Polymorphic forms of KRAS inhibitors and uses thereof

Abstract

The present disclosure relates generally to polymorphic forms of a KRAS inhibitor, and more specifically to polymorphic forms of a pyridopyrimidine derivative, and uses thereof.

Description

POLYMORPHIC FORMS OF KRAS INHIBITORS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to and the benefit of International Patent Application No. PCT / CN2024 / 129736, filed November 4, 2024, the disclosure of which is hereby incorporated herein by reference in its entirety.FIELD

[0002] The present disclosure relates generally to polymorphic forms of a KRAS inhibitor, and more specifically to polymorphic forms of a pyridopyrimidine derivative, and uses thereofBACKGROUND

[0003] KRAS is a molecular switch. Under normal physiological conditions, the protein is bound to guanosine diphosphate (GDP) in the “off state.'’ In response to signaling through receptor tyrosine kinases (RTKs) such as EGFR, the GDP is exchanged to guanosine triphosphate (GTP) in a process facilitated by guanine nucleotide exchange factors (GEFs) such as SOS. The GTP -bound form of KRAS is in the “on state,” and interacts with proteins such as RAF and PI3K to promote downstream signaling that leads to cell proliferation and survival. KRAS can slowly hydrolyze GTP back to GDP, thus returning to the off-state, in a process facilitated by GAPs (GTPase-activating Proteins).

[0004] KRAS mutations are found in approximately 30% of all human cancers, and are highly prevalent among three of the deadliest forms of cancer: pancreatic (95%), colorectal (45%), and lung (35%). Together, these cancers occur in more than 200,000 patients annually in the US alone. One particular mutation, a glycine to cysteine substitution at position 12 (G12C), occurs in more than 40,000 patients per year. The KRAS G12C mutation impairs hydrolysis of GTP to GDP, thus trapping KRAS in the on-state and promoting cancer cell proliferation.

[0005] The cysteine residue of G12C provides an opportunity to develop targeted covalent drugs for this mutant KRAS. Early clinical trial results for KRAS G12C inhibitors AMG 510 and MRTX849 have shown encouraging results for non-small cell lung cancer (NSCLC), but the data are less compelling for colorectal cancer (CRC). Moreover, even incases where patients respond to initial treatment, there are signs that the response may be limited in duration and that resistance could arise rapidly.

[0006] Most inhibitors of KR AS mutants bind preferentially to the GDP-bound form of the protein. For example, Amgen KRAS inhibitor AMG 510 and Mirati KRAS inhibitor MRTX849 react with the GDP -bound form of KRAS G12C at least 1000-fold more rapidly than with the GTP-bound form of the protein. One form of resistance that has been observed is for cancer cells to increase signaling through RTKs, thus increasing the amount of GTP-bound KRAS, which is less affected by current inhibitors. Thus, creating a molecule that could bind to and inhibit both the GDP- and GTP-bound forms of KRAS could have substantial utility.

[0007] What is needed is a compound useful in the treatment of cancer, such as cancers characterized by KRAS G12C. What is further needed is a compound useful in the treatment of cancers characterized by KRAS G12C, wherein the compounds bind to and inhibit both the inactive GDP- and activated GTP-bound forms of KRAS. What is further needed is a compound useful in the treatment of cancers characterized by KRAS G12C, wherein the compound has improved inhibition of the GTP-bound form of KRAS G12C. What is further needed is a crystalline form of such compound.BRIEF SUMMARY

[0008] In one aspect, provided herein is a crystalline form of l-((2R,3R)-3-((7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l-yl)prop-2-en-l-one (Compound 1).

[0009] In some embodiments, the crystalline form is an anhydrate.

[0010] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form A substantially as shown in FIG. 1 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 10.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.4. In some embodiments, the crystalline form is characterized by having anXRPD pattern comprising peaks at angles 2 -theta of about 5.0, about 5.9, about 7.3, about 10.0, about 13.4, about 15.0, and about 16.4. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 199.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. IB. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. IB. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 1C.

[0011] In some embodiments, the crystalline form is a solvate.

[0012] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form E substantially as shown in FIG. 2A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 9.9, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 14.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 8.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 4.9, about 6.9, about 8.9, about 9.9, about 14.9, about 16.5, about 17.0, and about 18.3. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 188.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 2B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 2B.

[0013] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form B substantially as shown in FIG. 3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 8.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 6.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 6.8, about 8.5, and about 16.6.

[0014] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form C substantially as shown in FIG. 4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 8.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 4.2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 4.2, about 6.8, about 8.4, about 9.8, about 15.6, about 16.6, and about 16.8.

[0015] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form D substantially as shown in FIG. 5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 9.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 4.3, about 6.9, about 8.5, about 9.9, about 14.9, about 15.6, and about 16.5.

[0016] In some embodiments, the crystalline form is a salt.

[0017] In some embodiments, the crystalline form is a hydrochloride salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of hydrochloride salt Form A substantially as shown in FIG. 6A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 13.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 14.6. In some embodiments, the crystalline form is, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 11.6, about 12.0, about 13.0, about 13.4, about 14.3, about 14.6, about 15.7, about 16.5, about 16.8, about 17.5, about 18.5, and about 18.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 179.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising anexothermic peak at about 221.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 6B, In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 6B. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 6C.

[0018] In some embodiments, the crystalline form is a citrate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of citrate salt Form A substantially as shown in FIG. 7A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 4.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 9.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 6.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 4.9, about 6.4, about 7.8, about 9.6, about 11.5, about 12.1, about 12.8, about 13.5, about 14.6, about 15.3, about 15.8, about 17.0, about 17.4, about 18.1, and about 18.8. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 173.7 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 7B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 7B. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 7C.

[0019] In some embodiments, the crystalline form is a succinate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of succinate salt Form A substantially as shown in FIG. 8A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.3. In some embodiments, the crystalline form is, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 8.0, about 8.7, about 10.1, about 11.3, about 11.9, about 15.1, about 15.9, about 17.0, about 18.1, and about 18.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprisingan endothermic peak at about 146.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 159.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG, 8B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 8B. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 8C. In some embodiments, the crystalline form is characterized by having an XRPD pattern of succinate salt Form B substantially as shown in FIG. 8A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11,1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 5.9, about 7.8, about 8.8, about 10.1, about 11.1, about 11.9, about 15.6, about 16.8, about 17.9, and about 19.0. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 145.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 157.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG, 8D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 8D. In some embodiments, the crystalline form is characteri zed by having an XRPD pattern of succinate salt Form C substantially as shown in FIG. 8A. In some embodiments, the crystalline form is, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.7, about 8.9, about 10.2, about 10.9, about 12.0, about 15.5, about 17.0, about 18.1, about 19.0, about 20.5, about 22.0, about 22.9, about 23.4, about 24.6, about 26.0, about 27.4, and about 29.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 140.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 157.9 °C. In someembodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 8E, In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 8E.

[0020] In some embodiments, the crystalline form is a tartrate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of tartrate salt Form A substantially as shown in FIG. 9 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.5, about 7.6, about 8.8, about 9.4, about 10.0, about 11.3, about 12.5, about 14.2, about 15.3, about 16.3, about 19.6, about 20.0, about 21.1, about 22.1, and about 22.8. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 52.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 170.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 9B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 9B.

[0021] In some embodiments, the crystalline form is a fumarate salt. In some embodiments, the crystalline form is characterized by ha ving an XRPD pattern of fumarate salt Form A substantially as shown in FIG. 10 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 7.8, about 9.3, about 11.0, about 12.3, about 15.7, about 22.5, and about 23.0. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 170.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graphsubstantially as shown in FIG. 10B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. I OB, In some embodiments, the crystalline form is characterized by having an XRPD pattern of fumarate salt Form B substantially as shown in FIG. 10A, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 5.8, about 7.8, about 8.9, about 11.0, about 12.0, about 15.5, about 16.9, and about 18.1. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 171.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 10C. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 10C. In some embodiments, the crystalline form is characterized by having an XRPD pattern of fumarate salt Form C substantially as shown in FIG. 10A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 6.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.5, about 6.8, about 7.9, about 9.7, about 11.0, about 11.7, about 13.1, about 15.3, about 15.9, about 16.8, and about 18.9. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 57.1 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 167.7 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 10D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 10D.

[0022] In some embodiments, the crystalline form is a malate salt. In some embodiments, the crystalline form is characteri zed by having an XRPD pattern of malate salt Form A substantially as shown in FIG. 11 A. In some embodiments, the crystalline form ischaracterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 13.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 6.3, about 7.3, about 7.9, about 9.1, about 13.6, about 15.1, about 15.9, about 16.7, and about 18.1. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 145.7 °C, In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 161.4 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 11B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 11B. In some embodiments, the crystalline form is characterized by having an XRPD pattern of salt Form B substantially as shown in FIG. 11 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.4, about 8.9, about 11.2, and about 15.0. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 49.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 113.4 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 162.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 11C. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 11C. In some embodiments, the crystalline form is characterized by having an XRPD pattern of salt Form C substantially as shown in FIG. 11 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.9. In some embodiments, the crystalline form is characterized by having an XRPD patterncomprising a peak at angle 2 -theta of about 15.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.9, about 8.9, about 11.1, about 15.1, about 15.7, about 17.2, and about 18.3. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 144.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 158.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 11D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 1 I D.

[0023] In some embodiments, the crystalline form is an adipate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of adipate salt Form A substantially as shown in FIG. 12. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 10.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 4.3, about 5.0, about 5.9, about 7.3, about 8.5, about 9.2, about 10.1, about 13.7, about 15.1, about 16.5, and about 17.0.

[0024] In some embodiments, the crystalline form is a napadisylate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of napadisylate salt Form A substantially as shown in FIG. 13A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 19.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 7.3, about 15.4, and about 19.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 56.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 160.0 °C. In some embodiments, the crystalline form is characterized by having a DSCgraph comprising an exothermic peak at about 257.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 13B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG, 13B. In some embodiments, the crystalline form is characterized by having an XRPD pattern of napadisylate salt Form B substantially as shown in FIG. 13 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.6. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 49.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 137.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 201.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 13C. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 13C. In some embodiments, the crystalline form is characterized by having an XRPD pattern of napadisylate salt Form C substantially as shown in FIG. 13 A. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 50.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 125.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 265.7 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 13D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 13D.

[0025] In some embodiments, the crystalline form is a tosylate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of tosylate salt Form A substantially as shown in FIG. 14A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 12.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.2, about 7.4, about 8.6, about 10.0, about 11.3, about 12.1, about 13.2, about 14.4, about 14.9, about 15.5, about 17.3, and aboutIl18.3. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 138.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 214.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 14B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 14B.

[0026] In some embodiments, the crystalline form is a mesylate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of mesylate salt Form A substantially as shown in FIG. 15 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 9.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.4, about 9.8, and about 17.5. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 222.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 15B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 15B.

[0027] In some embodiments, the crystalline form is an oxalate salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of oxalate salt Form A substantially as shown in FIG. 16 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 14.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.7, about 10.0, about 11.6, about 14.6, about 15.0, about 15.5, about 16.4, about 17.2, about 18.1, and about 18.8. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 82.4 °C. In some embodiments, the crystalline form ischaracterized by having a DSC graph comprising an exothermic peak at about 174.0 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 16B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 16B.

[0028] In some embodiments, the crystalline form is a hydrobromide salt. In some embodiments, the crystalline form is characterized by having an XRPD pattern of hydrobromide salt Form A substantially as shown in FIG. 17A. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 21.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 12.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 11.6, about 12.9, about 18.2, and about 21.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 57.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 215.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 17B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 17B.

[0029] In some embodiments, the purity of the crystalline form is at least about 95%.

[0030] In one aspect, provided is a pharmaceutical composition comprising a crystalline form provided herein, and a pharmaceutically acceptable excipient.

[0031] In one aspect, provided is a method of treating cancer in a subject in need thereof. In some embodiments, the method comprises administering a therapeutically effective amount of the crystalline form or the pharmaceutical composition provided herein to the subject. In some embodiments, the cancer is a lung, colorectal, pancreatic, bile duct, thyroid, gall bladder, uterine, mesothelioma, cervical, orbladder cancer. In some embodiments, the cancer is glioblastoma multiforme, lower grade glioma, head and neck squamous cell carcinoma, papillary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, breast invasive carcinoma, esophageal carcinoma, stomach adenocarcinoma, small intestineadenocarcinoma, colon adenocarcinoma, rectal adenocarcinoma, liver hepatocellular carcinoma, cholangiocarcinoma, gallbladder carcinoma, pancreatic adenocarcinoma, kidney renal clear cell carcinoma, bladder urothelial carcinoma, prostate adenocarcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, cervical squamous carcinoma and endocervical adenocarcinoma, skin cutaneous melanoma, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, plasma cell myeloma, uterine carcinosarcoma, mesothelioma, adrenocortical carcinoma, brain lower grade glioma, diffuse large B-cell lymphoma, esophageal adenocarcinoma, kidney chromophobe, kidney renal papillary cell carcinoma, pheochromocytoma and paraganglioma, sarcoma, testicular germ cell tumors, thymoma, uveal melanoma, metastatic colorectal cancer, bladder cancer, adenoid cystic carcinoma, myelodysplastic, breast cancer, thyroid carcinoma, glioma, esophageal / stomach cancer, pediatric Wilms’ tumor, pediatric acute lymphoid leukemia, chronic lymphocytic leukemia, mature B-cell malignancies, pediatric neuroblastoma, non-small cell lung cancer (NSCLC), or melanoma. In some embodiments, the cancer is a non-small cell lung cancer (NSCLC). In some embodiments, the cancer is a KRAS G12C mediated cancer. In some embodiments, the subject has been diagnosed as having a KRAS G12C mediated cancer. In some embodiments, the subject is human.In one aspect, provided is a method of preparing a crystalline form provided herein. In some embodiments, the method comprises: (i) contacting Compound 1 with a first solvent to form a mixture; and (ii) adding a second solvent to the mixture of step (i) to form the crystalline form of Compound 1. In some embodiments, the first solvent comprises 2-methyltetrahydrofuran. In some embodiments, the second solvent comprises diisopropylether. In some embodiments, the mixture of step (i) is heated prior to step (ii). In some embodiments, the mixture is heated to at least about 40°C. In some embodiments, the mixture is heated to at least about 50°C. In some embodiments, the mixture is heated to at least about 60°C. In some embodiments, the mixture is heated to about 60°C. In some embodiments, the second solvent is added to the mixture of step (i) in step (ii) at room temperature. In some embodiments, the second solvent is added to the mixture of step (i) in step (ii) at about 25°C.

[0032] In some embodiments, the method comprises: (i) placing a sample comprising a solid form of Compound 1 in a first container; (ii) placing the first container of step (i) insidea second container containing a solvent; and (iii) allowing vapor from the solvent to interact with the sample in the first container. In some embodiments, the sample of step (i) comprises freebase Form A. In some embodiments, step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container at a room temperature and for a duration of about 7 days. In some embodiments, the solvent comprises EtOH, MIBK, EtOAc, MTBE, 2-MeTHF, 1,4-Dioxane, acetonitrile, toluene, IP A, water, or DMSO, or any mixture thereof. In some embodiments, the solvent comprises EtOH, MIBK, EtOAc, MTBE, 2-MeTHF, acetonitrile, toluene, IP A, water, or DMSO, or any mixture thereof, and the cry stall ine form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises 1,4-dioxane and the crystalline form prepared from the method comprises freebase Form E. In some embodiments, step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container for the duration of about 19 days.

[0033] In some embodiments, the method comprises: (i) dissolving Compound 1 in a first solvent in a first container; (ii) placing the first container of step (i ) inside a second container containing a second solvent; (iii) sealing the second container of step (ii); (iv) allowing vapor of the second solvent to interact with Compound 1 in the first container to form precipitant; and (v) isolating the precipitant of step (iv) from the first solvent and / or the second solvent. In some embodiments. Compound 1 of step (i) comprises freebase Form A. In some embodiments, step (iv) comprises allowing vapor of the second solvent to interact with Compound 1 in the first container at room temperature. In some embodiments, isolating the precipitant in step (v) comprises evaporating the first solvent and / or the second solvent at room temperature. In some embodiments, the first solvent comprises MeOH, NMP, 1,4-dioxane, EtOH, acetone, EtOAC, DMAc, DCM, 2-MeTHF, CHCh, acetonitrile, or DMSO, or a mixture thereof, and the second solvent comprises MTBE, n-Heptane, water, or toluene, or any mixture thereof. In some embodiments, the first solvent comprises EtOH, EtOAC, 2-MeTHF, CHCh, acetonitrile, or 1,4-dioxane, or any mixture thereof, and the second solvent comprises MTBE, n-Heptane, or toluene, or a mixture thereof, and the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the first solvent comprises acetone, the second solvent comprises MTBE, and the crystalline form prepared from the method comprises freebase Form C. In some embodiments, the the first solvent comprises DCM, the second solvent comprises MTBE, and the crystalline form prepared from the method comprises freebase Form D. In some embodiments, the firstsolvent comprises MeOH, 1,4-di oxane, or EtOH, or any mixture thereof, the second solvent comprises water or n-heptane, or any mixture thereof and the crystalline form prepared from the method is amorphous. In some embodiments, the first solvent comprises NMP, DMAc, or DMSO, or any mixture thereof, the second solvent comprises water, MTBE, or toluene, or any mixture thereof, and the crystalline form prepared from the method comprises an oil.

[0034] In some embodiments, the method comprises: (i) preparing a suspension of Compound 1 in a solvent; (ii) heating the suspension of step (i) to a first temperature; (iii) filtering the suspension of step (ii ) to obtain filtrate; (iv) cooling the filtrate of step (iii) to a second temperature. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, the first temperature is about 50°C. In some embodiments, the second temperature is about 5°C or about -20°C. In some embodiments, the temperature of the filtrate in step (iv) is changed at a rate of about 0.1°C / min. In some embodiments, the method further comprises evaporating the solvent at room temperature. In some embodiments, the solvent comprises IP A, IP Ac, MIBK, acetonitrile, MTBE, 2-MeTHF, EtOH, or n-heptane, or any mixture thereof In some embodiments, the solvent comprises IP A, IP Ac, MIBK, a mixture of EtOH and n-Heptane at a volume ratio of about 1: 1, or any mixture thereof, wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a mixture of acetonitrile and MTBE at a volume ratio of about 1:1, or 2-MeTHF, or any mixture thereof, wherein the crystalline form prepared from the method is amorphous.

[0035] In some embodiments, the method comprises: (i) preparing a suspension of Compound 1 in solvent; and (ii) stirring the suspension of step (i) at a temperature for a duration. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, a solid forms from the suspension after step (ii), and the method further comprises centrifuging the suspension of step (ii) to isolate the solid. In some embodiments, the temperature is room temperature. In some embodiments, the duration is between about 2 days and about 6 days. In some embodiments, the solvent comprises EtOH, MTBE, acetone, water, EtOAc, MTBE, acetonitrile, THF, n-Heptane, toluene, DCM, 1,4-Dioxane, MeOH, DMSO, DMAc, or IP A, or any mixture thereof. In some embodiments, the solvent comprises a mixture of EtOH and MTBE at a volume ratio of about 1:9; a mixture of acetone and water at a volume ratio of about 1:9; a mixture of EtOAc and MTBE at a volume ratio of about 1:4; MTBE; a mixture of acetonitrile and water at a volume ratio ofabout 1:9; a mixture of THF and n -Heptane at a volume ratio of about 1:9; toluene; water; a mixture of DCM and MTBE at a volume ratio of about 1:9; a mixture of 1,4-di oxane and toluene at a volume ratio of about 1:9; a mixture of DMSO and water at a volume ratio of about 1:9; a mixture of DMAc and toluene at a volume ratio of about 1:9; a mixture of IPA and water at a volume ratio of about 98:2, 96:4, 92.8, or 85:15, wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a mixture of MeOH and toluene at a volume ratio of about 1:9, wherein the crystalline form prepared from the method comprises freebase Form B. In some embodiments, the temperature is between about 40°C and about 60°C, and the duration is between about 1 day and about 5 days. In some embodiments, the solvent comprises MeOH, toluene, MIBK, n-Heptane, IP Ac, MTBE, CIICI3, water, 2-MeTHF, 1,4-di oxane, acetonitrile, THF, NMP, or DMSO, or any mixture thereof. In some embodiments, the solvent comprises a mixture of MIBK and n-Heptane at a volume ratio of about 1:2; a mixture of IP Ac and MTBE at a volume ratio of about 1:2; water; n-Heptane; a mixture of 2-MeTHF and MTBE at a volume ratio of about 1:4; a mixture of 1,4-dioxane and n-Heptane at a volume ratio of about 1:9; a mixture of acetonitrile and toluene at a volume ratio of about 1:4; a mixture of THF and toluene at a volume ratio of about 1:9; a mixture of NMP and water at a volume ratio of about 1:9; a mixture of DM SO and toluene at a volume ratio of about 1:4; wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a mixture of MeOH and toluene at a volume ratio of about 1:9; a mixture of CHCh and toluene at a volume ratio of about 1: 4; wherein the crystalline form prepared from the method is amorphous.

[0036] In some embodiments, the method comprises: (i) preparing a suspension of Compound 1 in a solvent; (ii) heating the suspension to a first temperature and cooling the suspension to a second temperature; and (iii) heating the suspension to a third temperature, and cooling the suspension to a fourth temperature. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, a solid forms from the suspension after step (iii), and the method further comprises centrifuging the suspension of step (iii) to isolate the solid. In some embodiments, the first temperature and the third temperature are each independently in between about 40°C and about 50°C, and the second temperature and the fourth temperature are each independently in between about 0°C and about 10°C. In some embodiments, the heating and cooling of steps (ii) and (iii) are each independently conducted at a rate of between about 0.01 °C / min and about 1 °C / min. Insome embodiments, the solvent comprises MeOH, MTBE, EtOH, water, acetonitrile, EtOAc, n-Heptane, 2-MeTHF, acetone, toluene, IP Ac, DM Ac, NMP, or CHCI3, or any mixture thereof. In some embodiments, the solvent comprises a mixture of MeOH and MTBE at a volume ratio of 1:9; a mixture of EtOH and water at a volume ratio of 1:9; a mixture of acetonitrile and MTBE at a volume ratio of about 1:9; a mixture of EtOAc and n-Heptane at a volume ratio of about 1:4; 2-MeTHF; a mixture of acetone and toluene at a volume ratio of about 1:4; IP Ac; water; MTBE; a mixture of DMAc and water at a volume ratio of about 1:9; a mixture of NMP and MTBE at a volume ratio of about 1:9; a mixture of CIICI3 and MTBE at a volume ratio of about 1:4; wherein the crystalline form prepared from the method comprises freebase Form A.

[0037] In some embodiments, the method comprises: (i) dissolving Compound 1 in a solvent; and (ii) evaporating the solvent of step (i) at a temperature. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, the temperature of step (ii) is room temperature. In some embodiments, the solvent comprises MeOH, EtOH, acetonitrile, acetone, EtOAc, 2-MeTHF, DCM, THF, or water, or any mixture thereof. In some embodiments, the solvent comprises EtOH; acetonitrile; EtOAc; 2-MeTHF; wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a MeOH; acetone; DCM; a mixture of THF and water at a volume ratio of about 9: 1, wherein the crystalline form prepared from the method is amorphous.

[0038] In some embodiments, the method comprises grinding Compound 1. In some embodiments, Compound I comprises freebase Form A, In some embodiments, the method further comprises contacting Compound 1 with a solvent while grinding. In some embodiments, the solvent comprises water. In some embodiments, the crystalline form prepared from the method comprises freebase Form A.

[0039] In some embodiments, the method comprises: (i) adding Compound 1 to a solvent to form a first mixture; and (ii) adding an anti-solvent to the first mixture to form a second mixture. In some embodiments, Compound I of step (i) comprises freebase Form A. In some embodiments, the anti-solvent is added until a precipitate is produced. In some embodiments, the method further comprises cooling the second mixture to a cooling temperature. In some embodiments, the cooling temperature is between about -25°C and about 10°C. In some embodiments, the method further comprises evaporating the solventand the antisolvent from the second mixture at an evaporation temperature. In some embodiments, the evaporation temperature is room temperature. In some embodiments, the solvent comprises acetone, MeOH, THF, acetonitrile, DMSO, EtOH, EtOAc, 1,4-Dioxane, 2-MeTHF, CHCI3, DMAc, or DCM, or any mixture thereof; and the anti-solvent comprises water, n-Heptane, MTBE, or toluene, or any mixture thereof. In some embodiments, the solvent comprises acetone, THF, EtOH, EtOAc, THF, 1,4-dioxane, MeOH, 2-MeTHF, acetonitrile, CHCI3, DMAc, or DCM, or any mixture thereof, and the anti-solvent comprises water, n-Heptane, MTBE, or toluene; wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises MeOH, acetonitrile, or DMSO, and the anti-solvent comprises water; wherein the crystalline form prepared from the method is amorphous.

[0040] In some embodiments, the method comprises: (i) stirring Compound I in a solution for a duration; (ii) centrifuging the mixture of step (i); and (iii) drying the precipitant of step (ii) at a temperature. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, the solution comprises HC1 in IP A; L-tartaric acid in IP A; fumaric acid in IP A and MIBK, or fumaric acid in IP Ac; citric acid in acetone; malic acid in IPA and acetonitrile; malic acid in IP / Xc, succinic acid in IPA and MIBK; succinic acid in 2-MeTHF; adipic acid in 2-MeTHF; 1,5-naphthalenedisulfonic acid in IPA; MIBK and acetonitrile; p-toluenesulfonic acid in IP Ac; methanesulfonic acid in MIBK; oxalic acid in MIBK; or HBr in MIBK. In some embodiments, the method further comprises stirring the mixture of step (i) at a temperature between about 0°C and about 10°C for a duration before centrifugation in step (ii). In some embodiments, the duration is between 12 and 36 hours. In some embodiments, the method further comprises heatingcooling the mixture of step (i) before centrifugation in step (ii). In some embodiments, the mixture is heated to between about 40°C and about 50°C, and cooled to between about 0°C and about I0°C. In some embodiments, the heating and cooling are each independently conducted at a rate of between about 0.01 °C / min and about 1 °C / min. In some embodiments, the duration in step (i) is between 1 and 5 days. In some embodiments, the temperature of step (iii) is room temperature.BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The present application can be understood by reference to the following description taken in conjunction with the accompanying figures.

[0042] FIGS. 1A-1T depict XRPD data (FIG. 1 A); TGA and DSC data (FIG. 1B); DVS data (FIG. 1C); ¹H NMR spectrum in DMSO-d6 (FIG. 1D); ¹H NMR spectrum in MeOD (FIG. 1E); SEM imaging (FIG. 1G); XRPD overlay before and after grinding (FIG. 1H); XRPD overlay before and after DVS (FIG. II); XRPD overlay of after stability test (FIG. 1J); HPLC overlay of after stability evaluation (FIG. 1K); XRPD overlay of after equilibrium solubility test (FIG. 1L); XRPD overlay of after tableting (FIG. 1M); XRPD overlay of tableted stability evaluation (FIG. 1N); HPLC overlay of tableted stability evaluation (FIG.10); XRPD overlay of grinding experiments (FIG. IP); XRPD overlay of after solubility in H2O (FIG. 1Q); XRPD overlay of after solubility inFaSSIF (FIG. 1R); XRPD overlay of after solubility in FeSSIF (FIG. IS); and XRPD overlay of after dissolution test (FIG. IT) of freebase Form A of Compound 1.

[0043] FIG. 1U depicts XRPD overlay of freebase Forms A, B, C, D, and E of Compound 1.

[0044] FIGS. 2A and 2B depict XRPD data (FIG. 2A) and TGA and DSC data (FIG. 2B) of freebase Form E of Compound 1.

[0045] FIG. 3 depicts XRPD data of freebase Form B of Compound 1.

[0046] FIG. 4 depicts XRPD data of freebase Form C of Compound 1.

[0047] FIG. 5 depicts XRPD data of freebase Form D of Compound 1.

[0048] FIGS. 6A-6C depict XRPD data (FIG. 6A); TGA and DSC data (FIG. 6B); and DVS data (FIG. 6C) of HCl salt Form A of Compound 1.

[0049] FIGS. 7A-7C depict XRPD data (FIG. 7A); TGA and DSC data (FIG. 7B); and DVS data (FIG. 7C) of citrate salt Form A of Compound 1.

[0050] FIGS. 8A-8E depict XRPD data (FIG. 8A); TGA and DSC data (FIG. 8B) of Form A; DVS data (FIG. 8C) of Form A; TGA and DSC data of Form B (FIG. 8D); and TGA and DSC data of Form C (FIG. 8E) of succinate salt of Compound 1.

[0051] FIGS. 9A and 9B depict XRPD data (FIG. 9A) and TGA and DSC data (FIG. 9B) of tartrate salt Form A of Compound 1.

[0052] FIGS. 10A-10D depict XRPD data (FIG. 10A); TGA and DSC data of Form A (FIG. 10B); TGA and DSC data of Form B (FIG. 10C); and TGA and DSC data of Form C (FIG. 10D) of fumarate salt of Compound 1.

[0053] FIGS. 11A-11D depict XRPD data (FIG. 11 A); TGA and DSC data of Form A (FIG. 11B); TGA and DSC data of Form B (FIG. 11C); and TGA and DSC data of Form C (FIG. 11D) of malate salt of Compound 1.

[0054] FIG. 12 depicts XRPD data of re-prepared adipate salt Form A of Compound 1.

[0055] FIGS. 13A-13D depict XRPD data (FIG. 13A); TGA and DSC data of Form A (FIG. 13B); TGA and DSC data of Form B (FIG. 13C); and TGA and DSC data of Form C (FIG. 13D) of napadisylate salt of Compound 1.

[0056] FIGS. 14A and 14B depict XRPD data (FIG. 14A) and TGA and DSC data (FIG.14B) of tosylate salt Form A of Compound I.

[0057] FIGS. 15A and 15B depict XRPD data (FIG. 15 A) and TGA and DSC data (FIG.15B) of mesylate salt Form A of Compound 1.

[0058] FIGS. 16A and 16B depict XRPD data (FIG. 16A) and TGA and DSC data (FIG.16B) of oxalate salt Form A of Compound 1.

[0059] FIGS. 17A and 17B depict XRPD data (FIG. 17 A) and TGA and DSC data (FIG.17B) of HBr salt Form A of Compound 1.

[0060] FIG. 18A depicts VT-XRPD data of freebase Form A.

[0061] FIGS. 18B and 18C depict kinetic solubility (FIG. 18B) and two-stage dissolution in SGF-FaSSIF (FIG. 18C) of freebase Form A, HC1 salt Form A, citrate salt Form A, and succinate salt Form A of Compound I.

[0062] FIGS. 19A-19C depict1H NMR spectrum in 1,4-Dioxane (FIG. 19A); XRPD overlay of before and after heating (FIG. 19B); and1H NMR spectrum in 1,4-Dioxane after heating to 120 °C of freebase Form E of Compound 1.

[0063] FIG. 20 depicts XRPD pattern of freebase Form B of Compound I.

[0064] FIGS. 21A and 21B depict XRPD patterns of prepared (FIG. 21A) and reprepared (FIG. 21B) freebase Form C of Compound I.

[0065] FIGS. 22A and 22B depict XRPD patterns of prepared (FIG. 22A) and reprepared (FIG. 22B) freebase Form D of Compound 1.

[0066] FIGS. 23A-23T depict1H NMR spectrum (FIG. 23 A); PLM imaging (FIG. 23B); SEM imaging (FIG. 23C); XRPD overlay before and after DVS (FIG. 23D); XRPD overlay of after stability test (FIG. 23E); HPLC overlay of after stability evaluation (FIG. 23 F); XRPD overlay of after equilibrium solubility test (FIG. 23 G); XRPD overlay before and after grinding (FIG. 23H); XRPD overlay of after tableting (FIG. 231); XRPD overlay of tableted stability evaluation (FIG. 23J); HPLC overlay of tableted stability evaluation (FIG. 23K); XRPD data (FIG. 23L); TGA and DSC data (spectrum (FIG. 23N); PLM imaging (FIG. 230); XRPD overlay of after solubility in H2O (FIG. 23P); XRPD overlay of after solubility in SGF (FIG. 23Q); XRPD overlay of after solubility in FaSSIF (FIG. 23R); XRPD overlay of after solubility in FeSSIF (FIG. 23 S); and XRPD overlay after dissolution test (FIG. 23T) of HC1 salt Form A of Compound 1.

[0067] FIGS. 24A-24R depict1H NMR spectrum in MeOD (FIG. 24A); PLM imaging (FIG. 24B); SEM imaging (FIG. 24C); XRPD overlay before and after DVS (FIG. 24D); XRPD overlay of after stability test (FIG. 24E); HPLC overlay of after stability evaluation (FIG. 24F); XRPD overlay before and after grinding (FIG. 24G); XRPD overlay of after tableting (FIG. 24H); XRPD overlay of tableted stability evaluation (FIG. 241); HPLC overlay of tableted stability evaluati on (FIG. 24J); XRPD data (FIG. 24K); TGA and DSC data (FIG.24L); ’H NMR spectrum (FIG. 24M); PLM imaging (FIG. 24N); XRPD overlay of after solubility in H2O (FIG. 240); XRPD overlay of after solubility in FaSSIF (FIG. 24P); XRPD overlay of after solubility in FeSSIF (FIG. 24Q); and XRPD overlay after dissolution test (FIG. 24R) of citrate salt Form A of Compound 1.

[0068] FIGS. 25A-25H depict XRPD data (FIG. 25A);1H NMR spectrum (FIG. 25B); PLM imaging (FIG. 25C); SEM imaging (FIG. 25D); XRPD overlay before and after DVS (FIG. 25E); XRPD overlay of after stability test (FIG. 25F); HPLC overlay of after stability evaluation (FIG. 25G); and XRPD overlay before and after grinding (FIG. 25H) of succinate salt Form A of Compound 1.

[0069] FIGS. 251-250 depict TGA / DSC data of Form A (FIG. 251); ’H NMR spectrum of Form A (FIG. 25 J); PLM imaging of Form A (FIG. 25K);1H NMR spectrum of Form B (FIG. 25L); PLM imaging of Form B (FIG. 25M);1H NMR spectrum of Form C (FIG. 25N); and PLM imaging of Form C (FIG. 250) of succinate salt Form A of Compound 1.

[0070] FIGS. 25P-25R depict XRPD overlay of after solubility in FaSSIF (FIG. 25P); XRPD overlay of after solubility in FeSSIF (FIG. 25Q); and XRPD overlay after dissolution test (FIG. 25R) of succinate salt Form A of Compound 1.

[0071] FIGS. 26A and 26B depict ’H NMR spectrum (FIG. 26 A) and PLM imaging (FIG.26B) of tartrate salt Form A of Compound 1.

[0072] FIGS. 27A-27F depict ’H NMR spectrum of Form A (FIG. 27A); PLM imaging of Form A (FIG. 27B); ’H NMR spectrum of Form B (FIG. 27C); PLM imaging of Form B (FIG. 27D);1H NMR spectrum of Form C (FIG. 27E); and PLM imaging of Form C (FIG.27F) of fumarate salt of Compound 1.

[0073] FIGS. 28A-28F depict1H NMR spectrum of Form A (FIG. 28A); PLM imaging of Form A (FIG. 28B); ’H NMR spectrum of Form B (FIG. 28C); PLM imaging of Form B (FIG. 28D);1H NMR spectrum of Form C (FIG. 28E); and PLM imaging of Form C (FIG.28F) of malate salt of Compound 1.

[0074] FIG. 29 depicts the XRPD pattern of potential adipate.

[0075] FIGS. 30A-30F depict ’H N R spectrum of Form A (FIG. 30A); PLM imaging of Form A (FIG. 30B);1H NMR spectrum of Form B (FIG. 30C); PLM imaging of Form B (FIG. 30D); ’H NMR spectrum of Form C (FIG. 30E); and PLM imaging of Form C (FIG.30F) of napadisylate salt of Compound 1.

[0076] FIGS. 31A-31B depict ’ll NMR spectrum (FIG. 31 A) and PLM imaging (FIG.3 IB) of tosylate salt Form A of Compound 1.

[0077] FIGS. 32A-32B depict1H NMR spectrum (FIG. 32A) and PLM imaging (FIG.32B) of mesylate salt Form A of Compound 1.

[0078] FIGS. 33A-33B depict ’H NMR spectrum (FIG. 33 A) and PLM imaging (FIG.33B) of oxalate salt Form A of Compound 1.

[0079] FIGS. 34A-34B depict NMR spectrum (FIG. 34A) and PLM imaging (FIG.34B) of HBr salt Form A of Compound 1.DETAILED DESCRIPTION

[0080] The following description sets forth exemplary methods, parameters and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments.I. Definitions

[0081] As used herein, the following definitions shall apply unless otherwise indicated. Further, if any term or symbol used herein is not defined as set forth below, it shall have its ordinary meaning in the art.

[0082] As used herein, reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X”. As used herein, and unless otherwise specified, the terms “about” and “approximately,” when used in connection with doses, amounts, or weight percent of ingredients of a composition or a dosage form, mean a dose, amount, or weight percent that is recognized by those of ordinary skill in the art to provide a pharmacological effect equivalent to that obtained from the specified dose, amount, or weight percent. Specifically, the terms “about” and “approximately,” when used in this context, contemplate a dose, amount, or weight percent within 20%, within 15%, within 10%, within 5%, within 4%, within 3%, within 2%, within 1%, or within 0.5% of the specified dose, amount, or weight percent.

[0083] As used herein, the term “crystalline form” refers to a crystalline solid form of a chemical compound, including, but not limited to, a single-component or multiplecomponent crystal form, e.g., a polymorph of a compound. The term “crystal forms” and related terms herein refer to the various crystalline modifications of a given substance, including, but not limited to, anhydrates and solvates thereof. Crystal forms of a substance can be obtained by a number of methods, as known in the art. Such methods include, but are not limited to, melt recrystallization, melt cooling, solvent recrystallization, slurrying, recrystallization in confined spaces such as, e.g., in nanopores or capillaries, recrystallizationon surfaces or templates such as, e.g., on polymers, recrystallization in the presence of additives, such as, e.g., anti-solvents, co-crystal counter-molecules, desolvation, dehydration, rapid evaporation, rapid cooling, slow cooling, vapor diffusion, sublimation, grinding and solvent-drop grinding.

[0084] As used herein, “solvate” encompasses solvates, partial solvates, and channel solvates. As such, a solvate need not contain an exact stoichiometric ratio ofcompound solvent, but may include ratios of compound: solvent permitted by experimental variance. The term “solvate” is further intended to include aqueous and non-aqueous solvated forms (e.g., hydrates, ethanolates, etc.). Thus, it is understood that a solvate encompasses stoichiometric solvates, channel solvates and partial solvates. It is also understood that a hydrate encompasses stoichiometric hydrates, channel hydrates and partial hydrates.

[0085] As used herein, the term “substantially as shown in” when referring, for example, to an XRPD pattern, a DSC graph, a TGA graph, or a GVS graph, includes a pattern or graph that is not necessarily identical to those depicted herein, but that falls within the limits of experimental error or deviations when considered by one of ordinary skill in the art.

[0086] The term “excipient” as used herein means an inert or inactive substance that may be used in the production of a drug or pharmaceutical, such as a tablet containing a compound of the present disclosure as an active ingredient. Various substances may be embraced by the term excipient, including without limitation any substance used as a binder, disintegrant, coating, compression / encapsulation aid, cream or lotion, lubricant, solutions for parenteral administration, materials for chewable tablets, sweetener or flavoring, suspending / gelling agent, or wet granulation agent.

[0087] The terms “individual”, “subject” and “patient” refer to mammals and includes humans and non-human mammals. Examples of patients include, but are not limited to, mice, rats, hamsters, guinea pigs, pigs, rabbits, cats, dogs, goats, sheep, cows, and humans. In some embodiments, patient refers to a human.

[0088] As used herein, the term “mammal” includes, but is not limited to, humans, mice, rats, guinea pigs, monkeys, dogs, cats, horses, cows, pigs, and sheep.

[0089] “Pharmaceutically acceptable” refers to safe and non-toxic, and suitable for in vivo or for human administration.

[0090] The compounds of the present disclosure can also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the present disclosure also embraces isotopically-labeled variants of the present disclosure which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having the atomic mass or mass number different from the predominant atomic mass or mass number usually found in nature for the atom. All isotopes of any particular atom or element as specified are contemplated within the scope of the compounds of the present disclosure and include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine and iodine, such as2H (“D”),3H,11C,13C,14C,13N,15N,15O,17O,18O,32P,33P,35S,18F,36C1,123I and123I. Certain isotopically labeled compounds of the present disclosure (e.g., those labeled with3H or14C) are useful in Compound 1 and / or substrate tissue distribution assays. Tritiated (3H) and carbon- 14 (14C) isotopes are useful for their ease of preparation and detectability. Substitution with heavier isotopes such as deuterium (i.e.,2H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances. Positron emitting isotopes such as15O,13N,11C, and18F are useful for positron emission tomography (PET) studies to examine substrate receptor occupancy. Isotopically labeled compounds of the present disclosure can generally be prepared by following procedures analogous to those disclosed in the Schemes and / or in the Examples herein below, by substituting an isotopically labeled reagent for a non-isotopically labeled reagent.

[0091] “Treating” or “treatment” of a disease in a patient refers to inhibiting the disease or arresting its development; or ameliorating or causing regression of the disease. As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. For purposes of this disclosure, beneficial or desired results include, but are not limited to, one or more of the following: decreasing one more symptoms resulting from the disease or disorder, diminishing the extent of the disease or disorder, stabilizing the disease or disorder (e.g., preventing or delaying the worsening of the disease or disorder), delaying the occurrence or recurrence of the disease or disorder, delay or slowing the progression of the disease or disorder, ameliorating the disease or disorder state,providing a remission (whether partial or total) of the disease or disorder, decreasing the dose of one or more other medications required to treat the disease or disorder, enhancing the effect of another medication used to treat the disease or disorder, delaying the progression of the disease or disorder, increasing the quality of life, and / or prolonging survival of a patient. Also encompassed by “treatment” is a reduction of pathological consequence of the disease or disorder. The methods of the present disclosure contemplate any one or more of these aspects of treatment.

[0092] “Preventing”, “prevention”, or “prophylaxis” of a disease in a patient refers to preventing the disease from occurring in a patient that is predisposed or does not yet display symptoms of the disease.

[0093] The phrase “therapeutically effective amount” means an amount of a compound of the present disclosure that (i) treats or prevents the particular disease, condition, or disorder, (ii) attenuates, ameliorates, or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition, or disorder described herein.

[0094] The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth.

[0095] It is appreciated that certain features of the present disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.II. Crystalline forms

[0096] In one aspect, provided herein is a crystalline form of l-((2R,3R)-3-((7-(8- ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin- 7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l- yl)prop-2-en-l-one (Compound 1), having the structure shown below:(Compound 1).Compound 1 and an exemplary method of making Compound 1 are described herein and in International Patent Application No. PCT / US2024 / 027885, which is incorporated herein by reference in its entirety. Throughout this application, unless the context indicates otherwise, reference to a compound such as Compound 1 includes all tautomers thereof.

[0097] The crystalline forms disclosed herein may provide the advantages of bioavailability and stability and may be suitable for use as an active agent in a pharmaceutical composition. Variations in the crystal structure of a pharmaceutical drug substance may affect the dissolution rate (which may affect bioavailability, etc.), manufacturability (e.g., ease of handling, ease of purification, ability to consistently prepare doses of known strength, etc.) and stability (e.g., thermal stability, shelflife (including resistance to degradation), etc.) of a pharmaceutical drug product. Such variations may affect the methods of preparation or formulation of pharmaceutical compositions in different dosage or delivery forms, such as solid oral dosage forms including tablets and capsules. Compared to other forms such as non-crystalline or amorphous forms, crystalline forms may provide desired or suitable hygroscopicity, particle size control, dissolution rate, solubility, purity, physical and chemical stability, manufacturability, yield, reproducibility, and / or process control. Thus, the crystalline forms disclosed herein may provide advantages of improving the manufacturing process of an active agent or the stability or storability of a drug product form of the active agent or having suitable bioavailability and / or stability as an active agent.

[0098] In one aspect, provided herein is a crystalline form of l-((2R,3R)-3-((7-(8- ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin- 7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l- yl)prop-2-en-l-one (Compound 1).

[0099] In some embodiments, a crystalline form is interchangeably referenced as a “Form” or “Type.” For example, in some embodiments, “freebase Form A” indicates the same crystalline form as “freebase Type A,” and vice versa.

[0100] In some embodiments, the purity of the crystalline form is at least about 95%. In some embodiments, the purity of the crystalline form is at least about 96%. In some embodiments, the purity of the crystalline form is at least about 97%. In some embodiments, the purity of the crystalline form is at least about 98%. In some embodiments, the purity of the crystalline form is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 99.99%. In some embodiments, the crystalline form is substantially pure.

[0101] In some embodiments, “about” before an XRPD angle 2 -theta value indicates ±0.2 of that value. For example, an angle 2 -theta of about 5 can indicate 5±0.2. In some embodiments, “about” before an XRPD angle 2 -theta value indicates ±0.1, ±0.2, ±0.3, ±0.4, ±0.5, ±0.6, ±0.7, ±0.8, ±0.9, ±1.0, ±1.1, ±1.2, ±1.3, ±1.4, ±1.5, ±2.0, or ±2.5 of that value.

[0102] In one aspect, provided is a pharmaceutical composition comprising a crystalline form provided herein, and a pharmaceutically acceptable excipient.

[0103] In some embodiments, the crystalline form is a hydrate. In some embodiments, the crystalline form is a solvate. In some embodiments, the crystalline form is an anhydrate. In some embodiments, a freebase crystalline form of Compound 1 is advantageously more stable than a crystalline form of a salt of Compound 1.

[0104] In some embodiments, the X-ray source for XRPD is copper Ka. In some embodiments, the Kai wavelength is about 1.54 A. In some embodiments, the Ka2 wavelength is about 1.54 A. In some embodiments, the intensity ratio of Ka2 / Kal is about 0.5. In some embodiments, XRPD is measured at room temperature.Freebase Form A

[0105] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form A substantially as shown in FIG. 1 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 1. In some embodiments, the crystalline form is characterized by having an XRPD patterncomprising a peak at angle 2 -theta of about 15.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 10.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 16.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 10.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 13.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 20.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 22.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 24.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern compri sing peaks at angles 2-theta of about 5.0, about 5.9, about 7.3, about 10.0, about 13.4, about 15.0, about 16.4, about 20.0, about 22.9, and about 24.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising at least two, three, four, five, six, seven, eight, or nine peaks selected from angles 2-theta of about 5.0, about 5.9, about 7.3, about 10.0, about 13.4, about 15.0, about 16.4, about 20.0, about 22.9, and about 24.6. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 199.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. IB. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG, IB. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 1C.Table I. XRPD pattern of freebase Form A.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 4.9997 388.54 0.1023 17.68 16.56 5.8541 70.28 0.3070 15.10 2.99 7.2744 126.28 0.2047 12.15 5.38 9.9722 2153.12 0.1535 8.87 91.75 13.4099 45.90 0.6140 6.60 1.96 14.9611 2346.82 0.2047 5.92 100.00 16.4013 707.73 0.1791 5.40 30.16 19.9852 111.01 0.3070 4.44 4.73 22.8841 178.10 0.2047 3.89 7.59 24.6139 77.38 0.2047 3.62 3.30Freebase Form E

[0106] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form E substantially as shown in FIG. 2A, In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 9.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 14.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 8.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 4.9, about 6.9, about 8.9, about 9.9, about 14.9, about 16.5, about 17.0, about 18.3, about 19.6, about 20.6, about 23.0, about 26.0, and about 27.5. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 188.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 2B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 2B.Table 2. XRPD pattern of freebase Form E.Pos. [°20] Height [cts] FWHM Left [°28] d-spacing [A] Rel. Int. [%] 4.9182 356.41 0.1279 17.97 35.84 6.9062 247.70 0.2047 12.80 24.91 8.9135 449.10 0.2303 9.92 45.16 9.8980 994.52 0.1791 8.94 100.00 14.8691 976.86 0.1791 5.96 98.22 16.5027 351.12 0.2047 5.37 35.31 16.9721 283.79 0.2558 5.22 28.5418.2679 139.99 0.3070 4.86 14.08 19.5616 226.41 0.4093 4.54 22.77 20.5622 103.54 0.3582 4.32 10.41 23.0360 158.52 0.6140 3.86 15.94 26.0342 49.77 0.3070 3.42 5.00 27.5219 38.69 0.8187 3.24 3.89Freebase Form B

[0107] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form B substantially as shown in FIG. 3. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 8.5, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 6.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 6.8, about 8.5, and about 16.6.Table 3. XRPD pattern of freebase Form B (wet).Pos. [°20] Height [cts] FWHMLeft [°20] d-spacing [A] Rel. Int. [%] 6.8387 242.27 0.1023 12.93 72.01 8.5022 336.45 0.0768 10.40 100.00 16.6380 167.62 0.1535 5.33 49.82Freebase Form C

[0108] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form C substantially as shown in FIG. 4. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 8.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 4.2. In some embodiments, the crystalline form is characterized by having an XRPD patterncomprising a peak at angle 2 -theta of about 16.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 4.2, about 6.8, about 8.4, about 9.8, about 15.6, about 16.6, and about 16.8.Table 4. XRPD pattern of freebase Form C (wet).Pos. [°20] Height [cts] FWHMLeft [°20] d-spacing [A] Rel. Int. [%] 4.2344 1388.91 0.1023 20.87 54.69 6.8427 249.60 0.1535 12.92 9.83 8.4216 2539.58 0.1023 10.50 100.00 9.7861 254.90 0.4093 9.04 10.04 15.6229 377.00 0.2047 5.67 14.84 16.5795 869.01 0.1535 5.35 34.22 16.8399 858.80 0.0768 5.26 33.82Freebase Form D

[0109] In some embodiments, the crystalline form is characterized by having an XRPD pattern of freebase Form D substantially as shown in FIG. 5. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 16.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 9.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 4.3, about 6.9, about 8.5, about 9.9, about 14.9, about 15.6, and about 16.5.Table 5. XRPD pattern of freebase Form D.Pos. [°20] Height [cts] FWHMLeft [°20] d-spacing [A] Rel. Int. [%] 4.3434 103.54 0.3070 20.34 26.52 6.8901 36.92 0.6140 12.83 9.46 8.4768 115.86 0.4093 10.43 29.67 9.8736 136.67 0.2558 8.96 35.00 14.8735 132.74 0.3070 5.96 34.00 15.6136 179.36 0.1535 5.68 45.94 16.5126 390.45 0.1023 5.37 100.00Hydrochloride salt Form A

[0110] In some embodiments, the crystalline form is characterized by having an XRPD pattern of HO salt Form A substantially as shown in FIG. 6A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 13.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 14.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 5.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.6, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 12,0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 13.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 13.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 14.3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 14.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.7, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 16,5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 17.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 18.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 18.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 19.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 20,2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 21.3. In some embodiments, thecrystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 21.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 23.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 11.6, about 12.0, about 13.0, about 13.4, about 14.3, about 14.6, about 15.7, about 16.5, about 16.8, about 17.5, about 18.5, about 18.7, about 19.6, about 20.2, about 21.3, about 21.9, and about 23.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising at least two, three, four, five, six, seven, eight, or nine peaks selected from angles 2 -theta of about 5.8, about 11.6, about 12.0, about 13.0, about 13.4, about 14.3, about 14.6, about 15.7, about 16.5, about 16.8, about 17.5, about 18.5, about 18.7, about 19.6, about 20.2, about21.3, about 21.9, and about 23.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 24.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 26.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 26.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 28.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 29.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 29.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 31.2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 31.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 36.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 37.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 38.9. In some embodiments, the crystalline form is, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 11.6, about 12.0, about 13.0, about 13.4, about 14.3, about 14.6, about 15.7, about 16.5, about 16.8, about 17.5, about 18.5, about 18.7, about 19.6, about 20.2, about 21.3, about 21.9, about 23.4, about 24.1, about 26.4, about 26.9, about 28.8, about 29.5, about 29.9, about 31.2, about 31.7, about 36.0, about 37.9, and about 38.9. In some embodiments, the crystalline form is characterized by having an XRPD patterncomprising at least two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or fifteen peaks selected from angles 2-theta of about 5.8, about 11.6, about 12.0, about 13.0, about 13.4, about 14.3, about 14.6, about 15.7, about 16.5, about 16.8, about 17.5, about 18.5, about 18.7, about 19.6, about 20.2, about 21.3, about 21.9, about 23.4, about 24.1, about 26.4, about 26.9, about 28.8, about 29.5, about 29.9, about 31.2, about 31.7, about 36.0, about 37.9, and about 38.9. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 179.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 221.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 6B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 6B. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 6C.Table 6. XRPD pattern of hydrochloride salt Form APos. |°20| Height fcts ] FWHM Left [°2G] d-spacing [A] Rel. Int. [% | 5.8264 425.74 0.1023 15.17 10.64 11.6400 3999.53 0.1279 7.60 100.00 12.0270 644.59 0.1279 7.36 16.12 13.0313 1254.18 0.1023 6.79 31.36 13.3646 469.12 0.1023 6.63 11.73 14.2759 484.07 0.1023 6.20 12.10 14.5734 810.86 0.1279 6.08 20.27 15.6974 536.36 0.1279 5.65 13.41 16.4826 219.82 0.1023 5.38 5.50 16.7771 480.70 0.1023 5.28 12.02 17.4767 272.19 0.1279 5.07 6.81 18.4662 610.74 0.1023 4.80 15.27 18.7057 333.64 0.0768 4.74 8.34 19.5757 99.76 0.1535 4.53 2.49 20.2415 212.73 0.1279 4.39 5.32 21.2657 341.47 0.1023 4.18 8.54 21.8773 727.58 0.1279 4.06 18.19 23.3809 527.47 0.1279 3.80 13.19 24.1388 208.89 0.1279 3.69 5.22 26.3611 228.68 0.1279 3.38 5.72 26.8694 375.16 0.1535 3.32 9.38 28.7597 77.53 0.2047 3.10 1.94 29.5302 118.21 0.3070 3.02 2.96 29.9462 75.99 0.2047 2.98 1.90 31.2386 72.25 0.1535 2.86 1.81 31.6653 189.84 0.1279 2.83 4.7536.0409 33.86 0.6140 2.49 0.85 37.8674 48.22 0.1535 2.38 1.21 38.8966 41.00 0.1535 2,32 1.03Citrate salt Form A

[0111] In some embodiments, the crystalline form is characterized by having an XRPD pattern of citrate salt Form A substantially as shown in FIG. 7A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 4.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 9.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 6.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 4.9, about 6.4, about 7.8, about 9.6, about 11.5, about 12.1, about 12.8, about 13.5, about 14.6, about 15.3, about 15.8, about 17.0, about 17.4, about 18.1, about 18.8, about 19.5, about 20.4, about 20.8, about 21.8, about 22.7, about 24.4, about 25.2, and about 32.5. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 173.7 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 7B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 7B. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 7C.Table 7. XRPD pattern of citrate salt Form A.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 4.8564 6094.27 0.1023 18.20 100.00 6.3997 350.10 0.0768 13.81 5.74 7.8167 69.91 0.3070 11.31 1.15 9.5621 366.70 0.0768 9.25 6.02 11.4577 59.59 0.2558 7.72 0.98 12.1278 90.57 0.1535 7.30 1.49 12.8164 66.71 0.1535 6.91 1.09 13.4972 119.69 0.2047 6.56 1.96 14.5846 135.89 0.0768 6.07 2.23 15.3415 121.97 0.1023 5.78 2.0015.8280 63.76 0.1535 5.60 1.05 17.0061 98.68 0.1023 5.21 1.62 17.3539 72.07 0.1535 5.11 1.18 18.1369 201.03 0.0768 4.89 3.30 18.8366 108.89 0.0768 4.71 1.79 19.4737 73.37 0.1535 4.56 1.20 20.4327 103.55 0.1535 4.35 1.70 20.8296 81.49 0.1535 4.26 1.34 21.7922 109.90 0.0768 4.08 1.80 22.7315 142.67 0.1279 3.91 2.34 24.4221 240.51 0.0768 3.64 3.95 25.2111 153.84 0.1023 3.53 2.52 32.5217 30.90 0.3070 2.75 0.51Succinate salt Forms A / B / C

[0112] In some embodiments, the crystalline form is characterized by having an XRPD pattern of succinate salt Form A substantially as shown in FIG. 8A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 8-1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 11.3. In some embodiments, the crystalline form is, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 8.0, about 8.7, about 10.1, about 11.3, about 11.9, about 15.1, about 15.9, about 17.0, about 18.1, about 18.7, about 20.4, about 21.8, about 22.5, about 23.1, about 24.4, about 26.0, about 29.8, and about 32.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 146.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 159.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 8B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 8B. In some embodiments, the crystalline form is characterized by having a DVS graph substantially as shown in FIG. 8C.Table 8-1. XRPD pattern of succinate salt Form A.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 5.9070 585.05 0.1023 14.96 100.00 7.9653 463.76 0.0768 11.10 79.27 8.7045 299.52 0.1023 10.16 51.20 10.1227 72.79 0.1535 8.74 12.44 11.3258 583.03 0.1279 7.81 99.65 11.9314 261.42 0.1023 7.42 44.68 15.1492 57.87 0.1535 5.85 9.89 15.9438 484.75 0.1023 5.56 82.86 16.9785 145.68 0.2047 5.22 24.90 18.0573 269.41 0.1279 4.91 46.05 18.6923 141.77 0.1023 4.75 24.23 20.4271 87.39 0.1791 4.35 14.94 21.8162 350.80 0.1279 4.07 59.96 22.4611 107.70 0.1023 3.96 18.41 23.0569 156.65 0.1279 3.86 26.78 24.3859 67.44 0.2047 3.65 11.53 25.9506 111.35 0.1791 3.43 19.03 29.8044 81.55 0.2047 3.00 13.94 32.7022 34.81 0.3070 2.74 5.95

[0113] In some embodiments, the crystalline form is characterized by having an XRPD pattern of succinate salt Form B substantially as shown in FIG. 8A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 8-2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 7.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.9, about 7.8, about 8.8, about 10.1, about 11.1, about 11.9, about 15.6, about 16.8, about 17.9, about 19.0, about 20.4, about 22.0, about 22.9, about 24.4, about 25.8, and about 29.3. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 145.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 157.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 8D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 8D.Table 8-2. XRPD pattern of succinate salt Form B.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 5.8541 291.16 0.0768 15.10 79.21 7.7844 323.20 0.0768 11.36 87.93 8.7699 211.29 0.0768 10.08 57.48 10.1264 81.81 0.1535 8.74 22.26 11.1001 312.03 0.1023 7.97 84.89 11.8605 168.78 0.1023 7.46 45.92 15.5704 367.59 0.1279 5.69 100.00 16.8185 130.31 0.1535 5.27 35.45 17.9470 173.37 0.2047 4.94 47.16 18.9695 83.65 0.2047 4.68 22.76 20.3844 62.51 0.2047 4.36 17.01 21.9582 194.72 0.2047 4.05 52.97 22.8980 100.08 0.1535 3.88 27.23 24.3776 28.77 0.4093 3.65 7.83 25.8208 76.62 0.1535 3.45 20.84 29.2768 26.25 0.8187 3.05 7.14

[0114] In some embodiments, the crystalline form is characterized by having an XRPD pattern of succinate salt Form C substantially as shown in FIG. 8A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 8-3. In some embodiments, the crystalline form is, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 15.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.8, about 7.7, about 8.9, about 10.2, about 10.9, about 12.0, about 15.5, about 17.0, and about 18.1. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 140.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 157.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 8E. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 8E.Table 8-3. XRPD pattern of succinate salt Form C.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 5.8242 635.28 0.1023 15.17 100.00 7.7482 459.98 0.1023 11.41 72.418.8755 255.53 0.1535 9.96 40.22 10.2340 83.09 0.2047 8.64 13.08 10.9042 346.84 0.1279 8.11 54.60 12.0345 231.28 0.1279 7.35 36.41 15.5064 550.10 0.1279 5.71 86.59 17.0112 138.32 0.1535 5.21 21.77 18.1174 182.84 0.2558 4.90 28.78 19.0254 76.03 0.2047 4.66 11.97 20.5176 76.22 0.1535 4.33 12.00 22.0457 270.48 0.1791 4.03 42.58 22.9302 197.31 0.1535 3.88 31.06 23.4378 61.13 0.1535 3.80 9.62 24.6239 21.72 0.6140 3.62 3.42 26.0218 125.83 0.1791 3.42 19.81 27.4463 41.01 0.1535 3.25 6.46 29.6521 75.08 0.1535 3.01 11.82Tartrate salt Form A

[0115] In some embodiments, the crystalline form is characterized by having an XRPD pattern of tartrate salt Form A substantially as shown in FIG. 9A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.5, about 7.6, about 8.8, about 9.4, about 10.0, about 11.3, about 12.5, about 14.2, about 15.3, and about 16.3. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 52.6 °C, In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 170.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 9B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 9B.Table 9, XRPD pattern of tartrate salt Form A,Pos. [°20] Height jets] FWHM Left |°20] d-spacing [A] Rel. Int. [%]5.4971 484.54 0.0768 16.08 71.65 7.6323 676.22 0.1279 11.58 100.00 8.8493 219.35 0.1023 9.99 32.44 9.4161 113.26 0.1535 9.39 16.75 9.9580 163.49 0.1023 8.88 24.18 11.3473 210.05 0.1023 7.80 31.06 12.5435 202.15 0.1279 7.06 29.89 14.1762 263.22 0.1023 6.25 38.92 15.2741 278.56 0.1023 5.80 41.19 16.2503 126.12 0.1791 5.45 18.65 19.6263 84.33 0.1535 4.52 12.47 19.9858 94.02 0.1535 4.44 13.90 21.0806 92.27 0.1535 4.21 13.65 22.0858 70.20 0.3070 4.02 10.38 22.7999 197.03 0.1279 3.90 29.14Fumarate salt Forms A / B / C

[0116] In some embodiments, the crystalline form is characterized by having an XRPD pattern of fumarate salt Form A substantially as shown in FIG. 10A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 10-1, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 5.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.9, about 7.8, about 9.3, about 11.0, about 12.3, and about 15.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 170.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 10B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 10B.Table 10-1. XRPD pattern of fumarate salt Form A.Pos. [°20] Height |cts] FWHM Left |°20| d-spacing [. A] Rel. Int. [%] 5.9003 438.63 0.1023 14.98 99.14 7.8479 442.45 0.1023 11.27 100.00 9.2580 80.85 0.2047 9.55 18.2710.9949 383.11 0.1023 8.05 86.59 12.3083 158.62 0.1535 7.19 35.85 15.7088 366.16 0.1023 5.64 82.76 22.5148 122.48 0.1535 3.95 27.68 22.9537 113.38 0.1535 3.87 25.63

[0117] In some embodiments, the crystalline form is characterized by having an XRPD pattern of fumarate salt Form B substantially as shown in FIG. 10A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 10-2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 5.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.8, about 7.8, about 8.9, about 11.0, about 12.0, about 15.5, about 16.9, about 18.1, about 22.1, about 22.9, about 26.0, and about 29.4. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 171.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 10C. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 10C.Table 10-2. XRPD pattern of fumarate salt Form B.Pos. [°20] Height |cts] FWHM Left |°20| d-spacing [. A] Rel. Int. [%] 5.8221 491.92 0.1023 15.18 97.62 7.7590 355.96 0.0768 11.39 70.64 8.8544 143.58 0.1535 9.99 28.49 10.9691 503.91 0.1023 8.07 100.00 11.9777 165.30 0.1535 7.39 32.80 15.5172 298.51 0.1279 5.71 59.24 16.9372 122.95 0.1535 5.23 24.40 18.0863 146.13 0.1535 4.90 29.00 22.0533 258.14 0.2047 4.03 51.23 22.9014 136.43 0.1535 3.88 27.07 25.9741 76.01 0.3070 3.43 15.08 29.4484 57.42 0.6140 3.03 11.39

[0118] In some embodiments, the crystalline form is characterized by having an XRPD pattern of fumarate salt Form C substantially as shown in FIG. 10A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 10-3, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 6.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 16.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.5, about 6.8, about 7.9, about 9.7, about 11.0, about 11.7, about 13.1, about 15.3, about 15.9, about 16.8, about 18.9, about 21.5, and about 22.5. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 57.1 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 167.7 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 10D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 10D.Table 10-3. XRPD pattern of fumarate salt Form C.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 5.5025 180.22 0.1535 16.06 55.53 6.7960 324.53 0.1023 13.01 100.00 7.9440 197.35 0.1023 11.13 60.81 9.6715 195.01 0.1023 9.15 60.09 11.0321 143.95 0.2047 8.02 44.36 11.7313 205.75 0.1279 7.54 63.40 13.1201 76.88 0.2047 6.75 23.69 15.2781 82.99 0.1535 5.80 25.57 15.8932 178.65 0.0768 5.58 55.05 16.8364 251.40 0.1023 5.27 77.47 18.8832 100.27 0.2047 4.70 30.90 21.4566 119.73 0.1535 4.14 36.89 22.5106 143.72 0.2558 3.95 44.29Malate salt Forms A / B / C

[0119] In some embodiments, the crystalline form is characterized by having an XRPD pattern of malate salt Form A substantially as shown in FIG. 11 A. In some embodiments, thecrystalline form is characterized by having an XRPD pattern substantially as shown in Table 11-1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 7.3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 13.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.8, about 6.3, about 7.3, about 7.9, about 9.1, about 13.6, about 15.1, about 15.9, about 16.7, about 18.1, about 22.2, about 23.2, and about 25.3. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 145.7 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 161.4 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 11B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 11B.Table 11-1. XRPD pattern of malate salt Form A.Pos. [°20] Height [cts] FWHM Left [°28j d-spacing [A] Rel. Int. [%] 5.8269 144.16 0.1535 15.17 28.66 6.2705 140.39 0.1535 14.10 27.91 7.3121 456.02 0.1279 12.09 90.65 7.9285 113.40 0.1535 11.15 22.54 9.1454 40.49 0.7164 9.67 8.05 13.5827 229.08 0.1023 6.52 45.54 15.0704 503.05 0.1023 5.88 100.00 15.9032 124.88 0.1535 5.57 24.82 16.7102 118.96 0.3070 5.31 23.65 18.0943 94.93 0.2558 4.90 18.87 22.1693 143.51 0.1535 4.01 28.53 23.2355 75.73 0.3070 3.83 15.05 25.3078 42.10 0.3070 3.52 8.37

[0120] In some embodiments, the crystalline form is characterized by having an XRPD pattern of malate salt Form B substantially as shown in FIG. 11 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 11-2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.4. In some embodiments, thecrystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 5.6, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.0. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.6, about 7.4, about 8.9, about 11.2, and about 15.0. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 49.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 113.4 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 162.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG, 11C. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 11C.Table 11-2. XRPD pattern of malate salt Form B.Pos. [°20] Height [cts] FWHMLeft [°20] d-spacing [A] Rel. Int. [%] 5.5582 110.61 0.3070 15.90 83.02 7.4253 133.24 0.3070 11.91 100.00 8.8903 87.09 0.5117 9.95 65.36 11.2120 41.23 0.6140 7.89 30.94 15.0480 97.26 0.4093 5.89 73.00

[0121] In some embodiments, the crystalline form is characterized by having an XRPD pattern of malate salt Form C substantially as shown in FIG. 11A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 11-3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 7.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.8, about 7.9, about 8.9, about 11.1, about 15.1, about 15.7, about 17.2, about 18.3, and about 22.1. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 144.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 158.2 °C. In some embodiments, the crystalline form is characterized by having aDSC graph substantially as shown in FIG. 11D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 11D.Table 11-3. XRPD pattern of malate salt Form C,Pos. [°20] Height |cts] FWHM Left |°20| d-spacing [. A] Rel. Int. |%] 5.7606 268.44 0.1023 15.34 100.00 7.8649 215.21 0.1279 11.24 80.17 8.9017 137.15 0.2047 9.93 51.09 11.1184 134.50 0.2047 7.96 50.11 15.1080 114.44 0.2558 5.86 42.63 15.7431 195.57 0.1279 5.63 72.85 17.1681 108.87 0.2047 5.17 40.56 18.2792 56.81 0.6140 4.85 21.16 22.0954 94.43 0.3070 4.02 35.18Adipate salt

[0122] In some embodiments, the crystalline form is characterized by having an XRPD pattern of adipate salt Form A substantially as shown in FIG. 12. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 12. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 10.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 4.3, about 5.0, about 5.9, about 7.3, about 8.5, about 9.2, about 10.1, about 13.7, about 15.1, about 16.5, about 17.0, about 20.2, about 23.1, and about 28.4.Table 12. XRPD pattern of adipate salt.Pos. |°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 4.2935 229.05 0.1023 20.58 13.86 5.0126 112.66 0.1535 17.63 6.82 5.8625 71.07 0.3070 15.08 4.30 7.3339 78.35 0.3070 12.05 4.74 8.4964 264.06 0.1279 10.41 15.98 9.2294 146.16 0.1535 9.58 8.84 10.0569 1196.54 0.1279 8.80 72.39 13.7205 154.50 0.2047 6.45 9.3515.0964 1652.95 0.1535 5.87 100.00 16.5158 541.26 0.1279 5.37 32.75 16.9591 253.43 0.1535 5.23 15.33 20.1621 157.11 0.2047 4.40 9.50 23.1414 59.93 0.6140 3.84 3.63 28.3584 65.48 0.3070 3.15 3.96Napadisylate salt Forms A / B / C

[0123] In some embodiments, the crystalline form is characterized by having an XRPD pattern of napadisylate salt Form A substantially as shown in FIG. 13A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 13-1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7,3. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 19.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 7.3, about 15.4, and about 19.7. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 56.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 160.0 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 257.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 13B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 13B.Table 13-1. XRPD pattern of napadisylate salt Form A.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 7.3448 174.41 0.1023 12.04 100.00 15.4343 61.09 0.3070 5.74 35.03 19.7461 90.42 0.2047 4.50 51.84

[0124] In some embodiments, the crystalline form is characterized by having an XRPD pattern of napadisylate salt Form B substantially as shown in FIG. 13A. In someembodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 13-2. characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.6. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 49.3 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 137.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 201.5 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG, 13C. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 13C.Table 13-2. XRPD pattern of napadisylate salt Form B.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 7.6069 63.23 0.3744 11.61 100.00

[0125] In some embodiments, the crystalline form is characterized by having an XRPD pattern of napadisylate salt Form C substantially as shown in FIG. 13A. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 50.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 125.9 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 265.7 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 13D. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 13D,Tosylate salt Form A

[0126] In some embodiments, the crystalline form is characterized by having an XRPD pattern of tosylate salt Form A substantially as shown in FIG. 14A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 14. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.2. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 12.1. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.5. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.2, about 7.4, about 8.6, about 10.0, about 11.3, about 12.1, about 13.2, about 14.4, about 14.9, about 15.5, about 17.3, about 18.3, about 19.8, about 21.1, about 22.0, about 22.6, about 23.7, about 24.2, about 26.2, about 26.9, and about 29.1. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 138.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 214.2 °C, In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 14B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 14B.Table 14. XRPD pattern of tosylate salt Form A.Pos. [°20] Height [cts] FWHMLeft [°20] d-spacing [A] Rel. Int. [%] 5.1634 1314.55 0.1023 17.12 100.00 7.4367 215.08 0.1023 11.89 16.36 8.6249 234.82 0.1279 10.25 17.86 10.0281 65.13 0.6140 8.82 4.95 11.2710 92.77 0.1535 7.85 7.06 12.1074 642.57 0.1023 7.31 48.88 13.2206 72.06 0.2047 6.70 5.48 14.4327 180.28 0.1023 6.14 13.71 14.8773 248.64 0.1023 5.95 18.91 15.4512 322.05 0.1023 5.73 24.50 17.2704 105.93 0.1535 5.13 8.06 18.3391 259.58 0.1535 4.84 19.75 19.7738 157.41 0.1535 4.49 11.97 21.1388 192.79 0.1023 4.20 14.67 22.0092 94.57 0.1535 4.04 7.19 22.5757 207.44 0.2047 3.94 15.78 23.6900 77.33 0.4093 3.76 5.88 24.2421 127.73 0.1535 3.67 9.72 26.2239 196.27 0.1279 3.40 14.93 26.9381 107.41 0.2047 3.31 8.17 29.1351 96.48 0.3070 3.07 7.34Mesylate salt Form A

[0127] In some embodiments, the crystalline form is characterized by having an XRPD pattern of mesylate salt Form A substantially as shown in FIG. 15 A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 15, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.4. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 9.8. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.6, about 7.4, about 9.8, about 17.5, and about 19.5. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 222.8 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 15B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 15B.Table 15. XRPD pattern of mesylate salt Form A.Pos. [°20] Height [cts] FWHMLeft [°20] d-spacing [A] Rel. Int. [%] 5.6162 71.49 0.6140 15.74 36.54 7.3810 195.66 0.1023 11.98 100.00 9.7517 176.61 0.1023 9.07 90.26 17.5454 58.03 0.6140 5.05 29.66 19.5218 62.62 0.3070 4.55 32.01Oxalate salt Form A

[0128] In some embodiments, the crystalline form is characterized by having an XRPD pattern of oxalate salt Form A substantially as shown in FIG. 16A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 16. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2- theta of about 14.6. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 5.6, about 7.7, about 10.0, about 11.6, about 14.6, about 15.0, about 15.5,about 16.4, about 17.2, about 18.1, about 18.8, about 19.9, about 21.2, about 21.9, and about 24,3. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 82.4 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 174.0 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 16B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 16B.Table 16. XRPD pattern of oxalate salt Form A.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 5.5703 222.31 0.1535 15.87 100.00 7.7310 165.61 0.1279 11.44 74.50 10.0474 49.90 0.5117 8.80 22.45 11.5622 79.00 0.3070 7.65 35.53 14.5586 200.68 0.1279 6.08 90.27 14.9544 83.47 0.1535 5.92 37.54 15.5303 115.76 0.1535 5.71 52.07 16.4053 82.38 0.4093 5.40 37.06 17.2339 93.23 0.1535 5.15 41.94 18.1198 175.06 0.1023 4.90 78.74 18.8485 109.20 0.1279 4.71 49.12 19.8662 67.25 0.3070 4.47 30.25 21.1748 97.12 0.1535 4.20 43.68 21.8876 77.14 0.2047 4.06 34.70 24.3029 60.30 0.8187 3.66 27.12Hydrobromide salt Form A

[0129] In some embodiments, the crystalline form is characterized by having an XRPD pattern of HBr salt Form A substantially as shown in FIG. 17A. In some embodiments, the crystalline form is characterized by having an XRPD pattern substantially as shown in Table 17. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.6, In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 21.7. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 12.9. In some embodiments, the crystalline form is characterized by having an XRPD pattern comprising peaks at angles 2- theta of about 11.6, about 12.9, about 18.2, about 21.7, and about 26.6. In someembodiments, the crystalline form is characterized by having a DSC graph comprising an endothermic peak at about 57.2 °C. In some embodiments, the crystalline form is characterized by having a DSC graph comprising an exothermic peak at about 215.6 °C. In some embodiments, the crystalline form is characterized by having a DSC graph substantially as shown in FIG. 17B. In some embodiments, the crystalline form is characterized by having a TGA graph substantially as shown in FIG. 17B.Table 17. XRPD pattern of hydrobromide salt Form A.Pos. [°20] Height [cts] FWHM Left [°20] d-spacing [A] Rel. Int. [%] 11.5554 199.30 0.1535 7.66 100.00 12.8533 104.14 0.1535 6.89 52.25 18.1752 78.84 0.1535 4.88 39.56 21.7090 136.77 0.1279 4.09 68.62 26.6471 56.82 0.8187 3.35 28.51III. Methods of Preparing

[0130] In one aspect, provided herein is a method for preparing a crystalline form of Compound 1.

[0131] In some embodiments, “room temperature” indicates a temperature between about 15°C and about 35°C. In some embodiments, “room temperature” indicates a temperature between about 15°C and about 30°C. In some embodiments, “room temperature” indicates a temperature between about 20°C and about 30°C. In some embodiments, “room temperature” indicates a temperature at about 25°C.1. Vapor-solid diffusion

[0132] In some embodiments, the method comprises: (i) placing a sample comprising a solid form of Compound 1 in a first container; (ii) placing the first container of step (i) inside a second container containing a solvent; and (iii) allowing vapor from the solvent to interact with the sample in the first container. In some embodiments, the sample of step (i) comprises freebase Form A. In some embodiments, step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container at a room temperature and for a duration of about 7 days. In some embodiments, step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container at a room temperature. In someembodiments, step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container for a duration of about 7 days. In some embodiments, step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container for a duration of about between about 3 days and about 11 days; or between about 5 days and about 9 days. In some embodiments, the solvent comprises EtOH, MIBK, EtOAc, MTBE, 2-MeTHF, 1,4-Dioxane, acetonitrile, toluene, IP A, water, or DMSO, or any mixture thereof. In some embodiments, the solvent comprises EtOH, MIBK, EtOAc, MTBE, 2-MeTHF, acetonitrile, toluene, IP A, water, or DMSO, or any mixture thereof, and the cry stall ine form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises 1,4-dioxane and the crystalline form prepared from the method comprises freebase Form E. In some embodiments, step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container for the duration of about 19 days.2. Vapor-solid diffusion

[0133] In some embodiments, the method comprises: (i) dissolving Compound 1 in a first solvent in a first container; (ii) placing the first container of step (i ) inside a second container containing a second solvent; (iii) sealing the second container of step (ii); (iv) allowing vapor of the second solvent to interact with Compound 1 in the first container to form precipitant; and (v) isolating the precipitant of step (iv) from the first solvent and / or the second solvent. In some embodiments. Compound 1 of step (i) comprises freebase Form A. In some embodiments, step (iv) comprises allowing vapor of the second solvent to interact with Compound 1 in the first container at room temperature. In some embodiments, isolating the precipitant in step (v) comprises evaporating the first solvent and / or the second solvent at room temperature. In some embodiments, the first solvent comprises MeOH, NMP, 1,4-dioxane, EtOH, acetone, EtOAC, DM / Ac, DCM, 2-MeTHF, CHCh, acetonitrile, or DMSO, or a mixture thereof, and the second solvent comprises MTBE, n-Heptane, water, or toluene, or any mixture thereof. In some embodiments, the first solvent comprises EtOH, EtOAC, 2-MeTHF, CHCh, acetonitrile, or 1,4-dioxane, or any mixture thereof, and the second solvent comprises MTBE, n-Heptane, or toluene, or a mixture thereof, and the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the first solvent comprises acetone, the second solvent comprises MTBE, and the crystalline form prepared from the method comprises freebase Form C. In some embodiments, the firstsolvent comprises DCM, the second solvent comprises MTBE, and the crystalline form prepared from the method comprises freebase Form D. In some embodiments, the first solvent comprises MeOH, 1,4-dioxane, or EtOH, or any mixture thereof, the second solvent comprises water or n-heptane, or any mixture thereof and the crystalline form prepared from the method is amorphous. In some embodiments, the first solvent comprises NMP, DMAc, or DMSO, or any mixture thereof, the second solvent comprises w'ater, MTBE, or toluene, or any mixture thereof, and the crystalline form prepared from the method comprises an oil.3. Slow cooling

[0134] In some embodiments, the method comprises: (i) preparing a suspension of Compound 1 in a solvent; (ii) heating the suspension of step (i) to a first temperature; (iii) filtering the suspension of step (ii) to obtain filtrate; (iv) cooling the filtrate of step (iii) to a second temperature. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, the first temperature is about 50°C. In some embodiments, the second temperature is about 5°C or about -20°C. In some embodiments, the temperature of the filtrate in step (iv) is changed at a rate of about 0.1°C / min. In some embodiments, the method further comprises evaporating the solvent at room temperature. In some embodiments, the solvent comprises IP A, IP Ac, MIBK, acetonitrile, MTBE, 2-MeTHF, EtOH, or n-heptane, or any mixture thereof. In some embodiments, the solvent comprises IPA, IP Ac, MIBK, a mixture of EtOH and n-Heptane at a volume ratio of about 1: 1, or any mixture thereof, wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a mixture of acetonitrile and MTBE at a volume ratio of about 1:1, or 2-MeTHF, or any mixture thereof, wherein the crystalline form prepared from the method is amorphous.4. Slurry

[0135] In some embodiments, the method comprises: (i) preparing a suspension of Compound 1 in solvent; and (ii) stirring the suspension of step (i) at a temperature for a duration. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, a solid forms from the suspension after step (ii), and the method further comprises centrifuging the suspension of step (ii) to isolate the solid. In some embodiments, the temperature is room temperature. In some embodiments, the duration is about 4 days. In some embodiments, the duration is between about 2 days and about 6 days. In someembodiments, the duration is between about 3 days and about 5 days. In some embodiments, the solvent comprises EtOH, MTBE, acetone, water, EtOAc, MTBE, acetonitrile, THE, n-Heptane, toluene, DCM, 1,4-Dioxane, MeOH, DMSO, DMAc, or IP A, or any mixture thereof. In some embodiments, the solvent comprises a mixture of EtOH and MTBE at a volume ratio of about 1: 9; a mixture of acetone and water at a volume ratio of about 1:9; a mixture of EtOAc and MTBE at a volume ratio of about 1:4; MTBE; a mixture of acetonitrile and water at a volume ratio of about 1:9; a mixture of THF and n-Heptane at a volume ratio of about 1:9; toluene; water; a mixture of DCM and MTBE at a volume ratio of about 1:9; a mixture of 1,4-dioxane and toluene at a volume ratio of about 1:9; a mixture of DMSO and water at a volume ratio of about 1:9; a mixture of DMAc and toluene at a volume ratio of about 1.9; a mixture of IPA and water at a volume ratio of about 98:2, 96:4, 92.8, or 85:15, wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a mixture of MeOH and toluene at a volume ratio of about 1:9, wherein the crystalline form prepared from the method comprises freebase Form B. In some embodiments, the temperature is between about 40°C and about 60°C, and the duration is between about 1 day and about 5 days. In some embodiments, the solvent comprises MeOH, toluene, MIBK, n-Heptane, IP Ac, MTBE, CHCh, water, 2-MeTHF, 1,4-dioxane, acetonitrile, THF, NMP, or DMSO, or any mixture thereof. In some embodiments, the solvent comprises a mixture of MIBK and n-Heptane at a volume ratio of about 1:2; a mixture of IP Ac and MTBE at a volume ratio of about 1:2; water; n-Heptane; a mixture of 2-MeTHF and MTBE at a volume ratio of about 1:4; a mixture of 1,4-dioxane and n-Heptane at a volume ratio of about 1:9; a mixture of acetonitrile and toluene at a volume ratio of about 1:4; a mixture of THF and toluene at a volume ratio of about 1:9; a mixture of NMP and water at a volume ratio of about 1:9; a mixture of DMSO and toluene at a volume ratio of about 1:4; wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a mixture of MeOH and toluene at a volume ratio of about 1:9; a mixture of CHCh and toluene at a volume ratio of about 1: 4; wherein the crystalline form prepared from the method is amorphous.5. Temperature cycling

[0136] In some embodiments, the method comprises: (i) preparing a suspension of Compound 1 in a solvent; (ii) heating the suspension to a first temperature and cooling thesuspension to a second temperature; and (iii) heating the suspension to a third temperature, and cooling the suspension to a fourth temperature. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, a solid forms from the suspension after step (iii), and the method further comprises centrifuging the suspension of step (iii) to isolate the solid. In some embodiments, the first temperature and the third temperature are each independently in between about 40°C and about 50°C, and the second temperature and the fourth temperature are each independently in between about 0°C and about 10°C. In some embodiments, the heating and cooling of steps (ii) and (iii) are each independently conducted at a rate of between about 0.01 °C / min and about 1 °C / min. In some embodiments, the solvent comprises MeOH, MTBE, EtOH, water, acetonitrile, EtOAc, n-Heptane, 2-MeTHF, acetone, toluene, IPAc, DM Ac, NMP, or CHCI3, or any mixture thereof. In some embodiments, the solvent comprises a mixture of MeOH and MTBE at a volume ratio of 1:9; a mixture of EtOH and water at a volume ratio of 1:9; a mixture of acetonitrile and MTBE at a volume ratio of about 1:9; a mixture of EtOAc and n-Heptane at a volume ratio of about 1:4; 2-MeTHF; a mixture of acetone and toluene at a volume ratio of about 1:4; IPAc; water; MTBE; a mixture of DMAc and water at a volume ratio of about 1:9; a mixture of NMP and MTBE at a volume ratio of about 1:9; a mixture of CHCI3 and MTBE at a volume ratio of about 1:4; wherein the crystalline form prepared from the method comprises freebase Form A.6. Slow evaporation

[0137] In some embodiments, the method comprises: (i) dissolving Compound 1 in a solvent; and (ii) evaporating the solvent of step (i) at a temperature. In some embodiments, Compound 1 of step (i) comprises freebase Form A. In some embodiments, the temperature of step (ii) is room temperature. In some embodiments, the solvent comprises MeOH, EtOH, acetonitrile, acetone, EtOAc, 2-MeTHF, DCM, THF, or water, or any mixture thereof. In some embodiments, the solvent comprises EtOH; acetonitrile; EtOAc; 2-MeTHF; wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises a MeOH; acetone; DCM; a mixture of THF and water at a volume ratio of about 9: 1, wherein the crystalline form prepared from the method is amorphous.7. Grinding

[0138] In some embodiments, the method comprises grinding Compound 1. In some embodiments, Compound I comprises freebase Form A, In some embodiments, the method further comprises contacting Compound 1 with a solvent while grinding. In some embodiments, the solvent comprises water. In some embodiments, the crystalline form prepared from the method comprises freebase Form A.8. Anti -solvent addition

[0139] In some embodiments, the method comprises: (i) adding Compound 1 to a solvent to form a first mixture; and (ii) adding an anti-solvent to the first mixture to form a second mixture. In some embodiments, Compound I of step (i) comprises freebase Form A, In some embodiments, the anti-solvent is added until a precipitate is produced. In some embodiments, the method further comprises cooling the second mixture to a cooling temperature. In some embodiments, the cooling temperature is between about -25°C and about 10°C. In some embodiments, the cooling temperature is about 5°C. In some embodiments, the cooling temperature is about -20°C. In some embodiments, the method further comprises evaporating the solvent and the antisolvent from the second mixture at an evaporation temperature. In some embodiments, the evaporation temperature is room temperature. In some embodiments, the solvent comprises acetone, MeOH, THF, acetonitrile, DMSO, EtOH, EtOAc, 1,4-Di oxane, 2-MeTHF, CHCI3, DMAc, or DCM, or any mixture thereof; and the anti-solvent comprises water, n-Heptane, MTBE, or toluene, or any mixture thereof. In some embodiments, the solvent comprises acetone, THF, EtOH, EtOAc, THF, 1,4-dioxane, MeOH, 2-MeTHF, acetonitrile, CHCh, DMAc, or DCM, or any mixture thereof, and the anti -solvent comprises water, n-Heptane, MTBE, or toluene; wherein the crystalline form prepared from the method comprises freebase Form A. In some embodiments, the solvent comprises MeOH, acetonitrile, or DMSO, and the anti-solvent comprises water; wherein the crystalline form prepared from the method is amorphous.9. Solid-state characterization

[0140] In some embodiments, the method comprises: (i) stirring Compound 1 in a solution for a duration; (ii) centrifuging the mixture of step (i); and (iii) drying the precipitant of step (ii) at a temperature. In some embodiments, Compound 1 of step (i ) comprises freebase Form A. In some embodiments, the solution comprises HC1 in IP A; L-tartaric acid in IP A; fumaric acid in IPA and MIBK, or fumaric acid in IPAc; citric acid inacetone; malic acid in IP A and acetonitrile; malic acid in IP Ac, succinic acid in IP A and MIBK; succinic acid in 2-MeTHF; adipic acid in 2-MeTHF; 1,5-naphthalenedisulfonic acid in IP A; MIBK and acetonitrile; p-toluenesulfonic acid in IP Ac; methanesulfonic acid in MIBK; oxalic acid in MIBK; or HBr in MIBK, In some embodiments, the method further comprises stirring the mixture of step (i) at a temperature between about 0°C and about 10°C for a duration before centrifugation in step (ii). In some embodiments, the duration is between 12 and 36 hours. In some embodiments, the method further comprises heatingcooling the mixture of step (i) before centrifugation in step (ii). In some embodiments, the mixture is heated to between about 40°C and about 50°C, and cooled to between about 0°C and about 10°C. In some embodiments, the heating and cooling are each independently conducted at a rate of between about 0.01 °C / min and about 1 °C / min. In some embodiments, the duration in step (i) is between 1 and 5 days. In some embodiments, the temperature of step (iii) is room temperature.IV, Pharmaceutical Compositions and Formulations

[0141] Any of the crystalline forms described herein may be formulated as a pharmaceutically acceptable composition.

[0142] Pharmaceutical compositions of any of the crystalline forms detailed herein are embraced by this disclosure. Thus, the present disclosure includes pharmaceutical compositions comprising a crystalline form as detailed herein, and a pharmaceutically acceptable carrier or excipient. Pharmaceutical compositions may take a form suitable for oral, buccal, parenteral, nasal, topical, or rectal administration or a form suitable for administration by inhalation.

[0143] A crystalline form as detailed herein may in one aspect be in a purified form and compositions comprising a crystalline form in purified forms are detailed herein.Compositions comprising a crystalline form, as detailed herein are provided, such as compositions of substantially pure crystalline forms. In some embodiments, a composition containing a crystalline form, as detailed herein is in substantially pure form. In one variation, “substantially pure” intends a composition that contains no more than 35% impurity. In some embodiments, the impurity denotes a compound other than the crystalline form. In some embodiments, the impurity denotes a compound other than Compound 1. In some embodiments, the impurity denotes a compound other than Compound 1 and itsisomers. In one variation, a composition of substantially pure crystalline form, is provided wherein the composition contains no more than 25% impurity. In another variation, a composition of substantially pure crystalline form, is provided wherein the composition contains or no more than 20% impurity. In still another variation, a composition of substantially pure crystalline form, is provided wherein the composition contains or no more than 10% impurity. In a further variation, a composition of substantially pure crystalline form, is provided wherein the composition contains no more than 5% impurity. In another variation, a composition of substantially pure crystalline form, is provided wherein the composition contains no more than 3% impurity. In still another variation, a composition of substantially pure crystalline form, is provided wherein the composition contains no more than 1 % impurity. In a further variation, a composition of substantially pure cry stalline form, is provided wherein the composition contains no more than 0.5% impurity. In yet other variations, a composition of substantially pure crystalline form means that the composition contains no more than 15%, no more than 10%, no more than 5%, no more than 3%, or no more than 1% impurity, which impurity may be the crystalline form in a different stereochemical form. For instance, and without limitation, a composition of substantially pure (S) crystalline form means that the composition contains no more than 15% or no more than 10% or no more than 5% or no more than 3% or no more than 1% of the (R) form of the crystalline form.

[0144] In one variation, the crystalline forms herein are synthetic crystalline forms prepared for administration to an individual. In another variation, compositions are provided containing a crystalline form in substantially pure form. In another variation, the present disclosure embraces pharmaceutical compositions comprising a crystalline form detailed herein and a pharmaceutically acceptable carrier. In another variation, methods of administering a crystalline form are provided. The purified forms, pharmaceutical compositions and methods of administering the crystalline forms are suitable for any crystalline form or form thereof detailed herein. In some embodiments, the crystalline forms and compositions as provided herein are sterile. Methods for sterilization known in the art may be suitable for any crystalline forms or form thereof and compositions thereof as detailed herein.

[0145] A crystalline form detailed herein, may be formulated for any available delivery' route, including an oral, mucosal (e.g., nasal, sublingual, vaginal, buccal or rectal),parenteral (e.g., intramuscular, subcutaneous or intravenous), topical or transdermal delivery form. A crystalline form, may be formulated with suitable carriers to provide delivery' forms that include, but are not limited to, tablets, caplets, capsules (such as hard gelatin capsules or soft elastic gelatin capsules), cachets, troches, lozenges, gums, dispersions, suppositories, ointments, cataplasms (poultices), pastes, powders, dressings, creams, solutions, patches, aerosols (e.g., nasal spray or inhalers), gels, suspensions (e.g., aqueous or non-aqueous liquid suspensions, oil-in-water emulsions or water-in-oil liquid emulsions), solutions and elixirs.

[0146] A crystalline form detailed herein can be used in the preparation of a formulation, such as a pharmaceutical formulation, by combining the cry stal line form or cry stal line forms, with a pharmaceutically acceptable carrier. Depending on the therapeutic form of the system (e.g, transdermal patch vs. oral tablet), the carrier may be in various forms. In addition, pharmaceutical formulations may contain preservatives, solubilizers, stabilizers, rewetting agents, emulgators, sweeteners, dyes, adjusters, and salts for the adjustment of osmotic pressure, buffers, coating agents or antioxidants. Formulations comprising the crystalline form may also contain other substances which have valuable therapeutic properties. Pharmaceutical formulations may be prepared by known pharmaceutical methods. Suitable methods of preparing pharmaceutical formulations can be found, e.g, in Remington’s Pharmaceutical Sciences, Mack Publishing Company, Philadelphia, PA, 20th ed. (2000), which is incorporated herein by reference.

[0147] A crystalline form detailed herein, may be administered to individuals in a form of generally accepted oral compositions, such as tablets, coated tablets, and gel capsules in a hard or in soft shell, emulsions or suspensions. In addition, pharmaceutical formulations may contain preservatives, solubilizers, stabilizers, re-wetting agents, emulgators, sweeteners, dyes, adjusters, and salts for the adjustment of osmotic pressure, buffers, coating agents or antioxidants.

[0148] Any of the crystalline forms, described herein can be formulated in a tablet in any dosage form described.

[0149] Compositions comprising a crystalline form, provided herein are also described. In one variation, the composition comprises a crystalline form, and a pharmaceutically acceptable carrier or excipient. In another variation, a composition of substantially purecrystalline form, is provided. In some embodiments, the composition is for use as a human or veterinary medicament. In some embodiments, the composition is for use in a method described herein. In some embodiments, the composition is for use in the treatment of a disease or disorder described herein.

[0150] Compositions formulated for co-administration of a crystalline form provided herein and one or more additional pharmaceutical agents are also described. The coadministration can be simultaneous or sequential in any order. A crystalline form provided herein may be formulated for co-administration with the one or more additional pharmaceutical agents in the same dosage form (<?.g., single tablet or single i.v.) or separate dosage forms (e.g, two separate tablets, two separate i.v., or one tablet and one i.v.).Furthermore, co-administration can be, for example, 1) concurrent delivery, through the same route of delivery (e.g, tablet or i.v.), 2) sequential delivery on the same day, through the same route or different routes of delivery, or 3) delivery on different days, through the same route or different routes of delivery.V. Methods of Use

[0151] Crystalline forms and compositions disclosed herein, such as a pharmaceutical composition comprising a crystalline form of Compound 1 and a pharmaceutically acceptable carrier or excipient, may be used in a method of administration and treatment as provided herein. The crystalline forms and compositions may also be used in in vitro methods, such as in vitro methods of administering a crystalline form or composition to cells for screening purposes and / or for conducting quality control assays.

[0152] In one aspect, provided herein is a method of inhibiting the activity of KRAS G12C. In some embodiments, the method comprises contacting the KRAS G12C with a crystalline form or composition provided herein. In some embodiments, the crystalline form or composition provided herein is in a therapeutically effective amount.

[0153] In one aspect, provided herein is a method of inhibiting the activity of KRAS G12C in a cell. In some embodiments, the method comprises administering a crystalline form or composition provided herein to the cell. In some embodiments, the method comprises contacting the cell with a crystalline form or composition provided herein. In some embodiments, the crystalline form or composition provided herein is in a therapeutically effective amount.

[0154] In one aspect, provided is a method of treating cancer in a subject in need thereof. In some embodiments, the method comprises administering a therapeutically effective amount of the crystalline form or the pharmaceutical composition provided herein to the subject.

[0155] In some embodiments, the cancer is a lung, colorectal, pancreatic, bile duct, thyroid, gall bladder, uterine, mesothelioma, cervical, orbladder cancer. In some embodiments, the cancer is glioblastoma multiforme, lower grade glioma, head and neck squamous cell carcinoma, papillary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, breast invasive carcinoma, esophageal carcinoma, stomach adenocarcinoma, small intestine adenocarcinoma, colon adenocarcinoma, rectal adenocarcinoma, liver hepatocellular carcinoma, cholangiocarcinoma, gallbladder carcinoma, pancreatic adenocarcinoma, kidney renal clear cell carcinoma, bladder urothelial carcinoma, prostate adenocarcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, cervical squamous carcinoma and endocervical adenocarcinoma, skin cutaneous melanoma, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, plasma cell myeloma, uterine carcinosarcoma, mesothelioma, adrenocortical carcinoma, brain lower grade glioma, diffuse large B-cell lymphoma, esophageal adenocarcinoma, kidney chromophobe, kidney renal papillary cell carcinoma, pheochromocytom and paraganglioma, sarcoma, testicular germ cell tumors, thymoma, uveal melanoma, metastatic colorectal cancer, bladder cancer, adenoid cystic carcinoma, myelodysplastic, breast cancer, thyroid carcinoma, glioma, esophageal / stomach cancer, pediatric Wilms’ tumor, pediatric acute lymphoid leukemia, chronic lymphocytic leukemia, mature B-cell malignancies, pediatric neuroblastoma, non-small cell lung cancer (NSCLC), or melanoma. In some embodiments, the cancer is a non-small ceil lung cancer (NSCLC). In some embodiments, the cancer is a KRAS G12C mediated cancer. In some embodiments, the subject has been diagnosed as having a KRAS G12C mediated cancer.

[0156] In some embodiments, the subject is human.Combination therapy

[0001] Crystalline forms and compositions disclosed herein, such as a pharmaceutical composition comprising a crystalline form of Compound I and a pharmaceutically acceptableearner or excipient, may be used in combination with one or more other drags in the treatment of diseases or conditions for which crystalline forms and compositions disclosed herein or the other drags may have utility. Such other drag(s) may be administered contemporaneously or sequentially with a crystalline form or composition disclosed herein. When a crystalline form or composition disclosed herein is used contemporaneously with one or more other drags, a pharmaceutical composition in unit dosage form containing such other drags and the crystalline form or composition disclosed herein is contemplated. However, the combination therapy may also include therapies in which the crystalline form or composition disclosed herein and one or more other drugs are admini stered on different overlapping schedules. It is also contemplated that when used in combination with one or more other active ingredients, the crystalline form or composition disclosed herein and the other active ingredients may be used in lower doses than when each is used singly.

[0002] Accordingly, the pharmaceutical compositions of the present disclosure also include those that contain one or more other drugs, in addition to a crystalline form or composition disclosed herein.

[0003] The above combinations include combinations of a crystalline form or composition disclosed herein not only with one other drag, but also with two or more other active drags. Likewise, a crystalline form or composition disclosed herein may be used in combination with other drugs that are used in the prevention, treatment, control, amelioration, or reduction of risk of the diseases or conditions for which a crystalline form or composition disclosed herein is useful. Such other drags may be administered contemporaneously or sequentially with a crystalline form or composition disclosed herein. When a crystalline form or composition disclosed herein is used contemporaneously with one or more other drags, a pharmaceutical composition containing such other drags in addition to the crystalline form or composition disclosed herein can be used. Accordingly, the pharmaceutical compositions of the present disclosure also include those that also contain one or more other active ingredients, in addition to a crystalline form or composition disclosed herein. The weight ratio of the crystalline form or composition disclosed herein to the second active ingredient may be varied and will depend upon the effective dose of each ingredient. Generally, a therapeutically effective dose of each will be used.

[0004] Where the subject in need is suffering from or at risk of suffering from cancer, the subject can be treated with a crystalline form or composition disclosed herein in any combination with one or more other anti-cancer agents.

[0005] In some embodiments, the crystalline forms and compositions disclosed herein are used in combination with a CDK 4 / 6 inhibitor. Examples of CDK 4 / 6 inhibitors suitable for the provided compositions and methods include, but are not limited to, abemaciclib (N-(5-((4-ethylpi perazin-1 -yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-l-isopropyl-2-methyl-lH-benzo[d]imidazol-6-yl)pyrimidin-2-amine); palbociclib (6-acetyl-8- cyclopentyl-5-methyl-2-((5-(piperazin-l -yl)pyridin-2-yl)amino)-pyrido[2,3-d]pyrimidin-7(8H)-one) and ribociclib (7-cyclopentyl-N, N-dimethyl-2-((5-(piperazin-l-yl)pyridin-2-yl)amino)-7H- pyrrolo[2,3-d]pyrimidine-6-carboxamide) whereas the CDK 4 / 6 inhibitor trilaciclib (2'-((5-(piperazin-l -yl)pyridin-2-yl)amino)-7’,8'-dihydro-6’H-spiro-[cyclohexane-l,9’-pyrazino[l’,2':l,5]pyrrolo[2,3-d]pyrimidin]-6'-one) is in late stage clinical trials. Another CDK 4 / 6 inhibitor useful in the methods herein is the CDK 2 / 4 / 6 inhibitor PF-06873600 (pyrido[2,3- d]pyrimidin-7(8H)-one, 6-(difluoroniethyl)-8-[(lR,2R)-2-hydroxy-2-methylcyclopentyl]-2-[[l- (methylsulfonyl)-4-piperidinyl]amino]).

[0006] In another embodiment the crystalline forms and compositions disclosed herein are used in combination with Raf family kinase inhibitors. Examples of Raf family kinase inhibitors suitable for the provided compositions and methods include, but are not limited to, encorafenib (LGX818): methyl (S)-(l-((4-(3-(5-chloro- 2-fluoro-3-(methylsulfonamido)phenyl)-l-isopropyl-lH-pyrazol-4-yl)pyrimidin-2- yl)amino)propan-2-yl)carbamate; PLX-8394: N-(3-(5-(2-cyclopropylpyrimidin-5-yl)-3a,7a- dihydro-lH-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)-3-fluoropyrrolidine-l -sulfonamide; Raf-709: N-(2-methyl-5'-morpholino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'- bipyridin]-5-yl)-3-(trif1uoromethyl)benzamide; LXH254: N-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide; Sorafenib: 4-(4-(3 -(4-chl oro-3 -(trifluoromethy l)phenyl)urei do)phenoxy)-N -methyl pi colinamide; L Y 3009120: l-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido-[2,3-d]pyrimidin-6-yl)phenyl)urea; Lifirafenib (BGB-283); 5-(((lR,laS,6bS)-l-(6-(trifhioro-methyl)-lH-benzo[d]imidazol-2-yl)-la,6b-dihydro-lH-cyclopropa[b]benzofuran-5-yl)methyl)-3,4- dihydro- l,8-naphthyridin-2(lH)-one; Tak-632: N-(7-cyano-6-(4-fluoro-3-(2-(3- (trifluoromethyl)-phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yljcyclopropanecarboxamide; CEP-32496: l-(3-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-3-(5-(1, l,l-trifhioro-2- methylpropan-2-yl)isoxazol-3-yl)urea; CCT 196969: 1 -(3 -(tert-butyl)- 1 -phenyl- lH-pyrazol-5- yl)-3-(2-fluoro-4-((3-oxo-3,4-dihydropyrido [2,3 -b]pyrazin-8-yl)oxy)phenyl)urea; and R05126766: N-[3-fluoro-4-[[4-methyl-2-oxo-7-(2-pyrimidinyloxy)-2H- 1 -benzopyran-3 -y 1 ] methyl]-2-pyridinyl]-N' -methylsulfamide.

[0007] In another embodiment the crystalline forms and compositions disclosed herein are used in combination with Src family kinases. Examples of Src family kinase inhibitors suitable for the provided compositions and methods include, but are not limited to, Dasatinib (N-(2-chloro-6-methylphenyl)-2-((6-(4-(2- hydroxy ethyl)piperazin-l-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide); Ponatinib (3-(imidazo[l,2-b]pyridazin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-l-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide);Vandetanib (N-(4-bromo-2-fluorophenyl)-6-methoxy-7- ((1 -methylpiperidin-4-yl)methoxy)quinazolin-4-amine); Bosutinib (4-((2,4-di chi oro-5- methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-l -yl)-propoxy)quinoline-3- carbonitrile); Saracatinib (N-(5-chlorobenzo[d][l,3]dioxol-4-yl)-7-(2-(4-methylpiperazin-l- yl)ethoxy)-5-((tetrahydro-2H-pyran-4-yl)oxy)quinazolin-4-amine); KX2-391 (N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide); SU6656 ((Z)-N, N-dimethyl-2-oxo-3-((4,5,6,7-tetrahydro-lH-indol-2-yl)methylene)indoline-5-sulfonamide); PPI (l-(tert-butyl)-3-(p- tolyl)-lH-pyrazolo[3,4-d]pyrimidin-4-amine); WH-4-023 (2,6-dimethylphenyl (2,4-dimethoxyphenyl)(2-((4-(4-methylpiperazin-l-yl)phenyl)amino)pyrimidin-4-yl)carbamate) and KX-01 (N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide). In one embodiment, the Src inhibitor is Dasatinib. In one embodiment, the Src inhibitor is Saracatinib. In one embodiment, the Src inhibitor is Ponatinib. In one embodiment, the Src inhibitor is Vandetanib. In one embodiment, the Src inhibitor is KX-01.

[0008] In another embodiment the crystalline forms and compositions disclosed herein are used in combination with a SHP-2 inhibitor which include, but are not limited to SHP-099 (6-(4-amino-4-methylpiperidin-l-yl)-3-(2,3-dichlorophenyl)pyrazine-2-amine dihydrochloride), RMC-4550 (3(3S,4S)-(4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-6-(2,3-dichlorophenyl)pyrazin-2-yl)methanol), RMC-4360 (Revolution Medicines), TN0155 (Novartis), BBP-398 (BridgeBio), and ER / XS-601 (Erasca).

[0009] In another embodiment the crystalline forms and compositions disclosed herein are used in combination with an m FOR inhibitor. Examples of mTOR inhibitors suitable for the provided compositions and methods include, but are not limited to, Everolimus, Rapamycin, Zotarolimus (ABT-578), ridaforolimus (Deforolimus; MK-8669), Sapanisertib (INK128; 5-(4-amino-l-isopropyl-lH-pyrazolo[3,4-d]pyrimidin-3-yl)benzo[d]oxazol-2-amine), Torin-1; 1-(4-(4-propionylpiperazin-l-yl)-3- (trifluoromethyl)cyclohexyl)-9-(quinolin-3-yl)benzo[h][l,6]naphthyridin-2(lH)-one, dactolisib (BEZ235); 2-metliyl-2-(4-(3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-lH-imidazo[4,5-c]quinolin-l -yl)phenyl)propanenitrile, buparlisib (5-(2,6-dimorpholin-4-ylpyrimidin-4-yl)-4- (trifluoromethyl)pyridin-2-amine);GDC-0941 (pictilisib); 4-[2-(lH-indazol-4-yl)-6-[(4- methyl sulfonylpiperazin-1 -yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine); GDC-0349 ((S)- l-ethyl-3-(4-(4-(3-methylmorpholino)-7-(oxetan-3-yl)-5,6,7,8-tetrahydropyrido[3,4- d]pyrimidin-2-yl)phenyl)urea), VS-5584 (SB2343) (5-(8-methyl-2-moipholin-4-yl-9-propan-2-yl-purin-6-yl)pyrimidin-2-amine) and vistusertib (AZD-2014; 3-(2,4-bis((S)-3-methylmorpholino)pyrido-[2,3-d]pyrimidin-7-yl)-N-methylbenzamide).

[0010] In another embodiment the crystalline forms and compositions disclosed herein are used in combination with a pan ErbB family inhibitor. In one embodiment the KRAS and pan ErbB family inhibitors are the only active agents in the provided compositions and methods. In one embodiment, the pan ErbB family inhibitor is an irreversible inhibitor. Examples of irreversible pan ErbB family inhibitors suitable for the provided compositions and methods include, but are not limited to, Afatinib; Dacomitinib; Canertinib; Poziotinib, AV 412 (N-4-([3-(chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4-methyl-l-piperazin-l -butyn-l-yl]-6-quinazolinyl]-2-prepenamide); PF 6274484 N-4-([3-(chloro-4-fluorophenyl)aniino]-7-methoxy-6-quinazolinyl]-2-propenamide) and HKI 357 N-(2(E)-N-[[4-[[3-chloro-4-[(fluorophenyl)methoxy]phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide). In another embodiment, the pan ErbB family inhibitor is a reversible inhibitor. Examples of reversible pan ErbB family inhibitors suitable for the provided compositions and methods include, but are not limited to erlotinib, gefitinib, sapitinib; varlitinib; TAK-285 (N-[2-[4-[3- chloro-4-[3-(trifluoromethyl)phenoxy]phenylamino]-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-3-hydroxy-3-methylbutanamide); AEE788 (S)-(6-(4-((4-ethylpiperazin- 1 -ylmethyl)phenyl]-N-(l -phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine); tarloxotinib 3-[N-[4-(3-bromo-4-chlorophenylamino)-pyrido[3,4-d]pyrimidin-6-yl]carbamoyl]-N, N-dimethyl-N-(l-methyl-4-nitro-1FI-imidazol-5-ylmethyl)-2(E)-propen-l-aminium bromide); BMS 599626 ((3S)- 3-morpholinylmethyl-[4-[[l-[(3-fluorophenyl)methyl]-lH-indazol-5-yl]amino]-5-methylpurrolo[2, l-f][l,2,4]triazine-6-yl]carbamate dihydrochloride); and GW 583340 (N-[3-chloro-4-(3- fluorobenzyl oxy )phenyl]-6-[2-[2-(methylsulfonyl)ethylaminomethyl]thiazol-4-yl]quinazolin-4-amine dihydrochloride).

[0011] In one embodiment, the pan ErbB family inhibitor is a combination of an EGFR inhibitor and a HER2 inhibitor, wherein the EGFR inhibitor and the HER2 inhibitor are a combination of two of: AG 1478 (N-(3-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine hydrochloride); AG 555 ((E)-2-cyano-3-(3,4-dihydoxyphenyl)-N-(3-phenylpropyl)-2-propenamide); AG 556 ((E)-2- cyano-3-(3,4-dihydroxyphenyl)-N-(4-phenylbutyl)-2-propenamide; AG 825 (E-3-[3-benzothiazol-2- ylsulfanylmethyl)-4-hydroxy-5- 61methoxyphenyl]-2-cyano-2-propenamide); CP 724714 (2- methoxy-N-[(2E)-3-[4-[3-methyl-4-(6-methylpyridin-3-yloxy)phenylamino]quinazolin-6-yl]-2- propen-l-yl]acetamide; BIBU 1361 (N-(3-chloro-4-fluorophenyl)-6-[4-(diethylaminoniethyl)-piperidin-l-yl]pyriniido[5,4-d]pyrimidin-4-amine dihydrochloride); BIBU 1382; (N8-(3-chloro-4-fluorophenyl)-N2-(l-methyl-4-piperidinyl)pyrimidino[5,4-d]pyrimidin-4-amine di hydrochloride), JNJ 28871063 (5E-4-amino-6-[4-(benzyloxy)-3-chlorophenylamino]-pyrimidine-5-carbaldehyde N-[2-(4-morpholinyl)ethyl]oxime hydrochloride); PD 153035 (4-(3-bromophenylamino)-6,7-dimethoxyquinazoline hydrochloride); andPD 158780 (N4-(3-bromophenyl)-N6-methyl-pyrido[3,4-d]pyrimidine-4,6-di amine).

[0012] In one embodiment, the pan ErbB family inhibitor is an anti-EGFR antibody, an anti-HER2 antibody or combination of an anti-EGFR antibody and anti-HER2 antibody.Antibodies, including monoclonal antibodies, antibody conjugates and bispecific antibodies, targeting EGFR and / or FIER2 are well known and several antibodies are commercially available for research and human clinical use. Examples of anti-EGFR antibodies suitable for the provided compositions and methods include necitumumab, panitumumab and cetuximab. Examples of anti-HER2 antibodies suitable for the provided compositions and methods include, pertuzumab, trastuzumab, and trastuzumab emtansine.

[0013] In some embodiments, the crystalline forms and compositions disclosed herein are used in combination with an immune checkpoint inhibitor. Examples of immune checkpoint inhibitors suitable for the provided compositions and methods include, but are not limited to, PD-1, PD-L1, CTLA-4, and LAG-3 inhibitors, such as Pembrolizumab (Keytruda®), Nivolumab (Opdivo®), Cemiplimab (Libtayo®), Atezolizumab (Tecentriq®), Avelumab (Bavencio®), Durvalumab (ImfinziTM), Ipilimumab (Yervoy®), Relatlimab, Opdualag, and Dostarli m ab (J emperli ).

[0014] The compounds, pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising such compounds and salts also may be co-administered with other anti -neoplastic compounds, e.g, chemotherapy, or used in combination with other treatments, such as radiation or surgical intervention, either as an adjuvant prior to surgery or post-operatively.VI. Dosing and Method of Administration

[0157] The dose of a crystalline form described herein, administered to an individual (such as a human) may vary with the particular crystalline form, the method ofadministration, and the particular cancer, such as type and stage of cancer, being treated. In some embodiments, the amount of the crystalline form, is a therapeutically effective amount.

[0158] The crystalline forms provided herein, may be administered to an individual via various routes, including, e.g., intravenous, intramuscular, subcutaneous, oral, and transdermal.

[0159] The effective amount of the crystalline form may in one aspect be a dose of between about 0.01 and about 100 mg / kg. Effective amounts or doses of the crystalline forms of the present disclosure may be ascertained by routine method s, such as modeling, dose escalation, or clinical trials, taking into account routine factors, e.g., the mode or route of administration or drug delivery, the pharmacokinetics of the agent, the severity and course of the disease to be treated, the subject’s health status, condition, and weight.

[0160] Any of the methods provided herein may in one aspect comprise administering to an individual a pharmaceutical composition that contains an effective amount of a crystalline form provided herein, and a pharmaceutically acceptable excipient.

[0161] A crystalline form or composition provided herein may be administered to an individual in accordance with an effective dosing regimen for a desired period of time or duration. Any of the dosing frequencies can employ any of the crystalline forms described herein together with any of the dosages described herein.VII. Articles of Manufacture and Kits

[0162] The present disclosure further provides articles of manufacture comprising a crystalline form described herein, a composition described herein, or one or more unit dosages described herein in suitable packaging. In certain embodiments, the article of manufacture is for use in any of the methods described herein. Suitable packaging is known in the art and includes, for example, vials, vessels, ampules, bottles, jars, flexible packaging and the like. An article of manufacture may further be sterilized and / or sealed.

[0163] The present disclosure further provides kits for carrying out the methods of the present disclosure, which comprises one or more crystalline forms described herein or a composition comprising a crystalline form described herein. The kits may employ any of the crystalline forms disclosed herein. In one variation, the kit employs a crystalline formdescribed herein, thereof. The kits may be used for any one or more of the uses described herein, and, accordingly, may contain instructions for the treatment of any disease or described herein, for example for the treatment of cancer.

[0164] The kits optionally further comprise a container comprising one or more additional pharmaceutical agents and which kits further comprise instructions on or in the package insert for treating the subject with an effective amount of the one or more additional pharmaceutical agents.

[0165] Kits generally comprise suitable packaging. The kits may comprise one or more containers comprising any crystalline form described herein. Each component (if there is more than one component) can be packaged in separate containers or some components can be combined in one container where cross-reactivity and shelflife permit.

[0166] The kits may be in unit dosage forms, bulk packages (e.g, multi-dose packages) or sub-unit doses. For example, kits may be provided that contain sufficient dosages of a crystalline form as disclosed herein and / or an additional pharmaceutically active crystalline form useful for a disease detailed herein to provide effective treatment of an individual for an extended period. Kits may also include multiple unit doses of the crystalline forms and instructions for use and be packaged in quantities sufficient for storage and use in pharmacies (e.g., hospital pharmacies and compounding pharmacies).

[0167] The kits may optionally include a set of instructions, generally written instructions, although electronic storage media (e.g, magnetic diskette or optical disk) containing instructions are also acceptable, relating to the use of component(s) of the methods of the present disclosure. The instructions included with the kit generally include information as to the components and their administration to an individual.ENUMERATED EMBODIMENTS

[0168] The following enumerated embodiments are representative of some aspects of the invention.1, A crystalline form of l-((2R,3R)-3-((7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro- 2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3- d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin- 1 -yl)prop-2-en- 1 -one (Compound 1).The crystalline form of embodiment 1, wherein the crystalline form is an anhydrate. The crystalline form of embodiment 1 or 2, characterized by having an XRPD pattern of freebase Form A substantially as shown in FIG. 1 A.The crystalline form of any one of embodiments 1 to 3, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0.The crystalline form of any one of embodiments 1 to 4, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 10.0.The crystalline form of any one of embodiments 1 to 5, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.4,The crystalline form of any one of embodiments 1 to 6, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.0, about 5.9, about 7.3, about 10.0, about 13.4, about 15.0, and about 16.4.The crystalline form of any one of embodiments 1 to 7, characterized by having a DSC graph comprising an exothermic peak at about 199.9 °C.The crystalline form of any one of embodiments 1 to 8, characterized by having a DSC graph substantially as shown in FIG. IB.The crystalline form of any one of embodiments 1 to 9, characterized by having a TGA graph substantially as shown in FIG. IB.The crystalline form of any one of embodiments 1 to 10, characterized by having a DVS graph substantially as shown in FIG. 1C.The crystalline form of embodiment 1, wherein the crystalline form is a solvate. The crystalline form of embodiment 1 or 12, characterized by having an XRPD pattern of freebase Form E substantially as shown in FIG. 2A.The crystalline form of any one of embodiments 1, 12, and 13, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 9.9.The crystalline form of any one of embodiments 1 and 12 to 14, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 14.9.The crystalline form of any one of embodiments 1 and 12 to 15, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 8.9.The crystalline form of any one of embodiments 1 and 12 to 16, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 4.9, about 6.9, about 8.9, about 9.9, about 14.9, about 16.5, about 17.0, and about 18.3.The crystalline form of any one of embodiments 1 and 12 to 17, characterized by having a DSC graph comprising an exothermic peak at about 188.9 °C.The crystalline form of any one of embodiments 1 and 12 to 18, characterized by having a DSC graph substantially as shown in FIG. 2B,The crystalline form of any one of embodiments 1 and 12 to 19, characterized by having a TGA graph substantially as shown in FIG. 2B.The crystalline form of embodiment 1, characterized by having an XRPD pattern of freebase Form B substantially as shown in FIG. 3.The crystalline form of embodiment 1 or 21, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 8.5.The crystalline form of any one of embodiments 1 and 21 to 22, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 6.8.The crystalline form of any one of embodiments 1 and 21 to 23, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 16.6.The crystalline form of any one of embodiments 1 and 21 to 24, characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 6.8, about 8.5, and about 16.6.The crystalline form of embodiment 1, characterized by having an XRPD pattern of freebase Form C substantially as shown in FIG. 4.The crystalline form of embodiment 1 or 26, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 8.4.The crystalline form of any one of embodiments 1, 26, and 27, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 4.2.The crystalline form of any one of embodiments 1 and 26 to 28, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 16.6.The crystalline form of any one of embodiments 1 and 26 to 29, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 4.2, about 6.8, about 8.4, about 9.8, about 15.6, about 16.6, and about 16.8.The crystalline form of embodiment 1, characterized by having an XRPD pattern of freebase Form D substantially as shown in FIG. 5.The crystalline form of embodiment 1 or 31, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.5.The crystalline form of any one of embodiments 1, 31, and 32, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.6.The crystalline form of any one of embodiments 1 and 31 to 33, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 9.9.The crystalline form of any one of embodiments 1 and 31 to 34, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 6.9, about 8.5, about 9.9, about 14.9, about 15.6, and about 16.5.A crystalline form of a salt of l-((2R,3R)-3-((7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l-yl)prop-2-en-l-one (Compound 1).The crystalline form of embodiment 36, wherein the crystalline form is a hydrochloride salt.The crystalline form of embodiment 36 or 37, characterized by having an XRPD pattern of HQ salt Form A substantially as shown in FIG. 6A.The crystalline form of any one of embodiments 36 to 38, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.6,The crystalline form of any one of embodiments 36 to 39, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 13.0.The crystalline form of any one of embodiments 36 to 40, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 14.6.The crystalline form of any one of embodiments 36 to 41, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 11.6, about 12.0, about 13.0, about 13.4, about 14.3, about 14.6, about 15.7, about 16.5, about 16.8, about 17.5, about 18.5, and about 18.7.The crystalline form of any one of embodiments 36 to 42, characterized by having a DSC graph comprising an endothermic peak at about 179.3 °C.The crystalline form of any one of embodiments 36 to 43, characterized by having a DSC graph comprising an exothermic peak at about 221.8 °C.The crystalline form of any one of embodiments 36 to 44, characterized by having a DSC graph substantially as shown in FIG. 6B.The crystalline form of any one of embodiments 36 to 45, characterized by having a TGA graph substantially as shown in FIG. 6B.The crystalline form of any one of embodiments 36 to 46, characterized by having a DVS graph substantially as shown in FIG. 6C.The crystalline form of embodiment 36, wherein the crystalline form is a citrate salt. The crystalline form of embodiment 36 or 48, characterized by having an XRPD pattern of citrate salt Form A substantially as shown in FIG. 7A.The crystalline form of any one of embodiments 36, 48, and 49, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 4.9.The crystalline form of any one of embodiments 36 and 48 to 50, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 9.6.The crystalline form of any one of embodiments 36 and 48 to 51, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 6.4.The crystalline form of any one of embodiments 36 and 48 to 52, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 4.9, about 6.4, about 7.8, about 9.6, about 11.5, about 12.1, about 12.8, about 13.5, about 14.6, about 15.3, about 15.8, about 17.0, about 17.4, about 18.1, and about 18.8.The crystalline form of any one of embodiments 36 and 48 to 53, characterized by having a DSC graph comprising an exothermic peak at about 173.7 °C.The crystalline form of any one of embodiments 36 and 48 to 54, characterized by having a DSC graph substantially as shown in FIG. 7B.The crystalline form of any one of embodiments 36 and 48 to 55, characterized byhaving a TGA graph substantially as shown in FIG. 7B.The crystalline form of any one of embodiments 36 and 48 to 56, characterized by having a DVS graph substantially as shown in FIG. 7C.The crystalline form of embodiment 36, wherein the crystalline form is a succinate salt.The crystalline form of embodiment 36 or 58, characterized by having an XRPD pattern of succinate salt Form A substantially as shown in FIG. 8A.The crystalline form of any one of embodiments 36, 58, and 59, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.9.The crystalline form of any one of embodiments 36 and 58 to 60, characterized byhaving an XRPD pattern comprising a peak at angle 2-theta of about 11.3.The crystalline form of any one of embodiments 36 and 58 to 61, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.9.The crystalline form of any one of embodiments 36 and 58 to 62, characterized byhaving an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 8.0, about 8.7, about 10.1, about 11.3, about 11.9, about 15.1, about 15.9, about 17.0, about 18.1, and about 18.7.The crystalline form of any one of embodiments 36 and 58 to 63, characterized byhaving a DSC graph comprising an endothermic peak at about 146.3 °C.The crystalline form of any one of embodiments 36 and 58 to 64, characterized by having a DSC graph comprising an exothermic peak at about 159.6 °C.The crystalline form of any one of embodiments 36 and 58 to 65, characterized by having a DSC graph substantially as shown in FIG. 8B.The crystalline form of any one of embodiments 36 and 58 to 66, characterized by having a TGA graph substantially as shown in FIG. 8B.The crystalline form of any one of embodiments 36 and 58 to 67, characterized by having a DVS graph substantially as shown in FIG. 8C.The crystalline form of embodiment 36 or 58, characterized by having an XRPD pattern of succinate salt Form B substantially as shown in FIG. 8D.The crystalline form of any one of embodiments 36, 58, and 69, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.6.The crystalline form of any one of embodiments 36, 58, 69, and 70, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.8.The crystalline form of any one of embodiments 36, 58, and 69 to 71, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.1.The crystalline form of any one of embodiments 36, 58, and 69 to 72, characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 5.9, about 7.8, about 8.8, about 10.1, about 11.1, about 11.9, about 15.6, about 16.8, about 17.9, and about 19.0.The crystalline form of any one of embodiments 36, 58, and 69 to 73, characterized by having a DSC graph comprising an endothermic peak at about 145.6 °C.The crystalline form of any one of embodiments 36, 58, and 69 to 74, characterized by having a DSC graph comprising an exothermic peak at about 157.5 °C.The crystalline form of any one of embodiments 36, 58, and 69 to 75, characterized by having a DSC graph substantially as shown in FIG. 8E.The crystalline form of any one of embodiments 36, 58, and 69 to 76, characterized by having a TGA graph substantially as shown in FIG. 8E.The crystalline form of embodiment 36 or 58, characterized by having an XRPD pattern of succinate salt Form C substantially as shown in FIG. 8D.The crystalline form of any one of embodiments 36, 58, and 78, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.8.The crystalline form of any one of embodiments 36, 58, 78, and 79, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.5.The crystalline form of any one of embodiments 36, 58, and 78 to 80, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.7.The crystalline form of any one of embodiments 36, 58, and 78 to 81, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.7, about 8.9, about 10.2, about 10.9, about 12.0, about 15.5, about 17.0, and about 18.1.The crystalline form of any one of embodiments 36, 58, and 78 to 82, characterized by having a DSC graph comprising an endothermic peak at about 140.9 °C.The crystalline form of any one of embodiments 36, 58, and 78 to 83, characterized by having a DSC graph comprising an exothermic peak at about 157.9 °C.The crystalline form of any one of embodiments 36, 58, and 78 to 84, characterized by having a DSC graph substantially as shown in FIG. 8F.The crystalline form of any one of embodiments 36, 58, and 78 to 85, characterized by having a TGA graph substantially as shown in FIG. 8F.The crystalline form of embodiment 36, wherein the crystalline form is a tartrate salt. The crystalline form of embodiment 36 or 87, characterized by having an XRPD pattern of tartrate salt Form A substantially as shown in FIG. 9A.The crystalline form of any one of embodiments 36, 87, and 88, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.6.The crystalline form of any one of embodiments 36 and 87 to 89, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.5.The crystalline form of any one of embodiments 36 and 87 to 90, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.3.The crystalline form of any one of embodiments 36 and 87 to 91, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.5, about 7.6, about 8.8, about 9.4, about 10.0, about 11.3, about 12.5, about 14.2, about 15.3, and about 16.3.The crystalline form of any one of embodiments 36 and 87 to 92, characterized by having a DSC graph comprising an endothermic peak at about 52.6 °C.The crystalline form of any one of embodiments 36 and 87 to 93, characterized by having a DSC graph comprising an exothermic peak at about 170.2 °C.The crystalline form of any one of embodiments 36 and 87 to 94, characterized by having a DSC graph substantially as shown in FIG. 9B,The crystalline form of any one of embodiments 36 and 87 to 95, characterized by having a TGA graph substantially as shown in FIG. 9B.The crystalline form of embodiment 36, wherein the crystalline form is a fumarate salt.The crystalline form of embodiment 36 or 97, characterized by having an XRPD pattern of fumarate salt Form A substantially as shown in FIG. 10A.The crystalline form of any one of embodiments 36, 97, and 98, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.8.The crystalline form of any one of embodiments 36 and 97 to 99, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.9.The crystalline form of any one of embodiments 36 and 97 to 100, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.0.The crystalline form of any one of embodiments 36 and 97 to 101, characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 5.9, about 7.8, about 9.3, about 11.0, about 12.3, and about 15.7.The crystalline form of any one of embodiments 36 and 97 to 102, characterized by having a DSC graph comprising an exothermic peak at about 170.5 °C.The crystalline form of any one of embodiments 36 and 97 to 103, characterized by having a DSC graph substantially as shown in FIG. 10B.The crystalline form of any one of embodiments 36 and 97 to 104, characterized by having a TGA graph substantially as shown in FIG. 10B.The crystalline form of embodiment 36 or 97, characterized by having an XRPD pattern of fumarate salt Form B substantially as shown in FIG. 10A.The crystalline form of any one of embodiments 36, 97, and 106, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.0.The crystalline form of any one of embodiments 36, 97, 106, 107, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.8.The crystalline form of any one of embodiments 36, 97, and 106 to 108, characterized by having an XRPD pattern compri sing a peak at angle 2-theta of about 7.8.The crystalline form of any one of embodiments 36, 97, and 106 to 109, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.8, about 8.9, about 11.0, about 12.0, about 15.5, about 16.9, and about 18.1.The crystalline form of any one of embodiments 36, 97, and 106 to 110, characterized by having a DSC graph comprising an exothermic peak at about 171.6 °C.The crystalline form of any one of embodiments 36, 97, and 106 to 111, characterized by having a DSC graph substantially as shown in FIG. 10C.The crystalline form of any one of embodiments 36, 97, and 106 to 112, characterized by having a TGA graph substantially as shown in FIG. 10C.The crystalline form of embodiment 36 or 97, characterized by having an XRPD pattern of fumarate salt Form C substantially as shown in FIG. 10A.The crystalline form of any one of embodiments 36, 97, and 114, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 6.8.The crystalline form of any one of embodiments 36, 97, 114, and 115, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.8.The crystalline form of any one of embodiments 36, 97, and 114 to 116, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 11.7.The crystalline form of any one of embodiments 36, 97, and 114 to 117, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.5, about 6.8, about 7.9, about 9.7, about 11.0, about 11.7, about 13.1, about 15.3, about 15.9, about 16.8, and about 18.9.The crystalline form of any one of embodiments 36, 97, and 114 to 118, characterized by having a DSC graph comprising an endothermic peak at about 57.1 °C.The crystalline form of any one of embodiments 36, 97, and 114 to 119, characterized by having a DSC graph comprising an exothermic peak at about 167.7 °C.The crystalline form of any one of embodiments 36, 97, and 114 to 120, characterized by having a DSC graph substantially as shown in FIG. 10D.The crystalline form of any one of embodiments 36, 97, and 114 to 121, characterized by having a TGA graph substantially as shown in FIG. 10D.The crystalline form of embodiment 36, wherein the crystalline form is a malate salt. The crystalline form of embodiment 36 or 123, characterized by having an XRPD pattern of malate salt Form A substantially as shown in FIG. 11 A.The crystalline form of any one of embodiments 36, 123, and 124, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0.The crystalline form of any one of embodiments 36 and 123 to 125, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.3.The crystalline form of any one of embodiments 36 and 123 to 126, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 13.6.The crystalline form of any one of embodiments 36 and 123 to 127, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 6.3, about 7.3, about 7.9, about 9.1, about 13.6, about 15.1, about 15.9, about 16.7, and about 18.1.The crystalline form of any one of embodiments 36 and 123 to 128, characterized by having a DSC graph comprising an endothermic peak at about 145.7 °C.The crystalline form of any one of embodiments 36 and 123 to 129, characterized by having a DSC graph comprising an exothermic peak at about 161.4 °C.The crystalline form of any one of embodiments 36 and 123 to 130, characterized by having a DSC graph substantially as shown in FIG. 11B.The crystalline form of any one of embodiments 36 and 123 to 131, characterized by having a TGA graph substantially as shown in FIG. 11B.The crystalline form of embodiment 36 or 123, characterized by having an XRPD pattern of malate salt Form B substantially as shown in FIG. 11 A.The crystalline form of any one of embodiments 36, 123, and 133, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.4.The crystalline form of any one of embodiments 36, 123, 133, and 134, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.6.The crystalline form of any one of embodiments 36, 123, and 133 to 135, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.0.The crystalline form of any one of embodiments 36, 123, and 133 to 136, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.4, about 8.9, about 11.2, and about 15.0.The crystalline form of any one of embodiments 36, 123, and 133 to 137, characterized by having a DSC graph comprising an endothermic peak at about 49.3 °C.The crystalline form of any one of embodiments 36, 123, and 133 to 138, characterized by having a DSC graph comprising an endothermic peak at about 113.4 °C.The crystalline form of any one of embodiments 36, 123, and 133 to 139, characterized by having a DSC graph comprising an exothermic peak at about 162.5 orThe crystalline form of any one of embodiments 36, 123, and 133 to 140, characterized by having a DSC graph substantially as shown in FIG. 11C.The crystalline form of any one of embodiments 36, 123, and 133 to 141, characterized by having a TGA graph substantially as shown in FIG. 11C,The crystalline form of embodiment 36 or 123, characterized by having an XRPD pattern of malate salt Form C substantially as shown in FIG. 11 A.The crystalline form of any one of embodiments 36, 123, and 143, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.8.The crystalline form of any one of embodiments 36, 123, 143, and 144, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.9.The crystalline form of any one of embodiments 36, 123, and 143 to 145, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.7.The crystalline form of any one of embodiments 36, 123, and 143 to 146, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.9, about 8.9, about 11.1, about 15.1, about 15.7, about 17.2, and about 18.3.The crystalline form of any one of embodiments 36, 123, and 143 to 147, characterized by having a DSC graph comprising an endothermic peak at about 144.6 °C.The crystalline form of any one of embodiments 36, 123, and 143 to 148, characterized by having a DSC graph comprising an exothermic peak at about 158.2 °C.The crystalline form of any one of embodiments 36, 123, and 143 to 149, characterized by having a DSC graph substantially as shown in FIG. 11D.The crystalline form of any one of embodiments 36, 123, and 143 to 150, characterized by having a TGA graph substantially as shown in FIG. 11D.The crystalline form of embodiment 36, wherein the crystalline form is an adipate salt.The crystalline form of embodiment 36 or 152, characterized by having an XRPD pattern of adipate salt Form A substantially as shown in FIG. 12.The crystalline form of any one of embodiments 36, 152, and 153, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.1.The crystalline form of any one of embodiments 36 and 152 to 154, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 10.1.The crystalline form of any one of embodiments 36 and 152 to 155, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 16.5,The crystalline form of any one of embodiments 36 and 152 to 156, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 7.3, about 8.5, about 9.2, about 10.1, about 13.7, about 15.1, about 16.5, and about 17.0. The crystalline form of embodiment 36, wherein the crystalline form is a napadisylate salt.The crystalline form of embodiment 36 or 158, characterized by having an XRPD pattern of napadisylate salt Form A substantially as shown in FIG. 13 A.The crystalline form of any one of embodiments 36, 158, and 159, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.3.The crystalline form of any one of embodiments 36 and 158 to 160, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 19.7.The crystalline form of any one of embodiments 36 and 158 to 161, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 15.4.The crystalline form of any one of embodiments 36 and 158 to 162, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 7.3, about 15.4, and about 19.7.The crystalline form of any one of embodiments 36 and 158 to 163, characterized by having a DSC graph comprising an endothermic peak at about 56.8 °C.The crystalline form of any one of embodiments 36 and 158 to 164, characterized by having a DSC graph comprising an endothermic peak at about 160.0 °C.The crystalline form of any one of embodiments 36 and 158 to 165, characterized by having a DSC graph comprising an exothermic peak at about 257.8 °C.The crystalline form of any one of embodiments 36 and 158 to 166, characterized by having a DSC graph substantially as shown in FIG. 13B.The crystalline form of any one of embodiments 36 and 158 to 167, characterized by having a TGA graph substantially as shown in FIG. 13B.The crystalline form of embodiment 36 or 158, characterized by having an XRPD pattern of napadisylate salt Form B substantially as shown in FIG. 13A.The crystalline form of any one of embodiments 36, 158, and 169, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.6.The crystalline form of any one of embodiments 36, 158, 169, and 170, characterized by having a DSC graph comprising an endothermic peak at about 49.3 °C.The crystalline form of any one of embodiments 36, 158, and 169 to 171, characterized by having a DSC graph comprising an endothermic peak at about 137.6 °C.The crystalline form of any one of embodiments 36, 158, and 169 to 172, characterized by having a DSC graph comprising an exothermic peak at about 201.5 °C.The crystalline form of any one of embodiments 36, 158, and 169 to 173, characterized by having a DSC graph substantially as shown in FIG. 13C.The crystalline form of any one of embodiments 36, 158, and 169 to 174, characterized by having a TGA graph substantially as shown in FIG. 13C.The crystalline form of embodiment 36 or 158, characterized by having an XRPD pattern of napadisylate salt Form C substantially as shown in FIG. 13A.The crystalline form of any one of embodiments 36, 158, and 176, characterized by having a DSC graph comprising an endothermic peak at about 50.2 °C.The crystalline form of any one of embodiments 36, 158, 176, and 177, characterized by having a DSC graph comprising an endothermic peak at about 125.9 °C.The crystalline form of any one of embodiments 36, 158, and 176 to 178, characterized by having a DSC graph comprising an exothermic peak at about 265.7 °C.The crystalline form of any one of embodiments 36, 158, and 176 to 179, characterized by having a DSC graph substantially as shown in FIG. 13D.The crystalline form of any one of embodiments 36, 158, and 176 to 180, characterized by having a TGA graph substantially as shown in FIG. 13D.The crystalline form of embodiment 36, wherein the crystalline form is a tosylate salt. The crystalline form of embodiment 36 or 182, characterized by having an XRPD pattern of tosylate salt Form A substantially as shown in FIG. 14A.The crystalline form of any one of embodiments 36, 182, and 183, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.2.The crystalline form of any one of embodiments 36 and 182 to 184, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 12.1.The crystalline form of any one of embodiments 36 and 182 to 185, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 15.5.The crystalline form of any one of embodiments 36 and 182 to 186, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.2, about 7.4, about 8.6, about 10.0, about 11.3, about 12.1, about 13.2, about 14.4, about 14.9, about 15.5, about 17.3, and about 18.3.The crystalline form of any one of embodiments 36 and 182 to 187, characterized by having a DSC graph comprising an endothermic peak at about 138.6 °C.The crystalline form of any one of embodiments 36 and 182 to 188, characterized by having a DSC graph comprising an exothermic peak at about 214.2 °C.The crystalline form of any one of embodiments 36 and 182 to 189, characterized by having a DSC graph substantially as shown in FIG. 14B.The crystalline form of any one of embodiments 36 and 182 to 190, characterized by having a TGA graph substantially as shown in FIG. 14B.The crystalline form of embodiment 36, wherein the crystalline form is a mesylate salt.The crystalline form of embodiment 36 or 192, characterized by having an XRPD pattern of tosylate salt Form A substantially as shown in FIG. 15A.The crystalline form of any one of embodiments 36, 192, and 193, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 7.4.The crystalline form of any one of embodiments 36 and 192 to 194, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 9.8.The crystalline form of any one of embodiments 36 and 192 to 195, characterized by having an XRPD pattern comprising a peak at angle 2-theta of about 5.6.The crystalline form of any one of embodiments 36 and 192 to 196, characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.4, about 9.8, and about 17.5.The crystalline form of any one of embodiments 36 and 192 to 197, characterized by having a DSC graph comprising an exothermic peak at about 222.8 °C.The crystalline form of any one of embodiments 36 and 192 to 198, characterized by having a DSC graph substantially as shown in FIG. 15B.The crystalline form of any one of embodiments 36 and 192 to 199, characterized by having a TGA graph substantially as shown in FIG. 15B.The crystalline form of embodiment 36, wherein the crystalline form is an oxalate salt.The crystalline form of embodiment 36 or 201, characterized by having an XRPD pattern of oxalate salt Form A substantially as shown in FIG, 16A.The crystalline form of any one of embodiments 36, 201, and 202, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 5.6.The crystalline form of any one of embodiments 36 and 201 to 203, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 14.6.The crystalline form of any one of embodiments 36 and 201 to 204, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 7.7.The crystalline form of any one of embodiments 36 and 201 to 205, characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 5.6, about 7.7, about 10.0, about 11.6, about 14.6, about 15.0, about 15.5, about 16.4, about 17.2, about 18.1, and about 18.8.The crystalline form of any one of embodiments 36 and 201 to 206, characterized by having a DSC graph comprising an endothermic peak at about 82.4 °C.The crystalline form of any one of embodiments 36 and 201 to 207, characterized by having a DSC graph comprising an exothermic peak at about 174.0 °C.The crystalline form of any one of embodiments 36 and 201 to 208, characterized by having a DSC graph substantially as shown in FIG. 16B.The crystalline form of any one of embodiments 36 and 201 to 209, characterized by having a TGA graph substantially as shown in FIG. 16B.The crystalline form of embodiment 36, wherein the crystalline form is a hydrobromide salt.The crystalline form of embodiment 36 or 211, characterized by having an XRPD pattern of hydrobromide salt Form A substantially as shown in FIG, 17A,The crystalline form of any one of embodiments 36, 211, and 212, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 11.6.The crystalline form of any one of embodiments 36 and 211 to 213, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 21.7.The crystalline form of any one of embodiments 36 and 211 to 214, characterized by having an XRPD pattern comprising a peak at angle 2 -theta of about 12.9.The crystalline form of any one of embodiments 36 and 211 to 215, characterized by having an XRPD pattern comprising peaks at angles 2 -theta of about 11.6, about 12.9, about 18.2, and about 21.7.The crystalline form of any one of embodiments 36 and 211 to 216, characterized by having a DSC graph comprising an endothermic peak at about 57.2 °C.The crystalline form of any one of embodiments 36 and 211 to 217, characterized by having a DSC graph comprising an exothermic peak at about 215.6 °C.The crystalline form of any one of embodiments 36 and 211 to 218, characterized by having a DSC graph substantially as shown in FIG. 17B.The crystalline form of any one of embodiments 36 and 211 to 219, characterized by having a TGA graph substantially as shown in FIG. 17B.The crystalline form of any one of embodiments 1 to 220, wherein the purity of the crystalline form is at least about 95%.A pharmaceutical composition comprising a crystalline form of any one of embodiments 1 to 221, and a pharmaceutically acceptable excipient.A method of treating cancer in a subject in need thereof, the method comprising: administering a therapeutically effective amount of the crystalline form of any one of embodiments 1 to 221, or the pharmaceutical composition of embodiment 222, to the subject.The method of embodiment 223, wherein the cancer is a lung, colorectal, pancreatic, bile duct, thyroid, gall bladder, uterine, mesothelioma, cervical, or bladder cancer. The method of embodiment 223 or 224, wherein the cancer is glioblastoma multiforme, lower grade glioma, head and neck squamous cell carcinoma, papillary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, breast invasive carcinoma, esophageal carcinoma, stomach adenocarcinoma, small intestine adenocarcinoma, colon adenocarcinoma, rectal adenocarcinoma, liver hepatocellular carcinoma, cholangiocarcinoma, gallbladder carcinoma, pancreatic adenocarcinoma, kidney renal clear cell carcinoma, bladder urothelial carcinoma, prostate adenocarcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, cervical squamous carcinoma and endocervical adenocarcinoma, skin cutaneous melanoma, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, plasma cell myeloma, uterine carcinosarcoma, mesothelioma, adrenocortical carcinoma, brain lower grade glioma, diffuse large B-cell lymphoma, esophageal adenocarcinoma, kidney chromophobe, kidney renal papillary cell carcinoma, pheochromocytoma and paraganglioma, sarcoma, testicular germ cell tumors, thymoma, uveal melanoma, metastatic colorectal cancer, bladder cancer, adenoid cystic carcinoma,myelodysplastic, breast cancer, thyroid carcinoma, glioma, esophageal / stomach cancer, pediatric Wilms’ tumor, pediatric acute lymphoid leukemia, chronic lymphocytic leukemia, mature B-cell malignancies, pediatric neuroblastoma, nonsmall cell lung cancer (NSCLC), or melanoma,The method of any one of embodiments 223 to 225, wherein the cancer is a non-small cell lung cancer (NSCLC).The method of any one of embodiments 223 to 226, wherein the cancer is a KRAS G12C mediated cancer.The method of any one of embodiments 223 to 227, wherein the subject has been diagnosed as having a KRAS G12C mediated cancer.The method of any one of embodiments 223 to 228, wherein the subject is human, A method of preparing a crystalline form of any one of embodiments 1 to 221, the method comprising:(i) contacting Compound 1 with a first solvent to form a mixture; and(ii) adding a second solvent to the mixture of step (i) to form the crystalline form of Compound 1.The method of embodiment 230, wherein the first solvent comprises 2-methyltetrahydrofuran.The method of embodiment 230 or 231, wherein the second solvent comprises diisopropylether.The method of any one of embodiments 230 to 232, wherein the mixture of step (i) is heated prior to step (ii).The method of embodiment 233, wherein the mixture is heated to at least about 50°C. The method of any one of embodiments 230 to 234, wherein the second solvent is added to the mixture of step (i ) in step (ii) at room temperature.A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises:(i) placing a sample comprising a solid form of Compound 1 in a first container; (ii) placing the first container of step (i) inside a second container containing a solvent; and(iii) allowing vapor from the solvent to interact with the sample in the first container. The method of embodiment 236, wherein the sample of step (i) comprises freebase Form A.The method of embodiment 236 or 237, wherein step (iii) comprises allowing vapor from the solvent to interact with the sample in the first container at a room temperature and for a duration of about 7 days.The method of any one of embodiments 236 to 238, wherein the solvent comprises EtOH, MIBK, EtOAc, MTBE, 2-MeTHF, 1,4-Di oxane, acetonitrile, toluene, IP A, water, or DMSO, or any mixture thereof.The method of any one of embodiments 236 to 238, wherein the solvent comprises EtOH, MIBK, EtOAc, MTBE, 2-MeTHF, acetonitrile, toluene, IP A, water, or DMSO, or any mixture thereof, and the crystalline form prepared from the method comprises freebase Form A.The method of any one of embodiments 236 to 238, wherein the solvent comprises 1,4-di oxane and the crystalline form prepared from the method comprises freebase Form E.A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises:(i) dissolving Compound 1 in a first solvent in a first container;(ii) placing the first container of step (i) inside a second container containing a second solvent;(iii) sealing the second container of step (ii);(iv) allowing vapor of the second solvent to interact with Compound 1 in the first container to form precipitant; and(v) isolating the precipitant of step (iv) from the first solvent and / or the second solvent.The method of embodiment 242, wherein Compound 1 of step (i) comprises freebase Form A.The method of embodiment 242 or 243, wherein step (iv) comprises allowing vapor of the second solvent to interact with Compound 1 in the first container at room temperature.The method of any one of embodiments 240 to 242, wherein isolating the precipitant in step (v) comprises evaporating the first solvent and / or the second solvent at room temperature.The method of any one of embodiments 242 to 245, wherein the first solvent comprises MeOH, NMP, 1,4-di oxane, EtOH, acetone, EtOAC, DMAc, DCM, 2-MeTHF, CHCI3, acetonitrile, or DMSO, or a mixture thereof, and the second solvent comprises water, MTBE, n-Heptane, or toluene, or any mixture thereof.The method of any one of embodiments 242 to 245, wherein the first solvent comprises EtOH, EtOAC, 2-MeTHF, CHCI3, acetonitrile, or 1,4-dioxane, or any mixture thereof, and the second solvent comprises MTBE, n-Heptane, or toluene, or a mixture thereof, and the crystalline form prepared from the method comprises freebase Form A.The method of any one of embodiments 242 to 245, wherein the first solvent comprises acetone, the second solvent comprises MTBE, and the crystalline form prepared from the method comprises freebase Form C.The method of any one of embodiments 242 to 245, wherein the first solvent comprises DCM, the second solvent comprises MTBE, and the crystalline form prepared from the method comprises freebase Form D.The method of any one of embodiments 242 to 245, wherein the first solvent comprises MeOH, 1,4-dioxane, or EtOH, or any mixture thereof, the second solvent comprises water or n-Heptane, or any mixture thereof and the crystalline form prepared from the method is amorphous.The method of any one of embodiments 242 to 245, wherein the first solvent comprises NMP, DMAc, or DMSO, or any mixture thereof, the second solvent comprises water, MTBE, or toluene, or any mixture thereof, and the crystalline form prepared from the method comprises an oil.A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises:(i) preparing a suspension of Compound 1 in a solvent;(ii) heating the suspension of step (i) to a first temperature;(iii) filtering the suspension of step (ii) to obtain filtrate;(iv) cooling the filtrate of step (iii) to a second temperature.The method of embodiment 252, wherein Compound 1 of step (i) comprises freebase Form A.The method of embodiment 252 or 253, wherein the first temperature is about 50°C. The method of any one of embodiments 252 to 254, wherein the second temperature is about 5°C or about -20°C.The method of any one of embodiments 252 to 255, wherein the temperature of the filtrate in step (iv) is changed at a rate of about 0.1°C / min.The method of any one of embodiments 252 to 256, further comprising evaporating the solvent at room temperature.The method of any one of embodiments 252 to 257, wherein the solvent comprises IP A, IPAc, MIBK, acetonitrile, MTBE, 2-MeTHF, EtOH, or n-heptane, or any mixture thereof.The method of any one of embodiments 252 to 257, wherein the solvent comprises IP A, IP Ac, MIBK, a mixture of EtOH and n-Heptane at a volume ratio of about 1:1, or any mixture thereof, wherein the crystalline form prepared from the method comprises freebase Form A.The method of any one of embodiments 252 to 257, wherein the solvent comprises a mixture of acetonitrile and MTBE at a volume ratio of about 1:1, or 2-MeTHF, or any mixture thereof, wherein the crystalline form prepared from the method is amorphous. A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises:(i) preparing a suspension of Compound 1 in solvent; and(ii) stirring the suspension of step (i) at a temperature for a duration.The method of embodiment 261, wherein Compound 1 of step (i) comprises freebase Form A.The method of embodiment 261 or 262, wherein a solid forms from the suspension after step (ii), and the method further comprises centrifuging the suspension of step (ii) to isolate the solid.The method of any one of embodiments 261 to 263, wherein the temperature is room temperature, and the duration is between about 2 days and about 6 days.The method of any one of embodiments 261 to 264, wherein the solvent comprises EtOH, MTBE, acetone, water, EtOAc, MTBE, acetonitrile, THF, n-Heptane, toluene, DCM, 1,4-Dioxane, MeOH, DMSO, DMAc, or IP A, or any mixture thereof.The method of any one of embodiments 261 to 264, wherein the solvent comprises a mixture of EtOH and MTBE at a volume ratio of about 1:9; a mixture of acetone and water at a volume ratio of about 1:9; a mixture of EtOAc and MTBE at a volume ratio of about 1:4; MTBE; a mixture of acetonitrile and water at a volume ratio of about 1:9; a mixture of THF and n-Heptane at a volume ratio of about 1:9; toluene; water; a mixture of DCM and MTBE at a volume ratio of about 1:9; a mixture of 1,4-di oxane and toluene at a volume ratio of about 1:9; a mixture of DMSO and water at a volume ratio of about 1:9; a mixture of DMAc and toluene at a volume ratio of about 1:9; amixture of IP A and water at a volume ratio of about 98:2, 96:4, 92.8, or 85:15, wherein the crystalline form prepared from the method comprises freebase Form A. The method of any one of embodiments 261 to 264, wherein the solvent comprises a mixture of MeOH and toluene at a volume ratio of about 1:9, wherein the crystalline form prepared from the method comprises freebase Form B.The method of any one of embodiments 261 to 263, wherein the temperature is between about 40°C and about 60°C, and the duration is between about 1 day and about 5 days.The method of any one of embodiments 261 to 263 and 268, wherein the solvent comprises MeOH, toluene, MIBK, n-Heptane, IP Ac, MTBE, CHCh, water, 2-MeTHF, 1,4-di oxane, acetonitrile, THF, NMP, or DMSO, or any mixture thereof. The method of any one of embodiments 261 to 263 and 268, wherein the solvent comprises a mixture of MIBK and n-Heptane at a volume ratio of about 1:2; a mixture of IP Ac and MTBE at a volume ratio of about 1:2; water; n-Heptane; a mixture of 2-MeTHF and MTBE at a volume ratio of about 1:4; a mixture of 1,4-di oxane and n-Heptane at a volume ratio of about 1:9; a mixture of acetonitrile and toluene at a volume ratio of about 1:4; a mixture of THF and toluene at a volume ratio of about 1:9; a mixture of NMP and water at a volume ratio of about 1:9; a mixture of DMSO and toluene at a volume ratio of about 1:4; wherein the crystalline form prepared from the method comprises freebase Form A.The method of any one of embodiments 261 to 263 and 268, wherein the solvent comprises a mixture of MeOH and toluene at a volume ratio of about 1:9; a mixture of CHCh and toluene at a volume ratio of about 1:4; wherein the crystalline form prepared from the method is amorphous.A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises:(i ) preparing a suspension of Compound 1 in a solvent;(ii) heating the suspension to a first temperature and cooling the suspension to a second temperature; and(iii) heating the suspension to a third temperature, and cooling the suspension to a fourth temperature.The method of embodiment 272, wherein Compound 1 of step (i) comprises freebase Form A.The method of embodiment 272 or 273, wherein a solid forms from the suspension after step (iii), and the method further comprises centrifuging the suspension of step (iii) to isolate the solid.The method of any one of embodiments 272 to 274, wherein the first temperature and the third temperature are each independently in between about 40°C and about 50°C, and the second temperature and the fourth temperature are each independently in between about 0°C and about 10°C.The method of any one of embodiments 272 to 275, wherein the heating and cooling of steps (ii) and (iii) are each independently conducted at a rate of between about 0.01 °C / min and about 1 °C / min.The method of any one of embodiments 272 to 276, wherein the solvent comprises MeOH, MTBE, EtOH, water, acetonitrile, EtOAc, n-Heptane, 2-MeTHF, acetone, toluene, IPAc, DMAc, NMP, or CHCh or any mixture thereof.The method of any one of embodiments 272 to 276, wherein the solvent comprises a mixture of MeOH and MTBE at a volume ratio of 1:9; a mixture of EtOH and water at a volume ratio of 1:9; a mixture of acetonitrile and MTBE at a volume ratio of about 1:9; a mixture of EtOAc and n-Heptane at a volume ratio of about 1:4; 2-MeTHF; a mixture of acetone and toluene at a volume ratio of about 1:4; IPAc; water; MTBE; a mixture of DMAc and water at a volume ratio of about 1:9; a mixture of NMP and TBE at a volume ratio of about 1:9; a mixture of CHCh and MTBE at a volume ratio of about 1:4; wherein the crystalline form prepared from the method comprises freebase Form A.A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises:(i) dissolving Compound 1 in a solvent; and(ii) evaporating the solvent of step (i) at a temperature.The method of embodiment 279, wherein Compound 1 of step (i) comprises freebase Form A.The method of embodiment 279 or 280, wherein the temperature of step (ii) is room temperature.The method of any one of embodiments 279 to 281, wherein the solvent comprises MeOH, EtOH, acetonitrile, acetone, EtOAc, 2-MeTHF, DCM, THF, or water, or any mixture thereof.The method of any one of embodiments 279 to 281, wherein the solvent comprises EtOH; acetonitrile; EtOAc; 2-MeTHF; wherein the crystalline form prepared from the method comprises freebase Form A.The method of any one of embodiments 279 to 281, wherein the solvent comprises MeOH; acetone; DCM; a mixture of THF and water at a volume ratio of about 9:1, wherein the crystalline form prepared from the method is amorphous.A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises grinding Compound 1.The method of embodiment 285, wherein Compound 1 comprises freebase Form A. The method of embodiment 285 or 286, further comprising contacting Compound 1 with a solvent while grinding,The method of embodiment 285, wherein the solvent comprises water.The method of any one of embodiments 285 to 288, wherein the crystalline form prepared from the method comprises freebase Form A.A method of preparing a crystalline form of any one of embodiments 1 to 221, wherein the method comprises:(i) adding Compound 1 to a solvent to form a first mixture; and(ii) adding an anti-solvent to the first mixture to form a second mixture.The method of embodiment 290, wherein Compound 1 of step (i) comprises freebase Form A.The method of embodiment 290 or 291, wherein the anti-solvent is added until a precipitate is produced.The method of any one of embodiments 290 to 292, further comprising cooling the second mixture to a cooling temperature.The method of embodiment 293, wherein the cooling temperature is between about -25°C and about 10°C.The method of any one of embodiments 290 to 294, further comprising evaporating the solvent and the antisolvent from the second mixture at an evaporation temperature.The method of embodiment 295, wherein the evaporation temperature is room temperature.The method of any one of embodiments 290 to 296, wherein the solvent comprises acetone, MeOH, THF, acetonitrile, DMSO, EtOH, EtOAc, 1,4-Dioxane, 2-MeTHF,CHCh, DMAc, or DCM, and the anti-solvent comprises water, n-Heptane, MTBE, or toluene, or any mixture thereof.The method of any one of embodiments 290 to 296, wherein the solvent comprises acetone, THF, EtOH, EtOAc, THE, 1,4-di oxane, MeOH, 2-MeTHF, acetonitrile, CHCh, DMAc, or DCM, or any mixture thereof, and the anti-solvent comprises water, n-Heptane, MTBE, or toluene; wherein the crystalline form prepared from the method comprises freebase Form A.The method of any one of embodiments 290 to 296, wherein the solvent comprises MeOH, acetonitrile, or DMSO, and the anti-solvent comprises water; wherein the crystalline form prepared from the method is amorphous.A method of preparing a crystalline form of a salt of any one of embodiments 36 to 221, wherein the method comprises:(i) stirring Compound 1 in a solution for a duration;(ii) centrifuging the mixture of step (i); and(iii) drying the precipitant of step (ii) at a temperature.The method of embodiment 300, wherein Compound 1 of step (i) comprises freebase Form A.The method of any one of embodiments 300 to 301, wherein the solution comprises HC1 in IP A; L -tartaric acid in IP A; fumaric acid in IPA and MIBK; fumaric acid in IPAc; citric acid in acetone; malic acid in IPA and acetonitrile; malic acid in IP Ac, succinic acid in IPA and MIBK; succinic acid in 2-MeTHF; adipic acid in 2-MeTHF; 1, 5 -naphthalenedi sulfonic acid in IPA, MIBK, and acetonitrile; p-toluenesulfonic acid in IPAc; methanesulfonic acid in MIBK; oxalic acid in MIBK; or HBr in MIBK. The method of any one of embodiments 300 to 302, wherein the method further comprises stirring the mixture of step (i) at a temperature between about 0°C and about 10°C for a duration before centrifugation in step (ii).The method of embodiment 303, wherein the duration is between 12 and 36 hours. The method of any one of embodiments 300 to 304, wherein the method further comprises heating-cooling the mixture of step (i) before centrifugation in step (ii). The method of embodiment 305, wherein the mixture is heated to between about 40°C and about 50°C, and cooled to between about 0°C and about 10°C.The method of embodiment 304 or 305, wherein the heating and cooling are each independently conducted at a rate of between about 0.01 °C / min and about 1 °C / min.08. The method of any one of embodiments 300 to 307, wherein the duration in step (i) is between 1 and 5 days.09. The method of any one of embodiments 300 to 308, wherein the temperature of step (iii) is room temperature.EXAMPLES

[0169] The presently disclosed subject matter will be better understood by reference to the following Examples, which are provided as exemplary of the invention, and not by way of limitation.

[0170] The following abbreviations may be used herein:

[0171] The crystalline forms were characterized by various analytical techniques, including XRPD, DSC, TGA, DVS, 'HNMR, and HPLC using the procedures described below.

[0172] For XRPD, PANalytical Empyrean and X' Pert3 X-ray powder diffract meters were used. The XRPD parameters used are listed below. Unless otherwise specified, the XRPD was performed at room temperature.Parameters X’ Pert3 or Empyrean Empyrean (VT / VH-XRPD) Cu, Ka; Cu, Ka;, Kai (A): 1.540598 Kai (A): 1.540598X-Ray wavelength(A). ]544426 Ka2 (A).,544426intensity ratio Ka2. ZKal: 0.50 intensity ratio Ka2 / Kal: 0.50 X-Ray tube setting 45 kV, 40 mA 45 kV, 40 mA Divergence slit 1 / 8° 1 / 80Scan mode Continuous ContinuousScan range (20 / °) 3-40 3 40Step size (20 / °) 0.0263 17.8Scan step time (s) 46.665 0.0167Test time About 5 mins About 10 min

[0173] For TGA, TA Discovery 5500 TGA from TA Instruments was used. For DSC, TA Discovery' 2500 DSC from TA Instruments was used. TGA and DSC parameters used are listed below.Parameters TGA DSC Method Ramp Ramp Sample pan Aluminum, open Aluminum, crimped / open Temperature RT- Target temperature 25 °C- Target temperature Heating rate 10 °C / min 10 °C / min Purge gas N2 N2

[0174] For DVS, a Surface Measurement Systems (SMS) DVS Intrinsic Plus was used. The relative humidity at 25 °C was calibrated against deliquescence point of LiCl, Mg(NCh)2, and KCI. Parameters for DVS test are listed below.Parameters ValuesTemperature 25 °CSample size 10-20 mgGas and flow rate N2, 200 mL / mindm / dt 0.002% / minMin.dm / dt stability duration 10 minMax. equilibrium time 180 minRH range 0% RH-95% RH-0% RH10% (90% RH-0% RH-90% RH) RH step size5% (95% RH-90% RH and 90% RH-95% RH)

[0175] For solution NMR, Bruker 400M NMR Spectrometer was used, in DMSO-t / e and MeOD.

[0176] For HPLC / IC, Thermo Vanquish Core was used. Chromatographic conditions used are listed below.Parameters Thermo Vanquish Core with DAD detector Column Xbridge Cl 8, 150x4.6 mm, 5 pmA: 0.1%TFA in H2OB: 0.1%TFA mACNTime (min) %B0.0 5 Mobile phase 2.0 3010.0 6012.0 9512.1 515.0 5Run time 15 minFlow rate 1.0 mL / minInjection volume 8 pl.Detector wavelength UV at 302 nmColumn temperature 40 °CSampler temperature RTDiluent ACN / FLO (1:1, v / v )

[0177] IC parameters used are listed below.IC Thermo AQ RFICColumn Dionex lonPac™ ASH HC Analytical, 250*4 mm Mobile phase 35 mM KOHInjection volume 25 pLIC Thermo AQ RFICFlow rate 1.5 mL / minCell temperature 35 °CColumn temperature 35 °CCurrent 130 mARun time 10 min

[0178] PLM data were collected with Axio Lab. Al upright microscope. SEM images were captured on a GEMINI 300 scanning electron microscope. KF data was collected using Metrohm 870 KF Titrinoplus calibrated using purified water and Hydranal® R-Composite 5 provided by Sigma-aldrich. HPLC grade methanol was used to dissolve samples.Example 1: Preparation of freebase Form A (freebase starting material) of 1-((2R,3R)-3-((7-(8-ethynyI-7-fluoronaphthalen-l-yI)-8-fliioro-2-(((2R,7aS)-2-fliiorotetrahydro-lH-pyrro!izin-7a(5H)-yI)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l-yI)prop-2-en-l-one (Compound 1)BocStep 1: tert-butyl (2R,3R)-3-(benzyI(methyl)amino)-2-methyIpyrroIidine-l-carboxylate

[0179] To a solution of tert-butyl (2R,3R)-3-amino-2-methylpyrrolidine-l-carboxylate (20 g, 99.86 mmol), benzaldehyde (10.60 g, 99.86 mmol) and acetic acid (6,00 g, 99.86 mmol) in methanol (300 mL) was added sodium cyanoborohydride (18.83 g, 299.58 mmol) at 0 °C. The resulting mixture was stirred at 25 °C for 0.5 h. Then, formaldehyde (16.21 g, 199.72 mmol, 37% w / w water) was added to the above solution at 0 °C, and the mixture was stirred at 25 °C for an additional 1.5 h. After this time, the reaction mixture was quenched with saturated aqueous sodium bicarbonate (200 mL) at 0 °C and extracted with ethyl acetate (3 x 200 mL). The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The crude residue was purified by column chromatography (silica gel, 100-200 mesh, 0-100% ethyl acetate in petroleum ether) affording tert-butyl (2R,3R)-3- (benzyl(methyl)amino)-2-methylpyrrolidine- 1 -carboxylate (25.21 g, 82.93%) as a colorless oil: ‘HNMR (400 MHz, Chlorofomi-d) 67.29 - 7.21 (m, 4H), 7.20 - 7.14 (m, 1H), 4.13 -3.91 (m, 1H), 3.56 (br dd, J=13.20, 3.94Hz, 1H), 3.46 - 3.34 (m, 1H), 3.30 - 3.19 (m, 2H), 2.69 (tt,. / 12.55, 6.27 Hz, 1H), 2.01 (s, 3H), 1.97 (s, 1H), 1.87 - 1.76 (m, 1H), 1.40 (s, 9H), 1.10 (dd, J = 15.51, 6.38 Hz, 3H).BocStep 2: tert-butyl (2R,3R)-2-methyI-3-(niethylamino)pyrrolidine-l-carboxylate

[0180] To a solution of tert-butyl (2R,3R)-3-(benzyl(methyl)amino)-2- methylpyrrolidine-l-carboxylate (25.21 g, 82.81 mmol) in ethyl acetate (500 mL) was added Pd / C (17.63 g, 16.56 mmol, 10% purity). The resulting mixture was stirred at 30 °C for 1 h under hydrogen atmosphere (30 Psi). The reaction mixture was then filtered through Celite® and the filtrate was concentrated to dryness in vacuo affording tert-butyl (2R,3R)-2-methyl- 3 -(methyl amino)pyrrolidine-l -carboxylate (17 g, 95.77%) as a yellow oil, used in next step without further purification:rH NMR (400 MHz, Chloroform-d) 64.08 - 3.89 (m, 1H), 3.46 - 3.33 (m, 1H), 3.30 - 3.09 (m, 2H), 2.43 (s, 3H), 2.12 - 2.02 (m, 1H), 1.68 - 1.57 (m, 1H), 1.45 (s, 9H), 1.29 (s, 1H), 1.07 - 0.99 (m, 3H).BocStep 3: tert-butyl (2R,3R)-3-((2,7-dichIoro-8-fluoropyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l-carboxyIate

[0181] To a solution of 2,4,7-trichloro-8-fluoropyrido[4,3-d]pyrimidine (17.67 g, 69.99 mmol) and A^V-diisopropylethylamine (27.14 g, 209.98 mmol) in dichloromethane (200 mL) was added tert-butyl (2R,3R)-2-methyl-3-(methylamino)pyrrolidine-l-carboxylate (15 g, 69.99 mmol) in dichloromethane (60 mL) at 0 °C. The resulting mixture was stirred at 25°C for 0.5 h. The reaction mixture was then concentrated to dryness in vacuo. The crude residue was diluted with a mixture of petroleum ether: ethyl acetate (5:1, 360 mL) and the resulting precipitate was filtered affording tert-butyl (2R,3R)-3-((2,7-dichloro-8- fluoropy rido[4, 3 -d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l -carboxy late (35 g, crude) as a yellow solid: ’HNMR (400 MHz, Chloroform-d) 59.05 (s, 1H), 5.05 (dt, J = 11.79, 7.05 Hz, 1H), 4.57 - 4.51 (m, 1H), 3.67 - 3.62 (m, 1H), 3.58 (s, 3H), 3.41 (td, J = 10.63, 7.63Hz, 1H), 2.45 - 2.34 (m, 1H), 2.29 - 2.21 (m, 1H), 1.49 (s, 9H), 1.07 (d, J= 6.50 Hz, 3H). LCMS Rt = 0.574 min, m / z = 430.1 / 432.1 [M +H]+.Step 4: tert-butyl (2R,3R)-3-((7-chloro-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrro!izin-7a(5H)-yI)niethoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l-carboxylate

[0182] To a solution of ((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methanol (19,31 g, 121,31 mmol) and sodium tert-butoxide (9.72 g, 101.09 mmol) in toluene (500 mL) was added tert-butyl (2R,3R)-3-((2,7-dichloro-8-fluoropyrido[4,3-d]pyrimidin-4- yl)(methyl)amino)-2-methylpyrrolidine-l -carboxylate (29 g, 67.39 mmol). The resulting mixture was stirred at 0 °C for 10 min. The reaction mixture was then quenched with saturated aqueous ammonium chloride (300 mL) at 0 °C and extracted with dichloromethane (3 x 300 mL). The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The crude residue was purified by column chromatography (silica gel, 100-200 mesh, 0-100% tetrahydrofuran in petroleum ether) affording tert-butyl (2R,3R)-3-((7-chloro-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)- yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l -carboxylate (30 g, 80.49%) as a yellow solid: ’H NMR (400 MHz, Chloroform-d) 58.91 (s, 1H), 5.37 - 5.18 (m, 1H), 5.01 - 4.91 (m, 1H), 4.57 - 4.49 (m, 1H), 4.22 (s, 2H), 3.65 - 3.57 (m, 1H), 3.51 (s, 3H), 3.40 (td, J = 10.51, 7.00 Hz, 1H), 3.28 - 3.20 (m, 2H), 3.16 - 3.12 (m, 1H), 2.97(td, J= 9.29, 5.32 Hz, 1H), 2.43 - 2.31 (m, 1H), 2.27 - 2.20 (m, 2H), 2.20 - 2.15 (m, 1H), 2.13 - 2.07 (m, 1H), 1.97 - 1.85 (m, 3H), 1.48 (s, 9H), 1.03 (d, J - 6.38 Hz, 3H). LCMS Rt - 0.400 min, m / z = 553.4 / 555.3 [M +H]+.(2R,3R)-3-((8-fluoi'o-7-(7-fIuoro-8- ((triisopropylsi!yI)ethynyl)naphthaIen-l-yl)-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yI)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-1 -carboxylate

[0183] A mixture of tert-butyl (2R,3R)-3-((7-chloro-8-fluoro-2-(((2R,7aS)-2- fluorotetrahy dro- 1 H-py rrolizi n-7a(5 H)-yl)m ethoxy)py ri do[4,3 -d]pyrimi di n-4- yl)(methyl)amino)-2-methylpyrrolidine-l -carboxylate (27.33 g, 49.42 mmol), ((2-fluoro-8- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)naphthalen-l-yl)ethynyl)triisopropylsilane (24.60 g, 54.36 mmol), [2-(2-aminopheiiyl)pheiiyl]palladium bis( 1 - adamantyl)butylphosphane methanesulfonate (3.60 g, 4.94 mmol) and potassium phosphate (31.47 g, 148.25 mmol) in a mixture of 1,4-dioxane (480 mb) and water (150 mL) was degassed and purged with nitrogen three times, before stirring at 80 °C for 12 h under nitrogen atmosphere. After this time, the mixture was diluted with water (100 mL) and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The crude residue was purified by column chromatography (silica gel, 100-200 mesh, 0-100% tetrahydrofuran in petroleum ether) affording tert-butyl (2R,3R)-3-((8-fluoro-7-(7-fluoro-8- ((triisopropylsilyl)ethynyl)naphthalen-l-yl)-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin- 7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l - carboxylate (41 g, 98.41%) as a brown solid. LCMS Rt = 0.616 min, m / z = 843.6 [M +H]+.

[0184] To a solution of tert-butyl (2R,3R)-3-((8-fluoro-7-(7-fluoro-8- ((triisopropylsilyl)ethynyl)naphthalen-l-yl)-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin- 7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l- carboxylate (45.5 g, 53.97 mmol) in ethyl acetate (500 mL) was added Functionalised Silica Gels (99.55 g, 1.08 mol ) to remove Pd. The mixture was stirred at 70 °C for 12 h. The reaction mixture was then filtered and the filtrate was concentrated to dryness in vacuo affording tert-butyl (2R,3R)-3-((8-fluoro-7-(7-fluoro-8- ((triisopropylsilyl)ethynyl)naphthalen-l-yl)-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin- 7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l - carboxylate (44.14 g, 96.9%) as a yellow solid: ’HNMR (400 MHz, Chloroform-d) 59.26 - 9.23 (m, 1H), 7.97 - 7.88 (m, 2H), 7.60 - 7.52 (m, 2H), 7.34 (td,. / 8.69, 3.13Hz, 111). 5.40 - 5.21 (m, 1H), 5.18 - 4.91 (m, 1H), 4.62 - 4.52 (m, 1H), 4.33 - 4.21 (m, 2H), 3.67 - 3.60 (m, 1H), 3.58 (s, 1H), 3.54 (s, 2H), 3.47 - 3.39 (m, 1H), 3.35 - 3.23 (m, 2H), 3.22 - 3.16 (m, 1H), 3.03 - 2.95 (m, 1H), 2.25 - 2.19 (m, 2H), 2.00 - 1.92 (m, 3H), 1.85 (dt, J= 6.60, 3.27 Hz, 3H), 1.50 (d, J= 2.25 Hz, 9H), 1.24 (s, 3H), 1.14 (d, J= 6.25 Hz, 3H), 0.90 - 0.86 (m, 18H). LCMS Rt = 3.263 min, m / z = 843.3 [M H.Step 6: tert-butyl (2R,3R)-3-((7-(8-ethynyI-7-fliioronaphthaIen-l-yl)-8-fluoro-2- (((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l -carboxylate

[0185] To a solution of tert-butyl (2R,3R)-3-((8-fluoro-7-(7-fluoro-8- ((triisopropylsilyl)ethynyl)naphthalen-l-yl)-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin- 7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l- carboxylate (44 g, 52.19 mmol) in acetonitrile (800 mL) was added cesium fluoride (47.57 g, 313.13 mmol). The resulting mixture was stirred at 25°C for 12 h. The reaction mixturewas then diluted with water (50 mL) and concentrated under reduced pressure to remove almost all acetonitrile. Then the mixture was diluted with water (50 mL) and extracted with ethyl acetate (3 x 80 mL). The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The crude residue was diluted with a mixture of petroleum ether: methyl tert-butyl ether (1:1, 600 mL) and the resulting precipitate was filtered. The crude residue was diluted with a mixture of petroleum ether: ethyl acetate (10:1, 440 mL) and the resulting precipitate was filtered affording tert-butyl (2R,3R)-3-((7-(8-ethynyl-7- fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)- yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidine-l -carboxylate (30 g, 83.70%) as a brown solid: ’HNMR (400 MHz, Acetonitrile-ds) 59.21 (d, J= 1.79 Hz, 1H), 8.14 - 8.08 (m, 2H), 7.69 - 7.63 (m, 2H), 7.44 (t, J --- 9.06 Hz, 1H), 5.35 - 5.16 (m, 1H), 4.92 - 4.79 (m, 1H), 4.57 (quin, J= 6.71 Hz, 1H), 4.14 (s, 2H), 3.57 (d, J= 1.91 Hz, 3H), 3.55 - 3.49 (m, 1H), 3.38 - 3.30 (m, 1H), 3.25 (d, 15.38 Hz, 1H), 3.18 - 3.10 (m, 2H), 3.09 - 3.04 (m, 1H), 2.93 - 2.85 (m, 1H), 2.53 - 2.38 (m, 1H), 2.29 - 2.22 (m, 1H), 2.10 (d, J = 3.34 Hz, 1H), 2.07 - 2.02 (m, 1H), 1.97 (s, 2H), 1.89 - 1.83 (m, 2H), 1.46 (d, J= 4.05 Hz, 9H), 1.15 - 1.05 (m, 3H). LCMS Rt = 1.756 min, m / z = 687.2 [M +H]+.Step 8: 7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-! H-pyrroIizin-7a(5H)-yl)methoxy)-N-methyl-N-((2R,3R)-2-methyIpyrrolidin-3-yl)pyrido[43-d]pyrimidin-4-amine

[0186] A mixture of tert-butyl (2R,3R)-3-((7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8- fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3- d]pyrimidm-4-yl)(methyl)amino)-2-methylpyrrolidme-l -carboxy late (30 g, 43.68 mmol) in hydrochloric acid (4M in ethyl acetate, 400 mL) was stirred at 25 °C for 0.5 h. The reaction mixture was then concentrated in vacuo affording 7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8- fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)-N-methyl-N-((2R,3R)-2-methylpyrrolidin-3-yl)pyrido[4,3-d]pyrimidin-4-amine (27.22 g, crude, hydrochloride) as a yellow solid, used in next step without further purification. LCMS Rt:::0.335 min, m / z = 587.3 [M +H]+.Step 9:!-((2R,3R)-3-((7-(8-ethynyI-7-fIuoronaphthalen-l-yI)-8-fIuoro-2-(((2R,7aS)-2-fliiorotetrahydro-lH-pyrroIizin-7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l-yI)prop-2-en-l-one

[0187] To a solution of 7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2- fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)-N-methyl-N-((2R,3R)-2- niethylpyrrolidin-3-yi)pyrido[4,3-d]pyriniidin-4-amine (27.22 g, 43.68 mmol, hydrochloride) and sodium bicarbonate (11.01 g, 131.05 mmol) in tetrahydrofuran (300 mL) and water (100 mL) was added acryloyl chloride (7.91 g, 87.37 mmol). The resulting mixture was stirred at 0 °C for 0.5 h under nitrogen atmosphere. The mixture was diluted with water (200 mL) and extracted with ethyl acetate (3 x 200 mL). The combined organic layers were dried over sodium sulphate and concentrated in vacuo. The crude residue was diluted with a (1: 10) mixture of petroleum ether: ethyl acetate (220 mL) and the resulting precipitate was filtered. The crude residue was diluted with a (16:4:1) mixture of ethyl acetate: petroleum ether: ethanol (105 mL) and the resulting precipitate was filtered affording l-((2R,3R)-3-((7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2- fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl) ethoxy)pyrido[4,3-d]pyrimidin-4- yl)(methyl)amino)-2-methylpyrrolidin-l-yl)prop-2-en-l-one (11.18 g, 38.72%) as a yellow solid: ’H NMR (400 MHz, Acetonitrile-d3) 59.22 (d, J = 4.25 Hz, 1H), 8.16 - 8.07 (m, 2H), 7.70 - 7.63 (m, 2H), 7.45 (t, J= 9.07 Hz, 1H), 6.63 - 6.53 (m, 1H), 6.31 - 6.20 (m, 1H), 5.71 - 5.63 (tn, 1H), 5.34 - 5.16 (m, 1H), 4.96 - 4.80 (m, 2H), 4.26 - 4.08 (m, 2H), 3.89 - 3.64 (tn, 1H), 3.60 (d, J= 7.00 Hz, 3H), 3.58 - 3.47 (m, 1H), 3.28 - 3.24 (m, 1H), 3.18 - 3.08 (m, 2H),3.05 (s, 1H), 2.92 - 2.85 (m, 1H), 2.63 - 2.46 (m, 1H), 2.43 - 2.30 (m, 1H), 2.23 - 2.18 (m, III), 2.12 - 2.08 (m, 1H), 2.05 - 2.00 (m, III), 1.92 - 1.79 (m, 3H), 1.16 - 1.03 (m, 3H). LCMS (5% to 95% acetonitrile in water + 0.03% ammonium bicarbonate over 6 min); retention time 3.887 min, ESI+ found [M+H]h::::641.3.

[0188] Three grams of this yellow solid was dissolved into 2-methyltetrahydrofuran (80 mL). The mixture was stirred at 60°C, then filtered and cooled down at room temperature. Diisopropylether (160 mL) was added to the mixture at 25°C. The resulting precipitate was filtered affording l-((2R,3R)-3-((7-(8-ethynyl-7-fluoronaphthalen-l-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l-yl)prop-2-en-l-one (2.5 g, 84.63%) as a yellow solid: ’HNMR (400 MHz, Acetonitrile-d3) 69.22 (d, J= 3.9 Hz, 1H), 8.17 - 8.07 (m, 2H), 7.70 - 7.63 (m, 2H), 7.44 (t, J ------ 9.1 Hz, 1H), 6.63 - 6.53 (m, 1H), 6.32 - 6.20 (m, 1H), 5.67 (dd, J= 2.3, 10.3 Hz, 1H), 5.34 - 5.16 (m, 1H), 4.96 - 4.79 (m, 2H), 4.27 - 4.07 (m, 2H), 3.89 - 3.64 (m, 1H), 3.59 (d, J - 5.9 Hz, 3H), 3.58 - 3.47 (m, 1H), 3.27 - 3.23 (m, 1H), 3.18 -3.07 (m, 2H), 3.05 (s, 1H), 2.92 - 2.84 (m, 1H), 2.65 - 2.46 (m, 1H), 2.42 - 2.29 (m, 1H), 2.23 - 2.17 (m, 1H), 2.13 - 2.08 (m, 1H), 2.05 - 1.98 (m, 1H), 1.91 - 1.78 (m, 3H), 1.16 - 1.04 (m, 3H). LCMS Rt = 3.886 min, m / z = 641.3 [M +H]+.

[0189] The mother liquor from all trituration and recrystallization steps described above was purified by column chromatography (silica gel, 100-200 mesh, 0-100% tetrahydrofuran in petroleum ether) afforded 13.9 g with 90% purity. This material was dissolved in 2-methyltetrahydrofuran (650 mL) and stirred at 60 °C, then filtered and cooled to room temperature. Dii sopropyl ether (1.2 L) was added to the mixture at 25 °C. The resulting precipitate was collected by filtration affording l-((2R,3R)-3-((7-(8-ethynyl-7-fluoronaphthalen-1 -yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-lH-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpyrrolidin-l-yl)prop-2-en-l-one (12.57 g, 90.39%) as a yellow solid, which was used as the starting material for the polymorph screening and was identified as Freebase Form A:1H NMR (400 MHz, Acetonitrile-d3) 59.22 (d, 3.9 Hz, 1H), 8.15 - 8.07 (m, 2H), 7.70 - 7.63 (m, 2H), 7.44 (t,.7= 9.1 Hz, 1H), 6.63 - 6.51 (m, 1H), 6.33 - 6.20 (tn, 1H), 5.71 - 5.63 (m, 1H), 5.36 - 5.16 (m, 1H), 4.98 - 4.73 (m, 2H), 4.26 - 4.07 (m, 2H), 3.88 - 3.65 (m, 1H), 3.59 (d, J= 6.1 Hz, 3H), 3.58 - 3.46 (m, 1H), 3.27 - 3.24 (m, 1H), 3.18 - 3.07 (m, 2H), 3.05 (s, 1H), 2.92 - 2.84 (m, 1H), 2.66 - 2.44 (m, 1H), 2.42 - 2.28 (m, 1H), 2.17 - 2.12 (m, 1H), 2.10 (d, J= 3.1 Hz,1H), 2.06 - 2.00 (m, 1H), 1.92 - 1.81 (m, 3H), 1.16 - 1.04 (m, 3H). LCMS (5 to 95% acetonitrile in water + 0.1% tri fluoroacetic acid over 6 min); retention time 2.189 min, ESI+ found [M+H]+= 641.3.Example 2: Characterization of starting material

[0190] Freebase starting material was characterized by XRPD, TGA, DSC and ’HNMR. The XRPD pattern in FIG. 1 A showed the starting material was crystalline, which was named as freebase Form A. The TGA / DSC curves are displayed in FIG. IB, which shows a weight loss of 1.02% up to 150 °C and one exotherm at 199.9 °C (peak).1H NMR results were collected using DMSO-de and MeOD solvents, which are listed in FIGS. ID and IE. KF results show the water content was 1.84%. PLM and SEM images are listed in FIG. IF and FIG. 1G, which show small and irregular particles with aggregation.

[0191] Approximate solubility of starting material was determined in 20 solvents at RT. Approximately 2 mg of sample was added into a 3-niL glass vial. Solvents in Table A-l were then added stepwise into the vials until the solids were dissolved visually or a total volume of 2 mL was reached. Solubility results summarized in Table A-l were used to guide the solvent selection in screening experiment design.Table A- 1.Solvent Solubility (mg / mL) Solvent Solubility (mg / niL) MeOH S>40.0 1,4-Dioxane 21.0< S<42.0 EtOH 21.0< S<42.0 ACN 21.0< S<42.0 IPA 2.0< S<5.0CHC13S>40.0 Acetone S>40.0 DCM S>40.0 MIBK 5.3< S<10.5 n-Heptane S <1.0 EtOAc 10.0< S<20.0 Toluene S<1.0 IPAc 2.0< S<5.0 DMAc S>42.0 MTBEs<1 1DMSO S>42.0 THF S>42.0 NMP S>42.0 2-MeTHF 10.0< S<20.0 H2OS<1

[0192] In order to evaluate the hygroscopicity of freebase Form A, HQ salt Form A, citrate Form A and succinate Form A, DVS isotherm plot was collected at 25 °C between0%RH and 95%RH. XRPD characterization was performed for the sample after DVS test. The DVS plot and XRPD results for freebase Form A, HC1 salt Form A, citrate Form A, and succinate Form A are shown in FIGS. 1C, II, 6C, 23D, 7C, 24D, 8C, 25E, respectively. The results are summarized in Table A-2. Based on the results, a water uptake of 0.44%, 2.65%, 1.18%, 1.42% was observed at 25 °C / 80%RH for freebase Form A, HQ salt Form A, citrate Form A and succinate Form A, respectively, and no form change was observed for freebase Form A, HC1 salt Form A and citrate Form A after DVS test. Amorphous solids were obtained for succinate Form A after DVS test.Table A-2.„, ~ Water uptake „Salt lorm, o™»o / Form after DV (25 C / oU zoi U)Freebase Form A 0.44% Freebase Form A HC1 salt Form A 2.65% HC1 salt Form A Citrate Form A 1.18% Citrate Form A Succinate Form A 1.42% Amorphous* *: A water uptake of 16.36% was observed at 25 °C / 95%RH, and gel was observed after DVS test.

[0193] For solid stability evaluation, freebase Form A, HC1 salt Form A, citrate Form A and succinate Form A were placed under the conditions of 25 °C / 60%RH and 40 °C / 75%RH for 4 weeks. Only 1 week was evaluated for succinate Form A, because of the physical and chemical stability issues of succinate Form A after solid stability for 1 week. The physical and chemical stability were evaluated by XRPD and HPLC purity, respectively. The results are summarized in Table A- 3 and the XRPD results are shown in FIGS. IJ, 23E, 24E, 25F, and 25G. The impurities of freebase and salt hits are summarized in Table A-4 to Table A-7, HPLC overlays are displayed in FIGS. IK, 23F, 24F, and 25G. The results showed that no form change or obvious HPLC purity change was observed for freebase Form A and HQ salt Form A under 25 °C / 60%RH and 40 °C / 75%RH for 4 weeks. Slight purity decrease was observed for citrate Form A after 4 weeks under 40 °C / 75%RH. Purity decrease and amorphous solids were observed for succinate Form A after 1 week under 40 °C / 75%RH.Table A -3.HPLC purityForm(Area%)Initial - 97.45rtr25 °C / 60%RH 1 week 97.47 Freebase Form A Freebase Form A25 °C / 60%RH 4 weeks 97.45 Freebase Form A 40 °C / 75%RH I week 97.48 Freebase Form A 40 °C / 75%RH 4 weeks 97.52 Freebase Form A Initial - 98.04* 25 °C / 60%RH 1 week 98.06 FIC1 salt Form A HC1 salt Form A25 °C / 60%RH 4 weeks 98.28 HC1 salt Form A 40 °C / 75%RH I week 98.15 HC1 salt Form A 40 °C / 75%RH 4 weeks 98.15 HC1 salt Form A Initial - 97.59Citrate Form A 25 °C / 60%RH I week 97.54 Citrate Form A 25 °C / 60%RH 4 weeks 97.59 Citrate Form A 40 °C / 75%RH I week 97.21 Citrate Form A 40 °C / 75%RH 4 weeks 96.18 Citrate Form A Succinate Form Initial - 97.66A25 °C / 60%RH I week 97.64 Succinate Form B week 94.18 AmorphousTable A-4. Summary of impurities of freebase Form A after stability evaluation.. Initialar.# „„ 25 25 40 40 Pea oz °C / 60%RH / l °C / 60%RH / 4 °C / 75%RH / 1 °C / 75%RH / 41 0.95 0.48 0.49 0.49 0.48 0.48 2 0.97 0.14 0.14 0.14 0.14 0.14 3 1.00 97.45 97.47 97.45 97.48 97.52 4 1.07 0.40 0.40 0.40 0.40 0.39 5 1.10 1.06 1.05 1.05 1.05 1.04 6 1.12 0.21 0.20 0.21 0.20 0.20 7 1.27 0.10 0.09 0.09 0.08 0.06 8 1.38 0.16 0.16 0.16 0.16 0.16Table A-5. Summary' of impurities of HC1 salt Form A after stability evaluation1 0.95 0.39 0.39 0.37 0.38 0.382 0.97 0.17 0.18 0.14 0.18 0.203 LOO 98.04 98.06 98.28 98.15 98.154 1.07 0.3 0.39 0.38 0.38 0.385 1.10 0.74 0.72 0.66 0.69 0.686 1.12 0.16 0.16 0.16 0.17 0.167 1.27 0.05 0.058 1.38 0.07 0.05 - 0.05 0.05Table A-6. Summary of impurities of citrate Form A after stability evaluationInitial 25 25 40 40 4w1 0.66 - - - 0.10 0.14 2 0.67 - - - - 0.15 3 0.68 - - - - 0.08 4 0.69 - - _ - 0.07 5 0.71 - - - - 0.05 6 0.75 - - - 0.13 0.40 7 0.85 _ _ _ - 0.11 8 0.95 0.48 0.48 0.48 0.48 0.49 9 0.97 0.12 0.21 0.17 0.30 0.61 10 1.00 97.59 97.54 97.59 97.21 96.18 11 1.07 0.37 0.36 0.35 0.37 0.34 12 1.10 1.06 1.06 1.05 1.02 0.97 13 1.12 0.16 0.15 0.16 0.16 0.16 14 1.27 0.09 0.08 0.08 0.10 0.12 15 1.38 0.12 0.13 0.12 0.13 0.12Table A-7. Summary' of impurities of succinate Form A after stability evaluationInitial„ u i DDT 25 C / 60%RH / lw 40 C / 75%RH / lw JrCftK KK1,. n / \ / * n / \(Area* / .)< Area%) < Area%)1 0.65 - - 0.282 0.66 - - 0.343 0.68 - - 0.084 0.69 - - 0.065 0.75 - - 1.246 0.85 - - 0.077 0.90 - - 0.088 0.95 0.46 0.46 0.439 0.97 0.11 0.14 1.1510 LOO 97.66 97.64 94.1811 1.06 - - 0.0512 1.07 0.33 0.33 0.2013 1.10 1.05 1.04 0.5514 1.12 0.15 0.16 0.1615 1.27 0.06 0.07 0.9816 1.38 0.17 0.17 0.15

[0194] Kinetic solubility was measured for freebase Form A, HC1 salt Form A, citrate Form A and succinate Form A in water and three bio-relevant media. The material was added into H2O, SGF, FaSSIF or FeSSIF with solid loading of 5 mg / mL followed by rolling (with roller incubator) at 37 °C at 25 rpm for 1, 2 and 24 h. For each time point, centrifugation and filtration (0.45 pm PTFE filter) were performed. Solubility by HPLC and pH were tested for supernatants. Solids were tested by XRPD. The results are summarized in Table A-8 (the detailed XRPD results in FIGS. IQ, 1R, IS, 23P, 23Q, 23R, 23S, 240, 24P, 24Q, 25P, and 25Q) and the solubility plots are displayed in FIG. 18B (dashed lines indicate the sample was a clear solution). Based on the results, a) in water, all salts showed higher solubility than freebase Form A. No form change was observed for HC1 salt Form A and freebase Form A; amorphous solids were observed for citrate Form A; b) in SGF, allsamples exhibited high solubility, and HC1 salt Form A showed slightly lower solubility, potentially due to the common ion effect; c) in FaSSIF, citrate Form A and succinate Form A showed higher solubility, and freebase Form A exhibited the lowest solubility. No form change was observed for HC1 salt Form A and freebase Form A, amorphous solids were observed for citrate Form A and succinate Form A; d) in FeSSIF, all samples exhibited similar solubility. No form change was observed for HC1 salt Form A and freebase Form A, amorphous solids were observed for citrate Form A and succinate Form A.Table A-8.1 h 2 h 24 h Material MediaForm Form FormS pH S pH S pH change change change II2O 0.0045 8.9 No 0.0042 8.5 No 0.0027 8.9 No FreebaseForm A SGF >4 8 2-2 N / A>5.0 2.2 N / A >3.9* 2.2 N / A FaSSIF 0.14 6.5 No 0.11 6.5 No 0.11 6.5 No FeSSIF 2.7 5.0 No 2.7 5.1 No 2.6 5.1 A H2O 3.7 5.9 No 3.3 6.0 No 2.7 5,8 No HC1 salt FormA SGF 4.4 1.8 No 4.4 1.9 No 3.6* 1.8 A FaSSIF 0.24 6.5 No 0.30 6.5 No 0.24 6.3 No FeSSIF 2.6 4.9 No 2.8 5.0 No 2.7 4.9 No HjO 4.6 4.2 A 4.2 4.2 A 4.1 5.3 A Citrate FormA SGF >5.7 2.2 N / A >5.7 2.2 N / A >4.7* 2.2 N / A FaSSIF 4.5 5.4 A 2.9 5.4 A 2.2 5.4 A FeSSIF 1.5 4.8 A 1.9 4.9 A 2.4 4.8 A H2O >4.6 4.9 N / A >4.9 4.9 N / A >3.8* 5.0 N / A SuccinateForm A SGF >4-7 2-2 N / A>4-8 2-2N / A >3.8*2-2N / A FaSSIF 4.6 4.8 A 1.8 5.9 A 1.6 5.9 A FeSSIF 2.1 4.9 A 2.4 5.0 A 2.5 4.9 A S: solubility (mg / mL).N / A: Clear solution was obtained in the sample and no XRPD test was performed.A: Amorphous.*: Decreased HPLC purity was observed.

[0195] Two-stage dissolution was performed for freebase Form A, HC1 salt Form A, citrate Form A and succinate Form A in two bio-relevant media. The procedures are listed as follows.Stage 1: The material was suspended in SGF (5 mg / mL, 3 mL) and equilibrated by rolling (25 rpm) at 37 °C. At 15 and 30 min time points, about 1.0 mL of the suspension was pipetted for centrifugation (37 °C, 10000 rpm, 5 min). Supernatant was collected for pH and HPLC solubility tests, and solids were separated for XRPD test.Stage 2: After sampling at 30-min time point, 3 mL of FaSSIF was transferred into the remaining 1 mL of SGF suspension (volume ratio of SGF: FaSSIF = 1:3). Rolling was continued at 25 rpm at 37 °C.At 45 min and 1, 2 h time points, about 0.8 mL of the suspension was pipetted for centrifugation. Supernatant was collected for pH and HPLC solubility tests, and solids were separated for XRPD test.

[0196] The results were summarized in Table A-9 (the detailed XRPD results are shown in FIGS. IT, 23T, 24R, and 25R) and the dissolution evaluation plot was displayed in FIG.18C (dashed lines indicate the sample was clear). Based on the results, freebase Form A, citrate Form A and succinate Form A exhibited good solubility in SGF, and HC1 salt Form A showed slightly lower solubility. / Ml samples exhibited similar solubility after dilution in FaSSIF. No form change was observed for HC1 salt Form A during the dissolution test. Amorphous was observed for freebase Form A, HO salt Form A and succinate Form A after dilution in FaSSIF.

[0197] Based on the kinetic solubility, freebase and salts showed high solubility in SGF and similar solubility in FeSSIF, and solubility difference was observed in FaSSIF. Two- stage dissolution showed similar solubility after dilution into FaSSIF from SGF, which suggested freebase and salts may behave similarly in-vivo.Table A-9.SGF FaSSIF15 min 30 min 45 min Ih 2h Freebase Form Solubility (mg / mL) >5.1 >5.1 0.9 0.9 0.8ApH 2.2 2.2 6.3 6.4 6.3 From change N / A N / A A A N / A HC1 salt Form Solubility (mg / mL) 4,3 4.4 1.0 1.0 1.0IllSGF FaSSIF lv±3X ilcil IVi Qld 1 Ull15 min 30 min 45 min Ih 2hApH 1.8 1.8 6.1 6.2 6.2 From change No No No No No. Solubility (mg / mL) >5.1 >4.9 1.1 1.2 1.1 Citrate Form AJ bpH 2.1 2.1 5.7 5.8 5.8 From change N / A N / A A A A Succinate Form Solubility (mg / mL) >4.8 >4,9 1.1 1.1 1.1ApH 2.1 2.1 6.0 5.9 6.0 From change N / A N / A A A N / A N / A: Clear solution or a litle solid was obtained in the sample and no XRPD test was performed. A: Amorphous.

[0198] Equilibrium solubility was measured for freebase Form A and HC1 salt Form A in pH buffers. Around 5 mg (based on Freebase) sample was added into 1 mL media followed by slurry (500 rpm) at 37 °C for 24 h, and the sample was centrifuged and filtered. The solution was tested by pH and HPLC. The solid was tested by XRPD. The results are summarized in Table A-10. The XRPD results are shown in FIGS. IL and 23G. Higher solubility was observed in pH 1.2 / 2, 0 / 4.5 buffers, and the solubility HC1 salt Form A in pH 2.0 buffer was lower than freebase Form A, potentially due to the common ion effect. XRPD result showed no form change was observed for freebase Form A and HO salt Form A after equilibrium solubility.Table A-10.Starting material Media Solubility Form (mg / mL)pH 1.2 >4.1 1.33 N / Ak A pH 2.0 >4.4 2.12 N / A Freebase Form A1pH 4.5 >4.2 4.68 N / ApH 6.8 0.059 6.83 Freebase Form ApH 7.4 0.026 7.43 Freebase Form AHCl salt Form A pH 1.2 >3.9 1.02 N / ApH 2.0 2,5 1.91 HC1 salt Form ApH 4.5 >4.4 4.37 N / ASolubilityStartingmaterial Media pH(mg / mL) pH FormpH 6.8 0.11 6.66 HC1 salt Form ApH 7.4 0.023 7.45 HC1 salt Form AN / A: Clear solution was obtained in the sample and no XRPD test was performed.

[0199] Grinding and tableting was performed for freebase Form A, HO salt Form A, citrate Form A and succinate Form A. For grinding, around 10 mg sample was added into a mortar, and manually ground with a pestle for 3 min. Tableting was performed with a tablet press at 350 MPa. The solid was tested by XRPD. The XRPD results are shown in FIGS. 1H, IM, 23H, 231, 24G, 24H, and 25H. XRPD results show low crystallinity was observed for freebase Form A after grinding, while no form change but slightly decreased crystallinity was observed after tableting. For HO salt Form A, no form change but slightly decreased crystallinity was observed after grinding and tableting. For citrate Form A, no form change but low crystallinity was observed after grinding and tableting. Amorphous solids were observed for succinate Form A after grinding, and tableting was not performed.

[0200] Solid stability evaluation was performed for freebase Form A, HC1 salt Form A and citrate Form A after tableting. The tableted samples were placed under the conditions of 25 °C / 60%RH and 40 °C / 75%RH for 4 weeks. The physical and chemical stability were evaluated by XRPD and HPLC purity, respectively. The results were summarized in Table A-11 and the XRPD results are shown from FIGS. IN, 23J, and 241. The impurities of freebase and salt hits are summarized in Tables A-12 to A-14, HPLC overlays are displayed in FIGS. 10, 23K, and 24J. The results show that no form change was observed after solid stability evaluation for all samples. No significant HPLC purity decrease was observed for freebase Form A. Decreased HPLC purity was observed for HC1 salt Form A and citrate Form A at 40 °C / 75%RH for 4 weeks.Table A-11.HPLC purityStarting material Condition Time Form changeTableted Freebase Initial - 97.49P°rm A25 °C / 60%RH 4 weeks 97.49 No 40 °C / 75%RH 4 weeks 97.36 NoHPLC purity Starting material Condition Time Form change (Area%)Tableted HO salt Initial - 98.12Form A 25 °C / 60%RH 4 weeks 97.92 No 40 °C / 75%RH 4 weeks 97.13 No Tableted Citrate Initial - 97.60Form A 25 °C / 60%RH 4 weeks 97.11 No 40 °C / 75%RH 4 weeks 94.98 NoTable A-12. Summary of impurities of tableted freebase Form A after stability evaluation# Peak RRT Initial 25 °C / 60%RH / 4w 40 °C / 75%RH / 4w (Area%) (Area%) (Area%) 1 0.66 - - 0,102 0.75 - - 0.073 0.95 0.48 0.48 0.484 0.98 0.13 0.13 0.155 1.00 97.49 97.49 97.366 1.07 0.40 0.40 0.377 1.10 1.04 1.04 1.028 1.12 0.21 0.21 0.219 1.27 0.09 0.09 0.0710 1.37 0.16 0.16 0.16Table A-13. Summary of impurities of tableted HO salt Form A after stability evaluationInitial 25 °C / 60%RH / 4w 40 °C / 75%RH / 4w # Peak RRT (Area%) (Area%) (Area%)1 0.65 - - 0.142 0.66 - -3 0.68 - 0.05 0.124 0.75 - - 0.135 0.86 - - 0.116 0.90 - - 0.107 0.95 0.38 0.39 0.40Initial 25 °C / 60%RH / 4w 40 °C / 75%RH / 4w # Peak RRT (Area%) (Area%) (Area%)8 0.98 0.17 0.27 0.429 1.00 98.12 97.92 97.1310 1.07 0.38 0.38 0.3811 1.10 0.70 0.73 0.6712 1.12 0.16 0.17 0.1613 1.27 0.05 0.0514 1.37 0.05 0.05 0.05Table A-14. Summary of impurities of tableted citrate Form A after stability evaluation. _, Initial 25 "C / 60%RH / 4w 40 ”C / 75%RH / 4w # Peak RR1(ArM%) (Area%) (Area%)1 0.66 - 0.10 00.322 0.68 - - 0.163 0.69 - 0.06 0.064 0.70 - - 0.705 0.71 - - 0.156 0.75 - 0.12 0.847 0.85 - - 0.138 0.90 - - 0.089 0.95 0.48 0.48 0.4810 0.98 0.15 0.30 0.9811 1.00 97.60 97.11 94.9812 1.05 - - 0.0913 1.07 0.36 0.36 0.3314 1.10 1.05 1.01 0.9415 1.12 0.15 0.16 0.1516 1.27 0.09 0.11 0.1317 1.38 0.13 0.13 0.11Example 3: Polymorph screen: analysis

[0201] Using freebase Form A as starting material, a total of 100 polymorph screening experiments were performed using different methods, including vapor-solution diffusion,vapor-solid diffusion, slow evaporation, slow cooling, temperature cycling, slurry (RT and 50 °C), anti-solvent addition and grinding. Based on the XRPD results of polymorph screening and further experiments, a total of 5 polymorphs were obtained, which were characterized by XRPD, TGA, DSC andFreebase Form A was postulated to be an anhydrate, Form B / C7D were unidentified due to form conversion after drying, Form E was postulated to be a 1,4-Dioxane solvate. The characterization results of polymorphs are summarized in Table B-l and the XRPD results are displayed in FIG. 1U.Table B-l.TGA weig45htDSC endothermSalt hit0SSSpeculated form (%, 150 °C)Freebase Form A 1.02 (150) 199.9* Anhydrate Freebase Form B Converted to Freebase Form A after dried at RT.Freebase Form C Converted to Freebase Form A after dried at RT.Freebase Form D Converted to Freebase Form A after dried at RT.Freebase Form E 6.27 (170) 188.9 1,4-Dioxane solvate *: Exotherm.Freebase Form A

[0202] In order to determine the phase origin, a variable temperature XRPD (VT-XRPD) experiment was performed for Form A. VT-XRPD results (FIG. 18 A) show no form change for freebase Form A after N2 purge for 20 min, heated to 120 °C and cooled to 30 °C under N2 purge (The peak shift at high temperature is postulated to be due to the thermal expansion of crystal lattice with the increased temperature). Therefore, Form A is postulated to be an anhydrate.Freebase Type B

[0203] Freebase Form B was obtained by stirring -20 mg starting material in MeOH / Toluene (1:9, v / v). Almost clear solution was obtained after slurry at RT for 2 days, and solid was obtained by slurry at 5 °C for 5 days. After dried at RT, the sample almost completely converted to freebase Form A. The XRPD pattern is displayed in FIG. 20. Due to the form conversion to freebase Form A, no other characterization was performed.

[0204] Freebase Form B was re-prepared by stirring ~50 mg starting material in MeOH / Toluene (1:9, v / v) at 5 °C for 5 days. The XRPD pattern is displayed in FIG. 3. The wet sample was a mixture of freebase Form A and B. After dried at RT, the sample almost completely converted to freebase Form A.Freebase Type C

[0205] Freebase Form C was obtained by vapor-solution diffusion of ~20 mg starting material in Acetone / MTBE. After dried at RT, freebase Form C partially converted to freebase Form A. The XRPD pattern is displayed in FIG. 21 A. Due to the form conversion to freebase Form A, no other characterization was performed.

[0206] Freebase Form C was re-prepared by vapor-solution diffusion of ~20 mg starting material in Acetone / MTBE. After dried at RT, freebase Form C partially converted to freebase Form A. The XRPD patterns are displayed in FIGS. 4 and 21B.Freebase Type D

[0207] Freebase Form D was obtained by vapor-solution diffusion of ~20 mg starting material in DCM / MTBE. After dried at RT, freebase Form D almost converted to freebase Form A. The XRPD pattern is displayed in FIG. 22A. Due to the form conversion to freebase Form A, no other characterization was performed.

[0208] Freebase Form D were re-prepared by vapor-solution diffusion of ~20 mg starting material in DCM / MTBE After dried at RT, freebase Form D almost completely converted to freebase Form A. The XRPD patterns are displayed in FIGS. 5 and 22B.Freebase Type E

[0209] Freebase Form E was obtained by vapor-solid diffusion of ~20 mg starting material in 1,4-Dioxane. The XRPD pattern is displayed in FIG. 2A. The TGA / DSC curves are displayed in FIG. 2B, which show a weight loss of 6.27% up to 170 °C and one exotherm at 188.9 °C (peak).!HNMR results (FIG. 19A) show the molar ratio of 1,4-Dioxane / API is 1.2 (14.2 wt%).

[0210] In order to investigate the TGA weight loss, heating experiment was performed for freebase Form E. XRPD results (FIG. I9B) show freebase Form E converted to freebaseForm A after heated to 120 °C and cooled to RT. NMR results (FIG. 19C) show the molar ratio of 1,4-Dioxane / API is 0.01 (0.2 wt%) after heated to 120 °C. Combined with the large TGA weight loss, residual solvent and form change after heating, freebase Form E is postulated to be a 1,4-Di oxane solvate.Example 4: Polymorph screen: process

[0211] A total of 100 polymorph screening experiments were performed for freebase using different crystallization or solid transformation methods.Vapor-solid diffusion

[0212] Vapor-solid diffusion experiments were conducted using 11 different solvents. Approximately 20 mg of starting material was weighed into a 3-mL vial, which was placed into a 20-mL vial with 3 mL of volatile solvent. The 20-mL vial was sealed with a cap and kept at RT for 7 days allowing solvent vapor to interact with sample. The solids were tested by XRPD and the results summarized below show that freebase Form A / E were obtained.Experiment ID Solvent Result1 EtOH Freebase Form A 2 MIBK Freebase Form A 3 EtOAc Freebase Form A 4 MTBE Freebase Form A 5 2-MeTHF Freebase Form A 6 1,4-Dioxane Freebase Form E 7 ACN Freebase Form A 8 Toluene Freebase Form A 9 IPA Freebase Form A 10 H2O Freebase Form A 11 DMSO Freebase Form AVapor-solution diffusion

[0213] Vapor-solution diffusion experiments were conducted under 14 different conditions. Approximately 20 mg of starting material was dissolved in 0.8-1.5 mL of appropriate solvent to obtain a clear solution in a 3-mL vial, and filtered to a new vial (0.45 pm, PTFE). This solution was then placed into a 20-mL vial with 3 mL of volatile solvent.The 20-mL vial was sealed with a cap and kept at RT allowing sufficient time for organic vapor to interact with the solution. The solids were isolated for XRPD analysis. The results summarized below show that oil / freebase Form A / C / D were obtained.Experiment ID Solvent Anti-solvent Result1 MeOH Amorphous 2 NMP H2O Oil 3 1,4-Dioxane Amorphous 4 EtOFI Freebase Form A 5 Acetone Freebase Form C 6 EtOAc MTBE Freebase Form A 7 DMAc Oil 8 DCM Freebase Form D 9 EtOH Amorphous 10 2-MeTHF n-Heptane Freebase Form A 11 CHCI3 Freebase Form A 12 ACN Freebase Form A 13 DMSO Toluene Oil 14 1,4-Dioxane Freebase Form ASlow cooling

[0214] Slow cooling experiments were conducted in 6 solvent systems. 20 mg of starting material was suspended in 1.0 mL of solvent in a 3-mL glass vial at RT. The suspension was then heated to 50 °C, equilibrated for 2 h and filtered to a new vial (0.45 pm, PTFE).Filtrates were slowly cooled down to 5 °C at a rate of 0.1 °C / min. The obtained solids were kept isothermal at 5 °C and then solids were tested by XRPD. Results summarized below indicate that amorphous / freebase Form A were obtained.Experiment ID Solvent Result1 IPA Freebase Form A 2 IPAc Freebase Form A* 3 MIBK Freebase Form A* 4 ACN / MTBE (1:1) Amorphou s * 5 2-MeTHF Amorphous* 6 EtOH / n-Heptane (1:1) Freebase Form A* *: The sample was clear at 5 °C for 2 days followed by at -20 °C for 1 day. The sample was obtained by slow evaporation at RTSlurry at RT

[0215] About 20 mg of starting material was suspended in 0.5 mL of solvent in an HPLC glass vial. After the suspension was stirred magnetically (1000 rpm) at RT for 3 days, the remaining solids were centrifuged for XRPD analysis. Results summarized below indicate that freebase Form A / B were obtained.Experiment ID Solvent (v / v) Result1 EtOH / MTBE (1:9) Freebase Form A 2 Acetone / H2O (1:9) Freebase Form A 3 EtO Ac / MTBE (1:4) Freeb ase F orm A 4 MTBE Freebase Form A 5 ACN / H2O (1:9) Freebase Form A 6 THF / n-Heptane (1:9) Freeb ase F orm A 7 Toluene Freebase Form A 8 H2O Freebase Form A 9 DCM / MTBE (1:9) Freebase Form A 10 1,4-Dioxane / Toluene (1:9) Freebase Form A 11 MeOH / Toluene (1:9) Freebase Form B* 12 DMSO / H2O (1:9) Freebase Form A 13 DMAc / Toluene (1:9) Freebase Form A 14 IPA / H2O (98:2, aw~0.2) Freebase Form A 15 IPA / H2O (96:4, aw~0.4) Freebase Form A 16 IPA / H2O (92:8, aw~0.6) Freebase Form A 17 IPA / H2O (85:15, aw0.8) Freebase Form A *: All most clear solution was obtained after slurry at RT for 2 days, the sample was obtained by slurry at 5 °C for 5 days.Slurry at 50 °C

[0216] About 20 mg of starting material was suspended in 0.5 mL of solvent in an HPLC glass vial. After the suspension was stirred (1000 rpm) at 50 °C for 4 days, the remaining solids were centrifuged for XRPD analysis. Results summarized below indicate that amorphous / freebase Form A were obtained.Experiment ID Solvent (v / v) Result1 MeOH / Toluene (1:9) Amorphous 2 MIBK / n-Heptane (1:2) Freebase Form A 3 IPAc / MTBE ( 1:2) Freebase Form A 4 CHCh / Toluene (1:4) Amorphous 5 H? O Freebase Form A 6 n-Heptane Freebase Form A 7 2-MeTHF / MTBE (1:4) Freebase Form A 8 1,4-Dioxane / n-Heptane (1:9) Freebase Form A 9 ACN / Toluene (1:4) Freebase Form A 10 TFIF / Toluene (1:9) Freebase Form A 11 NMP / H2O (1:9) Freebase Form A 12 DMSO / Toluene (1:4) Freebase Form A *: The sample was clear at 50 °C and RT. The solid was obtained under 5 °C.Temperature cycling

[0217] About 20 mg of starting material was suspended in 0.5 niL of solvent in an HPLC glass vial. After heating-cooling (50 °C~5 °C, 0.1 °C / min) was performed for the suspension for 2 cycles, the remaining solids were centrifuged for XRPD analysis. Results summarized below indicate that freebase Form A was obtained.Experiment ID Solvent (v / v) Result1 MeOH / MTBE (1:9) Freebase Form A 2 EtOHZHzO (1:9) Freebase Form A 3 ACN / MTBE (1:9) Freebase Form A 4 EtOAc / n-Heptane (1:4) Freebase Form A 5 2-MeTHF Freebase Form AExperiment ID Solvent (v / v) Resuit6 Acetone / Toluene (1:4) Freebase Form A 7 IPAc Freebase Form A 8 H2O Freebase Form A 9 MTBE Freebase Form A 10 DMAc / FFO (1:9) Freebase Form A 11 NMP / MTBE (1:9) Freebase Form A 12 CHCI3 / MTBE (1:4) Freebase Form ASiow evaporation

[0218] Slow evaporation experiments were performed under 8 conditions. 20 nig of starting material was dissolved in 0.8-1.6 mL of solvent in a 3-mL glass vial. The resulting solution was subjected to slow evaporation at RT with vials sealed and poked with 4 pinholes. The solids were isolated for XRPD analysis and the results summarized below indicate that amorphous / freebase Form A were obtained.Experiment ID Solvent (v / v) Result1 MeOH Amorphous* 2 EtOH Freebase Form A 3 ACN Freebase Form A 4 Acetone Amorphous* 5 EtOAc Freebase Form A 6 2-MeTHF Freebase Form A* 7 DCM Amorphous* 8 THF / H2O (9:1) Amorphous* *: The sample was gel after slow evaporation at RT.Grinding

[0219] Grinding experiments were performed with or without solvent addition.Approximate 20 mg of starting material was weighed into the mortar. 20 pL solvent was added into the mortar. The solids were ground for 3-5 min. The solids were isolated for XRPD analysis. Results summarized below show that freebase Form A with low crystallinity was obtained. The XRPD results are displayed in FIG. IP.Experiment ID Solvent Result1 NA Freebase Form A* 2 H2O Freebase Form A* *: No form change but low crystallinity was observed for freebase Form A after grinding.Anti-solvent Addition

[0220] A total of 18 anti-solvent addition experiments were carried out. About 20 mg of starting material was dissolved in 0.6-1.2 mL solvent to obtain a clear solution, filtered the solution to a new vial (0.45 pm, PTFE) if the solids were not dissolved, and the solution was magnetically stirred (-1000 rpm) followed by addition of anti-solvent until precipitate appeared or the total amount of anti-solvent reached 10.0 mL. The samples without precipitate were transferred to slurry at 5 °C and then transferred to slurry at -20 °C. The clear samples were transferred to RT for evaporation. The solids were isolated for XRPD analysis. Results below show that amorphous / freebase Form A were obtained.Experiment ID Solvent Anti-solvent Result1 Acetone Freebase Form A* 2 MeOH Amorphous 3 THF H2O Freebase Form A* 4 AON Amorphous* 5 DMSO Amorphous 6 Acetone Freebase Form A 7 EtOH Freebase Form A#8 EtOAc n-Heptane Freebase Form A 9 IMF Freebase Form A 10 1,4-Dioxane Freebase Form A 11 Acetone Freebase Form A#12 MeOH Freebase Form A** 13 2-MeTHF MTBE Freebase Form A* 14 ACN Freebase Form A** 15 CHCI3 Freebase Form Aff16 DMAc Freebase Form A** 17 DCM Toluene Freebase Form A** 18 1,4-Dioxane Freebase Form A***: The sample was gel at RT and the suspension was obtained by temperature cycling (50 °C~5 °C, 0.1 °C / min, 2 cycles).The sample was clear at RT and the suspension was obtained by slurry' at 5 °C for 4 days.**: The sample was clear at RT followed by shiny’ at 5 °C for 4 days and at -20 °C for 1 day. The sample was obtained by slow evaporation at RT.Example 5: Salt Screen: analysis

[0221] Using freebase Form A as starting material, a total of 100 salt screening experiments were performed using 20 acids (HO, H2SO4, Maleic acid, H3PO4, Mucic acid, L-Tartaric acid, Fumaric acid, Citric acid, Glycolic acid, L-Malic acid, Hippuric acid, L- Lactic acid, Succinic acid, Adipic acid, 1,5 -Naphthalene disulfonic acid, p-Toluenesulfonic acid, Methanesulfonic acid, Oxalic acid, Benzoic acid, and HBr) in 5 solvent systems (IPA, MIBK, IP Ac, 2-MeTFIF, and ACN). Around 20 mg of starting material and equimolar corresponding acid were added in 0.5 mL solvent followed by slurry at RT for 3 days. 20 salt hits were obtained from salt screening and further experiments, which were characterized by XRPD, TGA and DSC. The salt stoichiometry was determined usingNMR. All the characterization results are summarized in the table below.TGA weight loss DSC endotherm Molar Salt hit ratio (%, 150 °C) (°C, peak) (acid / FB) HC1 salt Form A 3.81 (150) 65.6, 222.0* 1.1 Tartrate Form A 5.88 (150) 52.6, 170.2 1.0 Fumarate Form A 6.82 (130) 170.5* 1.0 Fumarate Form B 4.22 (130) 171.6* 1.0 Fumarate Form C 6.87 (130) 57.1, 167.7* 1.0 Citrate Form A 1.64 (150) 177.0 1.0? 10 (120)Malate FormAO / 1™ 145.7. 161.4 1.02,84 (160)Malate Form B?6™ 49.3, 113.4, 162.5* 1.03.64 (U0)Malate Form C 144.6, 158.2* 1.03.64 (150)Succinate Form A 1.34 (100) 145.4, 158.6 1.0 Succinate Form B 1.92 (130) 145.6, 157.5* 1.0 Succinate Form C 3.84 (120) 140.9, 157.9* 1.0 Adipate Form A NA NA NATGA weight loss DSC endotherm Molar Salt hit ratio (%, 150 °C) (°C, peak) (acid / FB) 5.95 (100)Napadisylate Form A 56.8, 160.0, 257.8* 1.02.35 (150)Napadisylate Form B 5.35(150) 49.3, 137.6, 201.5* 0.613.39 (120)Napadisylate Form C 50.2, 125.9, 265.7* 1.08.24 (180)0.95(150)Tosylate Form A 138.6, 214.2* 1.08.24 (180)Mesylate Form A 3.54 (150) 222.8* 1.0 OxalateFormA 0.55 (150) 82.4, 174.0* 1.0 HBr salt Form A 5.34 (150) 57.2, 215.6* 1.0 *: Exotherm.NA: XKPD result showed freebase Form A was observed in potential adipate Form A, and thus no other characterization was performed.HCI Salt

[0222] HCI salt Form A was obtained by stirring -20 mg freebase Form A with equimolar HCI in IPA at RT for 2 days, followed by centrifugation and vacuum drying at RT for 1 day. The XRPD pattern is displayed in FIG. 23L. The TGA / DSC curves of HCI salt Form A are displayed in FIG. 23M, which showed a weight loss of 3.81% up to 150 °C, and one endotherm at 65.6 °C (peak) and one exotherm at 222.0 °C (peak). The 'H NMR result in FIG. 23N showed the molar ratio of IP A / API was 0.1 (0.9 wt%). HPLC / IC results showed the molar ratio of acid / FB was 1.1. PLM image of HCI salt Form A is displayed in FIG. 230, which showed small particles.

[0223] Repreparation: HCI salt Form A was obtained by stirring -300 mg starting material with equimolar HCI (12M) in IPA at RT for 2 days, followed by centrifugation and vacuum drying at 50 °C for 1.5 h and at RT overnight. XRPD result (FIG. 6 A) shows HCI salt Form A was obtained. The TGA / DSC curves are displayed in FIG. 6B. A weight loss of 3.82% up to 150 °C was observed on the TGA curve, and one endotherm at 179.3 °C (peak) and one exotherm at 221.8 °C (peak) were observed on the DSC curve. HPLC / IC results show that the molar ratio of acid / API was 1.1. ThelH NMR result in FIG. 23 A. shows the molar ratio of IP A / API was 0.1 (1.2 wt %); acetone was also detected. KF result shows the water content is 3.23%. PLM image and SEM images are listed in FIG. 23B and FIG. 23C, which show small and irregular particles with aggregation.Citrate Salt

[0224] Citrate Form A was obtained by stirring -20 mg freebase Form A with equimolar citric acid in Acetone at RT for 1 day followed by temperature cycling (50 °C-5 °C, 0.1 °C / min, 1 cycle). The sample was obtained by centrifugation and vacuum drying at RT for 1 day. The XRPD pattern is displayed in FIG. 24K. The TGA / DSC curves of citrate Form A are displayed in FIG. 24L, which showed a weight loss of 1.65% up to 150 °C and one exotherm at 177.0 °C (peak). TheNMR result in FIG. 24M showed the molar ratio of acid / FB was 1.0, and the molar ratio of IP A / API was 0.2 (1.1 wt%). PLM image of citrate Form A is displayed in FIG. 24N, which showed small particles with aggregation.

[0225] Repreparation: Citrate Form A was obtained by stirring -300 mg starting material with equimolar citric acid in IPA at RT for 2 days, followed by centrifugation and vacuum drying at 50 °C for 1.5 h and at RT overnight. XRPD result (FIG. 7 A) shows citrate Form A was obtained. The TGA / DSC curves are displayed in FIG. 7B. A weight loss of 1.14% up to 150 °C was observed on the TGA curve, and one exotherm at 173.7 °C (peak) was observed on the DSC curve. TheNMR result in FIG. 24A shows the molar ratio of acid / API was 1.0 and no residual IP / X was detected. KF result shows the water content was 1.21%. PLM image and SEM images are listed in FIG. 24B and FIG. 24C, which show small and irregular particles with aggregation.Succinate Salt

[0226] Succinate Form A / B were obtained by stirring -20 mg freebase Form A with equimolar succinic acid in IPA and MIBK at RT for 2 days, followed by centrifugation and vacuum drying at RT for 1 day. Succinate Form C was obtained by stirring -20 mg freebase Form A with equimolar succinic acid in 2-MeTHF at RT for 1 day and 5 °C slurry for 1 day, followed by centrifugation and vacuum drying at RT for 1 day. The XRPD patterns were displayed in FIG. 8?\.

[0227] The TGA / DSC curves of succinate Form A are displayed in FIG. 251, which showed a weight loss of 1.34% up to 100 °C and one endotherm at 145.4 °C (peak) and one exotherm at 158.6 °C (peak). The1H NMR result in FIG. 25 J showed the molar ratio of acid / FB was 1.0, and the molar ratio of IP A / API was 0.4 (2.7 wt%). PLM image of succinate Form A is displayed in FIG. 25K, which showed small particles with aggregation.

[0228] The TGA / DSC curves of succinate Form B are in FIG. 8A, which showed a weight loss of 1.92% up to 130 °C and one endotherm at 145.6 °C (peak) and one exotherm at 157.5 °C (peak). The1H NMR result in FIG. 25L showed the molar ratio of acid / FB was 1.0, and no residual MIBK was detected. PLM image of succinate Form B is displayed in FIG. 25M, which showed small particles with aggregation.

[0229] The TG / DSC curves of succinate Form C are displayed in FIG. 8E, which showed a weight loss of 3.84% up to 120 °C and one endotherm at 140.9 °C (peak) and one exotherm at 157.9 °C (peak). TherH NMR result in FIG. 25N showed the molar ratio of acid / FB was 1.0, and the molar ratio of 2-MeTHF / API was 0.4 (3.0 wt%). PLM image of succinate Form C is displayed in FIG. 250, which showed small particles with aggregation.

[0230] Repreparation: Succinate Form A was obtained by stirring -300 mg starting material with equimolar succinic acid in IPA at RT for 2 days, followed by centrifugation and vacuum drying at 50 °C for 1.5 h and at RT overnight. XRPD result (FIG. 25A) shows succinate Form A was obtained. The TGA / DSC curves are displayed in FIG. 8B. A weight loss of 1.24% up to 100 °C was observed on the TGA curve, and one endotherm at 146.3 °C (peak) and one exotherm at 159.6 °C (peak) were observed on the DSC curve. TheNMR result in FIG. 25B shows the molar ratio of acid / API was 1.0, and the molar ratio ofIP A / API was 0.4 (2.8 wt%). KF result shows the water content was 0.76%. PLM image and SEM images are listed in FIG. 25C and FIG. 25D, which show small and irregular particles with aggregation.Tartrate Salt

[0231] Tartrate Form A was obtained by stirring ~20 mg freebase Form A with equimolar L-tartaric acid in IPA at RT for 2 days, followed by centrifugation and vacuum drying at RT for 1 day. The XRPD pattern is displayed in FIG. 9A. The TGA / DSC curves of tartrate Form A are displayed in FIG. 9B, which show a weight loss of 5.88% up to 150 °C, and one endotherm at 52.6 °C (peak) and one exotherm at 170.2 °C (peak). The1H NMR result in FIG. 26A show the molar ratio of acid / FB was 1.0, and the molar ratio of IP A / API was 0.3 (2.5 wt%). PLM image of tartrate Form A is displayed in FIG. 26B, which shows small particles.Fumarate Salt

[0232] Fumarate Forms A / B were obtained by stirring ~20 mg freebase Form A with equimolar fumaric acid in IP A and MIBK at RT for 2 days, followed by centrifugation and vacuum drying at RT for 1 day. Fumarate Form C was obtained by stirring ~20 mg freebase Form A with equimolar fumaric acid in IPAc at RT followed by temperature cycling (50 °C~5 °C, 0.1 °C / min, 1 cycle). The sample was obtained by centrifugation and vacuum drying at RT for 1 day. The XRPD patterns are displayed in FIG. 10A.

[0233] The TGA / DSC curves of fumarate Form A are displayed in FIG. 10B, which show a weight loss of 6.82% up to 130 °C, and one exotherm at 170.5 °C (peak). TherH NMR result in FIG. 27A shows the molar ratio of acid / FB was 1.0, and the molar ratio of IP A / API was 0.5 (3.5 wl%). PLM image of fumarate Form A is displayed in FIG. 27B, which shows small particles.

[0234] The TGA / DSC curves of fumarate Form B are displayed in FIG. 10C, which show a weight loss of 4.22% up to 130 °C and one exotherm at 171.6 °C (peak). TheTII NMR result in FIG. 27C shows the molar ratio of acid / FB was 1.0, and the molar ratio of MIBK / API was 0.4 (3.3 wt%). PLM image of fumarate Form B is displayed in FIG. 27D, which shows small particles.

[0235] The TGA / DSC curves of fumarate Form C are displayed in FIG. 10D, which showed a weight loss of 6.87% up to 130 °C and an endotherm at 57.1 °C (peak) and one exotherm at 167.7 °C (peak). TherH NMR result in FIG. 27E shows the molar ratio of acid / FB was 1.0, and the molar ratio of IP Ac / API was 0.2 (2.2 wt%). PLM image of fumarate Form C is displayed in FIG. 27F, which shows small particles.Malate Salt

[0236] Malate Form A / C were obtained by stirring ~20 mg freebase Form A with equimolar malic acid in IP A and ACN at RT for 2 days, followed by centrifugation and vacuum drying at RT for 1 day. Malate Form B was obtained by stirring ~20 mg freebase Form A with equimolar malic acid in IPAc at RT for 1 day followed by temperature cycling (50 °C~5 °C, 0.1 °C / min, 1 cycle). The sample was obtained by centrifugation and vacuum drying at RT for 1 day. The XRPD patterns are displayed in FIG. 11 A.

[0237] The TGA / DSC curves of malate Form A are displayed in FIG. 11B, which showed a two-step weight loss of 2.10% up to 120 °C and 2.84% from 120 °C to 160 °C.DSC result shows one endotherm at 145.7 °C (peak) and one exotherm at 161.4 °C (peak). The ’ll NMR result in FIG. 28A shows the molar ratio of acid / FB was 1.0, and the molar ratio of IP A / API was 0.4 (3.2 wt%). PLM image of malate Form A is displayed in FIG. 28B, which shows small particles.

[0238] The TGA / DSC curves of malate Form B are displayed in FIG. 11C, which showed a two-step weight loss of 2.66% up to 80 °C and 3.64% from 80 °C to 150 °C. DSC result shows two endotherms at 49.3 and 113.4 °C (peak) and one exotherm at 162.5 °C (peak). The1H NMR result in FIG. 28C shows the molar ratio of acid / FB was 1.0, and the molar ratio of IP Ac / API was 0.1 (1.7 wt%). PLM image of malate Form B is displayed in FIG. 28D, which shows small particles with aggregation.

[0239] The TGA / DSC curves of malate Form C are di splayed in FIG. 11D, which showed a two-step weight loss of 3.17% up to 130 °C and 2.50% from 130 °C to 150 °C. DSC result shows one endotherm at 144,6 °C (peak) and one exotherm at 158.2 °C (peak). The ’H NMR result in FIG. 28E shows the molar ratio of acid / FB was 1.0, and the molar ratio of 2-MeTHF / API was 0.3 (3.6 wt%). PLM image of malate Form C is displayed in FIG. 28F, which shows small particles.Adipate Salt

[0240] Adipate Form A was obtained by stirring -20 mg freebase Form A with equimolar adipic acid in 2-MeTHF at RT for 1 day, followed by slurry at 5 °C and then transferred to vacuum drying at RT for 1 day. XRPD result showed a mixture of adipate Form A and freebase Form A was obtained. The XRPD pattern is displayed in FIG. 29.

[0241] Re-prepared sample was obtained by stirring -20 mg starting material with two molar ratio of adipic acid in 2-MeTHF at 5 °C for 1 day followed by addition 1.0 m L MTBE and then transferred to vacuum drying at RT for 1 day. XRPD result showed freebase Form A was obtained. The XRPD pattern is displayed in FIG. 12.Napadisylate Salt

[0242] Napadisylate Forms A / B / C were obtained by stirring -20 mg freebase Form A with equimolar 1,5-naphthalenedisulfonic acid in IP A, M1BK and ACN at RT for 1 day followed by temperature cycling (50 °C~5 °C, 0.1 °C / min, 1 cycle). The samples wereobtained by centrifugation and vacuum drying at RT for 1 day. The XRPD patterns are displayed in FIG. 13 A.

[0243] The TGA / DSC curves of napadisylate Form A are displayed in FIG. 13B, which showed a two-step weight loss of 5.95% up to 100 °C and 2.35% from 100 °C to 150 °C. DSC result showed two endotherms at 56.8 and 160.0 °C (peak), and one exotherm at 257.8 °C (peak). The 'HNMR result in FIG. 30A shows the molar ratio of acid / FB was 1.0 and no residual IP A was detected. PLM image of napadisylate Form A is displayed in FIG. SOB, which shows small particles with aggregation.

[0244] The TGA / DSC curves of napadisylate Form B are displayed in FIG. 13C, which showed a weight loss of 5.35% up to 150 °C and two endotherms at 49.3 and 137.6 °C (peak), and one exotherm at 201.5 °C (peak). The ^ I NMR result in FIG. 30C shows the molar ratio of acid / FB was 0.6 and the molar ratio of MIBK / API was 0.3 (3.5 wt° / o). PLM image of napadisylate Form B is displayed in FIG. 30D, which shows small particles.

[0245] The TGA / DSC curves of napadisylate Form C are displayed in FIG. 13D, which showed a weight loss of 13.39% up to 120 °C, and two endotherms at 50.2 and 125.9 °C (peak) with one exotherm at 265.7 °C (peak). TheNMR result in FIG. 30E showed the molar ratio of acid / FB was 1.0 the molar ratio of ACN / API was 0.7 (4.0 wt%). PLM image of napadisylate Form C is displayed in FIG. 30F, which shows small particles with aggregation.Tosylate Salt

[0246] Tosylate Form A was obtained by stirring ~20 mg freebase Form A with equimolar p-toluenesulfonic acid in IP Ac at RT for 1 day followed by temperature cycling (50 °C~5 °C, 0.1 °C / min, 1 cycle). The sample was obtained by centrifugation and vacuum drying at RT for 1 day. The XRPD pattern is displayed in FIG. 14A. The TGA / DSC curves of tosylate Form A are displayed in FIG. 14B, which show a weight loss of 0.95% up to 150 °C, and one endotherm at 138.6 °C (peak), and one exotherm at 214.2 °C (peak). ThelH NMR result in FIG. 31 A showed the molar ratio of acid / FB was 1.0, and the molar ratio of IP Ac / API was 0.03 (0.3 wt%). PLM image of tosylate Form A is displayed in FIG. 3 IB, which shows small particles with aggregation.Mesylate Salt

[0247] Mesylate Form A was obtained by stirring ~20 mg freebase Form A with equimolar methanesulfonic acid in MIBK at RT for 1 day followed by temperature cycling (50 °C-~5 °C, 0.1 °C / min, 1 cycle). The sample was obtained by centrifugation and vacuum drying at RT for 1 day. The XRPD pattern is displayed in FIG. 15A. The TGA / DSC curves are displayed in FIG. 15B, which show a weight loss of 3.54% up to 150 °C and one exotherm at 222.8 °C (peak). The1H NMR result in FIG. 32 A shows the molar ratio of aid / FB was 1.0, and the molar ratio of MIBK / API was 0.2 (2.6 wt%). PLM image of mesylate Form is displayed in FIG. 32B, which showed small particles.Oxalate Sait

[0248] Oxalate Form A was obtained by stirring ~20 mg freebase Form A with equimolar oxalic acid in MIBK at RT for 1 day followed by temperature cycling (50 °C~5 °C, 0.1 °C / min, 1 cycle). The sample was obtained by centrifugation and vacuum drying at RT for 1 day. The XRPD pattern is displayed in FIG. 16A. The TGA / DSC curves of oxalate Form A are displayed in FIG. 16B, which show a weight loss of 0.55% up to 150 °C and one endotherm at 82.4 °C (peak), and one exotherm at 174.0 °C (peak). The1H NMR result in FIG. 33A shows no residual MIBK was detected. HPLC / IC results showed the molar ratio of acid / FB was 1.0. PLM image of oxalate Form A is displayed in FIG. 33B, which shows small particles with aggregation.HBr Salt

[0249] HBr salt Form A was obtained by stirring ~20 mg freebase Form A with equimolar HBr in MIBK at RT for 1 day followed by temperature cycling (50 °C~5 °C, 0.1 °C / min, 1 cycle). The sample was obtained by centrifugation and vacuum drying at RT for 1 day. The XRPD pattern is displayed in FIG. 17A. The TGA / DSC curves of HBr salt Form A are displayed in FIG. 17B, which show a weight loss of 5.34% up to 150 °C and one endotherm at 57.2 °C (peak), and one exotherm at 215.6 °C (peak). The1H NMR result in FIG. 34A shows the molar ratio of MIBK / API was 0.2 (2.8 wt%). HPLC / IC results showed the molar ratio of acid / FB was 1.0. PLM image of HBr salt Form A is displayed in FIG. 34B, which shows small particles with aggregation.Example 6: Summary

[0250] Using freebase Form A as starting material, a total of 100 salt screening experiments were performed using 20 acids in 5 solvent syste s. A total of 20 crystalline salt hits were obtained. The salt stoichiometry was determined using high performance liquid chromatography (HPLC) combined with ion chromatography (IC) or1H solution nuclear magnetic resonance (1H NMR). Based on the solid-state characterization results and safety class of acid, HC1 salt Form A, citrate Form A and succinate Form A were selected for re-preparation on -300 mg scale (based on freebase).

[0251] Using freebase Form A as starting material, a total of 100 polymorph screening experiments were performed using different methods. Based on the XRPD results of polymorph screening and further experiments, a total of 5 polymorphs were obtained.

[0252] The re-prepared HC1 salt Form A, citrate Form A and succinate Form A were used for salt evaluation and comparison with freebase Form A. Hygroscopicity, solid stability, kinetic solubility, two-stage dissolution and grinding were evaluated for all samples. Equilibrium solubility in pH buffers was measured for freebase Form A and HC1 salt Form A. Based on the evaluation results, succinate Form A exhibited physical and chemical instability issues under high humidity. The evaluation results for Freebase Form A, HC1 salt Form A, and Citrate Form A are summarized in Table S-l below.* Dynamic vapor sorption (DVS) results showed a water uptake of 0.442%, 2.645%, 1.183%, 1.42% at 25 °C / 80%RH for freebase Form A, HO salt Form A, citrate Form A and succinate Form A, respectively; no form change was observed for freebase Form A, HC1 salt Form A and citrate Form A after DVS. Amorphous solids were obtained starting from crystalline succinate Form A after DVS.* Solid stability results showed no form change or obvious HPLC purity change for freebase Form A and HC1 salt Form A after storage at 25 °C / 60%RH and 40 °C / 75%RH for 4 weeks. Slight purity decrease was observed for citrate Form A after 4 weeks under 40 °C / 75%RH. Purity decrease and amorphous solids were observed for succinate Form A after 1 week under 40 °C / 75%RH.* Kinetic solubility was measured for freebase Form A, HC1 salt Form A, citrate Form A and succinate Form A in water, SGF, FaSSlF and FeSSIF. In water, all salts showed higher solubility than freebase Form A. No form change was observed for HC1 salt Form A and freebase Form A, and amorphous solids were observed for citrate Form A, In SGF, all samples exhibited high solubility, and HC1 salt Form A showed slightly lower solubility,potentially due to the common ion effect. In FaSSIF, citrate Form A and succinate Form A showed higher solubility, and freebase Form A exhibited the lowest solubility. No form change was observed for HC1 salt Form A and freebase Form A; amorphous was observed for citrate Form A and succinate Form A. In FeSSIF, all samples exhibited similar solubility. No form change was observed for HC1 salt Form A and freebase Form A; amorphous solids were observed for citrate Form A and succinate Form A.* Two-stage dissolution was performed for freebase Form A, HC1 salt Form A, citrate Form A and succinate Form A in SGF and FaSSIF. Freebase Form A, citrate Form A and succinate Form A exhibited good solubility in SGF, and HC1 salt Form A showed slightly lower solubility. All samples exhibited similar solubility after dilution in FaSSIF. No form change was observed for HQ salt Form A during the dissolution test. / Amorphous solids were observed for freebase Form A, HC1 salt Form A and succinate Form A after dilution in FaSSIF.• Equilibrium pH-dependent solubility was measured in pH buffers for freebase Form A and HQ salt Form A. Higher solubility was observed in pH 1.2 / 2.0 / 4.5 buffers, and the solubility of HC1 salt Form A in pH 2.0 buffer was lower than freebase Form A, potentially due to the common ion effect.• Grinding and tableting were performed for freebase Form A, HQ salt Form A, citrate Form A and succinate Form A. The XRPD results showed low crystallinity was observed for freebase Form A after grinding, while no form change but slightly decreased crystallinity was observed after tableting. For HC1 salt Form A, no form change but slightly decreased crystallinity was observed after grinding and tableting. For citrate Form A, no form change but low crystallinity was observed after grinding and tableting. Amorphous solids were observed for succinate Form A after grinding, and tableting was not performed.* Solid stability evaluation w'as performed for freebase Form A, HC1 salt Form A and citrate Form A after tableting. The results showed that no form change was observed after solid stability for all tableted samples. No significant HPLC purity decrease was observed for freebase Form A. Decreased HPLC purity was observed for HQ salt Form A and citrate Form A at 40 °C / 75%RH for 4 weeks.

[0253] Freebase Form A showed similar solubility and better chemical stability compared with salts. The slight crystallinity decrease after manual grinding of freebase Form A may be due to the small amount of sample (~10 mg) used for grinding. Among the salts, HC1 salt Form A showed better chemical stability.Table S-l Summary of Compound 1 freebase and saltsTest item ResultSolid form Freebase Form A HC1 salt Form A Citrate Form A TGA weight loss (%, °C) 1.02 (150) 3.82 (150) 1.14 (150) DSC endothermI 99.0* 179.3, 221.8* 173.7* ( C, peak)Molar ratio (acid / FB) - 1.1 1.0 Form Anhydrate Hydrate Anhydrate Water content (KF) 1.84% 3.23% 1.21% D\ S water uptake „ 440 / 0 / 1 18° / (25 °C / 80%RH)0 4 / 0 2'65 / O 1 18 / 0Form change after D VS? No No Noc 1-,+ } rt, Physically stable Physically stable Physically stable0 1 s a 1 1Chemically stable Chemically stable Chemically unstable SGF > 3.9 mg / mL 3.6-4.4 mg / mL > 4.7 mg / mL sol litvFaSSIF0.11-0.14 mg / mL 0.24-0.30 mg / mL 2.2-4.5 mg / mL FeSSIF 2.6-2, 7 mg / mL 2.6-2.8 mg / mL 1.5-2.4 mg / mL SGF > 5.1 mg / mL 4.3-4.4 mg / mL > 4.9 mg / mL DissolutionFaSSIF 0.8-0.9 mg / mL -1.0 mg / mL 1.1-1.2 mg / mL pH 1.2 >4.1 mg / mL >3.9 mg / mL N / A pH 2.0 >4.4 mg / mL -2.5 mg / mL N / A solubility4?’m&'mF>4.4 mg / mL N / A pH 6.8 -0.059 mg / mL -0.11 mg / mL N / A pH 7.4 -0.026 mg / mL 0.023 mg / mL N / A Grinding Low crystallinity Crystalline Low crystallinity Tableting Crystalline Crystalline Low crystallinity Solid stability after Physically stable Physically stable Physically stable tableting Chemically stable Chemically unstable Chemically unstable Polymorphism 1 stable form Unknown Unknown *: Exotherm. N / 'A: The test was not performed.

Claims

1. CLAIMS2.What is claimed is:3.1.

4.

5. (Compound I), wherein the crystalline form is freebase Form A characterized by having an XRPD pattern comprising peaks at angle 2-theta of about 10.0, about 15.0, and about 16.4.6.The crystalline form of claim 1, characterized by having an XRPD pattern comprising additional peaks at angle 2-theta of about 5.0 and about 22.9.7.The crystalline form of claim 1 or 2, characterized by having an XRPD pattern comprising additional peaks at angle 2-theta of about 5.9, about 7.3, about 13.4, about 20.0, and about 24.6.

4. The crystalline form of any one of claims 1 to 3, characterized by having an XRPD pattern substantially as shown in FIG. 1A.

5. The crystalline form of any one of claims 1 to 4, wherein the crystalline form is an anhydrate.

6. The crystalline form of any one of claims 1 to 5, characterized by having (i) a DSC graph comprising an exothermic peak at about 199.9 °C; (ii) a DSC graph substantially as shown in FIG. IB; (iii) a TGA graph substantially as shown in FIG. IB; or (iv) a DVS graph substantially as shown in FIG. 1C; or any combination of (i) to (iv).

12.

13. wherein the crystalline form is HC1 salt Form A characterized by having an XRPD pattern comprising peaks at angles 2-theta of about 11.6, about 13.0, and about 14.

6. The crystalline form of claim 7, characterized by having an XRPD pattern comprising additional peaks at angles 2-theta of about 12.0 and about 21.9.14.The crystalline form of claim 7 or 8, characterized by having an XRPD pattern comprising additional peaks at angles 2-theta of about 5.8, about 13.4, about 14.3, about 15.7, about 16.5, about 16.8, about 17.5, about 18.5, about 18.7, about 19.6, about 20.2, about 21.3, and about 23.4.

10. The crystalline form of any one of claims 7 to 9, characterized by having an XRPD pattern substantially as shown in FIG. 6A.

11. The crystalline form of any one of claims 7 to 10, characterized by having (i) a DSC graph comprising an endothermic peak at about 179.3 °C; (ii) a DSC graph comprising an exothermic peak at about 221.8 °C; (iii) a DSC graph substantially as shown in FIG. 6B; (iv) a TGA graph substantially as shown in FIG. 6B; or (v) a DVS graph substantially as shown in FIG. 6C; or any combination of (i) to (v).17.12.

18.

19. thereof.

13. The crystalline form of claim 12, wherein:21.(1) the crystalline form is citrate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 4.9, about 6.4, and about 9.6; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 4.9, about 6.4, about 7.8, about 9.6, about 11.5, about 12.1, about 12.8, about 13.5, about 14.6, about 15.3, about 15.8, about 17.0, about 17.4, about 18.1, and about 18.8; (iii) an XRPD pattern of citrate salt Form A substantially as shown in FIG. 7A; (iv) a DSC graph comprising an exothermic peak at about 173.7 °C; (v) a DSC graph substantially as shown in FIG. 7B; ( vi ) a TGA graph substantially as shown in FIG. 7B; or (vii) a DVS graph substantially as shown in FIG. 7C; or any combination of (i ) to (vii);22.(2) the crystalline form is succinate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.9, about 11.3, and about 15.9; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 8.0, about 8.7, about 10.1, about 11.3, about 11.9, about 15.1, about 15.9, about 17.0, about 18.1, and about 18.7; (iii) an XRPD pattern substantially as shown in FIG.23.8A; (iv) a DSC graph comprising an endothermic peak at about 146.3 °C; (v) a DSC graph comprising an exothermic peak at about 159.6 °C; (vi) a DSC graph substantially as shown in FIG. 8B; (vii) a TGA graph substantially as shown in FIG. 8B; or (viii) a DVS graph substantially as shown in FIG. 8C; or any combination of (i) to (viii);24.(3) the crystalline form is succinate salt Form B characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 7.8, about 11.1, and about 15.6; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 7.8, about 8.8, about 10.1, about 11.1, about 11.9, about 15.6, about 16.8, about 17.9, and about 19.0; (iii) an XRPD pattern substantially as shown in FIG. 8D; (iv) a DSC graph comprising an endothermic peak at about 145.6 °C; (v) a DSC graph comprising an exothermic peak at about 157.5 °C; (vi) a DSC graph substantially as shown in FIG. 8E; (vii) a TGA graph substantially as shown in FIG. 8E; or any combination of (i) to (vii);25.(4) the crystalline form is succinate salt Form C characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.8, about 7.7, and about 15.5; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.7, about 8.9, about 10.2, about 10.9, about 12.0, about 15.5, about 17.0, and about 18,1; (iii) an XRPD pattern substantially as shown in FIG. 8D; (iv) a DSC graph comprising an endothermic peak at about 140.9CC; (v) a DSC graph comprising an exothermic peak at about 157.9 °C; (vi) a DSC graph substantially as shown in FIG. 8F; or (vii) a TGA graph substantially as shown in FIG. 8F; or any combination of (i) to (vii);26.(5) the crystalline form is tartrate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.5, about 7.6, and about 15.3; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.5, about 7.6, about 8.8, about 9.4, about 10.0, about 11.3, about 12.5, about 14.2, about 15.3, and about 16.3; (iii) an XRPD pattern substantially as shown in FIG. 9A; (iv) a DSC graph comprising an endothermic peak at about 52.6 °C; (v) a DSC graph comprising an exothermic peak at about 170.2 °C; (vi) a DSC graph substantially as shown in FIG. 9B; or (vii) a TGA graph substantially as shown in FIG. 9B; or any combination of (i) to (vii);27.(6) the crystalline form is fumarate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2 -theta of about 5.9, about 7.8, and about 11.0; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 7.8, about 9.3, about 11.0, about 12.3, and about 15.7; (iii) an XRPD pattern substantially as shown in FIG. 10A; (iv) a DSC graph comprising an exothermic peak at about 170.5 °C; (v) a DSC graph substantially as shown in FIG. 10B; or (vi) a TGA graph substantially as shown in FIG, 10B; or any combination of (i) to (vi);28.(7) the crystalline form is fumarate salt Form B characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.8, about 7.8, and about 11.0; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.8, about 8.9, about 11.0, about 12.0, about 15.5, about 16.9, and about 18.1; (iii) an XRPD pattern substantially as shown in FIG. 10A; (iv) a DSC graph comprising an exothermic peak at about 171.6 °C; (v) a DSC graph substantially as shown in FIG. 10C; or (vi) a TGA graph substantially as shown in FIG. 10C; or any combination of (i ) to (vi );29.(8) the crystalline form is fumarate salt Form C characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 6.8, about 11.7, and about 16.8; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.5, about 6.8, about 7.9, about 9.7, about 11.0, about 11.7, about 13.1, about 15.3, about 15.9, about 16.8, and about 18.9; (iii) an XRPD pattern substantially as shown in FIG.30.10A; (iv) a DSC graph comprising an endothermic peak at about 57.1 °C; (v) a DSC graph comprising an exothermic peak at about 167.7 °C; (vi) a DSC graph substantially as shown in FIG. 10D; or (vii) a TGA graph substantially as shown in FIG. 10D; or any combination of (i ) to (vii);31.(9) the crystalline form is malate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 7.3, about 13.6, and about 15.0; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 6.3, about 7.3, about 7.9, about 9.1, about 13.6, about 15.1, about 15.9, about 16.7, and about 18.1; (iii) an XRPD pattern substantially as shown in FIG. 11 A; (iv) a DSC graph comprising an endothermic peak at about 145.7 °C; (v) a DSC graph comprising an exothermic peak at about 161.4 °C; (vi) a DSC graph substantially as shown in FIG. 11B; or (vii) a TGA graph substantially as shown in FIG. I IB; or any combination of (i) to (vii);32.(10) the crystalline form is malate salt Form B characterized by having (i) an XRPD pattern comprising peaks at angle 2 -theta of about 5.6, about 7.4, and about 15.0; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.4, about 8.9, about 11.2, and about 15.0; (iii) an XRPD pattern substantially as shown in FIG. 11 A; (iv) a DSC graph comprising an endothermic peak at about 49.3 °C; (v) a DSC graph comprising an endothermic peak at about 113.4 °C; (vi) a DSC graph comprising an exothermic peak at about 162,5 °C; (vii) a DSC graph substantially as shown in FIG. 11C; or (viii) a TGA graph substantially as shown in FIG. 11C; or any combination of (i) to (viii);33.(11) the crystalline form is malate salt Form C characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.8, about 7.9, and about 15.7; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.8, about 7.9, about 8.9, about 11.1, about 15.1, about 15.7, about 17.2, and about 18.3; (iii) an XRPD pattern substantially as shown in FIG. 11 A; (iv) a DSC graph comprising an endothermic peak at about 144.6 °C; (v) a DSC graph comprising an exothermic peak at about 158.2 °C; (vi) a DSC graph substantially as shown in FIG. 11D; or (vii) a TGA graph substantially as shown in FIG. 11D; or any combination of (i) to (vii);34.(12) the crystalline form is adipate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 10.1, about 15.1, and about 16.5; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.9, about 7.3, about 8.5, about 9.2, about 10.1, about 13.7, about 15.1, about 16.5, and about 17.0; or (iii) an XRPD pattern substantially as shown in FIG. 12; or any combination of (i) to (iii);35.(13) the crystalline form is napadisylate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 7.3, about 15.4, and about 19.7; (ii) an XRPD pattern substantially as shown in FIG. 13 A; (iii) a DSC graph comprising an endothermic peak at about 56.8 °C; (iv) a DSC graph comprising an endothermic peak at about 160.0 °C; (v) a DSC graph comprising an exothermic peak at about 257.8 °C; (vi) a DSC graph substantially as shown in FIG. I3B; or (vii) a TGA graph substantially as shown in FIG. 13B; or any combination of (i) to (vii); (14) the crystalline form is napadisylate salt Form B characterized by having (i) an XRPD pattern comprising a peak at angle 2-theta of about 7,6; (ii) an XRPD pattern substantially as shown in FIG. 13 A; (iii) a DSC graph comprising an endothermic peak at about 49.3 °C; (iv) a DSC graph comprising an endothermic peak at about 137.6 °C; (v) a DSC graph comprising an exothermic peak at about 201.5 °C; (vi) a DSC graph substantially as shown in FIG. 13C; or (vii) a TGA graph substantially as shown in FIG. 13C; or any combination of (i) to (vii);36.(15) the crystalline form is napadisylate salt Form C characterized by having (i) an XRPD pattern substantially as shown in FIG, 13 A; (ii) a DSC graph comprising an endothermic peak at about 50.2 °C; (iii) a DSC graph comprising an endothermic peak at about 125.9 °C; (iv) a DSC graph comprising an exothermic peak at about 265.7 °C; (v) a DSC graph substantially as shown in FIG. 13D; or (vi) a TGA graph substantially as shown in FIG, 13D; or any combination of (i) to (vi);37.(16) the crystalline form is tosylate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.2, about 12.1, and about 15.5; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.2, about 7.4, about 8.6, about 10.0, about 11.3, about 12.1, about 13.2, about 14.4, about 14.9, about 15.5, about 17.3, and about 18.3; (iii) an XRPD pattern substantially as shown in FIG. 14A; (iv) a DSC graph comprising an endothermic peak at about 138.6 °C; (v) a DSC graph comprising an exothermic peak at about 214.2 °C; (vi) a DSC graph substantially as shown in FIG. 14B; or (vii) a TGA graph substantially as shown in FIG. 14B; or any combination of (i) to (vii);38.(17) the crystalline form is tosylate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.6, about 7.4, and about 9.8; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.4, about 9.8, and about 17.5; (iii) an XRPD pattern substantially as shown in FIG. 15 A; (iv) a DSC graph comprising an exothermic peak at about 222.8 °C; (v) a DSC graph substantially as shown in FIG. 15B; or (vi) a TGA graph substantially as shown in FIG. 15B; or any combination of (i) to (vi);39.(18) the crystalline form is oxalate salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 5.6, about 7.7, and about 14.6; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 5.6, about 7.7, about 10.0, about 11.6, about 14.6, about 15.0, about 15.5, about 16.4, about 17.2, about 18.1, and about 18.8; (iii) an XRPD pattern substantially as shown in FIG.40.16A; (iv) a DSC graph comprising an endothermic peak at about 82.4 °C; (v) a DSC graph comprising an exothermic peak at about 174.0 °C; (vi) a DSC graph substantially as shown in FIG. 16B; or (vii ) a TGA graph substantially as shown in FIG. 16B; or any combination of (i) to (vii); or41.(19) the crystalline form is hydrobromide salt Form A characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 11.6, about 12.9, and about 21.7; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 11.6, about 12.9, about 18.2, and about 21.7; (iii) an XRPD pattern substantially as shown in FIG. 17A; (iv) a DSC graph comprising an endothermic peak at about 57.2 °C; (v) a DSC graph comprising an exothermic peak at about 215.6 °C; (vi) a DSC graph substantially as shown in FIG. 17B; or (vii) a TGA graph substantially as shown in FIG. 17B; or any combination of (i) to (vii).

14. The crystalline form of claim 12, wherein:43.(1) the crystalline form is freebase Form E characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 8.9, about 9.9, about 14.9; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 4.9, about 6.9, about 8.9, about 9.9, about 14.9, about 16.5, about 17.0, and about 18.3; (iii) an XRPD pattern substantially as shown in FIG. 2A; (iv) a DSC graph comprising an exothermic peak at about 188.9 °C; (v) a DSC graph substantially as shown in FIG. 2B; or (vi) a TGA graph substantially as shown in FIG. 2B; or any combination of (i) to (vii);44.(2) the crystalline form is freebase Form B characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 6.8, about 8.5, and about 16.6; or (ii) an XRPD pattern substantially as shown in FIG. 3; or both (i) and (ii); (3) the crystalline form is freebase Form C characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 4.2, about 8.4, and about 16.6; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 4.2, about 6.8, about 8.4, about 9.8, about 15.6, about 16.6, and about 16.8; or (iii) an XRPD pattern substantially as shown in FIG. 4; or any combination of (i) to (iii); or (4) the crystalline form is freebase Form D characterized by having (i) an XRPD pattern comprising peaks at angle 2-theta of about 9.9, about 15.6, and about 16.5; (ii) an XRPD pattern comprising peaks at angles 2-theta of about 6.9, about 8.5, about 9.9, about 14.9, about 15.6, and about 16.5; or (iii) an XRPD pattern substantially as shown in FIG. 5; or any combination of (i) to (iii).

15. The crystalline form of any one of claims 1 to 14, wherein the purity of the crystalline form is at least about 95%.

16. A pharmaceutical composition comprising a crystalline form of any one of claims 1 to 15, and a pharmaceutically acceptable excipient.

17. A method of treating cancer in a subject in need thereof, the method comprising: administering a therapeutically effective amount of the crystalline form of any one of claims 1 to 15, or the pharmaceutical composition of claim 16, to the subject.

18. The method of claim 17, wherein the cancer is a lung, colorectal, pancreatic, bile duct, thyroid, gall bladder, uterine, mesothelioma, cervical, orbladder cancer.

19. The method of claim 17 or 18, wherein the cancer is glioblastoma multifomie, lower grade glioma, head and neck squamous cell carcinoma, papillary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, breast invasive carcinoma, esophageal carcinoma, stomach adenocarcinoma, small intestine adenocarcinoma, colon adenocarcinoma, rectal adenocarcinoma, liver hepatocellular carcinoma, cholangiocarcinoma, gallbladder carcinoma, pancreatic adenocarcinoma, kidney renal clear cell carcinoma, bladder urothelial carcinoma, prostate adenocarcinoma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, cervical squamous carcinoma and endocervical adenocarcinoma, skin cutaneous melanoma, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, plasma cell myeloma, uterine carcinosarcoma, mesothelioma, adrenocortical carcinoma, brain lower grade glioma, diffuse large B-cell lymphoma, esophageal adenocarcinoma, kidney chromophobe, kidney renal papillary cell carcinoma, pheochromocytoma and paraganglioma, sarcoma, testicular germ cell tumors, thymoma, uveal melanoma, metastatic colorectal cancer, bladder cancer, adenoid cystic carcinoma, myelodysplastic, breast cancer, thyroid carcinoma, glioma, esophageal / stomach cancer, pediatric Wilms’ tumor, pediatric acute lymphoid leukemia, chronic lymphocytic leukemia, mature B-cell malignancies, pediatric neuroblastoma, nonsmall cell lung cancer (NSCLC), or melanoma,20. The method of any one of claims 17 to 19, wherein the cancer is a non-small cell lung cancer (NSCLC).

21. The method of any one of claims 17 to 19, wherein the cancer is a KRAS G12C mediated cancer.

22. The method of any one of claims 17 to 21, wherein the subject has been diagnosed as having a KRAS G12C mediated cancer.

23. The method of any one of claims 17 to 22, wherein the subject is human.

24. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, the method comprising:54.(i) contacting Compound 1 with a first solvent to form a mixture; and55.(ii) adding a second solvent to the mixture of step (i) to form the crystalline form of Compound 1.

25. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises:57.(i) placing a sample comprising a solid form of Compound 1 in a first container; (ii) placing the first container of step (i) inside a second container containing a solvent; and58.(iii) allowing vapor from the solvent to interact with the sample in the first container.

26. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises:60.(i) dissolving Compound 1 in a first solvent in a first container;61.(ii) placing the first container of step (i) inside a second container containing a second solvent;62.(iii) sealing the second container of step (ii);63.(iv) allowing vapor of the second solvent to interact with Compound 1 in the first container to form precipitant; and64.(v) isolating the precipitant of step (iv) from the first solvent and / or the second solvent.

27. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises:66.(i) preparing a suspension of Compound 1 in a solvent;67.(ii) heating the suspension of step (i) to a first temperature;68.(iii) filtering the suspension of step (ii) to obtain filtrate;69.(iv) cooling the filtrate of step (iii) to a second temperature.

28. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises:(i) preparing a suspension of Compound 1 in solvent; and71.(ii) stirring the suspension of step (i) at a temperature for a duration.

29. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises:73.(i ) preparing a suspension of Compound 1 in a solvent;74.(ii) heating the suspension to a first temperature and cooling the suspension to a second temperature; and75.(iii) heating the suspension to a third temperature, and cooling the suspension to a fourth temperature.

30. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises:77.(i) dissolving Compound 1 in a solvent; and78.(ii) evaporating the solvent of step (i) at a temperature.

31. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises grinding Compound 1.

32. A method of preparing a crystalline form of any one of claims 1 to 6, 12, 14, and 15, wherein the method comprises:81.(i ) adding Compound 1 to a solvent to form a first mixture; and82.(ii) adding an anti-solvent to the first mixture to form a second mixture.

33. A method of preparing a crystalline form of any one of claims 7 to 13 and 15, wherein the method comprises:84.(i) stirring Compound 1 in a solution for a duration;85.(ii) centrifuging the mixture of step (i); and86.(iii) drying the precipitant of step (ii) at a temperature.

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