Pharmaceutical compositions comprising an inhibitor of EGFR

Abstract

Provided herein are pharmaceutical compositions comprising (R)-N-(2-(4-(4- cyclopropylpiperazin- 1 -yljpiperidin- 1 -y 1) -5 - ((6- (3- (3,5-difluorophenyl)isoxazolidin-2- yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and two or more lubricants. Further provided herein are tablets for oral administration to a subject, said tablet comprising (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6- (3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof; and two or more lubricants.

Description

Docket No. 21135-20013.40 PHARMACEUTICAL COMPOSITIONS COMPRISING AN INHIBITOR OF EGFR CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 778,299 filed on March 26, 2025, and U.S. Provisional Application No. 64 / 001,785 filed on March 10, 2026, which are hereby incorporated by reference in their entirety.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The content of the electronic sequence listing (211352001340SeqList.xml; Size: 3,106 bytes; and Date of Creation: March 23, 2026) is herein incorporated by reference in its entirety.FIELD

[0003] Provided herein are pharmaceutical compositions comprising (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide (hereinafter referred to as “Compound I” or enozertinib), or a pharmaceutically acceptable salt thereof, and two or more lubricants.Further provided herein are tablets for oral administration to a subject, said tablet comprising (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof; and two or more lubricants. Also provided herein are pharmaceutical compositions, said compositions comprising (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and (b) means for preventing sticking of the pharmaceutical composition to manufacturing equipment during manufacturing of tablets from the pharmaceutical composition. Further provided herein are pharmaceutical compositions, said compositions comprising (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and (b) means for preventing the sticking of the pharmaceutical composition to tablet press tooling during manufacturing of tablets from the pharmaceutical composition.BACKGROUND

[0004] Mutations in both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are oncogenic drivers most commonly found in non-small cell lung cancer (NSCLC) but also occurring in multiple other tumor types. Exon20 insertions render1MF-367743657Docket No. 21135-20013.40 the receptors resistant to currently approved inhibitors, giving subjects with tumors harboring such insertions a worse prognosis than with other activating EGFR mutations. Moreover, approximately one-third of subjects with exon20 insertion mutations may develop central nervous system (CNS) metastases over the course of their disease. Another set of mutations in EGFR in subjects having cancer are P-loop and alpha C-helix compressing (PACC) mutations, the majority of which lack effective targeted therapies.

[0005] Compound I has been demonstrated to be a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor that selectively targets EGFR and HER2 with high potency against Exon 20 insertion mutations and other atypical EGFR mutations, making it a promising therapeutic to potentially address this unmet medical need, including in NSCLC subjects with active central nervous system (CNS) metastases. Initial Phase 1 clinical data demonstrated a favorable safety profile of Compound I with a half-life supporting once daily dosing (NCT05315700). Moreover, evidence of intracranial and systemic antitumor activity was observed in heavily pre-treated subjects, including complete systemic and CNS response in Phase 1 clinical studies (Hong et al, ESMO 2023).SUMMARY

[0006] Provided herein are pharmaceutical compositions, said compositions comprising (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and (b) means for preventing sticking of the pharmaceutical composition to manufacturing equipment during manufacturing of tablets from the pharmaceutical composition.

[0007] Further provided herein are pharmaceutical compositions, said compositions comprising (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and (b) means for preventing the sticking of the pharmaceutical composition to tablet press tooling during manufacturing of tablets from the pharmaceutical composition.

[0008] Further provided herein are pharmaceutical compositions, said compositions comprising (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and (b) means for reducing a rate of tablet defects during the manufacturing of tablets from the pharmaceutical composition.2MF-367743657Docket No. 21135-20013.40

[0009] Further provided herein are pharmaceutical compositions, said compositions comprising (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and (b) means for reducing a rate of tablet defects during the manufacture of tablets from the pharmaceutical composition, wherein the tablet defects are caused by sticking of the pharmaceutical composition to manufacturing equipment during manufacturing of the tablets from the pharmaceutical composition.

[0010] Also provided herein are pharmaceutical compositions comprising (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof; and two or more lubricants.

[0011] Further provided herein are tablets for oral administration to a subject, said tablets comprising (R)-N-(2- (4- (4-cyclopropylpiperazin- 1 -yljpiperidin- 1 -y 1)- 5 - ((6- (3 - (3 ,5 -difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof; and two or more lubricants.DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 sets forth variations in tablet thickness observed during the preparation of tablets comprising Compound I malonate as described in Example 1.

[0013] FIG. 2 sets forth variations in compression force used by tableting machinery observed during the preparation of tablets comprising Compound I malonate as described in Example 1.

[0014] FIG. 3 sets forth variations in tablet hardness observed during the preparation of tablets comprising Compound I malonate as described in Example 1.

[0015] FIG. 4 sets forth variations in tablet weight observed during the preparation of tablets comprising Compound I malonate as described in Example 1.

[0016] FIG. 5A and FIG. 5B set forth XRPD patterns observed during analysis of final blend materials comprising Compound I malonate that exhibited sticking to tablet punches as described in Example 2.

[0017] FIG. 6 sets forth the results of in vitro dissolution tests of tablets comprising Compound I malonate as set forth in Example 5.

[0018] FIG. 7 sets forth variations in tablet thickness observed during the preparation of tablets comprising Compound I malonate as described in Example 6.3MF-367743657Docket No. 21135-20013.40

[0019] FIG. 8 sets forth variations in compression force used by tableting machinery observed during the preparation of tablets comprising Compound I malonate as described in Example 6.

[0020] FIG. 9 sets forth variations in tablet hardness observed during the preparation of tablets comprising Compound I malonate as described in Example 6.

[0021] FIG. 10 sets forth the results of the plasma concentration measurements of Compound I (enozertinib) in human subjects administered with the enozertinib-containing formulations as described in Example 7.DETAILED DESCRIPTION

[0022] Compound I can be administered to subjects in the form of pharmaceutical compositions, including in the form of tablets for oral administration. It has been unexpectedly discovered that the addition of two or more lubricants to pharmaceutical compositions comprising Compound I prior to tableting of the pharmaceutical composition decreases sticking of pharmaceutical compositions (comprising Compound I) to equipment during the tablet manufacturing process and reduces occurrences of (a) variations in tablet weight, (b) variations in tablet thickness, (c) variations in tablet hardness, (d) unacceptable tablet appearance, and (e) unacceptable tablet friability.Definitions

[0023] Unless specifically indicated otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this application belongs. In addition, any method or material similar or equivalent to a method or material described herein can be used in the practice of the present application. For purposes of the present application, the following terms are defined.

[0024] It is understood that embodiments of the application described herein include “consisting” and / or “consisting essentially of’ embodiments.

[0025] Reference to “about” a value or parameter herein includes (and describes) variations that are directed to that value or parameter per se. For example, description referring to “about X” includes description of “X”.

[0026] The term “about X-Y” used herein has the same meaning as “about X to about Y.” The expression “about X, Y and / or Z” used herein has the same meaning as “about X, about Y, and / or about Z.”4MF-367743657Docket No. 21135-20013.40

[0027] As used herein, reference to “not” a value or parameter generally means and describes “other than” a value or parameter. For example, the method is not used to treat cancer of type X means the method is used to treat cancer of types other than X.

[0028] The terms “a,” “an,” or “the” as used herein not only include aspects with one member, but also include aspects with more than one member. For instance, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and reference to “the agent” includes reference to one or more agents known to those skilled in the art, and so forth.

[0029] As used herein, the term “(R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide,” also referred to herein as enozertinib or “Compound I,” means the compound having Chemical Abstracts Registry No. 2489185-38-6, and having the chemicalstructure. Compound I can also be named as (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide. Compound I has been assigned CAS Registry No. 2489185-38-6. It is understood that descriptions herein to a salt or pharmaceutical composition provided herein refer to salts of Compound I, including pharmaceutically acceptable salts of Compound I, or pharmaceutical compositions comprising Compound I, or salts of Compound I, including pharmaceutically acceptable salts of Compound I. Compound I has been described in W02020 / 190119 and U.S. Patent No. 11,466,000, and may be prepared by methods described therein. The contents of W02020 / 190119 and U.S. Patent No. 11,466,000 are hereby incorporated by reference herein for that purpose. Alternatively, Compound I may be prepared by methods known to those having ordinary skill in the art.

[0030] As used herein, the term “polymorph” or “polymorphic form” refers to a crystalline form of a compound. Different polymorphs may have different physical properties such as, for 5MF-367743657Docket No. 21135-20013.40 example, melting temperatures, heats of fusion, solubilities, dissolution rates, and / or vibrational spectra as a result of the arrangement or conformation of the molecules or ions in the crystal lattice. The differences in physical properties exhibited by polymorphs may affect pharmaceutical parameters, such as storage stability, compressibility, density (important in formulation and product manufacturing), and dissolution rate (an important factor in bioavailability). Differences in stability can result from changes in chemical reactivity (e.g., differential oxidation, such that a dosage form discolors more rapidly when comprised of one polymorph than when comprised of another polymorph), mechanical changes (e.g., tablets crumble on storage as a kinetically favored polymorph converts to thermodynamically more stable polymorph), or both (e.g., tablets of one polymorph are more susceptible to breakdown at high humidity). As a result of solubility / dissolution differences, in the extreme case, some polymorphic transitions may result in lack of potency or, at the other extreme, toxicity. In addition, the physical properties of a crystalline form may be important in processing; for example, one polymorph might be more likely to form solvates or might be difficult to filter and wash free of impurities (e.g., particle shape and size distribution might be different between polymorphs).

[0031] As used herein, the term “substantially as shown in” when referring, for example, to an XRPD pattern, a DSC graph, or a TGA graph, includes a pattern or graph that is not necessarily identical to those depicted herein, but that falls within the limits of experimental error or deviations when considered by one of ordinary skill in the art.

[0032] As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. For purposes of this application, beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread (e.g., metastasis) of the disease, preventing or delaying the recurrence of the disease, reducing recurrence rate of the disease, delaying or slowing the progression of the disease, ameliorating the disease state, providing a remission (partial or total) of the disease, decreasing the dose of one or more other medications required to treat the disease, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival. In some embodiments, the treatment reduces the severity of one or more symptoms associated with cancer by at least about any of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% compared to the corresponding symptom in the same subject prior to treatment or compared to the corresponding symptom in other subjects not receiving the treatment. Also encompassed by “treatment” is a 6MF-367743657Docket No. 21135-20013.40 reduction of pathological consequence of cancer. The methods of the application contemplate any one or more of these aspects of treatment.

[0033] The term “effective amount” used herein refers to an amount of a compound or composition sufficient to treat a specified disorder, condition, or disease, such as to ameliorate, palliate, lessen, and / or delay one or more of its symptoms in a subject. In reference to cancer, an effective amount comprises an amount sufficient to cause a tumor to shrink and / or to decrease the growth rate of the tumor (such as to suppress tumor growth) or to prevent or delay other unwanted cell proliferation in cancer in a subject. In some embodiments, an effective amount is an amount sufficient to delay development of cancer in a subject. In some embodiments, an effective amount is an amount sufficient to prevent or delay recurrence of cancer in a subject. In some embodiments, an effective amount is an amount sufficient to reduce recurrence rate of cancer in a subject. An effective amount can be administered to a subject in one or more administrations. The effective amount of the drug or composition may: (i) reduce the number of cancer cells; (ii) reduce tumor size; (iii) inhibit, retard, slow to some extent and preferably stop cancer cell infiltration into peripheral organs; (iv) inhibit (z.e., slow to some extent and preferably stop) tumor metastasis; (v) inhibit tumor growth; (vi) prevent or delay occurrence and / or recurrence of tumor; (vii) reduce recurrence rate of tumor, and / or (viii) relieve to some extent one or more of the symptoms associated with the cancer in a subject.

[0034] As is understood in the art, an “effective amount” may be in one or more doses, i.e., a single dose or multiple doses may be required to achieve the desired treatment endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents, and a compound or composition described herein may be considered to be given in an effective amount if, optionally in conjunction with one or more other agents, a desirable or beneficial result may be or is achieved. The components (e.g., the first and second therapies) in a combination therapy of the application may be administered to a subject sequentially, simultaneously, or concurrently using the same or different routes of administration for each component. Thus, an effective amount of a combination therapy includes an amount of the first therapy and an amount of the second therapy that when administered sequentially, simultaneously, or concurrently to a subject produces a desired outcome in the individual.

[0035] As used herein, “therapeutically effective amount” indicates an amount administered to a subject that results in a desired pharmacological and / or physiological effect for the condition in the individual. The effect in the individual may be prophylactic in terms of completely or partially preventing a condition or symptom thereof and / or may be therapeutic in terms of a partial or complete cure for the condition and / or adverse effect attributable to the condition.7MF-367743657Docket No. 21135-20013.40

[0036] As used herein, “subject” means a mammal, including a human, dog, cat, or livestock. In one embodiment, subject means a human.

[0037] As used herein, by “pharmaceutically acceptable” or “pharmacologically compatible” is meant a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to a subject without causing any significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers or excipients have preferably met the required standards of toxicological and manufacturing testing and / or are included on the Inactive Ingredient Guide prepared by the U. S. Food and Drug administration.

[0038] It is understood by those of ordinary skill in the art, and specifically contemplated herein, that excipients comprising the pharmaceutical formulations and tablets for oral administration disclosed herein may perform more than one function in such formulations and tablets. By way of non-limiting example, a pharmaceutical composition or tablet disclosed herein may comprise microcrystalline cellulose, and those of ordinary skill in the art understand that microcrystalline cellulose may perform more than one function in such formulations and tablets including, but not limited to, acting as a binder, a disintegrant, a diluent, a lubricant, and antiadherent, a moisture adsorbent, and / or a stability enhancer. As such, one of ordinary skill in the art would understand that pharmaceutical formulations and tablets for oral administration disclosed herein that comprise microcrystalline cellulose may also be described as comprising, by way of non-limiting example only: a binder; or a disintegrant; or a diluent; or a lubricant; or an anti-adherent; or a moisture adsorbent; or a stability enhancer; or a binder and a disintegrant; or a binder and a diluent; or a binder and a lubricant; or a binder and an anti-adherent; or a binder and a moisture adsorbent; or a binder and a stability enhancer; or a disintegrant and a diluent; or a disintegrant and a lubricant; or a disintegrant and an anti-adherent; or a disintegrant and a moisture adsorbent; or a disintegrant and a stability enhancer; or a binder, a disintegrant and a diluent; or a binder, a disintegrant, and a lubricant; or a binder, disintegrant, a diluent, and a lubricant; or a binder, a disintegrant, a diluent, a lubricant, and an anti-adherent; or a binder, a disintegrant, a diluent, a lubricant, and anti- adherent, a moisture adsorbent, and a stability enhancer.

[0039] It is also to be understood that recitations of the compositions of specific pharmaceutical compositions and / or tablets for oral administration herein, whether recited by class of excipient or function of excipients (i.e., a binder, or a diluent) or by recitation of specific excipients (i.e., microcrystalline cellulose, or croscarmellose sodium), are not meant to limit the 8MF-367743657Docket No. 21135-20013.40 scope of the pharmaceutical formulations and tablets for oral administration contemplated to be within the scope of the present disclosure. By way of non-limiting example, the disclosure herein of specific examples of pharmaceutical compositions and / or tablets for oral administration comprising an excipient that may be understood by those of ordinary skill in the art to function as, for example, a diluent, is not meant to limit the scope of pharmaceutical compositions and / or tablets for oral administration contemplated to be within the scope of the present disclosure to only those pharmaceutical formulations and / or tablets for oral administration that comprise a diluent. In another non-limiting example, the disclosure herein of specific examples of pharmaceutical compositions and / or tablets for oral administration comprising microcrystalline cellulose is not meant to limit the scope of pharmaceutical compositions and / or tablets for oral administration contemplated to be within the scope of the present disclosure to only those pharmaceutical formulations and / or tablets for oral administration that comprise microcrystalline cellulose.

[0040] The disclosures of all publications, patents, patent applications and published patent applications referred to herein are hereby incorporated herein by reference in their entirety.

[0041] Provided herein are pharmaceutical compositions, said compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof, and (b) means for preventing sticking of the pharmaceutical composition to manufacturing equipment during manufacturing of tablets from the pharmaceutical composition. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments are provided such pharmaceutical compositions wherein the manufacturing of tablets from the pharmaceutical composition comprises at least 100 tablet compression events, at least 200 tablet compression events, at least 250 tablet compression events, at least 300 tablet compression events, at least 400 tablet compression events, at least 500 tablet compression events, at least 600 tablet compression events, at least 700 tablet compression events, at least 800 tablet compression events, at least 900 tablet compression events, or at least 1000 tablet compression events. In other embodiments, the tablet defects are selected from one 9MF-367743657Docket No. 21135-20013.40 or more of (a) unacceptable variation in tablet weight, (b) unacceptable variation in tablet thickness, (c) unacceptable variation in tablet hardness, (d) unacceptable tablet appearance and (e) unacceptable tablet friability. In some embodiments, the tablet defect is unacceptable variation in tablet weight. In other embodiments, the tablet defect is unacceptable variation in tablet thickness. In other embodiments, the tablet defect is unacceptable variation in tablet hardness. In other embodiments, the tablet defect is unacceptable tablet appearance. In other embodiments, the tablet defect is tablet friability.

[0042] Further provided herein are pharmaceutical compositions, said compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof, and (b) means for preventing the sticking of the pharmaceutical composition to tablet press tooling during manufacturing of tablets from the pharmaceutical composition. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments are provided such pharmaceutical compositions wherein the manufacturing of tablets from the pharmaceutical composition comprises at least 100 tablet compression events, at least 200 tablet compression events, at least 250 tablet compression events, at least 300 tablet compression events, at least 400 tablet compression events, at least 500 tablet compression events, at least 600 tablet compression events, at least 700 tablet compression events, at least 800 tablet compression events, at least 900 tablet compression events, or at least 1000 tablet compression events. In other embodiments, the tablet defects are selected from one or more of (a) unacceptable variation in tablet weight, (b) unacceptable variation in tablet thickness, (c) unacceptable variation in tablet hardness, (d) unacceptable tablet appearance and (e) unacceptable tablet friability. In some embodiments, the tablet defect is unacceptable variation in tablet weight. In other embodiments, the tablet defect is unacceptable variation in tablet thickness. In other embodiments, the tablet defect is unacceptable variation in tablet hardness. In other embodiments, the tablet defect is unacceptable tablet appearance. In other embodiments, the tablet defect is tablet friability.10MF-367743657Docket No. 21135-20013.40

[0043] Further provided herein are pharmaceutical compositions, said compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof, and (b) means for reducing a rate of tablet defects during the manufacturing of tablets from the pharmaceutical composition. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments are provided such pharmaceutical compositions wherein the manufacturing of tablets from the pharmaceutical composition comprises at least 100 tablet compression events, at least 200 tablet compression events, at least 250 tablet compression events, at least 300 tablet compression events, at least 400 tablet compression events, at least 500 tablet compression events, at least 600 tablet compression events, at least 700 tablet compression events, at least 800 tablet compression events, at least 900 tablet compression events, or at least 1000 tablet compression events. In other embodiments, the tablet defects are selected from one or more of (a) unacceptable variation in tablet weight, (b) unacceptable variation in tablet thickness, (c) unacceptable variation in tablet hardness, (d) unacceptable tablet appearance and (e) unacceptable tablet friability. In some embodiments, the tablet defect is unacceptable variation in tablet weight. In other embodiments, the tablet defect is unacceptable variation in tablet thickness. In other embodiments, the tablet defect is unacceptable variation in tablet hardness. In other embodiments, the tablet defect is unacceptable tablet appearance. In other embodiments, the tablet defect is tablet friability.

[0044] Further provided herein are pharmaceutical compositions, said compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof, and (b) means for reducing a rate of tablet defects during the manufacture of tablets from the pharmaceutical composition, wherein the tablet defects are caused by sticking of the pharmaceutical composition to manufacturing equipment during manufacturing of the tablets from the pharmaceutical composition. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a11MF-367743657Docket No. 21135-20013.40 malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments are provided such pharmaceutical compositions wherein the manufacturing of tablets from the pharmaceutical composition comprises at least 100 tablet compression events, at least 200 tablet compression events, at least 250 tablet compression events, at least 300 tablet compression events, at least 400 tablet compression events, at least 500 tablet compression events, at least 600 tablet compression events, at least 700 tablet compression events, at least 800 tablet compression events, at least 900 tablet compression events, or at least 1000 tablet compression events. In other embodiments, the tablet defects are selected from one or more of (a) unacceptable variation in tablet weight, (b) unacceptable variation in tablet thickness, (c) unacceptable variation in tablet hardness, (d) unacceptable tablet appearance and (e) unacceptable tablet friability. In some embodiments, the tablet defect is unacceptable variation in tablet weight. In other embodiments, the tablet defect is unacceptable variation in tablet thickness. In other embodiments, the tablet defect is unacceptable variation in tablet hardness. In other embodiments, the tablet defect is unacceptable tablet appearance. In other embodiments, the tablet defect is tablet friability.

[0045] Further provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof; and two or more lubricants. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal12MF-367743657Docket No. 21135-20013.40 silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0046] Also provided herein are the pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, and two or more lubricants, wherein the pharmaceutical compositions further comprise one or more excipients selected from (a) one or more diluents; (b) one or more disintegrants; and (c) one or more binders. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the pharmaceutical composition further comprises one or more diluents. In some embodiments, the one or more diluents is selected from (a) one or more carbohydrates, (b) one or more monosaccharides, and (c) one or more polysaccharides. In some embodiments, the one or more diluents is selected from one or more carbohydrates. In some embodiments, the one or more diluents is one or more carbohydrates selected from lactose, sucrose, glucose, maltose, mannitol, xylitol, dextrose, fructose, sorbitol, starch, starch derivatives, corn starch, hydroxypropyl starch. In some embodiments, the one or more diluents is selected from one or more monosaccharides. In some embodiments, the one or more diluents is one or more monosaccharides selected from glucose, fructose, galactose, mannose, ribose, xylose, arabinose, trehalose, rhamnose, and fucose. In some embodiments, the one or more diluents is selected from one or more polysaccharides. In some embodiments, the one or more diluents is one or more polysaccharides selected from starch, starch derivatives, corn starch, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC), cellulose, methyl cellulose, microcrystalline cellulose (MCC), carboxymethyl cellulose (CMC), guar gum, xanthan gum, pectin, sodium alginate, agar, carrageenan, and dextran. In some embodiments, the diluent is microcrystalline cellulose (MCC).13MF-367743657Docket No. 21135-20013.40 In some embodiments, the pharmaceutical composition further comprises one or more disintegrants. In some embodiments, the one or more disintegrants is selected from starch derivatives, microcrystalline cellulose (MCC), carboxymethylcellulose, croscarmellose sodium, sodium starch glycolate (SSG), crospovidone, aligantes, guar gum, polyvinylpyrrolidone (PVP), mannitol, talc, sodium bicarbonate, calcium carbonate, silica, colloidal silica, xanthan gum, and lactose. In some embodiments, the one or more disintegrants is croscarmellose sodium. In some embodiments, the pharmaceutical composition further comprises one or more binders. In some embodiments, the one or more binders is selected from microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), starch, starch derivatives, com starch, hydroxypropyl starch, methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), gum Arabic, gelatin, carboxymethylcellulose (CMC), sorbitol, xanthan gum, pectin, sodium alginate, ethylcellulose, maltodextrin, guar gum, croscarmellose sodium, magnesium stearate, lactose, sucrose, polyvinyl alcohol (PVA), mannitol, and tartaric acid. In some embodiments, the one or more binders is microcrystalline cellulose (MCC). In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0047] Also provided herein are pharmaceutical compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; (b) two or more lubricants; and (c) microcrystalline cellulose (MCC). In some embodiments, the pharmaceutical composition further comprises one or more disintegrants. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a14MF-367743657Docket No. 21135-20013.40 malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the one or more disintegrants is selected from selected from starch derivatives, carboxymethylcellulose, croscarmellose sodium, sodium starch glycolate (SSG), crospovidone, aligantes, guar gum, polyvinylpyrrolidone (PVP), mannitol, talc, sodium bicarbonate, calcium carbonate, silica, colloidal silica, xanthan gum, and lactose. In some embodiments, the one or more disintegrants is croscarmellose sodium. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0048] Further provided herein are pharmaceutical compositions comprising (a) a malonate salt of Compound I; (b) two or more lubricants; and (c) microcrystalline cellulose (MCC). In some embodiments, the pharmaceutical composition further comprises one or more disintegrants. In some embodiments, the one or more disintegrants is selected from selected from starch derivatives, carboxymethylcellulose, croscarmellose sodium, sodium starch glycolate (SSG), crospovidone, aligantes, guar gum, polyvinylpyrrolidone (PVP), mannitol, talc, sodium bicarbonate, calcium carbonate, silica, colloidal silica, xanthan gum, and lactose. In some embodiments, the one or more disintegrants is croscarmellose sodium. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0049] Also provided herein are pharmaceutical compositions comprising (a) a glycolate salt of Compound I; (b) two or more lubricants; and (c) microcrystalline cellulose (MCC). In some 15MF-367743657Docket No. 21135-20013.40 embodiments, the pharmaceutical composition further comprises one or more disintegrants. In some embodiments, the one or more disintegrants is selected from selected from starch derivatives, carboxymethylcellulose, croscarmellose sodium, sodium starch glycolate (SSG), crospovidone, aligantes, guar gum, polyvinylpyrrolidone (PVP), mannitol, talc, sodium bicarbonate, calcium carbonate, silica, colloidal silica, xanthan gum, and lactose. In some embodiments, the one or more disintegrants is croscarmellose sodium. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0050] Also provided herein are pharmaceutical compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; (b) two or more lubricants; and (c) croscarmellose sodium. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the pharmaceutical compositions further comprises one or more or more diluents selected from (a) one or more carbohydrates, (b) one or more monosaccharides, and (c) one or more polysaccharides. In some embodiments, the one or more diluents is selected from one or more carbohydrates. In some embodiments, the one or more diluents is one or more carbohydrates selected from lactose, sucrose, glucose, maltose, mannitol, xylitol, dextrose, fructose, sorbitol, starch, starch derivatives, corn starch, hydroxypropyl starch. In some embodiments, the one or more diluents is selected from one or more monosaccharides. In some embodiments, the one or more diluents is one or more monosaccharides selected from glucose,16MF-367743657Docket No. 21135-20013.40 fructose, galactose, mannose, ribose, xylose, arabinose, trehalose, rhamnose, and fucose. In some embodiments, the one or more diluents is selected from one or more polysaccharides. In some embodiments, the one or more diluents is one or more polysaccharides selected from starch, starch derivatives, corn starch, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC), cellulose, methyl cellulose, microcrystalline cellulose (MCC), carboxymethyl cellulose (CMC), guar gum, xanthan gum, pectin, sodium alginate, agar, carrageenan, and dextran. In some embodiments, the diluent is microcrystalline cellulose (MCC). In some embodiments, pharmaceutical compositions further comprise one or more binders. In some embodiments, the one or more binders is selected from microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), starch, starch derivatives, com starch, hydroxypropyl starch, methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), gum Arabic, gelatin, carboxymethylcellulose (CMC), sorbitol, xanthan gum, pectin, sodium alginate, ethylcellulose, maltodextrin, guar gum, croscarmellose sodium, magnesium stearate, lactose, sucrose, polyvinyl alcohol (PVA), mannitol, and tartaric acid. In other embodiments, the one or more binders is microcrystalline cellulose (MCC). In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0051] Also provided herein are pharmaceutical compositions comprising (a) a malonate salt of Compound I; (b) two or more lubricants; and (c) croscarmellose sodium. In some embodiments, the pharmaceutical compositions further comprises one or more or more diluents selected from (a) one or more carbohydrates, (b) one or more monosaccharides, and (c) one or more polysaccharides. In some embodiments, the one or more diluents is selected from one or more carbohydrates. In some embodiments, the one or more diluents is one or more carbohydrates selected from lactose, sucrose, glucose, maltose, mannitol, xylitol, dextrose, fructose, sorbitol, starch, starch derivatives, corn starch, hydroxypropyl starch. In some embodiments, the one or more diluents is selected from one or more monosaccharides. In some embodiments, the one or more diluents is one or more monosaccharides selected from glucose, fructose, galactose, mannose, ribose, xylose, arabinose, trehalose, rhamnose, and fucose. In some17MF-367743657Docket No. 21135-20013.40 embodiments, the one or more diluents is selected from one or more polysaccharides. In some embodiments, the one or more diluents is one or more polysaccharides selected from starch, starch derivatives, corn starch, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC), cellulose, methyl cellulose, microcrystalline cellulose (MCC), carboxymethyl cellulose (CMC), guar gum, xanthan gum, pectin, sodium alginate, agar, carrageenan, and dextran. In some embodiments, the diluent is microcrystalline cellulose (MCC). In some embodiments, pharmaceutical compositions further comprise one or more binders. In some embodiments, the one or more binders is selected from microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), starch, starch derivatives, com starch, hydroxypropyl starch, methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), gum Arabic, gelatin, carboxymethylcellulose (CMC), sorbitol, xanthan gum, pectin, sodium alginate, ethylcellulose, maltodextrin, guar gum, croscarmellose sodium, magnesium stearate, lactose, sucrose, polyvinyl alcohol (PVA), mannitol, and tartaric acid. In other embodiments, the one or more binders is microcrystalline cellulose (MCC). In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0052] Also provided herein are pharmaceutical compositions comprising (a) a glycolate salt of Compound I; (b) two or more lubricants; and (c) croscarmellose sodium. In some embodiments, the pharmaceutical compositions further comprises one or more or more diluents selected from (a) one or more carbohydrates, (b) one or more monosaccharides, and (c) one or more polysaccharides. In some embodiments, the one or more diluents is selected from one or more carbohydrates. In some embodiments, the one or more diluents is one or more carbohydrates selected from lactose, sucrose, glucose, maltose, mannitol, xylitol, dextrose, fructose, sorbitol, starch, starch derivatives, corn starch, hydroxypropyl starch. In some embodiments, the one or more diluents is selected from one or more monosaccharides. In some embodiments, the one or more diluents is one or more monosaccharides selected from glucose, fructose, galactose, mannose, ribose, xylose, arabinose, trehalose, rhamnose, and fucose. In some embodiments, the one or more diluents is selected from one or more polysaccharides. In some18MF-367743657Docket No. 21135-20013.40 embodiments, the one or more diluents is one or more polysaccharides selected from starch, starch derivatives, corn starch, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC), cellulose, methyl cellulose, microcrystalline cellulose (MCC), carboxymethyl cellulose (CMC), guar gum, xanthan gum, pectin, sodium alginate, agar, carrageenan, and dextran. In some embodiments, the diluent is microcrystalline cellulose (MCC). In some embodiments, pharmaceutical compositions further comprise one or more binders. In some embodiments, the one or more binders is selected from microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), starch, starch derivatives, com starch, hydroxypropyl starch, methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), gum Arabic, gelatin, carboxymethylcellulose (CMC), sorbitol, xanthan gum, pectin, sodium alginate, ethylcellulose, maltodextrin, guar gum, croscarmellose sodium, magnesium stearate, lactose, sucrose, polyvinyl alcohol (PVA), mannitol, and tartaric acid. In other embodiments, the one or more binders is microcrystalline cellulose (MCC). In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0053] Also provided herein are pharmaceutical compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; (b) two or more lubricants; (c) microcrystalline cellulose (MCC); and (d) croscarmellose sodium. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium19MF-367743657Docket No. 21135-20013.40 lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0054] Also provided herein are pharmaceutical compositions comprising (a) a malonate salt of Compound I; (b) two or more lubricants; (c) microcrystalline cellulose (MCC); and (d) croscarmellose sodium. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0055] Also provided herein are pharmaceutical compositions comprising (a) a glycolate salt of Compound I; (b) two or more lubricants; (c) microcrystalline cellulose (MCC); and (d) croscarmellose sodium. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0056] Also provided herein are pharmaceutical compositions comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; (b) microcrystalline cellulose (MCC); (c) croscarmellose sodium; (d) magnesium stearate; and (e) sodium stearyl fumarate. In some embodiments, the pharmaceutical compositions comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is 20MF-367743657Docket No. 21135-20013.40 selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, Compound I is used in the form of a malonate salt or a glycolate salt. In some embodiments, Compound is used in the form of a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt.

[0057] Also provided herein are pharmaceutical compositions comprising (a) a malonate salt of Compound I; (b) microcrystalline cellulose (MCC); (c) croscarmellose sodium; (d) magnesium stearate; and (e) sodium stearyl fumarate.

[0058] Also provided herein are pharmaceutical compositions comprising (a) a glycolate salt of Compound I; (b) microcrystalline cellulose (MCC); (c) croscarmellose sodium; (d) magnesium stearate; and (e) sodium stearyl fumarate.

[0059] Also provided are any of the pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein wherein the pharmaceutical compositions comprises an intragranular component and an extragranular component. In some embodiments, the intragranular component comprises Compound I, or a pharmaceutically acceptable salt thereof, and one or more lubricants. In some embodiments, the intragranular component comprises a pharmaceutically acceptable salt of Compound I, and one or more lubricants. In some embodiments, the intragranular component comprises a pharmaceutically acceptable salt of Compound I selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, the intragranular component comprises a pharmaceutically acceptable salt of Compound I selected from a malonate salt or a glycolate salt. In some embodiments, the intragranular component comprises a malonate salt of Compound I. In some embodiments, the intragranular component comprises a glycolate salt of Compound I. In some embodiments, the intragranular component comprises a fumarate salt of Compound I. In some embodiments, the intragranular component comprises a malate salt of Compound I. In some embodiments, the intragranular component comprises a citrate salt of Compound I. In some embodiments, the intragranular component further comprises one or more additional excipients. In some embodiments, the one or more additional excipients comprising the intragranular component is microcrystalline cellulose (MCC). In other embodiments, the one or more additional excipients comprising the intragranular component comprises a disintegrant. In some embodiments, the one or more additional excipients comprising the intragranular component is croscarmellose sodium. In some embodiments, the one or more lubricants21MF-367743657Docket No. 21135-20013.40 comprising the intragranular component is selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, the one or more lubricants comprising the intragranular component is selected from magnesium stearate and sodium stearyl fumarate. In still further embodiments, the lubricant comprising the intragranular component is magnesium stearate. In further embodiments, the lubricant comprising the intragranular component is sodium stearyl fumarate. In other embodiments, the extragranular component comprises one or more lubricants. In yet other embodiments, the one or more lubricants comprising the extragranular component is selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In still further embodiments, the one or more lubricants comprising the extragranular component is selected from magnesium stearate and sodium stearyl fumarate. In another embodiment, the lubricant comprising the extragranular component is magnesium stearate. In a further embodiment, the lubricant comprising the extragranular component is sodium stearyl fumarate. In yet other embodiment, the extragranular component comprises magnesium stearate and sodium stearyl fumarate.

[0060] Also provided are any of the pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein wherein the pharmaceutical compositions comprises an intragranular component and an extragranular component, and wherein (a) the intragranular component comprises Compound I, or a pharmaceutically acceptable salt thereof, and one or more lubricants; and (b) the extragranular component comprises one or more lubricants. In some embodiments, the intragranular component comprises a pharmaceutically acceptable salt of Compound I. In some embodiments, the intragranular component comprises a pharmaceutically acceptable salt of Compound I selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, the intragranular component comprises a pharmaceutically acceptable salt of Compound I selected from a malonate salt or a glycolate salt. In some embodiments, the intragranular component comprises a malonate salt of Compound I. In some embodiments, the intragranular component comprises a glycolate salt of Compound I. In some embodiments, the intragranular component comprises a fumarate salt of Compound I. In some embodiments, the intragranular component comprises a malate salt of Compound I. In some embodiments, the22MF-367743657Docket No. 21135-20013.40 intragranular component comprises a citrate salt of Compound I. In some embodiments, the one or more lubricants comprising the intragranular component and the extragranular component are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, the one or more lubricants comprising the intragranular component and the extragranular component are selected from magnesium stearate and sodium stearyl fumarate. In yet other embodiments, the lubricant comprising the intragranular component is magnesium stearate. In still other embodiments, the one or more lubricants comprising the extragranular component are selected from magnesium stearate and sodium stearyl fumarate. In yet other embodiments, the extragranular component comprises magnesium stearate and sodium stearyl fumarate.

[0061] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 75% w / w to about 95% w / w of one or more diluents. Also disclosed herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, wherein said compositions comprise from about 75% w / w to about 90% w / w, or from about 80w / w to about 90% w / w of microcrystalline cellulose, or from about 81% w / w to about 90% w / w, or from about 82% w / w to about 90% w / w, or from about 83% w / w to about 90% w / w, or from about 82% w / w to about 89% w / w, or from about 82% w / w to about 88% w / w of one or more diluents. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0062] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 75% w / w, or about 76% w / w, or about 77% w / w, or about 78% w / w, or about 79% w / w, or about 80% w / w, or about 81% w / w, or about 82% w / w, or about 83% w / w, or about 84% w / w, or about 85% w / w, or about 86% w / w, or about 87% w / w, or about 88% w / w, or about 89% w / w, or about 90% w / w of one or more diluents. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.23MF-367743657Docket No. 21135-20013.40

[0063] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 75% w / w to about 95% w / w of microcrystalline cellulose. Also disclosed herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, wherein said compositions comprise from about 75% w / w to about 90% w / w, or from about 80% w / w to about 90% w / w of microcrystalline cellulose, or from about 81% w / w to about 90% w / w, or from about 82% w / w to about 90% w / w, or from about 83% w / w to about 90% w / w, or from about 82% w / w to about 89% w / w, or from about 82% w / w to about 88% w / w of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0064] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 75% w / w, or about 76% w / w, or about 77% w / w, or about 78% w / w, or about 79% w / w, or about 80% w / w, or about 81% w / w, or about 82% w / w, or about 83% w / w, or about 84% w / w, or about 85% w / w, or about 86% w / w, or about 87% w / w, or about 88% w / w, or about 89% w / w, or about 90% w / w of microcrystalline cellulose. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0065] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 1% w / w to about 10% w / w of one or more disintegrants. In other embodiments, are provided such pharmaceutical compositions comprising from about 1% w / w to about 9% w / w, or from about 1% w / w to about 8% w / w, or from about 1% w / w to about 7% w / w, or from about 1% w / w to about 6% w / w, or from about 1% w / w to about 5% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w of one or more disintegrants. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.24MF-367743657Docket No. 21135-20013.40

[0066] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w of one or more disintegrants. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0067] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 1% w / w to about 10% w / w of croscarmellose sodium. In other embodiments, are provided such pharmaceutical compositions comprising from about 1% w / w to about 9% w / w, or from about 1% w / w to about 8% w / w, or from about 1% w / w to about 7% w / w, or from about 1% w / w to about 6% w / w, or from about 1% w / w to about 5% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w of croscarmellose sodium. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0068] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w of croscarmellose sodium. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0069] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 1% w / w to about 10% w / w of two or more lubricants. In other embodiments, are provided such pharmaceutical compositions comprising from about 1% w / w to about 9% w / w, or from about 1% w / w to about 8% w / w, or from about 1% w / w to about 7% w / w, or from about 1% w / w to about 6% w / w, or from about 1% w / w to about 5% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w of two or more lubricants. In some 25MF-367743657Docket No. 21135-20013.40 embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0070] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w of two or more lubricants. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0071] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise from about 0.5% w / w to about 5% w / w of magnesium stearate. In other embodiments, are provided such pharmaceutical compositions comprising from about 0.5% w / w to about 4% w / w, or from about 0.5% w / w to about 3% w / w, or from about 0.5% w / w to about 2% w / w, or from about 0.75% w / w to about 3% w / w, or from about 0.75% w / w to about 2% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w, or from about 1% w / w to about 1.75% w / w, or from about 1% w / w to about 1.5% w / w, or from about 1% w / w to about 1.25% w / w of magnesium stearate. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0072] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise about 0.5% w / w, or about 0.75% w / w, or about 1% w / w, or about 1.25% w / w, or about 1.5% w / w, or about 1.75% w / w, or about 2% w / w, or about 2.25% w / w, or about 2.5% w / w, or about 3% w / w of magnesium stearate. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0073] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise 26MF-367743657Docket No. 21135-20013.40 from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate. In other embodiments, are provided such pharmaceutical compositions comprising from about 0.5% w / w to about 4.75% w / w, or from about 0.5% w / w to about 4.5% w / w, or from about 0.5% w / w to about 4.25% w / w, or from about 0.5% w / w to about 4% w / w, or from about 0.5% w / w to about 3% w / w, or from about 0.5% w / w to about 2% w / w, or from about 0.75% w / w to about 3% w / w, or from about 0.75% w / w to about 2% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w, or from about 1% w / w to about 1.75% w / w, or from about 1% w / w to about 1.5% w / w, or from about 1% w / w to about 1.25% w / w of sodium stearyl fumarate. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0074] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise about 0.5% w / w, or about 0.75% w / w, or about 1% w / w, or about 1.25% w / w, or about 1.5% w / w, or about 1.75% w / w, or about 2% w / w, or about 2.25% w / w, or about 2.5% w / w, or about 3% w / w, or about 3.25% w / w, or about 3.5% w / w, or about 3.75% w / w, or about 4% w / w, or about 4.25% w / w, or about 4.5% w / w, or about 4.75% w / w, or about 5% w / w of sodium stearyl fumarate. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0075] Also provided herein are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said compositions comprise (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate. In other embodiments are provided such pharmaceutical compositions, wherein said compositions comprise (a) from about 0.5% w / w to about 4% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3.25% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 27MF-367743657Docket No. 21135-20013.40 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2.25% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.75% w / w to about 3% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; (a) from about 1% w / w to about 3% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2.25% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; (a) from about 1% w / w to about 1.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 1.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.75% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.75% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1% w / w to about 3% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1.25% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1.5% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1% w / w to about 4% w / w of sodium stearyl fumarate. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise 28MF-367743657Docket No. 21135-20013.40 a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0076] In other embodiments, are provided such pharmaceutical compositions comprising (a) about 1.75% w / w of magnesium stearate, and (b) about 4% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 3% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 2% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 1.75% w / w of sodium stearyl fumarate; (a) about 1.75% w / w of magnesium stearate, and (b) about 1.5% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 1.25% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 1% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 4% w / w of sodium stearyl fumarate. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a malonate salt of Compound I. In some embodiments, the pharmaceutical compositions comprise a glycolate salt of Compound I.

[0077] Also provided are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed in Tables 1 to 6, below. It is specifically contemplated that in preparing the pharmaceutical compositions disclosed herein, the amount of microcrystalline cellulose (MCC) comprising each such pharmaceutical composition may be adjusted as the amount of Compound I, or a pharmaceutically acceptable salt thereof, is varied such that the relative % w / w of the other components comprising the composition remain about the same. In some embodiments comprising intragranular and extragranular components, the amount of MCC comprising the intragranular component may be adjusted as the amount of Compound I, or a pharmaceutically acceptable salt thereof, comprising the intragranular component is varied such that the relative % w / w of the other components remains about the same. By way of example only, if it desired to prepare a second pharmaceutical composition in which the amount of Compound I, or a pharmaceutically acceptable salt thereof, is increased relative to a first pharmaceutical composition (for example, from 5% w / w Compound I malonate in the first composition to 10% w / w Compound I malonate in the second composition), then the amount of MCC comprising the second composition may be decreased accordingly such that the % w / w of the other components comprising the first and second compositions remain about the same.29MF-367743657Docket No. 21135-20013.40

[0078] Also provided are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed in Tables 1 and 2 below (wherein MCC is microcrystalline cellulose; CCS is croscarmellose sodium; MS is magnesium stearate; and SSF is sodium stearyl fumarate). Note that in Tables 1 and 2, below, the % w / w listed for Compound I malonate is the calculated % w / w of the free base form of Compound I. For example (a) Pharmaceutical Composition No. 1 comprises about 5.8% w / w of Compound I malonate, which is equivalent to about 5% w / w of the free base form of Compound I, and (b) Pharmaceutical Composition No. 2 comprises about 11.6% w / w of Compound I malonate, which is equivalent to about 10% w / w of the free base form of Compound I.Table 1PharmaceuticalComposition 1 2 3 4 5 No.Amount % w / w % w / w % w / w % w / w % w / w 10 10 5 (calculated 5 (calculated 10(calculated(calculated (calculated Compound I as as asas as malonate Compound I Compound I Compound ICompound I Compound I free base) free base) free base)free base) free base) MCC 88.25 83.25 85.25 80.25 82.25 CCS 4 4 4 4 5 MS 1.75 1.75 1.75 1.75 1.75 SSF 1 1 4 4 1 Total 100 100 100 100 100Table 2PharmaceuticalComposition 6 7 8 9 10 No.Amount % w / w % w / w % w / w % w / w % w / w Intragranular10 10 10 5 (calculated 5 (calculated(calculated (calculated (calculated Compound I as asas as as malonate Compound I Compound ICompound I Compound I Compound I free base) free base)free base) free base) free base) MCC 43.25 38.25 40.25 35.25 37.2530MF-367743657Docket No. 21135-20013.40 CCS 2 2 2 2 2.5 MS 0.25 0.25 0.25 0.25 0.25ExtragranularMCC 45 45 45 45 45 CMC 2 2 2 2 2.5 SSF 1 1 4 4 1 MS 1.5 1.5 1.5 1.5 1.5 Total 100 100 100 100 100

[0079] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; and (b) two or more lubricants. In some embodiments, the tablets comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt or a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0080] Also provided herein are tablets for oral administration to a subject, said tablets comprising(a) a malonate salt of Compound I; and (b) two or more lubricants. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon 31MF-367743657Docket No. 21135-20013.40 dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0081] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) a glycolate salt of Compound I; and (b) two or more lubricants. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0082] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; (b) two or more lubricants; and (c) microcrystalline cellulose (MCC). In some embodiments, the tablets comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt or a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still 32MF-367743657Docket No. 21135-20013.40 other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0083] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) a malonate salt of Compound I; (b) two or more lubricants; and (c) microcrystalline cellulose (MCC). In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0084] Also provided herein are tablets for oral administration to a subject, said tablet comprising (a) a glycolate salt of Compound I; (b) two or more lubricants; and (c) microcrystalline cellulose (MCC). In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0085] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; (b) two or more lubricants; and (c) croscarmellose sodium. In some embodiments, the tablets comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt or a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is glycolate salt. In some embodiments, the pharmaceutically 33MF-367743657Docket No. 21135-20013.40 acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0086] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) a malonate salt of Compound I; (b) two or more lubricants; and (c) croscarmellose sodium. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

[0087] Also provided herein are tablets for oral administration to a subject, said tablet comprising (a) a glycolate salt of Compound I; (b) two or more lubricants; and (c) croscarmellose sodium. In some embodiments, the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate. In other embodiments, one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate. In still other embodiments, one of the two or more lubricants is magnesium stearate. In other embodiments, one of the two or more lubricants is sodium stearyl fumarate. In still further embodiments, the two or more lubricants are magnesium stearate and sodium stearyl fumarate.34MF-367743657Docket No. 21135-20013.40

[0088] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) Compound I, or a pharmaceutically acceptable salt thereof; (b) microcrystalline cellulose (MCC); (c) croscarmellose sodium; (d) magnesium stearate; and (e) sodium stearyl fumarate. In some embodiments, the tablets comprise a pharmaceutically acceptable salt of Compound I. In some embodiments, the pharmaceutically acceptable salt of Compound I is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt or a glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malonate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is glycolate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a fumarate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a malate salt. In some embodiments, the pharmaceutically acceptable salt of Compound I is a citrate salt.

[0089] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) a malonate salt of Compound I; (b) microcrystalline cellulose (MCC); (c) croscarmellose sodium; (d) magnesium stearate; and (e) sodium stearyl fumarate.

[0090] Also provided herein are tablets for oral administration to a subject, said tablets comprising (a) a glycolate salt of Compound I; (b) microcrystalline cellulose (MCC); (c) croscarmellose sodium; (d) magnesium stearate; and (e) sodium stearyl fumarate.

[0091] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 75% w / w to about 95% w / w of one or more diluents. Also disclosed herein are such tablets comprising Compound I, or a pharmaceutically acceptable salt thereof, wherein said tablets comprise from about 75% w / w to about 90% w / w, or from about 80% w / w to about 90% w / w of microcrystalline cellulose, or from about 81% w / w to about 90% w / w, or from about 82% w / w to about 90% w / w, or from about 83% w / w to about 90% w / w, or from about 82% w / w to about 89% w / w, or from about 82% w / w to about 88% w / w of one or more diluents. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0092] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 75% w / w, or about 76% w / w, or about 77% w / w, or about 78% w / w, or about 79% w / w,35MF-367743657Docket No. 21135-20013.40 or about 80% w / w, or about 81% w / w, or about 82% w / w, or about 83% w / w, or about 84% w / w, or about 85% w / w, or about 86% w / w, or about 87% w / w, or about 88% w / w, or about 89% w / w, or about 90% w / w of one or more diluents. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0093] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 75% w / w to about 95% w / w of microcrystalline cellulose. Also disclosed herein are such tablets comprising Compound I, or a pharmaceutically acceptable salt thereof, wherein said compositions comprise from about 75% w / w to about 90% w / w, or from about 80% w / w to about 90% w / w of microcrystalline cellulose, or from about 81% w / w to about 90% w / w, or from about 82% w / w to about 90% w / w, or from about 83% w / w to about 90% w / w, or from about 82% w / w to about 89% w / w, or from about 82% w / w to about 88% w / w of microcrystalline cellulose. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0094] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 75% w / w, or about 76% w / w, or about 77% w / w, or about 78% w / w, or about 79% w / w, or about 80% w / w, or about 81% w / w, or about 82% w / w, or about 83% w / w, or about 84% w / w, or about 85% w / w, or about 86% w / w, or about 87% w / w, or about 88% w / w, or about 89% w / w, or about 90% w / w of microcrystalline cellulose. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0095] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 1% w / w to about 10% w / w of one or more disintegrants. In other embodiments, are provided such tablets comprising from about 1% w / w to about 9% w / w, or from about 1% w / w to about 8% w / w, or from about 1% w / w to about 7% w / w, or from about 1% w / w to about 6%36MF-367743657Docket No. 21135-20013.40 w / w, or from about 1% w / w to about 5% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w of one or more disintegrants. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0096] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w of one or more disintegrants. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0097] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 1% w / w to about 10% w / w of croscarmellose sodium. In other embodiments, are provided such tablets comprising from about 1% w / w to about 9% w / w, or from about 1% w / w to about 8% w / w, or from about 1% w / w to about 7% w / w, or from about 1% w / w to about 6% w / w, or from about 1% w / w to about 5% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w of croscarmellose sodium. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0098] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w of croscarmellose sodium. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.37MF-367743657Docket No. 21135-20013.40

[0099] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 1% w / w to about 10% w / w of two or more lubricants. In other embodiments, are provided such tablets comprising from about 1% w / w to about 9% w / w, or from about 1% w / w to about 8% w / w, or from about 1% w / w to about 7% w / w, or from about 1% w / w to about 6% w / w, or from about 1% w / w to about 5% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w of two or more lubricants. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0100] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise about 1% w / w, or about 2% w / w, or about 3% w / w, or about 4% w / w, or about 5% w / w, or about 6% w / w, or about 7% w / w, or about 8% w / w, or about 9% w / w, or about 10% w / w of two or more lubricants. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0101] Also provided herein tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 0.5% w / w to about 5% w / w of magnesium stearate. In other embodiments, are provided such tablets comprising from about 0.5% w / w to about 4% w / w, or from about 0.5% w / w to about 3% w / w, or from about 0.5% w / w to about 2% w / w, or from about 0.75% w / w to about 3% w / w, or from about 0.75% w / w to about 2% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w, or from about 1% w / w to about 1.75% w / w, or from about 1% w / w to about 1.5% w / w, or from about 1% w / w to about 1.25% w / w of magnesium stearate. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0102] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise about 0.5% w / w, or about 0.75% w / w, or about 1% w / w, or about 1.25% w / w, or about 1.5% w / w, or 38MF-367743657Docket No. 21135-20013.40 about 1.75% w / w, or about 2% w / w, or about 2.25% w / w, or about 2.5% w / w, or about 3% w / w of magnesium stearate. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0103] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate. In other embodiments, are provided such tablets comprising from about 0.5% w / w to about 4.75% w / w, or from about 0.5% w / w to about 4.5% w / w, or from about 0.5% w / w to about 4.25% w / w, or from about 0.5% w / w to about 4% w / w, or from about 0.5% w / w to about 3% w / w, or from about 0.5% w / w to about 2% w / w, or from about 0.75% w / w to about 3% w / w, or from about 0.75% w / w to about 2% w / w, or from about 1% w / w to about 3% w / w, or from about 1% w / w to about 2% w / w, or from about 1% w / w to about 1.75% w / w, or from about 1% w / w to about 1.5% w / w, or from about 1% w / w to about 1.25% w / w of sodium stearyl fumarate. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0104] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise about 0.5% w / w, or about 0.75% w / w, or about 1% w / w, or about 1.25% w / w, or about 1.5% w / w, or about 1.75% w / w, or about 2% w / w, or about 2.25% w / w, or about 2.5% w / w, or about 3% w / w, or about 3.25% w / w, or about 3.5% w / w, or about 3.75% w / w, or about 4% w / w, or about 4.25% w / w, or about 4.5% w / w, or about 4.75% w / w, or about 5% w / w of sodium stearyl fumarate. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0105] Also provided herein are tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed herein wherein said tablets comprise (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate. In other embodiments are provided such tablets, wherein said tablets comprise (a) from about 0.5% w / w to about 4% w / w of magnesium stearate,39MF-367743657Docket No. 21135-20013.40 and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3.25% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 3% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2.25% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 2% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.75% w / w to about 3% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; (a) from about 1% w / w to about 3% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2.25% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 2% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; (a) from about 1% w / w to about 1.75% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 1% w / w to about 1.5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 5% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.75% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.5% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 0.75% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1% w / w to about 3% w / w of sodium stearyl fumarate; or (a) from 40MF-367743657Docket No. 21135-20013.40 about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1.25% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1.5% w / w to about 4% w / w of sodium stearyl fumarate; or (a) from about 0.5% w / w to about 5% w / w of magnesium stearate, and (b) from about 1% w / w to about 4% w / w of sodium stearyl fumarate. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0106] In other embodiments, are provided tablets for oral administration comprising (a) about 1.75% w / w of magnesium stearate, and (b) about 4% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 3% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 2% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 1.75% w / w of sodium stearyl fumarate; (a) about 1.75% w / w of magnesium stearate, and (b) about 1.5% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 1.25% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 1% w / w of sodium stearyl fumarate; or (a) about 1.75% w / w of magnesium stearate, and (b) about 4% w / w of sodium stearyl fumarate. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I, or a glycolate salt of Compound I. In some embodiments, the tablets for oral administration comprise a malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise a glycolate salt of Compound I.

[0107] Also provided are pharmaceutical compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as disclosed in Tables 3 to 6 below (wherein MCC is microcrystalline cellulose; CCS is croscarmellose sodium; MS is magnesium stearate; and SSF is sodium stearyl fumarate). Note that in Tables 3 and 4 below, the % w / w listed for Compound I malonate is the calculated % w / w of the free base form of Compound I. For example (a) Tablet No. 1 comprises about 11.6% w / w of Compound I malonate, which is equivalent to about 10% w / w of the free base form of Compound I, and (b) Tablet No. 3 comprises about 5.8% w / w of Compound I malonate, which is equivalent to about 5% w / w of the free base form of Compound I.Table 341MF-367743657Docket No. 21135-20013.40Tablet No. 1 2 3 4 5 Amount % w / w % w / w % w / w % w / w % w / w 10 10 105 (calculated 5 (calculated (calculated (calculated (calculated Compound I as asas as as malonate Compound I Compound I Compound I Compound I Compound I free base) free base)free base) free base) free base) MCC 83.25 82.25 88.25 85.25 80.25 CCS 4 5 4 4 4 MS 1.75 1.75 1.75 1.75 1.75 SSF 1 1 1 4 4 Total 100 100 100 100 100Table 4Tablet No. 6 7 8 9 10 Amount % w / w % w / w % w / w % w / w % w / w Intragranular10 10 105 (calculated 5 (calculated (calculated (calculated (calculated Compound I as asas as as malonate Compound I Compound I Compound I Compound I Compound I free base) free base)free base) free base) free base) MCC 38.25 37.25 43.25 40.25 35.25 CCS 2 2.5 2 2 2 MS 0.25 0.25 0.25 0.25 0.25 ExtragranularMCC 45 45 45 45 45 CCS 2 2.5 2 2 2 SSF 1 1 1 4 4 MS 1.5 1.5 1.5 1.5 1.5 Total 100 100 100 100 100Table 5Tablet No. 11 12 13 14 15 Amount mg / tablet mg / tablet mg / tablet mg / tablet mg / tablet42MF-367743657Docket No. 21135-20013.40 23.15 23.15 23.15 23.15 23.15 (equivalent (equivalent (equivalent (equivalent (equivalent Compound Ito 20 mg to 20 mg to 20 mg to 20 mg to 20 mg malonateCompound I Compound I Compound I Compound I Compound I free base) free base) free base) free base) free base) MCC* 163.35 161.35 349.85 337.85 157.35 CCS 8 10 16 16 8 MS 3.5 3.5 7 7 3.5 SSF 2 2 4 16 8 Total 200.0 200.0 400.0 400.0 200.0* The actual amount of the intragranular microcrystalline cellulose can be adjusted, for example ± 5%, depending on the purity variation of the Compound I (enozertinib) malonate (e.g., 97%- 103%) in individual batches.Table 6Tablet No. 16 17 18 19 20 Amount mg / tablet mg / tablet mg / tablet mg / tablet mg / tablet Intragranular23.15 23.15 23.15 23.15 23.15 (equivalent (equivalent (equivalent (equivalent (equivalent Compound Ito 20 mg to 20 mg to 20 mg to 20 mg to 20 mg malonateCompound I Compound I Compound I Compound I Compound I free base) free base) free base) free base) free base) MCC* 73.35 or 76.5 71.35 169.85 157.85 67.35 CCS 4 5 8 8 4 MS 0.5 0.5 1 1 0.5 ExtragranularMCC 90 90 180 180 90 CCS 4 5 8 8 4 SSF 2 2 4 16 8 MS 3 3 6 6 3 Total 200.0 200.0 400.0 400.0 200.0* The actual amount of the intragranular microcrystalline cellulose can be adjusted, for example ± 5%, depending on the purity variation of the Compound I (enozertinib) malonate (e.g., 97%- 103%) in individual batches.

[0108] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition 43MF-367743657Docket No. 21135-20013.40 comprising Compound I, or a pharmaceutically acceptable salt thereof, one or more diluents, one or more disintegrants, and at least one lubricant; (b) combining the first mixture with one or more diluents, one or more disintegrants, and one or more lubricants to afford a second mixture; and (c) blending said second mixture afford said pharmaceutical compositions. In some embodiments, the first mixture is milled prior to combining it with the one or more diluents, the one or more disintegrants, and the one or more lubricants to afford the second mixture. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0109] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, one or more diluents, and one or more disintegrants; (b) combining the first mixture with one or more lubricants to afford a second mixture; (c) combining the second mixture with one or more diluents, one or more disintegrants, and one or more lubricants to afford a third mixture; and (d) blending said third mixture afford said pharmaceutical compositions. In some embodiments, the second mixture is milled prior to combining it with the one or more diluents, the one or more disintegrants, and the one or more lubricants to afford the third mixture. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0110] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, one or more diluents, and one or more disintegrants; (b) combining the first mixture with a first lubricant to afford a second mixture; (c) blending the second mixture to afford a blended second mixture; (d) combining the blended second mixture with one or more diluents, one or more disintegrants, and a second lubricant to afford a third mixture; and (d) blending said third mixture to afford said pharmaceutical compositions. In some embodiments, the third mixture further comprises an additional portion of the first lubricant. In some embodiments, the blended second mixture is 44MF-367743657Docket No. 21135-20013.40 compacted and milled prior to combining it with the one or more diluents, the one or more disintegrants, and the second lubricant to afford the third mixture. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0111] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, one or more diluents, and one or more disintegrants; (b) milling said first mixture to afford a milled first mixture; (c) combining the first milled mixture with a first lubricant to afford a second mixture; (d) blending the second mixture to afford a blended second mixture; (e) combining the blended second mixture with one or more diluents, one or more disintegrants, and a second lubricant to afford a third mixture; and (f) blending said third mixture to afford said pharmaceutical compositions. In some embodiments, the third mixture further comprises an additional portion of the first lubricant. In some embodiments, the blended second mixture is compacted and milled prior to combining it with the one or more diluents, the one or more disintegrants, and the second lubricant to afford the third mixture. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0112] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, one or more diluents, and one or more disintegrants; (b) milling said first mixture to afford a first milled mixture; (c) combining the first milled mixture with a first lubricant to afford a second mixture; (d) blending the second mixture to afford a blended second mixture; (e) compacting the blended second mixture to afford to compacted second mixture; (f) milling the compacted second mixture to afford a second milled mixture; (g) combining the second milled mixture with one or more diluents and one or more disintegrants to afford a third mixture; (h) combining the third mixture with an additional portion of a the first lubricant and a second lubricant to afford a fourth 45MF-367743657Docket No. 21135-20013.40 mixture; and (i) blending said fourth mixture to afford the pharmaceutical compositions. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0113] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, a first portion of croscarmellose sodium, and a first portion of magnesium stearate; (b) combining the first mixture with a second portion of microcrystalline cellulose, a second portion of croscarmellose sodium, and sodium stearyl fumarate to afford a second mixture; and (c) blending said second mixture afford said pharmaceutical compositions. In some embodiments, the second mixture further comprises a second portion of magnesium stearate. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0114] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, and a first portion of croscarmellose sodium; (b) combining the first mixture with a first portion of magnesium stearate to afford a second mixture; (c) combining the second mixture with a second portion of microcrystalline cellulose, a second portion of croscarmellose sodium, sodium stearyl fumarate, and a second portion of magnesium stearate to afford a third mixture; and (d) blending said third mixture afford said pharmaceutical compositions. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0115] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition 46MF-367743657Docket No. 21135-20013.40 comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, and a first portion of croscarmellose sodium; (b) milling said first mixture to afford a milled first mixture; (c) combining the first milled mixture with a first portion of magnesium stearate to afford a second mixture; (d) blending the second mixture to afford a blended second mixture; (e) combining the blended second mixture with a second portion of microcrystalline cellulose, a second portion of croscarmellose sodium, sodium stearyl fumarate, and a second portion of magnesium stearate to afford a third mixture; and (f) blending said third mixture to afford said pharmaceutical compositions. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0116] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, and a first portion of croscarmellose sodium; (b) milling said first mixture to afford a first milled mixture; (c) combining the first milled mixture with a first portion of magnesium stearate to afford a second mixture; (d) blending the second mixture to afford a blended second mixture; (e) compacting the blended second mixture to afford to compacted second mixture; (f) milling the compacted second mixture to afford a second milled mixture; (g) combining the second milled mixture with a second portion of microcrystalline cellulose, and a second portion of croscarmellose sodium to afford a third mixture; (h) combining the third mixture with sodium stearyl fumarate and a second portion of magnesium stearate to afford a fourth mixture; and (i) blending said fourth mixture to afford the pharmaceutical compositions. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I.

[0117] Also provided herein are methods of preparing the tablets for oral administration disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, a first portion of croscarmellose sodium, and a first portion of47MF-367743657Docket No. 21135-20013.40 magnesium stearate; (b) combining the first mixture with a second portion of microcrystalline cellulose, a second portion of croscarmellose sodium, and sodium stearyl fumarate to afford a second mixture; (c) blending the second mixture afford a tableting mixture; and (d) compressing the tableting mixture into tablets. In some embodiments, the second mixture further comprises a second portion of magnesium stearate. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I. In some embodiments, the tablets for oral administration further comprise a film coating.

[0118] Also provided herein are methods of preparing the tablets for oral administration disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, and a first portion of croscarmellose sodium; (b) combining the first mixture with a first portion of magnesium stearate to afford a second mixture; (c) combining the second mixture with a second portion of microcrystalline cellulose, a second portion of croscarmellose sodium, sodium stearyl fumarate, and a second portion of magnesium stearate to afford a third mixture; and (d) blending said third mixture afford a tableting mixture; and (e) compressing the tableting mixture into tablets. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I. In some embodiments, the tablets for oral administration further comprise a film coating.

[0119] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, and a first portion of croscarmellose sodium; (b) milling said first mixture to afford a milled first mixture; (c) combining the first milled mixture with a first portion of magnesium stearate to afford a second mixture; (d) blending the second mixture to afford a blended second mixture; (e) combining the blended second mixture with a second portion of microcrystalline cellulose, a second portion of croscarmellose sodium, sodium stearyl fumarate,48MF-367743657Docket No. 21135-20013.40 and a second portion of magnesium stearate to afford a third mixture; and (f) blending said third mixture to afford a tableting mixture; and (g) compressing said tableting mixture into tablets. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I. In some embodiments, the tablets for oral administration further comprise a film coating.

[0120] Also provided herein are methods of preparing the pharmaceutical compositions disclosed herein comprising Compound I, or a pharmaceutically acceptable salt thereof, the methods comprising the steps of: (a) preparing a first mixture by blending a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, a first portion of microcrystalline cellulose, and a first portion of croscarmellose sodium; (b) milling said first mixture to afford a first milled mixture; (c) combining the first milled mixture with a first portion of magnesium stearate to afford a second mixture; (d) blending the second mixture to afford a blended second mixture; (e) compacting the blended second mixture to afford to compacted second mixture; (f) milling the compacted second mixture to afford a second milled mixture; (g) combining the second milled mixture with a second portion of microcrystalline cellulose, and a second portion of croscarmellose sodium to afford a third mixture; (h) combining the third mixture with sodium stearyl fumarate and a second portion of magnesium stearate to afford a fourth mixture; (i) blending said fourth mixture to afford a tableting mixture; and (j) compressing the tableting mixture into tablets. In some embodiments, the methods utilize a pharmaceutically acceptable salt of Compound I. In some embodiments the methods utilize a malonate salt or a glycolate salt of Compound I. In some embodiments the methods utilize a malonate salt of Compound I. In some embodiments the methods utilize a glycolate salt of Compound I. In some embodiments, the tablets for oral administration further comprise a film coating.

[0121] Also provided herein are the pharmaceutical compositions and tablets for oral administration comprising a malonate salt of Compound I as disclosed herein, wherein the malonate salt is in a crystalline form. In some embodiments, the crystalline form of the malonate salt of Compound I exhibits an XRPD pattern comprising a peak at 5.9 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 6.8 ± 0.2 degrees 2-theta. In other embodiments, the XRPD pattern further comprises a peak at 16.0 ± 0.2 degrees 2-theta. In still further embodiments, the XRPD pattern further comprises peaks at 17.1 ± 0.2, 19.0 ± 0.2, and 21.6 ± 0.2 degrees 2-theta. In yet other embodiments, the XRPD pattern further comprises peaks at 12.2 ± 0.2, 20.5 ± 0.2, and 23.7 ± 0.2 degrees 2-theta.49MF-367743657Docket No. 21135-20013.40

[0122] Also provided herein are the pharmaceutical compositions and tablets for oral administration comprising a malonate salt of Compound I as disclosed herein, wherein the malonate salt is in a crystalline form, and wherein the crystalline form of the malonate salt of Compound I exhibits a differential scanning calorimetry trace comprising a peak of from about 147 °C to about 151 °C.

[0123] Also provided herein are the pharmaceutical compositions and tablets for oral administration comprising a malonate salt of Compound I as disclosed herein, wherein the malonate salt is in a crystalline form, and wherein the crystalline form of the malonate salt of Compound I exhibits (a) an XRPD pattern comprising a peak at 5.9 ± 0.2 degrees 2-theta, and (b) a differential scanning calorimetry trace comprising a peak of from about 147 °C to about 151 °C. In further embodiments, the XRPD pattern further comprises a peak at 6.8 ± 0.2 degrees 2-theta. In still further embodiments, the XRPD pattern further comprises a peak at 16.0 ± 0.2 degrees 2-theta. In other embodiments, the XRPD pattern further comprises peaks at 17.1 ± 0.2, 19.0 ± 0.2, and 21.6 ± 0.2 degrees 2-theta. In yet another embodiment, the XRPD pattern further comprises peaks at 12.2 ± 0.2, 20.5 ± 0.2, and 23.7 ± 0.2 degrees 2-theta.

[0124] In some embodiments, the crystalline form of the malonate salt maintains at least 95% of the crystalline form following storage in an open container for at least 7 days at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD. In some embodiments, the crystalline form of the malonate salt maintains at least about 95% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.25%, at least 99.5%, at least 99.75%, at least 99.8%, or at least 99.9%) of the crystalline form following storage in an open container for at least about 7 days (e.g., 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, one month, two months, three months, 6 months, 12 months, 18 months, or 24 months) at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD. In some embodiments, the crystalline form of the malonate salt maintains at least 95% of the crystalline form following storage in an open container for at least 14 days at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD. In some embodiments, the crystalline form of the malonate salt maintains at least about 95% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.25%, at least 99.5%, at least 99.75%, at least 99.8%, or at least 99.9%) of the crystalline form following storage in an open container for at least about 14 days (e.g., 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, one month, two months, three months, 6 months, 12 months, 18 months, or 24 months) at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD.50MF-367743657Docket No. 21135-20013.40

[0125] In some embodiments, the crystalline form of the malonate salt maintains at least 95% of the crystalline form following storage in a closed container for at least 7 days at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD. In some embodiments, the crystalline form of the malonate salt maintains at least about 95% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.25%, at least 99.5%, at least 99.75%, at least 99.8%, or at least 99.9%) of the crystalline form following storage in a closed container for at least about 7 days (e.g., 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, one month, two months, three months, 6 months, 12 months, 18 months, or 24 months) at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD. In some embodiments, the crystalline form of the malonate salt maintains at least 95% of the crystalline form following storage in a closed container for at least 14 days at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD. In some embodiments, the crystalline form of the malonate salt maintains at least about 95% (e.g., at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.25%, at least 99.5%, at least 99.75%, at least 99.8%, or at least 99.9%) of the crystalline form following storage in a closed container for at least about 14 days (e.g., 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, one month, two months, three months, 6 months, 12 months, 18 months, or 24 months) at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD.

[0126] In some embodiments, the malonate salt has a solubility in an aqueous solution having a pH of about 4.5 and at a temperature of about 37 °C, calculated as an amount of the free base of Compound I, of greater than about 2 mg / mL (e.g., greater than about 2.5 mg / mL, greater than about 2.75 mg / mL, greater than about 3 mg / mL, greater than about 3.25 mg / mL, greater than about 3.5 mg / mL, greater than about 3.75 mg / mL, greater than about 4 mg / mL, greater than about 4.25 mg / mL, greater than about 4.5 mg / mL, greater than about 4.75 mg / mL, or greater than about 5 mg / mL). In some embodiments, the malonate salt has a solubility in an aqueous solution having a pH of about 2.9 and at a temperature of about 37 °C, calculated as an amount of the free base of Compound I, of greater than about 2 mg / mL (e.g., greater than about 2.5 mg / mL, greater than about 2.75 mg / mL, greater than about 3 mg / mL, greater than about 3.25 mg / mL, greater than about 3.5 mg / mL, greater than about 3.75 mg / mL, greater than about 4 mg / mL, greater than about 4.25 mg / mL, greater than about 4.5 mg / mL, greater than about 4.75 mg / mL, or greater than about 5 mg / mL).51MF-367743657Docket No. 21135-20013.40

[0127] In some embodiments, the malonate salt has an XRPD pattern substantially as shown in FIG. 1A. Angles as measured in degrees 2-theta and peak intensities that may be observed for the malonate salt using XRPD are shown in Table 7.Table 7Angle [°20] d value (A) Intensity (counts)5.9 15.0 1619.956.8 13.0 424.5312.2 7.3 83.6016.0 5.5 360.3517.1 5.2 119.8019.0 4.7 93.8220.5 4.3 45.9220.9 4.3 71.2121.6 4.1 97.6123.7 3.8 77.6825.6 3.5 47.76

[0128] In some embodiments, the malonate salt has an XRPD pattern displaying at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten of the peaks at degrees 2-theta with the greatest intensity in the XRPD pattern substantially as shown in FIG. 1A or as provided in Table 7. It should be understood that peak intensities can vary depending on a number of factors, including sample preparation, mounting, and the instrument and analytical procedure and settings used to obtain the spectrum. Peak intensities and peak assignments can vary within experimental error. In some embodiments, peak assignments listed herein, including for the malonate salt, can vary by about ± 0.6 degrees, ± 0.4 degrees, ± 0.2 degrees, or ± 0.1 degrees 2-theta.

[0129] In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 12.2 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 19.0 ± 0.2, 20.5 ± 0.2, 20.9 ± 0.2, 21.6 ± 0.2, 23.7 ± 0.2, and 25.6 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 12.2 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 19.0 ± 0.2, 21.6 ± 0.2, and 23.7 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 16.0 ± 0.2, and 17.1 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 12.2 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 19.0 ± 0.4, 20.5 ± 0.4, 20.9 ± 0.4, 21.6 ± 0.4,52MF-367743657Docket No. 21135-20013.40 23.7 ± 0.4, and 25.6 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 12.2 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 19.0 ± 0.4, 21.6 ± 0.4, and 23.7 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 16.0 ± 0.4, and 17.1 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 12.2 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 19.0 ± 0.6, 20.5 ± 0.6, 20.9 ± 0.6, 21.6 ± 0.6, 23.7 ± 0.6, and 25.6 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 12.2 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 19.0 ± 0.6, 21.6 ± 0.6, and 23.7 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 16.0 ± 0.6, and 17.1 ± 0.6 degrees 2-theta. It is to be understood that additional peaks in the XRPD pattern other than those shown in FIG. 1A or as provided in Table 7 may be observed, for instance, due to the presence of impurities, solvent, or other polymorphs or amorphic forms present in the test sample.

[0130] In some embodiments, the malonate salt has an XRPD pattern substantially as shown in FIG. IB. Angles as measured in degrees 2-theta and peak intensities that may be observed for the malonate salt using XRPD are shown in Table 8.Table 8Angle [°20] d value (A) Intensity (counts)5.9 15.0 11406.76.8 13.1 2166.310.8 8.2 142.712.2 7.3 360.9713.9 6.4 43.5716.0 5.5 2587.2217.1 5.2 587.9218.5 4.8 159.6619.0 4.7 308.3820.4 4.4 368.7221.6 4.1 417.7423.7 3.8 270.0326.4 3.4 107.632.1 2.8 36.6653MF-367743657Docket No. 21135-20013.40

[0131] In some embodiments, the malonate salt has an XRPD pattern displaying at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten of the peaks at degrees 2-theta with the greatest intensity in the XRPD pattern substantially as shown in FIG. IB or as provided in Table 8. It should be understood that peak intensities can vary depending on a number of factors, including sample preparation, mounting, and the instrument and analytical procedure and settings used to obtain the spectrum. Peak intensities and peak assignments can vary within experimental error. In some embodiments, peak assignments listed herein, including for the malonate salt, can vary by about ± 0.6 degrees, ± 0.4 degrees, ± 0.2 degrees, or ± 0.1 degrees 2-theta.

[0132] In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 10.8 ± 0.2, 12.2 ± 0.2, 13.9 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 18.5 ± 0.2, 19.0 ± 0.2, 20.4 ± 0.2, 21.6 ± 0.2, 23.7 ± 0.2, 26.4 ± 0.2, and 32.1 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 12.2 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 18.5 ± 0.2, 19.0 ± 0.2, 20.4 ± 0.2, 21.6 ± 0.2, and 23.7 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, and 21.6 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 10.8 ± 0.4, 12.2 ± 0.4, 13.9 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 18.5 ± 0.4, 19.0 ± 0.4, 20.4 ± 0.4, 21.6 ± 0.4, 23.7 ± 0.4, 26.4 ± 0.4, and 32.1 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 12.2 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 18.5 ± 0.4, 19.0 ± 0.4, 20.4 ± 0.4, 21.6 ± 0.4, and 23.7 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, and 21.6 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 10.8 ± 0.6, 12.2 ± 0.6, 13.9 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 18.5 ± 0.6, 19.0 ± 0.6, 20.4 ± 0.6, 21.6 ± 0.6, 23.7 ± 0.6, 26.4 ± 0.6, and 32.1 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 12.2 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 18.5 ± 0.6, 19.0 ± 0.6, 20.4 ± 0.6, 21.6 ± 0.6, and 23.7 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, and 21.6 ± 0.6 degrees 2-theta. It is to be understood that additional peaks in the XRPD pattern other than those shown in FIG. IB or as provided in Table 8 may be observed, for instance, due to the presence of impurities, solvent, or other polymorphs or amorphic forms present in the test sample.54MF-367743657Docket No. 21135-20013.40

[0133] In some embodiments, the malonate salt has an XRPD pattern substantially as shown in FIG. 1C. Angles as measured in degrees 2-theta and peak intensities that may be observed for the malonate salt using XRPD are shown in Table 9.Table 9Angle [°20] d value (A) Intensity (counts)5.9 14.9 12373.96.8 13.1 1460.5710.8 8.2 129.0211.8 7.5 141.9312.2 7.3 265.8913.9 6.4 52.9916.0 5.5 2448.1717.1 5.2 524.4218.5 4.8 150.0419.0 4.7 298.3219.9 4.5 200.3120.4 4.4 236.0620.9 4.3 137.6221.7 4.1 384.4123.7 3.8 268.0325.6 3.5 104.8826.3 3.4 114.66

[0134] In some embodiments, the malonate salt has an XRPD pattern displaying at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten of the peaks at degrees 2-theta with the greatest intensity in the XRPD pattern substantially as shown in FIG. 1C or as provided in Table 9. It should be understood that peak intensities can vary depending on a number of factors, including sample preparation, mounting, and the instrument and analytical procedure and settings used to obtain the spectrum. Peak intensities and peak assignments can vary within experimental error. In some embodiments, peak assignments listed herein, including for the malonate salt, can vary by about ± 0.6 degrees, ± 0.4 degrees, ± 0.2 degrees, or ± 0.1 degrees 2-theta.

[0135] In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 10.8 ± 0.2, 11.8 ± 0.2, 12.2 ± 0.2, 13.9 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 18.5 ±55MF-367743657Docket No. 21135-20013.40 0.2, 19.0 ± 0.2, 19.9 ± 0.2, 20.4 ± 0.2, 20.9 ± 0.2, 21.7 ± 0.2, 23.7 ± 0.2, 25.6 ± 0.2, and 26.3 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 11.8 ± 0.2, 12.2 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 18.5 ± 0.2, 19.0 ± 0.2, 19.9 ± 0.2, 20.4 ± 0.2, 21.7 ± 0.2, and 23.7 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 19.0 ± 0.2, 21.7 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 10.8 ± 0.4, 11.8 ± 0.4, 12.2 ± 0.4, 13.9 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 18.5 ± 0.4, 19.0 ± 0.4, 19.9 ± 0.4, 20.4 ± 0.4, 20.9 ± 0.4, 21.7 ± 0.4, 23.7 ± 0.4, 25.6 ± 0.4, and 26.3 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 11.8 ± 0.4, 12.2 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 18.5 ± 0.4, 19.0 ± 0.4, 19.9 ± 0.4, 20.4 ± 0.4, 21.7 ± 0.4, and 23.7 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 19.0 ± 0.4, 21.7 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 10.8 ± 0.6, 11.8 ± 0.6, 12.2 ± 0.6, 13.9 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 18.5 ± 0.6, 19.0 ± 0.6, 19.9 ± 0.6, 20.4 ± 0.6, 20.9 ± 0.6, 21.7 ± 0.6, 23.7 ± 0.6, 25.6 ± 0.6, and 26.3 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 11.8 ± 0.6, 12.2 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 18.5 ± 0.6, 19.0 ± 0.6, 19.9 ± 0.6, 20.4 ± 0.6, 21.7 ± 0.6, and 23.7 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 19.0 ± 0.6, 21.7 ± 0.6 degrees 2-theta. It is to be understood that additional peaks in the XRPD pattern other than those shown in FIG. 1C or as provided in Table 9 may be observed, for instance, due to the presence of impurities, solvent, or other polymorphs or amorphic forms present in the test sample.

[0136] In some embodiments, the malonate salt has an XRPD pattern comprising a peak at 5.9 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2 and 6.8 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, and 16.0 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 19.0 ± 0.2, and 21.6 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.2, 6.8 ± 0.2, 12.2 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 19.0 ± 0.2, 20.5 ± 0.2, 21.6 ± 0.2, and 23.7 ± 0.2 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising a peak at 5.9 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4 and 6.8 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an56MF-367743657Docket No. 21135-20013.40 XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, and 16.0 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 19.0 ± 0.4, and 21.6 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.4, 6.8 ± 0.4, 12.2 ± 0.4, 16.0 ± 0.4, 17.1 ± 0.4, 19.0 ± 0.4, 20.5 ± 0.4, 21.6 ± 0.4, and 23.7 ± 0.4 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising a peak at 5.9 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6 and 6.8 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, and 16.0 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 19.0 ± 0.6, and 21.6 ± 0.6 degrees 2-theta. In some embodiments, the malonate salt has an XRPD pattern comprising peaks at 5.9 ± 0.6, 6.8 ± 0.6, 12.2 ± 0.6, 16.0 ± 0.6, 17.1 ± 0.6, 19.0 ± 0.6, 20.5 ± 0.6, 21.6 ± 0.6, and 23.7 ± 0.6 degrees 2-theta.

[0137] In some embodiments, the malonate salt has a differential scanning calorimetry trace substantially as shown in FIG. ID. In some embodiments, the malonate salt has a differential scanning calorimetry trace substantially as shown in FIG. IE. In some embodiments, the malonate salt has a differential scanning calorimetry trace substantially as shown in FIG. IF. In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 147 °C to about 151 °C. In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak at 147 ± 4 °C (e.g., 147 ± 3 °C, 147 ± 2 °C, or 147 ± 1 °C). In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak at 149 ± 4 °C (e.g., 149 ± 3 °C, 149 ± 2 °C, or 149 ± 1 °C). In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak at 151 ± 4 °C (e.g., 151 ± 3 °C, 151 ± 2 °C, or 151 ± 1 °C). In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 147 °C to about 150 °C. In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 148 °C to about 151 °C. In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 148 °C to about 150 °C. In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 147 °C to about 149 °C. In some embodiments, the malonate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 149 °C to about 151 °C.57MF-367743657Docket No. 21135-20013.40

[0138] In some embodiments of the malonate salt, at least one, at least two, at least three, at least four, at least five, at least six, at least seven, or all of the following (a)-(h) apply:(a) the malonate salt is a hemi-malonate salt;(b) the malonate salt is in a crystalline form;(c) the crystalline form of the malonate salt maintains at least 95% of the crystalline form following storage in an open container for at least 7 days at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD,(d) the crystalline form of the malonate salt maintains at least 95% of the crystalline form following storage in a closed container for at least 7 days at 40 °C and 75% relative humidity, and wherein the amount of the crystalline form of the salt is measured by XRPD,(e) the malonate salt has a solubility in an aqueous solution having a pH of about 4.5 and at a temperature of about 37 °C, calculated as an amount of the free base of Compound I, of greater than about 2 mg / mL;(f) the malonate salt has a solubility in an aqueous solution having a pH of about 2.9 and at a temperature of about 37 °C, calculated as an amount of the free base of Compound I, of greater than about 2 mg / mL;(g) the malonate salt exhibits an XRPD pattern comprising:(i) a peak at 5.9 ± 0.2 degrees 2-theta;(ii) peaks at 5.9 ± 0.2 and 6.8 ± 0.2 degrees 2-theta;(iii) peaks at 5.9 ± 0.2, 6.8 ± 0.2, and 16.0 ± 0.2 degrees 2-theta;(iv) peaks at 5.9 ± 0.2, 6.8 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 19.0 ± 0.2, and 21.6 ± 0.2 degrees 2-theta; or(v) peaks at 5.9 ± 0.2, 6.8 ± 0.2, 12.2 ± 0.2, 16.0 ± 0.2, 17.1 ± 0.2, 19.0 ± 0.2, 20.5 ± 0.2, 21.6 ± 0.2, and 23.7 ± 0.2 degrees 2-theta; and(h) the malonate salt exhibits a differential scanning calorimetry trace comprising a peak of from about 147 °C to about 151 °C.In some embodiments, (a) and (b) apply. In some embodiments, (a), (b), and (c) apply. In some embodiments, (a), (b), (c), and (d) apply. In some embodiments, (a), (b), (c), (d), and (e) apply. In some embodiments, (a), (b), (c), (d), (e), and (f) apply. In some embodiments, (a), (b), (c), (d), (e), (f), and (g) apply. In some embodiments, (a), (b), (c), (d), (e), (f), (g), and (h) apply. In some embodiments, (g) and (h) apply. In some embodiments, (g)(i) and (h) apply. In some58MF-367743657Docket No. 21135-20013.40 embodiments, (g)(ii) and (h) apply. In some embodiments, (g)(iii) and (h) apply. In some embodiments, (g)(iv) and (h) apply. In some embodiments, (g)(v) and (h) apply. In some embodiments, (e), (g), and (h) apply. In some embodiments, (e), (g)(i), and (h) apply. In some embodiments, (e), (g)(ii), and (h) apply. In some embodiments, (e), (g)(iii), and (h) apply. In some embodiments, (e), (g)(iv), and (h) apply. In some embodiments, (e), (g)(v), and (h) apply. In some embodiments, (f), (g), and (h) apply. In some embodiments, (f), (g)(i), and (h) apply. In some embodiments, (f), (g)(ii), and (h) apply. In some embodiments, (f), (g)(iii), and (h) apply. In some embodiments, (f), (g)(iv), and (h) apply. In some embodiments, (f), (g)(v), and (h) apply. In some embodiments, (e), (f), (g), and (h) apply. In some embodiments, (e), (f), (g)(i), and (h) apply. In some embodiments, (e), (f), (g)(ii), and (h) apply. In some embodiments, (e), (f), (g)(iii), and (h) apply. In some embodiments, (e), (f), (g)(iv), and (h) apply. In some embodiments, (e), (f), (g)(v), and (h) apply.Glycolate Salt

[0139] Also provided herein are the pharmaceutical compositions and tablets for oral administration comprising a glycolate salt of Compound I as disclosed herein, wherein the glycolate salt. In some embodiments, the glycolate salt of Compound I is a hemi-glycolate salt. In other embodiments, the glycolate salt of Compound I is in a crystalline form. In some embodiments, the glycolate salt has an XRPD pattern comprising one or more peaks shown in Table 10.Table 10Angle [°20] d value (A) Intensity (counts)5.4 16.3 271.166.7 13.1 85.197.1 12.5 90.567.4 12.0 66.169.6 9.2 240.5810.4 8.5 109.0910.7 8.3 21.5613.0 6.8 192.1613.3 6.6 110.3214.1 6.3 367.4915.5 5.7 179.2316.9 5.3 143.1359MF-367743657Docket No. 21135-20013.40 Angle [°20] d value (A) Intensity (counts)17.5 5.1 42.2319.4 4.6 311.9620.1 4.4 282.6620.9 4.3 53.921.5 4.1 61.722.4 4.0 188.5522.9 3.9 62.8823.3 3.8 23.4823.7 3.8 27.4624.0 3.7 41.8826.1 3.4 24.0932.5 2.8 49.51

[0140] In some embodiments, the glycolate salt has an XRPD pattern displaying at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten of the peaks at degrees 2-theta with the greatest intensity in the XRPD pattern substantially as shown in FIG. 2A or as provided in Table 10. It should be understood that peak intensities can vary depending on a number of factors, including sample preparation, mounting, and the instrument and analytical procedure and settings used to obtain the spectrum. Peak intensities and peak assignments can vary within experimental error. In some embodiments, peak assignments listed herein, including for the glycolate salt, can vary by about ± 0.6 degrees, ± 0.4 degrees, ± 0.2 degrees, or ± 0.1 degrees 2-theta.

[0141] In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.2, 6.7 ± 0.2, 7.1 ± 0.2, 7.4 ± 0.2, 9.6 ± 0.2, 10.4 ± 0.2, 10.7 ± 0.2, 13.0 ± 0.2, 13.3 ± 0.2, 14.1 ± 0.2, 15.5 ± 0.2, 16.9 ± 0.2, 17.5 ± 0.2, 19.4 ± 0.2, 20.1 ± 0.2, 20.9 ± 0.2, 21.5 ± 0.2, 22.4 ± 0.2, 22.9 ± 0.2, 23.3 ± 0.2, 23.7 ± 0.2, 24 ± 0.2, 26.1 ± 0.2, and 32.5 ± 0.2 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.2, 6.7 ± 0.2, 7.1 ± 0.2, 7.4 ± 0.2, 9.6 ± 0.2, 10.4 ± 0.2, 13.0 ± 0.2, 13.3 ± 0.2, 14.1 ± 0.2, 15.5 ± 0.2, 16.9 ± 0.2, 19.4 ± 0.2, 20.1 ± 0.2, 21.5 ± 0.2, 22.4 ± 0.2, and 22.9 ± 0.2 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.2, 9.6 ± 0.2, 13.0 ± 0.2, 14.1 ± 0.2, 15.5 ± 0.2, 19.4 ± 0.2, 20.1 ± 0.2, and 22.4 ± 0.2 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.4, 6.7 ± 0.4, 7.1 ± 0.4, 7.4 ± 0.4, 9.6 ± 0.4, 10.4 ± 0.4, 10.7 ± 0.4, 13.0 ± 0.4, 13.3 ± 0.4, 14.1 ± 0.4, 15.5 ±60MF-367743657Docket No. 21135-20013.40 0.4, 16.9 ± 0.4, 17.5 ± 0.4, 19.4 ± 0.4, 20.1 ± 0.4, 20.9 ± 0.4, 21.5 ± 0.4, 22.4 ± 0.4, 22.9 ± 0.4, 23.3 ± 0.4, 23.7 ± 0.4, 24 ± 0.4, 26.1 ± 0.4, and 32.5 ± 0.4 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.4, 6.7 ± 0.4, 7.1 ± 0.4, 7.4 ± 0.4, 9.6 ± 0.4, 10.4 ± 0.4, 13.0 ± 0.4, 13.3 ± 0.4, 14.1 ± 0.4, 15.5 ± 0.4, 16.9 ± 0.4, 19.4 ± 0.4, 20.1 ± 0.4, 21.5 ± 0.4, 22.4 ± 0.4, and 22.9 ± 0.4 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.4, 9.6 ± 0.4, 13.0 ± 0.4, 14.1 ± 0.4, 15.5 ± 0.4, 19.4 ± 0.4, 20.1 ± 0.4, and 22.4 ± 0.4 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.6, 6.7 ± 0.6, 7.1 ± 0.6, 7.4 ± 0.6, 9.6 ± 0.6, 10.4 ± 0.6, 10.7 ± 0.6, 13.0 ± 0.6, 13.3 ± 0.6, 14.1 ± 0.6, 15.5 ± 0.6, 16.9 ± 0.6, 17.5 ± 0.6, 19.4 ± 0.6, 20.1 ± 0.6, 20.9 ± 0.6, 21.5 ± 0.6, 22.4 ± 0.6, 22.9 ± 0.6, 23.3 ± 0.6, 23.7 ± 0.6, 24 ± 0.6, 26.1 ± 0.6, and 32.5 ± 0.6 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.6, 6.7 ± 0.6, 7.1 ± 0.6, 7.4 ± 0.6, 9.6 ± 0.6, 10.4 ± 0.6, 13.0 ± 0.6, 13.3 ± 0.6, 14.1 ± 0.6, 15.5 ± 0.6, 16.9 ± 0.6, 19.4 ± 0.6, 20.1 ± 0.6, 21.5 ± 0.6, 22.4 ± 0.6, and 22.9 ± 0.6 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.6, 9.6 ± 0.6, 13.0 ± 0.6, 14.1 ± 0.6, 15.5 ± 0.6, 19.4 ± 0.6, 20.1 ± 0.6, and 22.4 ± 0.6 degrees 2-theta. It is to be understood that additional peaks in the XRPD pattern other than those shown in FIG. 2A or as provided in Table 10 may be observed, for instance, due to the presence of impurities, solvent, or other polymorphs or amorphic forms present in the test sample.

[0142] In some embodiments, the glycolate salt has an XRPD pattern comprising a peak at 14.1 ± 0.2 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 14.1 ± 0.2 and 19.4 ± 0.2 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 14.1 ± 0.2, 19.4 ± 0.2, and 20.1 ± 0.2 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.2, 9.6 ± 0.2, 13.0 ± 0.2, 14.1 ± 0.2, 15.5 ± 0.2, 19.4 ± 0.2, 20.1 ± 0.2, and 22.4 ± 0.2 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising a peak at 14.1 ± 0.4 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 14.1 ± 0.4 and 19.4 ± 0.4 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 14.1 ± 0.4, 19.4 ± 0.4, and 20.1 ± 0.4 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 ± 0.4, 9.6 ± 0.4, 13.0 ± 0.4, 14.1 ± 0.4, 15.5 ± 0.4, 19.4 ± 0.4, 20.1 ± 0.4, and 22.4 ± 0.4 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising a peak at 14.1 ± 0.6 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 14.1 ± 0.6 and 19.4 ± 0.6 degrees 2-theta. In some embodiments, the61MF-367743657Docket No. 21135-20013.40 glycolate salt has an XRPD pattern comprising peaks at 14.1 + 0.6, 19.4 + 0.6, and 20.1 + 0.6 degrees 2-theta. In some embodiments, the glycolate salt has an XRPD pattern comprising peaks at 5.4 + 0.6, 9.6 + 0.6, 13.0 + 0.6, 14.1 + 0.6, 15.5 + 0.6, 19.4 + 0.6, 20.1 + 0.6, and 22.4 + 0.6 degrees 2-theta.

[0143] In some embodiments, the glycolate salt has a differential scanning calorimetry trace substantially as shown in FIG. 2B. In some embodiments, the glycolate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 162 °C to about 165 °C. In some embodiments, the glycolate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak at 162 ± 4 °C (e.g., 162 ± 3 °C, 162 + 2 °C, or 162 + 1 °C). In some embodiments, the glycolate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak at 163 + 4 °C (e.g., 163 + 3 °C, 163 + 2 °C, or 163 + 1 °C). In some embodiments, the glycolate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak at 165 + 4 °C (e.g., 165 + 3 °C, 165 + 2 °C, or 165 + 1 °C). In some embodiments, the glycolate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 162 °C to about 164 °C. In some embodiments, the glycolate salt is characterized as exhibiting a differential scanning calorimetry trace comprising a peak of from about 163 °C to about 165 °C.

[0144] In some embodiments of the glycolate salt, at least one, at least two, at least three, or all of the following (a)-(d) apply:(a) the glycolate salt is a hemi-glycolate salt;(b) the glycolate salt is in a crystalline form;(c) the glycolate salt exhibits an XRPD pattern comprising:(i) a peak at 14.1 + 0.2 degrees 2-theta;(ii) peaks at 14.1 + 0.2 and 19.4 + 0.2 degrees 2-theta;(iii) peaks at 14.1 + 0.2, 19.4 + 0.2, and 20.1 + 0.2degrees 2-theta; or(iv) peaks at 5.4 + 0.2, 9.6 + 0.2, 13.0 + 0.2, 14.1 + 0.2, 15.5 + 0.2, 19.4 + 0.2, 20.1 + 0.2, and 22.4 + 0.2 degrees 2-theta; and(d) the glycolate salt exhibits a differential scanning calorimetry trace comprising a peak of from about 162 °C to about 165 °C.

[0145] In some embodiments, (a) and (b) apply. In some embodiments, (a), (b), and (c) apply. In some embodiments, (a), (b), (c), and (d) apply. In some embodiments, (c) and (d)62MF-367743657Docket No. 21135-20013.40 apply. In some embodiments, (c)(i) and (d) apply. In some embodiments, (c)(ii) and (d) apply. In some embodiments, (c)(iii) and (d) apply. In some embodiments, (c)(iv) and (d) apply.Compositions

[0146] In some embodiments of the composition containing a malonate salt of Compound I, at least about 0.1%, at least about 0.3%, at least about 0.5%, at least about 0.8%, at least about 1.0%, at least about 5.0%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least 99.9% by weight of the total composition is the malonate salt. In some embodiments of the composition containing a malonate salt of Compound I, at least about 0.1%, at least about 0.3%, at least about 0.5%, at least about 0.8%, at least about 1.0%, at least about 5.0%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least 99.9% by weight of Compound I in the composition exists as the malonate salt.

[0147] In some embodiments of the composition containing a glycolate salt of Compound I, at least about 0.1%, at least about 0.3%, at least about 0.5%, at least about 0.8%, at least about 1.0%, at least about 5.0%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least 99.9% by weight of the total composition is the glycolate salt. In some embodiments of the composition containing a glycolate salt of Compound I, at least about 0.1%, at least about 0.3%, at least about 0.5%, at least about 0.8%, at least about 1.0%, at least about 5.0%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least 99.9% by weight of Compound I in the composition exists as the glycolate salt.

[0148] Also Provided herein are methods of treating cancer in a subject in need thereof, wherein the cancer in the individual has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR) and / or HER2, comprising administering to the individual the pharmaceutical compositions or tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein.63MF-367743657Docket No. 21135-20013.40

[0149] Provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the individual the pharmaceutical compositions or tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, wherein the cancer in the individual has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR) and / or HER2 prior to administration to the subject of the pharmaceutical compositions or tablets.

[0150] In some embodiments are provided such methods of treating cancer in a subject in need thereof, wherein the one or more mutations in epidermal growth factor receptor (EGFR) comprise (a) one or more classical EGFR mutations, (b) one or more P-loop and alpha C-helix compressing (PACC) mutations, (c) one or more Exonl8 mutations, (d) one or more Exonl9 mutations, (e) one or more Exon20 point mutations, (f) one or more Exon21 mutations, (g) one or more Exon20 insertion mutations, (h) one more extracellular EGFR mutations, and / or (i) one or more transmembrane EGFR mutations. In some embodiments, the cancer in the individual has been determined to further comprise one or more EGFR mutation selected from T790M and L858R.

[0151] Also provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the individual the pharmaceutical compositions or tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, wherein the cancer is a metastatic solid tumor. In some variations, the cancer is cancer is a metastatic solid tumor and is unresectable. In some variations, the cancer is a metastatic solid tumor and comprises one or more central nervous system (CNS) metastases (e.g., brain metastases). In some variations, the cancer is a metastatic solid tumor and is selected from the group consisting of metastatic brain cancer, breast cancer, and non-small cell lung cancer. In some variations, the cancer is a metastatic solid tumor comprising brain cancer. In some variations, the cancer is a metastatic solid tumor comprising metastatic brain cancer. In some variations, the cancer is a metastatic solid tumor comprising breast cancer. In some variations, the cancer is a metastatic solid tumor comprising non-small cell lung cancer. In some variations, the cancer is metastatic non-small cell lung cancer. In some variations, the cancer is metastatic non-small cell lung cancer, wherein the cancer comprises central nervous system (CNS) metastases (e.g., brain metastases).

[0152] Also provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the individual the pharmaceutical compositions or tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, wherein the cancer in the individual is locally advanced or metastatic non-small 64MF-367743657Docket No. 21135-20013.40 cell lung cancer, and wherein the cancer has progressed on or after platinum-based chemotherapy. In other embodiments are provided such methods, wherein the cancer in the individual is locally advanced or metastatic non- small cell lung cancer comprising one or more mutations in epidermal growth factor receptor (EGFR) as detected by an FDA-approved test, and wherein the cancer has progressed on or after platinum-based chemotherapy.

[0153] Also provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the individual the pharmaceutical compositions or tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, wherein the cancer in the individual is locally advanced or metastatic non- small cell lung cancer comprising one or more mutations in the epidermal growth factor receptor (EGFR), and wherein the cancer has progressed following prior EGFR therapy.

[0154] In another embodiment is provided such methods, wherein the cancer in the individual has been determined to further comprise an EGFR_C797S mutation.

[0155] In another embodiment is provided such methods, wherein the cancer in the individual has been determined not to comprise an EGFR_C797S mutation.

[0156] In some embodiments of the methods provided herein, the cancer in the individual is selected from the group consisting of pseudomyxoma, intrahepatic cholangiocarcinoma, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myeloid leukemia, acute lymphocytic leukemia, basal cell carcinoma, ovarian epithelial cancer, ovarian germ cell cancer, male breast cancer, brain cancer, pituitary adenomas, multiple myeloma, gallbladder cancer, biliary tract cancer, colorectal cancer, chronic myelogenous leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, ampulla of vater cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, nasal and paranasal sinus cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, childhood brain cancer, pediatric lymphoma, pediatric leukemia, small intestine cancer, meningioma, esophageal cancer, glioma, renal carcinoma, kidney cancer, heart cancer, duodenal cancer, malignant soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureter cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoid tumors, gastrointestinal stromal tumors, Wilms cancer, breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational trophoblastic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal cancer, rectal carcinoid tumors, vaginal cancer, spinal carcinoma, acoustic neuroma, pancreatic cancer,65MF-367743657Docket No. 21135-20013.40 salivary gland cancer, Kaposi's sarcoma, Paget's disease, tonsillar cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, lung squamous cell carcinoma, skin cancer, anal cancer, rhabdomyosarcoma, laryngeal cancer, pleural cancer, blood cancer, and thymic carcinoma. In some embodiments, the cancer is selected from the group consisting of metastatic brain cancer, breast cancer, and non-small cell lung cancer. In some embodiments, the cancer is metastatic brain cancer. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is non-small cell lung cancer. In some variations of any of the embodiments described herein, the cancer is a locally advanced cancer. In some variations, the cancer is unresectable. In some variations, the cancer comprises one or more central nervous system (CNS) metastases (e.g., brain metastases).

[0157] In some embodiments of the methods disclosed herein, the individual has not received one or more prior therapy for treatment of the cancer prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the individual has not received one or more (such as 1, 2, or 3) prior therapy for treatment of the cancer prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein.

[0158] In some embodiments of the methods disclosed herein, the cancer is non-small cell lung cancer and the individual has not received prior therapy for treatment of the cancer with an EGFR inhibitor prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the individual has not received prior therapy for treatment of the cancer with an EGFR inhibitor prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual has not received prior therapy for treatment of the cancer with an EGFR inhibitor prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is non-small cell lung cancer that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual has not received prior therapy for treatment of the cancer with an EGFR inhibitor prior to administration to the individual of a pharmaceutical composition or 66MF-367743657Docket No. 21135-20013.40 tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is metastatic non-small cell lung cancer that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual has not received prior therapy for treatment of the cancer with an EGFR inhibitor prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is non-small cell lung cancer comprising central nervous system (CNS) metastases (e.g., brain metastases) that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual has not received prior therapy for treatment of the cancer with an EGFR inhibitor prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I.

[0159] In some embodiments of the methods disclosed herein, the individual is EGFR inhibitor naive prior to administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the cancer is non-small cell lung cancer. In some embodiments, the cancer has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual is EGFR inhibitor naive prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is non-small cell lung cancer that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual is EGFR inhibitor naive prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is metastatic non-small cell lung cancer that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual is EGFR inhibitor naive prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is non-small cell lung cancer comprising central nervous system (CNS) metastases (e.g., brain metastases) that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual is EGFR inhibitor naive prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising67MF-367743657Docket No. 21135-20013.40 Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I.

[0160] In some embodiments of the methods disclosed herein the individual has received one or more prior therapy for treatment of the cancer prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the one or more prior therapies exhibit inhibitory activity against cancer comprising a T790M mutation in the epidermal growth factor receptor (EGFR) protein. In some embodiments, the one or more prior therapies exhibiting inhibitory activity against cancer comprising a T790M mutation in the epidermal growth factor receptor (EGFR) protein comprises osimertinib. In some embodiments, the one or more prior therapies comprise one or more standard therapies for the cancer.

[0161] In some embodiments of the methods disclosed herein, the individual has received one or more prior EGFR inhibitor therapies for treatment of the cancer before administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is non-small cell lung cancer. In some embodiments, the cancer is nonsmall cell lung cancer that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual has received one or more prior EGFR inhibitor therapies for treatment of the cancer prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is metastatic non-small cell lung cancer that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual has received one or more prior EGFR inhibitor therapies for treatment of the cancer prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the cancer is non-small cell lung cancer comprising central nervous system (CNS) metastases (e.g., brain metastases) that has been determined to comprise one or more mutations in epidermal growth factor receptor (EGFR), and the individual has received one or more prior EGFR inhibitor therapies for treatment of the cancer prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition68MF-367743657Docket No. 21135-20013.40 comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I.

[0162] In some embodiments, provided is a method of treating cancer in a subject in need thereof comprising administering to the individual a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, wherein the cancer in the individual comprises one or more central nervous system (CNS) metastases (e.g., brain metastases). In some embodiments, the CNS metastases developed in the individual following prior therapy comprising an EGFR or HER2 inhibitor. In some embodiments, the prior therapy comprises an EGFR inhibitor. In some embodiments, the prior therapy comprises an EGFR exon 20 mutant inhibitor. In some embodiments, the prior therapy comprises an EGFR atypical mutation inhibitor. In some embodiments, the prior therapy comprises a HER2 inhibitor. In some embodiments, the prior therapy comprises a HER2 exon 20 mutant inhibitor. In some embodiments, the administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein successfully treats the one or more one or more central nervous system (CNS) metastases (e.g., brain metastases).

[0163] In some embodiments of the methods disclosed herein, the individual has not received one or more prior EGFR inhibitor therapies for treatment of the cancer before administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, and wherein the individual is further administered a bispecific EGF receptor-directed and MET receptor-directed antibody. In some embodiments, the cancer is non-small cell lung cancer. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab wherein the amivantamab is administered to the subject in the form of a subcutaneous formulation.

[0164] In some embodiments of the methods disclosed herein, the individual has received one or more prior EGFR inhibitor therapies for treatment of the cancer before administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, and wherein the individual is further administered a bispecific EGF receptor-directed and MET receptor-directed 69MF-367743657Docket No. 21135-20013.40 antibody. In some embodiments, the cancer is non-small cell lung cancer. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab wherein the amivantamab is administered to the subject in the form of a subcutaneous formulation.

[0165] In some embodiments of the methods disclosed herein, (a) the cancer is non-small cell lung cancer and (b) the individual has received one or more prior EGFR inhibitor therapies for treatment of the cancer before administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, and wherein individual is further administered amivantamab. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab wherein the amivantamab is administered to the subject in the form of a subcutaneous formulation.

[0166] In some embodiments of the methods disclosed herein, the individual has received one or more prior therapies for treatment of the cancer before administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, and wherein the one or more prior therapies comprise an EGFR inhibitor and a bispecific EGF receptor-directed and MET receptor-directed antibody. In some embodiments, the cancer is non-small cell lung cancer. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I.

[0167] In some embodiments of the methods disclosed herein, the cancer is non-small cell lung cancer and the individual has received one or more prior therapies for treatment of the cancer before administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed 70MF-367743657Docket No. 21135-20013.40 herein, and wherein the one or more prior therapies comprise an EGFR inhibitor and amivantamab. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I.

[0168] In some embodiments, the individual has been administered osimertinib prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein. In some embodiments, the administration of osimertinib has been completed for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months at the time when the individual is administered the pharmaceutical compositions or tablets for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein.

[0169] In some variations of any of the embodiments described herein, the individual has received one or more prior therapies for treatment of the cancer before administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, and wherein the one or more prior therapies comprises chemotherapy. In some embodiments, the one or more prior therapies comprising chemotherapy comprises platinum-based chemotherapy. In some embodiments, the one or more prior therapies comprising chemotherapy does not comprise platinum-based chemotherapy. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I.

[0170] In some embodiments of the methods disclosed herein, the individual has failed one or more prior therapies prior to administration to the individual of a pharmaceutical composition or tablet for oral administration comprising Compound I, or a pharmaceutically acceptable salt thereof, disclosed herein, and wherein the one or more prior therapies is selected from (a) a bispecific EGF receptor-directed and MET receptor-directed antibody, and (b) chemotherapy. In some embodiments, the one or more prior therapies is a bispecific EGF receptor-directed and MET receptor-directed antibody. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab. In some embodiments, the one or more prior therapies is chemotherapy. In some embodiments, the one or more prior therapies comprising chemotherapy comprises platinum-based chemotherapy. In some embodiments, the one or more prior therapies comprising chemotherapy does not comprise platinum-based71MF-367743657Docket No. 21135-20013.40 chemotherapy. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I. In some embodiments, the tablets for oral administration comprise the malonate salt of Compound I.

[0171] In some embodiments, the method further comprises administering to the individual in need thereof one or more additional anticancer agents or a second therapy. In some embodiments, the one or more additional anticancer agents comprises one or more agents selected from the group consisting of HER2 inhibitors, HER2-CD3 bispecific antibodies, HER2-immune targeting bispecific antibodies, anti-HER2 chimeric antigen receptor (CAR) T cells, anti-HER2 chimeric antigen receptor (CAR) cytotoxic T-lymphocytes (CTLs), anti-HER2 chimeric antigen receptor (CAR) natural killer (NK) cells, anti-HER2 chimeric antigen receptor (CAR) cytokine-induced killer (CIK) cells, epidermal growth factor receptor (EGFR) inhibitors, poly-ADP-ribose polymerase (PARP) inhibitors, PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, and chemotherapeutic agents.

[0172] Exemplary HER2 inhibitors include, but are not limited to, trastuzumab, trastuzumab and hyaluronidase, trastuzumab and capecitabine, tucatinib, lapatinib, neratinib, dacomitinib, pertuzumab, margetuximab, trastuzumab emtansine, trastuzumab deruxtecan, ZW49 (Zymeworks), A166 (Klaus Pharma), ARX788 (Ambrx), RC48-ADC (RemeGen), victrastuzumab duocarmazine, zanidatamab (ZW25), zenocutuzamab (MCLA-128), ISB 1302, afatanib, poziotinib, pyrotinib, mobocertinib (TAK-788), andBDTX-189.

[0173] Exemplary EGFR inhibitors include, but are not limited to, erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, vandetanib, afatinib, brigatinib, and icotinib.

[0174] Exemplary PARP inhibitors include, but are not limited to, niraparib, olaparib, talazoparib, rucaparib, veliparib, iniparib, pamiparib (BGB-290), CEP-9722, and E7016.

[0175] Exemplary PD-1 inhibitors include, but are not limited to, pembrolizumab, nivolumab, cemiplimab, JTX-4014, spartalizumab (PDR001), camrelizumab (SHR1210), sintilimab (IB 1308), tislelizumab (BGB-A317), toripalimab (JS 001), dostarlimab (TSR-042, WBP-285), INCMGA00012 (MGA012), AMP-224, and AMP-514.

[0176] Exemplary PD-L1 inhibitors include, but are not limited to, atezolizumab, avelumab, durvalumab, KN035, CK-301, AUNP12, CA-170, and BMS-986189.

[0177] Exemplary CTLA-4 inhibitors include ipilimumab and tremelimumab.72MF-367743657Docket No. 21135-20013.40

[0178] In some embodiments, the one or more additional cancer agents are selected from the group consisting of bevacizumab, trastuzumab, trastuzumab and hyaluronidase, capecitabine, trastuzumab and capecitabine, tucatinib, lapatinib, neratinib, dacomitinib, pertuzumab, margetuximab, trastuzumab emtansine, trastuzumab deruxtecan, ZW49 (Zymeworks), A 166 (Klaus Pharma), ARX788 (Ambrx), RC48-ADC (RemeGen), vic-trastuzumab duocarmazine, zanidatamab (ZW25), zenocutuzamab (MCLA-128), ISB 1302, afatanib, poziotinib, pyrotinib, mobocertinib (TAK-788), and BDTX-189, erlotinib, osimertinib, gefitinib, cetuximab, panitumumab, necitumumab, vandetanib, afatinib, brigatinib, icotinib, niraparib, olaparib, talazoparib, rucaparib, veliparib, iniparib, pamiparib (BGB-290), CEP-9722, E7016, pembrolizumab, nivolumab, cemiplimab, JTX-4014, spartalizumab (PDR001), camrelizumab (SHR1210), sintilimab (IB 1308), tislelizumab (BGB-A317), toripalimab (JS 001), dostarlimab (TSR-042, WBP-285), INCMGA00012 (MGA012), AMP-224, AMP-514, atezolizumab, avelumab, durvalumab, KN035, CK-301, AUNP12, CA-170, and BMS-986189.

[0179] In some embodiments, the one or more additional cancer agents are selected from antibody-drug conjugates. In some embodiments, the antibody-drug conjugates are selected from the group consisting of trastuzumab emtansine and trastuzumab deruxtecan.

[0180] In some embodiments, the one or more additional anticancer agents comprises one or more chemotherapeutic agents. In some embodiments, the one or more chemotherapeutic agents is selected from the group consisting of doxorubicin, docetaxel, pemetrexed, paclitaxel, carboplatin, cisplatin, capecitabine, gemcitabine, vinorelbine, temozolomide, irinotecan, oxiplatin, and eribulin.

[0181] In some embodiments, the one or more additional anticancer agents comprise trastuzumab and capecitabine.

[0182] In some embodiments, the one or more additional anticancer agents comprise a PI3K inhibitor. Exemplary PI3K inhibitors include, but are not limited to, taselisib (GDC-0032), GDC-0077, perifosine, idelalisib, buparlisib (BKM120), duvelisib, (IPI-145), copanlisib (BAY SO-6946), PX-866, dactolisib, CUDC-907, voxtalisib (SAR245409, XL765), ME-401, IPI-549, SF1126, RP6530, INK1117, pictilisib (GDC-0941), XL147 (SAR245408), palomid 529, GSK1059615, ZSTK474, and PWT33597.

[0183] In some embodiments, the one or more additional cancer agents are selected from the group consisting of erlotinib, gefitinib, afatanib, bevacizumab, trastuzumab, trastuzumab and hyaluronidase, capecitabine, trastuzumab and capecitabine, tucatinib, lapatinib, neratinib, dacomitinib, pertuzumab, margetuximab, trastuzumab emtansine, trastuzumab deruxtecan,73MF-367743657Docket No. 21135-20013.40 ZW49 (Zymeworks), A166 (Klaus Pharma), ARX788 (Ambrx), RC48-ADC (RemeGen), victrastuzumab duocarmazine, zanidatamab (ZW25), zenocutuzamab (MCLA-128), ISB 1302, , poziotinib, pyrotinib, mobocertinib (TAK-788), and BDTX-189, osimertinib, cetuximab, panitumumab, necitumumab, vandetanib, brigatinib, icotinib, niraparib, olaparib, talazoparib, rucaparib, veliparib, iniparib, pamiparib (BGB-290), CEP-9722, E7016, pembrolizumab, nivolumab, cemiplimab, JTX-4014, spartalizumab (PDR001), camrelizumab (SHR1210), sintilimab (IB 1308), tislelizumab (BGB-A317), toripalimab (JS 001), dostarlimab (TSR-042, WBP-285), INCMGA00012 (MGA012), AMP-224, AMP-514, atezolizumab, avelumab, durvalumab, KN035, CK-301, AUNP12, CA-170, and BMS-986189.

[0184] In some embodiments, the one or additional cancer agents are selected from the group consisting of osimertinib, erlotinib, gefitinib, and afatinib.

[0185] In some embodiments, the one or additional cancer agents comprise osimertinib.

[0186] In some embodiments, the one or additional cancer agents comprise erlotinib.

[0187] In some embodiments, the one or additional cancer agents comprise gefitinib.

[0188] In some embodiments, the one or additional cancer agents comprise afatinib.

[0189] In some variations of any of the embodiments described herein, the method further comprises administering to the individual in need thereof one or more additional anticancer agents, wherein the one or more additional anticancer agents comprises a bispecific EGF receptor-directed and MET receptor-directed antibody. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab. In some embodiments, the bispecific EGF receptor-directed and MET receptor-directed antibody is amivantamab wherein the amivantamab is administered to the subject in the form of a subcutaneous formulation.

[0190] In some embodiments, the method further comprises treating the individual in need thereof with radiation.

[0191] In some variations, the cancer comprises a mutation in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein. In some variations, the cancer does not comprise a mutation in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein. In some variations, the cancer does not comprise a mutation in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein at histidine 1047. In some variations, the cancer does not comprise a mutation in74MF-367743657Docket No. 21135-20013.40 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein selected from H1047L and H1047R.

[0192] In some variations of any of the embodiments described herein, the cancer comprises one or more (such as 1, 2, or 3) mutations in the epidermal growth factor receptor (EGFR) protein. In some variations, the one or more mutations in the EGFR protein comprises one or more (such as 1, 2, or 3) mutations selected from the group consisting of I767M, D769H, D769Y, V777L, Y835F,V842I, R896C, G1201V, del.755-759EGFR Dell9 / T790M, EGFR L858R / T790M, EGFR L858R, EGFR del 19, EGFR L858R / C797S, EGFR dell9 / C797S, EGFR Exon20 ins NPH, EGFR Exon20 ins SVD, EGFR Exon20 ins FQEA, EGFR Exon20 ins H, and EGFR Exon20 ins ASV. In some variations, the cancer comprises one or more mutations selected from the group consisting I767M, D769H, D769Y, V777L, Y835F,V842I, R896C, G1201V, del.755-759EGFR Dell9 / T790M, EGFR L858R / T790M, EGFR L858R, EGFR del 19, EGFR L858R / C797S, EGFR dell9 / C797S, EGFR Exon20 ins NPH, EGFR Exon20 ins SVD, EGFR Exon20 ins FQEA, EGFR Exon20 ins H, and EGFR Exon20 ins ASV. In some variations, the cancer does not comprise any of the EGFR mutations described above. In some variations, the cancer does not comprise any mutation in the epidermal growth factor receptor (EGFR) protein

[0193] In some variations of any of the embodiments described herein, the cancer in the individual has been determined to comprise one or more mutations in the extracellular domain and / or transmembrane domain (the extracellular domain and the transmembrane domain, collectively, “ECTM domain”) of epidermal growth factor receptor (EGFR). In one embodiment is provided such methods, wherein the one or more mutations in the ECTM domain of epidermal growth factor receptor (EGFR) comprises one or more mutations in amino acid residues 25 to 668 of EGFR. It is specifically contemplated herein that when a cancer in an individual has been determined to comprise one or more mutations in the ECTM domain of EGFR, the cancer may comprise (a) one or more mutations in the extracellular domain of EGFR, (b) one or more mutations in the transmembrane domain of EGFR, or (c) one or more mutations in the extracellular domain of EGFR and one or more mutations in the transmembrane domain of EGFR. In some embodiments, the one or more mutations in the ECTM domain are in the extracellular domain of EGFR. In other embodiments, the one or more mutations in the ECTM domain are in the transmembrane domain of EGFR. In still further embodiments, there are one or more mutations in the extracellular domain of EGFR and one or more mutations in the transmembrane domain of EGFR. The term “extracellular domain of epidermal growth factor receptor (EGFR)” means the portion of the human EGFR protein that is outside a cell, including 75MF-367743657Docket No. 21135-20013.40 extracellular domains I-IV (also referred to as LI, CR1, L2 and CR2 or LI, SI, L2 and S2), and comprising amino acid residues 25 to 645 of the human EGFR protein (SEQ ID NO: 1). As used herein, the term “one or more mutations in the extracellular domain of epidermal growth factor receptor (EGFR)” means a mutation of one or more amino acid residues 25 to 645 in the amino acid sequence of the human, wild-type EGFR protein (SEQ ID NO: 1). In some embodiments, the one or more mutations in the extracellular domain of epidermal growth factor receptor (EGFR) is at one or more amino acid residues in the human EGFR protein selected from the group consisting of amino acid residue numbers 31, 53, 61, 62, 63, 65, 71, 80, 84, 86, 94, 98, 100, 103, 108, 114, 120, 127, 132, 136, 141, 147, 148, 149, 152, 159, 163, 165, 178, 184, 185, 186, 197, 200, 209, 211, 213, 221, 222, 228, 229, 231, 233, 237, 247, 252, 255, 256, 261, 263, 265, 274, 275, 277, 282, 289, 292, 297, 302, 303, 304, 306, 310, 311, 312, 314, 324, 325, 330, 333, 363, 368, 369, 377, 398, 403, 404, 410, 416, 421, 424, 425, 427, 439, 441, 442, 444, 447, 451, 462, 464, 465, 467, 477, 482, 485, 486, 491, 492, 494, 502, 508, 519, 520, 524, 526, 527, 535, 536, 537, 540, 549, 551, 554, 556, 561, 568, 572, 574, 582, 587, 588, 589, 595, 596, 598, 600, 606, 614, 616, 620, 621, 622, 626, 627, 628, 629, 637, 642, 644, and 645.

[0194] In some variations of any of the embodiments described herein, the cancer comprises one or more (such as 1, 2, or 3) mutations in the HER2 protein, wherein the one or more (such as 1, 2, or 3) mutations in the HER2 protein is selected from p.A775_G776insYVMA, p.778insGCP, p.G780_P781dupGSP, and p.G778_S779insCPG. In some variations, the cancer does not comprise any mutation in the HER2 protein. In some variations, the cancer does not comprise one or more mutations in the HER2 protein. In some variations, the cancer does not comprise one or more exon 20 insertion mutations in the HER2 protein. In some variations, the cancer does not comprise one or more exon 20 insertion mutations in the HER2 protein, selected from p.A775_G776insYVMA, p.778insGCP, p.G780_P781dupGSP, and p.G778_S779insCPG. In some variations, the cancer does not comprise an exon 20 insertion mutation in the HER2 protein that is p.A775_G776insYVMA. In some variations, the cancer does not comprise an exon 20 insertion mutation in the HER2 protein that is p.778insGCP. In some variations, the cancer does not comprise an exon 20 insertion mutation in the HER2 protein that is p.G780_P781dupGSP. In some variations, the cancer does not comprise an exon 20 insertion mutation in the HER2 protein that is p.G778_S779insCPG. In some variations, the cancer does not comprise a mutation in the HER2 protein that is L775S. In some variations, the cancer does not comprise a mutation in the HER2 protein that is G776C.

[0195] In some embodiments, the individual is a mammal. In some embodiments, the individual is a human.76MF-367743657Docket No. 21135-20013.40

[0196] In some instances, the subject or individual treated with the pharmaceutical composition or the tablet described herein is concomitantly administered with a gastric-acid reducing agent. In some embodiments, the subject or individual has taken the gastric-acid reducing agent before the pharmaceutical composition or the tablet described herein. In some embodiments, the subject or individual takes the gastric-acid reducing agent after the pharmaceutical composition or the tablet described herein. In some embodiments, the subject or individual takes the gastric-acid reducing agent simultaneously with the pharmaceutical composition or the tablet described herein. In some embodiments, one or more pharmacokinetic parameters of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide measured from the subject or individual is less than 20% different from the corresponding pharmacokinetic parameters when the subject or individual is administered without the gastric-acid reducing agent, optionally wherein the difference is less than 15% or less than 10%. In some embodiments, one or more pharmacokinetic parameters of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyljacrylamide in the subject or individual is less than 20% different from the corresponding pharmacokinetic parameters in a comparable subject or individual who is not concomitantly administered with the gastric-acid reducing agent, optionally wherein the difference is less than 15% or less than 10%. In some embodiments, the gastric-acid reducing agent is a proton pump inhibitor. In some embodiments, the gastric-acid reducing agent is an antiacid. In some embodiments, the gastric-acid reducing agent is a Histamine-2(H2) blocker. In some embodiments, the gastric-acid reducing agent is a promotility agent. In some embodiments, the proton pump inhibitor is esomeprazole. In some embodiments, the proton pump inhibitor is omeprazole, lansoprazole, pantoprazole, dexlansoprazole, or rabeprazole.Determination of EGFR mutational status

[0197] In some aspects of the methods disclosed herein, the EGFR mutational status of a cancer in a subject involve is derived from analysis of a biological sample obtained from the individual. The methods of obtaining such a biological sample may include methods of biopsy such as fine needle aspiration, core needle biopsy, vacuum assisted biopsy, incisional biopsy, excisional biopsy, punch biopsy, shave biopsy or skin biopsy. In certain embodiments the sample is obtained from a biopsy from lung tissue by any of the biopsy methods previously mentioned. In other embodiments the sample may be obtained from any of the tissues provided herein that include but are not limited to non-cancerous or cancerous tissue and non-cancerous or cancerous tissue from the serum, gall bladder, mucosal, skin, heart, lung, breast, pancreas, blood, liver,77MF-367743657Docket No. 21135-20013.40 muscle, kidney, smooth muscle, bladder, colon, intestine, brain, prostate, esophagus, or thyroid tissue. In some aspects, a sample is a cancerous or non-cancerous lung tissue sample.Alternatively, the sample may be obtained from any other source including but not limited to blood, sweat, hair follicle, buccal tissue, tears, menses, feces, or saliva. A sample may include but is not limited to, tissue, cells, or biological material from cells or derived from cells of a subject. The biological sample may be a heterogeneous or homogeneous population of cells or tissues. The biological sample may be obtained using any method known to the art that can provide a sample suitable for the analytical methods described herein.

[0198] In some cases, a biological sample is a cell-free sample (e.g., a serum sample). In such cases, a biological sample may contain cell-free nucleic acids such as DNA (e.g., cell-free tumor DNA, cell-free fetal DNA) or RNA (e.g., cell-free tumor RNA, cell-free fetal RNA). In some aspects, a cell-free biological sample contains, or is suspected of containing, DNA or RNA from lung cancer.

[0199] The EGFR mutational status of a cancer in a subject may be determined by analyzing the sample of biological materials derived from a subject by using commercial providers and / or methods known to those having ordinary skill in the art. Examples of such methods include, but are not limited to, next- generation sequencing (NGS) technologies [including FoundationOne (Foundation Medicine), Tempus xT (Tempus), Tempus xF (Tempus), Oncomine Dx target test (ODxTT; Thermo Fisher Scientific); Guardant360 TissueNext (Guardant Health); and GuardantOMNI (Guardant Health)], RT-PCR [including the RT-qPCR-based cobas EGFR mutation test v2 (cobas EGFR: Roche Molecular Systems)], fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), polony sequencing, Illumina (Solexa) sequencing, sequencing by oligonucleotide ligation and detection (SOEiD) sequencing, ion torrent semiconductor sequencing, DNA nanoball sequencing, Heliscope single molecule sequencing, and single molecule real time (SMRT) sequencing. Some of these methods are described in Dalurzo et al., OncoTargets and Therapy, 2021, vol. 14, pp. 4671-4692, which is hereby incorporated by reference in its entirety.

[0200] In some embodiments, methods involve amplifying and / or sequencing one or more target genomic regions using at least one pair of primers specific to the target genomic regions. In other embodiments, enzymes are added such as primases or primase / polymerase combination enzyme to the amplification step to synthesize primers.

[0201] In some embodiments, arrays can be used to detect nucleic acids of the disclosure. An array comprises a solid support with nucleic acid probes attached to the support. Arrays typically comprise a plurality of different nucleic acid probes that are coupled to a surface of a substrate in 78MF-367743657Docket No. 21135-20013.40 different, known locations. These arrays, also described as "microarrays" or colloquially "chips" have been generally described in the art, for example, U.S. Pat. Nos. 5,143,854, 5,445,934, 5,744,305, 5,677,195, 6,040,193, 5,424,186 and Fodor et al., 1991, each of which is incorporated by reference in its entirety for all purposes. Techniques for the synthesis of these arrays using mechanical synthesis methods are described in, e.g., U.S. Pat. No. 5,384,261, incorporated herein by reference in its entirety for all purposes. Arrays may be nucleic acids on beads, gels, polymeric surfaces, fibers such as fiber optics, glass or any other appropriate substrate, see U.S. Pat. Nos. 5,770,358, 5,789,162, 5,708,153, 6,040,193 and 5,800,992, which are hereby incorporated in their entirety for all purposes.

[0202] Other assays that may be used to analyze nucleic acids in order to determine the EGFR mutational status of a biological sample derived from a subject in need thereof that are known to those of ordinary skill in the art include, but are not limited to, nucleic amplification, polymerase chain reaction, quantitative PCR, RT-PCR, in situ hybridization, digital PCR, ddPCR (droplet digital PCR), nCounter (nanoString), BEAMing (Beads, Emulsions, Amplifications, and Magnetics) (Inostics), ARMS (Amplification Refractory Mutation Systems), RNA-Seq, TAm-Seg (Tagged- Amplicon deep sequencing), PAP (Pyrophosphorolysis-activation polymerization), next generation RNA sequencing, northern hybridization, hybridization protection assay (HP A) (GenProbe), branched DNA (bDNA) assay (Chiron), rolling circle amplification (RCA), single molecule hybridization detection (US Genomics), Invader assay (ThirdWave Technologies), and / or Bridge Litigation Assay (Genaco).Dosing and method of administration

[0203] The amount of Compound I, or a pharmaceutically acceptable salt thereof, as described herein administered to a subject (e.g., a human) may vary with the particular composition, the method of administration, and the particular cancer being treated. The amount should be sufficient to produce a desirable response, such as a therapeutic response against the cancer. In some embodiments, the amount of Compound I, or a pharmaceutically acceptable salt thereof, as described herein is below the level that induces a toxicological effect (e.g., an effect above a clinically acceptable level of toxicity) or is at a level where a potential side effect can be controlled or tolerated when a salt of Compound I as described herein is administered to the individual.

[0204] In some embodiments, Compound I, or a pharmaceutically acceptable salt thereof, as described herein, and a second agent or therapy are administered simultaneously to the individual. In some embodiments, Compound I, or a pharmaceutically acceptable salt thereof, as described herein, and a second agent or therapy are administered concurrently to the individual.79MF-367743657Docket No. 21135-20013.40 In some embodiments, Compound I, or a pharmaceutically acceptable salt thereof, as described herein and a second agent or therapy are administered sequentially to the individual.

[0205] In some embodiments, a dosage of from about 1 mg / kg to about 100 mg / kg of Compound I, or a pharmaceutically acceptable salt thereof, as described herein is administered into a subject, such as a human (e.g., from about 1 mg / kg to about 75 mg / kg, from about 2 mg / kg to about 75 mg / kg, from about 3 mg / kg to about 75 mg / kg, from about 4 mg / kg to about 75 mg / kg, from about 5 mg / kg to about 75 mg / kg, from about 1 mg / kg to about 50 mg / kg, from about 2 mg / kg to about 50 mg / kg, from about 3 mg / kg to about 50 mg / kg, from about 4 mg / kg to about 50 mg / kg, from about 5 mg / kg to about 50 mg / kg, from about 1 mg / kg to about 40 mg / kg, from about 2 mg / kg to about 40 mg / kg, from about 3 mg / kg to about 40 mg / kg, from about 4 mg / kg to about 40 mg / kg, from about 5 mg / kg to about 40 mg / kg, from about 1 mg / kg to about 30 mg / kg, from about 2 mg / kg to about 30 mg / kg, from about 3 mg / kg to about 30 mg / kg, from about 4 mg / kg to about 30 mg / kg, from about 5 mg / kg to about 30 mg / kg, from about 6 mg / kg to about 80 mg / kg, from about 10 mg / kg to about 80 mg / kg, from about 15 mg / kg to about 80 mg / kg, from about 20 mg / kg to about 80 mg / kg, from about 25 mg / kg to about 80 mg / kg, from about 30 mg / kg to about 80 mg / kg, from about 35 mg / kg to about 80 mg / kg, from about 40 mg / kg to about 80 mg / kg, from about 45 mg / kg to about 80 mg / kg, or from about 50 mg / kg to about 80 mg / kg). In some embodiments, a salt of Compound I as described herein is administered to a subject (e.g., human) once or twice daily, optionally orally or parentally. For oral administration, an exemplary daily dose of Compound I, or a pharmaceutically acceptable salt thereof, as described herein will be from about 0.001 to about 1000 mg / kg of body weight, with courses of treatment repeated at appropriate intervals.

[0206] Furthermore, Compound I, or a pharmaceutically acceptable salt thereof, as described herein may be administered according to the methods disclosed herein in an amount of about 10 mg to about 2000 mg, or from about 10 mg to about 1500 mg, or from about 10 mg to about 1000 mg, or from about 10 mg to about 750 mg, or from about 10 mg to about 500 mg, or from about 25 mg to about 500 mg, or from about 50 to about 500 mg, or from about 100 mg to about 500 mg, or from about 10 mg to about 750 mg, or from about 10 mg to about 700 mg, or from about 10 mg to about 650 mg, or from about 10 mg to about 600mg, or from about 10 mg to about 575 mg, or from about 10 mg to about 550 mg, or from about 10 mg to about 500 mg, or from about 10 mg to about 450 mg, or from about 10 mg to about 400 mg, or from about 10 mg to about 350 mg, or from about 10 mg to about 300 mg, or from about 10 mg to about 275 mg, or from about 10 mg to about 250 mg, or from about 10 mg to about 200 mg, or from about 10 mg to about 150 mg, or from about 10 mg to about 100 mg, or from about 10 mg to about 75 mg, or 80MF-367743657Docket No. 21135-20013.40 from about 10 mg to about 50 mg, or from about 10 mg to about 25 mg, or from about 80 mg to about 120 mg.

[0207] Furthermore, Compound I, or a pharmaceutically acceptable salt thereof, as described herein may be administered according to the methods disclosed herein once per day (QD).Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I, of about 6 mg QD, about 12 mg QD, about 20 mg QD, about 30 mg QD, about 45 mg QD, about 60 mg QD, about 75 mg QD, about 80 mg QD, about 85 mg QD, about 90 mg QD, about 95 mg QD, about 100 mg QD, about 105 mg QD, about 110 mg QD, about 115 mg QD, about 120 mg QD, about 125 mg QD, about 130 mg QD, about 135 mg QD, about 140 mg QD, about 145 mg QD, about 150 mg QD, about 155 mg QD, about 160 mg QD, about 165 mg QD, about 170 mg QD, about 175 mg QD, about 180 mg QD, about 185 mg QD, about 190 mg QD, about 195 mg QD, or about 200 mg QD. In one embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 6 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 12 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 20 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 30 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 45 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 60 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 75 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 80 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 90 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 105 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in81MF-367743657Docket No. 21135-20013.40 an amount that provides an amount of the free base of Compound I of about 110 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 115 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 120 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 125 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 130 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 135 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 140 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 145 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 150 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 155 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 160 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 165 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 170 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 175 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 180 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 185 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 190 mg QD. In 82MF-367743657Docket No. 21135-20013.40 another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 195 mg QD. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 200 mg QD.

[0208] In another embodiment, Compound I may be administered as a salt in an amount that provides an amount of the free base of Compound I of about 60 mg QD, or about 65 mg QD, or about 70 mg QD, or about 75 mg QD, or about 80 mg QD, or about 85 mg QD, or about 90 mg QD, or about 95 mg QD, or about 100 mg QD, or about 110 mg QD, or about 115 mg QD, or about 120 mg QD, or about 125 mg QD, or about 130 mg QD, or about 135 mg QD, or about 140 mg QD, or about 145 mg QD, or about 150 mg QD, or about 155 mg QD, or about 160 mg QD, or about 165 mg QD, or about 170 mg QD, or about 180 mg QD, or about 190 mg QD, or about 200 mg QD. In some embodiments, Compound I may be administered as a salt in an amount that provides an amount of the free base of Compound I of about 80 mg QD or about 120 mg QD. In some embodiments, Compound I may be administered as a salt in an amount that provides an amount of the free base of Compound I of about 80 mg QD. In some embodiments, Compound I may be administered as a salt in an amount that provides an amount of the free base of Compound I of about 120 mg QD.

[0209] In some embodiments, Compound I as administered in the form of a malonate salt in an amount that provides an amount of the free base of Compound I of about 60 mg QD, or about 65 mg QD, or about 70 mg QD, or about 75 mg QD, or about 80 mg QD, or about 85 mg QD, or about 90 mg QD, or about 95 mg QD, or about 100 mg QD, or about 110 mg QD, or about 115 mg QD, or about 120 mg QD, or about 125 mg QD, or about 130 mg QD, or about 135 mg QD, or about 140 mg QD, or about 145 mg QD, or about 150 mg QD, or about 155 mg QD, or about 160 mg QD, or about 165 mg QD, or about 170 mg QD, or about 180 mg QD, or about 190 mg QD, or about 200 mg QD. In some embodiments, Compound I may be administered as a malonate salt in an amount that provides an amount of the free base of Compound I of about 80 mg QD or about 120 mg QD. In some embodiments, Compound I as administered in the form of a malonate salt in an amount that provides an amount of the free base of Compound I of about 80 mg QD. In other embodiments, Compound I as administered in the form of a malonate salt in an amount that provides an amount of the free base of Compound I of about 120 mg QD.

[0210] Furthermore, Compound I, or a pharmaceutically acceptable salt thereof, as described herein may be administered according to the methods disclosed herein twice per day (BID). In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be83MF-367743657Docket No. 21135-20013.40 administered in an amount that provides an amount of the free base of Compound I, of about 3 mg BID, about 6 mg BID, about 10 mg BID, about 15 mg BID, about 20 mg BID, about 25 mg BID, about 30 mg BID, about 45 mg BID, or about 50 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 3 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 6 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 10 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 15 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 20 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 25 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 30 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 45 mg BID. In another embodiment, Compound I, or a pharmaceutically acceptable salt thereof, may be administered in an amount that provides an amount of the free base of Compound I of about 50 mg BID.

[0211] Furthermore, Compound I, or a pharmaceutically acceptable salt thereof, as described herein may be administered according to the methods disclosed herein in an amount that provides a total daily dose of Compound I selected from (a) more than 10 mg and less than about 45 mg, (b) more than about 45 mg but less than about 200 mg, (c) from about 45 mg to about 60 mg, (d) from about 45 mg to about 90 mg, (e) from about 45 mg to about 120 mg, (f) about 45 mg, (g) about 60 mg, (h) about 75 mg, (i) about 80 mg, j) about 90 mg, (k) about 100 mg, (1) about 120 mg, (m) about 150 mg, (n) about 175 mg, (o) about 200 mg, and (p) greater than about 120 mg but less than about 200 mg. In some embodiments, the salt of Compound I is the malonate salt. In some embodiments, the pharmaceutical composition comprises the malonate salt of Compound I.

[0212] Furthermore, Compound I may be administered in the form of a malonate salt according to the methods disclosed herein in an amount that provides a total daily dose of 84MF-367743657Docket No. 21135-20013.40 Compound I selected from (a) more than 10 mg and less than about 45 mg, (b) more than about 45 mg but less than about 200 mg, (c) from about 45 mg to about 60 mg, (d) from about 45 mg to about 90 mg, (e) from about 45 mg to about 120 mg, (f) about 45 mg, (g) about 60 mg, (h) about 75 mg, (i) about 80 mg, (j) about 90 mg, (k) about 100 mg, (1) about 120 mg, (m) about 150 mg, (n) about 175 mg, (o) about 200 mg, and (p) greater than about 120 mg but less than about 200 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 200 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 175 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 150 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 140 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 130 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 120 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 110 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 100 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 95 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 90 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 85 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 80 mg. In some embodiments, the individual in need thereof is administered the malonate salt in an amount that provides a total daily dose of Compound I of greater than about 45 mg but less than about 75 mg.85MF-367743657Docket No. 21135-20013.40

[0213] Furthermore, Compound I may be administered in the form of a malonate salt according to the methods disclosed herein in an amount that is about 30 mg BID, about 40 mg BID, about 45 mg QD, about 50 mg BID, about 60 mg QD, about 75 mg QD, about 80 mg QD, about 90 mg QD, or about 120 mg QD. In some embodiments, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 30 mg BID. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 40 mg BID. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 45 mg QD. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 50 mg BID. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 60 mg QD. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 75 mg QD. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 80 mg QD. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 85 mg QD. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 90 mg QD. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is 100 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is 110 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that about 120 mg QD. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 125 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 130 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 135 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 140 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 145 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 150 mg. In another embodiment, the individual in need thereof is administered the malonate salt or 86MF-367743657Docket No. 21135-20013.40 the pharmaceutical composition in an amount that is about 160 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is 170 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 180 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is 190 mg. In another embodiment, the individual in need thereof is administered the malonate salt or the pharmaceutical composition in an amount that is about 200 mg.

[0214] In another embodiment are provided the methods disclosed herein, wherein the individual is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.1 nM for at least 8 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 8 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt.

[0215] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.1 nM for at least 12 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 12 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt.

[0216] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound87MF-367743657Docket No. 21135-20013.40 concentration of Compound I in the plasma of the individual that is greater than or equal to 0.1 nM for at least 16 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 16 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt.

[0217] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.1 nM for at least 20 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 20 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt.

[0218] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.1 nM for at least 24 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 24 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt.88MF-367743657Docket No. 21135-20013.40

[0219] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.25 nM, or greater than or equal to 0.3 nM, or greater than or equal to 0.35 nM, or greater than or equal to 0.4 nM, or greater than or equal to 0.45 nM, or greater than or equal to 0.5 nM, or greater than or equal to 0.55 nM, or greater than or equal to 0.6 nM, or greater than or equal to 0.65 nM, or greater than or equal to 0.7 nM, or greater than or equal to 0.75 nM, or greater than or equal to 0.8 nM, or greater than or equal to 0.85 nM, or greater than or equal to 0.9 nM, or greater than or equal to 0.95 nM, or greater than or equal to 1 nM, or greater than or equal to 1.25 nM, or greater than or equal to 1.5 nM, or greater than or equal to 1.75 nM, or greater than or equal to 2 nM, or greater than or equal to 2.5 nM, or greater than or equal to 3 nM, or greater than or equal to 3.5 nM, or greater than or equal to 4 nM, or greater than or equal to 4.5 nM, or greater than or equal to 5 nM, or greater than or equal to 5.5 nM, or greater than or equal to 6 nM, or greater than or equal to 6.5 nM, or greater than or equal to 7 nM, or greater than or equal to 7.5 nM, or greater than or equal to 8 nM, or greater than or equal to 8.5 nM, or greater than or equal to 9 nM, or greater than or equal to 9.5 nM, or greater than or equal to 10 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt.

[0220] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM and less than or equal to 10 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM and less than or equal to 9 nM, or greater than or equal to 0.2 nM and less than or equal to 8.5 nM, or greater than or equal to 0.2 nM and less than or equal to 8 nM, or greater than or equal to 0.2 nM and less than or equal to 7.5 nM, or greater than or equal to 0.2 nM and less than or equal to 7 nM, or greater than or equal to 0.2 nM and less than or equal to 6.5 nM , or greater than or equal to 0.2 nM and less than or equal to 6 nM, or greater than or equal to 0.2 nM and less than or equal to89MF-367743657Docket No. 21135-20013.40 5.5 nM, or greater than or equal to 0.2 nM and less than or equal to 5 nM, or greater than or equal to 0.2 nM and less than or equal to 4.5 nM, or greater than or equal to 0.2 nM and less than or equal to 4 nM, or greater than or equal to 0.2 nM and less than or equal to 3.5 nM, greater than or equal to 0.2 nM and less than or equal to 3 nM, or greater than or equal to 0.2 nM and less than or equal to 2.75 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt.

[0221] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides in the plasma of the individual following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof, (a) a Cmax of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM, and (b) a mean unbound concentration of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM for at least 8 hours. In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM and less than or equal to 9 nM, or greater than or equal to 0.2 nM and less than or equal to 8.5 nM, or greater than or equal to 0.2 nM and less than or equal to 8 nM, or greater than or equal to 0.2 nM and less than or equal to 7.5 nM, or greater than or equal to 0.2 nM and less than or equal to 7 nM, or greater than or equal to 0.2 nM and less than or equal to 6.5 nM , or greater than or equal to 0.2 nM and less than or equal to 6 nM, or greater than or equal to 0.2 nM and less than or equal to 5.5 nM, or greater than or equal to 0.2 nM and less than or equal to 5 nM, or greater than or equal to 0.2 nM and less than or equal to 4.5 nM, or greater than or equal to 0.2 nM and less than or equal to 4 nM, or greater than or equal to 0.2 nM and less than or equal to 3.5 nM, greater than or equal to 0.2 nM and less than or equal to 3 nM, or greater than or equal to 0.2 nM and less than or equal to 2.75 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 8 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt. It is understood that the disclosure herein contemplates any combinations of the90MF-367743657Docket No. 21135-20013.40 values disclosed for Cmax with any values disclosed herein for mean unbound concentration of Compound I.

[0222] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides in the plasma of the individual following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof, (a) a Cmax of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM, and (b) a mean unbound concentration of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM for at least 12 hours. In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM and less than or equal to 9 nM, or greater than or equal to 0.2 nM and less than or equal to 8.5 nM, or greater than or equal to 0.2 nM and less than or equal to 8 nM, or greater than or equal to 0.2 nM and less than or equal to 7.5 nM, or greater than or equal to 0.2 nM and less than or equal to 7 nM, or greater than or equal to 0.2 nM and less than or equal to 6.5 nM , or greater than or equal to 0.2 nM and less than or equal to 6 nM, or greater than or equal to 0.2 nM and less than or equal to 5.5 nM, or greater than or equal to 0.2 nM and less than or equal to 5 nM, or greater than or equal to 0.2 nM and less than or equal to 4.5 nM, or greater than or equal to 0.2 nM and less than or equal to 4 nM, or greater than or equal to 0.2 nM and less than or equal to 3.5 nM, greater than or equal to 0.2 nM and less than or equal to 3 nM, or greater than or equal to 0.2 nM and less than or equal to 2.75 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 12 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt. It is understood that the disclosure herein contemplates any combinations of the values disclosed for Cmax with any values disclosed herein for mean unbound concentration of Compound I.

[0223] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides in the plasma of the individual following the administration to the individual of Compound I, or a pharmaceutically 91MF-367743657Docket No. 21135-20013.40 acceptable salt thereof, (a) a Cmax of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM, and (b) a mean unbound concentration of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM for at least 16 hours. In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM and less than or equal to 9 nM, or greater than or equal to 0.2 nM and less than or equal to 8.5 nM, or greater than or equal to 0.2 nM and less than or equal to 8 nM, or greater than or equal to 0.2 nM and less than or equal to 7.5 nM, or greater than or equal to 0.2 nM and less than or equal to 7 nM, or greater than or equal to 0.2 nM and less than or equal to 6.5 nM , or greater than or equal to 0.2 nM and less than or equal to 6 nM, or greater than or equal to 0.2 nM and less than or equal to 5.5 nM, or greater than or equal to 0.2 nM and less than or equal to 5 nM, or greater than or equal to 0.2 nM and less than or equal to 4.5 nM, or greater than or equal to 0.2 nM and less than or equal to 4 nM, or greater than or equal to 0.2 nM and less than or equal to 3.5 nM, greater than or equal to 0.2 nM and less than or equal to 3 nM, or greater than or equal to 0.2 nM and less than or equal to 2.75 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 16 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt. It is understood that the disclosure herein contemplates any combinations of the values disclosed for Cmax with any values disclosed herein for mean unbound concentration of Compound I.

[0224] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides in the plasma of the individual following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof, (a) a Cmax of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM, and (b) a mean unbound concentration of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM for at least 20 hours. In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the92MF-367743657Docket No. 21135-20013.40 individual that is greater than or equal to 0.2 nM and less than or equal to 9 nM, or greater than or equal to 0.2 nM and less than or equal to 8.5 nM, or greater than or equal to 0.2 nM and less than or equal to 8 nM, or greater than or equal to 0.2 nM and less than or equal to 7.5 nM, or greater than or equal to 0.2 nM and less than or equal to 7 nM, or greater than or equal to 0.2 nM and less than or equal to 6.5 nM , or greater than or equal to 0.2 nM and less than or equal to 6 nM, or greater than or equal to 0.2 nM and less than or equal to 5.5 nM, or greater than or equal to 0.2 nM and less than or equal to 5 nM, or greater than or equal to 0.2 nM and less than or equal to 4.5 nM, or greater than or equal to 0.2 nM and less than or equal to 4 nM, or greater than or equal to 0.2 nM and less than or equal to 3.5 nM, greater than or equal to 0.2 nM and less than or equal to 3 nM, or greater than or equal to 0.2 nM and less than or equal to 2.75 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 20 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt. It is understood that the disclosure herein contemplates any combinations of the values disclosed for Cmax with any values disclosed herein for mean unbound concentration of Compound I.

[0225] In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides in the plasma of the individual following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof, (a) a Cmax of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM, and (b) a mean unbound concentration of Compound I that is greater than or equal to 0.2 nM and less than or equal to 10 nM for at least 24 hours. In another embodiment, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a Cmax of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM and less than or equal to 9 nM, or greater than or equal to 0.2 nM and less than or equal to 8.5 nM, or greater than or equal to 0.2 nM and less than or equal to 8 nM, or greater than or equal to 0.2 nM and less than or equal to 7.5 nM, or greater than or equal to 0.2 nM and less than or equal to 7 nM, or greater than or equal to 0.2 nM and less than or equal to 6.5 nM , or greater than or equal to 0.2 nM and less than or equal to 693MF-367743657Docket No. 21135-20013.40 nM, or greater than or equal to 0.2 nM and less than or equal to 5.5 nM, or greater than or equal to 0.2 nM and less than or equal to 5 nM, or greater than or equal to 0.2 nM and less than or equal to 4.5 nM, or greater than or equal to 0.2 nM and less than or equal to 4 nM, or greater than or equal to 0.2 nM and less than or equal to 3.5 nM, greater than or equal to 0.2 nM and less than or equal to 3 nM, or greater than or equal to 0.2 nM and less than or equal to 2.75 nM following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the individual in need thereof is administered Compound I, or a pharmaceutically acceptable salt thereof, in an amount that provides a mean unbound concentration of Compound I in the plasma of the individual that is greater than or equal to 0.2 nM, or 0.25 nM, or 0.3 nM, or 0.35 nM, or 0.4 nM, or 0.45 nM, or 0.5 nM, or 0.55 nM, or 0.6 nM, or 0.65 nM, or 0.7 nM, 0.8 nM, or 0.9 nM, or 1 nM, or 1.25 nM, or 1.5 nM, or 1.75 nM, or 2 nM for at least 24 hours following the administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is the malonate salt. It is understood that the disclosure herein contemplates any combinations of the values disclosed for Cmax with any values disclosed herein for mean unbound concentration of Compound I.

[0226] In another embodiment are provided the methods disclosed herein, wherein the individual achieves stable disease, a partial response, or a complete response in the individual’s target tumors in accordance with RECIST 1.1 following administration to the individual of Compound I, or a pharmaceutically acceptable salt thereof. In some embodiments, the salt of Compound I is a malonate salt. In some embodiments, the response in accordance with RECIST 1.1 is a partial response or a complete response. In some embodiments, the response in accordance with RECIST 1.1 is a partial response. In some embodiments, the response in accordance with RECIST 1.1 is a complete response.

[0227] In another embodiment are provided the methods disclosed herein, wherein the individual does not experience any Grade 3 or Grade 4 treatment related adverse events following administration of Compound I, or a pharmaceutically acceptable salt thereof, to the individual. In some embodiments the salt of Compound I is a malonate salt.

[0228] Those of ordinary skill in the art will understand that with respect to Compound I, or a pharmaceutically acceptable salt thereof, as described herein the particular pharmaceutical formulation, the dosage, and the number of doses given per day to a subject requiring such treatment, are all choices within the knowledge of one of ordinary skill in the art and can be determined without undue experimentation.94MF-367743657Docket No. 21135-20013.40

[0229] Dosages of compositions described herein can be determined by any suitable method. Maximum tolerated doses (MTD) and maximum response doses (MRD) of a salt of Compound I, or a pharmaceutically acceptable salt thereof, as described herein can be determined via established animal and human experimental protocols as well as in the examples described herein. For example, toxicity and therapeutic efficacy of Compound I, or a pharmaceutically acceptable salt thereof, as described herein can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, including, but not limited to, for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between the toxic and therapeutic effects is the therapeutic index and it can be expressed as the molar ratio between LD50 and ED50. The data obtained from cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage of Compound I, or a pharmaceutically acceptable salt thereof, as described herein lies preferably within a range of circulating concentrations that include the ED50 with minimal toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. Additional relative dosages, represented as a percent of maximal response or of maximum tolerated dose, are readily obtained via the protocols.

[0230] In some embodiments, the amount of Compound I, or a pharmaceutically acceptable salt thereof, as described herein comprising a formulation that corresponds to such an amount varies depending upon factors such as the particular salt or form, disease condition and its severity, the identity (e.g., age, weight, sex) of the subject or host in need of treatment, but can nevertheless be determined according to the particular circumstances surrounding the case, including, e.g., the specific agent being administered, the formulation type, the condition being treated, and the subject or host being treated.

[0231] The length of a treatment cycle depends on the treatment being given. In some embodiments, the length of a treatment cycle ranges from two to six weeks. In some embodiments, the length of a treatment cycle ranges from three to six weeks. In some embodiments, the length of a treatment cycle ranges from three to four weeks. In some embodiments, the length of a treatment cycle is three weeks (or 21 days). In some embodiments, the length of a treatment cycle is four weeks (28 days). In some embodiments, the length of a treatment cycle is 56 days. In some embodiments, a treatment cycle lasts one, two, three, or four weeks. In some embodiments, a treatment cycle lasts three weeks. In some embodiments, a treatment cycle lasts four weeks. The number of treatment doses scheduled within each cycle also varies depending on the drugs being given.95MF-367743657Docket No. 21135-20013.40

[0232] In one aspect, compositions comprising Compound I, or a pharmaceutically acceptable salt thereof, as described herein are used for the treatment of cancer in a subject. In one embodiment, such compositions are in the form of suitable dosage forms. In some embodiments, the pharmaceutical composition is in a form for oral administration to a subject. Suitable dosage forms include, for example, liquids, suspensions, powders for reconstitution, tablets, pills, sachets, or capsules of hard or soft gelatin (See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 21st Ed. Mack Pub. Co., Easton, PA (2005)). In some embodiments, the dosage forms are in the form of a tablet, a capsule, a powder, a liquid, a suspension, or a cachet. In some embodiments, the pharmaceutical composition is in the form of a tablet or a capsule. In other embodiments, the pharmaceutical composition is in the form of a tablet. In other embodiments, the pharmaceutical composition is in the form of a capsule.

[0233] Compound I, or a pharmaceutically acceptable salt thereof, as described herein may be formulated into pharmaceutical compositions as described below in any pharmaceutical form recognizable to the skilled artisan as being suitable. Pharmaceutical compositions of the disclosure comprise a therapeutically effective amount of at least one salt of Compound I of the present disclosure and an inert, pharmaceutically acceptable carrier or diluent.

[0234] The pharmaceutical carriers employed may be either solid or liquid. Exemplary solid carriers are lactose, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, stearic acid and the like. Exemplary liquid carriers are syrup, peanut oil, olive oil, water and the like.Similarly, the inventive compositions may include time-delay or time-release material known in the art, such as glyceryl monostearate or glyceryl distearate alone or with a wax, ethylcellulose, hydroxypropylmethylcellulose, methylmethacrylate or the like. Further additives or excipients may be added to achieve the desired formulation properties. For example, a bioavailability enhancer, such as Labrasol, Gelucire or the like, or formulator, such as CMC (carboxymethylcellulose), PG (propyleneglycol), or PEG (polyethyleneglycol), may be added. Gelucire, a semi-solid vehicle that protects active ingredients from light, moisture and oxidation, may be added, e.g., when preparing a capsule formulation.

[0235] Additionally, the pharmaceutically acceptable formulations to be used according to the methods disclosed herein may comprise Compound I, or a pharmaceutically acceptable salt thereof, as described herein in an amount from about 0.5 w / w % to about 95 w / w %, or from about 1 w / w % to about 95 w / w %, or from about 1 w / w % to about 75 w / w %, or from about 5 w / w % to about 75 w / w %, or from about 10 w / w % to about 75 w / w %, or from about 10 w / w % to about 50 w / w %.96MF-367743657Docket No. 21135-20013.40 Articles of manufacture and kits

[0236] The kit or article of manufacture can comprise a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, etc. The containers may be formed from a variety of materials such as glass or plastic. Generally, the container holds a composition which is effective for treating a disease or disorder described herein, and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active ingredient in the composition is a) Compound I, or a pharmaceutically acceptable salt thereof, as described herein; and / or b) one or more additional anticancer agents such as any of the anticancer agents described herein. The label or package insert indicates that the composition is used for treating cancer (e.g., a particular cancer) in a subject. The label or package insert will further comprise instructions for administering the composition to the individual (e.g., according to any of the methods described herein). Articles of manufacture and kits comprising combination therapies described herein are also contemplated.

[0237] Package insert refers to instructions customarily included in commercial packages of therapeutic products that contain information about the indications, usage, dosage, administration, contraindications and / or warnings concerning the use of such therapeutic products. In some embodiments, the package insert indicates that the composition is used for treating cancer.

[0238] Additionally, the kit or article of manufacture may further comprise a second container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate-buffered saline, Ringer's solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes.

[0239] For example, the kit or article of manufacture comprises a) a composition comprising a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, as described herein and b) instructions for administering a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, as described herein to a subject for treatment of a cancer, optionally in combination with one or more additional anticancer agents. In some embodiments, the kit or article of manufacture comprises a) a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, as described herein b) one or more additional anticancer agents such as any of the anticancer agents described herein, and c) instructions for administering Compound I, or a pharmaceutically acceptable salt thereof, as97MF-367743657Docket No. 21135-20013.40 described herein and the one or more additional anticancer agents to a subject for treatment of a cancer.

[0240] The composition comprising Compound I, or a pharmaceutically acceptable salt thereof, as described herein and the one or more additional anticancer agents can be present in separate containers or in a single container. For example, the kit may comprise one distinct composition or two or more compositions wherein one composition comprises a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, as described herein and another composition comprises the one or more additional anticancer agents.

[0241] The kits or articles of manufacture of the application are in suitable packaging.Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. Kits or articles of manufacture may optionally provide additional components such as buffers and interpretative information. The present application thus also provides articles of manufacture, which include vials (such as sealed vials), bottles, jars, flexible packaging, and the like.

[0242] The instructions relating to the use of Compound I, or a pharmaceutically acceptable salt thereof, as described herein and one or more additional anticancer agents generally include information as to dosage, dosing schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi-dose packages) or subunit doses. For example, kits may be provided that contain sufficient dosages of a composition comprising Compound I, or a pharmaceutically acceptable salt thereof, as described herein and one or more additional anticancer agents as disclosed herein to provide effective treatment of a subject for an extended period, such as any of a week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months, 12 months, 24 months or more. Kits may also include multiple unit doses of Compound I, or a pharmaceutically acceptable salt thereof, as described herein and the one or more additional anticancer agents and instructions for use, packaged in quantities sufficient for storage and use in pharmacies, for example, hospital pharmacies and compounding pharmacies.

[0243] Compound I may be prepared using the methods known to those having ordinary skill in the art and those disclosed in United States Patent No. 11,466,000, which is hereby incorporated by reference for that purpose. Salts of Compound I, including but not limited to, malonate salts, glycolate salts, fumarate salts, malate salts, and citrate salts, and polymorphic forms thereof, may be prepared by methods known to those of ordinary skill in the art and those disclosed in International Application Nos. PCT / US2023 / 78473 and PCT / KR2023 / 017405.98MF-367743657Docket No. 21135-20013.40

[0244] Also disclosed herein are numbered embodiments:Embodiment 1. A pharmaceutical composition, said composition comprising(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and(b) means for preventing sticking of the pharmaceutical composition to manufacturing equipment during manufacturing of tablets from the pharmaceutical composition.Embodiment 2. A pharmaceutical composition, said composition comprising(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and(b) means for preventing the sticking of the pharmaceutical composition to tablet press tooling during manufacturing of tablets from the pharmaceutical composition.Embodiment 3. A pharmaceutical composition, said composition comprising(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and(b) means for reducing a rate of tablet defects during the manufacturing of tablets from the pharmaceutical composition.Embodiment 4. A pharmaceutical composition, said composition comprising(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and(b) means for reducing a rate of tablet defects during the manufacture of tablets from the pharmaceutical composition, wherein the tablet defects are caused by sticking of the pharmaceutical composition to manufacturing equipment during manufacturing of the tablets from the pharmaceutical composition.Embodiment 5. The pharmaceutical composition of any one of Embodiments 1 to 4, wherein the manufacturing of tablets from the pharmaceutical composition comprises at least 500 tablet compression events.Embodiment 6. The pharmaceutical composition of any one of Embodiments 3 to 5, wherein the tablet defects are selected from one or more of (a) unacceptable variation in tablet weight, (b) unacceptable variation in tablet thickness, (c) unacceptable variation in tablet hardness, (d) unacceptable tablet appearance and (e) unacceptable tablet friability.99MF-367743657Docket No. 21135-20013.40 Embodiment 7. A pharmaceutical composition comprising:(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof; and(b) two or more lubricants.Embodiment 8. A pharmaceutical composition comprising:(a) a malonate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide; and (b) two or more lubricants.Embodiment 9. A pharmaceutical composition comprising:(a) a glycolate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide; and (b) two or more lubricants.Embodiment 10. The pharmaceutical composition of any one of Embodiments 7 to 9, wherein the pharmaceutical composition further comprises one or more excipients selected from (a) one or more diluents; (b) one or more disintegrants; and (c) one or more binders.Embodiment 11. The pharmaceutical composition of Embodiment 10, wherein the pharmaceutical composition further comprises one or more diluents.Embodiment 12. The pharmaceutical composition of Embodiment 11, wherein the one or more diluents is selected from (a) one or more carbohydrates, (b) one or more monosaccharides, and (c) one or more polysaccharides.Embodiment 13. The pharmaceutical composition of Embodiment 12, wherein the one or more diluents is selected from one or more carbohydrates.Embodiment 14. The pharmaceutical composition of Embodiment 13, wherein the one or more diluents is one or more carbohydrates selected from lactose, sucrose, glucose, maltose, mannitol, xylitol, dextrose, fructose, sorbitol, starch, starch derivatives, corn starch, hydroxypropyl starch.Embodiment 15. The pharmaceutical composition of Embodiment 12, wherein the one or more diluents is selected from one or more monosaccharides.Embodiment 16. The pharmaceutical composition of Embodiment 15, wherein the one or more diluents is one or more monosaccharides selected from glucose, fructose, galactose, mannose, ribose, xylose, arabinose, trehalose, rhamnose, and fucose.Embodiment 17. The pharmaceutical composition of Embodiment 12, wherein the one or more diluents is selected from one or more polysaccharides.100MF-367743657Docket No. 21135-20013.40 Embodiment 18. The pharmaceutical composition of Embodiment 17, wherein the one or more diluents is one or more polysaccharides selected from starch, starch derivatives, com starch, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC), cellulose, methyl cellulose, microcrystalline cellulose (MCC), carboxymethyl cellulose (CMC), guar gum, xanthan gum, pectin, sodium alginate, agar, carrageenan, and dextran.Embodiment 19. The pharmaceutical composition of Embodiment 18, wherein the diluent is microcrystalline cellulose (MCC).Embodiment 20. The pharmaceutical composition of Embodiment 10, wherein the pharmaceutical composition further comprises one or more disintegrants.Embodiment 21. The pharmaceutical composition of Embodiment 20, wherein the one or more disintegrants is selected from starch derivatives, microcrystalline cellulose (MCC), carboxymethylcellulose, croscarmellose sodium, sodium starch glycolate (SSG), crospovidone, aligantes, guar gum, polyvinylpyrrolidone (PVP), mannitol, talc, sodium bicarbonate, calcium carbonate, silica, colloidal silica, xanthan gum, and lactose.Embodiment 22. The pharmaceutical composition of Embodiment 21, wherein the one or more disintegrants is croscarmellose sodium.Embodiment 23. The pharmaceutical composition of Embodiment 10, wherein the pharmaceutical composition further comprises one or more binders.Embodiment 24. The pharmaceutical composition of Embodiment 23, wherein the one or more binders is selected from microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), starch, starch derivatives, com starch, hydroxypropyl starch, methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), gum Arabic, gelatin, carboxymethylcellulose (CMC), sorbitol, xanthan gum, pectin, sodium alginate, ethylcellulose, maltodextrin, guar gum, croscarmellose sodium, magnesium stearate, lactose, sucrose, polyvinyl alcohol (PVA), mannitol, and tartaric acid.Embodiment 25. The pharmaceutical composition of Embodiment 24, wherein the one or more binders is microcrystalline cellulose (MCC).Embodiment 26. A pharmaceutical composition comprising(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof;(b) two or more lubricants; and(c) microcrystalline cellulose (MCC).Embodiment 27. A pharmaceutical composition comprising101MF-367743657Docket No. 21135-20013.40 (a) a malonate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) two or more lubricants; and(c) microcrystalline cellulose (MCC).Embodiment 28. A pharmaceutical composition comprising(a) a glycolate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) two or more lubricants; and(c) microcrystalline cellulose (MCC).Embodiment 29. The pharmaceutical composition of any one of Embodiments 26 to 28, wherein the pharmaceutical composition further comprises one or more disintegrants.Embodiment 30. The pharmaceutical composition of Embodiment 29, wherein the one or more disintegrants is selected from selected from starch derivatives, carboxymethylcellulose, croscarmellose sodium, sodium starch glycolate (SSG), crospovidone, aligantes, guar gum, polyvinylpyrrolidone (PVP), mannitol, talc, sodium bicarbonate, calcium carbonate, silica, colloidal silica, xanthan gum, and lactose.Embodiment 31. The pharmaceutical composition of Embodiment 30, wherein the one or more disintegrants is croscarmellose sodium.Embodiment 32. A pharmaceutical composition comprising(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof;(b) two or more lubricants; and(c) croscarmellose sodium.Embodiment 33. A pharmaceutical composition comprising(a) a malonate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) two or more lubricants; and(c) croscarmellose sodium.Embodiment 34. A pharmaceutical composition comprising(a) a glycolate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) two or more lubricants; and(c) croscarmellose sodium.102MF-367743657Docket No. 21135-20013.40 Embodiment 35. The pharmaceutical composition of any one of Embodiments 32 to 34, wherein the pharmaceutical composition further comprises one or more or more diluents selected from (a) one or more carbohydrates, (b) one or more monosaccharides, and (c) one or more polysaccharides.Embodiment 36. The pharmaceutical composition of Embodiment 35, wherein the one or more diluents is selected from one or more carbohydrates.Embodiment 37. The pharmaceutical composition of Embodiment 36, wherein the one or more diluents is one or more carbohydrates selected from lactose, sucrose, glucose, maltose, mannitol, xylitol, dextrose, fructose, sorbitol, starch, starch derivatives, com starch, hydroxypropyl starch.Embodiment 38. The pharmaceutical composition of Embodiment 35, wherein the one or more diluents is selected from one or more monosaccharides.Embodiment 39. The pharmaceutical composition of Embodiment 38, wherein the one or more diluents is one or more monosaccharides selected from glucose, fructose, galactose, mannose, ribose, xylose, arabinose, trehalose, rhamnose, and fucose.Embodiment 40. The pharmaceutical composition of Embodiment 35, wherein the one or more diluents is selected from one or more polysaccharides.Embodiment 41. The pharmaceutical composition of Embodiment 40, wherein the one or more diluents is one or more polysaccharides selected from starch, starch derivatives, com starch, hydroxypropyl starch, hydroxypropyl methylcellulose (HPMC), cellulose, methyl cellulose, microcrystalline cellulose (MCC), carboxymethyl cellulose (CMC), guar gum, xanthan gum, pectin, sodium alginate, agar, carrageenan, and dextran.Embodiment 42. The pharmaceutical composition of Embodiment 41, wherein the diluent is microcrystalline cellulose (MCC).Embodiment 43. The pharmaceutical composition of any one of Embodiments 32 to 42, wherein the pharmaceutical composition further comprises one or more binders.Embodiment 44. The pharmaceutical composition of Embodiment 43, wherein the one or more binders is selected from microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), starch, starch derivatives, com starch, hydroxypropyl starch, methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), gum Arabic, gelatin, carboxymethylcellulose (CMC), sorbitol, xanthan gum, pectin, sodium alginate, ethylcellulose, maltodextrin, guar gum, croscarmellose sodium, magnesium stearate, lactose, sucrose, polyvinyl alcohol (PVA), mannitol, and tartaric acid.Embodiment 45. The pharmaceutical composition of Embodiment 44, wherein the one or more binders is microcrystalline cellulose (MCC).103MF-367743657Docket No. 21135-20013.40 Embodiment 46. A pharmaceutical composition comprising(a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof;(b) two or more lubricants;(c) microcrystalline cellulose (MCC); and(d) croscarmellose sodium.Embodiment 47. A pharmaceutical composition comprising(a) a malonate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) two or more lubricants;(c) microcrystalline cellulose (MCC); and(d) croscarmellose sodium.Embodiment 48. A pharmaceutical composition comprising(a) a glycolate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) two or more lubricants;(c) microcrystalline cellulose (MCC); and(d) croscarmellose sodium.Embodiment 49. The pharmaceutical composition of any one of Embodiments 7 to 48, wherein the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate.Embodiment 50. The pharmaceutical composition of any one of Embodiments 7 to 49, wherein one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate.Embodiment 51. The pharmaceutical composition of any one of Embodiments 7 to 50, wherein one of the two or more lubricants is magnesium stearate.Embodiment 52. The pharmaceutical composition of any one of Embodiments 7 to 51, wherein one of the two or more lubricants is sodium stearyl fumarate.Embodiment 53. The pharmaceutical composition of any one of Embodiments 7 to 52, wherein the two or more lubricants are magnesium stearate and sodium stearyl fumarate.Embodiment 54. A pharmaceutical composition comprising104MF-367743657Docket No. 21135-20013.40 (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof;(b) microcrystalline cellulose (MCC);(c) croscarmellose sodium;(d) magnesium stearate; and(e) sodium stearyl fumarate.Embodiment 55. A pharmaceutical composition comprising(a) a malonate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) microcrystalline cellulose (MCC);(c) croscarmellose sodium;(d) magnesium stearate; and(e) sodium stearyl fumarate.Embodiment 56. A pharmaceutical composition comprising(a) a glycolate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide;(b) microcrystalline cellulose (MCC);(c) croscarmellose sodium;(d) magnesium stearate; and(e) sodium stearyl fumarate.Embodiment 57. The pharmaceutical composition of Embodiment 7, wherein the pharmaceutically acceptable salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl) acrylamide is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate salt, and a citrate salt.Embodiment 58. The pharmaceutical composition of Embodiment 57, wherein the pharmaceutically acceptable salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl) acrylamide is a malonate salt or a glycolate salt.Embodiment 59. The pharmaceutical composition of Embodiment 58, wherein the pharmaceutically acceptable salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl) acrylamide is a malonate salt.105MF-367743657Docket No. 21135-20013.40 Embodiment 60. The pharmaceutical composition of Embodiment 58, wherein the pharmaceutically acceptable salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl) acrylamide is a glycolate salt.Embodiment 61. The pharmaceutical composition of any one of Embodiments 7 to 60, wherein the pharmaceutical composition comprises an intragranular component and an extragranular component.Embodiment 62. The pharmaceutical composition of Embodiment 61, wherein the intragranular component comprises (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and one or more lubricants.Embodiment 63. The pharmaceutical composition of Embodiment 62, wherein the intragranular component comprises a pharmaceutically acceptable salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide.Embodiment 64. The pharmaceutical composition of Embodiment 63, wherein the pharmaceutically acceptable salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difhiorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl) acrylamide is selected from a malonate salt, a glycolate salt, a fumarate salt, a malate sa...

Claims

Docket No. 21135-20013.40CLAIMSWhat is claimed is:

1. A pharmaceutical composition, said composition comprising(a) (7?)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4- methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof, and (b) means for preventing sticking of the pharmaceutical composition to manufacturing equipment or tablet press tooling during manufacturing of tablets from the pharmaceutical composition, or means for reducing a rate of tablet defects during the manufacturing of tablets from the pharmaceutical composition.

2. The pharmaceutical composition of claim 1, wherein the manufacturing of tablets from the pharmaceutical composition comprises at least 500 tablet compression events.

3. The pharmaceutical composition of claim 1 or 2, wherein the tablet defects are selected from one or more of (a) unacceptable variation in tablet weight, (b) unacceptable variation in tablet thickness, (c) unacceptable variation in tablet hardness, (d) unacceptable tablet appearance and (e) unacceptable tablet friability.

4. A pharmaceutical composition comprising:(a) (7?)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4- methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof; and (b) two or more lubricants.

5. The pharmaceutical composition of claim 4, wherein the two or more lubricants are selected from stearic acid, calcium stearate, magnesium stearate, magnesium laurate, sodium lauryl sulfate, palmitic acid, talc, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oils, polyethylene glycol (PEG), silicon dioxide, colloidal silicon dioxide, poloxamers, beeswax, polyvinyl alcohol (PVA), and glyceryl dibehenate.

6. The pharmaceutical composition of claim 5, wherein one of the two or more lubricants is selected from magnesium stearate and sodium stearyl fumarate.

7. The pharmaceutical composition of claim 6, wherein the two or more lubricants are magnesium stearate and sodium stearyl fumarate.

8. A tablet for oral administration to a subject, said tablet comprising:132MF-367743657Docket No. 21135-20013.40 (a) (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5- difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4- methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt thereof; (b) microcrystalline cellulose (MCC);(c) croscarmellose sodium;(d) magnesium stearate; and(e) sodium stearyl fumarate.

9. A tablet for oral administration of claim 8, wherein the tablet comprises a malonate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide, and wherein the malonate salt is in a crystalline form.

10. A tablet for oral administration of claim 9, wherein the crystalline form of the malonate salt of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide exhibits an XRPD pattern comprising a peak at 5.9 ± 0.2 degrees 2-theta.

11. A method of treating cancer in a human subject, comprising administering to the subject the pharmaceutical composition of any one of claims 1 to 7 or the tablet of any one of claims 8 to 10, optionally wherein the cancer is non-small cell lung cancer.

12. The method of claim 11, wherein the subject is concomitantly administered a gastric-acid reducing agent.

13. The method of claim 12, wherein the subject has taken the gastric-acid reducing agent before the pharmaceutical composition or the tablet.

14. The method of claim 12 or 13, wherein the gastric-acid reducing agent is a proton pump inhibitor, optionally wherein the proton pump inhibitor is esomeprazole.

15. The method of any one of claims 11 to 14, wherein the subject is administered 80 mg once daily of (R)-N-(2-(4-(4-cyclopropylpiperazin-l-yl)piperidin-l-yl)-5-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxyphenyl)acrylamide from the pharmaceutical composition or the tablet.133MF-367743657

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