Salts of (r)-2-(4-((5,5-dimethyltetrahydrofuran-3-YL)amino)pyrido[3,4- d]pyrldazin-l-YL)-5-methylphenol and uses thereof

Abstract

The present disclosure relates to sulfate, phosphate, fumarate, and hydrochloride salts of Compound 1:. The present disclosure also relates to processes for the preparation of the salt forms, compositions comprising the salt forms, and uses thereof, e.g., in the treatment and prevention of disorders in which NLRP3 activity is implicated.

Description

43700-02297 (VNTS-031 / 001WO) SALTS OF (R)-2-(4-((5,5-DIMETHYLTETRAHYDROFURAN-3-YL)AMINO)PYRIDO[3,4- D]PYRIDAZIN-l-YL)-5-METHYLPHENOL AND USES THEREOFRELATED APPLICATION

[0001] This application claims priority to, and the benefit of, International Application PCT / CN2025 / 083419, filed March 19, 2025, the entire contents of which are incorporated herein by reference.BACKGROUND

[0002] Innate immune responses are mediated by different types of receptors termed pattern-recognition receptors (PRRs). PRRs recognize the presence of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Once engaged these receptors trigger the activation of downstream inflammatory' pathways that will help resolve injury'. However, in many instances this activation can be uncontrolled and leads to disease.

[0003] The inflammasomes represent a class of PRRs that are crucial components of the innate immune response. Activation of the inflammasomes trigger a cascade of events that releases IL-1β, IL-18, and promotes an inflammatory form of cell death called pyroptosis induced by the activation of Gasdermin. Pyroptosis is a unique form of inflammatory cell death that leads to the release of not only cytokines but also other intracellular components that promote a broader immune response both of the innate and acquired immune system. Thus, inflanimasome activation is a major regulatory' of the inflammatory’ cascade.

[0004] NLRP3 is the most characterized inflammasome and has been shown to be critical in innate immunity and inflammatory responses. While several other NLR complexes, such as NLRC4, are activated under very' specific circumstances, NLRP3 can be activated by numerous stimuli and should be seen as a sensor of intracellular homeostatic imbalance. Therefore, its precise functioning is essential. In addition to playing a role in host immune defense, dysregulation of NLRP3 has been linked to the pathogenesis of many inflammatory' disorders. These include genetic diseases such as cryopyrin-associated periodic syndromes (CAPS) which is caused by gain-of-function mutations in the NLRP3 gene, as well as many prevalent neurologic and systemic diseases. Importantly, NLRP3 hyperactivation has been demonstrated pre-clinically to play a critical role in a plethora of inflammatory and degenerative diseases including, Non-Alcoholic Steatohepatitis (NASH), atherosclerosis and other cardiovascular diseases, Alzheimer’s disease, Parkinson’s disease, diabetes, gout, and numerous other autoinflammatory diseases. See, e.g., Li et al., European Journal of Pharmacology (2022) 928:175091; Nguyen et al., Journal of Parkinson's Disease (2022) 12:2117-2133; Su et al., Current Medicinal Chemistry (2021) 25:569-582; Zahid etal... Frontiers in Immunology (2019) 10:2538.SUMMARY

[0005] Provided herein are sulfate, fumarate, phosphate, and hydrochloride salts of Compound 1.43700-02297 (VNTS-031 / 001WO)

[0006] “Compound 1” is (R)-2-(4-((5,5-dimethyltetrahydrofuran-3-yl)amino)pyrido[3,4-d]pyridazin-l-yl)-5-methylphenol, also referred to herein as 5-methyl-2-[4-[[(3R)-5,5-dimethyltetrahydrofuran-3-yl]aminojpyrido[3,4-d]pyridazin-l-yl]phenol, having the structure:N OHCompound 1

[0007] Compound 1 is an orally bioavailable, central nervous system (CNS) penetrant, potent and reversible small molecule inhibitor of NLRP3 being developed to treat neuroinflammatory and neurodegenerative diseases. Compound 1 is described in U. S. 11,618,751 and International Application No. PCT / US2023 / 064967, published as WO 2023 / 183943, incorporated herein by reference. Freebase forms of Compound 1 are described PCT / US2024 / 046642, filed on September 13, 2024 and published as WO 2025 / 059481, incorporated herein by reference. The present disclosure seeks to improve on the solubility and / or pharmacokinetic profile of Crystalline Compound 1 Form I Freebase.

[0008] Thus, in one aspect, provided is a sulfate salt of Compound 1,

[0009] In some embodiments, the sulfate salt is crystalline. In some embodiments, the crystalline sulfate salt is a hydrate. In some embodiments, the crystalline sulfate salt is a monohydrate. In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising a signal at 7.6±0,2 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising a signal at 9.5±0.2 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising a signal at 13.9±0.2 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, cry stalline sulfate salt is characterized by at least one endothermic event between about 178 °C and about 202 °C, inclusive, as measured by DSC. In some embodiments, the crystalline sulfate salt is characterized by two endothermic events between about 175 °C and about 185 °C, inclusive, as measured by DSC. In some embodiments, the crystalline sulfate salt is characterized by one endothermic event between about 190 °C and about 202 °C, inclusive, as measured by DSC. In some embodiments, the crystalline sulfate salt is characterized by a weight loss of at least about 3.5% up to about 150 °C, or up to about 180 °C. in some embodiments, the crystalline sulfate salt has a solubility greater than about 1.9 mg / mL at a pH of about 1.7, as measured in simulated gastric fluid (SGF) at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt has a solubility in water of greater than about 4 mg / mL at a pH of about 2.1 after 3 hours at 37 °C at approximately 25 rpm. in some embodiments, the crystalline sulfate salt has a solubility in fasted state simulated intestinal fluid (FaSSIF) of greater than about 4 mg / mL at a pH of about 3.1 after 3 hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt is characterized as having at least one of the following: (i) an XRPD pattern which is substantially similar to that as provided in FIG. 4A or FIG. 9 (Example 1 or Example 4); and / or (ii) a TGA scan which is substantially similar to that as set forth in43700-02297 (VNTS-031 / 001WO) FIG. 4B; and / or (iii) a DSC scan which is substantially similar to that as set forth in FIG. 4B; and / or (iv) a PLM image which is substantially similar to that as set forth in FIG. 4D. In some embodiments, the crystalline sulfate salt is characterized as having as least one of the following: (i) an XRPD pattern which is substantially similar to that as provided in FIG. 9 (Example 4); and / or (ii) a TGA scan which is substantially similar to that as set forth in FIG. 4C; and / or (iii) a DSC scan which is substantially similar to that as set forth in FIG. 4C; and / or (iv) a PLM image which is substantially similar to that as set forth in FIG. 4E.

[0010] In some embodiments, the sulfate salt is amorphous. In some embodiments, the amorphous sulfate salt’s XRPD pattern has a broad halo between about 12 and about 30 °20, inclusive, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the amorphous sulfate salt’s XRPD pattern is substantially similar to that as set forth in FIG. 7.

[0011] In some embodiments, the sulfate salt’s stoichiometric ratio of a sulfate counterion to protonated Compound 1 is 1:1.

[0012] In another aspect, provided is a phosphate salt of Compound 1.

[0013] In some embodiments, the phosphate salt is cry stalline. In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising a signal at 5.1±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising a signal at 10.2±0.2 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising signals at 18.4±0.5 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline phosphate salt is characterized by at least one endothermic event between about 160 °C and about 210 °C, inclusive, as measured by DSC. In some embodiments, the crystalline phosphate salt is characterized by two endothermic events between about 160 °C and about 210 °C, inclusive, as measured by DSC. In some embodiments, the cry stalline phosphate salt is characterized by a weight loss of at least about 2% up to about 150 °C, as measured by TGA. In some embodiments, the crystalline phosphate salt is characterized as having at least one of the following: (i) an XRPD pattern substantially similar to that as set forth in FIG. 3A; and / or (ii) a TGA scan substantially similar to that as set forth in FIG. 3B; and / or (iii) a DSC scan substantially similar to that as set forth in FIG. 3B.

[0014] In some embodiments, the phosphate salt’s stoichiometric ratio of a phosphate counterion to protonated Compound 1 is 2:1.

[0015] In yet another aspect, provided is a fumarate salt of Compound 1.

[0016] In some embodiments, the fumarate salt is cry stalline. In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising a signal at 7.1±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising a signal at 18.5±0.2 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising a signal at 21.5±0.5 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline fumarate salt is characterized by at least one endothermic event between about 180 °C and43700-02297 (VNTS-031 / 001WO) about 186 °C, inclusive, as measured by DSC. In some embodiments, the crystalline fumarate salt is characterized by a weight loss of at least about 4% up to about 150 °C, as measured by TGA. In some embodiments, the crystalline fumarate salt is characterized as having at least one of the following: (i) an XRPD pattern substantially similar to that as set forth in FIG. 1A; and / or (ii) a TGA scan substantially similar to that as set forth in FIG. IB; and / or (iii) a DSC scan substantially similar to that as set forth in FIG. 1B.

[0017] In some embodiments, the fumarate salt’s stoichiometric ratio of a fumarate counterion to protonated Compound 1 is 1:1.

[0018] In yet another aspect, provided is a hydrochloride salt of Compound 1.

[0019] In some embodiments, the hydrochloride salt is crystalline, in some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising a signal at 6.9±0.2 °20, using Cu K alpha radiation when measured at 25 °C, In some embodiments, the cry stalline hydrochloride salt of is characterized by an XRPD pattern comprising a signal at 10.8±0.2 °20, using Cu K alpha radiation when measured at 25 °C. in some embodiments, the crystalline hydrochloride salt is characterized by an XRPD patern comprising a signal at 10.8±0,5 °20, using Cu K alpha radiation when measured at 25 °C. In some embodiments, the crystalline hydrochloride salt is characterized by at least one endothermic event between about 275 °C and about 285 °C, inclusive, as measured by DSC. In some embodiments, the crystalline hydrochloride salt is characterized by a weight loss of at least about 6% up to about 130 °C, as measured by TGA. In some embodiments, the crystalline hydrochloride salt is characterized as having at least one of the following: (i) an XRPD pattern substantially similar to that as set forth in FIG. 2; and / or (ii) a TGA scan substantially similar to that as set forth in FIG. 2B; and / or (iii) a DSC scan substantially similar to that as set forth in FIG. 2B.

[0020] In some embodiments, the hydrochloride salt’s stoichiometric ratio of a chloride counterion to protonated Compound 1 is 1:1.

[0021] In yet another aspect, provided is a composition comprising a mixture of Compound 1 salts, wherein 75% (w / w%) of the mixture of salt forms is a salt of any one of the preceding claims. In some embodiments, 75% (w / w%) of the mixture is a crystalline sulfate salt.

[0022] In yet another aspect, provided is a pharmaceutical composition comprising a salt as described herein, and one or more pharmaceutically acceptable carriers.

[0023] In still yet another aspect, provided is a method of treating or preventing a disease or disorder, the method comprising administering to a subject a salt of Compound I or a composition, as described herein. In some embodiments, the disease or disorder is a disease or disorder of the central nervous system (CNS), a disease or disorder of the peripheral nervous system (PNS), a primary neurological disease of the muscles, an inflammatory disorder, an autoimmune disorder, cancer, an infection, a metabolic disease, a cardiovascular disease, a respirator}' disease, a kidney disease, a liver disease, an ocular disease, a skin disease, a lymphatic disease, a rheumatic disease, a psychological disease, graft versus host disease, pain (including disorders related to pain management), an NLRP3-related disease in a subject that has been determined to carry a germline or somatic non-silent mutation in NLRP3, or obesity.43700-02297 (VNTS-031 / 001WO)

[0024] In yet another aspect, provided is a method of preparing the salts as described herein.BRIEF DESCRIPTION OF THE FIGURES

[0025] FIG. 1 A depicts the XRPD of Cry stalline Compound 1 Form E Fumarate Salt.

[0026] FIG. IB depicts the TGA and DSC Curves of Crystalline Compound 1 Form E Fumarate Salt.

[0027] FIG. 2A depicts the XRPD of Cry stalline Compound 1 Form F Hydrochloride Salt.

[0028] FIG. 2B depicts the TGA and DSC Curves of Crystalline Compound 1 Form F Hy drochloride Salt.

[0029] FIG. 3A depicts the XRPD of Crystalline Compound 1 Form D Phosphate Salt.

[0030] FIG. 3B depicts the TGA and DSC Curves of Crystalline Compound 1 Form D Phosphate Salt.

[0031] FIG. 4A depicts the XRPD of Crystalline Compound 1 Form A Sulfate Salt as described in Example 1, initial small-scale procedure.

[0032] FIG. 4B depicts the TGA and DSC Curves of Cry stalline Compound 1 Form A Sulfate Salt as described in Example 1, initial small-scale procedure.

[0033] FIG. 4C depicts the TGA and DSC Curves of Cry stalline Compound 1 Form A Sulfate Salt as described in Example 4, large-scale procedure.

[0034] FIGS. 4D-4E depicts the PLM Images of Cry stalline Compound 1 Form A Sulfate Salt prepared as described in Example 1, initial-small scale procedure (FIG. 4D) and Example 4, large-scale procedure (FIG. 4E).

[0035] FIG. 4F depicts the asymmetric unit of Cry stalline Compound 1 Form A Sulfate Salt, confirming the form is a monohydrate.

[0036] FIG. 5 depicts the XRPD of Crystalline Compound 1 Form B Sulfate Salt.

[0037] FIG. 6 depicts the XRPD of Crystalline Compound 1 Form C Sulfate Salt.

[0038] FIG. 7 depicts the XRPD of Amorphous Compound 1 Sulfate Salt.

[0039] FIG. 8 depicts the XRPD Overlay of Crystalline Compound 1 Form A Sulfate Salt, Crystalline Compound 1 Form B Sulfate Salt, and Cry stalline Compound 1 Form C Sulfate Salt.

[0040] FIG. 9 depicts the XRPD Overlay of Crystalline Compound 1 Form A Sulfate Salt of Example 4, prepared from the seed and large-scale procedures.

[0041] FIG. 10 depicts the XRPD of Cry stalline Compound 1 Form I Freebase as described in PCT / US2024 / 046642.

[0042] FIG. 11 depicts the improved bioavailability of the Crystalline Compound 1 Form A Sulfate Salt compared to the Crystalline Compound 1 Form I Freebase in pentagastrin-treated dogs.DEFINITIONS

[0043] Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below.

[0044] Terms of degree such as “about / ’ “substantially similar,” and "approximately" as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly43700-02297 (VNTS-031 / 001WO) changed. These terms of degree should be construed as including a deviation of at least 5% of the modified term if this deviation would not negate the meaning of the word it modifies. In some embodiments, the symbol “~” means “about.”

[0045] “Morphic purity level” refers to a determination by solid-state NMR (ssNMR), vibrational (Raman) spectroscopy and / or X-ray Powder Diffraction (XRPD) of a given form’s purity percentage level (w / w%) relative to other known solid-state forms (e.g., crystalline forms, amorphous forms) of the same compound. See, for example, Mingyue et al.. TrAC Trends in Analytical Chemistry (2021) 135: 116152 (ss NMR); Griffen et al., Journal of Pharmaceutical and Biomedical Analysis, (2016) 128:35-45 (Raman); and Dobelin, Powder Diffraction (2020) 35(4), 262-275 (XRPD), for methods describing determining purity levels. A “morphic purity level” of 95 % or greater is considered “substantially free” of other known solid state forms of tire same compound.

[0046] “Pure-phase” refers to a qualitative assessment by XRPD of a given form, using Cu K alpha radiation when measured at 25 °C, wherein characteristic non-overlapping signals associated with the other crystalline forms of that same compound are not observed by XRPD. A “morphic purity level” of 100% of a given form as determined by XRPD, using Cu K alpha radiation when measured at 25 °C, and “pure-phase” form of that given form are used interchangeably herein.

[0047] Tlie term “stable” refers to a given form that maintains its form (i) over a period of time, e.g., at least one (1) week, at least six (6) months, or at least nine (9) months, at 25 °C / 60% relative humidity and / or at at 40 °C / 75% relative humidity or (ii) after exposing the form to physical challenge, such as grinding, with or without a solvent.

[0048] A “patient” or “subject” is used interchangeably herein, and refers to a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey, chimpanzee, baboon, or rhesus. In some embodiments, the patient or subject is human.

[0049] “Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a Compound I freebase equivalent sufficient to provide a therapeutic benefit in the treatment of a disease or disorder, or to delay or minimize one or more symptoms associated with tire disease or disorder in a subject in need thereof. An effective amount can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of disease or disorder, or enhances the therapeutic efficacy of another therapeutic agent. The effective amount of a compound may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, health, and condition of the subject.

[0050] “Disease” or “disorder” are used interchangeably herein,

[0051] “Treating,” “treat,” or “treatment” describes the management and care of a subject in need thereof, for the purpose of combating a disease or disorder in the subject, and includes tire administration of Compound 1 freebase equivalent, as described herein, to alleviate the symptoms or complications of a disease or disorder, or to eliminate the disease or disorder. The term “treat” can also include treatment of a cell in vitro or treatment of an animal model (in vivo). It is to be appreciated that references to “treating” or “treatment” include the alleviation of established symptoms of a disease or disorder in a subject in need43700-02297 (VNTS-031 / 001WO) thereof, and therefore includes: (1) delaying the appearance of at least one clinical or subclinical symptom of the disease or disorder developing in a subject that is afflicted with the disease or disorder, (2) arresting, reducing or delaying tire continued development of the disease or a relapse thereof in a subject (e.g., in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease in a subject, i.e., causing regression of the disease or disorder or at least one of its clinical or subclinical symptoms.

[0052] As used herein, the term "‘preventing,” “prevent,” or “protecting against” describes the management and care of a subject in need thereof that may have or has a predisposition for the disease or disorder but has not yet experienced or displayed clinical or subclinical symptoms of the disease or disorder, for the purpose of preventing the appearance of at least one clinical or subclinical symptom of the disease or disorder in the subject, and includes the administration of Compound 1 freebase equivalent, as described herein,

[0053] “Inhibition,” “inhibiting,” “inhibit,” and “inhibitor”, and the like, refer to the ability of Compound 1 freebase equivalent, to reduce, slow, halt or prevent activity of a particular biological process (e.g., NLRP3 activity) in a cell relative to vehicle.

[0054] Tire phrase “at least one” refers to one instance or more than one instance.

[0055] The articles “a” and “an” are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article.

[0056] The term “and / or” is used in this disclosure to mean either “and” or “or” unless indicated otherwise.

[0057] The term “freebase” of Compound I refers to a neutral non-ionized form of the compound. It is understood that a freebase is not a salt of Compound 1.

[0058] The term “freebase equivalent” refers to the calculated amount of Compound 1 freebase provided in the salt form, i.e., wherein the calculated amount does not include any co-former (e.g., non-water solvent or water molecule(s)) of a solvate or hydrate) of the freebase or salt, and does not include any counterions of the salt. It is understood that when a salt of Compound 1 is administered, the calculated or reported amount administered corresponds to the amount of the freebase present.

[0059] In some embodiments, a signal is a peak.

[0060] The term “amorphous” is understood to refer to a non-crystalline solid.

[0061] The term “hydrate” refers to a form with at least one stoichiometric or non-stoichiometric amount of a water molecule as a part of the unit cell within the crystalline lattice. A “monohydrate” refers to one water molecule per unit cell within the crystalline lattice of the form. Likewise, a “solvate” refers to a form with at least one stoichiometric or non-stoichiometric amount of a non-water solvent molecule as a part of the unit cell within the crystalline lattice.DETAILED DESCRIPTION OF SOME EMBODIMENTS

[0062] Salts of Compound 1, as well as compositions, including pharmaceutical compositions, comprising Compound 1 salts, methods of treatment and prevention using such salts, and methods of43700-02297 (VNTS-031 / 001WO) preparation are contemplated herein.(i) Compound 1 Sulfate Salt

[0063] The present disclosure provides sulfate salts of Compound 1.

[0064] In some embodiments, the sulfate salt is a hydrate.

[0065] In some embodiments, the sulfate salt is a monohydrate.

[0066] In some embodiments, the sulfate salt is amorphous,

[0067] In some embodiments, the sulfate salt is cry stalline.

[0068] In some embodiments, the crystalline form of Compound 1 sulfate salt is Crystalline Compound 1 Form A Sulfate Salt.

[0069] In some embodiments, the crystalline form of Compound 1 sulfate salt is a hydrate of Crystalline Compound 1 Form A Sulfate Salt.

[0070] In some embodiments, the crystalline form of Compound 1 sulfate salt is Cry stalline Compound 1 Form B Sulfate Salt.

[0071] In some embodiments, the crystalline form of Compound 1 sulfate salt is Crystalline Compound 1 Form C Sulfate Salt.

[0072] In some embodiments, the salt is a stable form.

[0073] In some embodiments, the salt is a pure-phase form.(i~a)

[0074] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising a signal at 7.6+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0075] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising a signal at 9.5.+ 0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0076] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising a signal at 13.9+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0077] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 7, 6+0., 9.5+0.5, and 13,9+0.5 °20 (e.g., 7.6±0.2, 9.5+0.2, and 13.9+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, and 13.9+0.1 °20 (e.g., 7.6, 9.5, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0078] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0, 5, 13,9+0.5, and 19,4+0,5 °20 (e.g., 7, 6+0.2, 9. +0.2, 13.9+0.2, and 19.4+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, 13.9+0.1, and 19.4+0.1 °20 (e.g., 7.6, 9.5, 13.9, and 19.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0079] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 13.9+0.5, 17.3+0.5, and 19.4+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 13.9+0.2, 17.3+0.2, and 19.4+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, 13.9+0.1, 17.3+0.1, and 19.4+0.1 °20 (e.g., 7.6, 9.5, 13.9, 17.3, and 19.4 °20))), using Cu K alpha radiation when measured at 25 °C.43700-02297 (VNTS-031 / 001WO)

[0080] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 13.9+0.5, 17.3+0.5, 19.4+0.5, and 19.9+0.5 °20 (e.g., 7.6±0.2, 9.5+0.2, 13.9+0.2, 17.3+0.2, 19.4+0.2, and 19.9+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, 13.9+0.1, 17.3+0.1, 19.4+0.1, and 19,9+0.1 °20 (e.g, 7.6, 9.5, 13,9, 17.3, 19,4, and 19.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0081] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0, 5, 13,9+0.5, 16,6+0.5, 17.3+0.5, 19.4+0,5, and 19.9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 13.9+0.2, 16.6+0.2, 17.3+0.2, 19.4+0.2, and 19.9+0.2 °20 (e.g., 7.6+0.1, 9 5+0.1, 13.9+0.1, 16.6+0.1, 17.3+0.1, 19.4+0.1, and 19.9+0.1 °20 (e.g, 7.6, 9.5, 13.9, 16.6, 17.3, 19.4, and 19.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0082] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7, 6+0.5, 9. +0.5, 13.9+0.5, 16.6+0.5, 17,3+0,5, 19.0+0.5, 19.4+0.5, and 19,9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 13.9+0.2, 16.6+0.2, 17.3+0.2, 19.0+0.2, 19.4+0.2, and 19.9+0.2 °20 (e.g, 7.6+0.1, 9.5+0.1, 13.9+0.1, 16.6+0.1, 17.3+0.1, 19.0+0.1, 19.4+0.1, and 19.9+0.1 °20 (e.g., 7.6, 9.5, 13.9, 16.6, 17.3, 19.0, 19.4, and 19,9 °20))), using Cu K alpha radiation when measured at 25 °C,

[0083] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 13.9+0.5, 16.6+0.5, 17.3+0.5, 19.0+0.5, 19.4+0.5, 19.9+0.5, and 21.9+0.5 °20 (e.g, 7.6+0.2, 9.5+0.2, 13.9+0.2, 16.6+0.2, 17.3+0.2, 19.0+0.2, 19.4+0.2, 19.9+0.2, and 21.9+0.2 °20 (e.g, 7.6+0.1, 9.5+0.1, 13.9+0.1, 16.6+0.1, 17.3+0.1, 19.0+0.1, 19.4+0.1, 19.9+0.1, and 21.9+0.1 °20 (e.g., 7.6, 9.5, 13,9, 16.6, 17.3, 19.0, 19.4, 19.9, and 21.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0084] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 7.6+0.5, 9.5+0.5, and 13.9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, and 13.9+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, and 13.9+0.1 °20 (e.g., 7.6, 9.5, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0085] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least two signal selected from 7.6+0.5, 9, 5+0,, and 13.9+0.5 °20 (e.g., 7, 6+0.2, 9. +0.2, and 13.9+0.2 °20 (e.g., 7.6+0, 1, 9, 5+0,1, and 13.9+0.1 °20 e.g., 7.6, 9.5, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0086] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least three signals selected from 7.6+0.5, 9.5+0.5, 13.9+0.5, and 19.4+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 13.9+0.2, and 19.4+0.2 °20 (e.g, 7.6+0.1, 9.5+0.1, 13.9+0.1, and 19.4+0.1 °20 (e.g, 7.6, 9.5, 13.9, and 19.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0087] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least four signals selected from 7.6+0.5, 9.5+0., 13.9+0.5, 17.3+0.5, and 19.4+0.5 °20 (e.g., 7.6+0, 2, 9.5+0.2, 13.9+0.2, 17.3+0.2, and 19.4+0.2 °2G (e.g, 7.6+0.1, 9.5+0.1, 13.9+0.1, 17.3+0.1, and 19.4+0.1 °20 (e.g., 7.6, 9.5, 13.9, 17.3, and 19.4 °20))), using Cu K alpha radiation when measured at 25 °C. |0088] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at43700-02297 (VNTS-031 / 001WO) least five signals selected from 7.6+0.5, 9.5+0.5, 13.9+0.5, 17.3+0.5, 19.4+0.5, and 19.9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 13.9+0.2, 17.3+0.2, 19.4+0.2, and 19.9+0.2 °29 (e.g., 7.6+0.1, 9.5+0.1, 13.9+0.1, 17.3+0.1, 19.4+0.1, and 19.9+0.1 °20 (e.g., 7.6, 9.5, 13.9, 17.3, 19.4, and 19.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0089] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 7.6 ± 0.5, 9.5 ± 0.5, 11.8 + 0.5, 12.7 + 0.5, 13.11 + 0.5, 13.9 + 0.5, 15.1 + 0.5, 15.4 + 0.5, 16.2 + 0.5, 16.6 + 0.5, 17.3 + 0.5, 18.4 + 0.5, 19.0 + 0.5, 19.4 + 0.5, 19.9 + 0.5, 20.1 + 0.5, 21.3 + 0.5, 21.9 + 0.5, 22.4 + 0.5, 23.3 + 0.5, 23.5 + 0.5, 24.0 + 0.5, 24.5 + 0.5, 25.3 + 0.5, 25.7 ± 0.5, 26.0 ± 0.5, 26.3 ± 0.5, 26.6 ± 0.5, 26.9 ± 0.5, 28.2 ± 0.5, 28.6 + 0.5, 29.1 + 0.5, 30.0 + 0.5, 30.1 ± 0.5, 30.9 ± 0.5, 32.0 ± 0.5, 32.9 ± 0.5, 34.2 ± 0.5, 35.3 ± 0.5, 36.1 + 0.5, 37.3 + 0.5, and 38.4 ± 0.5, using Cu K alpha radiation when measured at 25 °C.

[0090] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 7.6 + 0.2, 9.5 + 0.2, 11.8 + 0.2, 12.7 + 0.2, 13.11 + 0.2, 13.9 + 0.2, 15.1 + 0.2, 15.4 + 0.2, 16.2 + 0.2, 16.6 + 0.2, 17.3 + 0.2, 18.4 + 0.2, 19.0 + 0.2, 19.4 + 0.2, 19.9 ± 0.2, 20.1 ± 0.2, 21.3 + 0.2, 21.9 + 0.2, 22.4 + 0.2, 23.3 ± 0.2, 23.5 ± 0.2, 24.0 ± 0.2, 24.5 ± 0.2, 25.3 ± 0.2, 25.7 + 0.2, 26.0 + 0.2, 26.3 + 0.2, 26.6 + 0.2, 26.9 + 0.2, 28.2 + 0.2, 28.6 + 0.2, 29.1 + 0.2, 30.0 + 0.2, 30.1 ± 0.2, 30.9 ± 0.2, 32.0 ± 0.2, 32.9 ± 0.2, 34.2 ± 0.2, 35.3 ± 0.2, 36.1 + 0.2, 37.3 + 0.2, and 38.4 ± 0.2, using Cu K alpha radiation when measured at 25 °C.

[0091] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7, 6+0.5 and 9.5+0, 5 °20 (e.g., 7, 6+0, 2 and 9.5+0.2 °20 (e.g., 7.6+0.1 and 9.5+0.1 °20 (e.g., 7.6 and 9.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0092] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5 and 11.8+0.5 °20 (e.g., 7.6+0.2 and 11.8+0.2 °20 (e.g., 7.6+0.1 and 11.8+0.1 °20 (e.g., 7.6 and 11.8 °20))), using Cu K alpha radiation when measured at 25 °C.

[0093] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5 and 12.7+0.5 °20 (e.g., 7.6+0.2. and 12.7+0.2 °20 (e.g., 7.6+0.1 and 12.7+0.1 °20 (e.g., 7.6 and 12.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0094] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.5+0.5 and 11.8+0.5 °20 (e.g., 9.5+0.2 and 11.8+0.2 °20 (e.g., 9.5+0.1 and 11.8+0.1 °20 (e.g., 9.5 and 11.8 °20))), using Cu K alpha radiation when measured at 25 °C.

[0095] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9. +0.5 and 12,7+0.5 °20 (e.g., 9.5+0.2 and 12.7+0.2 °20 (e.g., 9.5+0.1 and 12.7+0.1 °20 (e.g., 9.5 and 12.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0096] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7, 6+0.5, 9.5+0.5, and 19,4+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, and 19.4+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, and 19.4+0.1 °20 (e.g., 7.6, 9.5, and 19.4 °20))), using Cu K alpha radiation when measured at 25

[0097] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising43700-02297 (VNTS-031 / 001WO) signals at 7.6+0.5, 11.8+0.5, and 13.9+0.5 °20 (e.g, 7.6+0.2, 11.8+0.2, and 13.9+0.2 °20 (e.g., 7.6+0.1, 11.8+0.1, and 13.9+0.1 °20 (e.g., 7.6, 11.8, and 13.9 20))). using Cu K alpha radiation when measured at 25 °C.

[0098] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 12.7+0.5, and 13.9+0.5 °20 (e.g., 7.6+0.2, 12.7+0.2, and 13.9+0.2 °20 (e.g, 7.6+0.1, 12.7+0.1, and 13.9+0.1 °20 (e.g., 7.6, 12.7, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0099] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.5+0.5, 11.8+0.5, and 13.9+0.5 °20 (e.g, 9.5+0.2, 11.8+0.2, and 13.9+0.2 °20 (e.g., 9.5+0.1, 11.8+0.1, and 13.9+0.1 °20 (e.g., 9.5, 11.8, and 13.9 20))). using Cu K alpha radiation when measured at 25 °C.

[0100] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.5+0.5, 12.7+0.5, and 13.9+0.5 °20 (e.g., 9.5+0.2, 12.7+0.2, and 13.9+0.2 °20 (e.g, 9.5+0.1, 12.7+0.1, and 13.9+0.1 °20 (e.g., 9.5, 12.7, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0101] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 17.3+0.5, and 19.4+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 17.3+0.2, and 19.4+0.2 °20 (e.g, 7.6+0.1, 9.5+0.1, 17.3+0.1, and 19.4±0.1 °2θ (e.g., 7.6, 9.5, 17.3, and 19.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0102] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 17.3+0.5, 19.4+0.5, and 19.9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 17.3+0.2, 19.4+0.2, and 19.9+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, 17.3+0.1, 19.4+0.1, and 19.9+0.1 °20 (e.g., 7.6, 9.5, 17.3, 19.4, and 19.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0103] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 16.6+0.5, 17.3+0.5, 19.4+0.5, and 19.9+0.5 °20 (e.g., 7.6±0.2, 9.5+0.2, 16.6+0.2, 17.3+0.2, 19.4+0.2, and 19.9+0.2 °20 (e.g. 7.6+0.1, 9.5+0.1, 16.6+0.1, 17.3+0.1, 19.4+0.1, and 19,9+0.1 °20 (e.g, 7.6, 9.5, 16,6, 17.3, 19,4, and 19.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0104] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 16.6+0.5, 17.3+0.5, 19.0+0.5, 19.4+0.5, and 19.9+0.5 °20 (e.g, 7.6+0.2, 9.5+0.2, 16.6+0.2, 17.3+0.2, 19.0+0.2, 19.4+0.2, and 19.9+0.2 °20 (e.g.. 7.6+0.1, 9.5+0.1, 16.6+0.1, 17.3+0.1, 19.0+0.1, 19.4+0.1, and 19.9+0.1 °20 (e.g, 7.6, 9.5, 16.6, 17.3, 19.0, 19.4, and 19.9 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0105] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6±0.5, 9.5±0.5, 16.6+0.5, 17.3+0.5, 19,0+0,5, 19.4+0.5, 19.9+0.5, and 21,9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 16.6+0.2, 17.3+0.2, 19.0+0.2, 19.4+0.2, 19.9+0.2, and 21.9+0.2 °20 (e.g, 7.6+0.1, 9.5+0.1, 16.6+0.1, 17.3+0.1, 19.0+0.1, 19.4+0.1, 19.9+0.1, and 21.9+0.1 °20 (e.g, 7.6, 9.5, 16.6, 17.3, 19.0, 19.4, 19.9, and 21.9 °20))), using Cu K alpha radiation when measured at 25 °C.43700-02297 (VNTS-031 / 001WO)

[0106] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 7.6+0.5 and 9.5+0.5 °2θ (e.g., 7.6±0.2 and 9.5±0.2 °2θ (e.g., 7.6+0.1 and 9.5+0.1 °20 (e.g., 7.6 and 9.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0107] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 7.6+0.5 and 11.8+0.5 °20 (e.g., 7.6+0.2 and 11.8+0.2 °20 (e.g., 7.6+0.1 and 11.8+0.1 °20 (e.g., 7.6 and 11.8 °20))), using Cu K alpha radiation when measured at 25 °C.

[0108] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 7.6±0.5 and 12.7±0.5 °20 (e.g., 7.6+0.2 and 12.7+0.2 °20 (e.g., 7.6+0.1 and 12.7+0.1 °20 (e.g., 7.6 and 12.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0109] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 9.5±0.5 and 11.8±0.5 °20 (e.g., 9.5+0.2 and 11.8+0.2 °20 (e.g., 9.5+0.1 and 11.8+0.1 °20 (e.g., 9.5 and 11.8 °20))), using Cu K alpha radiation when measured at 25 °C.

[0110] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 9.5+0.5 and 12.7+0.5 °20 (e.g., 9.5+0.2 and 12.7+0.2 °20 (e.g., 9.5+0.1 and 12.7+0.1 °20 (e.g., 9.5 and 12,7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0111] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least two signals selected from 7.6±0.5, 9.5±0.5, and 19.4±0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, and 19.4+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, and 19.4+0.1 °20 (e.g., 7.6, 9.5, and 19.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0112] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least two signals selected from 7.6+0.5, 11.8+0.5, and 13.9+0.5 °20 (e.g., 7.6±0.2, 11.8±0.2, and 13.9±0.2 °2θ (e.g., 7.6+0.1, 11.8+0.1, and 13.9+0.1 °20 (e.g., 7.6, 11.8, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0113] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least two signals selected from 7.6+0.5, 12.7+0.5, and 13.9+0.5 °20 (e.g., 7.6±0.2, 12.7±0.2, and 13.9±0.2 °20 (e.g., 7.6+0.1, 12.7+0.1, and 13.9+0.1 °20 (e.g., 7.6, 12.7, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C,

[0114] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least two signals selected from 9.5+0.5, 11.8+0.5, and 13.9+0.5 °20 (e.g., 9.5+0.2, 11.8+0.2, and 13.9+0.2 ”20 (e.g., 9.5+0.1, 11.8+0.1, and 13.9+0.1 °20 (e.g., 9.5, 11.8, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0115] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least two signals selected from 9.5±0.5, 12.7±0.5, and 13.9±0.5 °20 (e.g., 9.5+0.2, 12.7+0.2, and 13.9+0.2 °20 (e.g,, 9.5+0.1, 12.7+0.1, and 13.9+0.1 °20 (e.g., 9.5, 12.7, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0116] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least three signals selected from 7.6+0.5, 9.5+0.5, 17.3+0.5, and 19.4+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 17.3+0.2, and 19.4+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, 17.3+0.1, and 19.4+0.1 °20 (e.g., 7.6, 9.5, 17.3, and43700-02297 (VNTS-031 / 001WO) 19.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0117] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least four signals selected from 7.6+0.5, 9.5+0.5, 17.3+0.5, 19.4+0.5, and 19.9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 17.3+0.2, 19.4+0.2, and 19.9+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, 17.3+0.1, 19.4+0.1, and 19.9+0.1 °20 (e.g., 7.6, 9.5, 17.3, 19.4, and 19.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0118] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 7.6 ± 0.5, 9.5 ± 0.5, 11,8 + 0.5, 12.7 + 0.5, 13.11 ± 0.5, 15,1 ± 0.5, 15.4 + 0.5, 16.2 + 0.5, 16.6 + 0.5, 17.3 + 0.5, 18.4 + 0.5, 19.0 + 0.5, 19.4 + 0.5, 19.9 + 0.5, 20.1 + 0.5, 21.3 ± 0.5, 21.9 ± 0.5, 22.4 ± 0.5, 23.3 ± 0.5, 23.5 ± 0.5, 24.0 ± 0.5, 24.5 + 0.5, 25.3 + 0.5, 25.7 + 0.5, 26.0 ± 0.5, 26.3 ± 0.5, 26.6 ± 0.5, 26.9 ± 0.5, 28.2 ± 0.5, 28.6 ± 0.5, 29.1 + 0.5, 30.0 + 0.5, 30.1 + 0.5, 30.9 ± 0.5, 32.0 ± 0.5, 32.9 ± 0.5, 34.2 ± 0.5, 35.3 ± 0.5, 36.1 ± 0.5, 37.3 ± 0.5, and 38.4 ± 0.5, using Cu K alpha radiation when measured at 25 °C.

[0119] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 7.6 + 0.2, 9.5 ± 0.2, 11.8 + 0.2, 12.7 + 0.2, 13.11 + 0.2, 15.1 + 0.2, 15.4 + 0.2, 16.2 + 0.2, 16.6 + 0.2, 17.3 + 0.2, 18.4 + 0.2, 19.0 + 0.2, 19.4 + 0.2, 19.9 + 0.2, 20.1 ± 0.2, 21.3 + 0.2, 21.9 + 0.2, 22.4 + 0.2, 23.3 + 0.2, 23.5 + 0.2, 24.0 + 0.2, 24.5 + 0.2, 25.3 + 0.2, 25.7 + 0.2, 26.0 ± 0.2, 26.3 ± 0.2, 26.6 ± 0.2, 26.9 ± 0.2, 28.2 ± 0.2, 28.6 ± 0.2, 29.1 + 0.2, 30.0 + 0.2, 30.1 + 0.2, 30.9 ± 0.2, 32.0 ± 0.2, 32.9 ± 0.2, 34.2 ± 0.2, 35.3 ± 0.2, 36.1 ± 0.2, 37.3 ± 0.2, and 38.4 ± 0.2, using Cu K alpha radiation when measured at 25 °C.

[0120] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 7.6+0.5, 9.5+0.5, 11.8+0.5, 12.7+0.5, and 13.9+0.5 °20 (e.g., 7.6+0.2, 9.5+0.2, 11.8+0.2, 12.7+0.2, and 13.9+0.2 °20 (e.g., 7.6+0.1, 9.5+0.1, 11.8+0.1, 12.7+0.1, and 13.9+0.1 °20 (e.g., 7.6, 9.5, 11.8, 12.7, and 13.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0121] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern that does not have an X-ray powder diffraction signal at 6.4+0.5 °20 (e.g., 6.4+0.2 °20 (e.g., 6.4+0.1 °20 (e.g., 6.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0122] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern that does not have an X-ray powder diffraction signal at 10.1+0.5 °20 (e.g., 10.1+0,2 °20 (e.g., 10.1+0.1 °20 (e.g., 10.1 °20))), using Cu K alpha radiation when measured at 25 °C.

[0123] In some embodiments, the crystalline sulfate salt is Crystalline Compound 1 Form A Sulfate Salt, which is characterized by an XRPD pattern comprising one or more signals as described in Table 1 below.

[0124] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by an XRPD pattern comprising two or more signals as described in Table 1 below.

[0125] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by an XRPD pattern comprising three or more signals as described in Table 1 below.

[0126] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by an XRPD pattern comprising four or more signals as described in Table 1 below.43700-02297 (VNTS-031 / 001WO)

[0127] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by each of the XRPD signals as set forth in Table 1.

[0128] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by an XRPD pattern substantially similar to that set forth in FIG. 4A,Table 1. XRPD signals of Form A Sulfate SaltPeak No. 20[°] ReLint. [%]1 7.6 79.772 9.5 100.003 11.8 25.774 12.7 19.265 13.11 4.536 13.9 86.517 15.1 23.798 15.4 28.909 16.2 4.2410 16,6 40.0811 17.3 53.9712 18.4 14.2813 19.0 39.5714 19.4 56.0315 19.9 48.4616 20.1 24.5317 21.3 5.6518 21.9 35.0819 22.4 11.1020 23.3 26.2521 23.5 30.2822 24.0 6.6123 24.5 6.8024 25.3 18.3825 25.7 11.5926 26.0 4.6027 26.3 20.4828 26.6 16.4529 26.9 7.2130 28.2 29.5631 28.6 6.0632 29.1 8.1043700-02297 (VNTS-031 / 001WO) Table 1. XRPD signals of Form A Sulfate SaltPeak No. 201°| ReLint. [%] 33 30.0 1.59 34 30.1 5.18 35 30.9 13.62 36 32.0 3.71 37 32.9 2.78 38 34.2 1.38 39 35.3 2.77 40 36.1 3.15 41 37.3 1.6742 38.4 2.55

[0129] In some embodiments, the cry stalline sulfate salt is characterized by at least one endothermic event between about 175 °C and about 202 °C, inclusive, as measured by DSC.

[0130] In some embodiments, the crystalline sulfate salt is characterized by two endothermic events between about 175 °C and about 185 °C, inclusive, as measured by DSC. In some embodiments, the cry stalline sulfate salt is characterized by two endothermic events between about 178.3 °C and about 182.3 °C, inclusive, as measured by DSC.

[0131] In some embodiments, the cry stalline sulfate salt is characterized by an endothermic event at 178.3+20 °C, 178.3+15 °C, 178.3+10 °C, or 178.3+5 °C (e.g., at about 178.3 °C), as measured by DSC. In some embodiments, the crystalline sulfate salt is characterized by an endothermic event at 182.3+20 °C, 182.3+15 °C, 182.3+10 °C, or 182.3+5 °C (e.g., at about 182.3 °C), as measured by DSC. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0132] In some embodiments, the Cry stalline Compound 1 Form A Sulfate Salt is characterized by an endothermic event as measured by DSC substantially similar to that set forth in FIG. 4B.

[0133] In some embodiments, the crystalline sulfate salt is characterized by a weight loss of at least about 3.5% up to about 150 °C, In some embodiments, the crystalline sulfate salt is characterized by a weight loss of between about 3.5% to about 4.5%, inclusive, to about 150 °C. In some embodiments, the crystalline sulfate salt is characterized by a weight loss of between about 4.0% to about 4.5%, inclusive, to about 150 °C. In some embodiments, the crystalline sulfate salt is characterized by a weight loss of about 4.33% up to about 150 °C.

[0134] In some embodiments, the crystalline sulfate salt is characterized by a weight loss of at least about 4% up to about 150±40 °C, 150±30 °C, 150±20 °C, 150±15 °C, 150±10 °C, or 150±5 °C (e.g., at about 150 °C), as measured by TGA. In some embodiments, the crystalline sulfate salt is characterized by a weight loss of about 4.33% up to about 150±40 °C, 150±30 °C, 150±20 °C, 150±15 °C, 150±10 °C, or 150±5 °C (e.g.. at about 150 °C), as measured by TGA. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.43700-02297 (VNTS-031 / 001WO)

[0135] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by a weight loss as measured by TGA substantially similar to that set forth in FIG. 4B.

[0136] In some embodiments, the crystalline sulfate salt is characterized by one endothermic event between about 190 °C and about 202 °C, inclusive, as measured by DSC. In some embodiments, the crystalline sulfate salt is characterized by an endothermic event at about 196.6 °C, as measured by DSC.

[0137] In some embodiments, the crystalline sulfate salt is characterized by an endothermic event between 190+20 °C and 202+20 °C, 190+15 °C and 202+15 °C, 190+10 °C and 202+10 °C, or 190+5 and 202+20 °C °C (e.g., about 190 and 202 °C), each inclusive, as measured by DSC. In some embodiments, the crystalline sulfate salt is characterized by an endothermic event at 196.6+20 °C, 196.6+15 °C, 196.6+10 °C, or 196.6+5 °C (e.g., at about 196.6 °C), as measured by DSC. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0138] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by an endothermic event as measured by DSC substantially similar to that set forth in FIG. 4C.

[0139] In some embodiments, the crystalline sulfate salt is characterized by a weight loss of at least about 3.5% up to about 180 °C. In some embodiments, the crystalline sulfate salt is characterized by a weight loss of between about 3.5% to about 4.5%, inclusive, up to about 180 °C. In some embodiments, the crystalline sulfate salt is characterized by a weight loss of about 4.02% up to about 180 °C.

[0140] In some embodiments, the crystalline sulfate salt is characterized by a weight loss of about 4.02% up to about 180+40 °C, 180+30 °C, 180+20 °C, 180+15 °C, 180+10 °C, or 180+5 °C (e.g, at about 180 °C), as measured by TGA. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0141] In some embodiments, the Crystalline Compound 1 Form A Sulfate Salt is characterized by a weight loss as measured by TGA substantially similar to that set forth in FIG. 4C.

[0142] In some embodiments, the cry stalline sulfate salt is in a 1: 1 stoichiometric ratio of a sulfate counterion to protonated Compound 1. In some embodiments, tire crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0143] In some embodiments, the cry stalline sulfate salt is soluble in a solvent, e.g., methanol, ethanol, water, and dimethyl sulfoxide (DMSO), and mixtures thereof, at room temperature. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0144] In some embodiments, the solubility of the crystalline sulfate salt is measured in water or a phy siological buffer. In some embodiments, a physiological buffer is simulated gastric fluid (SGF) for two (2) hours at 37 °C at approximately 25 rpm, followed by dilution with fasted state simulated intestinal fluid (FaSSIF) for one (1) hour or two (2) hours at 37 °C at approximately 25 rpm.

[0145] In some embodiments, the crystalline sulfate salt has a solubility greater than about 1.9 mg / mL, as measured in SGF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt has a solubility greater than about 1.9 mg / mL at a pH of about 1.7, as measured in SGF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.43700-02297 (VNTS-031 / 001WO)

[0146] In some embodiments, the crystalline sulfate salt has a solubility of about 0.06 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at one hour at 37 °C at approximately 25 rpm. In some embodiments, the crystal l ine sulfate salt has a solubility of about 0.06 mg / mL at a pH of about 5.6, as measured in a 1:3 mixture of SGF and FaSSIF at one hour at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0147] In some embodiments, the crystalline sulfate salt has a solubility of about 0.05 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt has a solubility of about 0.05 mg / mL at a pH of about 5.5, as measured in a 1:3 mixture of SGF and FaSSIF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0148] In some embodiments, the crystalline sulfate salt converts to Form I Freebase after dilution in a 1:3 mixture of SGF and FaSSIF after I hour. In some embodiments, the crystalline sulfate salt so characterized is Cry stalline Compound 1 Form A Sulfate Salt.

[0149] In some embodiments, the crystalline sulfate salt has a solubility in water of greater than about 4 mg / mL at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt has a solubility in water of greater than about 4 mg / mL at a pH of about 2.1 after 3 hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt has a solubility in water of greater than about 4 mg / mL at a pH of about 2.1 after 24 hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0150] In some embodiments, the cry stalline sulfate salt has a solubility in FaSSIF of greater than about 4 mg / mL at 37 °C at approximately 25 rpm. In some embodiments, the cry stalline sulfate salt has a solubility in FaSSIF of greater than about 4 mg / mL at a pH of about 3.1 after 3 hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline sulfate salt has a solubility in FaSSIF of between about 3 mg / mL to about 4 mg / mL, inclusive, at a pH of about 3.0 after 24 hours at 37 °C at approximately 25 rpm. In some embodiments, after 24 hours of the crystalline sulfate salt in FaSSIF at a pH of about 3.0, Compound 1 Form I Freebase precipitates. In some embodiments, the crystalline sulfate salt so characterized is Cry stalline Compound 1 Form A Sulfate Salt.

[0151] In some embodiments, the cry stalline sulfate salt remains in solution after 3 hours in water and FaSSIF. In some embodiments, the crystalline sulfate salt so characterized is Crystalline Compound 1 Form A Sulfate Salt.

[0152] In some embodiments, Crystalline Compound 1 Form A Sulfate Salt is composed of irregular crystals. In some embodiments, Cry stalline Compound 1 Form A Sulfate Salt is composed of irregular crystals as shown in FIG. 4D.

[0153] In some embodiments, Crystalline Compound 1 Form A Sulfate Salt is composed of rod-like crystals. In some embodiments, Crystalline Compound 1 Form A Sulfate Salt is composed of rod-like crystals as shown in FIG. 4E.

[0154] In some embodiments, Crystalline Compound 1 Form A Sulfate Salt is a monohydrate. In some embodiments, Crystalline Compound 1 Form A Sulfate Salt monohydrate comprises an asymmetric unit43700-02297 (VNTS-031 / 001WO) as shown in FIG. 4F.(i-b)

[0155] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising a signal at 10.1+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0156] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising a signal at 9, 1+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0157] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signal at 22.7+0.5 ”20, using Cu K alpha radiation when measured at 25 °C.

[0158] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.1+0.5, 10.1+0.5, and 22.7+0.5 °20 (e.g, 9.1+0.2, 10.1+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.1±0.1, and 22.7±0.1 °2θ (e.g., 9.1, 10.1, and 22.7 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0159] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.1+0.5, 10.1+0.5, 16.4+0.5, and 22.7+0.5 °20 (e.g., 9.1+0.2, 10.1+0.2, 16.4+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.1+0.1, 16.4+0.1, and 22.7+0.1 °20 (e.g., 9.1, 10.1, 16.4, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0160] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 6.4+0.5, 9.1+0.5, 10.1+0.5, 16.4+0.5, and 22.7+0.5 °20 (e.g., 6.4+0.2, 9.1+0.2, 10.1+0.2, 16.4+0.2, and 22.7+0.2 °20 (e.g., 6.4+0.1, 9.1+0.1, 10.1+0.1, 16.4+0.1, and 22.7+0.1 °20 (e.g., 6.4, 9.1, 10.1, 16.4, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0161] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 6.4+0.5, 9.1+0.5, 10.1+0.5, 16.4+0.5, 19.2+0.5, and 22.7+0.5 °20 (e.g.. 6.4+0.2, 9.1+0.2, 10.1+0.2, 16.4+0.2, 19.2+0.2, and 22.7+0.2 °20 (e.g., 6.4+0.1, 9.1+0.1, 10.1+0.1, 16.4+0.1, 19.2+0.1, and 22.7+0.1 °20 (e.g., 6.4, 9.1, 10.1, 16.4, 19.2, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0162] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 6, 4+0.5, 9.1+0.5, 10.1+0.5, 16.4+0.5, 19,2+0.5, 20,1+0.5, and 22.7+0.5 °20 (e.g., 6.4+0.2, 9.1+0.2, 10.1+0.2, 16.4+0.2, 19.2+0.2, 20.1+0.2, and 22.7+0.2 °20 (e.g., 6.4+0.1, 9.1+0.1, 10.1+0.1, 16.4+0.1, 19.2+0.1, 20.1+0.1, and 22.7+0.1 °20 (e.g., 6.4, 9.1, 10.1, 16.4, 19.2, 20.1, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0163] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 6.4+0.5, 9.1+0.5, 10.1+0.5, 16.4+0.5, 18.8+0.5, 19.2+0.5, 20.1+0.5, and 22.7+0.5 °20 (e.g., 6.4+0.2, 9.1+0.2, 10.1+0.2, 16.4+0.2, 18.8+0.2, 19.2+0.2, 20.1+0.2, and 22.7+0.2 °20 (e.g.. 6.4+0.1, 9.1+0.1, 10.1+0.1, 16.4+0.1, 18.8+0.1, 19.2+0.1, 20.1+0.1, and 22.7+0.1 °20 (e.g., 6.4, 9.1, 10.1, 16.4, 18.8, 19.2, 20.1, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0164] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 6.4+0.5, 9.1+0.5, 10.1+0.5, 16.4+0.5, 18.8+0.5, 19.2+0.5, 20.1+0.5, 22.7+0.5, and 25.7+0.5 °2043700-02297 (VNTS-031 / 001WO) (e.g., 6.4+0.2, 9.1+0.2, 10.1+0.2, 16.4+0.2, 18.8+0.2, 19.2+0.2, 20.1+0.2, 22.7+0.2, and 25.7+0.2 °20 (e.g., 6.4+0.1, 9.1+0.1, 10.1+0.1, 16.4+0.1, 18.8+0.1, 19.2+0.1, 20.1+0.1, 22.7+0.1, and 25.7+0.1 °20 (e.g., 6.4, 9.1, 10.1, 16.4, 18.8, 19.2, 20.1, 22.7, and 25.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0165] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 9.1+0.5, 10.1+0.5, and 22.7+0.5 °2θ (e.g., 9.1±0.2, 10.1±0.2, and 22.7±0.2 °2θ (e.g., 9.1+0.1, 10.1±0.1, and 22.7±0.1 °2θ (e.g., 9.1, 10.1, and 22.7 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0166] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least two signal selected from 9.1+0.5, 10.1+0.5, and 22.7+0.5 °20 (e.g., 9.1+0.2, 10.1+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.1+0.1, and 22.7+0.1 °20 (e.g., 9.1, 10.1, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0167] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least three signals selected from 9.1+0.5, 10.1+0.5, 16.4+0.5, and 22.7+0.5 °20 (e.g., 9.1+0.2, 10.1+0.2, 16.4+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.1+0.1, 16.4+0.1, and 22.7+0.1 °20 (e.g., 9.1, 10.1, 16.4, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0168] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least four signals selected from 6.4+0.5, 9.1+0.5, 10.1+0.5, 16.4+0.5, and 22.7+0.5 °20 (e.g., 6.4+0.2, 9.1+0.2, 10.1+0.2, 16.4+0.2, and 22.7+0.2 °20 (e.g., 6.4+0.1, 9.1+0.1, 10.1+0.1, 16.4+0.1, and 22.7+0.1 °20 (e.g., 6.4, 9.1, 10.1, 16.4, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0169] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least five signals selected from 6.4+0.5, 9.1+0.5, 10.1+0.5, 16.4+0.5, 19.2+0.5, and 22.7+0.5 °20 (e.g., 6.4+0.2, 9.1+0.2, 10.1+0.2, 16.4+0.2, 19.2+0.2, and 22.7+0.2 °20 (e.g., 6.4+0.1, 9.1+0.1, 10.1+0.1, 16.4+0.1, 19.2+0.1, and 22.7+0.1 °20 (e.g., 6.4, 9.1, 10.1, 16.4, 19.2, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0170] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 6.4 ± 0.5, 7.6 ± 0.5, 9.1 ± 0.5, 9.5 ± 0.5, 10.1 ± 0.5, 11.8 ± 0.5, 12.8 + 0.5, 14.2 + 0.5, 15.3 + 0.5, 16.4 + 0.5, 18.8 + 0.5, 19.2 + 0.5, 20.1 ± 0.5, 20.4 + 0.5, 21.9 + 0.5, 22.7 + 0.5, 23.3 + 0.5, 24.6 + 0.5, 25.7 + 0.5, 26.4 + 0.5, 27.5 + 0.5, 28.6 + 0.5, 29.2 + 0.5, 30.7 + 0.5, 33.0 + 0.5, 36.3 + 0.5, or 39.4 + 0.5, using Cu K alpha radiation when measured at 25 °C.

[0171] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 6.4 ± 0.2, 7.6 ± 0.2, 9.1 ± 0.2, 9.5 ± 0.2, 10.1 + 0.2, 11.8 + 0.2, 12.8 ± 0.2, 14.2 ± 0.2, 15.3 ± 0.2, 16.4 ± 0.2, 18.8 ± 0.2, 19.2 ± 0.2, 20.1 + 0.2, 20.4 + 0.2, 21.9 + 0.2, 22.7 ± 0.2, 23.3 ± 0.2, 24.6 ± 0.2, 25.7 ± 0.2, 26.4 ± 0.2, 27.5 ± 0.2, 28.6 ± 0.2, 29.2 ± 0.2, 30.7 ± 0.2, 33.0 ± 0.2, 36.3 ± 0.2, or 39.4 ± 0.2, using Cu K alpha radiation when measured at 25 °C.

[0172] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern that does not have an X-ray powder diffraction signal at 18.3+0.5 °20 (e.g., 18.3+0.2 °20 (e.g., 18.3+0.1 °20 (e.g., 18.3 °20))), using Cu K alpha radiation when measured at 25 °C.43700-02297 (VNTS-031 / 001WO)

[0173] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern that does not have an X-ray powder diffraction signal at 17.3+0.5 °20 (e.g., 17.3±0.2 °20 (e.g., 17.3±0.1 °20 (e.g., 17.3 °20))), using Cu K alpha radiation when measured at 25 °C.

[0174] In some embodiments, the cry stalline sulfate salt is Cry stalline Compound 1 Form B Sulfate Salt, which is characterized by an XRPD pattern comprising one or more signals as described in Table 2 below.

[0175] In some embodiments, the Cry stalline Compound 1 Form B Sulfate Salt is characterized by an XRPD pattern comprising two or more signals as described in Table 2 below.

[0176] In some embodiments, the Crystalline Compound 1 Form B Sulfate Salt is characterized by an XRPD pattern comprising three or more signals as described in Table 2 below.

[0177] In some embodiments, the Crystalline Compound 1 Form B Sulfate Salt is characterized by an XRPD pattern comprising four or more signals as described in Table 2 below.

[0178] In some embodiments, the Crystalline Compound 1 Form B Sulfate Salt is characterized by each of the XRPD signals as set forth in Table 2.

[0179] In some embodiments, the Cry stalline Compound 1 Form B Sulfate Salt is characterized by an XRPD pattern substantially similar to that set forth in FIG. 5.Table 2. XRPD signals of Form B Sulfate SaltPeak No. 20 [°] Rel. Int. [%]1 6.4 36.862 7.6 13.333 9.1 74.444 9.5 5.615 10.1 100.006 11.8 1.927 12.8 18.128 14.2 3.299 15.3 0.9810 16.4 42.5211 18.8 26.8112 19.2 32.5513 20.1 27.1514 20.4 19.7615 21.9 1.4916 22.7 61.2717 23.3 7.8218 24.6 11.0119 25.7 23.2320 26.4 2.2743700-02297 (VNTS-031 / 001WO) Table 2. XRPD signals of Form B Sulfate SaltPeak No. 20 [°] ReLint. [%]21 27.5 6.0622 28.6 2.6723 29.2 8.4524 30.7 5.6925 33.0 2.5026 36.3 3.7027 39.4 1.52

[0180] As noted in the Examples, Crystalline Compound 1 Form B Sulfate Salt is a metastable form.

[0181] In some embodiments, the Crystalline Compound 1 Form B Sulfate Salt converts to Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the Crystalline Compound 1 Form B Sulfate Salt converts to Crystalline Compound 1 Form A Sulfate Salt upon drying.(i-c)

[0182] In some embodiments, the crystalline sulfate salt is characterized by an XRPD patern comprising a signal at 10.0+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0183] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising a signal at 9.1+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0184] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising a signal at 22.7+0.5 °20, using Cu K alpha radiation when measured at 25 °C.

[0185] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.1+0.5, 10.0+0.5, and 22.7+0.5 °20 (e.g., 9. l±0.2, 10.0+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.0+0.1, and 22.7+0.1 °20 (e.g., 9.1, 10.0, and 22,7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0186] In some embodiments, the crystalline sulfate salt is characterized by an XRPD patern comprising signals at 9.1+0.5, 10.0+0.5, 18.3+0.5, and 22.7+0.5 °20 (e.g, 9.1+0.2, 10.0+0.2, 18.3+0.2, and 22.7+0.2 °20 (e.g, 9.1+0.1, 10.0+0.1, 18.3+0.1, and 22.7+0.1 °20 (e.g, 9.1, 10.0, 18.3, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0187] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.1+0.5, 10.0+0.5, 15.3+0.5, 18.3+0.5, and 22.7+0.5 °20 (e.g, 9.1+0.2, 10.0+0.2, 15.3+0.2, 18.3+0.2, and 22.7+0.2 °20 (e.g, 9.1+0.1, 10.0+0.1, 15.3+0.1, 18.3+0.1, and 22.7+0.1 °20 (e.g, 9.1, 10.0, 15.3, 18.3, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0188] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.1+0.5, 10.0+0.5, 15.3+0.5, 18.3+0.5, 22.7+0.5, and 23.4+0.5 °20 (e.g, 9.1+0.2, 10.0+0.2, 15.3+0.2, 18.3+0.2, 22.7+0.2, and 23.4+0.2 °20 (e.g, 9.1+0.1, 10.0+0.1, 15.3+0.1, 18.3+0.1, 22.7+0.1, and 23.4+0.1 °20 (e.g, 9.1, 10.0, 15.3, 18.3, 22.7, and 23.4 °20))), using Cu K alpha radiation when43700-02297 (VNTS-031 / 001WO) measured at 25 °C.

[0189] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.1+0.5, 10.0+0.5, 15.3+0.5, 18.3+0.5, 20.1+0.5, 22.7+0.5, and 23.4+0.5 °20 (e.g., 9.1+0.2, 10.0+0.2, 15.3±0.2, 18.3+0.2, 20.1+0.2, 22.7+0.2, and 23.4+0.2 °20 (e.g, 9.1+0.1, 10.0+0.1, 15.3+0.1, 18.3+0.1, 20.1+0.1, 22.7+0.1, and 23.4+0.1 °20 (e.g, 9.1, 10.0, 15.3, 18.3, 20.1, 22.7, and 23.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0190] In some embodiments, the crystalline sulfate salt is characterized by an XRPD patern comprising signals at 9.1+0.5, 10.0+0.5, 15.3+0.5, 16.4+0.5, 18.3+0.5, 20.1+0.5, 22.7+0.5, and 23.4+0.5 °20 (e.g, 9.1+0.2, 10.0+0.2, 15.3+0.2, 16.4+0.2, 18.3+0.2, 20.1+0.2, 22.7+0.2, and 23.4+0.2 °20 (e.g., 9.1+0.1, 10.0+0.1, 15.3+0.1, 16.4+0.1, 18.3+0.1, 20.1+0.1, 22.7+0.1, and 23.4+0.1 °20 (e.g., 9.1, 10.0, 15.3, 16.4, 18.3, 20.1, 22.7, and 23.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0191] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern comprising signals at 9.1+0.5, 10.0+0.5, 15.3+0.5, 16.4+0.5, 18.3+0.5, 20.1+0.5, 22.7+0.5, 23.4+0.5, and 23.9+0.5 ”20 (e.g, 9.1+0.2, 10.0+0.2, 15.3+0.2, 16.4+0.2, 18.3+0.2, 20.1+0.2, 22.7+0.2, 23.4+0.2, and 23.9+0.2 °20 (e.g, 9.1+0.1, 10.0+0.1, 15.3+0.1, 16.4+0.1, 18.3+0.1, 20.1+0.1, 22.7+0.1, 23.4+0.1, and 23.9+0.1 °20 (e.g, 9.1, 10.0, 15.3, 16.4, 18.3, 20.1, 22.7, 23.4, and 23.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0192] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one signal selected from 9.1+0.5, 10.0+0.5, and 22.7+0.5 °20 (e.g., 9.1+0.2, 10.0+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.0+0.1, and 22.7+0,1 °20 (e.g., 9,1, 10.0, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0193] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least two signal selected from 9.1+0.5, 10.0+0.5, and 22.7+0.5 °20 (e.g., 9.1+0.2, 10.0+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.0+0.1, and 22.7+0.1 °20 (e.g., 9.1, 10.0, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0194] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least three signals selected from 9.1+0.5, 10,0+0,5, 18.3+0.5, and 22,7+0.5 °20 (e.g., 9.1+0.2, 10.0+0.2, 18.3+0.2, and 22.7+0.2 °20 (e.g, 9.1+0.1, 10.0+0.1, 18.3+0.1, and 22.7+0.1 °20 (e.g, 9.1, 10.0, 18.3, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0195] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least four signals selected from 9.1+0.5, 10.0+0.5, 15.3+0.5, 18.3+0.5, and 22.7+0.5 °20 (e.g., 9.1+0.2, 10.0+0.2, 15.3+0.2, 18.3+0.2, and 22.7+0.2 °20 (e.g., 9.1+0.1, 10.0+0.1, 15.3+0.1, 18.3+0.1, and 22.7+0.1 °20 (e.g., 9.1, 10.0, 15.3, 18.3, and 22.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0196] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least five signals selected from 9, 1+0.5, 10.0+0.5, 15.3+0,5, 18.3+0.5, 22.7+0.5, and 23.4+0,5 °20 (e.g., 9.1+0.2, 10.0+0.2, 15.3+0.2, 18.3+0.2, 22.7+0.2, and 23.4+0.2 °20 (e.g, 9.1+0.1, 10.0+0.1, 15.3+0.1, 18.3+0.1, 22.7+0.1, and 23.4+0.1 °20 (e.g., 9.1, 10.0, 15.3, 18.3, 22.7, and 23.4 °20))), using Cu K alpha radiation when measured at 25 °C.43700-02297 (VNTS-031 / 001WO)

[0197] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 9.1 ± 0.5, 10.0 ± 0.5, 12.3 ± 0.5, 13.1 ± 0.5, 15.3 ± 0.5, 16.4 ± 0.5, 18.3 ± 0.5, 18.8 ± 0.5, 19.2 ± 0.5, 20.1 ± 0.5, 21.4 ± 0.5, 21.8 ± 0.5, 22.0 ± 0.5, 22.7 ± 0.5, 23.4 ± 0.5, 23.9 ± 0,5, 24.6 ± 0,5, 25,2 ± 0.5, 25,7 ± 0.5, 28,3 ± 0.5, 30,8 ± 0.5, or 36.4 ± 0.5, using Cu K alpha radiation when measured at 25 °C.

[0198] In some embodiments, the cry stalline sulfate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 9.1 ± 0.2, 10,0 ± 0,2, 12.3 ± 0,2, 13,1 ± 0.2, 15,3 ± 0.2, 16,4 ± 0.2, 18.3 ± 0.2, 18.8 ± 0.2, 19.2 ± 0.2, 20.1 ± 0.2, 21.4 ± 0.2, 21.8 ± 0.2, 22.0 ± 0.2, 22.7 ± 0.2, 23.4 ± 0.2, 23.9 ± 0.2, 24.6 ± 0.2, 25.2 ± 0.2, 25.7 ± 0.2, 28.3 ± 0.2, 30.8 ± 0.2, or 36.4 ± 0.2, using Cu K alpha radiation when measured at 25 °C.

[0199] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern that does not have an X-ray powder diffraction signal at 6.4±0,5 °20 (e.g., 6,4±0,2 °20 (e.g., 6.4±0.1 °20 (e.g., 6.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0200] In some embodiments, the crystalline sulfate salt is characterized by an XRPD pattern that does not have an X-ray powder diffraction signal at 7.6±0.5 °20 (e.g., 7.6+0.2 °20 (e.g.. 7.6±0.1 °20 (e.g., 7,6 °20))), using Cu K alpha radiation when measured at 25 °C.

[0201] In some embodiments, the crystalline sulfate salt is Crystalline Compound 1 Form C Sulfate Salt, which is characterized by an XRPD pattern comprising one or more signals as described in Table 3 below.

[0202] In some embodiments, the Crystalline Compound 1 Form C Sulfate Salt is characterized by an XRPD pattern comprising two or more signals as described in Table 3 below.

[0203] In some embodiments, the Crystalline Compound 1 Form C Sulfate Salt is characterized by an XRPD pattern comprising three or more signals as described in Table 3 below.

[0204] In some embodiments, the Crystalline Compound 1 Form C Sulfate Salt is characterized by an XRPD pattern comprising four or more signals as described in Table 3 below'.

[0205] In some embodiments, the Crystalline Compound 1 Form C Sulfate Salt is characterized by each of the XRPD signals as set forth in Table 3.

[0206] In some embodiments, the Crystalline Compound 1 Form C Sulfate Salt is characterized by an XRPD pattern substantially similar to that set forth in FIG. 6.Table 3. XRPD signals of Form C Sulfate SaltPeak No. 20 [°] Rel. Int. [%] 1 9.1 78.32 2 10.0 100.00 3 12.3 27.49 4 13.1 12.00 5 15.3 59.00 6 16.4 42.597 18.3 59.9443700-02297 (VNTS-031 / 001WO) Table 3. XRPD signals of Form C Sulfate SaltPeak No. 20|°| ReLint. [%]8 18.8 33.349 19.2 33.2010 20.1 47.1711 21.4 27.8912 21.8 30.4813 22.0 32.9714 22.7 74.7815 23.4 54.5916 23.9 33.8717 24.6 18.0118 25.2 27.5119 25.7 33.6620 28.3 18.4421 30.8 11.5122 36.4 9.60

[0207] As noted in the Examples, Cry stalline Compound 1 Form C Sulfate Salt is a metastable form, comprising a mixture of Form B Sulfate Salt and at least one other metastable sulfate salt form,

[0208] In some embodiments, the Crystalline Compound 1 Form C Sulfate Salt converts to Cry stalline Compound 1 Form A Sulfate Salt. In some embodiments, the Crystalline Compound 1 Form C Sulfate Salt converts to Crystalline Compound 1 Form A Sulfate Salt upon drying.(i-cl)

[0209] In some embodiments, the sulfate salt form is amorphous. In some embodiments, the amorphous sulfate salt form is prepared from a solution of the sulfate salt in methanol (MeOH), followed by solvent evaporation. In some embodiments, the amorphous form is prepared from a solution of the sulfate salt in methanol (MeOH), followed by addition of methyl tert-butyl ether (MTBE) as the anti-solvent. In some embodiments, the amorphous form is prepared from a solution of the sulfate salt in dimethylsulfoxide (DMSO) followed by addition of isopropyl acetate (IP Ac) as the anti-solvent.

[0210] An exemplary’ XRPD of the amorphous sulfate salt, so obtained, has a broad halo between about 12 and about 30 °20, inclusive, using Cu K alpha radiation when measured at 25 °C, as provided in FIG 7.(ii) Compound 1 Phosphate Salt

[0211] The present disclosure provides phosphate salts of Compound I.

[0212] In some embodiments, the phosphate salt is crystalline.43700-02297 (VNTS-031 / 001WO)

[0213] In some embodiments, the phosphate salt is a stable form.

[0214] In some embodiments, the phosphate salt is a pure-phase form.

[0215] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising a signal at 5, 1+0,2 °20, using Cu K alpha radiation when measured at 25 °C,

[0216] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern comprising a signal at 10.2+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0217] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising a signal at 18.4+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0218] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising signals at 5.1+0.5, 10.2+0.5, and 18.4+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, and 18.4+0.2 °20 (e.g., 5.1+0.1, 10.2+0.1, and 18.4+0.1 °20 (e.g, 5.1, 10.2, and 18.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0219] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern comprising signals at 5.1+0.5, 10.2+0.5, 18.4+0.5, and 19.7+0.5 °20 (e.g, 5.1+0.2, 10.2+0.2, 18.4+0.2, and 19.7+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, 18.4+0.1, and 19.7+0.1 °20 (e.g, 5.1, 10.2, 18.4, and 19.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0220] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising signals at 5.1+0.5, 10.2+0.5, 16.9+0.5, 18.4+0.5, and 19.7+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, 16.9+0.2, 18.4+0.2, and 19.7+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, 16.9+0.1, 18.4+0.1, and 19.7+0.1 °20 (e.g., 5.1, 10.2, 16,9, 18,4, and 19.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0221] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern comprising signals at 5.1+0.5, 10.2+0.5, 16.9+0.5, 18.4+0.5, 19.7+0.5, and 21.4+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, 16.9+0.2, 18.4+0.2, 19.7+0.2, and 21.4+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, 16.9+0.1, 18.4+0.1, 19.7+0.1, and 21.4+0.1 °2θ (e.g, 5.1, 10.2, 16.9, 18.4, 19.7, and 21.4 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0222] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern comprising signals at 5.1+0.5, 10.2+0.5, 14.2+0.5, 16.9+0.5, 18,4+0.5, 19,7+0.5, and 21.4+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, 14.2+0.2, 16.9+0.2, 18.4+0.2, 19.7+0.2, and 21.4+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, 14.2+0.1, 16.9+0.1, 18.4+0.1, 19.7+0.1, and 21.4+0.1 °2θ (e.g, 5.1, 10.2, 14.2, 16.9, 18.4, 19.7, and 21.4 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0223] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern comprising signals at 5.1+0.5, 10.2+0.5, 14.2+0.5, 16.9+0.5, 17.3+0.5, 18.4+0,5, 19.7+0,5, and 21.4+0.5 °20 (e.g, 5.1+0.2, 10.2+0.2, 14.2+0.2, 16.9+0.2, 17.3+0.2, 18.4+0.2, 19.7+0.2, and 21.4+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, 14.2+0.1, 16.9+0.1, 17.3+0.1, 18.4+0.1, 19.7+0.1, and 21.4+0.1 °20 (e.g, 5.1, 10.2, 14.2, 16.9, 17.3, 18.4, 19.7, and 21,4 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0224] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern comprising signals at 5.1+0.5, 10.2+0.5, 14.2+0.5, 16.9+0.5, 17.3+0.5, 18.4+0.5, 19.7+0.5, 21.4+0.5, and 23.0+0.5 °20 (e.g, 5.1+0.2, 10.2+0.2, 14.2+0.2, 16.9+0.2, 17.3+0.2, 18.4+0.2, 19.7+0.2, 21.4+0.2, and43700-02297 (VNTS-031 / 001WO) 23.0+0.2 °20 (e.g., 5.1+0.1, 10.2+0.1, 14.2+0.1, 16.9+0.1, 17.3+0.1, 18.4+0.1, 19.7+0.1, 21.4+0.1, and 23.0+0.1 °20 (e.g, 5.1, 10.2, 14.2, 16.9, 17.3, 18.4, 19.7, 21.4, and 23.0 °20))), using Cu K alpha radiation when measured at 25 °C.

[0225] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern having at least one signal selected from 5.1+0.5, 10.2+0.5, and 18.4+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, and 18.4+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, and 18.4+0.1 °20 (e.g, 5.1, 10.2, and 18.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0226] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern having at least two signal selected from 5.1+0.5, 10.2+0.5, and 18.4+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, and 18.4+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, and 18.4+0.1 °20 (e.g, 5.1, 10.2, and 18.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0227] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern having at least three signals selected from 5.1+0.5, 10.2+0.5, 18.4+0.5, and 19.7+0.5 °20 (e.g, 5.1+0.2, 10.2+0.2, 18.4+0.2, and 19.7+0.2 °20 (e.g., 5.1+0.1, 10.2+0.1, 18.4+0.1, and 19.7+0.1 °20 (e.g, 5.1, 10.2, 18.4, and 19.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0228] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern having at least four signals selected from 5.1+0.5, 10.2+0.5, 16.9+0.5, 18.4+0.5, and 19.7+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, 16.9+0.2, 18.4+0.2, and 19.7+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, 16.9+0.1, 18.4+0.1, and 19.7+0.1 °20 (e.g., 5.1, 10.2, 16.9, 18.4, and 19.7 °20))), using Cu K alpha radiation when measured at 25 °C.

[0229] In some embodiments, the cry stalline phosphate salt is characterized by an XRPD pattern having at least five signals selected from 5.1+0.5, 10.2+0.5, 16.9+0.5, 18.4+0.5, 19.7+0.5, and 21.4+0.5 °20 (e.g., 5.1+0.2, 10.2+0.2, 16.9+0.2, 18.4+0.2, 19.7+0.2, and 21.4+0.2 °20 (e.g, 5.1+0.1, 10.2+0.1, 16.9+0.1, 18.4+0.1, 19.7+0.1, and 21.4+0.1 °20 (e.g, 5.1, 10.2, 16.9, 18.4, 19.7, and 21.4 °20))), using Cu K alpha radiation when measured at 25 °C.

[0230] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 5.1 ± 0.5, 10.2 ± 0.5, 11.8 + 0.5, 13.0 ± 0.5, 14.2 ± 0.5, 15.2 + 0.5, 16.9 + 0.5, 17.3 + 0.5, 18.4 + 0.5, 19.2 + 0.5, 19.7 + 0.5, 21.4 + 0.5, 22.6 + 0.5, 23.0 + 0.5, 24.3 ± 0,5, 26.5 + 0,5, 27,6 + 0.5, 30,5 + 0.5, or 31.8 ± 0.5, using Cu K alpha radiation when measured at 25 °C.

[0231] In some embodiments, the crystalline phosphate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 5.1 ± 0.2, 10.2 ± 0.2, 11.8 + 0.2, 13.0 + 0.2, 14.2 ± 0.2, 15.2 + 0.2, 16.9 + 0.2, 17.3 + 0.2, 18.4 + 0.2, 19.2 + 0.2, 19.7 + 0.2, 21.4 + 0.2, 22.6 + 0.2, 23.0 + 0.2, 24.3 ± 0.2, 26.5 ± 0.2, 27.6 ± 0.2, 30.5 ± 0.2, or 31.8 ± 0.2, using Cu K alpha radiation when measured at 25 °C.

[0232] In some embodiments, the cry stalline phosphate salt is Cry stalline Compound 1 Form D Phosphate Salt, which is characterized by an XRPD pattern comprising one or more signals as described in Table 4 below.

[0233] In some embodiments, die Crystalline Compound 1 Form D Phosphate Salt is characterized by an43700-02297 (VNTS-031 / 001WO) XRPD patern comprising two or more signals as described in Table 4 below.

[0234] In some embodiments, the Crystalline Compound 1 Form D Phosphate Salt is characterized by an XRPD patern comprising three or more signals as described in Table 4 below.

[0235] In some embodiments, the Crystalline Compound 1 Form D Phosphate Salt is characterized by an XRPD patern comprising four or more signals as described in Table 4 below.

[0236] In some embodiments, the Crystalline Compound 1 Form D Phosphate Salt is characterized by each of the XRPD signals as set forth in Table 4.

[0237] In some embodiments, the Crystalline Compound 1 Form D Phosphate Salt is characterized by an XRPD pattern substantially similar to that set forth in FIG. 3A.Table 4. XRPD Signals of Form D Phosphate SaltPeak No. 20 [°] Rel. Int.[%] 1 5.1 100.002 10.2 46.85 3 11.8 9.10 4 13.0 8.30 5 14.2 10.36 6 15.2 2.92 7 16.9 17.80 8 17.3 10.35 9 18.4 27.23 10 19.2 9.10 11 19.7 23.16 12 21.4 13.62 13 22.6 6.12 14 23.0 9.39 15 24.3 4.78 16 26.5 6.53 17 27.6 3.84 18 30.5 2.3219 31.8 2.53

[0238] In some embodiments, the crystalline phosphate salt is characterized by at least one endothermic event between about 160 °C and about 210 °C, inclusive, as measured by DSC. In some embodiments, the crystalline phosphate salt is characterized by two endothermic events between about 160 °C and about 210 °C, inclusive, as measured by DSC. In some embodiments, the crystalline phosphate salt is characterized by two endothermic events between about 166 °C and about 200 °C, inclusive, as measured by DSC.

[0239] In some embodiments, the crystalline phosphate salt is characterized by an endothermic event at43700-02297 (VNTS-031 / 001WO) 166+20 °C, 166+ 15 °C, 166+ 10 °C, or 166+5 °C (e.g., at about 166 °C), as measured by DSC. In some embodiments, the crystalline phosphate salt is characterized by an endothermic event at 200+20 °C, 200+15 °C, 200+10 °C, or 200+5 °C e.g., at about 200 °C), as measured by DSC. In some embodiments, the cry stalline phosphate salt so characterized is Crystalline Compound 1 Form D Phosphate Salt.

[0240] In some embodiments, the Crystalline Compound 1 Form D Phosphate Salt is characterized by an endothermic event as measured by DSC substantially similar to that set forth in FIG. 3B.

[0241] In some embodiments, the crystalline phosphate salt is characterized by a weight loss of at least about 2% up to about 150 °C as measured by TGA. In some embodiments, the crystalline phosphate salt is characterized by a weight loss of between about 2% and about 3%, inclusive, up to about 150 °C as measured by TGA. In some embodiments, the crystalline phosphate salt is characterized by a weight loss of about 2.57% up to about 150 °C as measured by TGA.

[0242] In some embodiments, the cry stalline phosphate salt is characterized by a weight loss of about 2.57% up to about 150±40 °C, 150±30 °C, 150±20 °C, 150±15 °C, 150±10 °C, or 150±5 °C (e.g., at about 150 °C), as measured by TGA. In some embodiments, the crystalline phosphate salt so characterized is Crystalline Compound 1 Form D Phosphate Salt.

[0243] In some embodiments, the Crystalline Compound 1 Form D Phosphate Salt is characterized by a weight loss as measured by TGA substantially similar to that set forth in FIG. 3B.

[0244] In some embodiments, the Crystalline Compound 1 Form D Phosphate Salt is in a 2: 1 stoichiometric ratio of two phosphate counterions to one protonated Compound 1.

[0245] In some embodiments, the cry stalline phosphate salt is soluble in a solvent. In some embodiments, the solubility of the crystalline phosphate salt is measured in water or a physiological buffer. In some embodiments, a physiological buffer is simulated gastric fluid (SGF) for two (2) hours at 37 °C at approximately 25 rpm, followed by dilution with fasted state simulated intestinal fluid (FaSSIF) for one (1) hour or two (2) hours at 37 °C at approximately 25 rpm.

[0246] In some embodiments, the crystalline phosphate salt has a solubility greater than about 1.6 mg / niL, as measured in SGF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline phosphate salt has a solubility greater than about 1.6 mg / mL at a pH of about 1.8, as measured in SGF at two hours at 37 °C at approximately' 25 rpm.

[0247] In some embodiments, the crystalline phosphate salt has a solubility of about 0.06 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at one hour at 37 °C at approximately 25 rpm. in some embodiments, the crystalline phosphate salt has a solubility of about 0.06 mg / mL at a pH of about 5.6, as measured in a 1:3 mixture of SGF and FaSSIF at one hour at 37 °C at approximately 25 rpm,

[0248] In some embodiments, the crystalline phosphate salt has a solubility of about 0.05 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline phosphate salt has a solubility of about 0.05 mg / mL at a pH of about 5,6, as measured in a 1:3 mixture of SGF and FaSSIF at two hours at 37 °C at approximately 25 rpm.

[0249] In some embodiments, the cry stalline phosphate salt converts to Form I Freebase after dilution in a 1:3 mixture of SGF and FaSSIF after 1 hour at 37 °C at approximately 25 rpm.43700-02297 (VNTS-031 / 001WO)(Hi) Compound 1 Fumarate. Salt

[0250] The present disclosure provides fumarate salts of Compound 1.

[0251] In some embodiments, the fumarate salt is cry stalline.

[0252] In some embodiments, the fumarate salt is a stable form.

[0253] In some embodiments, the fumarate salt is a pure-phase form.

[0254] In some embodiments, the cry stalline fumarate salt is characterized by an XRPD pattern comprising a signal at 7.1±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C.

[0255] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising a signal at 18.5+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0256] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signal at 21.5+0.5 °20, using Cu K alpha radiation when measured at 25 °C,

[0257] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signals at 7.1+0.5, 18.5+0.5, and 21.5+0.5 °20 (e.g., 7.1+0.2, 18.5+0.2, and 21.5+0.2 ”20 (e.g., 7.1+0.1, 18.5+0.1, and 21.5+0.1 °20 (e.g., 7.1, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0258] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signals at 7. HO., 9.3+0.5, 18.5+0.5, and 21.5+0.5 °20 (e.g., 7. HO.2, 9.3+0.2, 18.5+0.2, and 21.5+0.2 °20 (e.g, 7. H0.1, 9.3+0.1, 18.5+0.1, and 21.5+0.1 °20 (e.g, 7.1, 9.3, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C,

[0259] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signals at 7. HO.5, 9.3+0.5, 10.7+0.5, 18.5+0.5, and 21.5+0.5 °20 (e.g., 7.1+0.2, 9.3+0.2, 10.7+0.2, 18.5+0.2, and 21.5+0.2 °20 (e.g, 7.1+0.1, 9.3+0.1, 10.7+0.1, 18.5+0.1, and 21.5+0.1 °20 (e.g, 7.1, 9.3, 10.7, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0260] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signals at 7.1+0.5, 9.3+0.5, 10.7+0.5, 14.9+0.5, 18.5+0.5, and 21.5+0.5 °20 (e.g., 7.1+0.2, 9.3+0.2, 10.7+0,2, 14.9+0.2, 18.5+0.2, and 21.5+0.2 °20 (e.g, 7.1+0.1, 9.3+0.1, 10.7+0.1, 14.9+0.1, 18.5+0.1, and 21.5+0.1 °20 (e.g, 7.1, 9.3, 10.7, 14.9, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0261] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signals at 7.1+0.5, 9.3+0.5, 10.7+0.5, 14.9+0.5, 18.5+0.5, 21.5+0.5, and 21.9+0.5 °20 (e.g., 7.1+0.2, 9.3+0.2, 10.7+0.2, 14.9+0.2, 18.5+0.2, 21.5+0.2, and 21.9+0.2 °20 (e.g, 7.1+0.1, 9.3+0.1, 10.7+0.1, 14.9+0.1, 18.5+0.1, 21.5+0.1, and 21.9+0.1 °20 (e.g, 7.1, 9.3, 10.7, 14.9, 18.5, 21.5, and 21.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0262] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signals at 7.1+0.5, 9.3+0.5, 10.7+0.5, 14.9+0.5, 18.5+0.5, 21.2+0.5, 21.5+0.5, and 21.9+0.5 °20 (e.g, 7.1+0.2, 9.3+0.2, 10.7+0.2, 14.9+0.2, 18.5+0.2, 21.2+0.2, 21.5+0.2, and 21.9+0.2 °20 (e.g, 7.1+0.1, 9.3+0.1, 10.7+0.1, 14.9+0.1, 18.5+0.1, 21.2+0.1, 21.5+0.1, and 21.9+0.1 °20 (e.g, 7.1, 9.3, 10.7,43700-02297 (VNTS-031 / 001WO) 14.9, 18.5, 21.2, 21.5, and 21.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0263] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern comprising signals at 7.1+0.5, 9.3+0.5, 10.7+0.5, 14.5+0.5, 14.9+0.5, 18.5+0.5, 21.2+0.5, 21.5+0.5, and 21,9+0.5 °20 (e.g, 7.1+0.2, 9.3+0.2, 10.7+0.2, 14.5+0.2, 14.9+0.2, 18.5+0.2, 21.2+0.2, 21.5+0.2, and 21.9+0.2 °20 (e.g., 7.1+0.1, 9.3+0.1, 10.7+0.1, 14.5+0.1, 14.9+0.1, 18.5+0.1, 21.2+0.1, 21.5+0.1, and 21.9+0.1 °20 (e.g, 7.1, 9.3, 10.7, 14.5, 14.9, 18.5, 21.2, 21.5, and 21.9 °20))), using Cu K alpha radiation when measured at 25 °C.

[0264] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern having at least one signal selected from 7.1 ± 0.5, 18.5 + 0.5, and 21.5 ± 0.5 °20 (e.g., 7.1 ± 0.2, 18.5 + 0.2, and 21.5 ± 0.2 °20 (e.g, 7.1 ± 0.1, 18.5 ± 0.1, and 21.5 ± 0.1 °20 (e.g, 7 A, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0265] In some embodiments, the cry stalline fumarate salt is characterized by an XRPD pattern having at least two signal selected from 7.1 + 0.5, 18.5 + 0.5, and 21.5 + 0.5 °20 (e.g., 7.1 + 0.2, 18.5 + 0.2, and 21.5 + 0.2 °20 (e.g, 7.1 + 0.1, 18.5 + 0.1, and 21.5 + 0.1 °20 (e.g, 7.1, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0266] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern having at least three signals selected from 7.1 + 0.5, 9.3 + 0.5, 18.5 ± 0.5, and 21.5 + 0.5 °20 (e.g., 7.1 + 0.2, 9.3 ± 0.2, 18.5 ± 0.2, and 21.5 ± 0.2 °20 (e.g, 7.1 ± 0.1, 9.3 ± 0.1, 18.5 ± 0.1, and 21.5 ± 0.1 °20 (e.g., 7.1, 9.3, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0267] In some embodiments, the cry stalline fumarate salt is characterized by an XRPD pattern having at least four signals selected from 7.1 + 0.5, 9.3 + 0.5, 10.7 + 0.5, 18.5 + 0.5, and 21.5 + 0.5 °20 (e.g., 7.1 + 0.2, 9.3 + 0.2, 10.7 + 0.2, 18.5 + 0.2, and 21.5 ± 0.2 °20 (e.g, 7.1 + 0.1, 9.3 + 0.1, 10.7 + 0.1, 18.5 ± 0.1, and 21.5 ± 0.1 °20 (e.g., 7.1, 9.3, 10.7, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0268] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern having at least five signals selected from 7.1 ± 0.5, 9.3 ± 0.5, 10.7 ± 0.5, 14.9 ± 0.5, 18.5 ± 0.5, and 21.5 ± 0.5 °20 (e.g, 7.1 ± 0.2, 9.3 ± 0.2, 10.7 ± 0.2, 14.9 ± 0.2, 18.5 ± 0.2, and 21.5 ± 0.2 °20 (e.g, 7.1 ± 0.1, 9.3 ± 0.1, 10.7 + 0.1, 14.9 + 0.1, 18.5 ± 0.1, and 21.5 ± 0.1 °20 (e.g., 7.1, 9.3, 10.7, 14.9, 18.5, and 21.5 °20))), using Cu K alpha radiation when measured at 25 °C.

[0269] In some embodiments, the crystalline fumarate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 7.1 ± 0.5, 9.3 ± 0.5, 10.7 ± 0.5, 11.6 ± 0.5, 12.0 ± 0.5, 12.3 ± 0.5, 13.1 + 0.5, 14.5 + 0.5, 14.9 + 0.5, 15.4 + 0.5, 16.1 + 0.5, 16.6 + 0.5, 17.5 + 0.5, 18.0 + 0.5, 18.5 + 0.5, 19.5 ± 0.5, 20.0 ± 0.5, 20.8 ± 0.5, 21.2 ± 0.5, 21.5 ± 0.5, 21.9 ± 0.5, 22.3 + 0.5, 22.7 + 0.5, 23.3 + 0.5, 24.2 ± 0.5, 24.7 ± 0.5, 25.9 ± 0.5, 26.4 ± 0.5, 26.9 ± 0.5, 27.2 ± 0.5, 27.9 ± 0.5, 28.4 ± 0.5, 29.1 ± 0.5, 30.3 ± 0,5, 32.6 ± 0,5, 35,3 ± 0.5, 35, 9 + 0.5, 36,4 ± 0.5, and 38,0 ± 0,5, using Cu K alpha radiation when measured at 25 °C.

[0270] In some embodiments, the cry stalline fumarate salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 7.1 + 0.2, 9.3 ± 0.2, 10.7 ± 0.2, 11.6 ± 0.2, 12.0 + 0.2, 12.3 +43700-02297 (VNTS-031 / 001WO) 0.2, 13.1 ± 0.2, 14.5 ± 0.2, 14.9 ± 0.2, 15.4 ± 0.2, 16.1 ± 0.2, 16.6 ± 0.2, 17.5 ± 0.2, 18.0 ± 0.2, 18.5 ± 0.2, 19.5 ± 0.2, 20.0 ± 0.2, 20.8 ± 0.2, 21.2 ± 0.2, 21.5 ± 0.2, 21.9 ± 0.2, 22.3 ± 0.2, 22.7 ± 0.2, 23.3 ± 0.2, 24.2 ± 0.2, 24.7 ± 0.2, 25.9 ± 0.2, 26.4 ± 0.2, 26.9 ± 0.2, 27.2 ± 0.2, 27.9 ± 0.2, 28.4 ± 0.2, 29.1 ± 0.2, 30.3 ± 0,2, 32.6 ± 0,2, 35,3 ± 0.2, 35,9 ± 0.2, 36,4 ± 0.2, and 38,0 ± 0.2, using Cu K alpha radiation when measured at 25 °C.

[0271] In some embodiments, the crystalline fumarate salt is Crystalline Compound 1 Form E Fumarate Salt, which is characterized by an XRPD pattern comprising one or more signals as described in Table 5 below.

[0272] In some embodiments, the Crystalline Compound 1 Form E Fumarate Salt is characterized by an XRPD pattern comprising two or more signals as described in Table 5 below.

[0273] In some embodiments, the Crystalline Compound 1 Form E Fumarate Salt is characterized by an XRPD pattern comprising three or more signals as described in Table 5 below.

[0274] In some embodiments, the Crystalline Compound 1 Form E Fumarate Salt is characterized by an XRPD pattern comprising four or more signals as described in Table 5 below.

[0275] In some embodiments, the Cry stalline Compound 1 Form E Fumarate Salt is characterized by each of the XRPD signals as set forth in Table 5.

[0276] In some embodiments, the Crystalline Compound 1 Form E Fumarate Salt is characterized by an XRPD pattern substantially similar to that set forth in FIG. 1A.Table 5. XRPD signals of Form E Fumarate SaltPeak No. 20[°] Rel. Int.[%] 1 7.1 100.002 9.3 11.123 10.7 10.914 11.6 2.47 5 12.0 3.34 6 12.3 2.00 7 13.1 1.39 8 14.5 6.43 9 14.9 9.50 10 15.4 3.28 11 16.1 0.88 12 16,6 1.02 13 17.5 1.78 14 18.0 1.50 15 18.5 36.1716 19.5 0.77 17 20.0 2.1018 20.8 1.1043700-02297 (VNTS-031 / 001WO) Table 5. XRPD signals of Form E Fumarate SaltPeak No. 2θ[°] Rel.Int.[%] 19 21.2 7.60 20 21.5 13.61 21 21.9 9.10 22 22.3 3.39 23 22.7 5.15 24 23.3 3.68 25 24.2 3.07 26 24.7 5.04 27 25.9 0.66 28 26.4 0.87 29 26.9 3.56 30 27.2 2.83 31 27.9 1.92 32 28.4 4.76 33 29.1 0.82 34 30.3 1.08 35 32.6 2.71 36 35.3 0.69 37 35.9 0.07 38 36.4 0.7639 38.0 0.12

[0277] In some embodiments, the crystalline fumarate salt is characterized by at least one endothermic event between about 180 °C and about 186 °C, inclusive, as measured by DSC. In some embodiments, the crystalline fumarate salt is characterized by at least one additional endothermic event between about 56 °C and about 58 °C, inclusive, as measured by DSC, In some embodiments, the crystalline fumarate salt is characterized by at least one additional endothermic event between about 136°C and about 138 °C, inclusive, as measured by DSC. In some embodiments, the crystalline fumarate salt is characterized by at least one endothermic event between about 178 °C and about 183 °C, inclusive, as measured by DSC. In some embodiments, the crystalline fumarate salt is characterized by at least one endothermic event between about 183 °C and about 188 °C, inclusive, as measured by DSC.

[0278] In some embodiments, the crystalline fumarate salt is characterized by four endothermic events at about 57.5, at about 137.2, at about 181.8, and at about 184.8 °C, as measured by DSC.

[0279] In some embodiments, the cry stalline fumarate salt is characterized by an endothermic event at 57.5±20 °C, 57.5± 15 °C, 57.5±10 °C, or 57.5±5 °C (e.g., at about 57.5 °C), as measured by DSC. In some embodiments, the crystalline fumarate salt is characterized by an endothermic event at 137.2±20 °C,43700-02297 (VNTS-031 / 001WO) 137.2±15 °C, 137.2±10 °C, or 137.2±5 °C (e.g., at about 137.2 °C), as measured by DSC. In some embodiments, the crystalline fumarate salt is characterized by an endothermic event at 181.8±20 °C, 181.8±15 °C, 181.8±10 °C, or 181.8±5 °C (e.g., at about 181.8 °C), as measured by DSC. In some embodiments, the crystalline fumarate salt is characterized by an endothermic event at 184.8±20 °C, 184.8±15 °C, 184.8±10 °C, or 184.8±5 °C (e.g., at about 184.8 °C), as measured by DSC. In some embodiments, the crystalline fumarate salt so characterized is Crystalline Compound 1 Form E Fumarate Salt.

[0280] In some embodiments, the Crystalline Compound 1 Form E Fumarate Salt is characterized by an endothermic event substantially similar to that set forth in FIG. 1B.

[0281] In some embodiments, the crystalline fumarate salt is characterized by a weight loss of at least about 4% up to about 150 °C, as measured by TGA. In some embodiments, the crystalline fumarate salt is characterized by a weight loss of about 4.43% up to about 150 °C, as measured by TGA,

[0282] In some embodiments, the cry stalline fumarate salt is characterized by a weight loss of about 4.43% up to about 150±40 °C, 150±30 °C, 150±20 °C, 150±15 °C, 150±10 °C, or 150±5 °C (e.g., at about 150 °C), as measured by TGA. In some embodiments, the crystalline fumarate salt so characterized is Crystalline Compound 1 Form F Fumarate Salt.

[0283] In some embodiments, the Crystalline Compound 1 Form E Fumarate Salt is characterized by a weight loss as measured by TGA substantially similar to that set forth in FIG. 1B.

[0284] In some embodiments, the Crystalline Compound 1 Form E Fumarate Salt is in a 1: 1 stoichiometric ratio of one fumarate counterion to one protonated Compound 1,

[0285] In some embodiments, the cry stalline fumarate salt is soluble in a solvent. In some embodiments, the solubility of the crystalline fumarate salt is measured in water or a physiological buffer. In some embodiments, a physiological buffer is simulated gastric fluid (SGF) for two (2) hours at 37 °C at approximately 25 rpm, followed by dilution with fasted state simulated intestinal fluid (FaSSIF) for one (1) hour or two (2) hours at 37 °C at approximately 25 rpm.

[0286] In some embodiments, the crystalline fumarate salt has a solubility greater than about 1.9 mg / mL, as measured in SGF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline fumarate salt has a solubility greater than about 1,9 mg / mL at a pH of about 1.9, as measured in SGF at two hours at 37 °C at approximately 25 rpm.

[0287] In some embodiments, the crystalline fumarate salt has a solubility of about 0.06 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at one hour. In some embodiments, the cry stalline fumarate salt has a solubility of about 0,06 mg / mL at a pH of about 5.5, as measured in a 1:3 mixture of SGF and FaSSIF at one hour at 37 °C at approximately 25 rpm.

[0288] In some embodiments, the crystalline fumarate salt has a solubility of about 0.05 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at two hours. In some embodiments, the cry stalline fumarate salt has a solubility of about 0.05 mg / mL at a pH of about 5.5, as measured in a 1:3 mixture of SGF and FaSSIF at two hours at 37 °C at approximately 25 rpm.

[0289] In some embodiments, the crystalline fumarate salt converts to Form I Freebase after dilution in a43700-02297 (VNTS-031 / 001WO) 1:3 mixture of SGF and FaSSIF at 37 °C at approximately 25 rpm.(iv) Compound 1 Hydrochloride Salt

[0290] The present disclosure provides hydrochloride salts of Compound 1.

[0291] In some embodiments, the hydrochloride salt is crystalline.

[0292] In some embodiments, the hydrochloride salt is a stable form.

[0293] In some embodiments, the hydrochloride salt is a pure-phase form,

[0294] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising a signal at 6.9+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0295] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising a signal at 7.8+0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0296] In some embodiments, the cry stalline hydrochloride salt is characterized by an XRPD pattern comprising signal at 10.8+0.5 °20, using Cu K alpha radiation when measured at 25 °C

[0297] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising signals at 6.9±0.5, 7.8±0.5, and 10.8±0.5 °2θ (e.g., 6.9±0.2, 7.8±0.2, and 10.8±0.2 °2θ (e.g., 6.9±0.1, 7.8±0.1, and 10.8±0.1 °2θ (e.g., 6.9, 7.8, and 10.8 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0298] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising signals at 6.9+0.5, 7.8±0.5, 10.8±0.5, and 12.2±0.5 °2θ (e.g., 6.9±0.2, 7.8±0.2, 10.8±0.2, and 12.2±0.2 °2θ (e.g., 6.9±0.1, 7.8±0.1, 10.8±0.1, and 12.2±0.1 °2θ (e.g., 6.9, 7.8, 10.8, and 12.2 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0299] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising signals at 6.9+0.5, 7.8+0.5, 8.7+0.5, 10.8+0.5, and 12.2+0.5 °20 (e.g., 6.9±0.2, 7.8±0.2, 8.7±0.2, 10.8±0.2, and 12.2±0.2 °2θ (e.g., 6.9±0.1, 7.8±0.1, 8.7±0.1, 10.8±0.1, and 12.2±0.1 °2θ (e.g., 6.9, 7.8, 8.7, 10.8, and 12.2 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0300] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising signals at 6.9±0.5, 7.8±0.5, 8.7±0.5, 10.8±0.5, 12.2±0.5, and 13.3±0.5 °2θ (e.g., 6.9±0.2, 7.8±0.2, 8.7±0.2, 10.8±0.2, 12.2±0.2, and 13.3±0.2 °2θ (e.g., 6.9±0.1, 7.8±0.1, 8.7±0.1, 10.8±0.1, 12.2±0.1, and 13.3±0.1 °2θ (e.g., 6.9, 7.8, 8.7, 10.8, 12.2, and 13.3 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0301] In some embodiments, the cry stalline hydrochloride salt is characterized by an XRPD pattern comprising signals at 6.9±0.5, 7.8±0.5, 8.7±0.5, 10.8±0.5, 12.2±0.5, 13.3±0.5, and 15.8±0.5 °2θ (e.g., 6.9±0.2, 7.8±0.2, 8.7±0.2, 10.8±0.2, 12.2±0.2, 13.3±0.2, and 15.8±0.2 °2θ (e.g., 6.9±0.1, 7.8±0.1, 8.7±0.1, 10.8±0.1, 12.2±0.1, 13.3±0.1, and 15.8±0.1 °2θ (e.g., 6.9, 7.8, 8.7, 10.8, 12.2, 13.3, and 15.8 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0302] In some embodiments, the cry stalline hydrochloride salt is characterized by an XRPD pattern comprising signals at 6.9±0.5, 7.8±0.5, 8.7±0.5, 10.8±0.5, 12.2±0.5, 13.3±0.5, 15.8±0.5, and 23.7±0.5 °2θ (e.g., 6.9±0.2, 7.8±0.2, 8.7±0.2, 10.8±0.2, 12.2±0.2, 13.3±0.2, 15.8±0.2, and 23.7±0.2 °2θ (e.g., 6.9±0.1,43700-02297 (VNTS-031 / 001WO) 7.8±0.1, 8.7±0.1, 10.8±0.1, 12.2±0.1, 13.3±0.1, 15.8±0.1, and 23.7±0.1 °2θ (e.g., 6.9, 7.8, 8.7, 10.8, 12.2, 13.3, 15.8, and 23.7 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0303] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern comprising signals at 6.9±0.5, 7.8±0.5, 8.7±0.5, 10.8±0.5, 12.2±0.5, 12.7±0.5, 13.3±0.5, 15.8±0.5, and 23.7±0.5 °2θ (e.g., 6.9±0.2, 7.8±0.2, 8.7±0.2, 10.8±0.2, 12.2±0.2, 12.7±0.2, 13.3±0.2, 15.8±0.2, and 23.7±0.2 °2θ (e.g., 6.9±0.1, 7.8±0.1, 8.7±0.1, 10.8±0.1, 12.2±0.1, 12.7±0.1, 13.3±0.1, 15.8±0.1, and 23.7±0.1 °2θ (e.g., 6.9, 7.8, 8.7, 10.8, 12.2, 12.7, 13.3, 15.8, and 23.7 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0304] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern having at least one signal selected from 6.9 + 0.5, 7.8 ± 0.5, and 10.8 + 0.5 °20 (e.g., 6.9 ± 0.2, 7.8 + 0.2, and 10.8 ± 0.2 °20 (e.g., 6.9 ± 0.1, 7.8 ± 0.1, and 10.8 ± 0.1 °20 (e.g., 6.9, 7.8, and 10.8 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0305] In some embodiments, the cry stalline hydrochloride salt is characterized by an XRPD patern having at least two signal selected from 6.9 + 0.5, 7.8 + 0.5, and 10.8 + 0.5 °20 (e.g., 6.9 + 0.2, 7.8 ± 0.2, and 10.8 ± 0.2 °20 (e.g., 6.9 ± 0.1, 7.8 ± 0.1, and 10.8 ± 0.1 °20 (e.g., 6.9, 7.8, and 10.8 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0306] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern having at least three signals selected from 6.9 ± 0.5, 7.8 ± 0.5, 10.8 ± 0.5, and 12.2 ± 0.5 °20 (e.g., 6.9 ± 0.2, 7.8 ± 0.2, 10.8 ± 0.2, and 12.2 ± 0.2 °2θ (e.g., 6.9 ± 0.1, 7.8 ± 0.1, 10.8 ± 0.1, and 12.2 ± 0.1 °2θ (e.g., 6.9, 7.8, 10.8, and 12.2 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0307] In some embodiments, the cry stalline hydrochloride salt is characterized by an XRPD pattern having at least four signals selected from 6.9 ± 0.5, 7.8 ± 0.5, 8.7 ± 0.5, 10.8 ± 0.5, and 12.2 ± 0.5 °2θ (e.g., 6.9 ± 0.2, 7.8 ± 0.2, 8.7 ± 0.2, 10.8 ± 0.2, and 12.2 ± 0.2 °2θ (e.g., 6.9 ± 0.1, 7.8 ± 0.1, 8.7 ± 0.1, 10.8 ± 0.1, and 12.2 ± 0.1 °2θ (e.g., 6.9, 7.8, 8.7, 10.8, and 12.2 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0308] In some embodiments, the crystalline hydrochloride salt is characterized by an XRPD pattern having at least five signals selected from 6.9 ± 0.5, 7.8 ± 0.5, 8.7 ± 0.5, 10.8 ± 0.5, 12.2 ± 0.5, and 13.3 ± 0.5 °2θ (e.g., 6.9 ± 0.2, 7.8 ± 0.2, 8.7 ± 0.2, 10.8 ± 0.2, 12.2 ± 0.2, and 13.3 ± 0.2 °2θ (e.g., 6.9 ± 0.1, 7.8 ± 0.1, 8.7 ± 0.1, 10.8 ± 0.1, 12.2 ± 0.1, and 13.3 ± 0.1 °2θ (e.g., 6.9, 7.8, 8.7, 10.8, 12.2, and 13.3 °2θ))), using Cu K alpha radiation when measured at 25 °C.

[0309] In some embodiments, the cry stalline hydrochloride salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 6.9 ± 0.5, 7.8 ± 0.5, 8.7 ± 0.5, 10.8 ± 0.5, 11.8 ± 0.5, 12.2 ± 0.5, 12.7 ± 0.5, 13.3 ± 0.5, 13.9 ± 0.5, 14.6 ± 0.5, 15.8 ± 0.5, 16.1 ± 0.5, 17.6 ± 0.5, 18.9 ± 0.5, 19.9 ± 0.5, 20.7 ± 0.5, 22.4 ± 0.5, 22.9 ± 0.5, 23.2 ± 0.5, 23.7 ± 0.5, 24.2 ± 0.5, 24.6 ± 0.5, 25.2 ± 0.5, 26.8 ± 0.5, 28.9 ± 0.5, and 34.3 ± 0.5, using Cu K alpha radiation when measured at 25 °C.

[0310] In some embodiments, the cry stalline hydrochloride salt is characterized by an XRPD pattern having at least one X-ray powder diffraction signal at 6.9 ± 0.2, 7.8 ± 0.2, 8.7 ± 0.2, 10.8 ± 0.2, 11.8 ± 0.2, 12.2 ± 0.2, 12.7 ± 0.2, 13.3 ± 0.2, 13.9 ± 0.2, 14.6 ± 0.2, 15.8 ± 0.2, 16.1 ± 0.2, 17.6 ± 0.2, 18.9 ± 0.2,43700-02297 (VNTS-031 / 001WO) 19.9 ± 0.2, 20.7 ± 0.2, 22.4 ± 0.2, 22.9 ± 0.2, 23.2 ± 0.2, 23.7 ± 0.2, 24.2 ± 0.2, 24.6 ± 0.2, 25.2 ± 0.2, 26.8 ± 0.2, 28.9 ± 0.2, and 34.3 ± 0.2, using Cu K alpha radiation when measured at 25 °C.

[0311] In some embodiments, the crystalline hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt, which is characterized by an XRPD pattern comprising one or more signals as described in Table 6 below.

[0312] In some embodiments, the Crystalline Compound 1 Form F Hydrochloride Salt is characterized by an XRPD pattern comprising two or more signals as described in Table 6 below,

[0313] In some embodiments, the Crystalline Compound 1 Form F Hydrochloride Salt is characterized by an XRPD pattern comprising three or more signals as described in Table 6 below.

[0314] In some embodiments, the Crystalline Compound 1 Form F Hydrochloride Salt is characterized by an XRPD pattern comprising four or more signals as described in Table 6 below.

[0315] In some embodiments, the Cry stalline Compound 1 Form F Hydrochloride Salt is characterized by each of the XRPD signals as set forth in Table 6.

[0316] In some embodiments, the Crystalline Compound 1 Form F Hydrochloride Salt is characterized by an XRPD pattern substantially similar to that set forth in FIG. 2 A.Table 6. XRPD Signals of Form F Hydrochloride SaltPeak No. 20[°] Rel. Int.[%]1 6.93 100.002 7.78 49.373 8.71 31.194 10.80 64.185 11.77 8.346 12.17 41.597 12.70 11.308 13.25 26.079 13.89 11.0510 14.63 4.1711 15.80 21.4212 16.09 10.3313 17.56 2.2414 18.90 9.4815 19.85 3.8116 20.73 8.7617 22.43 8.6818 22.92 11.0119 23.18 8.6620 23.73 12.9321 24.16 3.2043700-02297 (VNTS-031 / 001WO) Table 6. XRPD Signals of Form F Hydrochloride SaltPeak No. 2θ[°] Rel.Int.[%] 22 24.63 4.44 23 25.19 11.14 24 26.84 3.91 25 28.89 6.1626 34.29 2.58

[0317] In some embodiments, the crystalline hydrochloride salt is characterized by at least one endothermic event between about 275 °C and about 285 °C, inclusive, as measured by DSC. In some embodiments, the crystalline hydrochloride salt is characterized by at least one additional endothermic event between about 150 °C and about 178 °C, inclusive, as measured by DSC. In some embodiments, the crystalline hydrochloride salt is characterized by at least one additional endothermic event between about 78 °C and about 81 °C, inclusive, as measured by DSC. In some embodiments, the crystalline hydrochloride salt is characterized by at least one additional endothermic event between about 150 °C and about 160 °C, inclusive, as measured by DSC. In some embodiments, the crystalline hydrochloride salt is characterized by at least one additional endothermic event between about 170 °C and about 180 °C, inclusive, as measured by DSC.

[0318] In some embodiments, the crystalline hydrochloride salt is characterized by four endothermic events at about 80.2, at about 155.1, at about 177.9 and at about 281.8 °C, as measured by DSC.

[0319] In some embodiments, the cry stalline hydrochloride salt is characterized by an endothermic event at 80.2±20 °C, 80.2± 15 °C, 80.2±10 °C, or 80.2±5 °C (e.g., at about 80.2 °C), as measured by DSC. In some embodiments, the crystalline hydrochloride salt is characterized by an endothermic event at 155.1±20 °C, 155.1±15 °C, 155.1±10 °C, or 155.1±5 °C (e.g., at about 155.1 °C), as measured by DSC. In some embodiments, the cry stalline hydrochloride salt is characterized by an endothermic event at 177.9±20 °C, 177.9±15 °C, 177.9±10 °C, or 177.9±5 °C (e.g., at about 177.9 °C), as measured by DSC. In some embodiments, the crystalline hydrochloride salt is characterized by an endothermic event at 281.8±20 °C, 281.8±15 °C, 281.8±10 °C, or 281.8+5 °C (e.g., at about 281.8 °C), as measured by DSC. In some embodiments, the crystalline hydrochloride salt so characterized is Crystalline Compound 1 Form F Hydrochloride Salt.

[0320] In some embodiments, the Crystalline Compound 1 Form F Hydrochloride Salt is characterized by an endothermic event substantially similar to that set forth in FIG. 2B.

[0321] In some embodiments, the crystalline hydrochloride salt is characterized by a weight loss of at least about 6% up to about 130 °C as measured by TGA.

[0322] In some embodiments, the crystalline hydrochloride salt is characterized by a weight loss of about 6.64% up to about 130 °C as measured by TGA.

[0323] In some embodim ents, the cry stalline hydrochloride salt is characterized by a weight loss of about 6.64% up to about 130+40 °C, 130±30 °C, 130±20 °C, 130±15 °C, 130±10 °C, or 130±5 °C (e.g., at43700-02297 (VNTS-031 / 001WO) about 130 °C), as measured by TGA. In some embodiments, the crystalline hydrochloride salt so characterized is Crystalline Compound 1 Form F Hydrochloride Salt.

[0324] In some embodiments, the Crystalline Compound 1 Form F Hydrochloride Salt is characterized by a weight loss as measured by TGA substantially similar to that set forth in FIG. 2B

[0325] In some embodiments, the Crystalline Compound 1 Form F Hydrochloride Salt is in a 1:1 stoichiometric ratio of one chloride counterion to one protonated Compound 1.

[0326] In some embodiments, the crystalline hydrochloride salt is soluble in a solvent. In some embodiments, the solubility of the crystalline hydrochloride salt is measured in water or a physiological buffer. In some embodiments, a physiological buffer is simulated gastric fluid (SGF) for two (2) hours at 37 °C at approximately 25 rpm, followed by dilution with fasted state simulated intestinal fluid (FaSSIF) for one (1) hour or two (2) hours at 37 °C at approximately 25 rpm.

[0327] In some embodiments, the cry stalline hydrochloride salt has a solubility' greater than about 1.8 mg / mL, as measured in SGF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline hydrochloride salt has a solubility greater than about 1.8 mg / mL at a pH of about 1.7, as measured in SGF at two hours at 37 °C at approximately 25 rpm,

[0328] In some embodiments, the cry stalline hydrochloride salt has a solubility of about 0.06 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at one hour at 37 °C at approximately 25 rpm. In some embodiments, the crystalline hydrochloride salt has a solubility of about 0.06 mg / mL at a pH of about 5.8, as measured in a 1:3 mixture of SGF and FaSSIF at one hour at 37 °C at approximately 25 rpm.

[0329] In some embodiments, the crystalline hydrochloride salt has a solubility' of about 0.05 mg / mL, as measured in a 1:3 mixture of SGF and FaSSIF at two hours at 37 °C at approximately 25 rpm. In some embodiments, the crystalline hydrochloride salt has a solubility of about 0.05 mg / mL at a pH of about 5.8, as measured in a 1:3 mixture of SGF and FaSSIF at two hours at 37 °C at approximately 25 rpm.

[0330] In some embodiments, the cry stalline hydrochloride salt converts to Form I Freebase after dilution in a 1:3 mixture of SGF and FaSSIF after 1 hour at 37 °C at approximately 25 rpm.(v) Compositions

[0331] Compositions, including pharmaceutical compositions, comprising a salt of Compound 1 are further contemplated herein. Salts include fumarate salts, hydrochloride salts, phosphate salts, and sulfate salts. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form B Sulfate Salt. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form C Sulfate Salt, In some embodiments, the salt of Compound 1 is Amorphous Compound 1 Sulfate Salt. In some embodiments, the salt of Compound 1 is Cry stalline Compound 1 Form D Phosphate Salt. In some embodiments, tire salt of Compound 1 is Crystalline Compound 1 Form E Fumarate Salt. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form F Hydrochloride Salt.

[0332] In some embodiments, the composition comprises Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the composition comprises Crystalline Compound 1 Form B Sulfate Salt. In some43700-02297 (VNTS-031 / 001WO) embodiments, the composition comprises Crystalline Compound 1 Form C Sulfate Salt. In some embodiments, the composition comprises Amorphous Compound 1 Sulfate Salt. In some embodiments, the composition comprises Crystalline Compound 1 Form D Phosphate Salt. In some embodiments, the composition comprises Cry stalline Compound 1 Form E Fumarate Salt, In some embodiments, the composition comprises Cry stalline Compound 1 Form F Hydrochloride Salt.

[0333] In some embodiments, provided is a composition comprising a mixture of Compound 1 salt forms, as described herein, wherein 75% (w / w%) of the mixture is a sulfate salt or sulfate salt form. It is understood that the mixture may comprise a mixture of salts, such as a mixture of sulfate, phosphate, HC1, and fumarate salts, wherein 75% (w / w%) of the mixture is a sulfate salt. It is also understood that 100% of the salt in the mixture are sulfate salts, but 75% (w / w%) of the mixture is a specific crystalline or amorphous sulfate salt form, as described herein. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0334] As noted herein, Crystalline Compound 1 Fonn B Sulfate Salt and Crystalline Compound 1 Form C Sulfate Salt are metastable forms, but which may be present in lesser amounts in a composition,

[0335] In some embodiments, provided is a composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 5% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Cry stalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0336] In some embodiments, provided is a composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 10% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Cry stalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Crystalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0337] In some embodiments, provided is a composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 15% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt, In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Crystalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0338] In some embodiments, provided is a composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 20% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Cry stalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0339] In some embodiments, provided is a composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 25% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the43700-02297 (VNTS-031 / 001WO) other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Crystalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0340] In some embodiments, the composition is a pharmaceutical composition comprising one or more pharmaceutically acceptable earners,

[0341] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 75% (w / w%) of the mixture of salt forms is a sulfate salt. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0342] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 80% (w / w%) of the mixture of salt forms is a sulfate salt. In some embodiments, the sulfate salt is Cry stalline Compound 1 Form A Sulfate Salt. In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0343] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 85% (w7w%) of the mixture of salt forms is a sulfate salt. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0344] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 90% (w / w%) of the mixture of salt forms is a sulfate salt. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0345] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 95% (w / w%) of the mixture of salt forms is a sulfate salt. In some embodiments, the sulfate salt is Cry stalline Compound I Form A Sulfate Salt. In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0346] In some embodiments, provided is a pharmaceutical composition comprising 100% (w / w%) of Crystalline Compound 1 Form A Sulfate Salt, and one or more pharmaceutically acceptable carriers. In some embodiments, provided is a pharmaceutical composition compri sing 100% (w / w%) of Amorphous Compound 1 Sulfate Salt, and one or more pharmaceutically acceptable carriers.

[0347] As noted herein, Crystalline Compound 1 Form B Sulfate Salt and Cry stalline Compound 1 Form C Sulfate Salt are metastable forms, but which may be present in lesser amounts in a composition, including a pharmaceutical composition.

[0348] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 5% (w / w%) of the mixture of salts43700-02297 (VNTS-031 / 001WO) comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Crystalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0349] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 10% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Cry stalline Compound 1 Form B Sulfate Salt and / or Cry stalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0350] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 15% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Crystalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0351] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 20% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Crystalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0352] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 sulfate salt forms, as described herein, wherein less than 25% (w / w%) of the mixture of salts comprises one or more sulfate salts which are not Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the other sulfate salt is Crystalline Compound 1 Form B Sulfate Salt and / or Crystalline Compound 1 Form C Sulfate Salt and / or Amorphous Compound 1 Sulfate Salt.

[0353] In some embodiments, provided is a composition comprising a mixture of Compound 1 salt forms, as described herein, wherein greater than 75% (w / w%) of the mixture of salts is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt.

[0354] In some embodiments, the composition is a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers,

[0355] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 75% (w / w%) of the mixture of salt forms is a phosphate salt. In some embodiments, the phosphate salt is Cry stalline Compound 1 Form D Phosphate Salt.

[0356] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 80% (w / w%) of the mixture of salt forms is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt.

[0357] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers,43700-02297 (VNTS-031 / 001WO) wherein greater than 85% (w / w%) of the mixture of salt forms is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt.

[0358] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 90% (w / w%) of the mixture of salt forms is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt.

[0359] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 95 % (w / w%) of the mixture of salt forms is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt.

[0360] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, wherein 100% (w / w%) of the mixture is Crystalline Compound 1 Form D Phosphate Salt.

[0361] In some embodiments, provided is a composition comprising a mixture of Compound 1 salt forms, as described herein, wherein greater than 75% (w / w%) of the mixture of salt forms is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt.

[0362] In some embodiments, the composition is a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers.

[0363] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 75% (w / w%) of the mixture of salt forms is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt.

[0364] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 80% (w / w%) of the mixture of salt forms is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt.

[0365] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 85% (w / w%) of the mixture of salt forms is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt.

[0366] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 90% (w / w%) of the mixture of salt forms is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt.

[0367] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 95% (w / w%) of the mixture of salt forms is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt.43700-02297 (VNTS-031 / 001WO)

[0368] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein 100% (w / w%) of the mixture is Crystalline Compound 1 Form E Fumarate Salt.

[0369] In some embodiments, provided is a composition comprising a mixture of Compound 1 salt forms, as described herein, wherein greater than 75% (w / w%) of the mixture of salt forms is a hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0370] In some embodiments, the composition is a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers.

[0371] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 75% (w / w%) of the mixture of salt forms is a hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0372] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 80% (w / w%) of the mixture of salt forms is a hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0373] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 85% (w / w%) of the mixture of salt forms is a hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0374] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 90% (w / w%) of the mixture of salt forms is a hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0375] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, and one or more pharmaceutically acceptable carriers, wherein greater than 95% (w / w%) of the mixture of salt forms is a hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0376] In some embodiments, provided is a pharmaceutical composition comprising a mixture of Compound 1 salt forms, as described herein, wherein 100% (w / w%) of the mixture is Crystalline Compound 1 Form F Hydrochloride Salt,

[0377] Exemplary pharmaceutical acceptable carriers may include diluents, e.g., purified water, triglyceride oils, such as hydrogenated or partially hydrogenated vegetable oil, or mixtures thereof, corn oil, olive oil, sunflower oil, safflower oil, fish oils, such as EPA or DHA, or their esters or triglycerides or mixtures thereof, omega-3 fatty acids or derivatives thereof, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, sodium, saccharin, glucose and / or glycine.

[0378] The pharmaceutical compositions containing a Compound 1 salt form, as described herein, may43700-02297 (VNTS-031 / 001WO) be manufactured in a manner that is generally known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes. Pharmaceutical compositions may be formulated in a conventional maimer using one or more pharmaceutically acceptable carriers comprising excipients and / or auxiliaries that facilitate processing of the Compound 1 salt form into preparations that can be used pharmaceutically. Tire appropriate formulation is dependent upon the route of administration chosen.

[0379] Administration of the composition to the subject can be accomplished via any mode of administration, for example, by oral administration, topical administration, or by injection. Depending on the intended mode of administration, the composition comprising the Compound 1 salt form can be in solid, semi-solid or liquid dosage formulation.

[0380] A Compound 1 salt may be administered alone in the pharmaceutical composition as the sole therapeutic agent, or may be administered in combination with another therapeutic agent. Combination treatment may be achieved by way of co-administration (e.g., the two agents being administered at the same time) or sequential administration (e.g., one agent being administered first, then the other). In the case of co-administration, the Compound 1 salt form may be administered in the same pharmaceutical composition as the other therapeutic agent, or may be administered in a separate pharmaceutical composition. The choice of the other therapeutic agent will depend upon the diagnosis of the attending physicians and their judgment of the condition of the subject and the appropriate treatment protocol.(vi) Methods of Treatment and Prevention

[0381] Compound 1 has been found useful as an inhibitor of NLRP3 activity.

[0382] In some aspects, provided is a method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject a salt of Compound 1, wherein the amount administered corresponds to an amount of Compound 1 freebase equivalent. In some aspects, provided is a method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject salt of Compound 1, or a pharmaceutical composition thereof. Salt forms of Compound 1 include fumarate salts, hydrochloride salts, phosphate salts, and sulfate salts. In some embodiments, the salt of Compound 1 is a sulfate salt. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the salt of Compound 1 is Amorphous Compound 1 Sulfate Salt. In some embodiments, the salt of Compound 1 is a phosphate salt. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form D Phosphate Salt. In some embodiments, the salt of Compound 1 is a fumarate salt. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form E Fumarate Salt. In some embodiments, the salt of Compound 1 is a hydrochloride salt. In some embodiments, the salt of Compound 1 is Crystalline Compound 1 Form F Hydrochloride Salt.

[0383] In some aspects, provided is a method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject an effective amount of a sulfate salt of Compound 1, or a pharmaceutical composition thereof, wherein the effective amount corresponds to the43700-02297 (VNTS-031 / 001WO) amount of Compound 1 freebase equivalent. In some aspects, provided is a method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject a sulfate salt of Compound 1, or a pharmaceutical composition thereof. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0384] In some aspects, provided is a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject an effective amount of a sulfate salt of Compound 1, or a pharmaceutical composition thereof, wherein the effective amount is an amount of Compound 1 freebase equivalent. In some aspects, provided is a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a sulfate salt of Compound 1, or a pharmaceutical composition thereof. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt, In some embodiments, the sulfate salt is Amorphous Compound 1 Sulfate Salt.

[0385] In some aspects, provided is a salt of Compound 1, or a pharmaceutical composition thereof, for use in treating or preventing a disease or disorder. In some aspects, provided is a salt of Compound 1, or a pharmaceutical composition thereof, for use in treating a disease or disorder. In some aspects, provided is a salt of Compound 1, or a pharmaceutical composition thereof, for use in preventing a disease or disorder. In some embodiments, the salt is a sulfate salt. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, sulfate salt is Amorphous Compound 1 Sulfate Salt. In some embodiments, the salt is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt. In some embodiments, the salt is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt. In some embodiments, the salt is a hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0386] In some aspects, provided is the use of a salt of Compound 1 in the manufacture of a medicament for the treatment or prevention of a disease or disorder. In some aspects, provided is the use of a salt of Compound 1 in the manufacture of a medicament for the treatment of a disease or disorder. In some aspects, provided is the use of a salt of Compound 1 in the manufacture of a medicament for the prevention of a disease or disorder. In some embodiments, the salt is a sulfate salt. In some embodiments, the sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, sulfate salt is Amorphous Compound 1 Sulfate Salt. In some embodiments, the salt is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt. In some embodiments, the salt is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt. In some embodiments, the salt is hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0387] In some aspects, provided is the use of a salt of Compound 1 for the treatment or prevention of a disease or disorder. In some aspects, provided is the use of a salt of Compound 1 for the treatment of a disease or disorder. In some aspects, provided is the use of a salt of Compound 1 for the prevention of a disease or disorder. In some embodiments, the salt is a sulfate salt. In some embodiments, the sulfate salt43700-02297 (VNTS-031 / 001WO) is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, sulfate salt is Amorphous Compound 1 Sulfate Salt. In some embodiments, the salt is a phosphate salt. In some embodiments, the phosphate salt is Crystalline Compound 1 Form D Phosphate Salt. In some embodiments, the salt is a fumarate salt. In some embodiments, the fumarate salt is Crystalline Compound 1 Form E Fumarate Salt. In some embodiments, the salt is hydrochloride salt. In some embodiments, the hydrochloride salt is Crystalline Compound 1 Form F Hydrochloride Salt.

[0388] In some embodiments, the disease or disorder is associated with aberrant NLRP3 activity, and the method comprises inhibiting the aberrant NLRP3 activity such that the subject is treated.

[0389] In some embodiments, the disease or disorder is a disease or disorder of the central nervous system (CNS), a disease or disorder of the peripheral nervous system (PNS), a primary neurological disease of the muscles, an inflammatory disorder, an autoimmune disorder, cancer, an infection, a metabolic disease, a cardiovascular disease, a respiratory disease, a kidney disease, a liver disease, an ocular disease, a skin disease, a lymphatic disease, a rheumatic disease, a psychological disease, graft versus host disease, pain (including disorders related to pain management), an NLRP3-related disease in a subject that has been determined to carry a germline or somatic non-silent mutation in NLRP3, or obesity (e.g., obesity related to neuroinflammation).

[0390] In some embodiments, the disease or disorder is a disease or disorder of central nervous system and / or peripheral nervous system (“PNS”), such as dementia, Alzheimer’s disease (“AD”) epilepsy e.g., refractory epilepsy), traumatic brain injury (“TBI”), multiple sclerosis (“MS”), a developmental disturbance, acute disseminated encephalopathy, transverse myelitis, Parkinson’s disease (“PD”), amyotrophic lateral sclerosis (“ALS”), Huntington’s disease (“HD”), or spinal cord injury.

[0391] In some embodiments, the disease or disorder is a primary neurological disease of the muscle, such as a dystrophy or spinal muscular atrophy.

[0392] In some embodiments, the disease or disorder is an inflammatory disorder, such as gout or anemia of inflammation.

[0393] In some embodiments, the disease or disorder is an autoimmune disease, such as ulcerative colitis.

[0394] In some embodiments, the disease or disorder is cancer, such as skin cancer or colon cancer.

[0395] In some embodiments, the disease or disorder is an infection, such as a neuro-infection.

[0396] In some embodiments, the disease or disorder is a metabolic disease, such as diabetes, e.g., type 2 diabetes.

[0397] In some embodiments, the disease or disorder is obesity. In some embodiments, the obesity is related to neuroinflammation, e.g., hypothalamic inflammation and / or gliosis. In some embodiments, the obesity is related to a metabolic disorder.

[0398] In some embodiments, the disease or disorder is a cardiovascular disease, such as stroke, atherosclerosis or atherosclerotic cardiovascular disease (ASCVD).

[0399] In some embodiments, the disease or disorder is a respiratory disease, such as asthma (e.g.. steroid-resistant asthma, severe steroid-resistant asthma) or chronic obstructive pulmonary disease43700-02297 (VNTS-031 / 001WO) (“COPD”).

[0400] In some embodiments, the disease or disorder is a kidney disease, such as acute kidney disease, a chronic kidney disease, or a rare kidney disease.

[0401] In some embodiments, the disease or disorder is a liver disease, such as nonalcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH, also known as MASH or metabolic dysfunction-associated steatohepatitis).

[0402] In some embodiments, the disease or disorder is an ocular disease, such as optic neuritis or macular degeneration.

[0403] In some embodiments, the disease or disorder is a skin disease, such as psoriasis, hidradenitis suppurativa (HS), or atopic dermatitis.

[0404] In some embodiments, the disease or disorder is a lymphatic disease.

[0405] In some embodiments, the disease or disorder is a rheumatic disease, such as osteoarthritis, dermatomyositis. Still’s disease, or juvenile idiopathic arthritis.

[0406] In some embodiments, the disease or disorder is a psychological disease, such as a neuropsychiatric condition, including depression, major depressive disorder, or refractory depression.

[0407] In some embodiments, the disease or disorder is a graft versus host disease.

[0408] In some embodiments, the disease or disorder is pain (including disorders related to pain management), such as headache pain, pain management addiction, osteoarthritis pain, or allodynia.

[0409] In some embodiments, the NLRP3-related disease in a subject that has been determined to carry a germline or somatic non -silent mutation in NLRP3 is cryopyrin-associated autoin flammatory syndrome. In some embodiments, the cryopyrin-associated autoinflammatory syndrome is familial cold autoinflammatory syndrome, Muckle-Wells syndrome, or neonatal onset multisystem inflammatory disease (NOMID).

[0410] In some embodiments, the disease or disorder is dementia, Alzheimer’s disease (‘AD”), epilepsy (e.g., refractory epilepsy), traumatic brain injury (“TBI”), multiple sclerosis (“MS”), developmental disturbances, acute disseminated encephalopathy, transverse myelitis, Parkinson’s disease ( “PD ”), amyotrophic lateral sclerosis (“ALS”), spinal muscular atrophy. Huntington’s disease (“HD”), spinal cord injury’, a dystrophy, a neuro-infection, pain (e.g., headache pain, osteoarthritis pain, or allodynia, pain management addiction), a neuropsychiatric condition (e.g. depression, major depressive disorder, refractory depression), neonatal onset multisystem inflammatory disease (“NOMID”), asthma, osteoarthritis, ulcerative colitis, gout, anemia of inflammation, Still’s disease, chronic obstructive pulmonary disease (“COPD ”), osteoarthritis pain, or hidradenitis suppurativa or obesity (e.g., obesity related to neuroinflammation).(vii) Methods of Preparation

[0411] Salts of Compound 1 may be prepared by any suitable technique known in the art. In some aspects, the present disclosure provides a salt of Compound 1 obtainable by, or obtained by, or directly obtained by a method for preparing as described in the Examples.43700-02297 (VNTS-031 / 001WO)

[0412] For example, in some embodiments, a salt of Compound 1 is prepared by combining Compound 1 freebase and an acid (e.g., sulfuric acid, fumaric acid, phosphoric acid, hydrochloric acid) in a solvent. In some embodiments, Compound 1 freebase, the acid, and the solvent form a slurry. In some embodiments, the solvent used is acetonitrile. In some embodiments, the solvent used is an ethanol / water mixture. In some embodiments, the solvent and acid are provided in a 1:1 molar ratio. In some embodiments, after a period of time (e.g., at least 1 day), the solid obtained is a salt of Compound 1. In some embodiments, after a period of time (e.g.. at least 1 day), the solid obtained is a mixture of salts of Compound 1. In some embodiments, the resultant salt, so obtained, is crystalline. In some embodiments, seed crystals of Crystalline Compound 1 Form A Sulfate Salt are added to the slurry, to provide Crystalline Compound 1 Form A Sulfate Salt. Additional methods of providing crystalline material, beyond slurry crystallization and seed inducing crystallization, include but are not limited to, anti-solvent addition crystallization, solid vapor diffusion, slow evaporation, and slow cooling. In some embodiments, the Compound 1 freebase is Crystalline Compound 1 Form I Freebase.

[0413] In some embodiments, the salt of Compound 1 is a crystalline sulfate salt. In some aspects, the present disclosure provides crystalline sulfate salts of Compound 1 obtainable by, or obtained by, or directly obtained by a method for preparing as described in the Examples. In some embodiments, the crystalline sulfate salt is Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the crystalline sulfate salt is obtainable by, or obtained by, or directly obtained by a method for preparing as described in Example 4. In some embodiments, the crystalline sulfate salt is obtainable by, or obtained by, or directly obtained by a method for preparing as described in Batches 1-7 of Example 4. In some embodiments, the crystalline sulfate salt is obtainable by, or obtained by, or directly obtained by a method for preparing as described in Batches 8-10 of Example 4. In some embodiments, the crystalline sulfate salt is obtainable by, or obtained by, or directly obtained by a method for preparing as described in the large-scale preparation of Example 4.

[0414] In some embodiments, the crystalline sulfate salt has rod-like morphology. In some embodiments, the crystalline sulfate salt has needle-like morphology.

[0415] In some embodiments, the crystalline sulfate salt is rod-like Crystalline Compound 1 Form A Sulfate Salt. In some embodiments, the crystalline sulfate salt is needle-like Crystalline Compound 1 Form A Sulfate Salt.

[0416] In some embodiments, the crystalline sulfate salt is prepared by crystallization in a solution comprising the sulfate salt of Compound 1.

[0417] In some embodiments, the crystalline sulfate salt is prepared by crystallization of the sulfate salt of Compound 1 from a mixture of solvents. In some embodiments, the crystalline sulfate salt is prepared by crystallization of the sulfate salt of Compound 1 from a mixture of polar solvents. In some embodiments, the crystalline sulfate salt is prepared by crystallization of the sulfate salt of Compound 1 from a mixture of a polar aprotic solvent and a polar protic solvent. In some embodiments, the crystalline sulfate salt is prepared by crystallization of the sulfate salt of Compound 1 from a mixture of polar protic solvents.43700-02297 (VNTS-031 / 001WO)

[0418] In some embodiments, the crystalline sulfate salt is prepared by crystallization of the sulfate salt of Compound 1 from a mixture of THF and water. In some embodiments, the mixture of THF and water is 25:1, 24:1, 23:1, 22:1, 21:1, 20:1, 19:1, 18:1, 17:1, 16:1, or 15:1, v / v. In some embodiments, the mixture of THF and water is 19:1, v / v.

[0419] In some embodiments, the crystalline sulfate salt is prepared by crystallization of the sulfate salt of Compound 1 from a mixture of EtOH and water. In some embodiments, the mixture of EtOH and water is 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8: 1, 7:1, 6:1, or 5:1, v / v. In some embodiments, the mixture of EtOH and water is 9: 1, v / v.

[0420] In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at about 0 °C, about 5 °C, about 10 °C, about 15 °C, about 20 °C, about 25 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, or about 80 °C.

[0421] In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at about room temperature. In some embodiments, the crystallization of the sulfate salt of Compormd 1 is performed at about 5 °C. In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at about 60 °C.

[0422] In some embodiments, the solution of the sulfate salt of Compound 1 is cooled to about 5 °C.

[0423] In some embodiments, the solution of the sulfate salt of Compound 1 is further aged at about 60 °C.

[0424] In some embodiments, the solution of the sulfate salt of Compound 1 is prepared by combining a solution of acid and a solution of Compound 1 freebase.

[0425] In some embodiments, the solution of the sulfate salt of Compound 1 is prepared by adding a solution of acid to a solution of Compound 1 freebase.

[0426] In some embodiments, the solution of the sulfate salt of Compound 1 is prepared by combining a solution of sulfuric acid and a solution of Compound 1 freebase.

[0427] In some embodiments, the solution of the sulfate salt of Compound 1 is prepared by adding a solution of sulfuric acid to a solution of Compound 1 freebase.

[0428] In some embodiments, the solution of sulfuric acid is in EtOH.

[0429] In some embodiments, the solution of sulfuric acid has a concen tration of about 0.1 mol / L, about 0.2 mol / L, about 0.3 mol / L, about 0.4 mol / L, about 0.5 mol / L, about 0.6 mol / L, about 0.7 mol / L, about 0.8 mol / L, about 0.9 mol / L, about 1.0 mol / L, about 1.1 mol / L, about 1.2 mol / L, about 1.3 mol / L, about 1.4 mol / L, about 1.5 mol / L, about 1.6 mol / L, about 1.7 mol / L, about 1.8 mol / L, about 1.9 mol / L, or about 2.0 mol / L of sulfuric acid.

[0430] In some embodiments, the solution of sulfuric acid has a concentration of about 1.5 mol / L of sulfuric acid in THF / H2O (19:1, v / v).

[0431] In some embodiments, the solution of sulfuric acid has a concentration of about 0.18 mol / L of sulfuric acid in THF / H₂O (19:1, v / v).

[0432] In some embodiments, the solution of sulfuric acid has a concentration of about 0.87 mol / L of43700-02297 (VNTS-031 / 001WO) sulfuric acid in EtOH.

[0433] In some embodiments, the solution of sulfuric acid is prepared from a mixture of about 0.01, about 0.02, about 0.03, about 0.04, about 0.05, about 0.06, about 0.07, about 0.08, about 0.09, or about 1.0 (v / v) of concentrated sulfuric acid and EtOH.

[0434] In some embodiments, the solution of sulfuric acid is prepared from a mixture of about 0.05 (v / v) of concentrated sulfuric acid and EtOH.

[0435] In some embodiments, the solution of Compound 1 freebase is in a mixture of THF and water.

[0436] In some embodiments, the solution of Compound 1 freebase is in a mixture of EtOH and water.

[0437] In some embodiments, the solution of Compound 1 freebase has a concentration of Compound 1 freebase of about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about 40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 55 mg / mL, about 60 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, or about 100 mg / mL.

[0438] In some embodiments, the solution of Compound 1 freebase has a concentration of about 77 mg / mL in THF / H2O (19: 1, v / v) at about room temperature.

[0439] In some embodiments, the solution of Compound 1 freebase has a concentration of about 55 mg / mL in EtOH / H₂O (9:1, v / v) at about 60 °C.

[0440] In some embodiments, the solution of Compound 1 freebase has a concentration of about 75 mg / mL in EtOH / H2O (9:1, v / v) at about 60 °C.

[0441] In some embodiments, the solution of Compound 1 freebase has an initial temperature of about 0 °C, about 5 °C, about 10 °C, about 15 °C, about 20 °C, about 25 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, or about 80 °C prior to the addition of acid.

[0442] In some embodiments, the solution of Compound 1 freebase has an initial temperature of about room temperature prior to the addition of acid.

[0443] In some embodiments, the solution of Compound 1 freebase has an initial temperature of about 60 °C prior to the addition of acid.

[0444] In some embodiments, the solution of sulfuric acid and the solution of Compound 1 freebase are combined to yield a final molar charge ratio of acid / freebase of about 0.85, about 0.90, about 0.95, about 1.00, about 1.05, about 1.10, about 1.15, or about 1.20.

[0445] In some embodiments, the solution of sulfuric acid and the solution of Compound 1 freebase are combined to yield a final molar charge ratio of acid / freebase of about 0.9 to about 1.1,

[0446] In some embodiments, the solution of sulfuric acid and the solution of Compound 1 freebase are combined to yield a final molar charge ratio of acid / freebase of about 1.0. In some embodiments, the solution of sulfuric acid and the solution of Compound 1 freebase are combined to yield a final molar charge ratio of acid / freebase of about 1.05. In some embodiments, the solution of sulfuric acid and the solution of Compound 1 freebase are combined to yield a final molar charge ratio of acid / freebase of about 1.11.43700-02297 (VNTS-031 / 001WO)

[0447] In some embodiments, the solution of sulfuric acid is added to the solution of Compound 1 freebase over an addition time of about 1 hr, about 2 hrs, about 3 hrs, about 4 hrs, about 5 hrs, about 6 hrs, about 7 hrs, about 8 hrs, about 9 hrs, or about 10 hrs.

[0448] In some embodiments, the addition time of the solution of sulfuric acid to the solution of Compound 1 freebase is between about 1 hr to about 8 hrs.

[0449] In some embodiments, the addition time of the solution of sulfuric acid to the solution of Compound 1 freebase is about 1 hr, about 2 hrs, about 3 hrs, or about 8 hrs.

[0450] In some embodiments, the addition time of tire solution of sulfuric acid to the solution of Compound 1 freebase is about 8 hrs.

[0451] In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 0.5 g, about 1.0 g, about 1.5 g, about 2.0 g, about 2.5 g, about 3.0 g, about 3.5 g, about 4.0 g, about 4.5 g, about 5.0 g, about 5.5 g, about 6.0 g, about 6.5 g, about 7.0 g, about 7,5 g, about 8.0 g, about 8.5 g, about 9.0 g, about 9.5 g, about 10.0 g, or greater than about 10.0 g scale of Compound 1 freebase.

[0452] In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 1.0 g scale of Compound 1 freebase. In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 5.0 g scale of Compound 1 freebase. In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 10 g scale of Compound 1 freebase.

[0453] In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 1.1 g scale of Compound 1 freebase. In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 5.5 g scale of Compound 1 freebase.

[0454] In some embodiments, the crystallization of the sulfate salt of Compound 1 comprises seeding the solution of the sulfate salt of Compound 1 with seed crystals of the sulfate salt of Compound 1.

[0455] In some embodiments, the crystallization of the sulfate salt of Compound 1 does not comprise seeding the solution of the sulfate salt of Compound 1 with seed crystals of the sulfate salt of Compound 1.

[0456] In some embodiments, seed crystals are added to the solution of the sulfate salt of Compound 1 at a seed loading of about 0.5%, about 1%, about 1.5%, about 2.0%, about 2.5%, about 3.0%, about 3.5%, about 4.0%, about 4.5%, or about 5.0%, wherein the seed loading is expressed as a percentage of the weight of the seed crystal compared to the weight of Compound 1 freebase.

[0457] In some embodiments, the seed loading is about 1%.

[0458] In some embodiments, the seed loading is about 2%.

[0459] In some embodiments, the seed crystals are in dried powder form.

[0460] In some embodiments, the seed crystals are in wet-milled suspension form.

[0461] In some embodiments, the seed crystals are Crystalline Compound 1 Form A Sulfate Salt.

[0462] In some embodiments, the seed crystals are prepared as described in Example 4.

[0463] In some embodiments, the seed crystals are added after a portion of the solution of an acid has been added to the solution of Compound 1 freebase.43700-02297 (VNTS-031 / 001WO)

[0464] In some embodiments, the seed crystals are added after a portion of the solution of sulfuric acid has been added to the solution of Compound 1 freebase.

[0465] In any of the above embodiments, in some embodiments, the Compound 1 freebase is Crystalline Compound 1 Form I Freebase,

[0466] In some embodiments, the crystalline sulfate salt has greater than about 98% purity.

[0467] In some embodiments, the crystalline sulfate salt has greater than about 99% purity.

[0468] In some embodiments, the crystalline sulfate salt has greater than 99% purity.

[0469] In some embodiments, the crystalline sulfate salt comprises about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 1%, about 1.5%, or about 2% of impurities.

[0470] In some embodiments, the crystalline sulfate salt comprises about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, or about 1% of impurities.

[0471] In some embodiments, the crystalline sulfate salt comprises about 2,0%, about 2,5%, about 3.0%, about 3.5%, about 4.0%, about 4.5%, about 5.0%, about 5.5%, or about 6.0% water.

[0472] In some embodiments, the crystalline sulfate salt comprises between about 4.0% to about 5.0% water.

[0473] In some embodiments, the crystalline sulfate salt comprises solvent residue at an amount lower than the ICH limit of said residual solvent.

[0474] In some embodiments, the crystalline sulfate salt comprises solvent residue at an amount higher than the ICH limit of said residual solvent.

[0475] In some embodiments, the crystalline sulfate salt comprises solvent residue at the ICH limit of said residual solvent.

[0476] In some embodiments, the crystalline sulfate salt comprises THF residue at an amount lower than the ICH limit of THF residual solvent (i.e., 720 ppm).

[0477] In some embodiments, the crystalline sulfate salt comprises THF residue at an amount higher than the ICH limit of THF residual solvent (i.e., 720 ppm).

[0478] In some embodiments, the crystalline sulfate salt comprises THF residue at the ICH limit of THF residual solvent (i.e., 720 ppm).

[0479] In some embodiments, the crystalline sulfate salt comprises EtOH residue at an amount lower than the ICH limit of EtOH residual solvent (i.e., 5000 ppm).

[0480] In some embodiments, the crystalline sulfate salt comprises EtOH residue at an amount higher than the ICH limit of EtOH residual solvent (i.e., 5000 ppm).

[0481] In some embodiments, the crystalline sulfate salt comprises EtOH residue at the ICH limit of EtOH residual solvent (i.e., 5000 ppm).

[0482] In some embodiments, the crystalline sulfate salt comprises about 500 ppm, about 1000 ppm, about 1500 ppm, about 2000 ppm, about 2500 ppm, about 3000 ppm, about 3500 ppm, about 4000 ppm, about 4500 ppm, or about 5000 ppm of solvent.

[0483] In some embodiments, the crystalline sulfate salt comprises about 500 ppm, about 1000 ppm, about 1500 ppm, about 2000 ppm, about 2500 ppm, about 3000 ppm, about 3500 ppm, about 4000 ppm,43700-02297 (VNTS-031 / 001WO) about 4500 ppm, or about 5000 ppm of THF.

[0484] In some embodiments, the crystalline sulfate salt comprises about 500 ppm, about 1000 ppm, about 1500 ppm, about 2000 ppm, about 2500 ppm, about 3000 ppm, about 3500 ppm, about 4000 ppm, about 4500 ppm, or about 5000 ppm of EtOH.

[0485] In some embodiments, the crystalline sulfate salt comprises about 800 to about 1700 ppm of THF.

[0486] In some embodiments, the crystalline sulfate salt comprises about 2000 to about 3000 ppm of EtOH

[0487] In some embodiments, the crystalline sulfate salt comprises about 2500 ppm of EtOH.

[0488] In some embodiments, the crystalline sulfate salt is prepared at a yield of about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100%.

[0489] In some embodiments, the crystalline sulfate salt is prepared at a yield of about 70% to about 90%.Large Scale Crystallization Methods

[0490] In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 50 g, about 100 g, about 150 g, about 200 g, about 250 g, about 300 g, or greater than about 300 g scale of Compound 1 freebase.

[0491] In some embodiments, the crystallization of the sulfate salt of Compound 1 is performed at an about 180 g scale of Compound 1 freebase.

[0492] In some embodiments, the solution of Compound 1 freebase comprises about 0.5 L, about 1.0 L, about 1.5 L, about 2.0 L, about 2.5 L, about 3.0 L, about 3.5 L, or about 4.0 L of EtOH / H2O (9:1, v / v).

[0493] In some embodiments, the solution of Compound 1 freebase comprises about 2.4 L of EtOH / H2O (9:1, v / v).

[0494] In some embodiments, the solution of sulfuric acid comprises about 15 mL, about 20 mL, about 25 mL, about 30 mL, about 35 mL, or about 40 mL of concentrated sulfuric acid.

[0495] In some embodiments, the solution of sulfuric acid comprises about 31 mL of concentrated sulfone acid.

[0496] In some embodiments, a portion of the solution of sulfuric acid is added to the solution of Compound 1 freebase, prior to the addition of seed crystals.

[0497] In some embodiments, about 50 mL, about 55 mL, about 60 mL, about 65 mL, about 70 mL, about 75 mL, about 80 mL, about 85 mL, about 90 mL, about 95 mL or about 100 mL of the solution of sulfuric acid is added to the solution of Compound 1 freebase, prior to the addition of seed crystals.

[0498] In some embodiments, about 82 mL of the solution of sulfuric acid is added to the solution of Compound 1 freebase, prior to the addition of seed crystals.

[0499] In some embodiments, the portion of the solution of sulfuric acid is added to the solution of Compound 1 freebase over the course of about 0.5 hr, about 1.0 hr, about 1.5 hrs, or about 2.0 hrs.

[0500] In some embodiments, the portion of the solution of sulfuric acid is added to the solution of43700-02297 (VNTS-031 / 001WO) Compound 1 freebase over the course of about 1.0 hr.

[0501] In some embodiments, about 0.5 g, about 1.0 g, about 1.5 g, about 2.0 g, about 2.5 g, about 3.0 g, about 3.5 g, about 4.0 g, about 4.5 g, about 5.0 g, about 5.5 g, about 6.0 g, about 6.5 g, about 7.0 g, about 7.5 g, about 8.0 g, about 8.5 g, about 9.0 g, about 9.5 g, or about 10.0 g of seed crystals are added to the solution of Compound 1 freebase and sulfuric acid.

[0502] In some embodiments, about 4.8 g of seed crystals are added to the solution of Compound 1 freebase and sulfuric acid, and the resulting reaction mixture is stirred at about 60 °C (e.g., for about 2 hrs).

[0503] In any of the above embodiments, in some embodiments, the Compound 1 freebase is Crystalline Compound 1 Form I Freebase.

[0504] In some embodiments, the remaining portion of the solution of sulfuric acid is added after the seed crystals are added,

[0505] In some embodiments, the solution of the sulfate salt of Compound 1 is cooled to about 5 °C overnight.

[0506] In some embodiments, the crystalline sulfate salt is isolated by filtration.

[0507] In some embodiments, the crystalline sulfate salt is isolated by suction filtration.

[0508] In some embodiments, the crystalline sulfate salt is dried under vacuum.

[0509] In some embodiments, the crystalline sulfate salt is dried at about 25 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, or about 80 °C.

[0510] In some embodiments, the crystalline sulfate salt is dried at about 25 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, or about 80 °C under vacuum.

[0511] In some embodiments, the crystalline sulfate salt is dried at about room temperature and / or about 50 °C.

[0512] In some embodiments, the crystalline sulfate salt is dried at about 50 °C under vacuum, and then dried at about room temperature under vacuum.(viii) Additional Embodiments

[0513] Embodiment 1: A sulfate salt of Compound 1:

[0514] Embodiment 2: The sulfate salt of Embodiment 1, wherein the sulfate salt is crystalline.

[0515] Embodiment 3: The sulfate salt of Embodiment 1, wherein the sulfate salt is a monohydrate.

[0516] Embodiment 4: The crystalline sulfate salt of Embodiments 2 or 3, characterized by an XRPD43700-02297 (VNTS-031 / 001WO) pattern comprising a signal at 7.6±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0517] Embodiment 5: The crystalline sulfate salt of any one of Embodiments 2-4, characterized by an XRPD pattern comprising a signal at 9.5±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0518] Embodiment 6: The crystalline sulfate salt of any one of Embodiments 2-5, characterized by an XRPD pattern comprising a signal at 13.9±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0519] Embodiment 7: The crystalline sulfate salt of any one of Embodiments 2-6, characterized by at least one endothermic event between about 178 °C and about 202 °C, inclusive, as measured by DSC.

[0520] Embodiment 8: The crystalline sulfate salt of Embodiment 7, characterized by two endothermic events between about 175 °C and about 185 °C, inclusive, as measured by DSC.

[0521] Embodiment 9: The crystalline sulfate salt of Embodiment 7, characterized by one endothermic event between about 190 °C and about 202 °C, inclusive, as measured by DSC.

[0522] Embodiment 10: The crystalline sulfate salt of any one of Embodiments 2-9, characterized by a weight loss of at least about 3.5% up to about 150 °C, or up to about 180 °C.

[0523] Embodiment 11: The crystalline sulfate salt of any one of Embodiments 2-10, having a solubility greater than about 1.9 mg / mL at a pH of about 1.7, as measured in SGF at two hours at 37 °C at approximately 25 rpm.

[0524] Embodiment 12: The crystalline sulfate salt of any one of Embodiments 2-11, having a solubility in water of greater than about 4 mg / mL at a pH of about 2.1 after 3 hours at 37 °C at approximately 25 rpm.

[0525] Embodiment 13: The crystalline sulfate salt of any one of Embodiments 2-12, having a solubility in FaSSIF of greater than about 4 mg / mL at a pH of about 3.1 after 3 hours at 37 °C at approximately 25 rpm.

[0526] Embodiment 14: The crystalline sulfate salt of any one of Embodiments 2-13, characterized as having at least one of the following:(i) an XRPD pattern which is substantially similar to that as provided in FIG. 4A or FIG. 9 (Example 1 or Example 4 XRPD patterns) and / or(ii) a TGA scan which is substantially similar to that as set forth in FIG. 4B; and / or (iii) a DSC scan which is substantially similar to that as set forth in FIG. 4B; and / or (iv) a PLM image which is substantially similar to that as set forth in FIG. 4D.

[0527] Embodiment 15: The crystalline sulfate salt of any one of Embodiments 2-13, characterized as having as least one of the following:(i) an XRPD pattern which is substantially similar to that as provided in FIG. 9 (Example 4 XRPD pattern); and / or(ii) a TGA scan which is substantially similar to that as set forth in FIG. 4C; and / or (iii) a DSC scan which is substantially similar to that as set forth in FIG. 4C; and / or (iv) a PLM image which is substantially similar to that as set forth in FIG. 4E.

[0528] Embodiment 16: The sulfate salt of Embodiment 1, wherein the salt is amorphous.

[0529] Embodiment 17: The amorphous sulfate salt of Embodiment 16, wherein the XRPD pattern has43700-02297 (VNTS-031 / 001WO) a broad halo between about 12 and about 30 °20, inclusive, using Cu K alpha radiation when measured at 25 °C.

[0530] Embodiment 18: lire amorphous sulfate salt of Embodiment 16, wherein the XRPD pattern is substantially similar to that as set forth in FIG. 7,

[0531] Embodiment 19: The sulfate salt of any one of Embodiments 1-18, wherein the stoichiometric ratio of a sulfate counterion to protonated Compound 1 is 1: 1.

[0532] Embodiment 20: A phosphate salt of Compound 1:

[0533] Embodiment 21: The phosphate salt of Embodiment 20, wherein the salt is crystalline.

[0534] Embodiment 22: The crystalline phosphate salt of Embodiment 21, characterized by an XRPD pattern comprising a signal at 5.1±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C.

[0535] Embodiment 23: The cry stalline phosphate salt of Embodiment 21 or Embodiment 22, characterized by an XRPD pattern comprising a signal at 10.2±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0536] Embodiment 24: The crystalline phosphate salt of any one of Embodiments 21-23, characterized by an XRPD pattern comprising signals at 18.4±0.5 °20, using Cu K alpha radiation when measured at 25 °C.

[0537] Embodiment 25: The crystalline phosphate salt of any one of Embodiments 21-24, characterized by at least one endothermic event between about 160 °C and about 210 °C, inclusive, as measured by DSC.

[0538] Embodiment 26: The crystalline phosphate salt of Embodiment 25, characterized by two endothermic events between about 160 °C and about 210 °C, inclusive, as measured by DSC.

[0539] Embodiment 27: The crystalline phosphate salt of any one of Embodiments 21-26, characterized by a weight loss of at least about 2% up to about 150 °C, as measured by TGA.

[0540] Embodiment 28: The crystalline phosphate salt of Embodiment 21, characterized as having at least one of the following:(i) an XRPD pattern substantially similar to that as set forth in FIG. 3A; and / or(ii) a TGA scan substantially similar to that as set forth in FIG. 3B; and / or(iii) a DSC scan substantially similar to that as set forth in FIG. 3B.

[0541] Embodiment 29: The phosphate salt of any one of Embodiments 20-28, wherein the stoichiometric ratio of a phosphate counterion to protonated Compound 1 is 2: 1.

[0542] Embodiment 30: A fumarate salt of Compound 1:43700-02297 (VNTS-031 / 001WO)

[0543] Embodiment 31: The fumarate salt of Embodiment 30, wherein the salt is crystalline.

[0544] Embodiment 32: The crystalline fumarate salt of Embodiment 31, characterized by an XRPD pattern comprising a signal at 7.1±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C.

[0545] Embodiment 33: The crystalline fumarate salt of Embodiment 31 or Embodiment 32, characterized by an XRPD pattern comprising a signal at 18.5±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0546] Embodiment 34: The crystalline fumarate salt of any one of Embodiments 31-33, characterized by an XRPD pattern comprising a signal at 21.5±0.5 °2θ, using Cu K alpha radiation when measured at 25 °C.

[0547] Embodiment 35: The crystalline fumarate salt of any one of Embodiments 31-34, characterized by at least one endothermic event between about 180 °C and about 186 °C, inclusive, as measured by DSC.

[0548] Embodiment 36: The crystalline fumarate salt of any one of Embodiments 31-35, characterized by a weight loss of at least about 4% up to about 150 °C, as measured by TGA.

[0549] Embodiment 37: The crystalline fumarate salt of Embodiment 31, characterized as having at least one of the following:(i) an XRPD pattern substantially similar to that as set forth in FIG. 1A; and / or(ii) a TGA scan substantially similar to that as set forth in FIG. IB; and / or(iii) a DSC scan substantially similar to that as set forth in FIG. 1B.

[0550] Embodiment 38: The fumarate salt of any one of Embodiments 30-37, wherein the stoichiometric ratio of a fumarate counterion to protonated Compound 1 is 1: 1.

[0551] Embodiment 39: A hydrochloride salt of Compound 1:

[0552] Embodiment 40: The hydrochloride salt of Embodiment 39, w herein the salt is crystalline.

[0553] Embodiment 41: The crystalline hydrochloride salt of Embodiment 40, characterized by an XRPD pattern comprising a signal at 6.9±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0554] Embodiment 42: The crystalline hydrochloride salt of Embodiment 40 or Embodiment 41, characterized by an XRPD pattern comprising a signal at 10.8±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

[0555] Embodiment 43: The crystalline hydrochloride salt of any one of Embodiments 40-42,43700-02297 (VNTS-031 / 001WO) characterized by an XRPD pattern comprising a signal at 10.8±0.5 °20, using Cu K alpha radiation when measured at 25 °C.

[0556] Embodiment 44: The crystalline hydrochloride salt of any one of Embodiments 40-43, characterized by at least one endothermic event between about 275 °C and about 285 °C, inclusive, as measured by DSC.

[0557] Embodiment 45: The crystalline hydrochloride salt of any one of Embodiments 40-44, characterized by a weight loss of at least about 6% up to about 130 °C, as measured by TGA.

[0558] Embodiment 46: The crystalline hydrochloride salt of Embodiment 40, characterized as having at least one of the following:(i) an XRPD pattern substantially similar to that as set forth in FIG. 2A; and / or(ii) a TGA scan substantially similar to that as set forth in FIG. 2B; and / or(iii) a DSC scan substantially similar to that as set forth in FIG. 2B.

[0559] Embodiment 47: The hydrochloride salt of any one of Embodiments 39-46, wherein the stoichiometric ratio of a chloride counterion to protonated Compound 1 is 1: 1.

[0560] Embodiment 48: A composition comprising a mixture of Compound 1 salts, wherein 75% (w / w%) of the mixture of salt forms is a salt of any one of the preceding Embodiments.

[0561] Embodiment 49: The composition of Embodiment 48, wherein 75% (w / w%) of the mixture is a crystalline sulfate salt of any one of Embodiments 2-15.

[0562] Embodiment 50: A pharmaceutical composition comprising a salt of any one of Embodiments 1-47, and one or more pharmaceutically acceptable carriers,

[0563] Embodiment 51: A method of treating or preventing a disease or disorder, the method comprising administering to a subject the salt of any one of Embodiments 1-47, or a composition of any one of Embodiments 48-50.

[0564] Embodiment 52: The method of 51, wherein the disease or disorder is a disease or disorder of the central nervous system (CNS), a disease or disorder of the peripheral nervous system (PNS), a primary neurological disease of the muscles, an inflammatory disorder, an autoimmune disorder, cancer, an infection, a metabolic disease, a cardiovascular disease, a respiratory disease, a kidney disease, a liver disease, an ocular disease, a skin disease, a lymphatic disease, a rheumatic disease, a psychological disease, graft versus host disease, pain (including disorders related to pain management), an NLRP3- related disease in a subject that has been determined to carry a germline or somatic non-silent mutation in NLRP3, or obesity.

[0565] Embodiment 53: A method of preparing the salts of any one of Embodiments 1-47, as described in the specification and / or in the Examples.EXEMPLIFICATION

[0566] In order that this disclosure may be more fully understood, the following Examples are set forth. It should be understood that these examples are for illustrative purposes only and are not to be construed as limiting this disclosure in any manner.43700-02297 (VNTS-031 / 001WO)Analytical MethodsX-Ray Powder Diffraction (XRPD)

[0567] X-ray powder diffraction data in the transmission mode was collected on a Empyrean and X’pert3 X-ray powder diffractometers from Panalytical using Cu Ka radiation (45 kV, 40 mA), divergence slit (1 / 8°), continuous scan mode, with a scan range °20 (degrees 2 -theta) of 3-40, step size of 0.0263 °(20) and scan step time of 46.67 seconds. Sample was spread on the middle of a zero-background Si holder.Thermal Gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC)

[0568] TGA data were collected using a Discovery IGA 5500 / TGA 550 TGA from TA Instruments. TGA parameters: ramp method, open aluminum sample pan, room temperature to 350 °C, 10 °C / minute heating rate, N2 purge gas.

[0569] DSC was performed using a Discovery DSC 2500 / DSC 250 DSC from TA Instruments. DSC parameters: ramp method, crimped aluminum sample pan, 25 °C to 300 °C, 10 °C / minute heating rate, N2 purge gas.High Pressure Liquid Chromatography (HPLC)

[0570] A Waters H-Class Ultra Performance Liquid Chromatography (UPLC) with photodiode array (PDA) detector was utilized. The detailed chromatographic conditions are provided in Table A1, Table A1. HPLC ConditionsHPLC Waters H-Class with PDA detectorColumn Eclipse XBD-phenyl, 3.0 x 150 mm, 3 pmA: 0.1% Trifluoroacetic acid (TFA) in H2OB: 0.05% Trifluoroacetic acid (TFA) in AcetonitrileTime (min) %B0.0 15Mobile phase 8.0 5510.0 9511.0 9511.1 1515.0 15Run time 15.0 minPost time 0.0 minFlow rate 1.0 mL / minInjection volume 4 pLDetector wavelength 262 nmColumn temperature 40 °C43700-02297 (VNTS-031 / 001WO) Table A1. HPLC ConditionsSampler temperature Room temperature (RT)Diluent Acetonitrile / H2O (1:1, v / v)Ion Chromatography (IC)

[0571] A Thermo AQ RFIC was utilized for IC testing. The detailed chromatographic conditions are provided in Table A2.Table A2. IC ConditionsIC Thermo AQ RFICColumn Dionex lonPac ASH HC Analytical (4 * 250 mm) Mobile phase 35 mM KOHInjection volume 25 pLFlow rate 1.0 mL / minCell temperature 35 °CColumn temperature 35 °CCurrent 87 mARun time 12 minGas Chromatography (GC)

[0572] Agilent 7820A GC system with 7697 A headspace was used for solvent residue measurement. The detailed chromatographic conditions are provided in Table A3.Table A3. GC ConditionsGC Agilent 7820A GC SystemColumn DB-624, 30 mx0.32 mm, 1.8 pmColumn flow rate 1.0 mL / minColumn temperature gradient 40 °C for 3 mins, then 20 °C / min to 240 °C for 3mins Run time 21 minPost run time 5.0 minInlet temperature 250 °CSplit ratio 40:1Detector FIDDetector temperature 300 °CH2flow rate 30 mL / minAir flow' rate 400 mL / minMakeup flow 26 mL / minHeadspace Agilent 7697A Headspace Sampler43700-02297 (VNTS-031 / 001WO) Table A3. GC ConditionsOven 120 °CLoop 125 °CTransfer line 130 °CGC cycle time 30 minInjection volume 1000 μLVial equilibration time 10 minPressure equilibration time 1.0 minInjection time 0.5 minKarl Fisher Titration

[0573] A Metrohm 831 KF Coulometer was used for water content test.

[0574] The water content in % w / w in the sample was calculated according to the following equation: Water content of sample (% w / w) = (M / (W -w)) x (100 / 1,000,000), where M = amount of water measured in the sample titration (ug); W = weight of the weighing boat and sample (g); w = weight of empty weighing boat after transferring sample to the KF titration cell (g); (W-w) = weight of material transferred (g); 1,000,000 = factor to convert ug to g; and 100 = factor to convert result to %.Polarized Light Microscopy (PLM)

[0575] PLM images were captured on an Axio Scope Al microscope from Carl Zeiss German.Example 1. Preliminary Evaporative Sait Screen

[0576] An evaporative salt screen was performed using Compound 1 Form I Freebase as the input material. Compound 1 Form I Freebase (see FIG. 10) is described in Example 1 of PCT / US2024 / 046642, filed on September 13, 2024, incorporated herein by reference. Four (4) of the twenty-four (24) salts evaluated in this preliminary salt screen were considered acceptable for further exploration. Preparation and characterization of these four (4) specific salts at 100 mg-scale are described in more detail below.(i) Crystalline Compound 1 Form E Fumarate Salt

[0577] A fumarate salt of Compound 1, also referred to herein as Crystalline Compound 1 Form E Fumarate Salt or Form E Fumarate Salt, was obtained via slurry’ of Compound 1 Form I Freebase and equal molar ratio of fumaric acid in acetonitrile at room temperature as follows: (1) Weighed 101.4 mg freebase and 33.0 mg fumaric acid into a 5-mL glass vial, then added 2.5 m acetonitrile. Magnetically stirred at room temperature for 1 day; (2) Isolated solid by centrifugation; and (3) Dried solid at room temperature under vacuum for approximately 2 hrs,

[0578] The XPRD and TGA / DSC curves of Crystalline Compound 1 Form E Fumarate Salt are provided in FIG. 1A and FIG. 1B. The TGA result showed a weight loss of 4.43% up to 150 °C. DSC result43700-02297 (VNTS-031 / 001WO) showed four endotherms at 57.5, 137.2, 181.8, and 184.8 °C (peak temperature). Purity was confirmed to be 99.45 area%by HPLC. A 1:1 stoichiometric ratio of the two salt components (fumarate counteranion to protonated Compound 1) by confirmed by NMR.(ii) Crystalline Compound 1 Form F Hydrochloride Salt

[0579] A hydrochloride salt of Compound 1, also referred to herein as Crystalline Compound 1 Form F Hydrochloride Salt or Form F Hydrochloride Salt, was obtained via slurry of Compound 1 Form I Freebase and equal (1:1) molar ratio of hydrochloric acid in cyclopentylmethylether (CPME) at room temperature as follows: (1) Added 101.2 mg freebase and 2.5 mL cyclopentylmethylether into a 5-mL glass vial, then added 25 uL HC1 (38% by mass in water). Magnetically stirred at room temperature for 1 day; (2) Added additional 6 pL HC1 (38% by mass in water). Magnetically stirred at room temperature for 1 day; (3) Isolated solid by centrifugation; and (4) Dried solid at room temperature under vacuum for approximately 8 hrs.

[0580] The XPRD and TGA / DSC curves of Crystalline Compound 1 Form F Hydrochloride Salt are provided in FIG. 2A and FIG. 2B. The TGA result showed a weight loss of 6.64% up to 130 °C. DSC result showed four endotherms at 80.2, 155.1, 177.9, and 281.8 °C (peak temperature). Purity was confirmed to be 99.44 area% by HPLC. ion chromatography confirmed a 1: 1 stoichiometric ratio of the two salt components (chloride counteranion to protonated Compound 1).(Hi) Crystalline Compound 1 Form D Phosphate Salt

[0581] A phosphate salt of Compound 1, also referred to herein as Crystalline Compound 1 Form D Phosphate Salt or Form D Phosphate Salt, was obtained via slurry of Compound 1 Form I Freebase and equal (1:1) molar ratio of H3PO4 in 2-methyl tetrahydrofuran (2-MeTHF) at room temperature as follows: (1) Added 99.8 mg freebase and 2.5 mL 2-MeTHF into a 5-mL glass vial, then added 20 μL H3PO4 (85% by mass in water). Magnetically stirred at room temperature for 1 day; (2) Added additional 10 μL H3PO4 (85% by mass in water). Magnetically stirred at room temperature for 1 day; (3) Added additional 12 μL H3PO4 (85% by mass in water). Magnetically stirred at room temperature for approximately 8 hours; (4) Isolated solid by centrifugation; and (5) Dried solid at room temperature under vacuum for 1 day.

[0582] The XPRD and TGA / DSC curves of Crystalline Compound 1 Form D Phosphate Salt are provided in FIG. 3A and FIG. 3B. The TGA result showed a weight loss of 2.57% up to 150 °C. DSC result showed two endotherms at 166.0 and 200.0 °C (peak temperature). Purity was confirmed to be 99.43 area% by HPLC. Ion chromatography confirmed a 2:1 stoichiometric ratio of the two salt components (phosphate counteranion to protonated Compound 1).(iv) Crystalline Compound 1 Form A Sulfate Salt

[0583] A sulfate salt of Compound 1, also referred to herein as Cry stalline Compound 1 Form A Sulfate Salt or Form A Sulfate Salt, was obtained via slurry' of Compound 1 Form I Freebase and equal (1:1) molar ratio of H2SO4 in acetonitrile at room temperature as follows: (1) Added 101.2 mg freebase and 2.543700-02297 (VNTS-031 / 001WO) mL acetonitrile into a 5-mL glass vial, then added 72 μL H2SO4. Magnetically stirred at room temperature for 1 day; (2) Isolated solid by centrifugation; and (3) Dried solid at room temperature under vacuum for 1 day. This procedure is referred to herein as the initial small-scale procedure.

[0584] A 10g scale up procedure was performed as follows:(i) Part 1 (1g seed preparation)'. (1) Added 1.0 g Compound 1 Form I Freebase and 25 mL acetonitrile into a 60-mL glass vial. Then added 0.72 mL H2SO4 (4 M). Magnetically stirred at room temperature for 1 day; (2) Isolated the suspension by filtration. Dried solid at room temperature under vacuum for 3 days. XRPD indicated the crystalline Form A Sulfate Salt from Part I (1g seed preparation) was consistent with crystalline material prepared from the initial small-scale procedure.(ii) Part 2 (10g scale up): (1) Added 9.03 g of Compound 1 Form I Freebase and 225 mL of acetonitrile into a 250-mL glass vial. Then added 500.7 mg of the dried solid from Part 1 as seeds; (2) Added 6.48 mL H2SO4 (4 M) dropwise into the mixture. Magnetically stirred at room temperature for 1 day; (3) Added additional 0.3 mL H2SO4 (4 M) into the suspension. Continued to stir at room temperature for 1 day; (4) Isolated the suspension by filtration. Dried solid at room temperature under vacuum for 1 day. XRPD indicated the crystalline Form A Sulfate Salt from Part 2 (10g scale up) was consistent with crystalline material prepared from the initial small-scale procedure.

[0585] The XPRD and TGA / DSC curves of the Crystalline Compound 1 Form A Sulfate Salt from the initial small-scale procedure are provided in FIG. 4A and FIG. 4B. TGA result showed a weight loss of 4.33% up to 150 °C. DSC result showed two endotherms at 178.3 and 182.3 °C (peak temperature). Purity was confirmed to be 99.46 area% by HPLC. Ion chromatography confirmed a 1: 1 stoichiometric ratio of the two salt components (sulfate counteranion to protonated Compound I). PLM image (FIG. 4D) indicates the crystalline sample provided from this preparation method comprised irregular particles,

[0586] A summary of the preliminary' characterization of the salts studied is provided in Table Bl. Table Bl. Preliminary Characterization of Salts StudiedTGA Weight DSC Endotherm Stoichiometry Purity SaltLoss (%) (°C, peak) (acid / base) (Area%)57.5, 137.2, 181.8,Form E Fumarate Salt 4.43 (150 °C) 1.0 99.45184.880.2. 155.1, 177.9,Form F Hydrochloride Salt 6.64 (130 °C) 1.3 99.44281.8Form D Phosphate Salt 2.57 (150 °C) 166.0, 200.0 2.3 99.43 Form A Sulfate Salt 4.33 (150 °C) 178.3, 182.3 1.1 99.46Example 2. Solubility Evaluation(i) 24-hour Solubility Assessment of Form I Freebase after 24 hours

[0587] The 24-hour solubility of Compound 1 Form I Freebase was assessed in fasted state simulated gastric fluid (FaSSGF, pH 1.6), fasted state simulated intestinal fluid (FaSSIF, pH 6.5), and fed state43700-02297 (VNTS-031 / 001WO) simulated intestinal fluid (FeSSIF, pH 5.0).

[0588] The detailed procedure was performed as follows: approximately 5 mg of Form I Freebase was weighed into three separate 1.5 mL vials. In each vial, 1 mL of the respective media (preheated at 37 ± 0.5 °C) was added and allowed to stir at 400 rpm while maintaining the temperature at 37 ± 0.5 °C, After 24 hours, the slurry was transferred into an Eppendorf fitted with an inline polytetrafluoroethylene (PTFE) filter of 0.2 pm pore size. The samples were centrifuged at 37 ± 0.5 °C at 13000 rpm for 10 minutes before the filtrate was diluted with the diluent (50% v / v water in acetonitrile) and analysed by HPLC.

[0589] As shown in Table B2, Compound 1 Form I Freebase was found to be 35-fold less soluble in simulated intestinal fluid media than simulated gastric fluid media after 24 hours.Table B2. Form I Freebase Solubility in MediaMedia Solubility (mg / mL) FaSSGF (pH 1.6) >5FaSSIF (pH 6.5) 0.14FeSSIF (pH 5.0) 0.15( ii) Salt Form SGF to FaSSIF Dilution Experiments

[0590] In order to determine the dissolution profile of the salts in gastric fluid and whether the salt will precipitate upon entry into the intestinal tract, the solubility of each salt was first measured in simulated gastric fluid (SGF, pH 1.6) for 2 hours and then diluted with fasted state simulated intestinal fluid (FaSSIF, pH 6.5), where the final volume ratio of SGF / FaSSIF was 1:3. The salts were prepared as described in Example 1, with Form A Sulfate Salt prepared as in Example 1, 10g scale up procedure.

[0591] The detailed procedure was performed as follows: (1) Weighed approximately 5 mg of the salt prepared as described in Example 1 into a glass vial and add 2 mL SGF. Rolled using a Kylin-Bell Lab Instruments Rotational Incubator QB-128 at 37 °C at approximately 25 rpm for 2 hours; (2) A 1 mL sample was taken and centrifuged at 12000 rpm for 3 minutes at 37 °C, then filtered through a 0.22 μm polytetrafluoroethylene (PTFE) membrane. The pH and concentration of the filtrate was then analyzed; (3) Added 3 mL FaSSIF into the remaining solution and continued to roll at 37 °C at approximately 25 rpm; and (4) Another 1 mL sample was taken at 1 and 2 hours. At each time-point, the sample was centrifuged at 12000 rpm for 3 minutes at 37 °C, then filtered through a 0.22 μm polytetrafluoroethylene (PTFE) membrane, and the pH and concentration of the filtrate were analyzed. Precipitated solids were analyzed by XRPD.

[0592] The results are summarized in Table B3. All the salts dissolved completely in SGF after 2 hours. After dilution into FaSSIF, at the 1 -hour time point, the solubility had decreased for all salts, with solid forming, which was confirmed by XRPD to be Compound 1 Form I Freebase. See FIG. 10 for the XRPD of Compound 1 Form I Freebase. At the 2 -hour time point, XRPD reconfirmed the solid formed was Compound 1 Form I Freebase.43700-02297 (VNTS-031 / 001WO) Table B3. Salt Form Dilution Experiments in SGF to FaSSIF (Stomach to Intestine Simulation)2 Hours (SGF) 1 Hour (SGF+FaSSIF) 2 Hours (SGF+FaSSIF) Salt * Solubility * Solubility SolubilitypH XRPD pH XRPD XRPD (mg / mL) (mg / mL) (mg / mL) pHForm EFumarate >1.90 1.9 0.056 5.5 0.051 5.5SaltForm FHydro>1.84 1.7 0.056 5.8 0.049 5.8 chloride Form I Form I NASalt Freebase Freebase Form DPhosphate >1.62 1.8 0.057 5.6 0.050 5.6SaltForm ASulfate >1.93 1.7 0.059 5.6 0.051 5.5SaltNA: Not applicable because no solid formation observed* Solubility calculated from the amount of freebase equivalent as measured by an HLPC standard curve.(iii) Salt Form Kinetic Solubility Experiments in Water and FaSSIF

[0593] Kinetic solubility is a measure of the rate of dissolution into a biorelevant system.

[0594] The kinetic solubility of Form E Fumarate Salt (prepared as in Example 1) and Form A Sulfate Salt (prepared as in Example 1, 10g scale up procedure), were measured in water (unbuffered) and fasted state simulated intestinal fluid (FaSSIF, pH 6.5) at 37 °C at both 3 hours and 24 hours.

[0595] Ihe detailed procedure was performed as follow s: (1) Weighed approximately 10 mg of the salt into a glass vial, and added 2 mL H2O or FaSSIF, wherein the loading concentration was approximately 5 mg freebase equivalent per mL; (2) Rolled using a Kylin-Bell Lab Instruments Rotational Incubator QB-128 at 37 °C at approximately 25 rpm, and then sampled at 3-hour and 24-hour timepoint; and (3) At each time-point, a 1 mL sample was taken, centrifuged at 12000 rpm for 3 minutes at 37 °C, then filtered through a 0.22 μm polytetrafluoroethylene (PTFE) membrane, and the pH and concentration of the filtrate were analyzed. Precipitated solids were analyzed by XRPD.

[0596] The results are summarized in Table B4. In both water and FaSSIF at the 3-hour and 24-hour timepoints, the Form A Sulfate Salt show ed higher solubility than Form E Fumarate Salt, i.e., a >4-fold (in w’ater) higher solubility and a >13-fold (in FaSSIF) higher solubility’ than the Form E Fumarate Salt at both the 3-hour and 24-hour timepoints. Furthermore, unlike Form E Fumarate Salt, in which most of the solid precipitated from both water and FaSSIF as the Compound 1 Form I Freebase (as confirmed by XRPD) measured at the 3- and 24-hour timepoints, Form A Sulfate Salt remained in solution, with little to no solid formation after 3 hours in water and FaSSIF, little to no solid formation after 24 hours in water, and solid precipitation to Compound 1 Form I Freebase (as confirmed by XRPD) in FaSSIF as43700-02297 (VNTS-031 / 001WO) measured at the 24-hour timepoint. Form A Sulfate Salt was also more soluble than Form 1 Freebase in simulated intestinal fluid (comparing 24-hour FaSSIF data for Form I Freebase and Form A Sulfate Salt, provided in Table B2 and Table B4). Thus, Form A Sulfate Salt was carried forward for further evaluation,Table B4. Fumarate and Sulfate Salt Kinetic Solubility Comparison in Water and FaSSIF3 Hours 24 HoursSalt Media *Solubility * SolubilitypH XRPD pH XRPD (mg / mL) (mg / mL)H2O 1.0 3.0 1.0 3.0Form E Form I Form I Fumarate Salt Freebase Freebase FaSSIF 0.31 3.6 0.29 3.6H2O >4.6 2.1 >4.6 2.1 NA Form ANASulfate SaltForm I FaSSIF >4.2 3.1 3.8 3.0FreebaseNA: Not applicable because little to no solid formation observed* Solubility calculated from the amount of freebase equivalent as measured by an HLPC standard curve.(iv) Solubility in Various Test Solvents at Room Temperature

[0597] The solubility of Crystalline Compound 1 Form A Sulfate Salt (material from Example 1, 10g procedure) was measured in different solvents at room temperature. For each experiment, around two (2) mg of sample was added into a 3-mL glass vial. Corresponding solvents were then added stepwise (50 / 50 / 200 / 700 / 1000 pL) into the vials till the solids were dissolved visually or a total volume of 2 mL was reached. Solubility results (S) listed in Table B5 was used to guide the Example 3 polymorph screening design.Table B5. Approximate Solubility of Form A Sulfate SaltSolvent Solubility (mg / mL) Solvent Solubility (S, mg / mL)CyclopentylmethylMethanol (MeOH) S>36.0 S<1.0ether (CPME)Ethanol (EtOH) 2.1< S<7.0 1, 4-Dioxane S<0.9 Isopropanol (IP A)1S< I.0 Anisole S<0.9 Acetone S<1.0 Acetonitrile S<0.9 Methyl isobutyl ketone DichloromethaneS<1.1 S< I. O (MIBK) (DCM)Ethyl acetate (EtOAc) S<1.0 CHCh S<1.1 Isopropyl acetate (IP Ac) S<0.9 n-Heptane S<1.0 Methyl tert-butyl etherS<1.0 Toluene S< I. O (MTBE)DimethylsulfoxideTetrahydrofuran (THF) S<0.9 S>36.0(DMSO)43700-02297 (VNTS-031 / 001WO) Table B5. Approximate Solubility of Form A Sulfate SaltSolvent Solubility (mg / mL) Solvent Solubility (S, mg / mL) 2-MeTHF S<1.0 H2O 6.7< S<20.01Dissolved at 50 °C.Example 3. Polymorph Screen of Form A Sulfate Salt

[0598] Using Form A Sulfate Salt as described in Example 1 (10g scale-up procedure) as the input material, polymorph screening experiments were performed using a variety of methods, as described below. The solids obtained from the polymorph screening were characterized by XRPD, and from this the Amorphous form and at least two additional crystalline forms, referred to herein as Crystalline Compound 1 Form B Sulfate Salt and Crystalline Compound 1 Form C Sulfate Salt, were identified. Both Form B Sulfate Salt and Form C Sulfate Salt are considered metastable forms, with Form C comprising a mixture of Form B and at least one additional metastable form, each converting to Form A Sulfate Salt upon drying, lire XRPD patterns of Crystalline Compound 1 Form B Sulfate Salt, Crystalline Compound 1 Form C Sulfate Salt, and the Amorphous Sulfate Salt are respectively provided in FIGS. 5, 6, and 7. The XRPD overlay of Crystalline Compound 1 Form A, Form B, and Form C Sulfate Salts is provided in FIG. 8.( i) Anti-Solvent Addition

[0599] A total of twelve (12) anti -solvent addition experiments were carried out. For each experimen t, about 20 mg of Form A Sulfate Salt was weighed into a 20-mL glass vial, follow ed by the addition of 0.1-1.0 mL of the corresponding test solvent to obtain a test solution. If the salt was not completely dissolved in the test solvent, the suspension was filtered through a 0.45 pm polytetrafluoroethylene (PTFE) membrane into a new vial to obtain the test solution. The test solution was then magnetically stirred at 1000 rpm, followed by addition of a specified anti-solvent dropwise until a precipitate appeared, or the total amount of anti-solvent reached 5.0 mL. All solids obtained from this method were isolated and characterized by XRPD,

[0600] Tire results of this method, provided in Table B6, show nine (9) of the twelve (12) anti-solvent addition experiments resulted in re-formation of Form A Sulfate Salt. Form C Sulfate Salt and the Amorphous Sulfate Salt were also obtained, with Form C Sulfate Salt converting to Form A Sulfate Salt after drying at room temperature for five (5) days.Table B6. Summary of Anti-solvent Addition ExperimentsTest Solution Anti-solvent ResultMethyl isobutyl ketone (MIBK) Form A Sulfate Salt Methanol Ethyl acetate (EtOAc) Form A Sulfate Salt(MeOH) Dichloromethane (DCM) Form A Sulfate Salt Anisole Form A Sulfate Salt43700-02297 (VNTS-031 / 001WO) Table B6. Summary of Anti-solvent Addition ExperimentsTest Solution Anti-solvent ResultMethy l tert-butyl ether (MTBE) Amorphous Sulfate Salt Isopropanol (IPA) Form A Sulfate Salt12 -methyl tetrahydrofuran (2-MeTHF) Form A Sulfate Salt2DimethylsulfoxideToluene Form C Sulfate Salt (DMSO)4Acetonitrile Form A Sulfate Salt Isopropyl acetate (IPAc) Amorphous Sulfate Salt3Acetone Form A Sulfate Salt1H2OAcetonitrile Form A Sulfate Salt11Clear solution was obtained after anti-solvent addition and slurry at 5 °C and -20 °C. Solid was obtained after evaporation at room temperature.2Oil was obtained after anti-solvent addition. Solid was obtained after slurry with temperature cycling at 5 °C to 50 °C.3Oil was obtained after anti-solvent addition. Clear solution was obtained after slurry with temperature cycling between 5 °C and 50 °C and slurry at -20 °C. Solid was obtained after evaporation at room temperature,4After drying at room temperature for five (5) days, Form C Sulfate Salt converted to Form A Sulfate Salt.(ii) Solid Vapor Diffusion

[0601] Solid vapor diffusion experiments were conducted using thirteen (13) different test solvents. For each experiment, approximately 20 mg of Form A Sulfate Salt was weighed into a 3-mL vial. A 20-mL vial with approximately 3 mL of the test solvent was prepared. The 3-mL vial w as placed in the larger vial, and the larger vial was sealed with a cap and kept at room temperature to allow the solvent vapor to interact with the solid sample. After seven (7) days, the solids in the 3-mL vial were characterized by XRPD. The results, as shown in Table B7, demonstrate Form A Sulfate Salt was obtained for all solvents tested.Table B7. Summary of Solid Vapor Diffusion ExperimentsTest Solvent ResultH2O Form A Sulfate Salt Dichloromethane (DCM) Form A Sulfate SaltEthanol (EtOH) Form A Sulfate Salt Acetonitrile Form A Sulfate Salt Tetrahydrofuran (THF) Form A Sulfate SaltToluene Form A Sulfate Salt Dimethylsulfoxide (DMSO) Form A Sulfate Salt Isopropanol (IP A) Form A Sulfate Salt Ethyl acetate (EtOAc) Form A Sulfate Salt43700-02297 (VNTS-031 / 001WO) Table B7. Summary of Solid Vapor Diffusion ExperimentsTest Solvent ResultChloroform (CHCl3) Form A Sulfate Salt Methanol (MeOH) Form A Sulfate Salt + additional peaks11,4-Dioxane Form A Sulfate Salt Methyl tert-butyl ether (MTBE) Form A Sulfate Salt1After drying at room temperature for four (4) days, the additional peaks disappeared.(Hi) Slurry at Room Temperature

[0602] A total of twenty -two (22) slurry conversion experiments were conducted at room temperature in different solvent systems. For each experiment, approximately 20 mg of Form A Sulfate Salt was suspended in 0.5 mL of a test solvent system in a glass vial, and the suspension was magnetically stirred at approximately 1000 rpm at room temperature for seven (7) days. The suspended solids were characterized by XRPD. The results, as shown in Table B8, demonstrate only Form A Sulfate Salt was obtained for all solvent systems tested.Table B8. Summary of Slurry Conversion Experiments at Room TemperatureSolvent System (v / v) ResultEthanol (EtOH) Form A Sulfate Salt Acetone Form A Sulfate Salt Ethyl acetate (EtOAc) Form A Sulfate Salt Tetrahydrofuran (THF) Form A Sulfate Salt1,4-Dioxane Form A Sulfate Salt Acetonitrile Form A Sulfate Salt Dichloromethane (DCM) Form A Sulfate Salt Methanol / Isopropyl acetate (1:4) Form A Sulfate Salt Isopropanol / 2 -Methyl tetrahydrofuran (1:1) Form A Sulfate Salt Methyl isobutyl ketone / Anisole (1:1) Form A Sulfate Salt Ethyl Acetate / 1,4-Dioxane (1:1) Form A Sulfate Salt Ethanol / m ethyl tert-butyl ether (1: 1) Form A Sulfate Salt Tetrahydrofuran / water (19:1) Form A Sulfate Salt Methanol / Acetonitrile (1:4) Form A Sulfate Salt Acetone / Dichloromethane (1:1) Form A Sulfate Salt Isopropanol / cyclopentyl methyl ether (1:1) Form A Sulfate Salt Dimethylsulfoxide / methyl tert-butyl ether (1:9) Form A Sulfate Salt43700-02297 (VNTS-031 / 001WO) Table B8. Summary of Slurry Conversion Experiments at Room TemperatureSolvent System (v / v) Result Dimethylacetamide / Toluene (1:9) Form A Sulfate Salt Acetonitrile / H2O (990:10) Form A Sulfate Salt Acetonitrile / H2O (978:22) Form A Sulfate Salt Acetonitrile / H2O (960:40) Form A Sulfate Salt Acetonitrile / H2O (926:74) Form A Sulfate Salt(iv) Slurry with Temperature Cycling (5 °C to 50 °C)

[0603] A total of twelve (12) temperature cycling experiments were conducted at 5 °C to 50 °C in different solvent systems. For each experiment, about 20 mg of Form A Sulfate Salt was suspended in 0.5 mL test solvent in a glass vial. The suspension was then placed into a biochemical incubator of 50 °C for cyclic temperature rising and cooling experiment, procedure as follows: (1) maintained a constant temperature for two (2) hours at 50 °C, (2) dropped from 50 °C to 5 °C at a rate of 0,1 °C / min, (3) maintained a constant temperature for two (2) hours at 5 °C, (4) heated up to 50 °C over 0.5 hours, (5) repeated steps 1-4 for a total of three (3) cycles, and (6) dropped from 50 °C to 5 °C at a rate of 0.1 °C / min, and maintained a constant temperature at 5 °C. After temperature cycling, the solids were characterized by XRPD. The results, as shown in Table B9, demonstrate Form B Sulfate Salt was obtained from one experiment (which formed Form A Sulfate Salt upon drying), with Form A Sulfate Salt being obtained for the remaining solvent systems tested.Table B9. Summary of Temperature Cycling ExperimentsTest Solvent (v / v) Resultn-Butanol Form A Sulfate Salt Methyl ethyl ketone (MEK) Form A Sulfate Salt Methyl acetate Form A Sulfate Salt Anisole Form A Sulfate Salt Methyl tert-butyl ether (MTBE) Form A Sulfate Salt2 -Methyl Tetrahydrofuran / Acetonitrile (1:1) Form A Sulfate Salt Methanol / MTBE (1:4) Form A Sulfate Salt Tetrahydrofuran / lsopropyl acetate (1:1) Form A Sulfate Salt Dimethylsulfoxide / m-Xylene (1:9) Form B Sulfate Salt1Acetone / H2O (19:1) Form A Sulfate Salt Ethanol / n-Heptane (1:1) Form A Sulfate Salt Isopropanol / Chloroform (1:1) Form A Sulfate Salt1After drying at room temperature under vacuum for approximately 7 hours, peaks of Form A Sulfate Salt43700-02297 (VNTS-031 / 001WO) were observed along with extra peaks.(v) Slow Evaporation

[0604] Slow evaporation experiments were performed under three (3) conditions. For each experiment, approximately 20 mg of Form A Sulfate Salt was weighed into a glass vial. Corresponding solvent (1 mL) was added and the samples were filtered using a 0.45 pm polytetrafluoroethylene (PTFE) membrane into a new glass vial to obtain clear solution. The vial w'as covered with Parafilm with four (4) pinholes to allow the solvent to evaporate slowly at room temperature to induce precipitation. The isolated solids were characterized by XRPD. The results, as shown in Table BIO, demonstrate Form A Sulfate Salt was obtained for all three solvent systems tested.Table B10. Summary of Slow Evaporation ExperimentsTest Solvent (v / v) ResultMethanol (MeOH) Form A Sulfate Salt Ethanol (EtOH) Form A Sulfate Salt MeOH / Acetonitrile (1:1) Form A Sulfate Salt(vi) Slow Cooling

[0605] Slow cooling experiments were performed under three (3) conditions. For each experiment, approximately 20 mg of Form A Sulfate Salt was suspended in 0,6-1.0 mL of test solvent in a glass vial at room temperature. Tire suspension was transferred to slurry' at 50 °C on a magnetic stir plate. The sample was equilibrated at 50 °C for two (2) hrs and filtered by a 0.45 pm polytetrafluoroethylene (PTFE) membrane. Hie filtrate was then slowly cooled down from 50 °C to 5 °C at a rate of 0.1 °C / min. A clear solution was obtained for each experiment after cooling to 5 °C and placing at -20 °C for three (3) days. After evaporating at room temperature, a solid was obtained. The results, as shown in Table BU, demonstrate Form A Sulfate Salt was produced from all three solvent sy stems tested, as confirmed by XRPD.Table Bll. Summary of Slow Cooling ExperimentsTest Solvent (v / v) Result Ethanol (EtOH) Form A Sulfate Salt Isopropanol (IP A) Form A Sulfate Salt Methanol (MeOH) / Acetone (1:1) Form A Sulfate Salt + additional peaksExample 4. Large-Scale Preparation of Form A Sulfate Salt and Characterization

[0606] A total of seven crystallization experiments were carried out for parameter optimization from tetrahydrofuran (THF) in water and three crystallization experiments from ethanol (EtOH) in water. The characterization of the obtained solids from Batches 1-7 (THF / FLO) and Batches 8-10 (EtOH / H₂O) are summarized in Table B12 and Table B13.43700-02297 (VNTS-031 / 001WO)

[0607] The 5 g procedure forthe seeds used in Batches 2-10 was performed as follows: (1) weighed 5.02 g Compound 1 Form I Freebase into a 150 mL glass vial. Added 125 mL acetonitrile. Magnetically stirred at room temperature to obtain suspension; (2) Added 250.1 mg Form A Sulfate Salt (10 g procedure from Example 1) as seed into the suspension; (3) Added 3.75 mL H2SO4 aqueous solution (4 M) dropwise into the suspension. Magnetically stirred at room temperature for 2 days. Isolated the suspension by suction filtration. Dried solid at room temperature under vacuum for -3 days. The XRPD of cry stalline Form A Sulfate Salt was found consistent with initial small-scale and 10g procedures of Example 1.(i) Crystallization experiments from THF / H2O

[0608] The cry stallization was first performed on 1 g scale via addition of acid solution to Compound 1 Form I Freebase solution at room temperature (Batch 1), with no seed addition. Tire initial concentration of Compound 1 Form I Freebase solution was set as -77 mg / mL in tetrahydrofuran (THF) / H2O (19: 1, v / v) at room temperature. The concentration of acid solution was 1.5 mol / L in THF / H2O (19: 1, v / v). The final molar charge ratio of acid / Compound 1 Form I Freebase was 1.05 (the volume ratio of freebase solution / acid solution was 13:2). The addition time of acid solution was set as 1 hour, XRPD showed that Form A Sulfate Salt was obtained with the yield calculated to be 90.0%. PLM image showed that it -was composed of needle-like particles and fine particles. Tire THF residue was tested by GC and the content was determined to be 1169.6 ppm, higher than the ICH limit of THF residual solvent (720 ppm, according to the International Counsel for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines).

[0609] To reduce tire solvent residue, parameter optimization was conducted in six batches on 1 g scale:a. Batch 2: Seed loading: -1%. XRPD and PLM results showed that the obtained Form A Sulfate Salt was composed of needle-like crystals. GC test showed that the content of residual THF was 1137.6 ppm, higher than the ICH limit of THF residual solvent. b. Batches 3, 4, and 6: the addition time of acid solution w as increased from 1 hour to 2-8 hours. XRPD results showed that the obtained samples were Form A Sulfate Salt. GC test showed that the content of residual THF was around 852-1209 ppm, higher than the ICH limit of THF residual solvent. PLM images showed that all the samples 'ere composed of needle-like or rod-like crystals with increased crystal size.c. Batch 5: the seed ty^pe was optimized from dried pow der to wet-milled suspension.XRPD and PLM results showed that the obtained Form A Sulfate Salt was composed of needle-like or rod-like crystals. GC test showed that the content of residual THF 'as 1699.9 ppm, higher than the ICH limit of THF residual solvent.d. Batch 7: the concentration of acid solution w as optimized from 1.5 mol / L to 0.18 mol / L (the volume ratio of freebase solution / acid solution was 13:17). XRPD and PLM results showed that the obtained Form A Sulfate Salt w as composed of needle-like or rod-like crystals. GC result showed the content of residual THF was 790.6 ppm, higher than the43700-02297 (VNTS-031 / 001WO) ICH limit of THF residual solvent.(ii) Crystallization experiments from EtOH / H₂O

[0610] Since the content of residual THF was higher than the ICH limit of THF residual solvent in Batches 1-7, the process solvent -was adjusted to EtOH / H₂O (9:1, v / v) for additional crystallization study. The ICH limit of EtOH residual solvent is 5000 ppm, according to ICH guidelines.a. Batch 8: The crystallization was first performed on 1 g scale via addition of acid solution to freebase solution. The initial concentration of freebase solution -was set as -55 mg / mL in EtOH / H₂O (9:1, v / v) at 60 °C. The concentration of acid solution was 0.874 mol / L in EtOH. The final molar charge ratio of acid / freebase was ~ I.11 (the volume ratio of freebase solution / acid solution was 5:1). lire seed loading was ~1% and the addition time of acid solution was set as 8 hours. To improve the yield, the system was cooled to 5 °C in 110 min after addition of acid solution and aging at 60 °C for 2 hours. XRPD and PLM results showed that rod-like Form A Sulfate Salt was obtained with the yield calculated to be 76.0%. Hie EtOH residue was tested to be 2702.8 ppm by GC, lower than the ICH limit of EtOH residual solvent.b. Batch 9: Tire crystallization was then performed on 5.5 g scale using the same parameters as Batch 8. XRPD and PLM results showed that rod-like Form A Sulfate Salt was obtained with the yield calculated to be 77.6%. GC test showed that the content of residual EtOH was 2452.5 ppm, lower than the ICH limit of EtOH residual solvent, c. Batch 10: To improve the yield, the initial temperature was set as 60 °C and the initial concentration of freebase solution was set as ~75 mg / mL in EtOH / H₂O (9:1, v / v). The concentration of acid solution was 0.874 mol / L in EtOH. The final molar charge ratio of acid / freebase was i.11 (the volume ratio of freebase solution / acid solution was 73:20). As a result, the yield was increased to 87.6%. XRPD and PLM results showed that rod¬ like Form A Sulfate Salt was obtained. GC test showed that the content of residual EtOH was 2633.5 ppm, lower than the ICH limit of EtOH residual solvent.Table B12. Parameters and results of solution crystallization in THF / H2O (19:1, v / v)Batch Batch 1 Batch 2 Batch 3 Batch 4 Batch 5 Batch 6 Batch 7 Scale (g) ~1.0 (Freebase) -1.0 (Freebase) -1.0 (Freebase) -1,0 (Freebase) -1,0 (Freebase) -1.0 (Freebase) —1.0 (Freebase) Solvent (v / v) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) Initial Cone.-77 -77 -77 -77 -77 -77 -77 (mg / mL)Temperature RT RT RT RT RT RT RT Magnetically Magnetically Magnetically MagneticallyStirring Method Overhead stirring Overhead stirring Overhead stirring stirring stirring stirring stirringSeed Loading(5g procedure of NA -1% -1% -1% - 1 % (wet milled) -1% -1% Example 4)Solvent for Acid THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) THF / H2O (19:1) Cone, of Acid1.5 1.5 1.5 1.5 1.5 1.5 0.1 Solution (mol / L)Addition Time of1 hour 1 hour 2 hours 3 hours 2 hours 8 hours 8 hours Acid SolutionFinal MolarCharge Ratio -1.05 -1.05 -1.05 -1.05 -1.05 -1.05 -1.05 (acid / FB)Form A Sulfate Form A Sulfate Form A Sulfate Form A Sulfate Form A Sulfate Form A Sulfate Form A Sulfate Crystal FormSalt Salt Salt Salt Salt Salt Salt HPLC Purity99.67 99.66 99.69 99741 Not performed Not performed Not performed (area%)Stoichiometry'1.0 1.0 0.9 Not performed Not performed Not performed Not performed (acid / freebase)Table B12. Parameters and results of solution crystallization in THF / H2O (19:1, v / v)Batch Batch 1 Batch 2 Batch 3 Batch 4 Batch 5 Batch 6 Batch 7 Needle-like and Needle-like or Needle-like or Needle-like or PLM Needle-like Needle-like Not performedfine particles rod-like rod-like rod-like Residual Solvent1169.6 (THF) 1137.6 (THF) 852.2 (THF) 888-1209 (THF)11699.9 (THF) 1117.5 (THF) 790.6 (THF) (ppm)Yield (%) 90.0 93.8 87.0 Not calculated 93.0 93.0 88.3® 'Before HPLC and GC test, the wet sample was divided into three parts. The first part was dried at room temperature under vacuum for -22 hrs. The secon part -was dried at 50 °C under vacuum for -22 hrs. The third part was slurred in acetone at 50 °C for -3 hrs, followed by drying at room temperature unde vacuum for -19 hrs. Tire THF residue of three parts samples was 1209 ppm, 1179 ppm and 888 ppm. The HPLC purity of the first and second parts wa determined to be 99,74 area%* RT = room temperatureTable B13. Parameters and results of solution crystallization in EtOH / H2O (9:1, v / v)Batch Batch 8 Batch 9 Batch 10 Scale (g) -1.1 (Freebase) -5.5 (Freebase) -5.5 (Freebase) Solvent (v / v) EtOH / H2O (9:1) EtOH / H2O (9:1) EtOH / H2O (9:1) Initial Cone. (mg / niL) ~55 -55 -75Initial Temperature 60 °C 60 °C 60 °CStirring Method Overhead stirring Overhead stirring Overhead stirring Solvent for Acid Eton Eton EtonCone, of Acid Solution0.874 0.874 0.874(mol / L)Seeding Point FB solution / acid solution (40:1, v / v) FB solution / acid solution (40:1, v / v) FB solution / acid solution (73:2.5, v / v) Seed Loading~1% -1% -1%(5g procedure of Example 4)Addition Time of Acid 8 hours 8 hours 8 hoursFinal Molar Charge Ratio~1.11 -1.11 -1.11(acid / FB)Aging Time after addition of2 hours 2 hours 2 hoursacidTemperature Progress Cool to 5 °C in 110 min Cool to 5 °C in 110 min Cool to 5 °C in 110 min Ending Temperature 5 °C 5 °C 5 °CEnding Solvent (v / v) EtOH / H₂O (~10.9:1) EtOH / H₂O (~10.9:1) EtOH / H2O (-11.6:1) Crystal Form Form A Sulfate Salt Form A Sulfate Salt Form A Sulfate Salt HPLC Purity (area%) 99.73 99.75 99.62 Stoichiometry (acid / freebase) 1.0 0.9 1.0PLM Rod-like Rod-like Rod-likeTable B13. Parameters and results of solution crystallization in EtOH / HiO (9:1, v / v)Batch Batch 8 Batch 9 Batch 10 Residual Solvent (ppm) 2702.8 (EtOH) 2452.5 (EtOH) 2633.5 (EtOH) Yield (%) 76.0 77.6 87.643700-02297 (VNTS-031 / 001WO)(Hi) Large-scale preparation

[0611] The crystallization procedure for a large-scale 180 g batch of Form A Sulfate Salt was performed as follows: (1) Added 180 g of Compound 1 Form I Freebase and 2.4 L ethanol / H₂O (9:1, v / v) into a 5 L reactor with overhead stirring at 60 °C to obtain a freebase solution; (2) Added 31.1 mL of concentrated H2SO4 into 623.5 mL ethanol (EtOH) to obtain an acid solution; (3) Added 82 mL of the acid solution to the freebase solution over 1 hour; (4) Added 4.8 g of Form A Sulfate Salt from Batch 10 to the reactor as seed (seed loading is approximately 2%), and overhead stirred at 60 °C for 2 hours; (5) Added all the remaining acid solution (572.6 mL) to the reactor over 7 hours and overhead stirred at 60 °C for 2 hours; (6) Cooled the mixture to 5 °C over 110 minutes and stirred at 5 °C overnight (approximately 11 hours) and then isolated the resulting suspension by suction filtration; and (7) Dried the solid at 50 °C under vacuum for 37.5 hours and at room temperature under vacuum for 42 hours, A total of 200.2 g sample was obtained (81.4% yield).|0612] The XRPD of the sample obtained from this large-scale preparation was consistent with the initial-small-scale procedure of Example 1 (see FIG. 4A), as well as the 10g scale-up procedure of Example 1, and the 5g seed crystal preparation of this Example 4, An overlay of the XRPD of the seed crystals prepared in from this Example 4 with the crystalline material from the 180 g large scale preparation is provided in FIG. 9. Ihe TGA / DSC scan revealed a weight loss of 4.02% up to 180 °C and one major endotherm at 196.6 °C (peak temperature). See FIG. 4C.

[0613] The TGA / DSC scan of this large-scale Example 4 (FIG. 4C) is shifted and broadened as compared to the TGA / DSC scan of Example 1 initial small-scale sample (FIG. 4B). Without wishing to be bound by any particular theory, the broadened and shifted TGA / DSC scan of this large-scale Example 4 may be due to differences in morphology and / or particle size of the solid obtained from the initial small-scale (Example 1) and large-scale (this Example 4) preparation. See, e.g., the PLM image of this large-scale Example (FIG. 4E) showing the sample was composed of rod-like crystals, compared to the PLM image (FIG. 4D) of the small-scale Example 1 showing irregular crystals.

[0614] Purity was confirmed to be 99,73 area% by HPLC. Gas Chromatography (GC) confirmed that the content of residual ethanol (EtOH) was 2762.4 ppm, which is significantly lower than the ICH guidelines setting a 5000 ppm EtOH residue limit. Consistent with Example 1, the ion chromatography confirmed a 1:1 stoichiometric ratio of the two salt components (sulfate anion to protonated Compound 1).

[0615] Ihe water content of the Form A Sulfate Salt was determined to be 4.96% by Karl Fischer titration (KF) (theoretical water content of a monohydrate is 4.0 wt%), Varied temperature XRPD was performed on Form A Sulfate Salt and no form change was observed after N2 purging for 20 minutes at 25 °C. After heating to 145 °C and cooling to 25 °C with N₂ purging, no obvious form change but slight peak shift and crystallinity decrease was observed. No further form change was observed after exposure to the ambient conditions for approximately 1 hour. Based on these results, Form A Sulfate Salt was proposed to be a hydrate.

[0616] Single crystal X-ray diffraction data for Form A Sulfate Salt, prepared as follows, confirmed the43700-02297 (VNTS-031 / 001WO) form to be a monohydrate salt: 5 mg of Form A Sulfate Salt was dissolved in 3 mL of a mixture of methyl isobutyl ketone / methanol / water (v / v / v, 10 / 1.5 / 0.5) at 70 °C and then filtered into a clean vial. The vial was covered by pin-hole film and placed at room temperature for slow evaporation. After 5 days, rod shaped single crystals were generated which were used for single crystal X-ray diffraction.

[0617] The cry stal structural data for Form A Sulfate Salt is summarized as set forth in Table B14. Form A Sulfate Salt cry stallizes as orthorhombic in P2₁2₁2₁ space group with formula of C20H26N4O7S. There is one Compound 1 cation, one HSO₄⁻ anion and one water molecule in each asymmetric unit (See FIG. 4F). Hie unit cell contains four asymmetric units.Table B14. Crystal Data and Structure Refinement for Form A Sulfate SaltEmpirical formula C20H26N4O7S Formula weight 466.51Temperature / K 179.99(10) Crystal system Orthorhombic Space group P2₁2₁2₁a / A 7.54459(13)b / A 15.0258(3)c / A 18.6643(4)a / ° 90PA' 9090Volume / A32115.85(7)Z 4ρcalc / g / cm³ 1.464 μ / mm⁻¹ 1.816F(000) 984.0Crystal size / mm³ 0.30 × 0.02 × 0.02Radiation Cu Kα (λ = 1.54184 Å)2θ range for data collection / ° 7.552 to 145.272Index ranges -9 ≤ h ≤ 9, -18 ≤ k ≤ 18, -21 ≤ l ≤ 22 Reflections collected 40606Independent reflections 4002 [Rint = 0.0698, Rsigma = 0.0256] Data / restraints / parameters 4002 / 6 / 307Goodness-of-fit on F21.054Final R indexes \I>=2a (7)] Pi = 0.0501, WR2= 0.1331 Final R indexes [all data] R1 = 0.0528, wR₂ = 0.1354 Largest diff. peak / hole / e Å⁻³ 0.50 / -0.40Flack parameter 0.004(11)43700-02297 (VNTS-031 / 001WO)Example 5. Stability Studies of Crystalline Compound 1 Form A Sulfate Salt(i) Stability at elevated humidity and / or elevated temperature

[0618] Solid-state stability of Form A Sulfate Salt at 25 °C / 60% relative humidity (RH) and 40 C / 75% relative humidity (RH) were evaluated. As shown in Table B15, after storage for one (1) week, no form change was observed by XRPD and no HPLC purity decrease was observed, indicating good physical stability’ of Form A, and good chemical stability of Compound 1, under the evaluated conditions. Six (6) and nine (9) month stability studies also confirmed no change to the Form or HPLC Purity.Table Bl 5. Summary of solid-state stability evaluationCondition HPLC Purity (Area%) Form change Initial 99.45 —25 °C / 60%RH 99.46 No40 °C / 75%RH 99.46 No(ii) Stability measured upon grinding with or without solvent

[0619] A total of three (3) grinding experiments were conducted. For each experiment, approximately 20 mg of Form A Sulfate Salt was added into a mortar. The sample was manually ground with or without 0.02 mL solvent for approximately 3 minutes, and the solids were isolated for XRPD analysis. Tire results, as summarized in Table B16, demonstrate that Form A Sulfate Salt was obtained. No crystallinity decrease was observed after grinding with / without test solvent, as confirmed by XRPD, indicating good physical and chemical stability under the evaluated conditions.Table B16. Summary of grinding experimentsTest Solvent Result(None) Form A Sulfate SaltH2O Form A Sulfate SaltEtOH Form A Sulfate SaltExample 6. Preparation of Amorphous Sulfate Salt

[0620] Preparation of Amorphous Compound 1 Sulfate Salt is described in Example 3, Table B6, from a MeOH solution of the Form A Sulfate Salt with MTBE as anti-solvent added, and from a DMSO solution of the Form A Sulfate Salt with IPAc as anti-solvent added.

[0621] Amorphous Sulfate Salt was also prepared as follows: (1) dissolve approximately 900 mg of Form A Sulfate Salt in 23 mL of methanol (MeOH); (2) filter the solution through a 0.45 pm polytetrafluoroethylene (PTFE) membrane to provide a filtrate; and (3) remove the MeOH solvent from the filtrate by rotary' evaporation at 40 °C to provide the amorphous solid as confirmed by XRPD (and which is consistent with the XRPD as provided in FIG. 7).43700-02297 (VNTS-031 / 001WO) Example 7. Comparison of Form I Freebase and Form A Sulfate Salt in Pentagastrin-Treated Dog

[0622] A two-way cross over study with pentagastrin-treated dog (n=6 per group) under fasted conditions was performed. Compound 1 Form I Freebase and Crystalline Compound 1 Form A Sulfate Salt were administered orally to pentagastrin-treated dog at a given dose, and plasma concentrations of Compound 1 were monitored at 2 -hour increments for 12 hours. As shown in FIG. 11, Form A Sulfate Salt demonstrated improved bioavailability (F, the fraction of the administered dose that reaches systemic circulation as the active drug) compared to Form I Freebase, with a calculated 1.5-fold increase in AUCssand approximately 1.4-fold increase in Cmaxssin steady state exposure in dogs treated with Form A Sulfate Salt compared to Form I Freebase, and with a consistent Ka (absorption rate constant) in dogs treated with Form A Sulfate Salt compared to Form I Freebase. Reduction in the variability of AUC and Cmax (approximately 1.85- fold and 1.75 -fold reduction in variability, CV%) was also observed in dogs treated with Form A Sulfate Salt compared to Form I Freebase.OTHER EMBODIMENTS

[0623] It should be understood that, in general, where the present disclosure, or aspects of the present disclosure, is / are referred to as comprising particular elements and / or features, certain embodiments of the present disclosure or aspects of the present disclosure also consist, or consist essentially of, such elements and / or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms “comprising” and “containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are understood to be included. Furthermore, unless otherwise indicated or otherwise evident from tire context and understanding of one of ordinary’ skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the present disclosure, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[0624] This application refers to various patents and publications, each of which is incorporated herein by reference. If there is a conflict between any of the incorporated references and the present disclosure, the present disclosure shall control.

[0625] The foregoing has been described of non-limiting embodiments of the present disclosure. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present disclosure, as defined in the following claims.

Claims

43700-02297 (VNTS-031 / 001WO)CLAIMS1. A sulfate salt of Compound 1:

2. The sulfate salt of claim 1, wherein the sulfate salt is crystalline.

3. The sulfate salt of claim 1, wherein the sulfate salt is a monohydrate.

4. The crystalline sulfate salt of claims 2 or 3, characterized by an XRPD pattern comprising a signal at 7.6±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

5. The crystalline sulfate salt of any one of claims 2-4, characterized by an XRPD pattern comprising a signal at 9.5±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

6. The crystalline sulfate salt of any one of claims 2-5, characterized by an XRPD pattern comprising a signal at 13.9±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

7. The crystalline sulfate salt of any one of claims 2-6, characterized by at least one endothermic event between about 178 °C and about 202 °C, inclusive, as measured by DSC.

8. The crystalline sulfate salt of claim 7, characterized by two endothermic events between about 175 °C and about 185 °C, inclusive, as measured by DSC.

9. The crystalline sulfate salt of claim 7, characterized by one endothermic event between about 190 °C and about 202 °C, inclusive, as measured by DSC.

10. The crystalline sulfate salt of any one of claims 2-9, characterized by a weight loss of at least about 3.5% up to about 150 °C, or up to about 180 °C.

11. The crystalline sulfate salt of any one of claims 2-10, having a solubility greater than about 1,9 mg / mL at a pH of about 1.7, as measured in SGF at two hours at 37 °C at approximately 25 rpm.43700-02297 (VNTS-031 / 001WO) 12. The crystalline sulfate salt of any one of claims 2-11, having a solubility in water of greater than about 4 mg / mL at a pH of about 2.1 after 3 hours at 37 °C at approximately 25 rpm.

13. The crystalline sulfate salt of any one of claims 2-12, having a solubility in FaSSIF of greater than about 4 mg / mL at a pH of about 3.1 after 3 hours at 37 °C at approximately 25 rpm.

14. The crystalline sulfate salt of any one of claims 2-13, characterized as having at least one of the following:(v) an XRPD pattern which is substantially similar to that as provided in FIG. 4A or FIG. 9 (Example 1 or Example 4 XRPD patterns ) and / or(vi) a TGA scan which is substantially similar to that as set forth in FIG. 4B; and / or (vii) a DSC scan which is substantially similar to that as set forth in FIG. 4B; and / or (viii) a PLM image which is substantially similar to that as set forth in FIG. 4D.

15. The crystalline sulfate salt of any one of claims 2-13, characterized as having as least one of the following:(v) an XRPD pattern which is substantially similar to that as provided in FIG. 9 (Example 4 XRPD pattern); and / or(vi) a TGA scan which is substantially similar to that as set forth in FIG. 4C; and / or (vii) a DSC scan which is substantially similar to that as set forth in FIG. 4C; and / or (viii) a PLM image which is substantially similar to that as set forth in FIG. 4E.

16. The sulfate salt of claim 1, wherein the salt is amorphous.

17. The amorphous sulfate salt of claim 16, wherein the XRPD pattern has a broad halo between about 12 and about 30 °20, inclusive, using Cu K alpha radiation when measured at 25 °C.

18. The amorphous sulfate salt of claim 16, wherein the XRPD pattern is substantially similar to that as set forth in FIG. 7.

19. The sulfate salt of any one of claims 1-18, wherein the stoichiometric ratio of a sulfate counterion to protonated Compound 1 is 1:1.43700-02297 (VNTS-031 / 001WO) 20. A phosphate salt of Compound 1:

21. The phosphate salt of claim 20, wherein the salt is crystalline.

22. The crystalline phosphate salt of claim 21, characterized by an XRPD pattern comprising a signal at 5.1±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C.

23. The crystalline phosphate salt of claim 21 or claim 22, characterized by an XRPD pattern comprising a signal at 10.2±0.2 °20, using Cu K alpha radiation when measured at 25 °C.

24. The cry stalline phosphate salt of any one of claims 21-23, characterized by an XRPD pattern comprising signals at 18.4±0.5 °20, using Cu K alpha radiation when measured at 25 °C.

25. The crystalline phosphate salt of any one of claims 21-24, characterized by at least one endothermic event between about 160 °C and about 210 °C, inclusive, as measured by DSC.

26. The crystalline phosphate salt of claim 25, characterized by two endothermic events between about 160 °C and about 210 °C, inclusive, as measured by DSC.

27. The crystalline phosphate salt of any one of claims 21-26, characterized by a weight loss of at least about 2% up to about 150 °C, as measured by TGA.

28. The crystalline phosphate salt of claim 21, characterized as having at least one of the following:(iv) an XRPD pattern substantially similar to that as set forth in FIG. 3A; and / or(v) a TGA scan substantially similar to that as set forth in FIG. 3B; and / or(vi) a DSC scan substantially similar to that as set forth in FIG. 3B29. The phosphate salt of any one of claims 20-28, wherein the stoichiometric ratio of a phosphate counterion to protonated Compound 1 is 2: 1.

30. A fumarate salt of Compound 1:43700-02297 (VNTS-031 / 001WO)HN31. The fumarate salt of claim 30, wherein the salt is crystalline.

32. The crystalline fumarate salt of claim 31, characterized by an XRPD pattern comprising a signal at 7.1±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C.

33. The crystalline fumarate salt of claim 31 or claim 32, characterized by an XRPD pattern comprising a signal at 18.5±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C.

34. The crystalline fumarate salt of any one of claims 31-33, characterized by an XRPD pattern comprising a signal at 21.5±0.5 °2θ, using Cu K alpha radiation when measured at 25 °C.

35. The crystalline fumarate salt of any one of claims 31-34, characterized by at least one endothermic event between about 180 °C and about 186 °C, inclusive, as measured by DSC.

36. The crystalline fumarate salt of any one of claims 31-35, characterized by a weight loss of at least about 4% up to about 150 °C, as measured by TGA.

37. The crystalline fumarate salt of claim 31, characterized as having at least one of the following:(iv) an XRPD pattern substantially similar to that as set forth in FIG. 1A; and / or(v) a TGA scan substantially similar to that as set forth in FIG. IB; and / or(vi) a DSC scan substantially similar to that as set forth in FIG. 1B.

38. The fumarate salt of any one of claims 30-37, wherein the stoichiometric ratio of a fumarate counterion to protonated Compound 1 is 1:1.

39. A hydrochloride salt of Compound 1:N OHThe hydrochloride salt of claim 39, wherein the salt is crystalline.43700-02297 (VNTS-031 / 001WO)41. The crystalline hydrochloride salt of claim 40, characterized by an XRPD pattern comprising a signal at 6.9±0.

2. °20, using Cu K alpha radiation when measured at 25 °C.

42. The crystalline hydrochloride salt of claim 40 or claim 41, characterized by an XRPD pattern comprising a signal at 10.8±0.2 °2θ, using Cu K alpha radiation when measured at 25 °C.

43. The crystalline hydrochloride salt of any one of claims 40-42, characterized by an XRPD pattern comprising a signal at 10.8±0.5 °20, using Cu K alpha radiation when measured at 25 °C.

44. The crystalline hydrochloride salt of any one of claims 40-43, characterized by at least one endothermic event between about 275 °C and about 285 °C, inclusive, as measured by DSC.

45. The crystalline hydrochloride salt of any one of claims 40-44, characterized by a weight loss of at least about 6% up to about 130 °C, as measured by TGA.

46. The crystalline hydrochloride salt of claim 40, characterized as having at least one of the following:(iv) an XRPD pattern substantially similar to that as set forth in FIG. 2A; and / or(v) a TGA scan substantially similar to that as set forth in FIG. 2B; and / or(vi) a DSC scan substantially similar to that as set forth in FIG. 2B.

47. The hydrochloride salt of any one of claims 39-46, wherein the stoichiometric ratio of a chloride counterion to protonated Compound 1 is 1:1.

48. A composition comprising a mixture of Compound 1 salts, wherein 75% (w / w%) of the mixture of salt forms is a salt of any one of the preceding claims,49. The composition of claim 48, wherein 75% (w / w%) of the mixture is a crystalline sulfate salt of any one of claims 2-15.

50. A pharmaceutical composition comprising a salt of any one of claims 1-47, and one or more pharmaceutically acceptable carriers.

51. A method of treating or preventing a disease or disorder, the method comprising administering to a subject the salt of any one of claims 1-47, or a composition of any one of claims 48-50.43700-02297 (VNTS-031 / 001WO) 52. The method of 51, wherein the disease or disorder is a disease or disorder of the central nervous system (CNS), a disease or disorder of the peripheral nervous system (PNS), a primary neurological disease of the muscles, an inflammatory disorder, an autoimmune disorder, cancer, an infection, a metabolic disease, a cardiovascular disease, a respiratory disease, a kidney disease, a liver disease, an ocular disease, a skin disease, a lymphatic disease, a rheumatic disease, a psychological disease, graft versus host disease, pain (including disorders related to pain management), an NLRP3-related disease in a subject that has been determined to carry a germline or somatic non-silent mutation in NLRP3, or obesity.

53. A method of preparing the salts of any one of claims 1-47, as described in the specification and / or in the Examples.

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