WO2024222725A1

WO2024222725A1 - Crystalline lysine acetyltransferase 6a (kat6a) inhibitor and uses thereof

Info

Publication number: WO2024222725A1
Application number: PCT/CN2024/089494
Authority: WO
Inventors: Yushu YIN; Xing LIANG; Xin Cheng; Luoheng QIN
Original assignee: InSilico Medicine IP Ltd
Current assignee: InSilico Medicine IP Ltd
Priority date: 2023-04-25
Filing date: 2024-04-24
Publication date: 2024-10-31
Anticipated expiration: 2025-10-25

Abstract

Described herein are crystalline forms of a small molecule lysine acetyltransferase 6A (KAT6A) inhibitor: Compound (1), as well as pharmaceutical compositions thereof, and methods of use thereof in the treatment of diseases or conditions that would benefit from treatment with a lysine acetyltransferase 6A (KAT6A) inhibitor.

Description

CRYSTALLINE LYSINE ACETYLTRANSFERASE 6A (KAT6A) INHIBITOR AND USES THEREOF

CROSS-REFERENCE

This patent application claims the benefit of International Application No. PCT/CN2023/090649, filed April 25, 2023; which is incorporated herein by reference in its entirety.

BACKGROUND

Lysine acetyltransferase 6A (KAT6A) belongs to the MYST family of acetyltransferases and was first discovered approximately 25 years ago. KAT6A controls fundamental cellular processes, including gene transcription, cellular senescence, cardiac septum development, memory T-cell diversity, and maintenance of normal hematopoietic stem cells. Dysregulation of KAT6A acetyltransferase activity or aberrant expression of KAT6A has been associated with oncogenic function in a number of cancers, including leukemia, glioma, endometrial serous carcinoma, and breast cancer. As such, compounds that inhibit KAT6A are potential agents for treating a variety of cancers, especially a stable crystalline form.

SUMMARY

Disclosed herein is a solid state form of 2, 4-dimethoxy-N- (4-methoxy-6- (thiazol-2-yloxy) benzo [d] isoxazol-3-yl) -6-methylpyridine-3-sulfonamide: (Compound 1) or a pharmaceutically acceptable salt thereof.

In some embodiments, the solid state form is a crystalline form.

In some embodiments, the solid state form is crystalline Compound 1 freeform Type A, crystalline Compound 1 freeform Type C, crystalline Compound 1 freeform Type D, crystalline Compound 1 freeform Type E, or crystalline Compound 1 freeform Type F.

In some embodiments, the solid state form is crystalline Compound 1 freeform Type B.

In some embodiments, the solid state form is in the form of a salt.

In some embodiments, the solid state form is in the form of a sodium, potassium, ammonium, or choline salt.

In some embodiments, the solid state form is in the form of an L-arginine salt.

BRIEF DESCRIPTION OF THE DRAWINGS

The features of the invention are set forth with particularity in the appended claims. A better understanding of the features of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

FIG. 1 shows the X-Ray Powder Diffraction (XRPD) pattern of amorphous Compound 1 freeform.

FIG. 2 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 freeform Type A.

FIG. 3 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 freeform Type A.

FIG. 4 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 freeform Type A.

FIG. 5 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 freeform Type B.

FIG. 6 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 freeform Type B.

FIG. 7 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 freeform Type B.

FIG. 8 shows the Dynamic Vapor Sorption (DVS) plot of Compound 1 freeform Type B.

FIG. 9 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 freeform Type C.

FIG. 10 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 freeform Type C.

FIG. 11 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 freeform Type C.

FIG. 12 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 freeform Type D.

FIG. 13 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 freeform Type D.

FIG. 14 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 freeform Type D.

FIG. 15 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 freeform Type E.

FIG. 16 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 freeform Type E.

FIG. 17 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 freeform Type E.

FIG. 18 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 freeform Type F.

FIG. 19 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 freeform Type F.

FIG. 20 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 freeform Type F.

FIG. 21 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Sodium Salt Type A.

FIG. 22 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 Sodium Salt Type A.

FIG. 23 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Sodium Salt Type A.

FIG. 24 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Sodium Salt Type B.

FIG. 25 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Sodium Salt Type C.

FIG. 26 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 Sodium Salt Type C.

FIG. 27 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Sodium Salt Type C.

FIG. 28 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Sodium Salt Type D.

FIG. 29 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 Sodium Salt Type D.

FIG. 30 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Sodium Salt Type D.

FIG. 31 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Potassium Salt Type A.

FIG. 32 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 Potassium Salt Type A.

FIG. 33 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Potassium Salt Type A.

FIG. 34 shows the X-Ray Powder Diffraction (XRPD) pattern of Ammonium Salt Type A

FIG. 35 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 Ammonium Salt Type A.

FIG. 36 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Ammonium Salt Type A.

FIG. 37 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Ammonium Salt Type B.

FIG. 38 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 Ammonium Salt Type B.

FIG. 39 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Ammonium Salt Type B.

FIG. 40 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Ammonium Salt Type C.

FIG. 41 shows the Differential Scanning Calorimetry (DSC) thermogram of Ammonium Salt Type C.

FIG. 42 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Ammonium Salt Type C.

FIG. 43 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 L-Arginine Salt Type A.

FIG. 44 shows the Differential Scanning Calorimetry (DSC) thermogram of L-Arginine Salt Type A.

FIG. 45 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 L-Arginine Salt Type A.

FIG. 46 shows the X-Ray Powder Diffraction (XRPD) pattern of Compound 1 Choline Salt Type A

FIG. 47 shows the Differential Scanning Calorimetry (DSC) thermogram of Compound 1 Choline Salt Type A.

FIG. 48 shows the Thermogravimetric Analysis (TGA) thermogram of Compound 1 Choline Salt Type A.

DETAILED DESCRIPTION

While small molecule inhibitors are often initially evaluated for their activity when dissolved in solution, solid state characteristics such as polymorphism are also important. Polymorphic forms of a drug substance can have different physical properties, including melting point, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure, and density. These properties can have a direct effect on the ability to process or manufacture a drug substance and the drug product. Moreover, differences in these properties can and often lead to different pharmacokinetics profiles for different polymorphic forms of a drug. Therefore, polymorphism is often an important factor under regulatory review of the ‘sameness’ of drug products from various manufacturers.

Compound 1

Compound 1 is 2, 4-dimethoxy-N- (4-methoxy-6- (thiazol-2-yloxy) benzo [d] isoxazol-3-yl) -6-methylpyridine-3-sulfonamide: (Compound 1) . In some embodiments, Compound 1 is in the form of a freeform. In some embodiments, Compound 1 is in the form of a pharmaceutically acceptable salt. In some embodiments, Compound 1 is in the form of a sodium salt. In some embodiments, Compound 1 is in the form of a potassium salt. In some embodiments, Compound 1 is in the form of an ammonium salt. In some embodiments, Compound 1 is in the form of a choline salt. In some embodiments, Compound 1 is in the form of an L-arginine salt. In some embodiments, Compound 1 is in the form of a co-crystal. In some embodiments, Compound 1 is in an amorphous form. In some embodiments, Compound 1 is in a non-ionized form. In some embodiments, a freeform of Compound 1 is in a non-ionized form.

Solid State Form of Compound 1

In one aspect, provided herein is a solid state form of 2, 4-dimethoxy-N- (4-methoxy-6- (thiazol-2-yloxy) benzo [d] isoxazol-3-yl) -6-methylpyridine-3-sulfonamide: (Compound 1) or a pharmaceutically acceptable salt thereof.

In some embodiments, the solid state form is a crystalline form.

In some embodiments, the solid state form is crystalline Compound 1 freeform. In some embodiments, the solid state form is crystalline Compound 1 freeform Type A, crystalline Compound 1 freeform Type B, or crystalline Compound 1 freeform Type D. In some embodiments, the solid state form is crystalline Compound 1 freeform Type A. In some embodiments, the solid state form is crystalline Compound 1 freeform Type B. In some embodiments, the solid state form is crystalline Compound 1 freeform Type C. In some embodiments, the solid state form is crystalline Compound 1 freeform Type D. In some embodiments, the solid state form is crystalline Compound 1 freeform Type E. In some embodiments, the solid state form is crystalline Compound 1 freeform Type F.

In some embodiments, the solid state form is crystalline Compound 1 freeform Type A, Compound 1 freeform Type C, Compound 1 freeform Type D, Compound 1 freeform Type E, or Compound 1 freeform Type F.

For avoidance of doubt the term “crystalline form” is used throughout the description to include any crystalline forms including any one of the following forms: the freeform (Type A, B, C, D, E, or F) , the sodium salt (Type A, B, C, or D) , the potassium salt (Type A) , the ammonium salt (Type A, B, or C) , the L-arginine salt (Type A) , and the choline salt (Type A) .

Compound 1 Freeform Type A

Disclosed herein is Compound 1 freeform Type A. In some embodiments, the crystalline form is Compound 1 freeform Type A characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 2 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 8.0 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, and 21.0 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 3; or

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 4;

(e) combinations thereof.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 2 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 1 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 8.0 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, and 21.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 6.9 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, and 18.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2°2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.5 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 25.4 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type A, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 3.

In some embodiments of Compound 1 freeform Type A, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 4.

Table 1: XRPD peaks table of Compound 1 Freeform Type A

Compound 1 Freeform Type B

Disclosed herein is Compound 1 freeform Type B. In some embodiments, the crystalline form is Compound 1 freeform Type B characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 12.8 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, and 24.7 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 6;

(d) a Differential Scanning Calorimetry (DSC) thermogram with an endothermic peak having a peak temperature at about 173.1 ℃;

(e) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 7;

(f) a Thermogravimetric Thermal Analysis (TGA) thermogram exhibiting a mass loss of about 1.29%from the onset of heating up to approximately 150 ℃; or

(g) combinations thereof.

In some embodiments, the crystalline form is Compound 1 freeform Type B characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern with peaks at 12.8 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, and 24.7 ± 0.2° 2θ as measured using Cu Kα. radiation;

(b) a Differential Scanning Calorimetry (DSC) thermogram with an endothermic peak having a peak temperature at about 173.1 ℃;

(c) a Thermogravimetric Thermal Analysis (TGA) thermogram exhibiting a mass loss of about 1.29%from the onset of heating up to approximately 150 ℃; or

(d) combinations thereof.

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 7; or

(e) combinations thereof.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 2 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 12.8 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, and 24.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, and 22.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 5.4 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 22.1 ± 0.2° 2θ and 25.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2°2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 27.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least nine peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2°2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least 10 peaks selected from 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type B, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 6.

In some embodiments of Compound 1 freeform Type B, the Differential Scanning Calorimetry (DSC) thermogram has an endothermic peak having a peak temperature at about 173.1 ℃.

In some embodiments of Compound 1 freeform Type B, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 7.

In some embodiments of Compound 1 freeform Type B, the Thermogravimetric Thermal Analysis (TGA) thermogram exhibits a mass loss of about 1.29%from the onset of heating up to approximately 150 ℃. In some embodiments of Compound 1 freeform Type B, the Thermogravimetric Thermal Analysis (TGA) thermogram exhibits a mass loss of less than 1.5%from the onset of heating up to approximately 150 ℃. In some embodiments of Compound 1 freeform Type B, the Thermogravimetric Thermal Analysis (TGA) thermogram exhibits a mass loss of less than 2%from the onset of heating up to approximately 150 ℃.

In some embodiments of Compound 1 freeform Type B, the crystalline form is non hygroscopic.

In some embodiments of Compound 1 freeform Type B, the crystalline form is an anhydrate.

In some embodiments of Compound 1 freeform Type B, 0.0679%water uptake was detected at 80%relative humidity (RH) /25 ℃ in the sorption curve from 0%RH to 95%RH. In some embodiments of Compound 1 freeform Type B, less than 0.1%, less than 0.2%, less than 0.5%, less than 0.8%, less than 1%, or less than 2%water uptake is detected at 80%relative humidity (RH) /25 ℃ in the sorption curve from 0%RH to 95%RH. In some embodiments of Compound 1 freeform Type B, less than 0.1%water uptake is detected at 80%relative humidity (RH) /25 ℃ in the sorption curve from 0%RH to 95%RH.

Table 2: XRPD peaks table of Compound 1 Freeform Type B

Compound 1 Freeform Type C

Disclosed herein is Compound 1 freeform Type C. In some embodiments, the crystalline form is Compound 1 freeform Type C characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 9 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 11.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, and 20.9 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 10;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 11; or

(e) combinations thereof.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 9 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 3 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, and 20.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 15.4 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 7.7 ± 0.2° 2θ and 23.4 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2°2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 7.7 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.3 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 23.4 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type C, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 10.

In some embodiments of Compound 1 freeform Type C, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 11.

Table 3: XRPD peaks table of Compound 1 Freeform Type C

Compound 1 Freeform Type D

Disclosed herein is Compound 1 freeform Type D. In some embodiments, the crystalline form is Compound 1 freeform Type D characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 12 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 7.5 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, and 20.5 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 13;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 14; or

(e) combinations thereof.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 12 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 4 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 7.5 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, and 20.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 11.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, and 21.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 23.3 ± 0.2° 2θ and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 7.5 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, 16.5 ± 0.2°2θ, 20.5 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 23.3 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 7.5 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 23.3 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 7.5 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 23.3 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 7.5 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 23.3 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 7.5 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 23.3 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 7.5 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 23.3 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 7.5 ± 0.2° 2θ, 11.3 ± 0.2° 2θ, 15.1 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 23.3 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type D, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 13.

In some embodiments of Compound 1 freeform Type D, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 14.

Table 4: XRPD peaks table of Compound 1 Freeform Type D

Compound 1 Freeform Type E

Disclosed herein is Compound 1 freeform Type E. In some embodiments, the crystalline form is Compound 1 freeform Type E characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 15 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 11.5 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, and 20.7 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 16;

(d) a Differential Scanning Calorimetry (DSC) thermogram with an endothermic peak having a peak temperature at about 101.0 ℃;

(e) a Differential Scanning Calorimetry (DSC) thermogram with an endothermic peak having a peak temperature at about 109.6 ℃;

(f) a Differential Scanning Calorimetry (DSC) thermogram with an exotherm peak having a peak temperature at about 173.4 ℃;

(g) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 17;

(h) a Thermogravimetric Thermal Analysis (TGA) thermogram exhibiting a mass loss of about 16.63 %from the onset of heating up to approximately 150 ℃; or

(i) combinations thereof.

In some embodiments, the crystalline form is Compound 1 freeform Type E characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern with peaks at 11.5 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, and 20.7 ± 0.2° 2θ as measured using Cu Kα. radiation;

(b) a Differential Scanning Calorimetry (DSC) thermogram with an endothermic peak having a peak temperature at about 101.0 ℃;

(c) a Differential Scanning Calorimetry (DSC) thermogram with an endothermic peak having a peak temperature at about 109.6 ℃;

(d) a Differential Scanning Calorimetry (DSC) thermogram with an exotherm peak having a peak temperature at about 173.4 ℃;

(e) a Thermogravimetric Thermal Analysis (TGA) thermogram exhibiting a mass loss of about 16.63 %from the onset of heating up to approximately 150 ℃; or

(f) combinations thereof.

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 17; or

(e) combinations thereof.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 15 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 5 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.5 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, and 20.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 6.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, and 21.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 19.8 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2°2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.5 ± 0.2° 2θ, 11.5 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 17.9 ± 0.2° 2θ, 19.8 ± 0.2° 2θ, 20.7 ± 0.2° 2θ, 21.9 ± 0.2° 2θ, 23.8 ± 0.2° 2θ, and 26.5 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type E, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 16.

In some embodiments of Compound 1 freeform Type E, the Differential Scanning Calorimetry (DSC) thermogram has an endothermic peak having a peak temperature at about 101.0 ℃.

In some embodiments of Compound 1 freeform Type E, the Differential Scanning Calorimetry (DSC) thermogram has an endothermic peak having a peak temperature at about 109.6 ℃.

In some embodiments of Compound 1 freeform Type E, the Differential Scanning Calorimetry (DSC) thermogram has an exotherm peak having a peak temperature at about 173.4 ℃.

In some embodiments of Compound 1 freeform Type E, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 17.

In some embodiments of Compound 1 freeform Type E, the Thermogravimetric Thermal Analysis (TGA) thermogram exhibits a mass loss of about 16.63 %from the onset of heating up to approximately 150 ℃.

Table 5: XRPD peaks table of Compound 1 Freeform Type E

Compound 1 Freeform Type F

Disclosed herein is Compound 1 freeform Type F. In some embodiments, the crystalline form is Compound 1 freeform Type F characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 18 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 8.0 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, and 25.1 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 19;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 20; or

(e) combinations thereof.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 18 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 6 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 8.0 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, and 25.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 11.2 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, and 25.8 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 6.9 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, and 22.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2°2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.9 ± 0.2° 2θ, 8.0 ± 0.2° 2θ, 11.2 ± 0.2° 2θ, 12.9 ± 0.2° 2θ, 18.3 ± 0.2° 2θ, 21.0 ± 0.2° 2θ, 22.5 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 25.8 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 freeform Type F, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 19.

In some embodiments of Compound 1 freeform Type F, the Thermogravimetric Thermal

Analysis (TGA) thermogram is substantially the same as shown in FIG. 20.

Table 6: XRPD peaks table of Compound 1 Freeform Type F

Compound 1 Sodium Salt Type A

Disclosed herein is Compound 1 sodium salt Type A. In some embodiments, the crystalline form is Compound 1 sodium salt Type A characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 21 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 9.2 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 22;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 23; or

(e) combinations thereof.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 21 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 7 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 9.2 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 11.1 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, and 25.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 20.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2°2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 9.2 ± 0.2° 2θ, 11.1 ± 0.2° 2θ, 17.8 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 24.6 ± 0.2° 2θ, 25.2 ± 0.2° 2θ, 25.9 ± 0.2° 2θ, and 26.9 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type A, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 22.

In some embodiments of Compound 1 sodium salt Type A, wherein the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 23.

Table 7: XRPD peaks table of Compound 1 Sodium Salt Type A

Compound 1 Sodium Salt Type B

Disclosed herein is Compound 1 sodium salt Type B. In some embodiments, the crystalline form is Compound 1 sodium salt Type B characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 24 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 8.7 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, and 22.7 ± 0.2° 2θ as measured using Cu Kα. radiation; or

(c) combinations thereof.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 24 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 8 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 8.7 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, and 22.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 5.3 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, and 21.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 14.5 ± 0.2° 2θ and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.3 ± 0.2° 2θ, 8.7 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 14.5 ± 0.2°2θ, 17.4 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 5.3 ± 0.2° 2θ, 8.7 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 5.3 ± 0.2° 2θ, 8.7 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 5.3 ± 0.2° 2θ, 8.7 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 5.3 ± 0.2° 2θ, 8.7 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 5.3 ± 0.2° 2θ, 8.7 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 5.3 ± 0.2° 2θ, 8.7 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 17.4 ± 0.2° 2θ, 21.5 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, and 24.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

Table 8: XRPD peaks table of Compound 1 Sodium Salt Type B

Compound 1 Sodium Salt Type C

Disclosed herein is Compound 1 sodium salt Type C. In some embodiments, the crystalline form is Compound 1 sodium salt Type C characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 25 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 8.2 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, and 21.7 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 26;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 27; or

(e) combinations thereof.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 25 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 9 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 8.2 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, and 21.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 10.5 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, and 24.8 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 5.4 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2° 2θ, and 31.1 ± 0.2°2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2°2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2° 2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2° 2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2°2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2°2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2° 2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2° 2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2°2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2°2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least nine peaks selected from 5.4 ± 0.2° 2θ, 8.2 ± 0.2° 2θ, 10.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 17.5 ± 0.2° 2θ, 21.7 ± 0.2° 2θ, 24.8 ± 0.2° 2θ, 26.6 ± 0.2° 2θ, 30.2 ± 0.2°2θ, and 31.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type C, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 26.

In some embodiments of Compound 1 sodium salt Type C, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 27.

Table 9: XRPD peaks table of Compound 1 Sodium Salt Type C

Compound 1 Sodium Salt Type D

Disclosed herein is Compound 1 sodium salt Type D. In some embodiments, the crystalline form is Compound 1 sodium salt Type D characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 28 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 9.3 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, and 22.6 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 29;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 30; or

(e) combinations thereof.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 28 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 10 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 9.3 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, and 22.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 5.3 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, and 21.3 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, and 26.2 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2°2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ± 0.2° 2θas measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 5.3 ± 0.2° 2θ, 9.3 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.8 ± 0.2° 2θ, 16.0 ± 0.2° 2θ, 19.1 ± 0.2° 2θ, 21.3 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 26.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 sodium salt Type D, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 29.

In some embodiments of Compound 1 sodium salt Type D, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 30.

Table 10: XRPD peaks table of Compound 1 Sodium Salt Type D

Compound 1 Potassium Salt Type A

Disclosed herein is Compound 1 potassium salt Type A. In some embodiments, the crystalline form is Compound 1 potassium salt Type A characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 31 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 6.3 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, and 20.2 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 32;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 33; or

(e) combinations thereof.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 31 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 11 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.3 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, and 20.2 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 12.7 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, and 26.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, and 27.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.3 ± 0.2° 2θ, 12.7 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, 16.5 ±0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.3 ± 0.2° 2θ, 12.7 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.3 ± 0.2° 2θ, 12.7 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.3 ± 0.2° 2θ, 12.7 ± 0.2°2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.3 ± 0.2° 2θ, 12.7 ± 0.2°2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.3 ± 0.2° 2θ, 12.7 ± 0.2° 2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.3 ± 0.2° 2θ, 12.7 ± 0.2°2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.3 ± 0.2° 2θ, 12.7 ± 0.2°2θ, 13.3 ± 0.2° 2θ, 16.5 ± 0.2° 2θ, 18.8 ± 0.2° 2θ, 19.7 ± 0.2° 2θ, 20.2 ± 0.2° 2θ, 26.5 ± 0.2° 2θ, and 27.1 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 potassium salt Type A, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 32.

In some embodiments of Compound 1 potassium salt Type A, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 33.

Table 11: XRPD peaks table of Compound 1 Potassium Salt Type A

Compound 1 Ammonium Salt Type A

Disclosed herein is Compound 1 ammonium salt Type A. In some embodiments, the crystalline form is Compound 1 ammonium salt Type A characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 34 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 11.9 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, and 21.8 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 35;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 36; or

(e) combinations thereof.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 34 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 12 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.9 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, and 21.8 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 6.0 ± 0.2° 2θ, 16.2 ± 0.2° 2θ, and 18.2 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 20.9 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.0 ± 0.2° 2θ, 11.9 ± 0.2° 2θ, 16.2 ± 0.2° 2θ, 16.8 ±0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.0 ± 0.2° 2θ, 11.9 ± 0.2° 2θ, 16.2 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.0 ± 0.2° 2θ, 11.9 ± 0.2°2θ, 16.2 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.0 ± 0.2° 2θ, 11.9 ± 0.2°2θ, 16.2 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.0 ± 0.2° 2θ, 11.9 ± 0.2°2θ, 16.2 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.0 ± 0.2° 2θ, 11.9 ± 0.2° 2θ, 16.2 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.0 ± 0.2° 2θ, 11.9 ± 0.2°2θ, 16.2 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.0 ± 0.2° 2θ, 11.9 ± 0.2°2θ, 16.2 ± 0.2° 2θ, 16.8 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 20.9 ± 0.2° 2θ, 21.8 ± 0.2° 2θ, 22.6 ± 0.2° 2θ, and 23.2 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type A, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 35.

In some embodiments of Compound 1 ammonium salt Type A, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 36.

Table 12: XRPD peaks table of Compound 1 Ammonium Salt Type A

Compound 1 Ammonium Salt Type B

Disclosed herein is Compound 1 ammonium salt Type B. In some embodiments, the crystalline form is Compound 1 ammonium salt Type B characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 37 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 6.5 ± 0.2° 2θ, 14.7 ± 0.2° 2θ, and 26.1 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 38;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 39; or

(e) combinations thereof.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 37 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 13 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.5 ± 0.2° 2θ, 14.7 ± 0.2° 2θ, and 26.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 13.0 ± 0.2° 2θ and 19.5 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 18.1 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.5 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.7 ± 0.2° 2θ, 18.1 ±0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.5 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.7 ± 0.2° 2θ, 18.1 ± 0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.5 ± 0.2° 2θ, 13.0 ± 0.2°2θ, 14.7 ± 0.2° 2θ, 18.1 ± 0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.5 ± 0.2° 2θ, 13.0 ± 0.2°2θ, 14.7 ± 0.2° 2θ, 18.1 ± 0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.5 ± 0.2° 2θ, 13.0 ± 0.2°2θ, 14.7 ± 0.2° 2θ, 18.1 ± 0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.5 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.7 ± 0.2° 2θ, 18.1 ± 0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.5 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.7 ± 0.2° 2θ, 18.1 ± 0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.5 ± 0.2° 2θ, 13.0 ± 0.2°2θ, 14.7 ± 0.2° 2θ, 18.1 ± 0.2° 2θ, 19.5 ± 0.2° 2θ, 20.1 ± 0.2° 2θ, 26.1 ± 0.2° 2θ, and 26.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type B, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 38.

In some embodiments of Compound 1 ammonium salt Type B, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 39.

Table 13: XRPD peaks table of Compound 1 Ammonium Salt Type B

Compound 1 Ammonium Salt Type C

Disclosed herein is Compound 1 ammonium salt Type C. In some embodiments, the crystalline form is Compound 1 ammonium salt Type C characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 40 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 6.1 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, and 24.4 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 41;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 42; or

(e) combinations thereof.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 40 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 14 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.1 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, and 24.4 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 13.0 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, and 25.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 12.2 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, and 22.1 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.1 ± 0.2° 2θ, 12.2 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.0 ±0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.1 ± 0.2° 2θ, 12.2 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.1 ± 0.2° 2θ, 12.2 ± 0.2°2θ, 13.0 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.1 ± 0.2° 2θ, 12.2 ± 0.2°2θ, 13.0 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.1 ± 0.2° 2θ, 12.2 ± 0.2°2θ, 13.0 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.1 ± 0.2° 2θ, 12.2 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.1 ± 0.2° 2θ, 12.2 ± 0.2° 2θ, 13.0 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.1 ± 0.2° 2θ, 12.2 ± 0.2°2θ, 13.0 ± 0.2° 2θ, 14.0 ± 0.2° 2θ, 15.6 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 24.4 ± 0.2° 2θ, and 25.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 ammonium salt Type C, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 41.

In some embodiments of Compound 1 ammonium salt Type C, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 42.

Table 14: XRPD peaks table of Compound 1 Ammonium Salt Type C

Compound 1 L-Arginine Salt Type A

Disclosed herein is Compound 1 L-Arginine Salt Type A. In some embodiments, the crystalline form is Compound 1 L-Arginine Salt Type A characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 43 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 11.0 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, and 18.6 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 44;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 45; or

(e) combinations thereof.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 43 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 15 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.0 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, and 18.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 6.1 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, and 15.3 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.1 ± 0.2° 2θ, 11.0 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, 13.7 ±0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 6.1 ± 0.2° 2θ, 11.0 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 6.1 ± 0.2° 2θ, 11.0 ± 0.2°2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 6.1 ± 0.2° 2θ, 11.0 ± 0.2°2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 6.1 ± 0.2° 2θ, 11.0 ± 0.2°2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 6.1 ± 0.2° 2θ, 11.0 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 6.1 ± 0.2° 2θ, 11.0 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 6.1 ± 0.2° 2θ, 11.0 ± 0.2°2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 L-Arginine salt Type A, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 44.

In some embodiments of Compound 1 L-Arginine salt Type A, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 45.

Table 15: XRPD peaks table of Compound 1 L-Arginine Salt Type A

Compound 1 Choline Salt Type A

Disclosed herein is Compound 1 Choline Salt Type A. In some embodiments, the crystalline form is Compound 1 Choline Salt Type A characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 46 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 11.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, and 20.6 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 47;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 48; or

(e) combinations thereof.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 46 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 16 as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, and 20.6 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 12.5 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, and 24.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the X-ray powder diffraction (XRPD) pattern further comprises peaks at 5.3 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, and 22.9 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2°2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ± 0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least two peaks selected from 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least three peaks selected from 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least four peaks selected from 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least five peaks selected from 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least six peaks selected from 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least seven peaks selected from 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the crystalline form has an X-ray powder diffraction (XRPD) pattern with at least eight peaks selected from 5.3 ± 0.2° 2θ, 11.4 ± 0.2° 2θ, 12.5 ± 0.2° 2θ, 15.4 ± 0.2° 2θ, 18.2 ± 0.2° 2θ, 19.2 ± 0.2° 2θ, 20.6 ± 0.2° 2θ, 22.9 ± 0.2° 2θ, and 24.0 ±0.2° 2θ as measured using Cu Kα. radiation.

In some embodiments of Compound 1 choline salt Type A, the Differential Scanning Calorimetry (DSC) thermogram is substantially the same as shown in FIG. 47.

In some embodiments of Compound 1 choline salt Type A, the Thermogravimetric Thermal Analysis (TGA) thermogram is substantially the same as shown in FIG. 48.

Table 16: XRPD peaks table of Compound 1 Choline Salt Type A

Method of Treatment

Disclosed herein is a method of treating a disease in which inhibition of KAT6A is beneficial, the method comprising administering a crystalline form disclosed herein. In some embodiment, the crystalline form is freeform Type B of Compound 1. In some embodiments, the method comprises administering a pharmaceutical composition comprising crystalline form disclosed herein.

Disclosed herein is a method of treating a disease or disorder associated with KAT6A, the method comprising administering to the subject crystalline form disclosed herein. In some embodiment, the crystalline form is freeform Type B of Compound 1. In some embodiments, the method comprises administering a pharmaceutical composition comprising crystalline form disclosed herein.

In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal crystalline form disclosed herein. In some embodiment, the crystalline form is freeform Type B of Compound 1.

In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form (such as the crystalline form is freeform Type B of Compound 1) disclosed herein, wherein the cancer is selected from lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, stomach cancer, hepatocellular carcinoma, colon cancer, breast cancer, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, Hodgkin’s disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, hematology malignancy, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS) , primary CNS lymphoma, spinal axis tumors, glioblastoma, brain stem glioma, pituitary adenoma, or a combination of two or more of the foregoing cancers. In some embodiment the method is a method of treating breast cancer in a mammal in need thereof, comprising administering to the mammal the crystalline freeform Type B of Compound 1.

In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein (such as the crystalline form is freeform Type B of Compound 1) , wherein the cancer is selected from ER-positive breast cancer, glioblastoma, non-small cell lung cancer (NSCLC) , small cell lung cancer (SCLC) , melanoma, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer (CRC) , hepatocellular carcinoma (HCC) , renal cell carcinoma (RCC) , leukemia, lymphoma or multiple myeloma, acute lymphocytic leukemia (ALL) , acute myeloid leukemia (AML) , chronic lymphocytic leukemia (CLL) , chronic myeloid leukemia (CML) , and non-Hodgkin’s lymphoma. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is ER-positive breast cancer. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is glioblastoma. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is non-small cell lung cancer (NSCLC) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is small cell lung cancer (SCLC) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is melanoma. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is ovarian cancer. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is prostate cancer. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is pancreatic cancer. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is colorectal cancer (CRC) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is hepatocellular carcinoma (HCC) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is renal cell carcinoma (RCC) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is leukemia. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is lymphoma. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is multiple myeloma. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is acute lymphocytic leukemia (ALL) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is acute myeloid leukemia (AML) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is chronic lymphocytic leukemia (CLL) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is chronic myeloid leukemia (CML) . In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is non-Hodgkin’s lymphoma. In some embodiment, the crystalline form is freeform Type B of Compound 1. In some embodiment the method is a method of treating ER-positive breast cancer in a mammal in need thereof, comprising administering to the mammal the crystalline freeform Type B of Compound 1.

In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is a solid tumor with KAT6A/6B amplification or overexpression, or leukemia or solid tumor with KAT6A/6B fusion protein resulting from chromosomal translocation. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is a solid tumor with KAT6A/6B amplification or overexpression. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is a leukemia or solid tumor with KAT6A/6B fusion protein resulting from chromosomal translocation. In some embodiment, the crystalline form is freeform Type B of Compound 1.

In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is a MYST overexpressing cancer. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer overexpresses more than one KATs of the MYST family. In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer overexpresses more than one KATs of the MYST family selected from TIP60, KAT6A, KAT6B, HBO1, and MOF. In some embodiment, the crystalline form is freeform Type B of Compound 1.

In some embodiments is a method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer is a bromodomain overexpressing cancer. In some embodiments is a method of treating a bromodomain overexpressing cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form disclosed herein, wherein the cancer overexpresses one or more bromodomain proteins selected from BRD2, BRD3, BRD4, BRD7, BRD8, BRD9, BRDT, TAF1/TAF1L, TFIID, SMARC2, and SMARC4. In some embodiment, the crystalline form is freeform Type B of Compound 1.

Dosing

In certain embodiments, the compositions containing the compound (s) described herein are administered for prophylactic and/or therapeutic treatments. In certain therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest at least one of the symptoms of the disease or condition. Amounts effective for this use depend on the severity and course of the disease or condition, previous therapy, the patient’s health status, weight, and response to the drugs, and the judgment of the treating physician. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose escalation and/or dose ranging clinical trial.

In prophylactic applications, compositions containing the compounds described herein are administered to a patient susceptible to or otherwise at risk of a particular disease, disorder or condition. Such an amount is defined to be a “prophylactically effective amount or dose. ” In this use, the precise amounts also depend on the patient’s state of health, weight, and the like. When used in patients, effective amounts for this use will depend on the severity and course of the disease, disorder or condition, previous therapy, the patient’s health status and response to the drugs, and the judgment of the treating physician. In one aspect, prophylactic treatments include administering to a mammal, who previously experienced at least one symptom of or risk factor for the disease being treated and is currently in remission, a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt thereof, in order to prevent a return of the symptoms of the disease or condition.

In certain embodiments wherein the patient’s condition does not improve, upon the doctor’s discretion the administration of the compounds are administered chronically, that is, for an extended period of time, including throughout the duration of the patient’s life in order to ameliorate or otherwise control or limit the symptoms of the patient’s disease or condition.

In any of the aforementioned aspects are further embodiments in which the effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, is: (a) systemically administered to the mammal; and/or (b) administered orally to the mammal; and/or (c) intravenously administered to the mammal; and/or (d) administered by injection to the mammal; and/or (e) administered topically to the mammal; and/or (f) administered non-systemically or locally to the mammal.

Routes of Administration

Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ophthalmic, pulmonary, transmucosal, transdermal, vaginal, otic, nasal, and topical administration. In addition, by way of example only, parenteral delivery includes intramuscular, subcutaneous, intravenous, intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injections.

Pharmaceutical Compositions/Formulations

The compounds described herein are administered to a subject in need thereof, either alone or in combination with pharmaceutically acceptable carriers, excipients or diluents, in a pharmaceutical composition, according to standard pharmaceutical practice. In one embodiment, the compounds of this disclosure may be administered to animals. The compounds can be administered orally or parenterally, including the intravenous, intramuscular, intraperitoneal, subcutaneous, rectal and topical routes of administration.

In another aspect, provided herein are pharmaceutical compositions comprising a crystalline form disclosed herein, and at least one pharmaceutically acceptable excipient.

Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable excipients that facilitate processing of the active compounds into preparations that can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. A summary of pharmaceutical compositions described herein can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995) ; Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams &Wilkins1999) , herein incorporated by reference for such disclosure.

In some embodiments, the pharmaceutically acceptable excipient is selected from carriers, binders, filling agents, suspending agents, flavoring agents, sweetening agents, disintegrating agents, dispersing agents, surfactants, lubricants, colorants, diluents, solubilizers, moistening agents, plasticizers, stabilizers, penetration enhancers, wetting agents, anti-foaming agents, antioxidants, preservatives, and any combinations thereof.

The pharmaceutical compositions described herein are administered to a subject by appropriate administration routes, including, but not limited to, oral, parenteral (e.g., intravenous, subcutaneous, intramuscular) , intranasal, buccal, topical, rectal, or transdermal administration routes. The pharmaceutical formulations described herein include, but are not limited to, aqueous liquid dispersions, liquids, gels, syrups, elixirs, slurries, suspensions, self-emulsifying dispersions, solid solutions, liposomal dispersions, aerosols, solid oral dosage forms, powders, immediate release formulations, controlled release formulations, fast melt formulations, tablets, capsules, pills, powders, dragees, effervescent formulations, lyophilized formulations, delayed release formulations, extended release formulations, pulsatile release formulations, multiparticulate formulations, and mixed immediate and controlled release formulations.

Pharmaceutical compositions including compounds described herein, or a pharmaceutically acceptable salt or solvate thereof are manufactured in a conventional manner, such as, by way of example only, by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or compression processes.

Pharmaceutical compositions for oral use are obtained by mixing one or more solid excipient with one or more of the compounds described herein, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients include, for example, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose; or others such as polyvinylpyrrolidone (PVP or povidone) or calcium phosphate. If desired, disintegrating agents are added, such as the cross-linked croscarmellose sodium, polyvinylpyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. In some embodiments, dyestuffs or pigments are added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

Pharmaceutical compositions that are administered orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds are dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In some embodiments, stabilizers are added.

Pharmaceutical compositions for parental use are formulated as infusions or injections. In some embodiments, the pharmaceutical composition suitable for injection or infusion includes sterile aqueous solutions, or dispersions, or sterile powders comprising a compound described herein, or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the pharmaceutical composition comprises a liquid carrier. In some embodiments, the liquid carrier is a solvent or liquid dispersion medium comprising, for example, water, saline, ethanol, a polyol (for example, glycerol, propylene glycol, liquid polyethylene glycols, and the like) , vegetable oils, nontoxic glyceryl esters, and any combinations thereof. In some embodiments, the pharmaceutical compositions further comprise a preservative to prevent growth of microorganisms.

Definitions

Unless otherwise stated, the following terms used in this application have the definitions given below. The use of the term “including” as well as other forms, such as “include” , “includes, ” and “included, ” is not limiting. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

The term “acceptable” with respect to a formulation, composition or ingredient, as used herein, means having no persistent detrimental effect on the general health of the subject being treated.

The terms “administer, ” “administering, ” “administration, ” and the like, as used herein, refer to the methods that may be used to enable delivery of compounds or compositions to the desired site of biological action. These methods include, but are not limited to oral routes, intraduodenal routes, parenteral injection (including intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular or infusion) , topical and rectal administration. Those of skill in the art are familiar with administration techniques that can be employed with the compounds and methods described herein. In some embodiments, the compounds and compositions described herein are administered orally.

The terms “effective amount” or “therapeutically effective amount, ” as used herein, refer to a sufficient amount of an agent or a compound being administered, which will relieve to some extent one or more of the symptoms of the disease or condition being treated. The result includes reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an “effective amount” for therapeutic uses is the amount of the composition comprising a compound as disclosed herein required to provide a clinically significant decrease in disease symptoms. An appropriate “effective” amount in any individual case is optionally determined using techniques, such as a dose escalation study.

The terms “enhance” or “enhancing, ” as used herein, means to increase or prolong either in potency or duration a desired effect. Thus, in regard to enhancing the effect of therapeutic agents, the term “enhancing” refers to the ability to increase or prolong, either in potency or duration, the effect of other therapeutic agents on a system. An “enhancing-effective amount, ” as used herein, refers to an amount adequate to enhance the effect of another therapeutic agent in a desired system.

The term “subject” or “patient” encompasses mammals. Examples of mammals include, but are not limited to, any member of the Mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. In one aspect, the mammal is a human.

The terms “treat, ” “treating” or “treatment, ” as used herein, include alleviating, abating or ameliorating at least one symptom of a disease or condition, preventing additional symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and/or therapeutically.

The term “about” means within a statistically meaningful range of a value, such as a stated concentration range, time frame, molecular weight, particle size, temperature, or pH. Such a range can be within an order of magnitude, typically within 10%, more typically within 5%, and even more typically within 3%of the indicated value or range. Sometimes, such a range can be within the experimental error typical of standard methods used for the measurement and/or determination of a given value or range. The allowable variation encompassed by the term “about” will depend upon the particular system under study, and can be readily appreciated by one of ordinary skill in the art. Whenever a range is recited within this application, every whole number integer within the range is also contemplated as an embodiment of the disclosure. In the context of the disclosure, when used or whether or not used the word, such as “about” , it means that within a given value or range of 10%, appropriately within 5%, especially within 1%.

If multiple diffraction patterns are available, then assessments of particle statistics (PS) and/or preferred orientation (PO) are possible. Consistency of relative intensity among XRPD patterns from multiple diffractometers indicates good orientation statistics. Alternatively, the observed XRPD pattern may be compared with a calculated XRPD pattern based upon a single crystal structure, if available. Two-dimensional scattering patterns using area detectors can also be used to evaluate PS/PO. If the effects of both PS and PO are determined to be negligible, then the XRPD pattern is representative of the powder average intensity for the sample and prominent peaks may be identified as “Representative Peaks. ” In general, the more data collected to determine Representative Peaks, the more confident one can be of the classification of those peaks.

“Characteristic peaks, ” to the extent they exist, are a subset of representative peaks and are used to differentiate one crystalline polymorph from another crystalline polymorph (polymorphs being crystalline forms having the same chemical composition) . Characteristic peaks are determined by evaluating which representative peaks, if any, are present in one crystalline polymorph of a compound against all other known crystalline polymorphs of that compound to within ±0.2 °2Θ. Not all crystalline polymorphs of a compound necessarily have at least one characteristic peak.

The term “preferred orientation” as used herein refers to an extreme case of non-random distribution of the crystallites of a solid state form. In XRPD, the ideal sample is homogenous and the crystallites are randomly distributed in the bulk solid. In a truly random sample, each possible reflection from a given set of planes will have and equal number of crystallites contributing to it. However, when the solid state form is in a preferred orientation this is not the case. Accordingly, comparing the intensity between a randomly oriented diffraction pattern and a preferred oriented diffraction pattern can look entirely different. Quantitative analysis depending on intensity ratios are greatly distorted by preferred orientation. Careful sample preparation is important for decreasing the incidence of a preferred orientation.

The term “substantially the same, ” as used herein to reference a figure is intended to mean that the figure is considered representative of the type and kind of characteristic data that is obtained by a skilled artisan in view of deviations acceptable in the art. Such deviations may be caused by factors related to sample size, sample preparation, particular instrument used, operation conditions, and other experimental condition variations known in the art. For example, one skilled in the art can appreciate that the endotherm onset and peak temperatures as measured by differential scanning calorimetry (DSC) may vary significantly from experiment to experiment. For example, one skilled in the art can readily identify whether two X-ray diffraction patterns or two DSC thermograms are substantially the same. In some embodiments, when characteristic peaks of two X-ray diffraction patterns do not vary more than ± 0.2° 2-θ, it is deemed that the X-ray diffraction patterns are substantially the same.

As used herein, salts of Compound 1 include compounds where the corresponding acid is in an ionized, non-ionized, associated, or unassociated form. In some embodiments, the corresponding acid is in an ionized and/or associated forms. In some embodiments, the corresponding acid is in a nonionized and/or unassociated forms. Salts of Compound 1 also include mono-acid, di-acid, etc. forms of the salts.

Dosing

In certain embodiments, the compositions containing the crystalline form described herein are administered for prophylactic and/or therapeutic treatments. In certain therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest at least one of the symptoms of the disease or condition. Amounts effective for this use depend on the severity and course of the disease or condition, previous therapy, the patient’s health status, weight, and response to the drugs, and the judgment of the treating physician. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose escalation and/or dose ranging clinical trial.

The amount of a given agent that corresponds to such an amount varies depending upon factors such as the particular compound, disease condition and its severity, the identity (e.g., weight, sex) of the subject or host in need of treatment, but nevertheless is determined according to the particular circumstances surrounding the case, including, e.g., the specific agent being administered, the route of administration, the condition being treated, and the subject or host being treated.

In general, however, doses employed for adult human treatment are typically in the range of 0.01 mg-5000 mg per day. In one aspect, doses employed for adult human treatment are from about 1 mg to about 1000 mg per day. In one embodiment, the desired dose is conveniently presented in a single dose or in divided doses administered simultaneously or at appropriate intervals, for example as two, three, four or more sub-doses per day.

In one embodiment, the daily dosages appropriate for the crystalline form described herein, or a pharmaceutically acceptable salt thereof, are from about 0.01 to about 50 mg/kg per body weight. In some embodiments, the daily dosage, or the amount of active in the dosage form are lower or higher than the ranges indicated herein, based on a number of variables in regard to an individual treatment regime. In various embodiments, the daily and unit dosages are altered depending on a number of variables including, but not limited to, the activity of the compound used, the disease or condition to be treated, the mode of administration, the requirements of the individual subject, the severity of the disease or condition being treated, and the judgment of the practitioner.

In any of the aforementioned aspects are further embodiments in which the effective amount of the crystalline form described herein, or a pharmaceutically acceptable salt thereof, is: (a) systemically administered to the mammal; and/or (b) administered orally to the mammal; and/or (c) intravenously administered to the mammal; and/or (d) administered by injection to the mammal; and/or (e) administered topically to the mammal; and/or (f) administered non-systemically or locally to the mammal.

In any of the aforementioned aspects are further embodiments comprising single administrations of the effective amount of the crystalline form disclosed herein, including further embodiments in which (i) the compound is administered once a day; or (ii) the compound is administered to the mammal multiple times over the span of one day.

EXAMPLES

The following examples are provided for illustrative purposes only and not to limit the scope of the claims provided herein.

Example 1: Preparation of Freeform Compound 1 Type A

To a mixture of 1-1 (10.0 g, 59.5 mmol) in MeCN (100 mL) were added dibenzyl disulfide (29.3 g, 119 mmol) and L-ascorbic acid (5.24 g, 29.8 mmol) . Then isoamyl nitrite (25.8 g, 220 mmol) was added to this reaction mixture at 0 ℃ and this reaction mixture was stirred at 25 ℃ for 12 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography to afford 1-2 (4.4 g, 27%yield) as a yellow oil. LCMS: 276.1 [M+H] ⁺.

To a mixture of 1-2 (1.00 g, 3.63 mmol) in MeCN (20 mL) , AcOH (2.5 mL) and water (5 mL) was added 1, 3-dichloro-5, 5-dimethylhydantoin (858 mg, 4.36 mmol) at -15 ℃. This reaction mixture was stirred at -15-25 ℃ for 1 h. Water (10 mL) was added to the mixture. The mixture was extracted with DCM (20 mL x 3) . The combined organic phase was washed with brine, dried over anhydrous Na₂SO₄, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography to afford 1-3 (660 mg, 72%yield) as a white solid. LCMS: 251.9 [M+H] ⁺.

To a solution of 1-4 (5 g, 32.2 mmol) in xylene (30 mL) were added 2-bromo-1, 3-thiazole (15.9 g, 96.7 mmol) , Josiphos SL-J009-1 Pd G3 (0.9 g, 0.97 mmol) and K₂CO₃ (8.9 g, 64.4 mmol, 100 mesh) . The reaction mixture was stirred at 150℃ under N₂ for 48 h. The mixture was filtered and concentrated. The obtained residue was purified by flash silica gel chromatography to afford the 1-5 (2.5 g, 32%yield) as a yellow solid. LCMS: 239.1 [M+H] ⁺.

To a solution of 1-5 (11 g, 46.18 mmol) in THF (110 mL) was added sodium methanolate (2.49 g, 46.18 mmol) . The reaction mixture was stirred at room temperature under N₂ for 1 h. Water was added. The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over anhydrous Na₂SO₄, and filtered. The residue was purified by flash silica gel chromatography to afford the 1-6 (8.6 g, 74%yield) as a yellow solid. LCMS: 251.1 [M+H] ⁺.

To a solution of 1-6 (8.6 g, 34.37 mmol) in MeCN (90 mL) and H₂O (10 mL) were added 1, 1, 3, 3-tetramethylguanidine (23.75 g, 206.19 mmol) and N-hydroxyacetamide (7.74 g, 103.10 mmol) . The reaction mixture was stirred at 70℃ under N₂ for 6 h. The mixture was concentrated. Water was added. The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over anhydrous Na₂SO₄, and filtered. The residue was purified by flash silica gel chromatography to afford the 1-7 (4.8 g, 53%) as a white solid. LCMS: 264.1 [M+H] ⁺.

To a solution of 1-7 (5 g, 19 mmol) in MeCN (50 mL) was added 1-3 (7.2 g, 28 mmol) . The mixture was stirred at 25 ℃ for 1 h. DMSO (150 mg, 1.9 mmol) and 3, 5-lutidine (6.1 g, 57 mmol) were added. The reaction mixture was stirred at 25 ℃ for 1.5 h. The mixture was then concentrated. The obtained residue was first purified by flash silica gel chromatography to give a solid which was then lyophilized (MeCN/H₂O) to afford compound 1 as a white solid. Take sample of the white solid for XRPD, DSC, TGA, ¹H-NMR, and LCMS analysis. LCMS: 479.2 [M+H] +. ¹H NMR (400 MHz, DMSO-d₆) δ 10.13 (s, 1H) , 7.37-7.31 (m, 2H) , 7.26 (d, J = 1.6 Hz, 1H) , 6.89 (d, J = 1.6 Hz, 1H) , 6.82 (s, 1H) , 3.89 (s, 3H) , 3.84 (s, 3H) , 3.82 (s, 3H) , 2.39 (s, 3H) .

The XRPD pattern of the obtained solid is shown in FIG. 2. Major peaks and their related intensities in the XRPD pattern are shown in Table 1. DSC and TGA results are shown in FIG. 3 and FIG. 4.

Inhibition of KAT6A enzymatic activity Compound 1 was determined using a radiometric 384-well format assay. A 10-point serial dilution of Compound 1were conducted in DMSO and then a volume of 200 nL was transferred into 384-well assay plate by Echo (Labcyte) . 10 μL of 2x enzyme solution (5 nM KAT6A (Active Motif) in assay buffer (50 mM Tris–HCl pH 8.0, 50 mM KCl, 0.1 mM EDTA , 5%glycerol, 1 mM DTT) ) was dispensed into assay plate except for low control wells, in which 10 μL of assay buffer was transferred. The plate was incubated at room temperature for 15 min before addition of 10 μL of 2x [³H] -acetyl coenzyme A (Ac-CoA) and substrate peptide mix solution (500 nM (KAT6A) [³H] -Ac-CoA (PerkinElmer) and 800 nM (KAT6A) biotinylated H4 (1-30) peptide (GL Biochem) in assay buffer) to each well to start reaction. The plate was incubated at room temperature for 60 min (KAT6A) , and then the reaction was stopped by adding 10 μL of stop solution (cold Ac-CoA (Cayman) in 1x assay buffer) . 25 μL of reaction in each well was transferred to Flashplate (PerkinElmer) and incubated for another 1 hour at room temperature. The plate was read on Microbeta and the inhibition percentage of each compound treated well was calculated based on the equation inh %= (Max-sample) /(Max-Min) *100 where Max is signal from high control wells with enzyme, and Min is signal from low control wells with assay buffer only. The inh%data were further fit in XL-Fit to obtain IC50 values using a 4-parameter logistic (4PL) sigmoidal curve model. KAT6A IC50s for Compound 1 is 5.9 nM.

Permeability of Compound 1 was determined in Caco-2 Assay. Caco-2 cells purchased from ATCC were seeded onto polyethylene membranes (PET) in 96-well Corning Insert plates at 1 x 105 cells/cm2, and refreshed medium every 4～5 days until to the 21st to 28th day for confluent cell monolayer formation. The transport buffer in the study was HBSS with 10.0 mM HEPES at pH 7.40±0.05. Compound 1 was tested at 2.00 μM bi-directionally in duplicate. Final DMSO concentration was adjusted to less than 1%. The plate was incubated for 2 hours in CO₂ incubator at 37±1℃, with 5%CO₂ at saturated humidity without shaking. And all samples after mixed with acetonitrile containing internal standard were centrifuged at 3200 xg for 10 min. Concentrations of test and control compounds in starting solution, donor solution, and receiver solution were quantified by LC-MS/MS methodologies, using peak area ratio of analyte/internal standard. After transport assay, lucifer yellow rejection assay was applied to determine the Caco-2 cell monolayer integrity. Permeability results of Compound 1 and PF-9363 are shown in the table below.

*PF-9363 is Example 98 in WO2020/254946 A1 having the following structure:

Example 2: Preparation of Freeform Amorphous of compound 1

400.2 mg Freeform Compound 1 Type A was dissolved in 5 mL DCM and filter it by 0.45 μm PTFE membrane. Concentrate the clear solution to dryness via rotary evaporation at 40 ℃. Take sample of the white solid for XRPD. The XRPD pattern of the obtained solid is shown in FIG. 1. It is Form Amorphous of compound (I) .

Example 3: Alternative preparation of Compound 1 Type A

About 20 mg of freeform amorphous of compound 1 was weighed into a 20-mL glass vial and dissolved with ACN to obtain a clear solution (filter the suspension by 0.45 μm PTFE membrane) . The solution was magnetically stirred with addition of water till precipitates appeared. The obtained precipitates were isolated for XRPD analysis. The XRPD pattern was same as that in FIG. 2 and confirmed to be Compound 1 Type A.

Example 4: Preparation of Compound 1 Freeform Type B

Compound 1 Freeform Type B was obtained by slurry Freeform Compound 1 Type A (50 mg) in MeOH (0.5 mL) at room temperature (RT) for 6 days. Solids were isolated by centrifugation and RT air dried. before characterization. Samples are taken for XRPD, DSC, TGA, 1H-NMR, and DVS analysis.

The XRPD pattern was shown in FIG. 5. Major peaks and their related intensities in the XRPD pattern are shown in Table 2. The TGA curve in FIG. 7 showed a weight loss of 1.29%up to 150 ℃. The DSC curve in FIG. 6 showed one endotherm at 173.1 ℃ (peak temperature) . ¹H NMR spectrum showed no obvious residual organic solvents. Based on limited TGA weight loss and neat DSC, freeform Type B was speculated to be anhydrate. DVS plot in FIG. 8 showed that 0.0679%water uptake was detected at 80%relative humidity (RH) /25 ℃ in the sorption curve from 0%RH to 95%RH, indicating that freeform Compound 1 Freeform Type B was non-hygroscopic.

Example 5: Preparation of Compound 1 Type C

About 20 mg of freeform amorphous of compound 1 was weighed into a 20-mL glass vial and dissolved with 1, 4-dioxane to obtain a clear solution (filter the suspension by 0.45 μm PTFE membrane) . The solution was magnetically stirred with addition of water till precipitates appeared. The obtained precipitates were isolated for XRPD, DSC, TGA, and ¹H NMR analysis.

The XRPD pattern of the obtained solid is shown in FIG. 9. Major peaks and their related intensities in the XRPD pattern are shown in Table 3. DSC and TGA results are shown in FIG. 10 and FIG. 11.

Example 6: Preparation of Compound 1 Type D

About 20 mg of freeform amorphous of compound 1 was weighed into a 20-mL glass vial and dissolved with 2-MeTHF to obtain a clear solution (filter the suspension by 0.45 μm PTFE membrane) . The solution was magnetically stirred with addition of n-Heptane till precipitates appeared. The obtained precipitates were isolated for XRPD, DSC, TGA, and ¹H NMR analysis.

The XRPD pattern of the obtained solid is shown in FIG. 12. Major peaks and their related intensities in the XRPD pattern are shown in Table 4. DSC and TGA results are shown in FIG. 13 and FIG. 14.

Example 7: Preparation of Compound 1 Type E

About 20 mg of freeform Compound 1 Type A was dissolved in 0.5 mL toluene in an HPLC vial at 50 ℃. After cooled back to RT and evaporated at RT, precipitation appeared. The obtained solids were isolated by centrifugation and air dried at RT for XRPD, DSC, TGA, and ¹H-NMR analysis.

The XRPD pattern was shown in FIG. 15. Major peaks and their related intensities in the XRPD pattern are shown in Table 5. The TGA curve in FIG. 16 showed a weight loss of 16.63 %up to 150 ℃. The DSC curve in FIG. 17 showed three endotherms at 101.0, 109.6 and 173.4 ℃ and one exotherm at 104.0 ℃ (peak temperature) .

Example 8: Preparation of Compound 1 Type F

About 20 mg of freeform Compound 1 Type A was suspended in 0.5 mL MEK. The suspension was stirred and subjected to temperature cycling for 4 days. The temperature range was between 50 ℃ and 5 ℃. The temperature was firstly heating to 50 ℃ at a rate of 4.5 ℃/min, followed by equilibration for 2 hours, then cooled down to 5 ℃ at a rate of 0.1 ℃/min, and kept isothermal at 5 ℃for 2 hours. The last step was cooled down to 5 ℃ at a rate of 0.1 ℃/min and kept isothermal at 5 ℃. The obtained solids were isolated and air dried for XRPD, DSC, TGA, and ¹H NMR analysis.

The XRPD pattern of the obtained solid is shown in FIG. 18. Major peaks and their related intensities in the XRPD pattern are shown in Table 6. DSC and TGA results are shown in FIG. 19 and FIG. 20.

Example 9: Preparation of Compound 1 Sodium Salt Type A

Sodium salt Type A was obtained by 1-day -20 ℃ slurry of freeform Type B and NaOH (1 eq. ) in acetone/H₂O, (19: 1, v: v) . Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 21. Major peaks and their related intensities in the XRPD pattern are shown in Table 7. DSC and TGA results are shown in FIG. 22 and FIG. 23.

Example 10: Preparation of Compound 1 Sodium Salt Type B

Sodium salt Type B was obtained by 3-day RT slurry of freeform Type B and NaOH (1 eq. ) in EtOAc. The XRPD overlay showed the peaks of freeform Type B was observed.

The XRPD pattern of the obtained solid is shown in FIG. 24. Major peaks and their related intensities in the XRPD pattern are shown in Table 8.

Example 11: Preparation of Compound 1 Sodium Salt Type C

Sodium salt Type C was obtained via slurry sodium salt Type B and freeform and NaOH (～1 eq. ) in EtOAc at RT for 2 days. Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 25. Major peaks and their related intensities in the XRPD pattern are shown in Table 9. DSC and TGA results are shown in FIG. 26 and FIG. 27.

Example 12: Preparation of Compound 1 Sodium Salt Type D

Sodium salt Type D was obtained by RT slurry of freeform Type B and NaOH (2 eq. ) in IPA. Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 28. Major peaks and their related intensities in the XRPD pattern are shown in Table 10. DSC and TGA results are shown in FIG. 29 and FIG. 30.

Example 13: Preparation of Compound 1 Potassium Salt Type A

Potassium salt Type A was obtained by 3-day RT slurry of freeform Type B and KOH (1 eq. ) in acetone/H₂O, (19: 1, v: v) . Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 31. Major peaks and their related intensities in the XRPD pattern are shown in Table 11. DSC and TGA results are shown in FIG. 32 and FIG. 33.

Example 14: Preparation of Compound 1 Ammonium Salt Type A

Ammonium salt Type A was obtained by 3-day RT slurry of freeform Type B and ammonia (1 eq. ) in acetone/H₂O, (19: 1, v: v) . Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 34. Major peaks and their related intensities in the XRPD pattern are shown in Table 12. DSC and TGA results are shown in FIG. 35 and FIG. 36.

Example 15: Preparation of Compound 1 Ammonium Salt Type B

Ammonium salt Type B was obtained from 3-day RT slurry of freeform Type B and ammonia (1 eq. ) in EtOAc. Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 37. Major peaks and their related intensities in the XRPD pattern are shown in Table 13. DSC and TGA results are shown in FIG. 38 and FIG. 39.

Example 16: Preparation of Compound 1 Ammonium Salt Type C

Ammonium salt Type C was obtained from 3-day RT slurry of freeform Type B and ammonia (1 eq. ) in IPA. Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 40. Major peaks and their related intensities in the XRPD pattern are shown in Table 14. DSC and TGA results are shown in FIG. 41 and FIG. 42.

Example 17: Preparation of Compound 1 L-Arginine Salt Type A

L-Arginine salt Type A was obtained from 3-day RT slurry of freeform Type B and arginine (1 eq. ) in acetone/H₂O, (19: 1, v: v) . Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 43. Major peaks and their related intensities in the XRPD pattern are shown in Table 15. DSC and TGA results are shown in FIG. 44 and FIG. 45.

Example 18: Preparation of Compound 1 Choline Salt Type A

Choline salt Type A was obtained from RT slurry of freeform Type B and choline (2 eq. ) in IPA. Solids were isolated by centrifugation and RT vacuum dried before characterization.

The XRPD pattern of the obtained solid is shown in FIG. 46. Major peaks and their related intensities in the XRPD pattern are shown in Table 16. DSC and TGA results are shown in FIG. 47 and FIG. 48.

Abbreviation for solvents 1

Analytical methods for free form

Thermal Gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC)

TGA data was collected using a Discovery TGA 5500 from TA Instruments. DSC was performed using a Discovery DSC 2500 from TA Instruments. Detailed parameters used are listed below.

X-ray Powder Diffractometer (XRPD)

For XRPD analysis, a PANalytical Empyrean and X’ Pert3 X-ray powder diffract meter was used. The XRPD parameters used are listed below.

Dynamic Vapor Sorption (DVS)

DVS was measured via a SMS (Surface Measurement Systems) DVS Intrinsic. The relative humidity at 25 ℃ were calibrated against deliquescence point of LiCl, Mg (NO₃) ₂ and KCl. Parameters for DVS test are listed below.

¹H-NMR

Solution NMR was collected on Bruker 400M NMR Spectrometer using DMSO-d6 as the solvent. Detailed parameters used were listed below.

High Performance Liquid Chromatography (HPLC)

Agilent 1260 with VWD detector was utilized and detailed chromatographic condition was listed below.

Analytical methods for salts

Differential Scanning Calorimetry (DSC) and Thermal Gravimetric Analysis (TGA)

X-ray Powder Diffractometer (XRPD)

For XRPD analysis, a PANalytical Empyrean and X’ Pert³ X-ray powder diffract meter was used. The XRPD parameters used are listed below.

Dynamic Vapor Sorption (DVS)

Dynamic vapor sorption was performed with an ADVENTURE series DVS at 25 ℃ under nitrogen blow. Approximately 30 milligrams of material was used. Samples were analyzed using methods below:

0%RH to 95%RH at 10%RH (5%from 90 to 95%RH)

95%RH to 0%RH at 10%RH (5%from 95 to 90%RH)

¹H-NMR

¹H NMR data was taken using Bruker 400M in DMSO-d6 solvent.

High Performance Liquid Chromatography (HPLC)

Agilent 1260 with VWD detector was utilized and detailed chromatographic condition are listed below.

IC Analysis

Thermo Scientific^TM Dionex^TM Aquion^TM Ion Chromatography (IC) System 1100 with conductivity detector was utilized and detailed chromatographic condition are listed below.

Claims

A solid state form of 2, 4-dimethoxy-N- (4-methoxy-6- (thiazol-2-yloxy) benzo [d] isoxazol-3-yl) -6-methylpyridine-3-sulfonamide: or a pharmaceutically acceptable salt thereof.
The solid state form of claim 1, wherein the solid state form is a crystalline form.
The solid state form of claim 1 or 2, wherein the solid state form is crystalline Compound 1 freeform Type A, crystalline Compound 1 freeform Type C, crystalline Compound 1 freeform Type D, crystalline Compound 1 freeform Type E, or crystalline Compound 1 freeform Type F.
The solid state form of claim 1 or 2, wherein the solid state form is crystalline Compound 1 freeform Type B.
The solid state form of claim 1 or 2, wherein the solid state form is in the form of a salt.
The solid state form of claim 1 or 2, wherein the solid state form is in the form of a sodium, potassium, ammonium, or choline salt.
The solid state form of claim 1 or 2, wherein the solid state form is in the form of an L-arginine salt.
The crystalline form of claim 2, wherein the crystalline form is Compound 1 freeform Type B characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 12.8 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, and 24.7 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 6;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 7; or

(e) combinations thereof.
The crystalline form of claim 8, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 5 as measured using Cu Kα. radiation.
The crystalline form of claim 8 or 9, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 2 as measured using Cu Kα. radiation.
The crystalline form of any one of claims 8-10, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 12.8 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, and 24.7 ± 0.2° 2θ as measured using Cu Kα. radiation.
The crystalline form of any one of claims 8-11, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 12.0 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, and 22.7 ± 0.2° 2θ as measured using Cu Kα. radiation.
The crystalline form of any one of claims 8-12, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 5.4 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.
The crystalline form of any one of claims 8-13, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 22.1 ± 0.2° 2θ and 25.1 ± 0.2° 2θ as measured using Cu Kα.radiation.
The crystalline form of any one of claims 8-10, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 5.4 ± 0.2° 2θ, 12.0 ± 0.2° 2θ, 12.8 ± 0.2° 2θ, 14.5 ± 0.2° 2θ, 21.6 ± 0.2° 2θ, 22.1 ± 0.2° 2θ, 22.7 ± 0.2° 2θ, 23.0 ± 0.2° 2θ, 24.7 ± 0.2° 2θ, 25.1 ± 0.2° 2θ, and 27.0 ± 0.2° 2θ as measured using Cu Kα. radiation.
The crystalline form of any one of claims 8-15, wherein the crystalline form is non hygroscopic.
The crystalline form of any one of claims 8-16, wherein the crystalline form is an anhydrate.
The crystalline form of any one of claims 8-17, wherein 0.0679%water uptake was detected at 80%relative humidity (RH) /25 ℃ in the sorption curve from 0%RH to 95%RH.
The crystalline form of claim 2, wherein the crystalline form is Compound 1 L-Arginine Salt Type A characterized as having at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 43 as measured using Cu Kα. radiation;

(b) an X-Ray powder diffraction (XRPD) pattern with peaks at 11.0 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, and 18.6 ± 0.2° 2θ as measured using Cu Kα. radiation;

(c) a Differential Scanning Calorimetry (DSC) thermogram substantially the same as shown in FIG. 44;

(d) a Thermogravimetric Thermal Analysis (TGA) thermogram substantially the same as shown in FIG. 45; or

(e) combinations thereof.
The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 43 as measured using Cu Kα. radiation.
The crystalline form of claim 19 or 20, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks found in Table 15 as measured using Cu Kα. radiation.
The crystalline form of any one of claims 19-21, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 11.0 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, and 18.6 ± 0.2° 2θ as measured using Cu Kα. radiation.
The crystalline form of any one of claims 19-22, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 6.1 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, and 15.3 ± 0.2° 2θ as measured using Cu Kα. radiation.
The crystalline form of any one of claims 19-23, wherein the X-ray powder diffraction (XRPD) pattern further comprises peaks at 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ± 0.2° 2θ as measured using Cu Kα. radiation.
The crystalline form of any one of claims 19-21, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern with peaks at 6.1 ± 0.2° 2θ, 11.0 ± 0.2° 2θ, 12.6 ± 0.2° 2θ, 13.7 ± 0.2° 2θ, 15.3 ± 0.2° 2θ, 18.6 ± 0.2° 2θ, 19.6 ± 0.2° 2θ, 20.5 ± 0.2° 2θ, and 21.7 ± 0.2° 2θ as measured using Cu Kα. radiation.
A pharmaceutical composition comprising a crystalline form of any one of claims 2-25, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.
A method of inhibiting a Lysine Acetyltransferase 6A (KAT6A) in a subject in need thereof, comprising administering to the subject a crystalline form of any one of claims 2-25, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 26.
A method of modulating Lysine Acetyltransferase 6A (KAT6A) activity in a subject in need thereof, comprising administering to the subject a crystalline form of any one of claims 2-25, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 26.
The method of claim 27 or 28, wherein the subject has cancer.
A method of treating cancer in a mammal in need thereof, comprising administering to the mammal a crystalline form of any one of claims 2-25, or a pharmaceutically acceptable salt thereof.
A method of treating cancer in a mammal in need thereof, comprising administering to the mammal a pharmaceutical composition of claim 26.
The method of any one of claims 29-31, wherein the cancer is selected from lung cancer, mesothelioma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, stomach cancer, hepatocellular carcinoma, colon cancer, breast cancer, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, Hodgkin’s disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, hematology malignancy, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS) , primary CNS lymphoma, spinal axis tumors, glioblastoma, brain stem glioma, pituitary adenoma, or a combination of two or more of the foregoing cancers.
The method of any one of claims 29-31, wherein the cancer is selected from ER-positive breast cancer, glioblastoma, non-small cell lung cancer (NSCLC) , small cell lung cancer (SCLC) , melanoma, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer (CRC) , hepatocellular carcinoma (HCC) , renal cell carcinoma (RCC) , leukemia, lymphoma or multiple myeloma, acute lymphocytic leukemia (ALL) , acute myeloid leukemia (AML) , chronic lymphocytic leukemia (CLL) , chronic myeloid leukemia (CML) , and non-Hodgkin’s lymphoma.
The method of any one of claims 29-31, wherein the cancer is a solid tumor with KAT6A/6B amplification or overexpression, or leukemia or solid tumor with KAT6A/6B fusion protein resulting from chromosomal translocation.