected from those set forth in Table D, as measured with Cu Ka radiation.

[0133] In some embodiments, Form Y is prepared by a method comprising: combining Compound A (e.g., Form G) with a solvent comprising toluene to form a mixture; heating the mixture to form a solution, and evaporating the solvent; and optionally isolating Form Y. In some embodiments, the solvent is a mixture of toluene. In some embodiments, the solution is heated to a temperature of approximately 65 °C. In some embodiments, the solution is heated to a temperature of approximately 60 °C. In some embodiments, the solution is heated to a temperature of approximately 55 °C. In some embodiments, the solution is heated to a temperature of approximately 50 °C. In some embodiments, the solution is heated to a temperature of approximately 45 °C. In some embodiments, the solution is heated to a temperature of approximately 40 °C. In some embodiments, the solution is heated to a temperature of greater than 35 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 60 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 55 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 50 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 45 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 40 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 35 °C. In some embodiments, the solvent is evaporated at a temperature of approximately or below 30 °C.

Form Uu

[0134] In one aspect, the present disclosure provides Form Uu, characterized by having XRPD signals at approximately 8.2, 12.5, and 15.7 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at approximately 6.4, 8.2, 12.5, and 15.7, and at least one of 9.0 and 15.1 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at approximately 6.4, 8.2, 9.0, 12.5, and 15.7 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at approximately 6.4, 8.2, 12.5, 15.1, and 15.7 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at approximately 6.4, 8.2, 9.0, 12.5, 15.1, 15.7, and 20.7 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at approximately 6.4, 8.2, 9.0, 10.3, 12.5, 15.1, 15.7, and 20.7 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at approximately 6.4, 8.2, 9.0, 10.3, 11.3, 12.5, 15.1, 15.7, 19.2, and 20.7 °29 using Cu Ka radiation.

[0135] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In one aspect, the present disclosure provides Form Uu, characterized by having XRPD signals at 8.2 ± 0.2, 12.5 ± 0.2, and 15.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 12.5 ± 0.2, and 15.7 ± 0.2, and at least one of 9.0 ± 0.2 and 15.1 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 9.0 ± 0.2, 12.5 ± 0.2, and 15.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 12.5 ± 0.2, 15.1 ± 0.2, and 15.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 9.0 ± 0.2, 12.5 ± 0.2, 15.1 ± 0.2, 15.7 ± 0.2, and 20.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 9.0 ± 0.2, 10.3 ± 0.2, 12.5 ± 0.2, 15.1 ± 0.2, 15.7 ± 0.2, and 20.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.2, 8.2 ± 0.2, 9.0 ± 0.2, 10.3 ± 0.2, 11.3 ± 0.2, 12.5 ± 0.2, 15.1 ± 0.2, 15.7 ± 0.2, 19.2 ± 0.2, and 20.7 ± 0.2 °29 using Cu Ka radiation.

[0136] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In one aspect, the present disclosure provides Form Uu, characterized by having XRPD signals at 8.2 ± 0.1, 12.5 ± 0.1, and 15.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 12.5 ± 0.1, and 15.7 ± 0.1, and at least one of 9.0 ± 0.1 and 15.1 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 9.0 ± 0.1, 12.5 ± 0.1, and 15.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 12.5 ± 0.1, 15.1 ± 0.1, and 15.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 9.0 ± 0.1, 12.5 ± 0.1, 15.1 ± 0.1, 15.7 ± 0.1, and 20.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 9.0 ± 0.1, 10.3 ± 0.1, 12.5 ± 0.1, 15.1 ± 0.1, 15.7 ± 0.1, and 20.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Uu is characterized by having XRPD signals at 6.4 ± 0.1, 8.2 ± 0.1, 9.0 ± 0.1, 10.3 ± 0.1, 11.3 ± 0.1, 12.5 ± 0.1, 15.1 ± 0.1, 15.7 ± 0.1, 19.2 ± 0.1, and 20.7 ± 0.1 °20 using Cu Ka radiation.

[0137] In some embodiments, Form Uu is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 19.

[0138] In some embodiments, Form Uu is characterized by endothermic events with onset temperatures at approximately 111 °C and/or 184 °C as measured by DSC. In some embodiments, Form Uu is characterized by endothermic events with peak temperatures at approximately 119 °C and/or 190 °C as measured by DSC. In some embodiments, Form Uu is characterized by an exothermic event with an onset temperature at approximately 151 °C as measured by DSC. In some embodiments, Form Uu is characterized by an exothermic event with a peak temperature at approximately 165 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Uu is characterized by endothermic events with onset temperatures at 111 ± 2 °C and/or 184 ± 2 °C as measured by DSC. In some embodiments, Form Uu is characterized by endothermic events with peak temperatures at 119 ± 2 °C and/or 190 ± 2 °C as measured by DSC. In some embodiments, Form Uu is characterized by an exothermic event with an onset temperature at 151 ± 2 °C as measured by DSC. In some embodiments, Form Uu is characterized by an exothermic event with a peak temperature at 165 °C ± 2 as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Uu is characterized by endothermic events with onset temperatures at 111 ± 1 °C and/or 184 ± 1 °C as measured by DSC. In some embodiments, Form Uu is characterized by endothermic events with peak temperatures at 119 ± 1 °C and/or 190 ± 1 °C as measured by DSC. In some embodiments, Form Uu is characterized by an exothermic event with an onset temperature at 151 ± 1 °C as measured by DSC. In some embodiments, Form Uu is characterized by an exothermic event with a peak temperature at 165 °C ± 1 as measured by DSC. [0139] In some embodiments, Form Uu is characterized by a DSC thermogram substantially the same as that set forth in Fig. 20.

[0140] In some embodiments, Form Uu is characterized by a weight loss of chlorobenzene of approximately 2.8% between approximately 74 °C and approximately 210 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Uu is characterized by a weight loss of chlorobenzene of approximately 2.8% between 74 ± 2 °C and 210 ± 2 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Uu is characterized by a weight loss of chlorobenzene of approximately 2.8% between 74 ± 1 °C and 210 ± 1 °C as measured by TGA.

[0141] In some embodiments, Form Uu is characterized by a weight loss of chlorobenzene of between approximately 74 °C and approximately 210 °C as measured by TGA.

[0142] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Uu is characterized by a weight loss of chlorobenzene of between 74 ± 2 °C and 210 ± 2 °C as measured by TGA.

[0143] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Uu is characterized by a weight loss of chlorobenzene of between 74 ± 1 °C and 210 ± 1 °C as measured by TGA.

[0144] In some embodiments, Form Uu has at least one of the characteristics listed in the table below:

exo: exotherm.

[0145] In some embodiments, Form Uu is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table E. Table E. XRPD signal table for Form Uu

[0146] In some embodiments, Form Uu is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, or thirty-two XRPD signals selected from those set forth in Table E, as measured with Cu Ka radiation.

[0147] In some embodiments, Form Uu is prepared by a method comprising: combining Compound A (e.g., Form G) with a solvent comprising chlorobenzene to form a mixture; heating the mixture, filtering the mixture and collecting a filtrate, and drying the filtrate, optionally isolating Form Uu. In some embodiments, the solvent is chlorobenzene. In some embodiments, the mixture is heated to a temperature of approximately 65 °C. In some embodiments, the mixture is heated to a temperature of approximately 60 °C. In some embodiments, the mixture is heated to a temperature of approximately 55 °C. In some embodiments, the mixture is heated to a temperature of approximately 50 °C. In some embodiments, the mixture is heated to a temperature of approximately 45 °C. In some embodiments, the mixture is heated to a temperature of approximately 40 °C. In some embodiments, the mixture is heated to a temperature of greater than 35 °C. In some embodiments, the filtrate is dried at a temperature of approximately 65 °C. In some embodiments, the filtrate is dried at a temperature of approximately 60 °C. In some embodiments, the filtrate is dried at a temperature of approximately 55 °C. In some embodiments, the filtrate is dried at to a temperature of approximately 50 °C. In some embodiments, the filtrate is dried at a temperature of approximately 45 °C. In some embodiments, the filtrate is dried at a temperature of approximately 40 °C. In some embodiments, the filtrate is dried at a temperature of greater than 35 °C.

Form Tt

[0148] In one aspect, the present disclosure provides Form Tt, characterized by having XRPD signals at approximately 8.8 and 17.8 and at least one of 19.7 and 20.8 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at approximately 8.8, 17.8, and 19.7 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at approximately 8.8, 17.8, and 20.8 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at approximately 8.8, 17.8, 19.7, 20.8, and 23.7 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at approximately 8.8, 15.4, 17.8, 19.7, 20.8, 23.7, and 26.6 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at approximately 8.8, 13.0, 15.4, 17.8, 19.7, 20.8, 23.7, and 26.6 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at approximately 8.8, 13.0, 15.4, 17.8, 19.7, 20.8, 23.7, and 26.6 and at least two of 10.9, 13.7, 14.3, 15.7, and 21.5 °20 using Cu Ka radiation.

[0149] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In one aspect, the present disclosure provides Form Tt, characterized by having XRPD signals at 8.8 ± 0.2 and 17.8 ± 0.2 and at least one of 19.7 ± 0.2 and 20.8 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.2, 17.8 ± 0.2, and 19.7 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.2, 17.8 ± 0.2, and

20.8 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.2, 17.8 ± 0.2, 19.7 ± 0.2, 20.8 ± 0.2, and 23.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at

8.8 ± 0.2, 15.4 ± 0.2, 17.8 ± 0.2, 19.7 ± 0.2, 20.8 ± 0.2, 23.7 ± 0.2, and 26.6 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at

8.8 ± 0.2, 13.0 ± 0.2, 15.4 ± 0.2, 17.8 ± 0.2, 19.7 ± 0.2, 20.8 ± 0.2, 23.7 ± 0.2, and 26.6 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.2, 13.0 ± 0.2, 15.4 ± 0.2, 17.8 ± 0.2, 19.7 ± 0.2, 20.8 ± 0.2, 23.7 ± 0.2, and 26.6 ± 0.2 and at least two of 10.9 ± 0.2, 13.7 ± 0.2, 14.3 ± 0.2, 15.7 ± 0.2, and 21.5 ± 0.2 °20 using Cu Ka radiation.

[0150] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In one aspect, the present disclosure provides Form Tt, characterized by having XRPD signals at 8.8 ± 0.1 and 17.8 ± 0.1 and at least one of 19.7 ± 0.1 and 20.8 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.1, 17.8 ± 0.1, and 19.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.1, 17.8 ± 0.1, and

20.8 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.1, 17.8 ± 0.1, 19.7 ± 0.1, 20.8 ± 0.1, and 23.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at

8.8 ± 0.1, 15.4 ± 0.1, 17.8 ± 0.1, 19.7 ± 0.1, 20.8 ± 0.1, 23.7 ± 0.1, and 26.6 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.1, 13.0 ± 0.1, 15.4 ± 0.1, 17.8 ± 0.1, 19.7 ± 0.1, 20.8 ± 0.1, 23.7 ± 0.1, and 26.6 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form Tt is characterized by having XRPD signals at 8.8 ± 0.1, 13.0 ± 0.1, 15.4 ± 0.1, 17.8 ± 0.1, 19.7 ± 0.1, 20.8 ± 0.1, 23.7 ± 0.1, and 26.6 ± 0.1 and at least two of 10.9 ± 0.1, 13.7 ± 0.1, 14.3 ± 0.1, 15.7 ± 0.1, and 21.5 ± 0.1 °20 using Cu Ka radiation.

[0151] In some embodiments, Form Tt is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 23 (trace 3).

[0152] In some embodiments, Form Tt is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 24 (trace 1).

[0153] In some embodiments, Form Tt is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 26.

[0154] In some embodiments, Form Tt is characterized by an endothermic event with an onset temperature at approximately 190 °C as measured by DSC. In some embodiments, Form Tt is characterized by an endothermic event with a peak temperature at approximately 193 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Tt is characterized by an endothermic event with an onset temperature at 190 ± 2 °C as measured by DSC. In some embodiments, Form Tt is characterized by an endothermic event with a peak temperature at 193 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Tt is characterized by an endothermic event with an onset temperature at 190 ± 1 °C as measured by DSC. In some embodiments, Form Tt is characterized by an endothermic event with a peak temperature at 193 ± 1 °C as measured by DSC.

[0155] In some embodiments, Form Tt is characterized by a DSC thermogram substantially the same as that set forth in Fig. 29.

[0156] In some embodiments, Form Tt is characterized by a weight loss of 2-MeTHF of approximately 0.7% between approximately 54 °C and approximately 194 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Tt is characterized by a weight loss of 2-MeTHF of approximately 0.7% between 54 ± 2 °C and 194 ± 2 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Tt is characterized by a weight loss of 2-MeTHF of approximately 0.7% between 54 ± 1 °C and 194 ± 1 °C as measured by TGA. [0157] In some embodiments, Form Tt is characterized by a weight loss of 2-MeTHF of between approximately 54 °C and approximately 194 °C as measured by TGA.

[0158] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form Tt is characterized by a weight loss of 2- MeTHF of between 54 ± 2 °C and 194 ± 2 °C as measured by TGA.

[0159] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form Tt is characterized by a weight loss of 2- MeTHF of between 54 ± 1 °C and 194 ± 1 °C as measured by TGA.

[0160] In some embodiments, Form Tt has at least one of the characteristics listed in the table below:

[0161] In some embodiments, Form Tt is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table F.

Table F. XRPD signal table for Form Tt

[0162] In some embodiments, Form Tt is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen XRPD signals selected from those set forth in Table F, as measured with Cu Ka radiation.

[0163] In some embodiments, the solid Form Tt is prepared by a method comprising: thermal treating Compound A (Form SV2).

[0164] In some embodiments, the solid Form Tt is prepared by a method comprising: combining Compound A (e.g., Form G) with a solvent comprising 2-MeTHF to form a mixture; heating the mixture, evaporating the solvent, , drying the filtrate, optionally isolating Form SV2, and heating Form SV2 resulting in Form Tt. In some embodiments, the solvent is 2-MeTHF. In some embodiments, the mixture is heated to a temperature of approximately 65 °C. In some embodiments, the mixture is heated to a temperature of approximately 60 °C. In some embodiments, the mixture is heated to a temperature of approximately 55 °C. In some embodiments, the mixture is heated to a temperature of approximately 50 °C. In some embodiments, the mixture is heated to a temperature of approximately 45 °C. In some embodiments, the mixture is heated to a temperature of approximately 40 °C. In some embodiments, the mixture is heated to a temperature of greater than 35 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 150 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 145 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 140 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 135 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 130 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 125 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 120 °C. In some embodiments, Form SV2 is heated at a temperature of approximately up to 115 °C.

Form HD

[0165] In one aspect, the present disclosure provides Form HD, characterized by having XRPD signals at approximately 5.1 and at least two of 14.9, 17.4, and 20.5 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 14.9, and 17.4 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 14.9, and 20.5 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 17.4, and 20.5 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 14.9, 17.4, 20.5, and 24.7 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 14.9, 17.4, 20.5, 22.6, and 24.7 and at least one of 11.5 and 21.9 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 11.5, 14.9, 17.4, 20.5, 22.6, and 24.7 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 14.9, 17.4, 20.5, 21.9, 22.6, and 24.7 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 11.5, 14.9, 17.4, 20.5, 21.9, 22.6, and 24.7 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 11.5, 14.8, 14.9,

17.4, 20.5, 21.9, 22.6, and 24.7 and at least one of 17.6 and 18.8 °20 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1, 11.5, 14.8, 14.9, 17.4, 17.6, 20.5, 21.9, 22.6, and 24.7 °20 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at approximately 5.1,

11.5, 14.8, 14.9, 17.4, 18.8, 20.5, 21.9, 22.6, and 24.7 °20 using Cu Ka radiation.

[0166] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In one aspect, the present disclosure provides Form HD, characterized by having XRPD signals at 5.1 ± 0.2 and at least two of 14.9 ± 0.2, 17.4 ± 0.2, and 20.5 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 14.9 ± 0.2, and 17.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 14.9 ± 0.2, and 20.5 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 17.4 ± 0.2, and 20.5 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 20.5 ± 0.2, and 24.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 20.5 ± 0.2, 22.6 ± 0.2, and 24.7 ± 0.2 and at least one of 11.5 ± 0.2 and 21.9 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 11.5 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 20.5 ± 0.2, 22.6 ± 0.2, and 24.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 20.5 ± 0.2, 21.9 ± 0.2, 22.6 ± 0.2, and 24.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 11.5 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 20.5 ± 0.2, 21.9 ± 0.2, 22.6 ± 0.2, and 24.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 11.5 ± 0.2, 14.8 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 20.5 ± 0.2, 21.9 ± 0.2, 22.6 ± 0.2, and 24.7 ± 0.2 and at least one of 17.6 ± 0.2 and 18.8 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 11.5 ± 0.2, 14.8 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 17.6 ± 0.2, 20.5 ± 0.2, 21.9 ± 0.2, 22.6 ± 0.2, and 24.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.2, 11.5 ± 0.2, 14.8 ± 0.2, 14.9 ± 0.2, 17.4 ± 0.2, 18.8 ± 0.2, 20.5 ± 0.2, 21.9 ± 0.2, 22.6 ± 0.2, and 24.7 ± 0.2 °20 using Cu Ka radiation.

[0167] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In one aspect, the present disclosure provides Form HD, characterized by having XRPD signals at 5.1 ± 0.1 and at least two of 14.9 ± 0.1, 17.4 ± 0.1, and 20.5 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 14.9 ± 0.1, and 17.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 14.9 ± 0.1, and 20.5 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 17.4 ± 0.1, and 20.5 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 20.5 ± 0.1, and 24.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 20.5 ± 0.1, 22.6 ± 0.1, and 24.7 ± 0.1 and at least one of 11.5 ± 0.1 and 21.9 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 11.5 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 20.5 ± 0.1, 22.6 ± 0.1, and 24.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 20.5 ± 0.1, 21.9 ± 0.1, 22.6 ± 0.1, and 24.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 11.5 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 20.5 ± 0.1, 21.9 ± 0.1, 22.6 ± 0.1, and 24.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 11.5 ± 0.1, 14.8 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 20.5 ± 0.1, 21.9 ± 0.1, 22.6 ± 0.1, and 24.7 ± 0.1 and at least one of 17.6 ± 0.1 and 18.8 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 11.5 ± 0.1, 14.8 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 17.6 ± 0.1, 20.5 ± 0.1, 21.9 ± 0.1, 22.6 ± 0.1, and 24.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form HD is characterized by having XRPD signals at 5.1 ± 0.1, 11.5 ± 0.1, 14.8 ± 0.1, 14.9 ± 0.1, 17.4 ± 0.1, 18.8 ± 0.1, 20.5 ± 0.1, 21.9 ± 0.1, 22.6 ± 0.1, and 24.7 ± 0.1 °20 using Cu Ka radiation.

[0168] In some embodiments, Form HD is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 31.

[0169] In some embodiments, Form HD is characterized by endothermic events with onset temperatures at approximately 62 °C, 130 °C, and/or 190 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at approximately 77 °C, 141 °C, and/or 192 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 62 ± 2 °C, 130 ± 2 °C, and/or 190 ± 2 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 77 ± 2 °C, 141 ± 2 °C, and/or 192 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 62 ± 1 °C, 130 ± 1 °C, and/or 190 ± 1 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 77 ± 1 °C, 141 ± 1 °C, and/or 192 ± 1 °C as measured by DSC.

[0170] In some embodiments, Form HD is characterized by a DSC thermogram substantially the same as that set forth in Fig. 33.

[0171] In some embodiments, Form HD is characterized by endothermic events with onset temperatures at approximately 71 °C, 133 °C, and/or 187 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at approximately 86 °C, 142 °C, and/or 192 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 71 ± 2 °C, 133 ± 2 °C, and/or 187 ± 2 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 86 ± 2 °C, 142 ± 2 °C, and/or 192 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 71 ± 1 °C, 133 ± 1 °C, and/or 187 ± 1 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 86 ± 1 °C, 142 ± 1 °C, and/or 192 ± 1 °C as measured by DSC.

[0172] In some embodiments, Form HD is characterized by a DSC thermogram substantially the same as that set forth in Fig. 34.

[0173] In some embodiments, Form HD is characterized by endothermic events with onset temperatures at approximately 84 °C, 133 °C, and/or 190 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at approximately 98 °C, 142 °C, and/or 192 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 84 ± 2 °C, 133 ± 2 °C, and/or 190 ± 2 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 98 ± 2 °C, 142 ± 2 °C, and/or 192 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 84 ± 1 °C, 133 ± 1 °C, and/or 190 ± 1 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 98 ± 1 °C, 142 ± 1 °C, and/or 192 ± 1 °C as measured by DSC. [0174] In some embodiments, Form HD is characterized by a DSC thermogram substantially the same as that set forth in Fig. 35A.

[0175] In some embodiments, Form HD is characterized by endothermic events with onset temperatures at approximately 89 °C, 134 °C, and/or 187 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at approximately 104 °C, 144 °C, and/or 192 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 89 ± 2 °C, 134 ± 2 °C, and/or 187 ± 2 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 104 ± 2 °C, 144 ± 2 °C, and/or 192 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 89 ± 1 °C, 134 ± 1 °C, and/or 187 ± 1 °C as measured by DSC. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 104 ± 1 °C, 144 ± 1 °C, and/or 192 ± 1 °C as measured by DSC.

[0176] In some embodiments, Form HD is characterized by a DSC thermogram substantially the same as that set forth in Fig. 35B.

[0177] In some embodiments, Form HD is characterized by endothermic events with onset temperatures at approximately 89 °C, 134 °C, and/or 187 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 89 ± 2 °C, 134 ± 2 °C, and/or 187 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 89 ± 1 °C, 134 ± 1 °C, and/or 187 ± 1 °C as measured by DSC.

[0178] In some embodiments, Form HD is characterized by a weight loss of methanol of approximately 2.1% between approximately 40 °C and approximately 97 °C as measured by TGA. In some embodiments, Form HD is characterized by a weight loss of methanol of approximately 2.1% between 40 ± 2 °C and 97 ± 2 °C as measured by TGA. In some embodiments, Form HD is characterized by a weight loss of methanol of approximately 2.1% between 40 ± 1 °C and 97 ± 1 °C as measured by TGA.

[0179] In some embodiments, Form HD is characterized by a weight loss of methanol of between approximately 40 °C and approximately 97 °C as measured by TGA. [0180] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 89 ± 2 °C, 134 ± 2 °C, and/or 187 ± 2 °C as measured by DSC. In some embodiments, Form HD is characterized by a weight loss of methanol of between 40 ± 2 °C and 97 ± 2 °C as measured by TGA.

[0181] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form HD is characterized by endothermic events with onset temperatures at 89 ± 1 °C, 134 ± 1 °C, and/or 187 ± 1 °C as measured by DSC. In some embodiments, Form HD is characterized by a weight loss of methanol of between 40 ± 1 °C and 97 ± 1 °C as measured by TGA.

[0182] In some embodiments, Form HD is characterized by a weight loss of methanol of approximately 3.7% as measured by TGA, for example, as shown in Fig. 35B.

[0183] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 104 ± 2 °C, 144 ± 2 °C, and/or 192 ± 2 °C as measured by DSC. In some embodiments, Form HD is characterized by a weight loss of methanol of approximately 3.7% as measured by TGA.

[0184] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form HD is characterized by endothermic events with peak temperatures at 104 ± 1 °C, 144 ± 1 °C, and/or 192 ± 1 °C as measured by DSC. In some embodiments, Form HD is characterized by a weight loss of methanol of approximately 3.7% as measured by TGA.

[0185] In some embodiments, Form HD has at least one of the characteristics listed in the table below:

[0186] In some embodiments, Form HD is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table G. Table G. XRPD signal table for Form HD

[0187] In some embodiments, Form HD is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, or thirty -two, thirty -four, thirty- five, thirty-six, thirty-seven, thirty-eight, thirty-nine, forty, forty-one, or forty -two, forty- four, forty-five, forty-six, forty-seven, forty-eight XRPD signals selected from those set forth in Table G, as measured with Cu Ka radiation.

[0188] In some embodiments, Form HD is prepared by a method comprising: combining Compound A (e.g., Form G) with a solvent comprising methanol to form a mixture; stirring the mixture to form a solution, and evaporating the solvent; and optionally isolating Form HD. In some embodiments, the solvent is a mixture of methanol and water. In some embodiments, the solution is stirred for about 30 hours. In some embodiments, the solution is stirred for about 25 hours. In some embodiments, the solution is stirred for about 20 hours. In some embodiments, the solution is stirred for about 15 hours. In some embodiments, the solution is stirred for about 10 hours. In some embodiments, the solution is stirred for about 5 hours. In some embodiments, the solution is stirred for about 1 hour. In some embodiments, the solution is stirred at a temperature of approximately or below 40 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 35 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 30 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 25 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 20 °C. In some embodiments, the solution is stirred at a temperature of approximately or below 15 °C.

Form SV1

[0189] In one aspect, the present disclosure provides Form SV1, characterized by having XRPD signals at approximately 4.7, 8.1, and 9.3 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 8.1, 9.3, and 16.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 8.1, 9.3, 11.3, 12.3, and 16.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 8.1, 9.3, 11.3, 12.3, 16.1, and 19.7 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 8.1, 9.3, 10.1, 11.3, 12.3, 16.1, and 19.7 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 8.1, 9.3, 10.1, 11.3, 12.3, 16.1, and 19.7, and at least one of 7.9, 16.5, and 22.2 °20 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 7.9, 8.1, 9.3, 10.1, 11.3, 12.3, 16.1, and 19.7 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 8.1, 9.3, 10.1, 11.3, 12.3, 16.1, 16.5, and 19.7 °20 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7, 7.7, 8.1, 9.3, 10.1, 11.3, 12.3, 16.1, 19.7, and 22.2 °20 using Cu Ka radiation. [0190] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In one aspect, the present disclosure provides Form SV1, characterized by having XRPD signals at approximately 4.7 ± 0.2, 8.1 ± 0.2, and 9.3 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.2, 7.7 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, and 16.1 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.2, 7.7 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, 11.3 ± 0.2, 12.3 ± 0.2, and 16.1 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.2, 7.7 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, 11.3 ± 0.2, 12.3 ± 0.2, 16.1 ± 0.2, and 19.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.2, 7.7 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, 10.1 ± 0.2, 11.3 ± 0.2, 12.3 ± 0.2, 16.1 ± 0.2, and 19.7 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately

4.7 ± 0.2, 7.7 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, 10.1 ± 0.2, 11.3 ± 0.2, 12.3 ± 0.2, 16.1 ± 0.2, and

19.7 ± 0.2, and at least one of 7.9 ± 0.2, 16.5 ± 0.2, and 22.2 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately

4.7 ± 0.2, 7.7 ± 0.2, 7.9 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, 10.1 ± 0.2, 11.3 ± 0.2, 12.3 ± 0.2, 16.1 ± 0.2, and 19.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.2, 7.7 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, 10.1 ± 0.2, 11.3 ± 0.2, 12.3 ± 0.2, 16.1 ± 0.2, 16.5 ± 0.2, and 19.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.2, 7.7 ± 0.2, 8.1 ± 0.2, 9.3 ± 0.2, 10.1 ± 0.2, 11.3 ± 0.2, 12.3 ± 0.2, 16.1 ± 0.2, 19.7 ± 0.2, and 22.2 ± 0.2 °29 using Cu Ka radiation.

[0191] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In one aspect, the present disclosure provides Form SV1, characterized by having XRPD signals at approximately 4.7 ± 0.1, 8.1 ± 0.1, and 9.3 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, and 16.1 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, 11.3 ± 0.1, 12.3 ± 0.1, and 16.1 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, 11.3 ± 0.1, 12.3 ± 0.1, 16.1 ± 0.1, and 19.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, 10.1 ± 0.1, 11.3 ± 0.1, 12.3 ± 0.1, 16.1 ± 0.1, and 19.7 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, 10.1 ± 0.1, 11.3 ± 0.1, 12.3 ± 0.1, 16.1 ± 0.1, and 19.7 ± 0.1, and at least one of 7.9 ± 0.1, 16.5 ± 0.1, and 22.2 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 7.9 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, 10.1 ± 0.1, 11.3 ± 0.1, 12.3 ± 0.1, 16.1 ± 0.1, and 19.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, 10.1 ± 0.1, 11.3 ± 0.1, 12.3 ± 0.1, 16.1 ± 0.1, 16.5 ± 0.1, and 19.7 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form SV1 is characterized by having XRPD signals at approximately 4.7 ± 0.1, 7.7 ± 0.1, 8.1 ± 0.1, 9.3 ± 0.1, 10.1 ± 0.1, 11.3 ± 0.1, 12.3 ± 0.1, 16.1 ± 0.1, 19.7 ± 0.1, and 22.2 ± 0.1 °29 using Cu Ka radiation.

[0192] In some embodiments, Form SV1 is characterized by having XRPD pattern substantially the same as that set forth in Fig. 43.

[0193] In some embodiments, Form SV1 is characterized by an endothermic event with an onset temperature at approximately 105 °C as measured by DSC. In some embodiments, Form SV1 is characterized by an endothermic event with a peak temperature at approximately 112 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV1 is characterized by an endothermic event with an onset temperature at 105 ± 2 °C as measured by DSC. In some embodiments, Form SV1 is characterized by an endothermic event with a peak temperature at 112 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV1 is characterized by an endothermic event with an onset temperature at 105 ± 1 °C as measured by DSC. In some embodiments, Form SV1 is characterized by an endothermic event with a peak temperature at 112 ± 1 °C as measured by DSC.

[0194] In some embodiments, Form SV1 is characterized by a DSC thermogram substantially the same as that set forth in Fig. 44.

[0195] In some embodiments, Form SV1 is characterized by a weight loss of 2-MeTHF of approximately 3.6% between approximately 45 °C and approximately 125 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV1 is characterized by a weight loss of 2- MeTHF of approximately 3.6% between 45 ± 2 °C and 125 ± 2 °C as measured by TGA. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV1 is characterized by a weight loss of 2-MeTHF of approximately 3.6% between 45 ± 1 °C and 125 ± 1 °C as measured by TGA.

[0196] In some embodiments, Form SV1 is characterized by a weight loss of 2-MeTHF of between approximately 45 °C and approximately 125 °C as measured by TGA.

[0197] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV1 is characterized by a weight loss of 2- MeTHF of between 45 ± 2 °C and 125 ± 2 °C as measured by TGA.

[0198] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV1 is characterized by a weight loss of 2- MeTHF of between 45 ± 1 °C and 125 ± 1 °C as measured by TGA.

[0199] In some embodiments, Form SV1 is is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table H below: Table H. XRPD signal table for Form SV1 (4-30 °20)

[0200] In some embodiments, Form SV1 is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, or thirty-one XRPD signals selected from those set forth in Table H, as measured with Cu Ka radiation.

[0201] In some embodiments, Form SV1 is prepared by a method comprising: combining Compound A with a solvent comprising 2-MeTHF, and optionally isolating Form SV1. In some embodiments, the solvent is 2-MeTHF.

Form SV2

[0202] In one aspect, the present disclosure provides Form SV2, characterized by having XRPD signals at approximately 8.3, 12.4, and 19.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 12.4, 18.3, and 19.2, and at least one of 12.8 and 20.3 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 12.4, 12.8, 18.3, and 19.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 12.4, 18.3, 19.2, and 20.3 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 9.6, 12.4, 12.8, 18.3, 19.2, and 20.3 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 9.6, 12.4, 12.8, 18.1, 18.3, 19.2, and 20.3 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 9.6,

12.4, 12.8, 16.5, 18.1, 18.3, 19.2, and 20.3 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 9.6, 12.4, 12.8,

16.5, 18.1, 18.3, 19.2, and 20.3, and at least one of 9.0, 17.8, and 20.6 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 9.0, 9.6, 12.4, 12.8, 16.5, 18.1, 18.3, 19.2, and 20.3 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 9.6, 12.4, 12.8, 16.5, 17.8, 18.1, 18.3, 19.2, and 20.3, and °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3, 9.6, 12.4, 12.8, 16.5, 18.1, 18.3, 19.2, 20.3, and 20.6 °29 using Cu Ka radiation.

[0203] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In one aspect, the present disclosure provides Form SV2, characterized by having XRPD signals at approximately 8.3 ± 0.2, 12.4 ± 0.2, and 19.2 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 12.4 ± 0.2, 18.3 ± 0.2, and 19.2 ± 0.2, and at least one of 12.8 ± 0.2 and 20.3 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 18.3 ± 0.2, and 19.2 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 12.4 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, and 20.3 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, and 20.3 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 18.1 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, and 20.3 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 16.5 ± 0.2, 18.1 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, and 20.3 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 16.5 ± 0.2, 18.1 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, and 20.3 ± 0.2, and at least one of 9.0 ± 0.2, 17.8 ± 0.2, and 20.6 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 9.0 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 16.5 ± 0.2, 18.1 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, and 20.3 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 16.5 ± 0.2, 17.8 ± 0.2, 18.1 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, and 20.3 ± 0.2, and °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.2, 9.6 ± 0.2, 12.4 ± 0.2, 12.8 ± 0.2, 16.5 ± 0.2, 18.1 ± 0.2, 18.3 ± 0.2, 19.2 ± 0.2, 20.3 ± 0.2, and 20.6 ± 0.2 °20 using Cu Ka radiation.

[0204] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In one aspect, the present disclosure provides Form SV2, characterized by having XRPD signals at approximately 8.3 ± 0.1, 12.4 ± 0.1, and 19.2 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 12.4 ± 0.1, 18.3 ± 0.1, and 19.2 ± 0.1, and at least one of 12.8 ± 0.1 and 20.3 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 18.3 ± 0.1, and 19.2 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 12.4 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, and 20.3 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 9.6 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, and 20.3 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 9.6 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 18.1 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, and 20.3 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 9.6 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 16.5 ± 0.1, 18.1 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, and 20.3 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 9.6 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 16.5 ± 0.1, 18.1 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, and 20.3 ± 0.1, and at least one of 9.0 ± 0.1, 17.8 ± 0.1, and 20.6 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 9.0 ± 0.1, 9.6 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 16.5 ± 0.1, 18.1 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, and 20.3 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 9.6 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 16.5 ± 0.1, 17.8 ± 0.1, 18.1 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, and 20.3 ± 0.1, and °29 using Cu Ka radiation. In some embodiments, Form SV2 is characterized by having XRPD signals at approximately 8.3 ± 0.1, 9.6 ± 0.1, 12.4 ± 0.1, 12.8 ± 0.1, 16.5 ± 0.1, 18.1 ± 0.1, 18.3 ± 0.1, 19.2 ± 0.1, 20.3 ± 0.1, and 20.6 ± 0.1 °20 using Cu Ka radiation.

[0205] In some embodiments, Form SV2 is characterized by having XRPD pattern substantially the same as that set forth in Fig. 23.

[0206] In some embodiments, Form SV2 is characterized by having XRPD pattern substantially the same as that set forth in Fig. 25.

[0207] In some embodiments, Form SV2 is characterized by having XRPD pattern substantially the same as that set forth in Fig. 39.

[0208] In some embodiments, Form SV2 is characterized by an endothermic event with an onset temperature at approximately 114 °C as measured by DSC. In some embodiments, Form SV2 is characterized by an endothermic event with a peak temperature at approximately 116 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV2 is characterized by an endothermic event with an onset temperature at 114 ± 2 °C as measured by DSC. In some embodiments, Form SV2 is characterized by an endothermic event with a peak temperature at 116 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV2 is characterized by an endothermic event with an onset temperature at 114 ± 1 °C as measured by DSC. In some embodiments, Form SV2 is characterized by an endothermic event with a peak temperature at 116 ± 1 °C as measured by DSC.

[0209] In some embodiments, Form SV2 is characterized by a DSC thermogram substantially the same as that set forth in Fig. 30.

[0210] In some embodiments, Form SV2 is characterized by a weight loss of 2-MeTHF of approximately 5.2% between approximately 100 °C and approximately 140 °C as measured by TGA.

[0211] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV2 is characterized by a weight loss of 2- MeTHF of approximately 5.2% between 100 ± 2 °C and 140 ± 2 °C as measured by TGA. [0212] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV2 is characterized by a weight loss of 2- MeTHF of approximately 5.2% between 100 ± 1 °C and 140 ± 1 °C as measured by TGA. [0213] In some embodiments, Form SV2 is characterized by a weight loss of 2-MeTHF of between approximately 100 °C and approximately 140 °C as measured by TGA.

[0214] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV2 is characterized by a weight loss of 2- MeTHF of between 100 ± 2 °C and 140 ± 2 °C as measured by TGA.

[0215] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV2 is characterized by a weight loss of 2- MeTHF of between 100 ± 1 °C and 140 ± 1 °C as measured by TGA.

[0216] In some embodiments, Form SV2 is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table I below: Table I. XRPD signal table for Form SV2 (4-30 °20)

[0217] In some embodiments, Form SV2 is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, thirty-two, thirty-three, thirty- four, thirty-five, thirty-six, or thirty-seven XRPD signals selected from those set forth in Table I, as measured with Cu Ka radiation.

[0218] In some embodiments, the solid Form SV2 is prepared by a method comprising: combining Compound A with a solvent comprising 2-MeTHF, and optionally isolating Form SV2. In some embodiments, the solvent is 2-MeTHF.

Form SV3

[0219] In one aspect, the present disclosure provides Form SV3, characterized by having XRPD signals at approximately 9.2, 11.3, and 19.7 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 9.2,

11.3, 16.0, and 19.7, and at least one of 8.4 and 25.4 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4, 9.2,

11.3, 16.0, and 19.7 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 9.2, 11.3, 16.0, 19.7, and 25.4 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4, 9.2, 11.3, 16.0, 18.4, 19.7, and 25.4 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4, 9.2, 11.3, 16.0, 18.4, 19.7, 21.8, and 25.4 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4, 9.2,

11.3, 16.0, 18.4, 19.7, 21.8, 24.6, and 25.4 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4, 9.2, 11.3, 15.2, 16.0, 18.4, 19.7, 21.8, 24.6, and 25.4 °29 using Cu Ka radiation.

[0220] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.2 °29. In one aspect, the present disclosure provides Form SV3, characterized by having XRPD signals at approximately 9.2 ± 0.2, 11.3 ± 0.2, and 19.7 ± 0.2 °20 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 9.2 ± 0.2, 11.3 ± 0.2, 16.0 ± 0.2, and 19.7 ± 0.2, and at least one of 8.4 ± 0.2 and 25.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.2, 9.2 ± 0.2, 11.3 ± 0.2, 16.0 ± 0.2, and 19.7 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 9.2 ± 0.2, 11.3 ± 0.2, 16.0 ± 0.2, 19.7 ± 0.2, and 25.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.2, 9.2 ± 0.2, 11.3 ± 0.2, 16.0 ± 0.2, 18.4 ± 0.2, 19.7 ± 0.2, and 25.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.2, 9.2 ± 0.2, 11.3 ± 0.2, 16.0 ± 0.2, 18.4 ± 0.2, 19.7 ± 0.2, 21.8 ± 0.2, and 25.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.2, 9.2 ± 0.2, 11.3 ± 0.2, 16.0 ± 0.2, 18.4 ± 0.2, 19.7 ± 0.2, 21.8 ± 0.2, 24.6 ± 0.2, and 25.4 ± 0.2 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.2, 9.2 ± 0.2, 11.3 ± 0.2, 15.2 ± 0.2, 16.0 ± 0.2, 18.4 ± 0.2, 19.7 ± 0.2, 21.8 ± 0.2, 24.6 ± 0.2, and 25.4 ± 0.2 °29 using Cu Ka radiation. [0221] In some embodiments, “approximately” means that the recited XRPD signal may vary by ± 0.1 °29. In one aspect, the present disclosure provides Form SV3, characterized by having XRPD signals at approximately 9.2 ± 0.1, 11.3 ± 0.1, and 19.7 ± 0.1 °20 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 9.2 ± 0.1, 11.3 ± 0.1, 16.0 ± 0.1, and 19.7 ± 0.1, and at least one of 8.4 ± 0.1 and 25.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.1, 9.2 ± 0.1, 11.3 ± 0.1, 16.0 ± 0.1, and 19.7 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 9.2 ± 0.1, 11.3 ± 0.1, 16.0 ± 0.1, 19.7 ± 0.1, and 25.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.1, 9.2 ± 0.1, 11.3 ± 0.1, 16.0 ± 0.1, 18.4 ± 0.1, 19.7 ± 0.1, and 25.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.1, 9.2 ± 0.1, 11.3 ± 0.1, 16.0 ± 0.1, 18.4 ± 0.1, 19.7 ± 0.1, 21.8 ± 0.1, and 25.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.1, 9.2 ± 0.1, 11.3 ± 0.1, 16.0 ± 0.1, 18.4 ± 0.1, 19.7 ± 0.1, 21.8 ± 0.1, 24.6 ± 0.1, and 25.4 ± 0.1 °29 using Cu Ka radiation. In some embodiments, Form SV3 is characterized by having XRPD signals at approximately 8.4 ± 0.1, 9.2 ± 0.1, 11.3 ± 0.1, 15.2 ± 0.1, 16.0 ± 0.1, 18.4 ± 0.1, 19.7 ± 0.1, 21.8 ± 0.1, 24.6 ± 0.1, and 25.4 ± 0.1 °29 using Cu Ka radiation.

[0222] In some embodiments, Form SV3 is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 40.

[0223] In some embodiments, Form SV3 is characterized by having an XRPD pattern substantially the same as that set forth in Fig. 41.

[0224] In some embodiments, Form SV3 is characterized by endothermic events with onset temperatures at approximately 120 °C and/or 159 °C as measured by DSC. In some embodiments, Form SV3 is characterized by endothermic events with peak temperatures at approximately 126 °C and/or 167 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV3 is characterized by endothermic events with onset temperatures at 120 ± 2 °C and/or 159 ± 2 °C as measured by DSC. In some embodiments, Form SV3 is characterized by endothermic events with peak temperatures at 126 ± 2 °C and/or 167 ± 2 °C as measured by DSC. In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV3 is characterized by endothermic events with onset temperatures at 120 ± 1 °C and/or 159 ± 1 °C as measured by DSC. In some embodiments, Form SV3 is characterized by endothermic events with peak temperatures at 126 ± 1 °C and/or 167 ± 1 °C as measured by DSC.

[0225] In some embodiments, Form SV3 is characterized by a DSC thermogram substantially the same as that set forth in Fig. 42.

[0226] In some embodiments, Form SV3 is characterized by a weight loss of DMF of approximately 9.7% between approximately 106 °C and approximately 240 °C as measured by TGA.

[0227] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV3 is characterized by a weight loss of DMF of approximately 9.7% between 106 ± 2 °C and 240 ± 2 °C as measured by TGA.

[0228] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV3 is characterized by a weight loss of DMF of approximately 9.7% between 106 ± 1 °C and 240 ± 1 °C as measured by TGA.

[0229] In some embodiments, Form SV3 is characterized by a weight loss of DMF of between approximately 106 °C and approximately 240 °C as measured by TGA.

[0230] In some embodiments, “approximately” means that the variability of the temperature is within ± 2 °C. In some embodiments, Form SV3 is characterized by a weight loss of DMF of between 106 ± 2 °C and 240 ± 2 °C as measured by TGA.

[0231] In some embodiments, “approximately” means that the variability of the temperature is within ± 1 °C. In some embodiments, Form SV3 is characterized by a weight loss of DMF of between 106 ± 1 °C and 240 ± 1 °C as measured by TGA.

[0232] In some embodiments, Form SV3 is characterized by having XRPD signals at approximately the positions (in °29, degrees 2-theta or ° 2-theta) shown in Table J below: Table J. XRPD signal table for Form SV3 (4-30 °20)

[0233] In some embodiments, Form SV3 is characterized by one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, twenty-six, twenty-seven, twenty-eight, twenty-nine, thirty, thirty-one, thirty-two, thirty-three, thirty- four, thirty-five, thirty-six, thirty-seven, thirty-eight, or thirty-nine XRPD signals selected from those set forth in Table J, as measured with Cu Ka radiation.

[0234] In some embodiments, Form SV3 is prepared by a method comprising: combining Compound A with a solvent comprising MeCN:DMF, and optionally isolating Form SV3. In some embodiments, the solvent is 80:20 mixture of MeCN:DMF.

[0235] The terms “crystalline polymorphs”, “crystal polymorphs”, “crystal forms”, “polymorphs”, or “polymorphic forms” means crystal structures in which a compound (e.g., free base, salts, or solvates thereof) can crystallize in different crystal packing arrangements, all of which have the same elemental composition. Different crystal forms usually have different X-ray diffraction patterns, infrared spectra, melting points, density, crystal shape, optical and electrical properties, stability, and solubility. Crystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. Crystal polymorphs of the compounds can be prepared by crystallization under different conditions. In addition, crystal polymorphism may be present but is not limiting, but any crystal form may be a single or a crystal form mixture, or an anhydrous or hydrated crystal form.

[0236] The term “amorphous form” refers to a noncrystalline solid state form of a substance. [0237] Additionally, compounds e.g., free bases, and amorphous forms, crystalline forms, and polymorphs thereof) can exist in either hydrated or unhydrated (the anhydrous) form or as solvates with other solvent molecules or in an unsolvated form. Nonlimiting examples of hydrates include hemihydrates, monohydrates, dihydrates, etc. Nonlimiting examples of solvates include DMSO solvates, DMSO hemisolvates, acetone solvates, acetone hemisolvates, acetonitrile solvates, acetonitrile hemisolvates etc.

[0238] All forms of the compounds of the present application are contemplated, either in a mixture or in pure or substantially pure form, including crystalline forms of racemic mixtures and crystalline forms of individual isomers. [0239] Polymorphs of a molecule can be obtained by a number of methods, as known in the art. Such methods include, but are not limited to, melt recrystallization, melt cooling, solvent recrystallization, desolvation, rapid evaporation, rapid cooling, slow cooling, vapor diffusion, and sublimation.

[0240] Techniques for characterizing solid forms of a compound, such as polymorphs, include, but are not limited to, DSC , X-ray powder diffractometry (XRPD), single crystal X- ray diffractometry, vibrational spectroscopy (e.g., IR or Raman spectroscopy), TGA, DTA, DVS, solid state NMR, hot stage optical microscopy, scanning electron microscopy (SEM), electron crystallography and quantitative analysis, particle size analysis (PSA), surface area analysis, solubility studies, and dissolution studies.

[0241] As used herein, the term “solvate” means solvent addition forms that contain either stoichiometric or non stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. If the solvent is water, the solvate formed is a hydrate, when the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more molecules of water with one of the substances in which the water retains its molecular state as H2O, such combination being able to form one or more hydrate. For example, the solvate may be a DMSO solvate, a dichloromethane (DCM) solvate, a methyl ethyl ketone (MEK solvate), an acetone solvate, an acetonitrile solvate, or a tetrahydrofuran (THF) solvate.

[0242] As used herein, the terms “unsolvated” or “desolvated” refer to a solid state form (e.g., crystalline forms, amorphous forms, and polymorphs) of a compound which does not contain solvent.

[0243] As used herein, the term “pure” means about the recited compound is present at a weight ratio or molar ratio of 90-100%, preferably 95-100%, more preferably 98-100% or 99- 100%; e.g., less than about 10%, less than about 5%, less than about 2%, or less than about 1% impurity is present. Such impurities include, e.g., degradation products, oxidized products, solvents, and/or other undesirable impurities.

[0244] As used herein, a compound is “stable” where significant amount of degradation products are not observed under constant conditions of humidity (e.g., 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, or 95% relative humidity [RH]), light exposure and temperatures (e.g, higher than 0 °C, e.g., 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, 65 °C, or 70 °C) over a certain period (e.g, one week, two weeks, three weeks, or four weeks). A compound is not considered to be stable at a certain condition when degradation impurities appear or an area percentage (e.g, AUC as characterized by HPLC) of existing impurities begins to grow. The amount of degradation growth as a function of time is important in determining compound stability.

[0245] As used herein, the term “mixing” means combining, blending, stirring, shaking, swirling, or agitating. The term “stirring” means mixing, shaking, agitating, or swirling. The term “agitating” means mixing, shaking, stirring, or swirling.

[0246] Unless explicitly indicated otherwise, the terms “approximately” and “about” are synonymous. In some embodiments, “approximately” and “about” refer to a recited amount, value, or duration ± 10%, ± 8%, ± 6%, ± 5%, ± 4%, ± 2%, ± 1%, or ± 0.5%. In some embodiments, “approximately” and “about” refer to a listed amount, value, or duration ± 10%, ± 8 %, ± 6%, ± 5%, ± 4%, or ± 2%. In some embodiments, “approximately” and “about” refer to a listed amount, value, or duration ± 5%. In some embodiments, “approximately” and “about” refer to a listed amount, value, or duration ± 2% or ± 1%.

[0247] When the terms “approximately” and “about” are used when reciting XRPD signals, these terms refer to the recited XRPD signal ± 0.3 °29, ± 0.2 °29, or ± 0.1 °29. In some embodiments, the terms “approximately” and “about” refer to the listed XRPD signal ± 0.2 °29. In some embodiments, the terms “approximately” and “about” refer to the listed XRPD signal ± 0.1 °29.

[0248] When the terms “approximately” and “about” are used when reciting temperature or temperature range, these terms refer to the recited temperature or temperature range ± 5 °C, ± 2 °C , or ± 1 °C. In some embodiments, the terms “approximately” and “about” refer to the recited temperature or temperature range ± 2 °C.

[0249] It is to be understood that the compounds of the present disclosure can exist in either hydrated or unhydrated (the anhydrous) form or as solvates with other solvent molecules. Nonlimiting examples of hydrates include monohydrates, dihydrates, etc. Nonlimiting examples of solvates include ethanol solvates, acetone solvates, etc.

[0250] As used herein, the term “solvate” means solvent addition forms that contain either stoichiometric or non-stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. If the solvent is water, the solvate formed is a hydrate; and if the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more molecules of water with one molecule of the substance in which the water retains its molecular state as H2O.

[0251] As used herein, the term “analog” refers to a chemical compound that is structurally similar to another but differs slightly in composition (as in the replacement of one atom by an atom of a different element or in the presence of a particular functional group, or the replacement of one functional group by another functional group). Thus, an analog is a compound that is similar or comparable in function and appearance, but not in structure or origin to the reference compound.

[0252] As used herein, the term “derivative” refers to compounds that have a common core structure and are substituted with various groups as described herein.

[0253] As used herein, the term “bioisostere” refers to a compound resulting from the exchange of an atom or of a group of atoms with another, broadly similar, atom or group of atoms. The objective of a bioisosteric replacement is to create a new compound with similar biological properties to the parent compound. The bioisosteric replacement may be physicochemically or topologically based. Examples of carboxylic acid bioisosteres include, but are not limited to, acyl sulphonamides, tetrazoles, sulphonates and phosphonates. See, e.g., Patani and LaVoie, Chem. Rev. 96, 3147-3176, 1996.

[0254] It is also to be understood that certain any one of the Forms of Compound A disclosed herein may exist in solvated as well as unsolvated forms such as, for example, hydrated forms. A suitable pharmaceutically acceptable solvate is, for example, a hydrate such as hemi-hydrate, a mono-hydrate, a di-hydrate or a tri-hydrate. It is to be understood that the disclosure encompasses all such solvated forms that possess MCT inhibitory activity. [0255] It is also to be understood that certain any one of the Forms of Compound A disclosed herein may exhibit polymorphism, and that the disclosure encompasses all such forms, or mixtures thereof, which possess MCT inhibitory activity. It is generally known that crystalline materials may be analysed using conventional techniques such as X-Ray Powder Diffraction analysis, Differential Scanning Calorimetry, Thermal Gravimetric Analysis, Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy, Near Infrared (NIR) spectroscopy, solution and/or solid state nuclear magnetic resonance spectroscopy. The water content of such crystalline materials may be determined by Karl Fischer analysis.

[0256] Any one of the Forms of Compound A disclosed herein may be administered in the form of a prodrug which is broken down in the human or animal body to release a compound of the disclosure. A prodrug may be used to alter the physical properties and/or the pharmacokinetic properties of a compound of the disclosure. A prodrug can be formed when the compound of the disclosure contains a suitable group or substituent to which a propertymodifying group can be attached. Examples of prodrugs include derivatives containing in vivo cleavable alkyl or acyl substituents at the sulphonylurea group in a compound of the any one of the Forms of Compound A disclosed herein. [0257] Accordingly, the present disclosure includes those Forms of Compound A disclosed (also referred to as “compounds of the present disclosure”) herein as defined hereinbefore when made available within the human or animal body by way of cleavage of a prodrug thereof. Accordingly, the present disclosure includes any one of the Forms of Compound A disclosed herein that is produced in the human or animal body by way of metabolism of a precursor compound, that is any one of the Forms of Compound A disclosed herein may be a synthetically-produced compound or a metabolically-produced compound.

[0258] A suitable pharmaceutically acceptable prodrug of a compound of any one of the Forms of Compound A disclosed herein is one that is based on reasonable medical judgment as being suitable for administration to the human or animal body without undesirable pharmacological activities and without undue toxicity. Various forms of prodrug have been described, for example in the following documents: a) Methods in Enzymology, Vol. 42, p. 309-396, edited by K. Widder, et al. (Academic Press, 1985); b) Design of Pro-drugs, edited by H. Bundgaard, (Elsevier, 1985); c) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 “Design and Application of Pro-drugs”, by H. Bundgaard p. 113-191 (1991); d) H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1-38 (1992); e) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988); f) N. Kakeya, et al., Chem. Pharm. Bull., 32, 692 (1984); g) T. Higuchi and V. Stella, “ProDrugs as Novel Delivery Systems”, A.C.S. Symposium Series, Volume 14; andH) E. Roche (editor), “Bioreversible Carriers in Drug Design”, Pergamon Press, 1987.

[0259] A suitable pharmaceutically acceptable prodrug of a compound of any one of the Forms of Compound A disclosed herein that possesses a hydroxy group is, for example, an in vivo cleavable ester or ether thereof. An in vivo cleavable ester or ether of a compound of any one of the Forms of Compound A disclosed herein containing a hydroxy group is, for example, a pharmaceutically acceptable ester or ether which is cleaved in the human or animal body to produce the parent hydroxy compound. Suitable pharmaceutically acceptable ester forming groups for a hydroxy group include inorganic esters such as phosphate esters (including phosphoramidic cyclic esters). Further suitable pharmaceutically acceptable ester forming groups for a hydroxy group include Ci-Cio alkanoyl groups such as acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups, Ci-Cio alkoxycarbonyl groups such as ethoxycarbonyl, N,N-(Ci-Ce alkyl)2carbamoyl, 2-dialkylaminoacetyl and 2- carboxyacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, piperazin- 1-ylmethyl and 4-(CI-C4 alkyl)piperazin-l-ylmethyl. Suitable pharmaceutically acceptable ether forming groups for a hydroxy group include a-acyloxyalkyl groups such as acetoxymethyl and pivaloyloxymethyl groups.

[0260] A suitable pharmaceutically acceptable prodrug of a compound of any one of the Forms of Compound A disclosed herein that possesses a carboxy group is, for example, an in vivo cleavable amide thereof, for example an amide formed with an amine such as ammonia, a Ci-4alkylamine such as methylamine, a (C1-C4 alkyl)2amine such as dimethylamine, N- ethyl-N-methylamine or diethylamine, a C1-C4 alkoxy-C2-C4 alkylamine such as

2-methoxy ethylamine, a phenyl-Ci-C4 alkylamine such as benzylamine and amino acids such as glycine or an ester thereof.

[0261] A suitable pharmaceutically acceptable prodrug of a compound of any one of the Forms of Compound A disclosed herein that possesses an amino group is, for example, an in vivo cleavable amide derivative thereof. Suitable pharmaceutically acceptable amides from an amino group include, for example an amide formed with C1-C10 alkanoyl groups such as an acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, N- alkylaminom ethyl, N,N-dialkylaminomethyl,morpholinomethyl,piperazin-l-ylmethyl and 4- (C1-C4 alkyl)piperazin-l-ylmethyl.

[0262] The in vivo effects of a compound of any one of the Forms of Compound A disclosed herein may be exerted in part by one or more metabolites that are formed within the human or animal body after administration of a compound of any one of the Forms of Compound A disclosed herein. As stated hereinbefore, the in vivo effects of a compound of any one of the Forms of Compound A disclosed herein may also be exerted by way of metabolism of a precursor compound (a prodrug).

[0263] Suitably, the present disclosure excludes any individual compounds not possessing the biological activity defined herein.

[0264] The resultant Form of Compound A can be isolated and purified using techniques well known in the art.

Pharmaceutical Compositions

[0265] In some aspects, the present disclosure provides a pharmaceutical composition comprising a compound or a pharmaceutically acceptable prodrug or solvate thereof of the present disclosure as an active ingredient. [0266] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a Form of compound described herein and one or more pharmaceutically acceptable carriers or excipients. In some embodiments, the present disclosure provides a pharmaceutical composition comprising at least one Form of Compound A. In certain embodiments, the solid form is Form G. In certain embodiments, the solid form is Form B. In certain embodiments, the solid form is Form I. In certain embodiments, the solid form is Form Y. In certain embodiments, the solid form is Form Uu. In certain embodiments, the solid form is Form Tt. In certain embodiments, the solid form is Form SV1. In certain embodiments, the solid form is Form SV2. In certain embodiments, the solid form is Form SV3. In certain embodiments, the solid form is Form HD.

[0267] In another aspect, the present disclosure also provides pharmaceutical compositions comprising a solid form of Compound A in combination with at least one pharmaceutically acceptable excipient or carrier.

[0268] The compounds of present disclosure can be formulated for oral administration in forms such as tablets, capsules (each of which includes sustained release or timed-release formulations), pills, powders, granules, elixirs, tinctures, suspensions, syrups and emulsions. The compounds of present disclosure on can also be formulated for intravenous (bolus or infusion), intraperitoneal, topical, subcutaneous, intra-muscular or transdermal (e.g., patch) administration, all using forms well known to those of ordinary skill in the pharmaceutical arts.

[0269] The formulation of the present disclosure may be in the form of an aqueous solution comprising an aqueous vehicle. The aqueous vehicle component may comprise water and at least one pharmaceutically acceptable excipient. Suitable acceptable excipients include those selected from the group consisting of a solubility enhancing agent, chelating agent, preservative, tonicity agent, viscosity/suspending agent, buffer, and pH modifying agent, and a mixture thereof.

[0270] Any suitable solubility enhancing agent can be used. Examples of a solubility enhancing agent include cyclodextrin, such as those selected from the group consisting of hydroxypropyl-P-cyclodextrin, methyl-P-cyclodextrin, randomly methylated-P-cyclodextrin, ethylated-P-cyclodextrin, triacetyl-P-cyclodextrin, peracetylated-P-cyclodextrin, carboxymethyl-P-cyclodextrin, hydroxy ethyl-P-cyclodextrin, 2-hydroxy-3- (trimethylammonio)propyl-P-cyclodextrin, glucosyl-P-cyclodextrin, sulphated P-cyclodextrin (S-P-CD), maltosyl-P-cyclodextrin, P-cyclodextrin sulphobutyl ether, branched-P- cyclodextrin, hydroxypropyl-y-cyclodextrin, randomly methylated-y-cyclodextrin, and trimethyl-y-cyclodextrin, and mixtures thereof.

[0271] Any suitable chelating agent can be used. Examples of a suitable chelating agent include those selected from the group consisting of ethylenediaminetetraacetic acid and metal salts thereof, di sodium edetate, trisodium edetate, and tetrasodium edetate, and mixtures thereof.

[0272] Any suitable preservative can be used. Examples of a preservative include those selected from the group consisting of quaternary ammonium salts such as benzalkonium halides (preferably benzalkonium chloride), chlorhexidine gluconate, benzethonium chloride, cetyl pyridinium chloride, benzyl bromide, phenylmercury nitrate, phenylmercury acetate, phenylmercury neodecanoate, merthiolate, methylparaben, propylparaben, sorbic acid, potassium sorbate, sodium benzoate, sodium propionate, ethyl p-hydroxybenzoate, propylaminopropyl biguanide, and butyl-p-hydroxybenzoate, and sorbic acid, and mixtures thereof.

[0273] The aqueous vehicle may also include a tonicity agent to adjust the tonicity (osmotic pressure). The tonicity agent can be selected from the group consisting of a glycol (such as propylene glycol, diethylene glycol, triethylene glycol), glycerol, dextrose, glycerin, mannitol, potassium chloride, and sodium chloride, and a mixture thereof.

[0274] The aqueous vehicle may also contain a viscosity/suspending agent. Suitable viscosity/ suspending agents include those selected from the group consisting of cellulose derivatives, such as methyl cellulose, ethyl cellulose, hydroxyethylcellulose, polyethylene glycols (such as polyethylene glycol 300, polyethylene glycol 400), carboxymethyl cellulose, hydroxypropylmethyl cellulose, and cross-linked acrylic acid polymers (carbomers), such as polymers of acrylic acid cross-linked with polyalkenyl ethers or divinyl glycol (Carbopols - such as Carbopol 934, Carbopol 934P, Carbopol 971, Carbopol 974 and Carbopol 974P), and a mixture thereof.

[0275] In order to adjust the formulation to an acceptable pH (typically a pH range of about 5.0 to about 9.0, more preferably about 5.5 to about 8.5, particularly about 6.0 to about 8.5, about 7.0 to about 8.5, about 7.2 to about 7.7, about 7.1 to about 7.9, or about 7.5 to about 8.0), the formulation may contain a pH modifying agent. The pH modifying agent is typically a mineral acid or metal hydroxide base, selected from the group of potassium hydroxide, sodium hydroxide, and hydrochloric acid, and mixtures thereof, and preferably sodium hydroxide and/or hydrochloric acid. These acidic and/or basic pH modifying agents are added to adjust the formulation to the target acceptable pH range. Hence it may not be necessary to use both acid and base - depending on the formulation, the addition of one of the acid or base may be sufficient to bring the mixture to the desired pH range.

[0276] The aqueous vehicle may also contain a buffering agent to stabilise the pH. When used, the buffer is selected from the group consisting of a phosphate buffer (such as sodium dihydrogen phosphate and disodium hydrogen phosphate), a borate buffer (such as boric acid, or salts thereof including disodium tetraborate), a citrate buffer (such as citric acid, or salts thereof including sodium citrate), and 8-aminocaproic acid, and mixtures thereof.

[0277] The formulation may further comprise a wetting agent. Suitable classes of wetting agents include those selected from the group consisting of polyoxypropylenepolyoxyethylene block copolymers (poloxamers), polyethoxylated ethers of castor oils, polyoxyethylenated sorbitan esters (polysorbates), polymers of oxyethylated octyl phenol (Tyloxapol), polyoxyl 40 stearate, fatty acid glycol esters, fatty acid glyceryl esters, sucrose fatty esters, and polyoxyethylene fatty esters, and mixtures thereof.

[0278] According to a further aspect of the disclosure there is provided a pharmaceutical composition which comprises a compound or a pharmaceutically acceptable prodrug or solvate thereof of the disclosure as defined hereinbefore, or a pharmaceutically acceptable hydrate or solvate thereof, in association with a pharmaceutically acceptable diluent or carrier.

[0279] The compositions of the disclosure may be in a form suitable for oral use (for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions), for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by insufflation (for example as a finely divided powder) or for parenteral administration (for example as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular dosing or as a suppository for rectal dosing).

[0280] The compositions of the disclosure may be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art. Thus, compositions intended for oral use may contain, for example, one or more colouring, sweetening, flavouring and/or preservative agents.

[0281] An effective amount of a compound or a pharmaceutically acceptable prodrug or solvate thereof of the present disclosure for use in therapy is an amount sufficient to treat or prevent an MCT related condition referred to herein, slow its progression and/or reduce the symptoms associated with the condition. [0282] The size of the dose for therapeutic or prophylactic purposes of Compound A will naturally vary according to the nature and severity of the conditions, the age and sex of the animal or patient and the route of administration, according to well-known principles of medicine.

Methods of Use

[0283] In one aspect, the present disclosure provides a pharmaceutical composition comprising a solid form of Compound A and a pharmaceutically acceptable carrier or excipient.

[0284] In one aspect, the present disclosure provides a method of treating or preventing a disease or disorder, comprising administering to a subject in need thereof a solid form of Compound A, or a pharmaceutical composition thereof.

[0285] In some aspects, the present disclosure provides a method of modulating MCT (e.g., the MCT1) activity (e.g., in vitro or in vivo), comprising contacting a cell with an effective amount of a Form of Compound A (also referred to “compound of the present disclosure”) or a pharmaceutically acceptable prodrug or solvate thereof.

[0286] In some aspects, the present disclosure provides a method of modulating MCT (e.g., the MCT1) activity (e.g., in vitro or in vivo), comprising contacting a cell with a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof.

[0287] In some aspects, the present disclosure provides a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof, or a pharmaceutical composition of the present disclosure.

[0288] In some aspects, the present disclosure provides a method of treating or preventing a disease or disorder disclosed herein in a subject in need thereof, comprising administering to the subject a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof, or a pharmaceutical composition of the present disclosure.

[0289] In some embodiments, the disease or disorder is associated with an implicated MCT activity. In some embodiments, the disease or disorder is a disease or disorder in which MCT activity is implicated.

[0290] In some embodiments, the disease or disorder is associated with an implicated MCT1 activity. In some embodiments, the disease or disorder is a disease or disorder in which MCT1 activity is implicated. [0291] In some embodiments, the disease or disorder is associated with an implicated MCT4 activity. In some embodiments, the disease or disorder is a disease or disorder in which MCT4 activity is implicated.

[0292] In some embodiments, the disease or disorder is a cancer, an autoimmune disease, an immune deficiency, or a neurodegenerative disease.

[0293] In some aspects, the present disclosure provides a method of treating or preventing a cancer or a neurodegenerative disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof, or a pharmaceutical composition of the present disclosure.

[0294] In some aspects, the present disclosure provides a method of treating or preventing a cancer or a neurodegenerative disease in a subject in need thereof, comprising administering to the subject a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof, or a pharmaceutical composition of the present disclosure.

[0295] In some aspects, the present disclosure provides a method of treating a cancer or a neurodegenerative disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof, or a pharmaceutical composition of the present disclosure.

[0296] In some aspects, the present disclosure provides a method of treating a cancer or a neurodegenerative disease in a subject in need thereof, comprising administering to the subject a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof, or a pharmaceutical composition of the present disclosure.

[0297] In some aspects, the present disclosure provides a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof for use in modulating MCT (e.g., the MCT1) activity (e.g., in vitro or in vivo).

[0298] In some aspects, the present disclosure provides a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof for use in treating or preventing a disease or disorder disclosed herein.

[0299] In some aspects, the present disclosure provides a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof for use in treating a disease or disorder disclosed herein. [0300] In some aspects, the present disclosure provides a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof for use in treating or preventing a cancer or a neurodegenerative disease in a subject in need thereof.

[0301] In some aspects, the present disclosure provides a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof for use in treating a cancer or a neurodegenerative disease in a subject in need thereof.

[0302] In some aspects, the present disclosure provides use of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof in the manufacture of a medicament for modulating MCT (e.g., the MCT1) activity (e.g., in vitro or in vivo).

[0303] In some aspects, the present disclosure provides use of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein.

[0304] In some aspects, the present disclosure provides use of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof in the manufacture of a medicament for treating a disease or disorder disclosed herein.

[0305] In some aspects, the present disclosure provides use of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof in the manufacture of a medicament for treating or preventing a cancer or a neurodegenerative disease in a subject in need thereof.

[0306] In some aspects, the present disclosure provides use of a compound of the present disclosure or a pharmaceutically acceptable prodrug or solvate thereof in the manufacture of a medicament for treating a cancer or a neurodegenerative disease in a subject in need thereof.

[0307] In some embodiments, the disease or disorder is a cancer, an autoimmune disease, an immune deficiency, or a neurodegenerative disease.

[0308] In some embodiments, the cancer to be treated is a B-cell neoplasm.

[0309] In some embodiments, the cancer is selected from the group consisting of lymphoma, leukemia, and a plasma cell neoplasm. In some embodiments, the cancer selected from the group consisting of carcinoma and sarcoma.

[0310] In some embodiments, the cancer to be treated is a lymphoma. Lymphomas which can be treated by the disclosed methods include Non-Hodgkin’s lymphoma; Burkitt’s lymphoma; small lymphocytic lymphoma; lymphoplasmacytic lymphoma; MALT lymphoma; follicular lymphoma; diffuse large B-cell lymphoma; and T-cell lymphoma. [0311] In some embodiments, leukemias which can be treated by the disclosed methods include acute lymphoblastic leukemia (ALL); Burkitt’s leukemia; B-cell leukemia; B-cell acute lymphoblastic leukemia; chronic lymphocytic leukemia (CLL); acute myelogenous leukemia (AML); chronic myelogenous leukemia (CML); and T-cell acute lymphoblastic leukemia (T-ALL).

[0312] In some embodiments the cancer to be treated is B-cell neoplasms, B-cell leukemia, B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Burkitt's leukemia, acute myelogenous leukemia and/or T-ALL. In some embodiments the cancer to be treated is chronic lymphocytic leukemia (CLL) or chronic myelogenous leukemia (CML).

[0313] In some embodiments, the cancer to be treated is a plasma cell neoplasm. Examples for plasma cell neoplasms include multiple myeloma; plasma cell myeloma; plasma cell leukemia and plasmacytoma.

[0314] Carcinomas which can be treated by the disclosed methods include colon cancer; liver cancer; gastric cancer; intestinal cancer; esophageal cancer; breast cancer; ovarian cancer; head and neck cancer; lung cancer; and thyroid cancer.

[0315] Sarcomas which can be treated by the disclosed methods include soft tissue sarcoma and bone sarcoma.

[0316] In some embodiments, the cancer that can be treated by the disclosed methods include cancer of the bladder, blood, bone, bone marrow, brain, breast, colon, esophagus, gastrointestine, gum, head, kidney, liver, lung, nasopharynx, neck, ovary, prostate, skin, stomach, testis, tongue, or uterus. In addition, the cancer may specifically be of the following histological type, though it is not limited to these: neoplasm, malignant; carcinoma; carcinoma, undifferentiated; giant and spindle cell carcinoma; sarcomas; small cell carcinoma; papillary carcinoma; squamous cell carcinoma; lymphoepithelial carcinoma; basal cell carcinoma; pilomatrix carcinoma; transitional cell carcinoma; papillary transitional cell carcinoma; adenocarcinoma; gastrinoma, malignant; cholangiocarcinoma; hepatocellular carcinoma; combined hepatocellular carcinoma and cholangiocarcinoma; trabecular adenocarcinoma; adenoid cystic carcinoma; adenocarcinoma in adenomatous polyp; adenocarcinoma, familial polyposis coli; solid carcinoma; carcinoid tumor, malignant; branchiolo-alveolar adenocarcinoma; papillary adenocarcinoma; chromophobe carcinoma; acidophil carcinoma; oxyphilic adenocarcinoma; basophil carcinoma; clear cell adenocarcinoma; granular cell carcinoma; follicular adenocarcinoma; papillary and follicular adenocarcinoma; nonencapsulating sclerosing carcinoma; adrenal cortical carcinoma; endometroid carcinoma; skin appendage carcinoma; apocrine adenocarcinoma; sebaceous adenocarcinoma; ceruminous adenocarcinoma; mucoepidermoid carcinoma; cystadenocarcinoma; papillary cystadenocarcinoma; papillary serous cystadenocarcinoma; mucinous cystadenocarcinoma; mucinous adenocarcinoma; signet ring cell carcinoma; infiltrating duct carcinoma; medullary carcinoma; lobular carcinoma; inflammatory carcinoma; paget’s disease, mammary; acinar cell carcinoma; adenosquamous carcinoma; adenocarcinoma w/squam ous metaplasia; thymoma, malignant; ovarian stromal tumor, malignant; thecoma, malignant; granulosa cell tumor, malignant; androblastoma, malignant; sertoli cell carcinoma; leydig cell tumor, malignant; lipid cell tumor, malignant; paraganglioma, malignant; extra-mammary paraganglioma, malignant; pheochromocytoma; glomangiosarcoma; malignant melanoma; amelanotic melanoma; superficial spreading melanoma; malig melanoma in giant pigmented nevus; epithelioid cell melanoma; blue nevus, malignant; sarcoma; fibrosarcoma; fibrous histiocytoma, malignant; myxosarcoma; liposarcoma; leiomyosarcoma; rhabdomyosarcoma; embryonal rhabdomyosarcoma; alveolar rhabdomyosarcoma; stromal sarcoma; mixed tumor, malignant; mullerian mixed tumor; nephroblastoma; hepatoblastoma; carcinosarcoma; mesenchymoma, malignant; brenner tumor, malignant; phyllodes tumor, malignant; synovial sarcoma; mesothelioma, malignant; dysgerminoma; embryonal carcinoma; teratoma, malignant; struma ovarii, malignant; choriocarcinoma; mesonephroma, malignant; hemangiosarcoma; hemangioendothelioma, malignant; Kaposi’s sarcoma; hemangiopericytoma, malignant; lymphangiosarcoma; osteosarcoma; juxtacortical osteosarcoma; chondrosarcoma; chondroblastoma, malignant; mesenchymal chondrosarcoma; giant cell tumor of bone; Ewing’s sarcoma; odontogenic tumor, malignant; ameloblastic odontosarcoma; ameloblastoma, malignant; ameloblastic fibrosarcoma; pinealoma, malignant; chordoma; glioma, malignant; ependymoma; astrocytoma; protoplasmic astrocytoma; fibrillary astrocytoma; astroblastoma; glioblastoma; oligodendroglioma; oligodendroblastoma; primitive neuroectodermal; cerebellar sarcoma; ganglioneuroblastoma; neuroblastoma; retinoblastoma; olfactory neurogenic tumor; meningioma, malignant; neurofibrosarcoma; neurilemmoma, malignant; granular cell tumor, malignant; malignant lymphoma; Hodgkin’s disease; hodgkin’s; paragranuloma; malignant lymphoma, small lymphocytic; malignant lymphoma, large cell, diffuse; malignant lymphoma, follicular; mycosis fungoides; other specified non-Hodgkin’s lymphomas; malignant histiocytosis; multiple myeloma; mast cell sarcoma; immunoproliferative small intestinal disease; leukemia; lymphoid leukemia; plasma cell leukemia; erythroleukemia; lymphosarcoma cell leukemia; myeloid leukemia; basophilic leukemia; eosinophilic leukemia; monocytic leukemia; mast cell leukemia; megakaryoblastic leukemia; myeloid sarcoma; and hairy cell leukemia.

[0317] In some embodiments, the disease or disorder is Lynch syndrome.

[0318] Lynch syndrome is a hereditary disorder caused by a mutation in a mismatch repair gene in which affected individuals have a higher than normal chance of developing colorectal cancer, endometrial cancer, and various other types of aggressive cancers, often at a young age - also called hereditary nonpolyposis colon cancer (HNPCC). The mutations of specific mismatch repair (MMR) genes including but not limited to MLH1, MSH2, MSH6, PMS2, and EPCAM-TACSTD1 deletions are responsible for Lynch syndrome. These genes work in repairing mistakes made when DNA is copied in preparation for cell division. The defects in the genes disallow repair of DNA mistakes and as cells divide, errors stack and uncontrollable cell growth may result in cancer. Those with Lynch syndrome carry up to an 85% risk of contracting colon cancer as well as a higher than average risk for endometrial cancer, stomach cancer, pancreatic cancer, kidney/ureter tract cancer, hepatobiliary tract cancer, gastric tract cancer, prostate cancer, ovarian cancer, gallbladder duct cancer, brain cancer, small intestine cancer, breast cancer, and skin cancer.

[0319] Thus, in one embodiment for the disclosed method, the method is a method of treating cancer derived from Lynch syndrome, selected from the group consisting of colon cancer, endometrial cancer, stomach cancer, pancreatic cancer, kidney/ureter tract cancer, hepatobiliary tract cancer, gastric tract cancer, prostate cancer, ovarian cancer, gallbladder duct cancer, brain cancer, small intestine cancer, breast cancer, and skin cancer.

[0320] In some embodiments, the neurodegenerative disorder is selected from the group consisting of multiple sclerosis, Parkinson's disease (PD), Alzheimer's disease (AD), Dentatorubropallidoluysian atrophy (DRPLA), Huntington's Disease (HD), Spinocerebellar ataxia Type 1 (SCA1), Spinocerebellar ataxia Type 2 (SCA2), Spinocerebellar ataxia Type 3 (SCA3), Spinocerebellar ataxia 6 (SCA6), Spinocerebellar ataxia Type 7 (SCA7), Spinocerebellar ataxia Type 8 (SCA8), Spinocerebellar ataxia Type 12 (SCA12), Spinocerebellar ataxia Type 17 (SC Al 7), Spinobulbar Muscular Ataxia/Kennedy Disease (SBMA), Fargile X syndrome (FRAXA), Fragile XE mental retardation (FRAXE), and Myotonic dystrophy (DM).

[0321] The present disclosure provides a compound that functions as modulator of MCT activity. The present disclosure therefore provides a method of modulating MCT activity in vitro or in vivo, said method comprising contacting a cell with an effective amount of a compound, or a pharmaceutically acceptable salt thereof, as defined herein. [0322] In some aspects, the present disclosure provides a method of treating or preventing a disease or disorder associated with the abnormal expression or activity of monocarboxylate transporters (MCTs), or dependency on the expression or activity of at least one MCT, wherein the method comprises administering to a subject in need thereof a compound or a pharmaceutically acceptable prodrug or solvate thereof of the present disclosure, or a pharmaceutical composition thereof.

[0323] In some aspects, the present disclosure provides a method of treating or preventing a disease or disorder, wherein the method comprises administering to a subject in need thereof a Form of Compound A or a pharmaceutically acceptable prodrug or solvate thereof of the present disclosure, or a pharmaceutical composition thereof, and wherein the Form of Compound A is administered in a therapeutically effective amount to modulate the activity of monocarboxylate transporters (MCTs).

[0324] Effectiveness of compounds of the disclosure can be determined by industry- accepted assays/ disease models according to standard practices of elucidating the same as described in the art and are found in the current general knowledge.

[0325] The present disclosure also provides a method of treating a disease or disorder in which MCT activity is implicated in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable prodrug or solvate thereof, or a pharmaceutical composition as defined herein.

[0326] Suitably, the compounds according to the present disclosure can be used for the treatment of a disease selected from a cancer, an autoimmune disease, an immune deficiency, or a neurodegenerative disease.

[0327] Compounds of the present disclosure, or pharmaceutically acceptable prodrugs or solvates thereof, may be administered alone as a sole therapy or can be administered in addition with one or more other substances and/or treatments. Such conjoint treatment may be achieved by way of the simultaneous, sequential or separate administration of the individual components of the treatment.

[0328] For example, therapeutic effectiveness may be enhanced by administration of an adjuvant (i.e. by itself the adjuvant may only have minimal therapeutic benefit, but in combination with another therapeutic agent, the overall therapeutic benefit to the individual is enhanced). Alternatively, by way of example only, the benefit experienced by an individual may be increased by administering the Compound A with another therapeutic agent (which also includes a therapeutic regimen) that also has therapeutic benefit. [0329] In the instances where the compound of the present disclosure is administered in combination with other therapeutic agents, the compound of the disclosure need not be administered via the same route as other therapeutic agents, and may, because of different physical and chemical characteristics, be administered by a different route. For example, the compound of the disclosure may be administered orally to generate and maintain good blood levels thereof, while the other therapeutic agent may be administered intravenously. The initial administration may be made according to established protocols known in the art, and then, based upon the observed effects, the dosage, modes of administration and times of administration can be modified by the skilled clinician.

[0330] The particular choice of other therapeutic agent will depend upon the diagnosis of the attending physicians and their judgment of the condition of the individual and the appropriate treatment protocol. According to this aspect of the disclosure there is provided a combination for use in the treatment of a disease in which MCT activity is implicated comprising a compound of the disclosure as defined hereinbefore, or a pharmaceutically acceptable prodrug or solvate thereof, and another suitable agent.

[0331] According to a further aspect of the disclosure there is provided a pharmaceutical composition which comprises a compound of the disclosure, or a pharmaceutically acceptable prodrug or solvate thereof, in combination with a suitable therapeutic agent, in association with a pharmaceutically acceptable diluent or carrier.

[0332] In addition to its use in therapeutic medicine, Compound A and pharmaceutically acceptable prodrugs or solvates thereof are also useful as pharmacological tools in the development and standardisation of in vitro and in vivo test systems for the evaluation of the effects of inhibitors of MCT in laboratory animals such as dogs, rabbits, monkeys, rats and mice, as part of the search for new therapeutic agents.

[0333] In any of the above-mentioned pharmaceutical composition, process, method, use, medicament, and manufacturing features of the instant disclosure, any of the alternate embodiments of macromolecules of the present disclosure described herein also apply. Routes of Administration

[0334] The compounds of the disclosure or pharmaceutical compositions comprising these compounds may be administered to a subject by any convenient route of administration, whether systemically/ peripherally or topically (i.e., at the site of desired action).

[0335] Routes of administration include, but are not limited to, oral (e.g. by ingestion); buccal; sublingual; transdermal (including, e.g., by a patch, plaster, etc.); transmucosal (including, e.g., by a patch, plaster, etc.); intranasal (e.g., by nasal spray); ocular (e.g., by eye drops); pulmonary (e.g., by inhalation or insufflation therapy using, e.g., via an aerosol, e.g., through the mouth or nose); rectal (e.g., by suppository or enema); vaginal (e.g., by pessary); parenteral, for example, by injection, including subcutaneous, intradermal, intramuscular, intravenous, intra-arterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, and intrasternal; by implant of a depot or reservoir, for example, subcutaneously or intramuscularly.

Definitions

[0336] Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below.

[0337] Without wishing to be limited by this statement, it is understood that, while various options for variables are described herein, the disclosure intends to encompass operable embodiments having combinations of the options. The disclosure may be interpreted as excluding the non-operable embodiments caused by certain combinations of the options. [0338] It is to be understood that a compound of the present disclosure may be depicted in a neutral form, a cationic form (e.g., carrying one or more positive charges), or an anionic form (e.g., carrying one or more negative charges), all of which are intended to be included in the scope of the present disclosure. For example, when a compound of the present disclosure is depicted in an anionic form, such depiction also refers to the various neutral forms, cationic forms, and anionic forms of the compound. For another example, when a compound the present disclosure is depicted in an anionic form, such depiction also refers to various salts (e.g., sodium salt) of the anionic form of the compound.

[0339] A “therapeutically effective amount” means the amount of a compound that, when administered to a mammal for treating a disease, is sufficient to effect such treatment for the disease. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, etc., of the mammal to be treated.

[0340] As used herein, the expressions “one or more of A, B, or C,” “one or more A, B, or C,” “one or more of A, B, and C,” “one or more A, B, and C,” “selected from the group consisting of A, B, and C”, “selected from A, B, and C”, and the like are used interchangeably and all refer to a selection from a group consisting of A, B, and/or C, i.e., one or more As, one or more Bs, one or more Cs, or any combination thereof, unless indicated otherwise. [0341] It is to be understood that the present disclosure provides methods for the synthesis of the Forms of Compound A described herein. The present disclosure also provides detailed methods for the synthesis of various disclosed Forms of Compound A of the present disclosure according to the Examples.

[0342] It is to be understood that, unless otherwise stated, any description of a method of treatment includes use of the compounds to provide such treatment or prophylaxis as is described herein, as well as use of the compounds to prepare a medicament to treat or prevent such condition. The treatment includes treatment of human or non-human animals including rodents and other disease models.

[0343] As used herein, the term “subject” is interchangeable with the term “subject in need thereof’, both of which refer to a subject having a disease or having an increased risk of developing the disease. A “subject” includes a mammal. The mammal can be e.g., a human or appropriate non-human mammal, such as primate, mouse, rat, dog, cat, cow, horse, goat, camel, sheep or a pig. The subject can also be a bird or fowl. In one embodiment, the mammal is a human. A subject in need thereof can be one who has been previously diagnosed or identified as having a disease or disorder disclosed herein. A subject in need thereof can also be one who has (e.g., is suffering from a disease or disorder disclosed herein. Alternatively, a subject in need thereof can be one who has an increased risk of developing such disease or disorder relative to the population at large (z.e., a subject who is predisposed to developing such disorder relative to the population at large). A subject in need thereof can have a refractory or resistant a disease or disorder disclosed herein (i.e., a disease or disorder disclosed herein that doesn't respond or hasn’t yet responded to treatment). The subject may be resistant at start of treatment or may become resistant during treatment. In some embodiments, the subject in need thereof received and failed all known effective therapies for a disease or disorder disclosed herein. In some embodiments, the subject in need thereof received at least one prior therapy.

[0344] As used herein, the term “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of a compound of the present disclosure, or a pharmaceutically acceptable prodrug or solvate thereof, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model.

[0345] It is to be understood that a compound of the present disclosure, or a pharmaceutically acceptable prodrug or solvate thereof, can or may also be used to prevent a relevant disease, condition, or disorder, or used to identify suitable candidates for such purposes.

[0346] The terms “inhibiting”, “reducing”, or any variation of these terms in relation of MCT, includes any measurable decrease or complete inhibition to achieve a desired result. For example, there may be a decrease of about, at most about, or at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or more, or any range derivable therein, reduction of MCT activity compared to its normal activity.

[0347] As used herein, the term “preventing,” “prevent,” or “protecting against” describes reducing or eliminating the onset of the symptoms or complications of such disease, condition or disorder.

[0348] The term "disorder" is used in this disclosure to mean, and is used interchangeably with, the terms disease, condition, or illness, unless otherwise indicated.

[0349] It is to be understood that one skilled in the art may refer to general reference texts for detailed descriptions of known techniques discussed herein or equivalent techniques. These texts include Ausubel et al., Current Protocols in Molecular Biology, John Wiley and Sons, Inc. (2005); Sambrook et al. , Molecular Cloning, A Laboratory Manual (3^rd edition), Cold Spring Harbor Press, Cold Spring Harbor, New York (2000); Coligan et al., Current Protocols in Immunology, John Wiley & Sons, N.Y.; Enna et al., Current Protocols in Pharmacology, John Wiley & Sons, N.Y.; Fingl et al., The Pharmacological Basis of Therapeutics (1975), Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 18^th edition (1990). These texts can, of course, also be referred to in making or using an aspect of the disclosure.

[0350] It is to be understood that the present disclosure also provides pharmaceutical compositions comprising any compound described herein in combination with at least one pharmaceutically acceptable excipient or carrier.

[0351] As used herein, the term “pharmaceutical composition” is a formulation containing the compounds of the present disclosure in a form suitable for administration to a subject. In one embodiment, the pharmaceutical composition is in bulk or in unit dosage form. The unit dosage form is any of a variety of forms, including, for example, a capsule, an IV bag, a tablet, a single pump on an aerosol inhaler or a vial. The quantity of active ingredient (e.g., a formulation of the disclosed compound or salt, hydrate, solvate or isomer thereof) in a unit dose of composition is an effective amount and is varied according to the particular treatment involved. One skilled in the art will appreciate that it is sometimes necessary to make routine variations to the dosage depending on the age and condition of the patient. The dosage will also depend on the route of administration. A variety of routes are contemplated, including oral, pulmonary, rectal, parenteral, transdermal, subcutaneous, intravenous, intramuscular, intraperitoneal, inhalational, buccal, sublingual, intrapleural, intrathecal, intranasal, and the like. Dosage forms for the topical or transdermal administration of a compound of this disclosure include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. In one embodiment, the active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that are required.

[0352] As used herein, the term “pharmaceutically acceptable” refers to those compounds, anions, cations, materials, compositions, carriers, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

[0353] As used herein, the term “pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, nontoxic and neither biologically nor otherwise undesirable, and includes excipient that is acceptable for veterinary use as well as human pharmaceutical use. A “pharmaceutically acceptable excipient” as used in the specification and claims includes both one and more than one such excipient.

[0354] It is to be understood that a pharmaceutical composition of the disclosure is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., ingestion), inhalation, transdermal (topical), and transmucosal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulphite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. [0355] It is to be understood that a compound or pharmaceutical composition of the disclosure can be administered to a subject in many of the well-known methods currently used for chemotherapeutic treatment. For example, a compound of the disclosure may be injected into the blood stream or body cavities or taken orally or applied through the skin with patches. The dose chosen should be sufficient to constitute effective treatment but not so high as to cause unacceptable side effects. The state of the disease condition (e.g., a disease or disorder disclosed herein) and the health of the patient should preferably be closely monitored during and for a reasonable period after treatment.

[0356] As used herein, the term “therapeutically effective amount”, refers to an amount of a pharmaceutical agent to treat, ameliorate, or prevent an identified disease or condition, or to exhibit a detectable therapeutic or inhibitory effect. The effect can be detected by any assay method known in the art. The precise effective amount for a subject will depend upon the subject’s body weight, size, and health; the nature and extent of the condition; and the therapeutic or combination of therapeutics selected for administration. Therapeutically effective amounts for a given situation can be determined by routine experimentation that is within the skill and judgment of the clinician.

[0357] It is to be understood that, for any compound, the therapeutically effective amount can be estimated initially either in cell culture assays, e.g., of neoplastic cells, or in animal models, usually rats, mice, rabbits, dogs, or pigs. The animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans. Therapeutic/prophylactic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., EDso (the dose therapeutically effective in 50% of the population) and LDso (the dose lethal to 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED50. Pharmaceutical compositions that exhibit large therapeutic indices are preferred. The dosage may vary within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration.

[0358] Dosage and administration are adjusted to provide sufficient levels of the active agent(s) or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions may be administered every 3 to 4 days, every week, or once every two weeks depending on half-life and clearance rate of the particular formulation.

[0359] The pharmaceutical compositions containing active compounds of the present disclosure may be manufactured in a manner that is generally known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilising processes. Pharmaceutical compositions may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers comprising excipients and/or auxiliaries that facilitate processing of the active compounds into preparations that can be used pharmaceutically. Of course, the appropriate formulation is dependent upon the route of administration chosen.

[0360] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol and sorbitol, and sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0361] Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilisation. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. [0362] Oral compositions generally include an inert diluent or an edible pharmaceutically acceptable carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0363] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser, which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebuliser.

[0364] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

[0365] The active compounds can be prepared with pharmaceutically acceptable carriers that will protect Compound A against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems.

Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.

[0366] It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the disclosure are dictated by and directly dependent on the unique characteristics of the active Compound A and the particular therapeutic effect to be achieved.

[0367] In therapeutic applications, the dosages of the pharmaceutical compositions used in accordance with the disclosure vary depending on the agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage. Generally, the dose should be sufficient to result in slowing, and preferably regressing, the symptoms of the disease or disorder disclosed herein and also preferably causing complete regression of the disease or disorder. Dosages can range from about 0.01 mg/kg per day to about 5000 mg/kg per day. In preferred aspects, dosages can range from about 1 mg/kg per day to about 1000 mg/kg per day. In an aspect, the dose will be in the range of about 0.1 mg/day to about 50 g/day; about 0.1 mg/day to about 25 g/day; about 0.1 mg/day to about 10 g/day; about 0.1 mg to about 3 g/day; or about 0.1 mg to about 1 g/day, in single, divided, or continuous doses (which dose may be adjusted for the patient’s weight in kg, body surface area in m², and age in years). An effective amount of a pharmaceutical agent is that which provides an objectively identifiable improvement as noted by the clinician or other qualified observer. Improvement in survival and growth indicates regression. As used herein, the term “dosage effective manner” refers to amount of an active compound to produce the desired biological effect in a subject or cell.

[0368] It is to be understood that the pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0369] As used herein, the term “pharmaceutically acceptable salts” refer to derivatives of the compounds of the present disclosure wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 2-acetoxybenzoic, 2-hydroxy ethane sulphonic, acetic, ascorbic, benzene sulphonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulphonic, 1,2-ethane sulphonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulphonic, maleic, malic, mandelic, methane sulphonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicylic, stearic, subacetic, succinic, sulphamic, sulphanilic, sulphuric, tannic, tartaric, toluene sulphonic, and the commonly occurring amine acids, e.g., glycine, alanine, phenylalanine, arginine, etc.

[0370] In some embodiments, the pharmaceutically acceptable salt is a sodium salt, a potassium salt, a calcium salt, a magnesium salt, a diethylamine salt, a choline salt, a meglumine salt, a benzathine salt, a tromethamine salt, an ammonia salt, an arginine salt, or a lysine salt.

[0371] Other examples of pharmaceutically acceptable salts include hexanoic acid, cyclopentane propionic acid, pyruvic acid, malonic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, 4-chlorobenzenesulphonic acid, 2-naphthalenesulphonic acid, 4- toluenesulphonic acid, camphorsulphonic acid, 4-methylbicyclo-[2.2.2]-oct-2-ene-l- carboxylic acid, 3 -phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, muconic acid, and the like. The present disclosure also encompasses salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, tromethamine, N-m ethylglucamine, and the like. In the salt form, it is understood that the ratio of the compound to the cation or anion of the salt can be 1 : 1, or any ratio other than 1 : 1, e.g., 3: 1, 2: 1, 1 :2, or 1 :3.

[0372] The compounds, or pharmaceutically acceptable salts thereof, are administered orally, nasally, transdermally, pulmonary, inhalationally, buccally, sublingually, intraperitoneally, subcutaneously, intramuscularly, intravenously, rectally, intrapleurally, intrathecally, and parenterally. In one embodiment, the compound is administered orally. One skilled in the art will recognise the advantages of certain routes of administration. [0373] The dosage regimen utilising the compounds is selected in accordance with a variety of factors including type, species, age, weight, sex and medical condition of the patient; the severity of the condition to be treated; the route of administration; the renal and hepatic function of the patient; and the particular compound or salt thereof employed. An ordinarily skilled physician or veterinarian can readily determine and prescribe the effective amount of the drug required to prevent, counter, or arrest the progress of the condition.

[0374] Techniques for formulation and administration of the disclosed compounds of the disclosure can be found in Remington: the Science and Practice of Pharmacy, 19^th edition, Mack Publishing Co., Easton, PA (1995). In an embodiment, the compounds described herein, and the pharmaceutically acceptable prodrugs, solvates, or salt thereof, are used in pharmaceutical preparations in combination with a pharmaceutically acceptable carrier or diluent. Suitable pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions. The compounds will be present in such pharmaceutical compositions in amounts sufficient to provide the desired dosage amount in the range described herein.

[0375] All percentages and ratios used herein, unless otherwise indicated, are by weight. Other features and advantages of the present disclosure are apparent from the different examples. The provided examples illustrate different components and methodology useful in practicing the present disclosure. The examples do not limit the claimed disclosure. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present disclosure.

[0376] In some embodiments, the term “XRPD signal” may be referred to as “XRPD peak”. [0377] All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an admission that any is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description and examples below are for purposes of illustration and not limitation of the claims that follow.

[0378] As use herein, the phrase “compound of the disclosure” refers to those compounds which are disclosed herein, both generically and specifically. EXAMPLES

[0379] The application is further illustrated by the following examples, which are not to be construed as limiting this application in scope or spirit to the specific procedures herein described. It is to be understood that the examples are provided to illustrate certain embodiments and that no limitation to the scope of the application is intended thereby. It is to be further understood that resort may be had to various other embodiments, modifications, and equivalents thereof which may suggest themselves to those skilled in the art without departing from the spirit of the present application and/or scope of the appended claims.

Analytical Techniques

Differential Scanning Calorimetry (DSC)

[0380] DSC was performed using a Mettler Toledo DSC³⁺. The sample (1-5 mg) was weighed directly in a 40 pL hermetic aluminum pan with a pinhole and analyzed according to the parameters below:

Dynamic Vapor Sorption (DVS)

[0381] DVS was performed using a Q5000SA. The sample (5-15 mg) was loaded into a metallic quartz sample pan, suspended from a microbalance, and exposed to a humidified stream of nitrogen gas. Weight changes were relative to a matching empty reference pan opposite the sample, suspended from the microbalance. The sample was held for a minimum of 10 min at each level and only progressed to the next humidity level if there was < 0.002 % change in weight between measurements (interval: 5 s) or 45 min had elapsed (for 5-65 % RH) or 2 h had elapsed (for 80 and 95 % RH). The following program was used:

1- Equilibration at 50 % RH

2- 50 % to 5 %. (50 %, 35 %, 20 %, and 5 %)

3- 5 % to 95 % (5 %, 20 %, 35 %, 50 %, 65 %, 80 %, and 95 %)

4- 95 % to 5 % (95 %, 80 %, 65 %, 50 %, 35 %, 20 %, and 5 %)

5- 5 % to 50 % (5 %, 20 %, 35 %, and 50 %)

High Performance Liquid Chromatography (HPLC)

[0382] HPLC was conducted using an Agilent 1220 Infinity 2 LC equipped with diode array detector (DAD). Flow rate range of the instrument is 0.2-5.0 mL/min, operating pressure range is 0-600 bar, temperature range is 5 °C above ambient to 60 °C, and wavelength range is 190-600 nm.

[0383] The HPLC method used in this study is shown below:

TGA-IR

[0384] IR spectroscopy was performed using a Thermo Scientific Nicol et iSlO FTIR Spectrometer with a helium-neon laser. The beam splitter was potassium bromide/germanium optimized for mid IR. The source type was Ever-Glo and tungsten/halogen. The spectral range was 7800-350 cm’¹ and spectral resolution was < 0.4 cm’¹. The detector type was deuterated triglycine sulfate. Data was analyzed using Thermo Scientific OMNIC software (Version 9.8).

[0385] The evolved gas emitted from samples upon TGA using the Mettler Toledo TGA/DSC³⁺ was analyzed with IR spectroscopy via a TGA-IR Module for Nicolet FTIR Spectrometers. The TGA-IR accessory facilitated time-based correlation of evolved gas emissions in IR analysis. The accessory was connected directly to the furnace of the TGA/DSC unit with 5 feet insulated, glass-lined, stainless steel transfer line (1/8" O.D.) and compression fittings. The transfer line temperature was maintained at 250 °C with a digital controller. The flow cell was nickel-plated aluminum, with a volume of 22 mL and an optical path length of 10 cm.

Karl Fischer (KF) Titration

[0386] KF titration for water determination was performed using a Mettler Toledo C20S Coulometric KF Titrator equipped with a current generator cell with a diaphragm, and a double-platinum-pin electrode. The range of detection of the instrument is 1 ppm to 5 % water. Aquastar™ CombiCoulomat fritless reagent was used in both the anode and cathode compartments. Samples of approximately 0.03-0.10 g were dissolved in the anode compartment and titrated until the solution potential dropped below 100 mV. Hydranal 1 wt. % water standard was used for validation prior to sample analysis.

Microscopy

[0387] Optical microscopy was performed using a Zeiss AxioScope Al digital imaging microscope equipped with 2.5X, 10X, 20X, and 40X objectives and polarizer. Images were captured through a built-in Axiocam 105 digital camera and processed using ZEN 2 (blue edition) software provided by Zeiss.

[0388] Hot stage microscopy was performed using the Linkam hot stage with the LTS420 Stage controller and using the 20X objective. Profiles were programmed such that once a ramp segment was completed the next programmed segment would begin after the indicated hold temperature time, as follows:

Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy

[0389] ¹ H NMR was performed on a Bruker Avance 300 MHz spectrometer. Solids were dissolved in 0.75 mL deuterated solvent in a 4 mL vial, transferred to an NMR tube (Wilmad 5 mm thin wall 8" 200 MHz, 506-PP-8) and analyzed according to the following parameters:

pH Measurement

[0390] pH was measured using a Mettler Toledo FP20 bench meter equipped with a Mettler Toledo InLab Micro pH electrode. The electrode has a ceramic junction and membrane resistance of < 600 MQ. The internal reference electrolyte solution used is KC1 and the operating range is 0-14 pH units at 0-80 °C.

[0391] pH was measured using a Mettler Toledo FP20 bench meter equipped with an InLab Expert NTC30 pH electrode. The electrode has two open junctions and U-glass membrane resistance of < 250 MQ. The electrode uses the ARGENTHAL™ reference system and XEROL YT® polymer reference electrolyte. The operating range is 0-14 pH units at 0-100 °C.

Simultaneous Thermogravimetric Analysis and Differential Scanning Calorimetry (TGA/DSC)

[0392] TGA and DSC were performed on the same sample simultaneously using a Mettler Toledo TGA/DSC³⁺. Protective and purge gas was nitrogen at a flowrate of 20-30 mL/min and 50-100 mL/min, respectively. The desired amount of sample (5-10 mg) was weighed directly in a hermetic aluminum pan with pinhole and analyzed according to the parameters below:

X-Ray Powder Diffraction (XRPD)

[0393] XRPD was performed using a Bruker D8 Advance equipped with LYNXEYE detector in reflection mode (i.e. Bragg-Brentano geometry). Samples were prepared on Si zero-return wafers. The parameters for XRPD methods used are listed below:

Preparation of Simulated Fluids

Fasted State Simulated Intestinal Fluid (FaSSIF) - pH = 6.50 o Weigh 2.082 g FaSSIF Biorelevant buffer concentration; o Add 48.056 g of distilled water; and o Add 112.0 mg of Biorelevant powder containing bile salt (taurocholate) and phospholipid (lecithin). o The prepared solution was allowed to stand for 2 h as per Biorelevant instruction.

Fasted State Simulated Gastric Fluid (FaSSGF) - pH = 1.60 o Weigh 1.839 g FaSSGF Biorelevant buffer concentration; o Add 48.094 g of distilled water; and o Add 3.0 mg of Biorelevant powder containing bile salt (taurocholate) and phospholipid (lecithin).

Fed State Simulated Intestinal Fluid (FeSSIF) - pH = 5.00 o Weigh 4.071 g FeSSIF Biorelevant buffer concentration; o Add 45.972 g of distilled water; and o Add 560.0 mg of Biorelevant powder containing bile salt (taurocholate) and phospholipid (lecithin).

Preparation of Buffers

HC1 Buffer - pH = 1.2 o 40 mL of 0.5 N standard HC1 transferred into a 100 mL volumetric flask and filled to the line with distilled water. o pH was adjusted by adding 1 N NaOH solution or 1 N HC1.

Acetate Buffer - pH = 4.5 o Transferred 2.99 g of sodium acetate (NaC2H3O2.3H2O) in 1000 mL volumetric flask. o Added 14 mL of 2 N acetic acid to the flask, then added distilled water to the line. o pH was adjusted by adding 1 N acetic acid.

Phosphate Buffer - pH = 6.8 o Dissolved 6.9 g of sodium phosphate monobasic in 50 mL distilled water in a volumetric flask. o Dissolved 7.1 g of sodium phosphate dibasic in 50 mL distilled water in a volumetric flask. o Mixed 25.5 mL of the 1 M sodium phosphate monobasic with 24.5 mL of the 1 M sodium phosphate dibasic. o pH was adjusted by adding 1 N NaOH solution or 1 N HC1.

SLS solutions in Phosphate Buffer - pH = 6.8 o To make 2 % SLS solution, for example, 0.2 g of SLS weighed into a 100 mL beaker then phosphate buffer added to the beaker reaching a total of 10 g.

Abbreviations

Example 1: Form G (Anhydrous Form)

Preparation of Form G

[0394] Form G was prepared from conditions involving acetonitrile as solvent, including mixed systems. The final crystallization of Compound A proceeded from acetonitrile resulting in Form G.

[0395] Representative experimental conditions: Acetonitrile was added to Compound A to form a slurry. The slurry was heated to 75 °C leading to complete dissolution. The solution was cooled first to 50 °C (optional seeding) and then to 15 °C and finally 5 °C. Filtration and drying afforded Form G.

Characterization of Form G

[0396] Characterization of Form G is summarized in Tables 1 and 2 and shown in Fig. 1 through Fig. 4.

Table 1. Characterization of Form G

Table 2. XRPD signal table for Form G

[0397] Form G is stable in ACN:water (9: 1 and 98:2 vol.) and ACN:2-MeTHF (9:1 and 95:5 vol.) at 50 °C.

Example 2: Form B (Anhydrous Form)

Preparation of Form B

[0398] Form B was prepared by evaporative crystallization. 302.1 mg of Compound A (e.g., Form G) was mixed with 3021 pL of MeOH in a 4 mL vial at RT. After 3 h of stirring, the mixture was filtered into a new 4 mL vial using a syringe filter. The vial was uncapped to let the solvent evaporate at RT. The level of solution was marked and, once the solution was below the mark, approximately 1 mg of solid Compound A (e.g., Form B) was added as the seed for Form B. The solution sat until all of the solvent evaporated. The resulting solid was analyzed by XRPD. The sample was then dried in an oven at 50 °C under -29.5 inHg overnight.

[0399] Form B also formed from acetone/water or MEK/water and mixtures containing the above-mentioned solvents.

Characterization of Form B

[0400] The results are summarized in Tables 3 and 4 and shown in Fig. 5 through Fig. 8. Table 3. Characterization of Form B

Table 4. XRPD signal table for Form B

Example 3: Form I (Anhydrous Form)

[0401] Form I was prepared by evaporative crystallization. 300.5 mg of Compound A (e.g., Form G) was mixed with 6.9 mL of EtOH: water (85: 15 vol.) in a 20 mL vial at 50 °C. After 3 h of stirring, the mixture was filtered into a new 20 mL vial using a syringe filter. The vial was uncapped to let the solvent evaporate at 50 °C. The solution sat until all of the solvent evaporated. The resulting solid was analyzed by XRPD. The sample was then dried in an oven at 50 °C under -29.5 inHg overnight. The XRPD results are shown in Fig. 9 and Fig. 14.

[0402] The results are summarized in Tables 5 and 6 and shown in Fig. 9 through Fig. 14.

Table 5. Characterization of Form I

Table 6. XRPD signal table for Form I

Example 4: Form Y (Anhydrous Pattern)

Preparation of Form Y

[0403] Pattern Y was prepared by evaporative crystallization. 169.4 mg of Compound A (e.g., Form G) was mixed with 3.1 mL of toluene in a 4 mL vial at 50 °C. After 3 h of stirring, the mixture was filtered into a new 4 mL vial using a syringe filter. The vial was uncapped to let the solvent evaporate at 50 °C. The level of solution was marked and, once the solution was below the mark, approximately 1 mg of solid Compound A (e.g., Form Y)was added as the seed for Pattern Y. The solution sat until all of the solvent evaporated. The resulting solid was analyzed by XRPD. The sample was then dried in an oven at 50 °C under -29.5 inHg overnight.

Characterization of Form Y

[0404] The results are summarized in Table 7 and Table 8 and shown in Fig. 15 through Fig. 18

Table 7. Characterization of Form Y

Table 8. XRPD signal table for Form Y

Example 5: Form Uu

Preparation of Form Uu

[0405] Form Uu was obtained using the slurry method. 301.6 mg of Compound A (e.g., Form G) was mixed with 2.4 mL of chlorobenzene in a 4 mL vial at 50 °C. After 1 h of stirring, approximately 1 mg of solid Compound A (e.g., Form R) was added as the seed. The mixture was stirred overnight and filtered using filtration paper. The filtered sample was washed with 1.5 vol. of chlorobenzene and analyzed by XRPD. The sample was then dried in an oven at 50 °C under -29.5 inHg overnight. The yield was 269.8 mg (89 % w/w).

Characterization of Form Uu

[0406] The results are summarized in Table 9 and Table 10 and shown in Fig. 19 through Fig. 22

Table 9. Characterization of Form Uu

exo: exotherm.

Table 10. XRPD signal table for Form Uu

Example 6: Form SV2 and Form Tt

Preparation of Forms SV2 and Tt

[0407] Form SV2 was prepared by evaporative crystallization as a starting pattern to obtain Form Tt through thermal treatment. 204.6 mg of Compound A (e.g., Form G) was mixed with 1.0 mL of 2-MeTHF in a 4 mL vial at 50 °C. After 3 h of stirring, the mixture was filtered into a new 4 mL vial using a syringe filter. The vial was uncapped to let the solvent evaporate at 50 °C. The level of solution was marked and, once the solution was below the mark, approximately 1 mg of Form SV2 was added as the seed. The solution sat until all of the solvent evaporated. The resulting solid was analyzed by XRPD. The sample was then dried in an oven at 50 °C under -29.5 inHg overnight. The solid was heated up to 135 °C and held for 10 min at 10 °C/min, after which it was cooled down to RT at 10 °C/min. The production of Form Tt through the thermal treatment of Form SV2 was reproducible.

Characterization of Forms SV2 and Tt

[0408] The results are summarized in Table 11 and Table 12 and shown in Figs. 23-30.

Table 11. Characterization of Form Tt

Table 12. XRPD signal table for Form Tt

Stability Test on Form Tt

[0409] Solid form stability of Form Tt was assessed by weighing approximately 10 mg of solid Compound A (e.g., Form SV2) into a 4 mL vial and covering with a Kimwipe. This vial was placed inside a chamber producing 95 % RH at RT for one day. No change in Form Tt was observed via XRPD.

[0410] A higher melting form, Form Tt was formed that confirmed to be less stable than Form G in ACN at 40 °C. Example 7: Form HD

Preparation of Form HD

[0411] Form HD was prepared by the slurry method. 301.1 mg of Compound A (e.g., Form G) was mixed with 6022 pL of MeOH:water (1 : 1 vol.) in a 20 mL vial at RT. After 1 h of stirring, approximately 1 mg of solid L1MA59-44-21 was added as the seed. The mixture was stirred overnight and filtered. The filtered sample was washed with 1.5 vol. of MeOH:water (1 : 1 vol.) and analyzed by XRPD. The sample was then dried in an oven at 50 °C under -29.5 inHg overnight. The yield was 272.8 mg (91 % w/w).

[0412] Slurry experiments in acetonitrile with high (>20%) amounts of water have also generated Form HD.

Characterization of Form HD

The results are summarized in Table 13 through Table 15 and shown in Fig. 31 through Fig.

38.

Table 13. Characterization of Form HD

Table 14. XRPD signal table for Form HD

Hot Stage Microscopy

[0413] Approximately 0.1 mg of Form HD, was placed on a glass slide (without mineral oil) in a hot stage compartment to perform hot stage microscopy. Details regarding the heating ramps and holding temperature are explained in Microscopy section. The results are summarized in Table 15. Fig. 38 shows that Form HD contains all of Form Tt signals.

Table 15. Summary of hot stage microscopy results of Form HD

[0414] Form HD, which is a hydrate, is stable in the presence of > 10 % water.

Example 8: Forms SV1, SV2, and SV3

Preparation of Forms SV1, SV2, and SV3

[0415] The last chemical reaction in the synthetic process for Compound A used a

DMF: Water mixture. The solubility in DMF alone is very high and no solids were obtained from any experiments using neat DMF.

[0416] An evaporative crystallization using an 80:20 mixture of MeCN:DMF or a slurry in the same solvent ratio afforded Compound A (Form SV3). A crystallization from adding water to a DMF solution of Compound A also afforded this form. Use of higher amount of water led to the previously describe Form HD.

[0417] Form SV3 appears to be a DMF solvate.

[0418] Work-up solvent: The work up procedure for Compound A involved use of 2- MeTHF. Two main forms were obtained from crystallizations using 2-MeTHF, Form SV1 and Form SV2, both appear to be 2-MeTHF solvates.

Characterization of Forms SV1, SV2, and SV 3

[0419] The results are shown in Fig. 39 through Fig. 44 and Table 16 through Table 18.

Table 16. XRPD signal table for Form SV1 (4-30 °20)

Table 17. XRPD signal table for Form SV2 (4-30 °20)

Table 18. XRPD signal table for Form SV3 (4-30 °20)

Example 9: Screening

[0420] During the screening Form G was obtained from the slurry experiment in ACN, Form B was obtained from evaporative crystallization in methanol (MeOH, undersaturated), Form I was obtained from the standard evaporative crystallization in ethanol (EtOH): water (85: 15 volumes (vol.), saturated), Form Y was obtained from the standard evaporative crystallization in toluene (saturated), Form R was obtained from a slurry experiment in chlorobenzene at 50 °C, and Form Tt was obtained from the heating of Form SV2 to 135 °C. The hydrate form (Form HD) was obtained from a slurry experiment in MeOH: water (1 : 1 vol.).

[0421] Forms B, I, Y, R, and HD were scaled up successfully. Scale up of Form R converted Form B into Form Uu. The scale-up forms were found to be stable to both drying and humidity (40 °C and 75 % relative humidity (RH)). A summary of the data for the scaled-up patterns is summarized in Table 19.

Table 19. Summary of scaled-up patterns

exo: exotherm; L.C.: low-crystalline. Hyphen

no data collected.

[0422] The crystallinity of Form Y decreased after drying at 40 °C and 75 % RH, while other patterns were stable. Form Uu and Y showed relatively higher residual solvent content (1.10 and 2.64 wt. %, respectively) compared to other scaled-up patterns. Although Form Tt had a higher melt compared to other patterns (190.18 °C), it converted to Form G in ACN at 40 °C. The solubility of all of the above patterns in Table 19 was lower than 0.05 mg/mL in water and simulated fluids. The results from competitive slurries showed that Form G was stable in ACN:water (9: 1 and 98:2 vol.), ACN:2-methyltetrahydrofuran (2-MeTHF) (9: 1 and 95:5 vol.) at 50 °C, and in ACN at 5 °C, where Forms HD, B, I, Y, Tt, SV2, SV1, and Uu were seeded. Form HD was stable in ACN:water (9: 1 vol.) at RT. The solubility of Form G increased over time in FeSSIF and FaSSIF while it decreased in FaSSGF due to a form conversion. The solubility of Form G did not change in water in the course of 24 hours. However, the solubility of spray-dried solid increased in FaSSIF reaching just above 0.3 mg/mL after 24 hours whereas it decreased gradually in FaSSGF and FeSSIF as it converted into Form Tt and HD, respectively, over time.

Example 10: Quantitative Solubility in Process Solvents of Forms HD and B [0423] Solubility of Form HD and Form B was qualitatively assessed in MeOH at RT. The addition method was used for this experiment. A summary of the results is shown in Table 20.

Table 20. Qualitative solubility of Form HD and Form B at RT

Example 11: One-Week Stability

[0424] Solid form stability of Form G, Form HD, Form B , Form I , Form Y , and Form Uu was completed by weighing approximately 10 mg of solid into a 4 mL vial and covering with a Kimwipe. This vial was placed inside a stability chamber producing 75 % RH at 40 C for one week. The results are summarized in Table 21.

Table 21. Summary of one-week stability experiments for scaled-up patterns

Example 12: Solubility in Simulated Fluids

[0425] Solubility in simulated fluids (fasted state simulated gastric fluid (FaSSGF), fed state simulated intestinal fluid (FeSSIF), and fasted state simulated intestinal fluid (FaSSIF)) and water was assessed for Forms Uu, HD, B, I, and Y. Approximately 6 mg of solid was weighed into a 4 mL vial, and a 10 mm stir bar was added. The simulated fluids were left to equilibrate at 37 °C, prior to adding 3 mL of solvent to each vial.

[0426] Calibration samples were prepared in volumetric flasks using the Compound A (e.g., Form G) and MeOH as diluent. The results for the calibration curve are given in Table 22. After 30 min, a portion of each solution was sampled, and syringe filtered directly into high performance liquid chromatography (HPLC) vials for analysis. After 24 h, the stirring was stopped, and another aliquot was syringe filtered for HPLC analysis. The pH of the remaining solution/ slurry was then taken prior to filtering the solids for XRPD analysis. The HPLC results are outlined in Table 23.

Table 22. Calibration samples for HPLC analysis using Compound A (e.g., Form G)

no Table 23. Solubility of Compound A in simulated fluids at 37 °C

indicates the concentration was doubled due to 2X dilution of the sample.

Example 13: Kinetic Solubility in Simulated Fluids

[0427] Kinetic solubility in simulated fluids and water was assessed for solid Compound A (e.g., Form G). Approximately 20 mg of solid was weighed into a 20 mL vial, and a stir bar was added. The simulated fluids were left to equilibrate at 37 °C, prior to adding 10 mL of fluid to each vial. After 30 min, 2 h, 4 h, and 24 h, a portion of each solution was sampled, and syringe filtered directly into HPLC vials for analysis. The pH of the solution/slurry was then taken prior to filtering the solids for XRPD analysis. The HPLC results are outlined in Table 24 and shown in Fig. 45.

Table 24. Kinetic solubility of solid Compound A (e.g., Form G) in simulated fluids at 37 °C

Example 14: Solubility in Different Buffers

[0428] Solubility in three buffers (HC1, pH = 1.2; acetate, pH = 4.5; phosphate, pH = 6.8) was assessed for solid Compound A (e.g., Form G). Approximately 20 mg of solid was weighed into a 20 mL vial, and a stir bar was added. The buffer solutions were left to equilibrate at 37 °C, prior to adding 10 mL to each vial. After 30 min, 2 h, 4 h, and 24 h, a portion of each solution was sampled, and syringe filtered (0.2 pm PTFE) directly into HPLC vials for analysis. The pH of the solution/slurry was then taken prior to filtering the solids for XRPD analysis. The HPLC results are outlined in Table 25 and shown in Fig. 46.

[0429] The solubility results in the three buffers illustrated that the solubility of Form G was low (< 0.003 mg/mL and 0.02 mg/mL, respectively). Additionally, Form G did not show strong pH dependency. The XRPD results illustrated that Form G was stable until 6 h, but Form HD was observed in all cases along with Form G after 24 h.

Table 25. Solubility of solid Compound A (e.g., Form G) in three buffers at 37 °C

Example 15: Solubility in Phosphate Buffer/Surfactant

[0430] Solubility in 0.1 M sodium phosphate buffer (pH = 6.8) was assessed for solid Compound A (e.g., Form G) using different sodium laureth/dodecyl sulfate (SLS) loadings (0.25 %, 0.50 %, 0.75 %, 1.00 %, 1.50 %, and 2.00 %). Approximately 10 mg of solid was weighed into a 20 mL vial, and a stir bar was added. SLS solutions were then left to equilibrate at 37 °C, prior to adding 5 mL to each vial. After 30 min, 2 h, 4 h, and 24 h, a portion of each solution was sampled, and syringe filtered directly into HPLC vials for analysis. The pH of the solution/slurry was then taken prior to filtering the solids for XRPD analysis. The HPLC results are outlined in Table 26.

[0431] Solubility of Form G increased as the amount of SLS increased, and conversion of Form G into Form HD was observed. Prior to the solubility measurements in the presence of SLS and phosphate buffer, it was found that solid crashes out after SLS is dissolved in 0.2 M potassium phosphate. It was suggested that the potassium ion is replaced with the sodium in the SLS and it crashes out. Therefore, sodium phosphate was used to make the phosphate solution. Also, it is worth noting that the concentration of sodium phosphate buffer should be 0.1 M because it was observed that solid crash out if 1 M sodium phosphate buffer is used. Fig. 47 shows the XRPD results obtained from control studies carried out on potassium phosphate (0.2 M) and sodium phosphate (1 M) after being dissolved in SLS 2%.

[0432] Fig. 48 depicts the solubility of Form G in different SLS % loadings and Fig. 49 depicts the XRPD results for solubility experiment in phosphate buffer and SLS loadings.

Table 26. Solubility of solid Compound A (e.g., Form G) in phosphate buffers using SLS at 37 °C

Example 16: Summary of Crystalline Forms

[0433] A summary of crystalline forms of Compound A is provided in Table 27.

Table 27. Summary of crystalline patterns of Compound A

exo: exotherm; hyphen: no data collected due to lack of enough sample or patterns not being stable on drying or over time

EQUIVALENTS

[0434] The details of one or more embodiments of the disclosure are set forth in the accompanying description above. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms include plural referents unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated by reference.

[0435] The foregoing description has been presented only for the purposes of illustration and is not intended to limit the disclosure to the precise form disclosed, but by the claims appended hereto.

Claims

WHAT CLAIMED IS:

1. A solid form of Compound A:

Compound A), or a hydrate or solvate thereof.

2. The solid form of claim 1, wherein the solid form is a solid form of Compound A, selected from:

Form G: characterized by having X-ray powder diffraction (XRPD) signals at approximately 6.3, 8.6, and 12.6 °29 using Cu Ka radiation,

Form B: characterized by having XRPD signals at approximately 5.3, 7.2, and 15.8 °29 using Cu Ka radiation,

Form I: characterized by having XRPD signals at approximately 11.5 and 14.9 and at least one of 12.9 and 17.4 °29 using Cu Ka radiation,

Form Y: characterized by having XRPD signals at approximately 6.4, 9.9, and 12.5 °29 using Cu Ka radiation,

Form Uu: characterized by having XRPD signals at approximately 8.2, 12.5, and 15.7 °29 using Cu Ka radiation, and

Form Tt: characterized by having XRPD signals at approximately 8.8 and 17.8 and at least one of 19.7 and 29.8 °29 using Cu Ka radiation.

3. The solid form of claim 1, wherein the solid form is a solid form of a hydrate of Compound A, and is Form HD: characterized by having XRPD signals at approximately 5.1 and at least two of 14.9, 17.4, and 20.5 °29 using Cu Ka radiation.

4. The solid form of claim 1, wherein the solid form is a solid form of a Compound A 2- MeTHF solvate, selected from: Form SV1: characterized by having XRPD signals at approximately 4.7, 8.1, and 9.3 °29 using Cu Ka radiation, and

Form SV2: characterized by having XRPD signals at approximately 8.3, 12.4, and 19.2 °29 using Cu Ka radiation.

5. The solid form of claim 1, wherein the solid form is a solid form of a Compound A 2- DMF solvate, and is Form SV3: characterized by having XRPD signals at approximately 9.2, 11.3, and 19.7 °29 using Cu Ka radiation.

6. The solid form of claim 1 or 2, wherein the solid form is Form G, characterized by having XRPD signals at approximately 6.3, 8.3, 8.6, 12.6, and 18.0 °29 using Cu Ka radiation.

7. The solid form of claim 1 or 2, wherein the solid form is Form B, characterized by having XRPD signals at approximately 5.3, 7.2, 13.4, 15.8, and 17.5 °29 using Cu Ka radiation.

8. The solid form of claim 1 or 2, wherein the solid form is Form I, characterized by having XRPD signals at approximately 11.3, 11.5, 12.9, 14.9, and 17.4 °29 using Cu Ka radiation.

9. The solid form of claim 1 or 2, wherein the solid form is Form Y, characterized by having XRPD signals at approximately 6.4, 9.9, 11.1, 11.5, and 12.5 °29 using Cu Ka radiation.

19. The solid form of claim 1 or 2, wherein the solid form is Form Uu, characterized by having XRPD signals at approximately 6.4, 8.2, 9.9, 12.5, 15.1, and 15.7 °29 using Cu Ka radiation.

11. The solid form of claim 1 or 2, wherein the solid form is Form Tt, characterized by having XRPD signals at approximately 8.8, 17.8, 19.7, 29.8, and 23.7 °29 using Cu Ka radiation.

12. The solid form of claim 1 or 3, wherein the solid form is Form HD, characterized by having XRPD signals at approximately 5.1, 14.9, 17.4, 20.5, and 24.7 °29 using Cu Ka radiation.

13. The solid form of claim 1 or 4, wherein the solid form is Form SV1, characterized by having XRPD signals at approximately 4.7, 8.1, and 9.3 °29 using Cu Ka radiation.

14. The solid form of claim 1 or 4, wherein the solid form is Form SV2, characterized by having XRPD signals at approximately 8.3, 12.4, and 19.2 °29 using Cu Ka radiation.

15. A pharmaceutical composition comprising the solid form of any one of claims 1-14 and a pharmaceutically acceptable carrier or excipient.

16. A method of treating or preventing a disease or disorder, comprising administering to a subject in need thereof the solid form of any one of claims 1-14, or a pharmaceutical composition thereof.