Compositions comprising alkyne substituted quinazoline derivatives and related uses

Abstract

The present disclosure relates to formulations comprising Compound No. 1: or a pharmaceutically acceptable salt thereof. The present disclosure also relates to uses of the formulations, e.g., in treating or preventing cancer.

Description

Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)COMPOSITIONS COMPRISING ALKYNE SUBSTITUTED QUINAZOLINE DERIVATIVES AND RELATED USESRELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Application No. 63 / 682,081, filed on August 12, 2024, which is incorporated by reference herein in its entirety.BACKGROUND

[0002] Specific mutations in the human gene BRAF, which encodes for the protein B-Raf, are known to drive oncogenic activity in a variety of different cancers. Targeted inactivation of mutant B-Raf proteins by the administration of protein kinase inhibitors has been used to treat a number of different cancers in patients. However, there are subsets of patients administered these treatments that either fail to respond, eventually relapse or experience secondary lesions / pathway rebound. More specifically, many of the existing B-Raf-targeting kinase inhibitors either exhibit low specificity for B-Raf, leading to undesirable off-target effects, or only target a specific subset of / / / M / ’ B-Raf mutation(s). Thus, there is a long-felt need in the art for new therapies (e.g., formulations) that target specific oncogenic forms of B-Raf produced by mutations or alterations of the BRAF gene that could be used in preventing or treating cancer in a subject, e.g., a subject that has a cancer with one of the aforementioned oncogenic mutations. The present disclosure addresses this need.SUMMARY

[0003] In some aspects, the present disclosure provides a formulation comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0004] In some aspects, the present disclosure provides an oral formulation comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0005] In some aspects, the present disclosure provides a formulation comprising:(i) Compound No. 1 :294245842 1Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(Compound No. 1), or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a glidant; and(v) a lubricant.

[0006] In some aspects, the present disclosure provides a tablet comprising:(i) Compound No. 1 :(Compound No. 1), or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a glidant; and(v) a lubricant.

[0007] In some aspects, the present disclosure provides a capsule comprising:(i) Compound No. 1 :294245842 2Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(Compound No. 1), or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a glidant; and(v) a lubricant.

[0008] In some embodiments, the formulation, tablet, or capsule comprises an intragranular mixture and an extragranular mixture. In some embodiments, the formulation, tablet, or capsule comprises Compound No. 1.

[0009] In some embodiments, the formulation, tablet, or capsule comprises an amorphous solid dispersion comprising Compound No. 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the formulation, tablet, or capsule comprises an amorphous solid dispersion comprising Compound No. 1.

[0010] In some embodiments, the amorphous solid dispersion comprises HPMC ASMG. In some embodiments, the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 : 1 w / w, about a 1 :2 w / w, about a 1 :3 w / w, about a 1 :4 w / w, or about a 1 :5 w / w ratio of Compound No. 1 to HPMC ASMG.

[0011] In some embodiments, the filler is silicified microcrystalline cellulose. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the lubricant is magnesium stearate. In some embodiments, the glidant is colloidal silicon dioxide.

[0012] In some embodiments, the formulation, tablet, or capsule comprises about 35% w / w to about 60% w / w of the filler. In some embodiments, the formulation, tablet, or capsule comprises about 0.5% w / w to about 5% w / w of the disintegrant. In some embodiments, the formulation, tablet, or capsule comprises about 0.5% w / w to about 3% w / w of the lubricant. In some embodiments, the formulation, tablet, or capsule comprises about 0.1% w / w to about 3% w / w of the glidant.294245842 3Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0013] In some aspects, the present disclosure provides a method for preparing the formulation, tablet, or capsule of any one of the preceding claims.

[0014] In some aspects, the present disclosure provides a formulation disclosed herein for use in the inhibition of an oncogenic mutant of a B-Raf protein in a subject.

[0015] In some aspects, the present disclosure provides a method of inhibiting an oncogenic mutant of a B-Raf protein in a subject, the method comprising administering to the subject a formulation disclosed herein.

[0016] In some aspects, the present disclosure provides use of a formulation disclosed herein in the manufacture of a medicament for the inhibition of an oncogenic mutant of a B-Raf protein in a subject.

[0017] In some aspects, the present disclosure provides use of a formulation disclosed herein for the inhibition of an oncogenic mutant of a B-Raf protein in a subject.

[0018] In some aspects, the present disclosure provides a formulation disclosed herein for use in the treatment or prevention of cancer in a subject.

[0019] In some aspects, the present disclosure provides a method of treating or preventing cancer in a subject, the method comprising administering to the subject a formulation disclosed herein.

[0020] In some aspects, the present disclosure provides use of a formulation disclosed herein in the manufacture of a medicament for the treatment or prevention of cancer in a subject.

[0021] In some aspects, the present disclosure provides use of a formulation disclosed herein for the treatment or prevention of cancer in a subject.

[0022] In some embodiments, the subject is a human.

[0023] In some embodiments, the cancer is a carcinoma, a lymphoma, a blastoma, a sarcoma, a leukemia, a brain cancer, a breast cancer, a blood cancer, a bone cancer, a lung cancer, a skin cancer, a liver cancer, an ovarian cancer, a bladder cancer, a renal cancer, a kidney cancer, a gastric cancer, a thyroid cancer, a pancreatic cancer, an esophageal cancer, a prostate cancer, a cervical cancer, a uterine cancer, a stomach cancer, a soft tissue cancer, a laryngeal cancer, a small intestine cancer, a testicular cancer, an anal cancer, a vulvar cancer, a joint cancer, an oral cancer, a pharynx cancer or a colorectal cancer.

[0024] In some embodiments, the cancer is a hematological cancer. In some embodiments, the hematological cancer is acute myeloid leukemia.

[0025] In some embodiments, the cancer is a solid cancer. In some embodiments, the solid cancer is a carcinoma. In some embodiments, the carcinoma is pancreatic adenocarcinoma. In some embodiments, the solid cancer is non-small cell lung cancer (NSCLC), brain cancer,294245842 4Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) colorectal cancer, melanoma, thyroid cancer, histiocytosis, small bowel cancer, gastrointestinal neuroendocrine cancer, carcinoma of unknown primary, non-melanoma skin cancer, prostate cancer, gastric cancer, non-Hodgkin's lymphoma, papillary thyroid carcinoma, or glioblastoma. In some embodiments, the solid cancer is NSCLC. In some embodiments, the solid cancer is brain cancer. In some embodiments, the solid cancer is thyroid carcinoma, colorectal carcinoma, melanoma, or a histiocytic neoplasm.

[0026] In some embodiments, the cancer is characterized by at least one oncogenic mutation in the BRAF gene. In some embodiments, the cancer is characterized by at least one oncogenic variant of a RAS GTPase. In some embodiments, the cancer is characterized by at least one oncogenic mutation in the KRAS gene. In some embodiments, the oncogenic mutation is not KRAS G12C. In some embodiments, the cancer is characterized by at least one oncogenic mutation in the NRAS gene. In some embodiments, the cancer is advanced or metastatic.

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods and examples are illustrative only and are not intended to be limiting. In the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures will control.

[0028] Other features and advantages of the disclosure will be apparent from the following detailed description and claims.BRIEF DESCRIPTIONS OF FIGURES

[0029] FIGs. 1A & IB depict graphs showing exemplary schemes of preparing capsules disclosed herein. FIG. 1 A describes an exemplary process for preparing capsules comprising 3 mg of Compound No. 1. FIG. IB describes an exemplary process for preparing capsules comprising 25 mg of Compound No. 1. HPMC: hydroxypropyl methylcellulose; L: liter; RPM: revolutions per minute; SDD: spray-dried dispersion; BU: blend uniformity; BD / TD: bulk density / tapped density; EA: each; CC: cubic centimeter; CRC: child resistant cap.294245842 5Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0030] FIGs. 2A-2C depict graphs showing exemplary schemes of preparing tablets disclosed herein. FIG. 2A describes an exemplary process for preparing a common blend. FIGs. 2B and 2C describe exemplary processes to use the common blend to prepare tablets comprising 50 mg or 200 mg of Compound No. 1, respectively. SMCC: silicified microcrystalline cellulose; CCNa: croscarmellose sodium; L: liter; RPM: revolutions per minute; SDD: spray-dried dispersion; BU: blend uniformity; EA: each; CC: cubic centimeter; CRC: child resistant cap.DETAILED DESCRIPTIONCompounds of the Present Disclosure

[0031] It is understood that, as used herein, the term “Compound No. 1” refers to a compound having the following structure:(Compound No. 1), also known as 4-(2-cyanopropan-2-yl)-N-(4-methyl-3-(7-(methylamino)-l,6-naphthyridin-3- yl)phenyl)picolinamide.

[0032] In some embodiments, the compound of the present disclosure is Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0033] In some embodiments, the compound of the present disclosure is Compound No. 1.

[0034] Compound No. 1, or pharmaceutically acceptable salts thereof, may be synthesized using methods described in PCT Publication No. W02023 / 039505, the contents of which are incorporated in its entirety for all purposes.Formulations of the Present Disclosure

[0035] In some aspects, the present disclosure provides a formulation comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0036] In some embodiments, the present disclosure provides a formulation comprising Compound No. 1.294245842 6Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0037] In some embodiments, the present disclosure provides a formulation comprising Compound No. 1, or a pharmaceutically acceptable salt thereof, and one or more of a pharmaceutically acceptable carrier, diluent, adjuvant, or excipient.

[0038] In some embodiments, the present disclosure provides a formulation comprising Compound No. 1, and one or more of a pharmaceutically acceptable carrier, diluent, adjuvant, or excipient.

[0039] In some embodiments, the formulation comprises Compound No. 1.

[0040] In some embodiments, the formulation is an oral formulation.

[0041] In some embodiments, the formulation is a capsule or a tablet.

[0042] In some embodiments, the formulation is a capsule.

[0043] In some embodiments, the formulation is an immediate release capsule.

[0044] In some embodiments, the formulation is a tablet.

[0045] In some embodiments, the formulation is a film-coated tablet.

[0046] In some embodiments, the formulation is an immediate release tablet.

[0047] In some embodiments, the formulation is an immediate release film-coated tablet.

[0048] In some embodiments, the formulation is prepared from a bulk formulation.

[0049] In some embodiments, the formulation is stable for at least 1 month, at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, and / or at least 18 months at 5±3°C. In some embodiments, the formulation is stable for at least 1 month, at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, and / or at least 18 months at 25±2°C / 60±5%RH. In some embodiments, the formulation is stable for at least 1 month, at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, and / or at least 18 months at 30±2°C / 60±5%RH. In some embodiments, the formulation is stable for at least 1 month, at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, and / or at least 18 months at 40±2°C / 75±5%RH.

[0050] In some embodiments, the present disclosure provides a formulation comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0051] In some embodiments, the present disclosure provides a formulation comprising:(i) Compound No. 1;(ii) a filler;294245842 7Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(iii) a disintegrant; and(iv) a lubricant.

[0052] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0053] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0054] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium; and(iv) magnesium stearate.

[0055] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium; and(iv) magnesium stearate.

[0056] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0057] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and294245842 8Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0058] In some embodiments, the present disclosure provides a formulation comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0059] In some embodiments, the present disclosure provides a formulation comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0060] In some embodiments, the present disclosure provides a formulation comprising:(i) about 57% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0061] In some embodiments, the present disclosure provides a formulation comprising:(i) about 57% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0062] In some embodiments, the present disclosure provides a formulation comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0063] In some embodiments, the present disclosure provides a formulation comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No.294245842 9Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0064] In some embodiments, the present disclosure provides a formulation comprising:(i) about 40% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 57% w / w silicified microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0065] In some embodiments, the present disclosure provides a formulation comprising:(i) about 40% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 57% w / w silicified microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0066] In some embodiments, the present disclosure provides a formulation comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0067] In some embodiments, the present disclosure provides a formulation comprising:(i) Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0068] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.294245842 10Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0069] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0070] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate; and(v) colloidal silicon dioxide.

[0071] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate; and(v) colloidal silicon dioxide.

[0072] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0073] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0074] In some embodiments, the present disclosure provides a formulation comprising:294245842 11Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0075] In some embodiments, the present disclosure provides a formulation comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0076] In some embodiments, the present disclosure provides a formulation comprising:(i) about 17% of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 1% w / w colloidal silicon dioxide.

[0077] In some embodiments, the present disclosure provides a formulation comprising:(i) about 17% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 1% w / w colloidal silicon dioxide.

[0078] In some embodiments, the present disclosure provides a formulation comprising:(i) about 57% of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 0.5% w / w colloidal silicon dioxide.

[0079] In some embodiments, the present disclosure provides a formulation comprising:294245842 12Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(i) about 57% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 0.5% w / w colloidal silicon dioxide.

[0080] In some embodiments, the present disclosure provides a formulation comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0081] In some embodiments, the present disclosure provides a formulation comprising:(i) Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0082] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0083] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.294245842 13Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0084] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate;(v) colloidal silicon dioxide; and(vi) maize starch.

[0085] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate;(v) colloidal silicon dioxide; and(vi) maize starch.

[0086] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0087] In some embodiments, the present disclosure provides a formulation comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0088] In some embodiments, the present disclosure provides a formulation comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;294245842 14Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0089] In some embodiments, the present disclosure provides a formulation comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0090] In some embodiments, the present disclosure provides a formulation comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 39% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate;(v) about 1% w / w colloidal silicon dioxide; and(vi) about 39% w / w maize starch.

[0091] In some embodiments, the present disclosure provides a formulation comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 39% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate;(v) about 1% w / w colloidal silicon dioxide; and(vi) about 39% w / w maize starch.

[0092] In some embodiments, the present disclosure provides a capsule comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0093] In some embodiments, the present disclosure provides a capsule comprising:294245842 15Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(i) Compound No. 1;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0094] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0095] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0096] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium; and(iv) magnesium stearate.

[0097] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium; and(iv) magnesium stearate.

[0098] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0099] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;294245842 16Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(ii) about 35% w / w to about 60% w / w microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0100] In some embodiments, the present disclosure provides a capsule comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0101] In some embodiments, the present disclosure provides a capsule comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0102] In some embodiments, the present disclosure provides a capsule comprising:(i) about 57% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0103] In some embodiments, the present disclosure provides a capsule comprising:(i) about 57% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0104] In some embodiments, the present disclosure provides a capsule comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0105] In some embodiments, the present disclosure provides a capsule comprising:294245842 17Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0106] In some embodiments, the present disclosure provides a capsule comprising:(i) about 40% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 57% w / w silicified microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0107] In some embodiments, the present disclosure provides a capsule comprising:(i) about 40% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 57% w / w silicified microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0108] In some embodiments, the present disclosure provides a capsule comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0109] In some embodiments, the present disclosure provides a capsule comprising:(i) Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0110] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;294245842 J gAttorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(iv) a lubricant; and(v) a glidant.[OHl] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0112] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate; and(v) colloidal silicon dioxide.

[0113] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate; and(v) colloidal silicon dioxide.

[0114] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0115] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.294245842 19Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0116] In some embodiments, the present disclosure provides a capsule comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0117] In some embodiments, the present disclosure provides a capsule comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0118] In some embodiments, the present disclosure provides a capsule comprising:(i) about 17% of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 1% w / w colloidal silicon dioxide.

[0119] In some embodiments, the present disclosure provides a capsule comprising:(i) about 17% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 1% w / w colloidal silicon dioxide.

[0120] In some embodiments, the present disclosure provides a capsule comprising:(i) about 57% of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 0.5% w / w colloidal silicon dioxide.294245842 20Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0121] In some embodiments, the present disclosure provides a capsule comprising:(i) about 57% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 0.5% w / w colloidal silicon dioxide.

[0122] In some embodiments, the present disclosure provides a capsule comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0123] In some embodiments, the present disclosure provides a capsule comprising:(i) Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0124] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0125] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and294245842 21Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(vi) a diluent.

[0126] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate;(v) colloidal silicon dioxide; and(vi) maize starch.

[0127] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate;(v) colloidal silicon dioxide; and(vi) maize starch.

[0128] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0129] In some embodiments, the present disclosure provides a capsule comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0130] In some embodiments, the present disclosure provides a capsule comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;294245842 22Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0131] In some embodiments, the present disclosure provides a capsule comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0132] In some embodiments, the present disclosure provides a capsule comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 39% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate;(v) about 1% w / w colloidal silicon dioxide; and(vi) about 39% w / w maize starch.

[0133] In some embodiments, the present disclosure provides a capsule comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 39% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate;(v) about 1% w / w colloidal silicon dioxide; and(vi) about 39% w / w maize starch.

[0134] In some embodiments, the present disclosure provides a tablet comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.294245842 23Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0135] In some embodiments, the present disclosure provides a tablet comprising:(i) Compound No. 1;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0136] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0137] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant; and(iv) a lubricant.

[0138] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium; and(iv) magnesium stearate.

[0139] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium; and(iv) magnesium stearate.

[0140] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0141] In some embodiments, the present disclosure provides a tablet comprising:294245842 24Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0142] In some embodiments, the present disclosure provides a tablet comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0143] In some embodiments, the present disclosure provides a tablet comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium; and(iv) about 0.5% w / w to about 3% w / w magnesium stearate.

[0144] In some embodiments, the present disclosure provides a tablet comprising:(i) about 57% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0145] In some embodiments, the present disclosure provides a tablet comprising:(i) about 57% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0146] In some embodiments, the present disclosure provides a tablet comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.294245842 25Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0147] In some embodiments, the present disclosure provides a tablet comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0148] In some embodiments, the present disclosure provides a tablet comprising:(i) about 39% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 57% w / w silicified microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0149] In some embodiments, the present disclosure provides a tablet comprising:(i) about 39% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 57% w / w silicified microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0150] In some embodiments, the present disclosure provides a tablet comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0151] In some embodiments, the present disclosure provides a tablet comprising:(i) Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0152] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;294245842 26Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0153] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant; and(v) a glidant.

[0154] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate; and(v) colloidal silicon dioxide.

[0155] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate; and(v) colloidal silicon dioxide.

[0156] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0157] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and294245842 27Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0158] In some embodiments, the present disclosure provides a tablet comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0159] In some embodiments, the present disclosure provides a tablet comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate; and(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0160] In some embodiments, the present disclosure provides a tablet comprising:(i) about 17% of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 1% w / w colloidal silicon dioxide.

[0161] In some embodiments, the present disclosure provides a tablet comprising:(i) about 17% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 1% w / w colloidal silicon dioxide.

[0162] In some embodiments, the present disclosure provides a tablet comprising:(i) about 57% of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and294245842 28Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(v) about 0.5% w / w colloidal silicon dioxide.

[0163] In some embodiments, the present disclosure provides a tablet comprising:(i) about 57% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 0.5% w / w colloidal silicon dioxide.

[0164] In some embodiments, the present disclosure provides a tablet comprising:(i) Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0165] In some embodiments, the present disclosure provides a tablet comprising:(i) Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0166] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;(v) a glidant; and(vi) a diluent.

[0167] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) a filler;(iii) a disintegrant;(iv) a lubricant;294245842 29Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(v) a glidant; and(vi) a diluent.

[0168] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate;(v) colloidal silicon dioxide; and(vi) maize starch.

[0169] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) microcrystalline cellulose;(iii) croscarmellose sodium;(iv) magnesium stearate;(v) colloidal silicon dioxide; and(vi) maize starch.

[0170] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0171] In some embodiments, the present disclosure provides a tablet comprising:(i) an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0172] In some embodiments, the present disclosure provides a tablet comprising:294245842 30Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0173] In some embodiments, the present disclosure provides a tablet comprising:(i) about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 35% w / w to about 60% w / w silicified microcrystalline cellulose;(iii) about 0.5% w / w to about 5% w / w croscarmellose sodium;(iv) about 0.5% w / w to about 3% w / w magnesium stearate;(v) about 0.1% w / w to about 3% w / w colloidal silicon dioxide; and(vi) about 15% w / w to about 50% w / w maize starch.

[0174] In some embodiments, the present disclosure provides a tablet comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof;(ii) about 39% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate;(v) about 1% w / w colloidal silicon dioxide; and(vi) about 39% w / w maize starch.

[0175] In some embodiments, the present disclosure provides a tablet comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 39% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate;(v) about 1% w / w colloidal silicon dioxide; and(vi) about 39% w / w maize starch.

[0176] In some embodiments, the present disclosure provides a 3 mg capsule comprising:(i) about 17% w / w of an amorphous solid dispersion comprising Compound No.294245842 31Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(ii) about 39% w / w microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate;(v) about 1% w / w colloidal silicon dioxide; and(vi) about 39% w / w maize starch.

[0177] In some embodiments, the present disclosure provides a 25 mg capsule comprising:(i) about 39% w / w of an amorphous solid dispersion comprising Compound No. 1;(ii) about 57% w / w silicified microcrystalline cellulose;(iii) about 3% w / w croscarmellose sodium; and(iv) about 1% w / w magnesium stearate.

[0178] In some embodiments, the present disclosure provides a 50 mg tablet comprising:(i) about 57% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 0.5% w / w colloidal silicon dioxide.

[0179] In some embodiments, the present disclosure provides a 200 mg tablet comprising:(i) about 57% of an amorphous solid dispersion comprising Compound No. 1;(ii) about 40% w / w silicified microcrystalline cellulose;(iii) about 1% w / w croscarmellose sodium;(iv) about 1% w / w magnesium stearate; and(v) about 0.5% w / w colloidal silicon dioxide.

[0180] In some embodiments, the formulation comprises an intragranular mixture.

[0181] In some embodiments, the formulation comprises an extragranular mixture.

[0182] In some embodiments, the formulation comprises an intragranular mixture and an extragranular mixture.

[0183] In some embodiments, Compound No. 1, or a pharmaceutically acceptable salt thereof, and the polymer are present at a ratio of about 1 :4 (w / w).

[0184] In some embodiments, the solid dispersion is prepared by spray drying.

[0185] In some embodiments, the formulation further comprises one or more of a filler, a diluent, a disintegrant, a glidant, and a lubricant.

[0186] In some embodiments, the formulation further comprises one or more of a filler, a binder, a diluent, a disintegrant, a glidant, and a lubricant.294245842 32Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0187] In some embodiments, the formulation further comprises a filler.

[0188] In some embodiments, the formulation further comprises a binder.

[0189] In some embodiments, the formulation further comprises a diluent.

[0190] In some embodiments, the formulation further comprises a disintegrant.

[0191] In some embodiments, the formulation further comprises a glidant.

[0192] In some embodiments, the formulation further comprises a lubricant.

[0193] In some embodiments, the formulation further comprises a filler, a diluent, a disintegrant, a glidant, and a lubricant.

[0194] In some embodiments, the formulation further comprises a filler, a binder, a diluent, a disintegrant, a glidant, and a lubricant.

[0195] In some embodiments, the formulation comprises about 16.7% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0196] In some embodiments, the formulation comprises about 15.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0197] In some embodiments, the formulation comprises about 3.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0198] In some embodiments, the formulation comprises about 39.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the formulation comprises about 57.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0199] In some embodiments, the formulation comprises about 100.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the formulation comprises about 125.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the formulation comprises about 400.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0200] In some embodiments, the formulation comprises about 25.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the formulation comprises about 50.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the formulation comprises about 200.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0201] In some embodiments, the intragranular mixture of the formulation comprises about 39.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the intragranular mixture of the formulation294245842 33Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) comprises about 57.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0202] In some embodiments, the intragranular mixture of the formulation comprises about 25.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the intragranular mixture of the formulation comprises about 50.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the intragranular mixture of the formulation comprises about 200.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0203] In some embodiments, the intragranular mixture of the formulation comprises about 100.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the intragranular mixture of the formulation comprises about 125.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof. In some embodiments, the intragranular mixture of the formulation comprises about 400.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0204] In some embodiments, the formulation comprises one or more of the ingredients described in Table Al. In some embodiments, the tablet comprises one or more of the ingredients described in Table Al. In some embodiments, the capsule comprises one or more of the ingredients described in Table Al.

[0205] In some embodiments, the filler is microcrystalline cellulose. In some embodiments, the diluent is partially pregelatinized maize starch. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the glidant is colloidal silicon dioxide. In some embodiments, the lubricant is magnesium stearate.Table Al294245842 34Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0206] In some embodiments, the formulation comprises one or more of the ingredients described in Table A2. In some embodiments, the tablet comprises one or more of the ingredients described in Table A2. In some embodiments, the capsule comprises one or more of the ingredients described in Table A2.

[0207] In some embodiments, the filler is microcrystalline cellulose. In some embodiments, the diluent is partially pregelatinized maize starch. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the glidant is colloidal silicon dioxide. In some embodiments, the lubricant is magnesium stearate.Table A2

[0208] In some embodiments, the formulation comprises one or more of the ingredients described in Table A3. In some embodiments, the tablet comprises one or more of the294245842 35Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) ingredients described in Table A3. In some embodiments, the capsule comprises one or more of the ingredients described in Table A3.

[0209] In some embodiments, the filler is silicified microcrystalline cellulose. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the lubricant is magnesium stearate.Table A3

[0210] In some embodiments, the formulation comprises one or more of the ingredients described in Table A4. In some embodiments, the tablet comprises one or more of the ingredients described in Table A4. In some embodiments, the capsule comprises one or more of the ingredients described in Table A4.

[0211] In some embodiments, the filler is silicified microcrystalline cellulose. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the lubricant is magnesium stearate.Table A4294245842 36Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0212] In some embodiments, the formulation comprises one or more of the ingredients described in Table Bl. In some embodiments, the tablet comprises one or more of the ingredients described in Table Bl. In some embodiments, the capsule comprises one or more of the ingredients described in Table Bl.Table Bl

[0213] In some embodiments, the formulation comprises one or more of the ingredients described in Table B2. In some embodiments, the tablet comprises one or more of the294245842 37Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) ingredients described in Table B2. In some embodiments, the capsule comprises one or more of the ingredients described in Table B2.Table B2

[0214] In some embodiments, the formulation comprises one or more of the ingredients described in Table B3. In some embodiments, the tablet comprises one or more of the ingredients described in Table B3. In some embodiments, the capsule comprises one or more of the ingredients described in Table B3.Table B3294245842 38Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0215] In some embodiments, the formulation is selected from the formulations described in Tables 1 A & IB. In some embodiments, the capsule is selected from the formulations described in Tables 1A & IB.

[0216] In some embodiments, the weight ratios (% w / w) described in Tables 1 A & IB refer to the proportion of the mass of the agent per unit mass of the total weight of the bulk formulation. In some embodiments, the 3 mg capsule comprises about 90 mg of the bulk formulation. In some embodiments, the 25 mg capsule comprises about 320 mg of the bulk formulation.Table 1A294245842 39Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)Table IB

[0217] In some embodiments, the formulation is selected from the formulations described in Table 2. In some embodiments, the tablet is selected from the formulations described in Table 2.

[0218] In some embodiments, the weight ratios (% w / w) described in Table 2 refer to the proportion of the mass of the agent per unit mass of the total weight of the bulk formulation. In some embodiments, the 50 mg tablet comprises about 175 mg of the bulk formulation. In some embodiments, the 200 mg tablet comprises about 700 mg of the bulk formulation.Table 2Compounds of the Present Disclosure294245842 40Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0219] In some embodiments, the formulation comprises Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0220] In some embodiments, the formulation comprises Compound No. 1.

[0221] Without wishing to be bound by theory, an amorphous solid dispersion comprising Compound No. 1 provides increased homogeneity. In some embodiments, an amorphous solid dispersion comprising Compound No. 1 provides increased homogeneity in an intragranular mixture. In some embodiments, the homogeneity is improved by reducing stickiness of an intragranular mixture.

[0222] In some embodiments, the formulation comprises a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0223] In some embodiments, the formulation comprises a solid dispersion comprising Compound No. 1.

[0224] In some embodiments, the solid dispersion is an amorphous solid dispersion.

[0225] In some aspects, the solid dispersion further comprises a polymer.

[0226] In some embodiments, the polymer is hydroxypropyl methylcellulose (HPMC).

[0227] In some embodiments, the polymer is hydroxypropyl methylcellulose acetate succinate.

[0228] In some embodiments, the polymer is hydroxypropyl methylcellulose ASMG grade (HPMC ASMG).

[0229] In some embodiments, the polymer is sold as HPMC ASMG.

[0230] In some embodiments, the formulation comprises about 1% w / w, about 2% w / w, about 3% w / w, about 4% w / w, about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9 % w / w, about 10% w / w, about 15% w / w, about 20% w / w, about 25% w / w, or about 30% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0231] In some embodiments, the formulation comprises about 1% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0232] In some embodiments, the formulation comprises about 2% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0233] In some embodiments, the formulation comprises about 3% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0234] In some embodiments, the formulation comprises about 4% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0235] In some embodiments, the formulation comprises about 5% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.294245842 41Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0236] In some embodiments, the formulation comprises about 6% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0237] In some embodiments, the formulation comprises about 7% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0238] In some embodiments, the formulation comprises about 8% w / w of Compound No. 1 or a pharmaceutically acceptable salt thereof.

[0239] In some embodiments, the formulation comprises about 9 % w / w of Compound No.1 or a pharmaceutically acceptable salt thereof.

[0240] In some embodiments, the formulation comprises about 10% w / w of Compound No.1 or a pharmaceutically acceptable salt thereof.

[0241] In some embodiments, the formulation comprises about 15% w / w of Compound No.1 or a pharmaceutically acceptable salt thereof.

[0242] In some embodiments, the formulation comprises about 20% w / w of Compound No.1 or a pharmaceutically acceptable salt thereof.

[0243] In some embodiments, the formulation comprises about 25% w / w of Compound No.1 or a pharmaceutically acceptable salt thereof.

[0244] In some embodiments, the formulation comprises about 30% w / w of Compound No.1 or a pharmaceutically acceptable salt thereof.

[0245] In some embodiments, the formulation comprises about 1% w / w, about 2% w / w, about 3% w / w, about 4% w / w, about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9 % w / w, about 10% w / w, about 15% w / w, about 20% w / w, about 25% w / w, or about 30% w / w of Compound No. 1.

[0246] In some embodiments, the formulation comprises about 1% w / w of Compound No.1.

[0247] In some embodiments, the formulation comprises about 2% w / w of Compound No.1.

[0248] In some embodiments, the formulation comprises about 3% w / w of Compound No.1.

[0249] In some embodiments, the formulation comprises about 3.3% w / w of Compound No.1.

[0250] In some embodiments, the formulation comprises about 4% w / w of Compound No.1.

[0251] In some embodiments, the formulation comprises about 5% w / w of Compound No.1.294245842 42Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0252] In some embodiments, the formulation comprises about 6% w / w of Compound No.1.

[0253] In some embodiments, the formulation comprises about 7% w / w of Compound No.1.

[0254] In some embodiments, the formulation comprises about 7.8% w / w of Compound No.1.

[0255] In some embodiments, the formulation comprises about 8% w / w of Compound No.1.

[0256] In some embodiments, the formulation comprises about 9 % w / w of Compound No.1.

[0257] In some embodiments, the formulation comprises about 10% w / w of Compound No.1.

[0258] In some embodiments, the formulation comprises about 15% w / w of Compound No.1.

[0259] In some embodiments, the formulation comprises about 20% w / w of Compound No.1.

[0260] In some embodiments, the formulation comprises about 25% w / w of Compound No.1.

[0261] In some embodiments, the formulation comprises about 28.6% w / w of Compound No. 1.

[0262] In some embodiments, the formulation comprises about 30% w / w of Compound No. 1.

[0263] In some embodiments, the formulation comprises about 3 mg to about 10 mg of Compound No. 1. In some embodiments, the formulation comprises about 25 mg to about 50 mg of Compound No. 1. In some embodiments, the formulation comprises about 25 mg to about 40 mg of Compound No. 1. In some embodiments, the formulation comprises about 3 mg of Compound No. 1. In some embodiments, the formulation comprises about 25 mg of Compound No. 1. In some embodiments, the formulation comprises about 50 mg of Compound No. 1.

[0264] In some embodiments, the formulation comprises about 50 mg to about 200 mg of Compound No. 1. In some embodiments, the formulation comprises about 200 mg of Compound No. 1.294245842 43Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0265] In some embodiments, the formulation comprises about 5% w / w, about 10% w / w, about 15% w / w, about 20% w / w, about 25% w / w, about 30% w / w, or about 35% w / w of HPMC ASMG.

[0266] In some embodiments, the formulation comprises about 5% w / w of HPMC ASMG.

[0267] In some embodiments, the formulation comprises about 10% w / w of HPMC ASMG.

[0268] In some embodiments, the formulation comprises about 13.4% w / w of HPMC ASMG.

[0269] In some embodiments, the formulation comprises about 15% w / w of HPMC ASMG.

[0270] In some embodiments, the formulation comprises about 20% w / w of HPMC ASMG.

[0271] In some embodiments, the formulation comprises about 25% w / w of HPMC ASMG.

[0272] In some embodiments, the formulation comprises about 28.6% w / w of HPMCASMG.

[0273] In some embodiments, the formulation comprises about 30% w / w of HPMC ASMG.

[0274] In some embodiments, the formulation comprises about 31.2% w / w of HPMC ASMG.

[0275] In some embodiments, the formulation comprises about 35% w / w of HPMC ASMG.

[0276] In some embodiments, the formulation comprises a solid dispersion of Compound No. 1. In some embodiments, the formulation comprises an amorphous solid dispersion of Compound No. 1.

[0277] In some embodiments, the formulation comprises about 10% w / w to about 60% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0278] In some embodiments, the formulation comprises about 10% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0279] In some embodiments, the formulation comprises about 15% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0280] In some embodiments, the formulation comprises about 16.7% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0281] In some embodiments, the formulation comprises about 20% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0282] In some embodiments, the formulation comprises about 25% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0283] In some embodiments, the formulation comprises about 30% w / w of an amorphous solid dispersion comprising Compound No. 1.294245842 44Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0284] In some embodiments, the formulation comprises about 35% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0285] In some embodiments, the formulation comprises about 39.1% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0286] In some embodiments, the formulation comprises about 40% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0287] In some embodiments, the formulation comprises about 45% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0288] In some embodiments, the formulation comprises about 50% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0289] In some embodiments, the formulation comprises about 55% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0290] In some embodiments, the formulation comprises about 57.1% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0291] In some embodiments, the formulation comprises about 60% w / w of an amorphous solid dispersion comprising Compound No. 1.

[0292] In some embodiments, the amorphous solid dispersion comprises HPMC ASMG.

[0293] In some embodiments, the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 : 1 w / w, about a 1 :2 w / w, about a 1 :3 w / w, about a 1 :4 w / w, or about a 1 :5 w / w ratio of Compound No. 1 to HPMC ASMG.

[0294] In some embodiments, the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 : 1 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :2 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :3 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :4 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :5 w / w ratio of Compound No. 1 to HPMC ASMG.Fillers

[0295] In some embodiments, the formulation comprises a filler.294245842 45Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0296] In some embodiments, the filler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or cellulose.

[0297] In some embodiments, the filler comprises cellulose.

[0298] In some embodiments, the filler comprises microcrystalline cellulose.

[0299] In some embodiments, the filler comprises silicified microcrystalline cellulose.

[0300] In some embodiments, the formulation comprises about 35% w / w to about 60% w / w of the filler.

[0301] In some embodiments, the formulation comprises about 35% w / w of the filler.

[0302] In some embodiments, the formulation comprises about 39.2% w / w of the filler.

[0303] In some embodiments, the formulation comprises about 40% w / w of the filler.

[0304] In some embodiments, the formulation comprises about 40.4% w / w of the filler.

[0305] In some embodiments, the formulation comprises about 45% w / w of the filler.

[0306] In some embodiments, the formulation comprises about 50% w / w of the filler.

[0307] In some embodiments, the formulation comprises about 55% w / w of the filler.

[0308] In some embodiments, the formulation comprises about 56.9% w / w of the filler.

[0309] In some embodiments, the formulation comprises about 60% w / w of the filler.

[0310] In some embodiments, the formulation comprises about 35.3 mg of the filler. In some embodiments, the formulation comprises about 70.7 mg of the filler. In some embodiments, the formulation comprises about 182.2 mg of the filler. In some embodiments, the formulation comprises about 282.5 mg of the filler.

[0311] In some embodiments, the intragranular mixture of the formulation comprises about 35.4% w / w of the filler.

[0312] In some embodiments, the intragranular mixture of the formulation comprises about 56.9% w / w of the filler.

[0313] In some embodiments, the intragranular mixture of the formulation comprises about 61.9 mg of the filler. In some embodiments, the intragranular mixture of the formulation comprises about 182.2 mg of the filler. In some embodiments, the intragranular mixture of the formulation comprises about 247.5 mg of the filler.

[0314] In some embodiments, the extragranular mixture of the formulation comprises about 5.0% w / w of the filler.

[0315] In some embodiments, the extragranular mixture of the formulation comprises about 8.8 mg of the filler. In some embodiments, the extragranular mixture of the formulation comprises about 35.0 mg of the filler.294245842 46Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0316] In some embodiments, the formulation comprises about 35% w / w to about 60% w / w microcrystalline cellulose.

[0317] In some embodiments, the formulation comprises about 35% w / w microcrystalline cellulose.

[0318] In some embodiments, the formulation comprises about 39.2% w / w microcrystalline cellulose.

[0319] In some embodiments, the formulation comprises about 40% w / w microcrystalline cellulose.

[0320] In some embodiments, the formulation comprises about 40.4% w / w microcrystalline cellulose.

[0321] In some embodiments, the formulation comprises about 45% w / w microcrystalline cellulose.

[0322] In some embodiments, the formulation comprises about 50% w / w microcrystalline cellulose.

[0323] In some embodiments, the formulation comprises about 55% w / w microcrystalline cellulose.

[0324] In some embodiments, the formulation comprises about 56.9% w / w microcrystalline cellulose.

[0325] In some embodiments, the formulation comprises about 60% w / w microcrystalline cellulose.

[0326] In some embodiments, the formulation comprises about 35.3 mg microcrystalline cellulose. In some embodiments, the formulation comprises about 70.7 mg microcrystalline cellulose. In some embodiments, the formulation comprises about 182.2 mg microcrystalline cellulose. In some embodiments, the formulation comprises about 282.5 mg microcrystalline cellulose.

[0327] In some embodiments, the intragranular mixture of the formulation comprises about 35.4% w / w microcrystalline cellulose.

[0328] In some embodiments, the intragranular mixture of the formulation comprises about 56.9% w / w microcrystalline cellulose.

[0329] In some embodiments, the intragranular mixture of the formulation comprises about 61.9 mg microcrystalline cellulose. In some embodiments, the intragranular mixture of the formulation comprises about 182.2 mg microcrystalline cellulose. In some embodiments, the intragranular mixture of the formulation comprises about 247.5 mg microcrystalline cellulose.294245842 47Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0330] In some embodiments, the extragranular mixture of the formulation comprises about 5.0% w / w microcrystalline cellulose.

[0331] In some embodiments, the extragranular mixture of the formulation comprises about 8.8 mg microcrystalline cellulose. In some embodiments, the extragranular mixture of the formulation comprises about 35.0 mg microcrystalline cellulose.Binders

[0332] In some embodiments, the binder comprises polyvinylpyrrolidone (also referred to as Kollidon), copovidone, com starch, pregelatinized starch, hydroxypropyl methylcellulose (HPMC; also referred to as hypromellose), hydroxyethyl cellulose, hydroxypropyl cellulose, dextrin, magnesium aluminum silicate, sodium alginate.Diluents

[0333] In some embodiments, the formulation comprises a diluent.

[0334] In some embodiments, the diluent comprises microcrystalline cellulose, lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or any combination thereof.

[0335] In some embodiments, the diluent comprises maize starch.

[0336] In some embodiments, the diluent comprises pregelatinized maize starch.

[0337] In some embodiments, the diluent comprises partially pregelatinized maize starch.

[0338] In some embodiments, the diluent comprises microcrystalline cellulose.

[0339] In some embodiments, the diluent comprises silicified microcrystalline cellulose.

[0340] In some embodiments, the formulation comprises about 15% w / w to about 50% w / w of the diluent.

[0341] In some embodiments, the formulation comprises about 15% w / w of the diluent.

[0342] In some embodiments, the formulation comprises about 20% w / w of the diluent.

[0343] In some embodiments, the formulation comprises about 25% w / w of the diluent.

[0344] In some embodiments, the formulation comprises about 30% w / w of the diluent.

[0345] In some embodiments, the formulation comprises about 35% w / w of the diluent.

[0346] In some embodiments, the formulation comprises about 39.2% w / w of the diluent.

[0347] In some embodiments, the formulation comprises about 40% w / w of the diluent.

[0348] In some embodiments, the formulation comprises about 45% w / w of the diluent.

[0349] In some embodiments, the formulation comprises about 50% w / w of the diluent.294245842 48Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0350] In some embodiments, the formulation comprises about 35.3 mg of the diluent.

[0351] In some embodiments, the formulation comprises about 15% w / w to about 50% w / w of partially pregelatinized maize starch.

[0352] In some embodiments, the formulation comprises about 15% w / w of partially pregelatinized maize starch.

[0353] In some embodiments, the formulation comprises about 20% w / w of partially pregelatinized maize starch.

[0354] In some embodiments, the formulation comprises about 25% w / w of partially pregelatinized maize starch.

[0355] In some embodiments, the formulation comprises about 30% w / w of partially pregelatinized maize starch.

[0356] In some embodiments, the formulation comprises about 35% w / w of partially pregelatinized maize starch.

[0357] In some embodiments, the formulation comprises about 39.2% w / w of partially pregelatinized maize starch.

[0358] In some embodiments, the formulation comprises about 40% w / w of partially pregelatinized maize starch.

[0359] In some embodiments, the formulation comprises about 45% w / w of partially pregelatinized maize starch.

[0360] In some embodiments, the formulation comprises about 50% w / w of partially pregelatinized maize starch.

[0361] In some embodiments, the formulation comprises about 35.3 mg of partially pregelatinized maize starch.Disintegrants

[0362] In some embodiments, the formulation comprises a disintegrant.

[0363] In some embodiments, the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate, chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

[0364] In some embodiments, the disintegrant comprises a sodium salt.

[0365] In some embodiments, the disintegrant comprises sodium carboxymethylcellulose.

[0366] In some embodiments, the disintegrant comprises croscarmellose sodium.294245842 49Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0367] In some embodiments, the formulation comprises about 0.5% w / w to about 5% w / w of the disintegrant.

[0368] In some embodiments, the formulation comprises about 0.5% w / w of the disintegrant.

[0369] In some embodiments, the formulation comprises about 1% w / w of the disintegrant.

[0370] In some embodiments, the formulation comprises about 1.5% w / w of the disintegrant.

[0371] In some embodiments, the formulation comprises about 2% w / w of the disintegrant.

[0372] In some embodiments, the formulation comprises about 2.5% w / w of the disintegrant.

[0373] In some embodiments, the formulation comprises about 3% w / w of the disintegrant.

[0374] In some embodiments, the formulation comprises about 3.5% w / w of the disintegrant.

[0375] In some embodiments, the formulation comprises about 4% w / w of the disintegrant.

[0376] In some embodiments, the formulation comprises about 4.5% w / w of the disintegrant.

[0377] In some embodiments, the formulation comprises about 5% w / w of the disintegrant.

[0378] In some embodiments, the formulation comprises about 1.8 mg of the disintegrant. In some embodiments, the formulation comprises about 2.7 mg of the disintegrant. In some embodiments, the formulation comprises about 9.6 mg of the disintegrant.

[0379] In some embodiments, the intragranular mixture of the formulation comprises about 1.0% w / w of the disintegrant.

[0380] In some embodiments, the intragranular mixture of the formulation comprises about 3.0% w / w of the disintegrant.

[0381] In some embodiments, the intragranular mixture of the formulation comprises about 1.8 mg of the disintegrant. In some embodiments, the intragranular mixture of the formulation comprises about 7.0 mg of the disintegrant. In some embodiments, the intragranular mixture of the formulation comprises about 9.6 mg of the disintegrant.

[0382] In some embodiments, the formulation comprises about 0.5% w / w to about 5% w / w croscarmellose sodium.

[0383] In some embodiments, the formulation comprises about 0.5% w / w croscarmellose sodium.

[0384] In some embodiments, the formulation comprises about 1% w / w croscarmellose sodium.

[0385] In some embodiments, the formulation comprises about 1.5% w / w croscarmellose sodium.

[0386] In some embodiments, the formulation comprises about 2% w / w croscarmellose sodium.294245842 50Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0387] In some embodiments, the formulation comprises about 2.5% w / w croscarmellose sodium.

[0388] In some embodiments, the formulation comprises about 3% w / w croscarmellose sodium.

[0389] In some embodiments, the formulation comprises about 3.5% w / w croscarmellose sodium.

[0390] In some embodiments, the formulation comprises about 4% w / w croscarmellose sodium.

[0391] In some embodiments, the formulation comprises about 4.5% w / w croscarmellose sodium.

[0392] In some embodiments, the formulation comprises about 5% w / w croscarmellose sodium.

[0393] In some embodiments, the formulation comprises about 1.8 mg croscarmellose sodium. In some embodiments, the formulation comprises about 2.7 mg croscarmellose sodium. In some embodiments, the formulation comprises about 9.6 mg croscarmellose sodium.

[0394] In some embodiments, the intragranular mixture of the formulation comprises about 1.0% w / w croscarmellose sodium.

[0395] In some embodiments, the intragranular mixture of the formulation comprises about 3.0% w / w croscarmellose sodium.

[0396] In some embodiments, the intragranular mixture of the formulation comprises about 1.8 mg croscarmellose sodium. In some embodiments, the intragranular mixture of the formulation comprises about 7.0 mg croscarmellose sodium. In some embodiments, the intragranular mixture of the formulation comprises about 9.6 mg croscarmellose sodium.Glidants

[0397] In some embodiments, the formulation comprises a glidant.

[0398] In some embodiments, the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

[0399] In some embodiments, the glidant comprises silicon dioxide.

[0400] In some embodiments, the glidant comprises colloidal silicon dioxide.

[0401] In some embodiments, the formulation comprises about 0.1% w / w to about 3% w / w of the glidant.294245842 51Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0402] In some embodiments, the formulation comprises about 0.1% w / w of the glidant.

[0403] In some embodiments, the formulation comprises about 0.5% w / w of the glidant.

[0404] In some embodiments, the formulation comprises about 1% w / w of the glidant.

[0405] In some embodiments, the formulation comprises about 1.5% w / w of the glidant.

[0406] In some embodiments, the formulation comprises about 2% w / w of the glidant.

[0407] In some embodiments, the formulation comprises about 2.5% w / w of the glidant.

[0408] In some embodiments, the formulation comprises about 3% w / w of the glidant.

[0409] In some embodiments, the formulation comprises about 0.9 mg of the glidant.

[0410] In some embodiments, the extragranular mixture of the formulation comprises about 0.5% w / w of the glidant.

[0411] In some embodiments, the extragranular mixture of the formulation comprises about 0.9 mg of the glidant. In some embodiments, the extragranular mixture of the formulation comprises about 3.5 mg of the glidant.

[0412] In some embodiments, the formulation comprises about 0.1% w / w to about 3% w / w colloidal silicon dioxide.

[0413] In some embodiments, the formulation comprises about 0.1% w / w colloidal silicon dioxide.

[0414] In some embodiments, the formulation comprises about 0.5% w / w colloidal silicon dioxide.

[0415] In some embodiments, the formulation comprises about 1% w / w colloidal silicon dioxide.

[0416] In some embodiments, the formulation comprises about 1.5% w / w colloidal silicon dioxide.

[0417] In some embodiments, the formulation comprises about 2% w / w colloidal silicon dioxide.

[0418] In some embodiments, the formulation comprises about 2.5% w / w colloidal silicon dioxide.

[0419] In some embodiments, the formulation comprises about 3% w / w colloidal silicon dioxide.

[0420] In some embodiments, the formulation comprises about 0.9 mg colloidal silicon dioxide.

[0421] In some embodiments, the extragranular mixture of the formulation comprises about 0.5% w / w colloidal silicon dioxide.294245842 52Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0422] In some embodiments, the extragranular mixture of the formulation comprises about 0.9 mg colloidal silicon dioxide. In some embodiments, the extragranular mixture of the formulation comprises about 3.5 mg colloidal silicon dioxide.Lubricants

[0423] In some embodiments, the formulation comprises a lubricant.

[0424] In some embodiments, the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

[0425] In some embodiments, the lubricant comprises a magnesium salt.

[0426] In some embodiments, the lubricant comprises magnesium stearate.

[0427] In some embodiments, the formulation comprises about 0.5% w / w to about 3% w / w of the lubricant. In some embodiments, the formulation comprises about 1% w / w to about 3% w / w of the lubricant.

[0428] In some embodiments, the formulation comprises at least about 0.5% w / w of the lubricant.

[0429] In some embodiments, the formulation comprises at least about 1% w / w of the lubricant.

[0430] In some embodiments, the formulation comprises at least about 1.5% w / w of the lubricant.

[0431] In some embodiments, the formulation comprises at least about 2% w / w of the lubricant.

[0432] In some embodiments, the formulation comprises at least about 2.5% w / w of the lubricant.

[0433] In some embodiments, the formulation comprises at least about 3% w / w of the lubricant.

[0434] In some embodiments, the formulation comprises about 0.5% w / w of the lubricant.

[0435] In some embodiments, the formulation comprises about 1% w / w of the lubricant.

[0436] In some embodiments, the formulation comprises about 1.5% w / w of the lubricant.

[0437] In some embodiments, the formulation comprises about 2% w / w of the lubricant.

[0438] In some embodiments, the formulation comprises about 2.5% w / w of the lubricant.

[0439] In some embodiments, the formulation comprises about 3% w / w of the lubricant.

[0440] In some embodiments, the formulation comprises about 0.9 mg of the lubricant. In some embodiments, the formulation comprises about 1.8 mg of the lubricant. In some294245842 53Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) embodiments, the formulation comprises about 3.2 mg of the lubricant. In some embodiments, the formulation comprises about 7.0 mg of the lubricant.

[0441] In some embodiments, the intragranular mixture of the formulation comprises about 0.5% w / w of the lubricant.

[0442] In some embodiments, the intragranular mixture of the formulation comprises about 0.9 mg of the lubricant. In some embodiments, the intragranular mixture of the formulation comprises about 1.6 mg of the lubricant. In some embodiments, the intragranular mixture of the formulation comprises about 3.5 mg of the lubricant.

[0443] In some embodiments, the extragranular mixture of the formulation comprises about 0.5% w / w of the lubricant.

[0444] In some embodiments, the extragranular mixture of the formulation comprises about 0.9 mg of the lubricant. In some embodiments, the extragranular mixture of the formulation comprises about 1.6 mg of the lubricant. In some embodiments, the extragranular mixture of the formulation comprises about 3.5 mg of the lubricant.

[0445] In some embodiments, the formulation comprises about 0.5% w / w to about 3% w / w magnesium stearate.

[0446] In some embodiments, the formulation comprises about 0.5% w / w magnesium stearate.

[0447] In some embodiments, the formulation comprises about 1% w / w magnesium stearate.

[0448] In some embodiments, the formulation comprises about 1.5% w / w magnesium stearate.

[0449] In some embodiments, the formulation comprises about 2% w / w magnesium stearate.

[0450] In some embodiments, the formulation comprises about 2.5% w / w magnesium stearate.

[0451] In some embodiments, the formulation comprises about 3% w / w magnesium stearate.

[0452] In some embodiments, the formulation comprises about 0.9 mg magnesium stearate. In some embodiments, the formulation comprises about 1.8 mg magnesium stearate. In some embodiments, the formulation comprises about 3.2 mg magnesium stearate. In some embodiments, the formulation comprises about 7.0 mg magnesium stearate.

[0453] In some embodiments, the intragranular mixture of the formulation comprises about 0.5% w / w magnesium stearate.

[0454] In some embodiments, the intragranular mixture of the formulation comprises about 0.9 mg magnesium stearate. In some embodiments, the intragranular mixture of the formulation294245842 54Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) comprises about 1.6 mg magnesium stearate. In some embodiments, the intragranular mixture of the formulation comprises about 3.5 mg magnesium stearate.

[0455] In some embodiments, the extragranular mixture of the formulation comprises about 0.5% w / w magnesium stearate.

[0456] In some embodiments, the extragranular mixture of the formulation comprises about 0.9 mg magnesium stearate. In some embodiments, the extragranular mixture of the formulation comprises about 1.6 mg magnesium stearate. In some embodiments, the extragranular mixture of the formulation comprises about 3.5 mg magnesium stearate.Capsules

[0457] In some embodiments, the formulation is a capsule.

[0458] In some embodiments, the capsule comprises Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0459] In some embodiments, the capsule comprises an intragranular mixture.

[0460] In some embodiments, the capsule comprises an extragranular mixture.

[0461] In some embodiments, the capsule comprises an intragranular mixture and an extragranular mixture.

[0462] In some embodiments, the capsule comprises Compound No. 1.

[0463] In some embodiments, the capsule comprises a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0464] In some embodiments, the capsule comprises a solid dispersion comprising Compound No. 1.

[0465] In some embodiments, the capsule further comprises one or more of a filler, a diluent, a disintegrant, a glidant, and a lubricant.

[0466] In some embodiments, the capsule further comprises one or more of a filler, a binder, a diluent, a disintegrant, a glidant, and a lubricant.

[0467] In some embodiments, the capsule further comprises a filler.

[0468] In some embodiments, the capsule further comprises a binder.

[0469] In some embodiments, the capsule further comprises a diluent.

[0470] In some embodiments, the capsule further comprises a disintegrant.

[0471] In some embodiments, the capsule further comprises a glidant.

[0472] In some embodiments, the capsule further comprises a lubricant.

[0473] In some embodiments, the capsule further comprises a filler, a diluent, a disintegrant, a glidant, and a lubricant.294245842 55Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0474] In some embodiments, the capsule further comprises a filler, a binder, a diluent, a disintegrant, a glidant, and a lubricant.

[0475] In some embodiments, the capsule comprises about 16.7% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0476] In some embodiments, the capsule comprises about 15.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0477] In some embodiments, the capsule comprises about 3.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0478] In some embodiments, the capsule comprises about 39.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0479] In some embodiments, the capsule comprises about 125.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0480] In some embodiments, the capsule comprises about 25.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0481] In some embodiments, the intragranular mixture of the capsule comprises about 39.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0482] In some embodiments, the intragranular mixture of the capsule comprises about 125.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0483] In some embodiments, the intragranular mixture of the capsule comprises about 25.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.Fillers

[0484] In some embodiments, the capsule comprises about 39.2% w / w of the filler.

[0485] In some embodiments, the capsule comprises about 56.9% w / w of the filler.

[0486] In some embodiments, the capsule comprises about 35.3 mg of the filler. In some embodiments, the capsule comprises about 182.2 mg of the filler.

[0487] In some embodiments, the intragranular mixture of the capsule comprises about 56.9% w / w of the filler.

[0488] In some embodiments, the intragranular mixture of the capsule comprises about 182.2 mg of the filler.

[0489] In some embodiments, the capsule comprises about 39.2% w / w of microcrystalline cellulose.294245842 56Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0490] In some embodiments, the capsule comprises about 56.9% w / w of silicified microcrystalline cellulose.

[0491] In some embodiments, the capsule comprises about 35.3 mg of microcrystalline cellulose. In some embodiments, the capsule comprises about 182.2 mg of silicified microcrystalline cellulose.

[0492] In some embodiments, the intragranular mixture of the capsule comprises about 56.9% w / w of silicified microcrystalline cellulose.

[0493] In some embodiments, the intragranular mixture of the capsule comprises about 182.2 mg of silicified microcrystalline cellulose.Diluents

[0494] In some embodiments, the capsule comprises about 39.2% w / w of the diluent.

[0495] In some embodiments, the capsule comprises about 35.3 mg of the diluent.

[0496] In some embodiments, the capsule comprises about 39.2% w / w partially pregelatinized maize starch.

[0497] In some embodiments, the capsule comprises about 35.3 mg partially pregelatinized maize starch.Disintegrants

[0498] In some embodiments, the capsule comprises about 3.0% w / w of the disintegrant.

[0499] In some embodiments, the capsule comprises about 2.7 mg of the disintegrant. In some embodiments, the capsule comprises about 9.6 mg of the disintegrant.

[0500] In some embodiments, the intragranular mixture of the capsule comprises about 3.0% w / w of the disintegrant.

[0501] In some embodiments, the intragranular mixture of the capsule comprises about 9.6 mg of the disintegrant.

[0502] In some embodiments, the capsule comprises about 3.0% w / w croscarmellose sodium.

[0503] In some embodiments, the capsule comprises about 2.7 mg croscarmellose sodium. In some embodiments, the capsule comprises about 9.6 mg croscarmellose sodium.

[0504] In some embodiments, the intragranular mixture of the capsule comprises about 3.0% w / w croscarmellose sodium.

[0505] In some embodiments, the intragranular mixture of the capsule comprises about 9.6 mg croscarmellose sodium.294245842 57Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)Glidants

[0506] In some embodiments, the capsule comprises about 1.0% w / w of the glidant.

[0507] In some embodiments, the capsule comprises about 0.9 mg of the glidant.

[0508] In some embodiments, the capsule comprises about 1.0% w / w colloidal silicon dioxide.

[0509] In some embodiments, the capsule comprises about 0.9 mg colloidal silicon dioxide.Lubricants

[0510] In some embodiments, the capsule comprises about 1.0% w / w of the lubricant.

[0511] In some embodiments, the capsule comprises about 0.9 mg of the lubricant. In some embodiments, the capsule comprises about 3.2 mg of the lubricant.

[0512] In some embodiments, the intragranular mixture of the capsule comprises about 0.5% w / w of the lubricant.

[0513] In some embodiments, the extragranular mixture of the capsule comprises about 0.5% w / w of the lubricant.

[0514] In some embodiments, the intragranular mixture of the capsule comprises about 1.6 mg of the lubricant.

[0515] In some embodiments, the extragranular mixture of the capsule comprises about 1.6 mg of the lubricant.

[0516] In some embodiments, the capsule comprises about 1.0% w / w magnesium stearate.

[0517] In some embodiments, the capsule comprises about 0.9 mg magnesium stearate. In some embodiments, the capsule comprises about 3.2 mg magnesium stearate.

[0518] In some embodiments, the intragranular mixture of the capsule comprises about 0.5% w / w magnesium stearate.

[0519] In some embodiments, the extragranular mixture of the capsule comprises about 0.5% w / w magnesium stearate.

[0520] In some embodiments, the intragranular mixture of the capsule comprises about 1.6 mg magnesium stearate.

[0521] In some embodiments, the extragranular mixture of the capsule comprises about 1.6 mg magnesium stearate.Tablets

[0522] In some embodiments, the tablet comprises Compound No. 1, or a pharmaceutically acceptable salt thereof.294245842 58Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0523] In some embodiments, the tablet comprises an intragranular mixture.

[0524] In some embodiments, the tablet comprises an extragranular mixture.

[0525] In some embodiments, the tablet comprises an intragranular mixture and an extragranular mixture.

[0526] In some embodiments, the tablet comprises Compound No. 1.

[0527] In some embodiments, the tablet comprises a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0528] In some embodiments, the tablet comprises a solid dispersion comprising Compound No. 1.

[0529] In some embodiments, the tablet has a hardness range of about 50 N to about 300 N.

[0530] In some embodiments, the tablet has a hardness range of about 70 N to about 130 N. In some embodiments, the tablet has a hardness range of about 100 N to about 121 N.

[0531] In some embodiments, the tablet has a hardness range of about 230 N to about 300 N. In some embodiments, the tablet has a hardness range of about 233 N to about 285 N.

[0532] In some embodiments, the tablet has a disintegration time of about 30 seconds to about 70 seconds. In some embodiments, the tablet has a disintegration time of about 40 seconds to about 60 seconds. In some embodiments, the tablet has a disintegration time of about 45 seconds to about 57 seconds.

[0533] In some embodiments, the tablet has a disintegration time of less than about 45 seconds, less than about 50 seconds, less than about 55 seconds, less than about 60 seconds, less than about 65 seconds, or less than about 70 seconds.

[0534] In some embodiments, the tablet further comprises a filler.

[0535] In some embodiments, the tablet further comprises a disintegrant.

[0536] In some embodiments, the tablet further comprises a glidant.

[0537] In some embodiments, the tablet further comprises a lubricant.

[0538] In some embodiments, the tablet further comprises a filler, a disintegrant, a glidant, and a lubricant.

[0539] In some embodiments, the tablet comprises about 57.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0540] In some embodiments, the tablet comprises about 100.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0541] In some embodiments, the tablet comprises about 400.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.294245842 59Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0542] In some embodiments, the tablet comprises about 50.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0543] In some embodiments, the tablet comprises about 200.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0544] In some embodiments, the intragranular mixture of the tablet comprises about 57.1% w / w of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0545] In some embodiments, the intragranular mixture of the tablet comprises about 100.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0546] In some embodiments, the intragranular mixture of the tablet comprises about 400.0 mg of a solid dispersion comprising Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0547] In some embodiments, the intragranular mixture of the tablet comprises about 50.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0548] In some embodiments, the intragranular mixture of the tablet comprises about 200.0 mg of Compound No. 1, or a pharmaceutically acceptable salt thereof.Fillers

[0549] In some embodiments, the tablet comprises about 40.4% w / w of the filler.

[0550] In some embodiments, the tablet comprises about 70.7 mg of the filler. In some embodiments, the tablet comprises about 282.5 mg of the filler.

[0551] In some embodiments, the intragranular mixture of the tablet comprises about 35.4% w / w of the filler.

[0552] In some embodiments, the extragranular mixture of the tablet comprises about 5.0% w / w of the filler.

[0553] In some embodiments, the intragranular mixture of the tablet comprises about 61.9 mg of the filler. In some embodiments, the intragranular mixture of the tablet comprises about 247.5 mg of the filler.

[0554] In some embodiments, the extragranular mixture of the tablet comprises about 8.8 mg of the filler. In some embodiments, the extragranular mixture of the tablet comprises about 35.0 mg of the filler.

[0555] In some embodiments, the tablet comprises about 40.4% w / w of silicified microcrystalline cellulose.294245842 60Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0556] In some embodiments, the tablet comprises about 70.7 mg of silicified microcrystalline cellulose. In some embodiments, the tablet comprises about 282.5 mg of silicified microcrystalline cellulose.

[0557] In some embodiments, the intragranular mixture of the tablet comprises about 35.4% w / w of silicified microcrystalline cellulose.

[0558] In some embodiments, the extragranular mixture of the tablet comprises about 5.0% w / w of silicified microcrystalline cellulose.

[0559] In some embodiments, the intragranular mixture of the tablet comprises about 61.9 mg of silicified microcrystalline cellulose. In some embodiments, the intragranular mixture of the tablet comprises about 247.5 mg of silicified microcrystalline cellulose.

[0560] In some embodiments, the extragranular mixture of the tablet comprises about 8.8 mg of silicified microcrystalline cellulose. In some embodiments, the extragranular mixture of the tablet comprises about 35.0 mg of silicified microcrystalline cellulose.Disintegrants

[0561] In some embodiments, the tablet comprises about 1.0% w / w of the disintegrant.

[0562] In some embodiments, the tablet comprises about 1.8 mg of the disintegrant.

[0563] In some embodiments, the intragranular mixture of the tablet comprises about 1.0% w / w of the disintegrant.

[0564] In some embodiments, the intragranular mixture of the tablet comprises about 1.8 mg of the disintegrant. In some embodiments, the intragranular mixture of the tablet comprises about 7.0 mg of the disintegrant.

[0565] In some embodiments, the tablet comprises about 1.0% w / w croscarmellose sodium.

[0566] In some embodiments, the tablet comprises about 1.8 mg croscarmellose sodium.

[0567] In some embodiments, the intragranular mixture of the tablet comprises about 1.0% w / w croscarmellose sodium.

[0568] In some embodiments, the intragranular mixture of the tablet comprises about 1.8 mg croscarmellose sodium. In some embodiments, the intragranular mixture of the tablet comprises about 7.0 mg croscarmellose sodium.Glidants

[0569] In some embodiments, the tablet comprises about 0.5% w / w of the glidant.

[0570] In some embodiments, the tablet comprises about 0.9 mg of the glidant.294245842 61Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0571] In some embodiments, the extragranular mixture of the tablet comprises about 0.5% w / w of the glidant.

[0572] In some embodiments, the extragranular mixture of the tablet comprises about 0.9 mg of the glidant. In some embodiments, the extragranular mixture of the tablet comprises about3.5 mg of the glidant.

[0573] In some embodiments, the tablet comprises about 0.5% w / w colloidal silicon dioxide.

[0574] In some embodiments, the tablet comprises about 0.9 mg colloidal silicon dioxide.

[0575] In some embodiments, the extragranular mixture of the tablet comprises about 0.5% w / w colloidal silicon dioxide.

[0576] In some embodiments, the extragranular mixture of the tablet comprises about 0.9 mg colloidal silicon dioxide. In some embodiments, the extragranular mixture of the tablet comprises about 3.5 mg colloidal silicon dioxide.Lubricants

[0577] In some embodiments, the tablet comprises about 1.0% w / w of the lubricant.

[0578] In some embodiments, the tablet comprises about 1.8 mg of the lubricant. In some embodiments, the tablet comprises about 7.0 mg of the lubricant.

[0579] In some embodiments, the intragranular mixture of the tablet comprises about 0.5% w / w of the lubricant.

[0580] In some embodiments, the extragranular mixture of the tablet comprises about 0.5% w / w of the lubricant.

[0581] In some embodiments, the intragranular mixture of the tablet comprises about 0.9 mg of the lubricant. In some embodiments, the intragranular mixture of the tablet comprises about3.5 mg of the lubricant.

[0582] In some embodiments, the extragranular mixture of the tablet comprises about 0.9 mg of the lubricant. In some embodiments, the extragranular mixture of the tablet comprises about3.5 mg of the lubricant.

[0583] In some embodiments, the tablet comprises about 1.0% w / w magnesium stearate.

[0584] In some embodiments, the tablet comprises about 1.8 mg magnesium stearate. In some embodiments, the tablet comprises about 7.0 mg magnesium stearate.

[0585] In some embodiments, the intragranular mixture of the tablet comprises about 0.5% w / w magnesium stearate.

[0586] In some embodiments, the extragranular mixture of the tablet comprises about 0.5% w / w magnesium stearate.294245842 62Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0587] In some embodiments, the intragranular mixture of the tablet comprises about 0.9 mg magnesium stearate. In some embodiments, the intragranular mixture of the tablet comprises about 3.5 mg magnesium stearate.

[0588] In some embodiments, the extragranular mixture of the tablet comprises about 0.9 mg magnesium stearate. In some embodiments, the extragranular mixture of the tablet comprises about 3.5 mg magnesium stearate.Processes of Preparing Formulations

[0589] In some aspects, the present disclosure provides a method for preparing a formulation disclosed herein. In some aspects, the present disclosure provides a method for preparing a tablet disclosed herein. In some aspects, the present disclosure provides a method for preparing a capsule disclosed herein.

[0590] In some embodiments, the method comprises:(i) sieving and blending a diluent;(ii) co-sieving the mixture of Step (i) with Compound No. 1 and blending the resulting mixture;(iii) co-sieving a filler, a disintegrant, and a glidant into the mixture of Step (ii), and blending the resulting mixture;(iv) sieving and blending the mixture of Step (iii); and(v) sieving a lubricant into the mixture of Step (iv) to yield a bulk formulation.

[0591] In some embodiments, the method comprises:(i) sieving and blending a filler;(ii) co-sieving the mixture of Step (i) with Compound No. 1 and a glidant and blending the resulting mixture;(iii) sieving and blending the mixture of Step (ii);(iv) sieving a lubricant into the mixture of Step (iii);(v) dry granulating the mixture of Step (iv); and(vi) sieving a lubricant into the mixture of Step (v) to yield a bulk formulation.

[0592] In some embodiments, the method comprises:(i) sieving and blending a filler;(ii) sieving a disintegrant into the mixture of Step (i);(iii) co-sieving Compound No. 1 and a filler into the mixture of Step (ii) and blending the resulting mixture;(iv) sieving a lubricant into the mixture of Step (iii) and blending the resulting mixture;294245842 63Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(v) dry granulating the mixture of Step (iv);(vi) sieving a filler and a glidant into the mixture of Step (v) and blending the resulting mixture; and(vii) sieving a lubricant into the mixture of Step (vi) to yield a bulk formulation.

[0593] In some embodiments, the method comprises a dry granulation step.

[0594] In some embodiments, Compound No. 1 is added as a solid dispersion. In some embodiments, the solid dispersion comprises Compound No. 1 and HPMC ASMG.

[0595] In some embodiments, the solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 : 1 w / w, about a 1 :2 w / w, about a 1 :3 w / w, about a 1 :4 w / w, or about a 1 :5 w / w ratio of Compound No. 1 to HPMC ASMG.

[0596] In some embodiments, the solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 : 1 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :2 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :3 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :4 w / w ratio of Compound No. 1 to HPMC ASMG. In some embodiments, the solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :5 w / w ratio of Compound No. 1 to HPMC ASMG.

[0597] In some embodiments, the filler is microcrystalline cellulose. In some embodiments, the filler is silicified microcrystalline cellulose. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the glidant is colloidal silicon dioxide. In some embodiments, the lubricant is magnesium stearate. In some embodiments, the diluent is pregelatinized maize starch.

[0598] In some embodiments, the bulk formulation is the common blend. In some embodiments, the bulk formulation is prepared as described in FIG. 2A.

[0599] In some embodiments, the bulk formulation is encapsulated to provide a capsule.

[0600] In some embodiments, the bulk formulation is compressed to provide a tablet. In some embodiments, the bulk formulation is compressed and coated to provide a tablet.

[0601] In some embodiments, the coating of the tablet results in about 3% w / w to about 5% w / w coating weight gain. In some embodiments, the coating of the tablet results in about 4% w / w coating weight gain.

[0602] In some embodiments, the formulation comprises about 80 mg to about 100 mg of the bulk formulation. In some embodiments, the formulation comprises about 300 mg to about 350294245842 64Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) mg of the bulk formulation. In some embodiments, the formulation comprises about 150 mg to about 200 mg of the bulk formulation. In some embodiments, the formulation comprises about 650 mg to about 750 of the bulk formulation.

[0603] In some embodiments, the formulation comprises about 90 mg of the bulk formulation. In some embodiments, the formulation comprises about 320 mg of the bulk formulation. In some embodiments, the formulation comprises about 175 mg of the bulk formulation. In some embodiments, the formulation comprises about 700 mg of the bulk formulation.

[0604] In some embodiments, the capsule comprises about 90 mg of the bulk formulation. In some embodiments, the capsule comprises about 320 mg of the bulk formulation. In some embodiments, the 3 mg capsule comprises about 90 mg of the bulk formulation. In some embodiments, the 25 mg capsule comprises about 320 mg of the bulk formulation.

[0605] In some embodiments, the tablet comprises about 175 mg of the bulk formulation. In some embodiments, the tablet comprises about 700 mg of the bulk formulation. In some embodiments, the 50 mg tablet comprises about 175 mg of the bulk formulation. In some embodiments, the 200 mg tablet comprises about 700 mg of the bulk formulation.

[0606] In some embodiments, the bulk formulation has a particle size of about 50 pm to about 1000 pm.

[0607] In some embodiments, the bulk formulation has a blend uniformity of about 95%, about 96%, about 97%, about 98%, about 99%, about 100%, about 101%, about 102%, about 103%, about 104%, or about 105%.

[0608] In some embodiments, the formulation described herein is prepared in bulk.

[0609]

[0610] In some embodiments, the method comprises: (i) preparing a mixture of a solid dispersion comprising Compound No. 1, a filler (e.g., microcrystalline cellulose or silicified microcrystalline cellulose), a diluent (e.g., pregelatinized maize starch), a disintegrant (e.g., croscarmellose sodium), and a glidant (e.g., colloidal silicon dioxide).

[0611] In some embodiments, the method further comprises sieving and / or blending the mixture.

[0612] In some embodiments, the method further comprises: (ii) adding a lubricant (e.g., magnesium stearate) to the mixture.

[0613] In some embodiments, the method further comprises: (iii) encapsulating and / or packing the mixture, thereby forming the capsule.

[0614] In some embodiments, the method comprises one or more steps as described in FIGs. 1A and IB.294245842 65Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0615] In some embodiments, the method comprises: (i) preparing an intragranular mixture comprising a solid dispersion comprising Compound No. 1, a filler (e.g., silicified microcrystalline cellulose), a disintegrant (e.g., croscarmellose sodium), and a glidant (e.g., colloidal silicon dioxide).

[0616] In some embodiments, the method further comprises: (ii) adding a lubricant (e.g., magnesium stearate) to the intragranular mixture.

[0617] In some embodiments, the method further comprises: (iii) adding an extragranular disintegrant (e.g., silicified microcrystalline cellulose), and an extragranular glidant (e.g., colloidal silicon dioxide) to the mixture.

[0618] In some embodiments, the method further comprises: (iv) adding an extragranular lubricant (e.g., magnesium stearate) to the mixture, thereby forming the tablet.

[0619] In some embodiments, the method comprises one or more steps as described in FIGs. 2A-2C.

[0620] The formulations containing compounds of the present disclosure may be manufactured in a manner that is generally known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping, or lyophilizing processes. Pharmaceutical compositions may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers comprising excipients and / or auxiliaries that facilitate processing of the active compounds into preparations that can be used pharmaceutically. In some embodiments, pharmaceutical compositions may be formulated by a method comprising evaporation or by spray drying.Methods of Use

[0621] In some aspects, the present disclosure provides a method of treating or preventing cancer in a subject, the method comprising administering to the subject a formulation disclosed herein.

[0622] In some aspects, the present disclosure provides a method of treating cancer in a subject, the method comprising administering to the subject a formulation disclosed herein.

[0623] In some aspects, the present disclosure provides a formulation disclosed herein for treating or preventing cancer in a subject.

[0624] In some aspects, the present disclosure provides a formulation disclosed herein for the treatment of cancer in a subject.

[0625] In some aspects, the present disclosure provides a formulation disclosed herein for use in the treatment or prevention of cancer in a subject.294245842 66Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0626] In some aspects, the present disclosure provides a formulation disclosed herein for use in the treatment of cancer in a subject.

[0627] In some aspects, the present disclosure provides use of a formulation disclosed herein in the manufacture of a medicament for the treatment or prevention of cancer in a subject.

[0628] In some aspects, the present disclosure provides use of a formulation disclosed herein in the manufacture of a medicament for the treatment of cancer in a subject.

[0629] In some aspects, the present disclosure provides use of a formulation disclosed herein for the treatment or prevention of cancer in a subject.

[0630] In some aspects, the present disclosure provides use of a formulation disclosed herein for the treatment of cancer in a subject.

[0631] In some aspects, the present disclosure provides a method of treating cancer in a subject, the method comprising administering to the subject a 3 mg capsule disclosed herein.

[0632] In some aspects, the present disclosure provides a 3 mg capsule disclosed herein for the treatment of cancer in a subject.

[0633] In some aspects, the present disclosure provides a 3 mg capsule disclosed herein for use in the treatment of cancer in a subject.

[0634] In some aspects, the present disclosure provides use of a 3 mg capsule disclosed herein in the manufacture of a medicament for the treatment of cancer in a subject.

[0635] In some aspects, the present disclosure provides use of a 3 mg capsule disclosed herein for the treatment of cancer in a subject.

[0636] In some aspects, the present disclosure provides a method of treating cancer in a subject, the method comprising administering to the subject a 25 mg capsule disclosed herein.

[0637] In some aspects, the present disclosure provides a 25 mg capsule disclosed herein for the treatment of cancer in a subject.

[0638] In some aspects, the present disclosure provides a 25 mg capsule disclosed herein for use in the treatment of cancer in a subject.

[0639] In some aspects, the present disclosure provides use of a 25 mg capsule disclosed herein in the manufacture of a medicament for the treatment of cancer in a subject.

[0640] In some aspects, the present disclosure provides use of a 25 mg capsule disclosed herein for the treatment of cancer in a subject.

[0641] In some aspects, the present disclosure provides a method of treating cancer in a subject, the method comprising administering to the subject a 50 mg tablet disclosed herein.

[0642] In some aspects, the present disclosure provides a 50 mg tablet disclosed herein for the treatment of cancer in a subject.294245842 67Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0643] In some aspects, the present disclosure provides a 50 mg tablet disclosed herein for use in the treatment of cancer in a subject.

[0644] In some aspects, the present disclosure provides use of a 50 mg tablet disclosed herein in the manufacture of a medicament for the treatment of cancer in a subject.

[0645] In some aspects, the present disclosure provides use of a 50 mg tablet disclosed herein for the treatment of cancer in a subject.

[0646] In some aspects, the present disclosure provides a method of treating cancer in a subject, the method comprising administering to the subject a 200 mg tablet disclosed herein.

[0647] In some aspects, the present disclosure provides a 200 mg tablet disclosed herein for the treatment of cancer in a subject.

[0648] In some aspects, the present disclosure provides a 200 mg tablet disclosed herein for use in the treatment of cancer in a subject.

[0649] In some aspects, the present disclosure provides use of a 200 mg tablet disclosed herein in the manufacture of a medicament for the treatment of cancer in a subject.

[0650] In some aspects, the present disclosure provides use of a 200 mg tablet disclosed herein for the treatment of cancer in a subject.

[0651] In some embodiments, the subject is administered the formulation daily.

[0652] In some embodiments, the subject is administered the formulation once or twice daily.

[0653] In some embodiments, the subject is administered the formulation once daily.

[0654] In some embodiments, the subject is administered the formulation twice daily.

[0655] In some embodiments, the formulation described herein is administered orally.

[0656] In some embodiments, the formulation described herein is administered orally daily.

[0657] In some embodiments, the formulation described herein is administered orally once daily.

[0658] In some embodiments, the formulation described herein is administered orally twice daily.

[0659] In some embodiments, the present disclosure provides a method of treating or preventing acute myeloid leukemia, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer in a subject, comprising administering to the subject a formulation of the present disclosure.

[0660] In some embodiments, the present disclosure provides a method of treating or preventing acute myeloid leukemia in a subject, comprising administering to the subject a formulation of the present disclosure.294245842 68Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0661] In some embodiments, the present disclosure provides a method of treating or preventing non-small cell lung cancer (NSCLC) in a subject, comprising administering to the subject a formulation of the present disclosure.

[0662] In some embodiments, the present disclosure provides a method of treating or preventing colorectal cancer in a subject, comprising administering to the subject a formulation of the present disclosure.

[0663] In some embodiments, the present disclosure provides a method of treating or preventing pancreatic cancer in a subject, comprising administering to the subject a formulation of the present disclosure.

[0664] In some embodiments, the present disclosure provides a method of treating acute myeloid leukemia, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer in a subject, comprising administering to the subject a formulation of the present disclosure.

[0665] In some embodiments, the present disclosure provides a method of treating acute myeloid leukemia in a subject, comprising administering to the subject a formulation of the present disclosure.

[0666] In some embodiments, the present disclosure provides a method of treating non-small cell lung cancer (NSCLC) in a subject, comprising administering to the subject a formulation of the present disclosure.

[0667] In some embodiments, the present disclosure provides a method of treating colorectal cancer in a subject, comprising administering to the subject a formulation of the present disclosure.

[0668] In some embodiments, the present disclosure provides a method of treating pancreatic cancer in a subject, comprising administering to the subject a formulation of the present disclosure.

[0669] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating or preventing acute myeloid leukemia, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer in a subject.

[0670] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating or preventing acute myeloid leukemia in a subject.

[0671] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating or preventing non-small cell lung cancer (NSCLC) in a subject.

[0672] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating or preventing colorectal cancer in a subject.294245842 69Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0673] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating or preventing pancreatic cancer in a subject.

[0674] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating acute myeloid leukemia, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer in a subject.

[0675] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating acute myeloid leukemia in a subject.

[0676] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating non-small cell lung cancer (NSCLC) in a subject.

[0677] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating colorectal cancer in a subject.

[0678] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in treating pancreatic cancer in a subject.

[0679] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating or preventing acute myeloid leukemia, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer in a subject.

[0680] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating or preventing acute myeloid leukemia in a subject.

[0681] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating or preventing non-small cell lung cancer (NSCLC) in a subject.

[0682] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating or preventing colorectal cancer in a subject.

[0683] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating or preventing pancreatic cancer in a subject.

[0684] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating acute myeloid leukemia, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer in a subject.294245842 7QAttorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0685] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating acute myeloid leukemia in a subject.

[0686] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating non-small cell lung cancer (NSCLC) in a subject.

[0687] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating colorectal cancer in a subj ect.

[0688] In some embodiments, the present disclosure provides the formulation of the present disclosure for use in the manufacture of a medicament for treating pancreatic cancer in a subject.Suitable Subjects and Diseases

[0689] In some embodiments, the subject is a mammal.

[0690] In some embodiments, the subject is a human.

[0691] In some embodiments, the subject is a mouse.

[0692] In some embodiments, the subject is a rat.

[0693] In some embodiments, the subject is a dog.

[0694] In some embodiments, the subject is a monkey.

[0695] In some embodiments, the cancer is characterized by at least one oncogenic mutation in the BRAF gene.

[0696] It may be understood that a cancer that is characterized by at least one oncogenic mutation in the BRAF gene includes, but is not limited to, cancers whose primary oncogenic activity is thought to be driven by the at least one oncogenic mutation in the BRAF gene.

[0697] In some embodiments, the cancer is characterized by at least one oncogenic variant of B-Raf.

[0698] It may be understood that a cancer that is characterized by least one oncogenic variant of B-Raf includes, but is not limited to, cancers whose primary oncogenic activity is thought to be driven by the at least one oncogenic variant of B-Raf.

[0699] It is understood that an oncogenic variant of B-Raf is a B-Raf protein that comprises at least one oncogenic mutation and that is produced as the result of the expression of a BRAF gene that comprises at least one oncogenic mutation.

[0700] In some embodiments, the subject has at least one oncogenic mutation in the BRAF gene.294245842 71Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0701] In some embodiments, the subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of B-Raf.

[0702] As would be appreciated by the skilled artisan, in the context of a gene (e.g. BRAF), an oncogenic mutation can include, but is not limited to a mutation that results in the substitution of one amino acid for another at a specific position within B-Raf, a mutation that results in the substitution of one or more amino acids for one or more amino acids between two specific positions within B-Raf, a mutation that results in an insertion of one or more amino acids between two positions within B-Raf, a mutation that results in the deletion of one more amino acids between two positions within B-Raf, and mutation that results in a fusion of B- Raf, or portion thereof, with another protein, or portion thereof, or any combination thereof. As would be appreciated by the skilled artisan, in the context of a gene, an oncogenic mutation can include, but is not limited to, a missense mutation, a nonsynonymous mutation, an insertion of one or more nucleotides, a deletion of one or more nucleotides, an inversion and a deletioninsertion. As would be appreciated by the skilled artisan, in the context of a gene (e.g. BRAF), the gene can have one or more of the aforementioned types of oncogenic mutations, including combinations of different types of oncogenic mutations.

[0703] As would be appreciated by the skilled artisan, in the context of a protein (e.g. B-Raf), an oncogenic mutation can include, but is not limited to, the substitution of one amino acid for another at a specific position within B-Raf, the substitution of one or more amino acids for one or more amino acids between two specific positions within B-Raf, an insertion of one or more amino acids between two positions within B-Raf, a deletion of one more amino acids between two positions within B-Raf, and a fusion of B-Raf, or portion thereof, with another protein, or portion thereof, or any combination thereof. As would be appreciated by the skilled artisan, in the context of a protein (e.g. B-Raf), the protein can have one or more of the aforementioned types of oncogenic mutations, including combinations of different types of oncogenic mutations.

[0704] In some embodiments, the cancer is characterized by at least one oncogenic mutation in the CRAF gene.

[0705] It may be understood that a cancer that is characterized by at least one oncogenic mutation in the CRAF gene includes, but is not limited to, cancers whose primary oncogenic activity is thought to be driven by the at least one oncogenic mutation in the CRAF gene.

[0706] In some embodiments, the cancer is characterized by at least one oncogenic variant of C-Raf.294245842 72Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0707] It may be understood that a cancer that is characterized by least one oncogenic variant of C-Raf includes, but is not limited to, cancers whose primary oncogenic activity is thought to be driven by the at least one oncogenic variant of C-Raf.

[0708] It is understood that an oncogenic variant of C-Raf is a C-Raf protein that comprises at least one oncogenic mutation and that is produced as the result of the expression of a CRAF gene that comprises at least one oncogenic mutation.

[0709] In some embodiments, the subject has at least one oncogenic mutation in the CRAF gene.

[0710] In some embodiments, the subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of C-Raf.

[0711] As would be appreciated by the skilled artisan, in the context of a gene (e.g. CRAF), an oncogenic mutation can include, but is not limited to a mutation that results in the substitution of one amino acid for another at a specific position within C-Raf, a mutation that results in the substitution of one or more amino acids for one or more amino acids between two specific positions within C-Raf, a mutation that results in an insertion of one or more amino acids between two positions within C-Raf, a mutation that results in the deletion of one more amino acids between two positions within C-Raf, and mutation that results in a fusion of C- Raf, or portion thereof, with another protein, or portion thereof, or any combination thereof. As would be appreciated by the skilled artisan, in the context of a gene, an oncogenic mutation can include, but is not limited to, a missense mutation, a nonsynonymous mutation, an insertion of one or more nucleotides, a deletion of one or more nucleotides, an inversion and a deletioninsertion. As would be appreciated by the skilled artisan, in the context of a gene (e.g. CRAF), the gene can have one or more of the aforementioned types of oncogenic mutations, including combinations of different types of oncogenic mutations.As would be appreciated by the skilled artisan, in the context of a protein (e.g. C-Raf), an oncogenic mutation can include, but is not limited to, the substitution of one amino acid for another at a specific position within C-Raf, the substitution of one or more amino acids for one or more amino acids between two specific positions within C-Raf, an insertion of one or more amino acids between two positions within C-Raf, a deletion of one more amino acids between two positions within C-Raf, and a fusion of C-Raf, or portion thereof, with another protein, or portion thereof, or any combination thereof. As would be appreciated by the skilled artisan, in the context of a protein (e.g. C-Raf), the protein can have one or more of the aforementioned types of oncogenic mutations, including combinations of different types of oncogenic mutations.294245842 73Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0712] In some embodiments, the oncogenic mutation is a class I mutation. Accordingly, in some embodiments, the oncogenic variant of B-Raf comprises a class I mutation. Accordingly, in some embodiments, the oncogenic variant of C-Raf comprises a class I mutation.

[0713] In some embodiments, the oncogenic mutation is a class II mutation. Accordingly, in some embodiments, the oncogenic variant of B-Raf comprises a class II mutation. Accordingly, in some embodiments, the oncogenic variant of C-Raf comprises a class II mutation.

[0714] In some embodiments, the oncogenic mutation is a class III mutation. Accordingly, in some embodiments, the oncogenic variant of B-Raf comprises a class III mutation. Accordingly, in some embodiments, the oncogenic variant of C-Raf comprises a class III mutation.

[0715] In some embodiments, a subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of B-Raf and at least one additional protein in the RAF and / or MAPK / ERK signaling pathways that comprises at least one mutation. In some embodiments, the at least one additional protein can be selected from N-Ras, K-Ras, Neurofibromin 1 (NF1). In some embodiments, the at least one mutation in the at least one additional protein can be an oncogenic mutation.

[0716] In some embodiments, a subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of C-Raf and at least one additional protein in the RAF and / or MAPK / ERK signaling pathways that comprises at least one mutation. In some embodiments, the at least one additional protein can be selected from N-Ras, K-Ras, Neurofibromin 1 (NF1). In some embodiments, the at least one mutation in the at least one additional protein can be an oncogenic mutation.

[0717] In some embodiments, the cancer is characterized by at least one oncogenic mutation in at least one protein in the RAF and / or MAPK / ERK signaling pathways. In some embodiments, the at least one protein in the RAF and / or MAPK / ERK signaling pathways can be selected from N-Ras, K-Ras, and NF 1.

[0718] In some embodiments, the cancer is characterized by at least one oncogenic mutation in the KRAS gene.

[0719] In some embodiments, the cancer is characterized by at least one oncogenic variant of K-Ras.

[0720] In some embodiments, the subject has at least one oncogenic mutation in the KRAS gene.

[0721] In some embodiments, the oncogenic mutation in the KRAS gene is not KRAS G12C.294245842 74Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0722] In some embodiments, the subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of K-Ras.

[0723] In some embodiments, the cancer is characterized by at least one oncogenic mutation in the NRAS gene.

[0724] In some embodiments, the cancer is characterized by at least one oncogenic variant of N-Ras.

[0725] In some embodiments, the subject has at least one oncogenic mutation in the NRAS gene.

[0726] In some embodiments, the subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of N-Ras.

[0727] In some embodiments, the cancer is characterized by at least one oncogenic variant of NF1.

[0728] In some embodiments, the subject has at least one oncogenic mutation in the NF 1 gene.

[0729] In some embodiments, the cancer is characterized by at least one oncogenic mutation in a gene encoding a RAS GTPase.

[0730] In some embodiments, the cancer is characterized by at least one oncogenic variant of a RAS GTPase.

[0731] In some embodiments, the subject has at least one oncogenic mutation in a gene encoding a RAS GTPase.

[0732] In some embodiments, the subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of a RAS GTPase.

[0733] In some embodiments, the cancer is characterized by at least one oncogenic mutation in the HRAS gene.

[0734] In some embodiments, the cancer is characterized by at least one oncogenic variant of H-Ras.

[0735] In some embodiments, the subject has at least one oncogenic mutation in the HRAS gene.

[0736] In some embodiments, the subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of H-Ras.

[0737] In some embodiments, the cancer is characterized by at least one oncogenic mutation in the NRAS gene.

[0738] In some embodiments, the cancer is characterized by at least one oncogenic variant of N-Ras.294245842 75Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0739] In some embodiments, the subject has at least one oncogenic mutation in the NRAS gene.

[0740] In some embodiments, the subject has at least one tumor and / or cancerous cell that expresses an oncogenic variant of N-Ras.

[0741] In some embodiments, the cancer is a carcinoma, a lymphoma, a blastoma, a sarcoma, a leukemia, a brain cancer, a breast cancer, a blood cancer, a bone cancer, a lung cancer, a skin cancer, a liver cancer, an ovarian cancer, a bladder cancer, a renal cancer, a kidney cancer, a gastric cancer, a thyroid cancer, a pancreatic cancer, an esophageal cancer, a prostate cancer, a cervical cancer, a uterine cancer, a stomach cancer, a soft tissue cancer, a laryngeal cancer, a small intestine cancer, a testicular cancer, an anal cancer, a vulvar cancer, a joint cancer, an oral cancer, a pharynx cancer or a colorectal cancer.

[0742] In some embodiments, the cancer is adrenocortical carcinoma, bladder urothelial carcinoma, breast invasive carcinoma, cervical squamous cell carcinoma, endocervical adenocarcinoma, cholangiocarcinoma, colon adenocarcinoma, lymphoid neoplasm diffuse large B-cell lymphoma, esophageal carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, acute myeloid leukemia, brain lower grade glioma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, mesothelioma, ovarian serous cystadenocarcinoma, pancreatic adenocarcinoma, pheochromocytoma, paraganglioma, prostate adenocarcinoma, rectum adenocarcinoma, sarcoma, skin cutaneous melanoma, stomach adenocarcinoma, testicular germ cell tumors, thyroid carcinoma, thymoma, uterine carcinosarcoma, uveal melanoma. Other examples include breast cancer, lung cancer, lymphoma, melanoma, liver cancer, colorectal cancer, ovarian cancer, bladder cancer, renal cancer or gastric cancer. Further examples of cancer include neuroendocrine cancer, non-small cell lung cancer (NSCLC), small cell lung cancer, thyroid cancer, endometrial cancer, biliary cancer, esophageal cancer, anal cancer, salivary, cancer, vulvar cancer, cervical cancer, Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), Adrenal gland tumors, Anal cancer, Bile duct cancer, Bladder cancer, Bone cancer, Bowel cancer, Brain tumors, Breast cancer, cancer of unknown primary (CUP), cancer spread to bone, cancer spread to brain, cancer spread to liver, cancer spread to lung, carcinoid, cervical cancer, children's cancers, chronic lymphocytic leukemia (CLL), chrome myeloid leukemia (CML), colorectal cancer, ear cancer, endometrial cancer, eye cancer, Follicular dendritic cell sarcoma, gallbladder cancer, gastric cancer, gastro esophageal junction cancers, germ cell tumors, gestational trophoblastic disease (GIT)), hairy cell leukemia, head and neck294245842 76Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) cancer, Hodgkin lymphoma, Kaposi’s sarcoma, kidney cancer, laryngeal cancer, leukemia, gastric linitis plastica, liver cancer, lung cancer, lymphoma, malignant schwannoma, mediastinal germ cell tumors, melanoma skin cancer, men's cancer, merkel cell skin cancer, mesothelioma, molar pregnancy, mouth and oropharyngeal cancer, myeloma, nasal and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, neuroendocrine tumors, nonHodgkin lymphoma (NHL), esophageal cancer, ovarian cancer, pancreatic cancer, penile cancer, persistent trophoblastic disease and choriocarcinoma, pheochromocytoma, prostate cancer, pseudomyxoma peritonei, rectal cancer, retinoblastoma, salivary gland cancer, secondary' cancer, signet cell cancer, skin cancer, small bowel cancer, soft tissue sarcoma, stomach cancer, T cell childhood non Hodgkin lymphoma (NHL), testicular cancer, thymus gland cancer, thyroid cancer, tongue cancer, tonsil cancer, tumors of the adrenal gland, uterine cancer, vaginal cancer, vulval cancer, Wilms’ tumor, womb cancer and gynecological cancer.

[0743] Examples of cancer also include, but are not limited to, hematologic malignancies, lymphoma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, multiple myeloma, chrome lymphocytic leukemia, chronic myeloid leukemia, acute myeloid leukemia, myelodysplastic syndromes, myelofibrosis, biliary tract cancer, hepatocellular cancer, colorectal cancer, breast cancer, lung cancer, non-small cell lung cancer, ovarian cancer, thyroid carcinoma, renal cell carcinoma, pancreatic cancer, bladder cancer, skin cancer, malignant melanoma, merkel cell carcinoma, uveal melanoma or glioblastoma multiforme.

[0744] In some embodiments, the cancer is a hematological cancer.

[0745] In some embodiments, the cancer is acute myeloid leukemia.

[0746] In some embodiments, the cancer is a solid cancer (also referred to as a solid malignancy or a solid tumor).

[0747] In some embodiments, the cancer is melanoma, breast cancer, head and neck cancer, esophagogastric cancer, stomach and small intestine cancer, lung cancer, mesothelioma, hepatobiliary cancer, pancreatic cancer, kidney cancer, colorectal cancer, endometrial cancer, cervical cancer, ovarian cancer, bladder cancer, prostate cancer, soft tissue sarcoma, CNS and brain cancer, or thyroid cancer.

[0748] In some embodiments, the cancer is non-small cell lung cancer (NSCLC), colorectal cancer, melanoma, thyroid cancer, histiocytosis, small bowel cancer, gastrointestinal neuroendocrine cancer, carcinoma of unknown primary, non-melanoma skin cancer, prostate cancer, gastric cancer, non-Hodgkin's lymphoma, papillary thyroid carcinoma or glioblastoma.294245842 77Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0749] In some embodiments, the cancer is acute myeloid leukemia, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer.

[0750] In some embodiments, the cancer is non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic cancer.

[0751] In some embodiments, the cancer is NSCLC. In some embodiments, the NSCLC has not undergone small cell lung cancer transformation. In some embodiments, the cancer is lung non-small cell carcinoma. In some embodiments, the cancer is non-small cell carcinoma of the lung. In some embodiments, the cancer is adenocarcinoma of the lung.

[0752] In some embodiments, the cancer is a histiocytic neoplasm. In some embodiments, the histiocytic neoplasm is Langerhans cell histiocytosis (LCH). In some embodiments, the histiocytic neoplasm is Erdheim Chester disease (ECD). In some embodiments, the cancer is a histiocytic and dendritic cell neoplasm.

[0753] In some embodiments, the cancer is a histiocytic neoplasm characterized by at least one oncogenic mutation in the BRAF or NBAS genes. In some embodiments, the cancer is a histiocytic neoplasm characterized by at least one oncogenic mutation in the BRAF gene. In some embodiments, the cancer is a histiocytic neoplasm characterized by at least one oncogenic mutation in the NRAS gene.

[0754] In some embodiments, the cancer is melanoma.

[0755] In some embodiments, the cancer is melanoma characterized by at least one oncogenic mutation in the BRAF, CRAF, or NRAS genes. In some embodiments, the cancer is melanoma characterized by at least one oncogenic mutation in the BRAF gene. In some embodiments, the cancer is melanoma characterized by at least one oncogenic mutation in the CRAF gene. In some embodiments, the cancer is melanoma characterized by at least one oncogenic mutation in the NRAS gene.

[0756] In some embodiments, the cancer is thyroid cancer.

[0757] In some embodiments, the cancer is thyroid carcinoma.

[0758] In some embodiments, the cancer is thyroid carcinoma characterized by at least one oncogenic mutation in the BRAF gene.

[0759] In some embodiments, the cancer is colorectal cancer.

[0760] In some embodiments, the cancer is colorectal carcinoma.

[0761] In some embodiments, the cancer is colorectal carcinoma characterized by at least one oncogenic mutation in the BRAF gene. In some embodiments, the oncogenic mutation in the BRAF gene is a class II or class III mutation. In some embodiments, the oncogenic mutation294245842 78Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) in the BRAF gene is a class II mutation. In some embodiments, the oncogenic mutation in the BRAF gene is a class III mutation.

[0762] In some embodiments, the cancer is pancreatic cancer.

[0763] In some embodiments, the cancer is pancreatic ductal adenocarcinoma.

[0764] In some embodiments, the cancer is pancreatic adenosquamous carcinoma.

[0765] In some embodiments, the cancer is pancreatic squamous cell carcinoma.

[0766] In some embodiments, the cancer is glioma.

[0767] In some embodiments, the cancer is astrocytoma, brain stem glioma, ependymoma, oligo-astrocytoma, oligodendroglioma, or optic pathway glioma.

[0768] In some embodiments, the cancer is low-grade glioma (e.g., glioma arising from astrocytes and / or oligodendrocytes).

[0769] In some embodiments, the cancer is glioma (e.g., low-grade glioma) in a subject having an age of 18 years or older.

[0770] In some embodiments, the cancer is glioma (e.g., low-grade glioma) in a subject having an age of younger than 18 years.

[0771] In some embodiments, the cancer is glioblastoma.

[0772] In some embodiments, the cancer is a recurrent cancer.

[0773] In some embodiments, the cancer is an advanced cancer.

[0774] In some embodiments, the cancer is a metastatic cancer.

[0775] In some embodiments, the tumor is a recurrent tumor.

[0776] In some embodiments, the tumor is an advanced tumor.

[0777] In some embodiments, the tumor is a metastatic tumor.

[0778] In some embodiments, the cancer is brain cancer.

[0779] In some embodiments, the cancer is recurrent brain cancer.

[0780] In some embodiments, the cancer is advanced brain cancer.

[0781] In some embodiments, the cancer is metastatic brain cancer.

[0782] In some embodiments, the cancer is lung cancer.

[0783] In some embodiments, the cancer is recurrent lung cancer.

[0784] In some embodiments, the cancer is advanced lung cancer.

[0785] In some embodiments, the cancer is metastatic lung cancer.

[0786] In some embodiments, the cancer is non-small cell lung cancer (NSCLC).

[0787] In some embodiments, the cancer is recurrent non-small cell lung cancer (NSCLC).

[0788] In some embodiments, the cancer is advanced non-small cell lung cancer (NSCLC).

[0789] In some embodiments, the cancer is metastatic non-small cell lung cancer (NSCLC).294245842 79Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0790] In some embodiments, the cancer is NSCLC characterized by at least one oncogenic mutation in the KRAS, BRAF, or CRAF genes. In some embodiments, the cancer is NSCLC characterized by at least one oncogenic mutation in the KRAS gene. In some embodiments, the cancer is NSCLC characterized by at least one oncogenic mutation in the BRAF gene. In some embodiments, the cancer is NSCLC characterized by at least one oncogenic mutation in the CRAF gene. In some embodiments, the oncogenic mutation in the KRAS gene is not KRAS G12C.

[0791] In some embodiments, the cancer is relap sed / refractory. In some embodiments, the cancer is relapsed. In some embodiments, the cancer is refractory.

[0792] In some embodiments, the subject has at least one central nervous system metastasis. In some embodiments, the at least one central nervous system metastasis is stable. As used herein, a “stable” tumor means that the tumor is neither growing nor shrinking.

[0793] In some embodiments, the subject has no central nervous system metastases.

[0794] In some embodiments, the subject has at least one brain metastasis. In some embodiments, the at least one brain metastasis is stable.

[0795] In some embodiments, the subject has no brain metastases.

[0796] In some embodiments, the subject has histiocytosis.

[0797] In some embodiments, the subject has previously been administered a therapy for treatment of cancer. In some embodiments, the previously administered therapy is a BRAF inhibitor or an MEK inhibitor. In some embodiments, the previously administered therapy is a BRAF inhibitor. In some embodiments, the previously administered therapy is an MEK inhibitor.

[0798] In some embodiments, the subject developed resistance to the previously administered therapy. In some embodiments, the previously administered therapy was not effective in treating the cancer.Definitions

[0799] Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below.

[0800] Without wishing to be limited by this statement, it is understood that, while various options for variables are described herein, the disclosure intends to encompass operable embodiments having combinations of the options. The disclosure may be interpreted as excluding the non-operable embodiments caused by certain combinations of the options.294245842 80Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0801] As disclosed herein, “% w / w” refers to the proportion of the mass of the agent e.g., Compound No. 1) per unit mass of the total weight of the formulation. When the formulation comprises a pharmaceutically acceptable salt of Compound No. 1, “% w / w” is calculated based on the mass of the free base / acid form of Compound No. 1 per unit mass of the total weight of the formulation. In some embodiments, “% w / w” refers to the proportion of the mass of the agent per unit mass of the total weight of the bulk formulation.

[0802] Unless explicitly indicated otherwise, the terms “approximately” and “about” are synonymous. In some embodiments, “approximately” and “about” refer to the recited amount, value, dose, or duration ± 20%, ± 15%, ± 10%, ± 8%, ± 6%, ± 5%, ± 4%, ± 2%, ± 1%, or ± 0.5%. In some embodiments, “approximately” and “about” refer to the listed amount or duration ± 10%, ± 8%, ± 6%, ± 5%, ± 4%, or ± 2%. In some embodiments, “approximately” and “about” refer to the listed amount, value, dose, or duration ± 5%. In some embodiments, “approximately” and “about” refer to the listed amount, value, dose, or duration ± 2%. In some embodiments, “approximately” and “about” refer to the listed amount, value, dose, or duration ± 1%.

[0803] It is to be understood that the compounds of the present disclosure include the compounds themselves, as well as their salts, if applicable. A salt, for example, can be formed between an anion and a positively charged group (e.g., amino) on a substituted benzene compound. Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate (e.g., trifluoroacetate).

[0804] It is to be understood that the compound of the present disclosure can be prepared in a variety of ways using commercially available starting materials, compounds known in the literature, or from readily prepared intermediates, by employing standard synthetic methods and procedures either known to those skilled in the art, or which will be apparent to the skilled artisan in light of the teachings herein. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be obtained from the relevant scientific literature or from standard textbooks in the field. Although not limited to any one or several sources, classic texts such as Smith, M. B., March, J., March ’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5thedition, John Wiley & Sons: New York, 2001; Greene, T.W., Wuts, P.G. M., Protective Groups in Organic Synthesis, 3rdedition, John Wiley & Sons: New York, 1999; R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); L. Fieser and M. Fieser,294245842 81Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)Fieser and Fieser ’s Reagents for Organic Synthesis, John Wiley and Sons (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995), incorporated by reference herein, are useful and recognized reference textbooks of organic synthesis known to those in the art.

[0805] It is to be understood that one skilled in the art may refer to general reference texts for detailed descriptions of known techniques discussed herein or equivalent techniques. These texts include Ausubel et al., Current Protocols in Molecular Biology, John Wiley and Sons, Inc. (2005); Sambrook et al. , Molecular Cloning, A Laboratory Manual (3rdedition), Cold Spring Harbor Press, Cold Spring Harbor, New York (2000); Coligan et al., Current Protocols in Immunology, John Wiley & Sons, N.Y.; Enna et al., Current Protocols in Pharmacology, John Wiley & Sons, N.Y.; Fingl et al., The Pharmacological Basis of Therapeutics (1975), Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 18thedition (1990). These texts can, of course, also be referred to in making or using an aspect of the disclosure.

[0806] It is to be understood that, throughout the description, where compositions are described as having, including, or comprising specific components, it is contemplated those compositions also consist essentially of, or consist of, the recited components. Similarly, where methods or processes are described as having, including, or comprising specific process steps, the processes also consist essentially of, or consist of, the recited processing steps. Further, it should be understood that the order of steps or order for performing certain actions is immaterial so long as the invention remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

[0807] It is to be understood that the present disclosure provides methods for the preparation of the formulations described herein. The present disclosure also provides detailed methods for preparation of various formulations of the present disclosure according to the following Examples.

[0808] Techniques for formulation and administration of the formulations of the disclosure can be found in Remington: the Science and Practice of Pharmacy, 19thedition, Mack Publishing Co., Easton, PA (1995). In an embodiment, the compound described herein, and the pharmaceutically acceptable salts thereof, are used in pharmaceutical preparations in combination with a pharmaceutically acceptable carrier or diluent. Suitable pharmaceutically acceptable carriers include inert solid fillers or diluents and sterile aqueous or organic solutions. The compound will be present in such formulations in amounts sufficient to provide the desired dosage amount in the range described herein.294245842 82Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0809] It is to be understood that, unless otherwise stated, any description of a method of treatment includes use of the compound or formulation to provide such treatment as is described herein, as well as use of the compound or formulation to prepare a medicament to treat such condition. The treatment includes treatment of human or non-human animals including rodents and other disease models.

[0810] It is to be understood that, unless otherwise stated, any description of a method of prevention includes use of the compound or formulation to provide such prevention as is described herein, as well as use of the compounds to prepare a medicament to prevent such condition. The prevention includes prevention in human or non-human animals including rodents and other disease models.

[0811] As used herein, the term “subject” is interchangeable with the term “subject in need thereof,” both of which refer to a subject having a disease or having an increased risk of developing the disease. A “subject” includes a mammal. The mammal can be e.g., a human or appropriate non-human mammal, such as primate, mouse, rat, dog, cat, cow, horse, goat, camel, sheep or a pig. The subject can also be a bird or fowl. In one embodiment, the mammal is a human.

[0812] As used herein, the term “treating” or “treat” describes the management and care of a subject for the purpose of combating a disease, condition, or disorder and includes the administration of a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, or a formulation of the present disclosure, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model.

[0813] It is to be understood that a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, or a formulation of the present disclosure, can or may also be used to prevent a relevant disease, condition or disorder, or used to identify suitable candidates for such purposes.

[0814] As used herein, the term “preventing,” “prevent,” or “protecting against” describes reducing or eliminating the onset of the symptoms or complications of such disease, condition or disorder.

[0815] As used herein, the term “pharmaceutically acceptable” refers to those compounds, anions, cations, materials, compositions, carriers, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.294245842 83Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0816] It is to be understood that the pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0817] As used herein, the term “formulation” is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the exemplified ingredients in the exemplified amounts, in a form suitable for administration to a subject. In one embodiment, the formulation is in bulk. The formulation is any of a variety of forms, including, for example, a capsule, an IV bag, a tablet, a single pump on an aerosol inhaler or a vial. The quantity of active ingredient (e.g., a formulation of the disclosed compound or salt thereof) in a unit dose of composition is an effective amount and is varied according to the particular treatment involved. One skilled in the art will appreciate that it is sometimes necessary to make variations to the dosage depending on the age and condition of the patient. The dosage will also depend on the route of administration. A variety of routes are contemplated, including oral, pulmonary, rectal, parenteral, transdermal, subcutaneous, intravenous, intramuscular, intraperitoneal, inhalational, buccal, sublingual, intrapleural, intrathecal, intranasal, and the like. Dosage forms for the topical or transdermal administration of a formulation of this disclosure include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants.

[0818] As used herein, the term “capsule” refers to a formulation that is enclosed in an outer shell. In some embodiments, the outer shell is a capsule shell.

[0819] As used herein, the term “tablet” refers to a formulation that is compressed. In some embodiments, the tablet is prepared by compressing a bulk formulation.

[0820] As used herein, the term “pharmaceutically acceptable” refers to those compounds, anions, cations, materials, compositions, carriers, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0821] As used herein, the term “pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, nontoxic and neither biologically nor otherwise undesirable, and includes excipient that is acceptable for veterinary use as well as human pharmaceutical use. A “pharmaceutically acceptable excipient” as used in the specification and claims includes both one and more than one such excipient.294245842 84Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0822] It is to be understood that a pharmaceutical composition of the disclosure is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., ingestion), inhalation, transdermal (topical), and transmucosal administration.

[0823] It is to be understood that the present disclosure also provides formulations comprising Compound No. 1, or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable excipient, diluent, adjuvant, or carrier.

[0824] As used herein, the term “pharmaceutically acceptable salt” refers to a derivative of a compound of the present disclosure wherein the parent compound is modified by making acid or base salts thereof. In some embodiments, the pharmaceutically acceptable salt of a compound (e.g., a P-lactam compound or probenecid described herein) is also a prodrug of the compound. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids, and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 2-acetoxybenzoic, 2-hydroxyethane sulfonic, acetic, ascorbic, benzene sulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, 1,2-ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methane sulfonic, napsylic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic, propionic, salicylic, stearic, subacetic, succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, toluene sulfonic, and the commonly occurring amine acids, e.g., glycine, alanine, phenylalanine, arginine, etc.

[0825] Other examples of pharmaceutically acceptable salts include hexanoic acid, cyclopentane propionic acid, pyruvic acid, malonic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo-[2.2.2]-oct-2-ene-l -carboxylic acid, 3- phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, muconic acid, and the like. The present disclosure also encompasses salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine,294245842 85Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) diethanolamine, triethanolamine, tromethamine, N-methylglucamine, and the like. In the salt form, it is understood that the ratio of the compound to the cation or anion of the salt can be 1 : 1, or any ratio other than 1 : 1, e.g., 3: 1, 2: 1, 1 :2, or 1 :3.

[0826] It is to be understood that all references to compounds include crystal forms (polymorphs) as defined herein, of the same compound.

[0827] It is to be understood that all references to pharmaceutically acceptable salts include crystal forms (polymorphs) as defined herein, of the same salt.

[0828] All percentages and ratios used herein, unless otherwise indicated, are by weight. Other features and advantages of the present disclosure are apparent from the different examples. The provided examples illustrate different components and methodology useful in practicing the present disclosure. The examples do not limit the claimed disclosure. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present disclosure.

[0829] As used herein, the expressions “one or more of A, B, or C,” “one or more A, B, or C,” “one or more of A, B, and C,” “one or more A, B, and C,” “selected from the group consisting of A, B, and C”, “selected from A, B, and C”, and the like are used interchangeably and all refer to a selection from a group consisting of A, B, and / or C, i.e., one or more As, one or more Bs, one or more Cs, or any combination thereof, unless indicated otherwise.

[0830] As used herein, the phrase “compound of the disclosure” or “compound of the present disclosure” refers to Compound No. 1, or a pharmaceutically acceptable salt thereof.

[0831] All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an admission that any is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description and examples below are for purposes of illustration and not limitation of the claims that follow.EXEMPLARY EMBODIMENTS

[0832] Embodiment No. Al : A formulation comprising Compound No. 1 :294245842 86Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)(Compound No. 1) or a pharmaceutically acceptable salt thereof.

[0833] Embodiment No. A2: The formulation of Embodiment No. Al, wherein the formulation is a capsule.

[0834] Embodiment No. A3: The formulation of Embodiment No. Al or A2, comprising an intragranular mixture and an extragranular mixture.

[0835] Embodiment No. A4: The formulation of any one of the preceding Embodiments, further comprising a filler, a diluent, a disintegrant, a glidant, and a lubricant.

[0836] Embodiment No. A5:The formulation of any one of the preceding Embodiments, comprising: about 16.7% w / w of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 15.0 mg of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 3.0 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; about 39.1% w / w of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 125.0 mg of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; or about 25.0 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof.

[0837] Embodiment No. A6: The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 39.1% w / w of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 125.0 mg of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; or294245842 87Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) about 25.0 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof.

[0838] Embodiment No. A7:The formulation of any one of the preceding Embodiments, wherein the filler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, cellulose, or any combination thereof.

[0839] Embodiment No. A8: The formulation of any one of the preceding Embodiments, wherein the filler comprises microcrystalline cellulose or silicified microcrystalline cellulose.

[0840] Embodiment No. A9:The formulation of any one of the preceding Embodiments, comprising: about 39.2% w / w of microcrystalline cellulose; or about 35.3 mg of microcrystalline cellulose.

[0841] Embodiment No. A10: The formulation of any one of the preceding Embodiments, comprising: about 56.9% w / w of silicified microcrystalline cellulose; or about 182.2 mg of silicified microcrystalline cellulose;

[0842] Embodiment No. Al 1 : The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 56.9% w / w of silicified microcrystalline cellulose; or about 182.2 mg of silicified microcrystalline cellulose.

[0843] Embodiment No. A12: The formulation of any one of the preceding Embodiments, wherein the diluent comprises microcrystalline cellulose, lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, or any combination thereof.

[0844] Embodiment No. A13: The formulation of any one of the preceding Embodiments, wherein the diluent comprises partially pregelatinized maize starch.

[0845] Embodiment No. A14: The formulation of any one of the preceding Embodiments, comprising: about 39.2% w / w of partially pregelatinized maize starch; or about 35.3 mg of partially pregelatinized maize starch.

[0846] Embodiment No. Al 5: The formulation of any one of the preceding Embodiments, wherein the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch294245842 88Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) glycolate, chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

[0847] Embodiment No. A16: The formulation of any one of the preceding Embodiments, wherein the disintegrant comprises croscarmellose sodium.

[0848] Embodiment No. Al 7: The formulation of any one of the preceding Embodiments, comprising: about 3.0% w / w of croscarmellose sodium; about 2.7 mg of croscarmellose sodium; or about 9.6 mg of croscarmellose sodium.

[0849] Embodiment No. Al 8: The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 3.0% w / w of croscarmellose sodium; or about 9.6 mg of croscarmellose sodium.

[0850] Embodiment No. A19: The formulation of any one of the preceding Embodiments, wherein the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

[0851] Embodiment No. A20: The formulation of any one of the preceding Embodiments, wherein the glidant comprises colloidal silicon dioxide.

[0852] Embodiment No. A21 : The formulation of any one of the preceding Embodiments, comprising: about 1.0% w / w of colloidal silicon dioxide; or about 0.9 mg of colloidal silicon dioxide.

[0853] Embodiment No. A22: The formulation of any one of the preceding Embodiments, wherein the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

[0854] Embodiment No. A23 : The formulation of any one of the preceding Embodiments, wherein the lubricant comprises magnesium stearate.

[0855] Embodiment No. A24: The formulation of any one of the preceding Embodiments, comprising: about 1.0% w / w of magnesium stearate; about 0.9 mg of magnesium stearate; about 3.2 mg of magnesium stearate; or294245842 89Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) about 0.5% w / w of magnesium stearate.

[0856] Embodiment No. A25: The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 0.5% w / w of the lubricant (e.g., magnesium stearate); or about 1.6 mg of the lubricant (e.g., magnesium stearate).

[0857] Embodiment No. A26: The formulation of any one of the preceding Embodiments, wherein the extragranular mixture comprises: about 0.5% w / w of magnesium stearate; or about 1.6 mg of magnesium stearate.

[0858] Embodiment No. A27: The formulation of any one of the preceding Embodiments, comprising one or more of the ingredients described in Table A1-A4.

[0859] Embodiment No. A28: The formulation of any one of the preceding Embodiments, being selected from the formulations described in Table 1 A or IB.

[0860] Embodiment No. A29: The formulation of any one of the preceding Embodiments, wherein the formulation is a tablet.

[0861] Embodiment No. A30: The formulation of any one of the preceding Embodiments, comprising an intragranular mixture and an extragranular mixture.

[0862] Embodiment No. A31 : The formulation of any one of the preceding Embodiments, further comprising a filler, a disintegrant, a glidant, and a lubricant.

[0863] Embodiment No. A32: The formulation of any one of the preceding Embodiments, comprising: about 57.1% w / w of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 100.0 mg of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 400.0 mg of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 50.0 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; or about 200.0 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof.

[0864] Embodiment No. A33: The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 57.1% w / w of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof;294245842 90Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) about 100.0 mg of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 400.0 mg of a solid dispersion comprising Compound No. 1 or the pharmaceutically acceptable salt thereof; about 50.0 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof; or about 200.0 mg of Compound No. 1 or the pharmaceutically acceptable salt thereof.

[0865] Embodiment No. A34: The formulation of any one of the preceding Embodiments, wherein the filler comprises lactose, mannitol, starch, pregelatinized starch, sorbitol, sucrose, dextrin, calcium phosphate, calcium carbonate, maltose, maltodextrin, cellulose acetate, magnesium carbonate, magnesium oxide, talc, trehalose, cellulose, or any combination thereof.

[0866] Embodiment No. A35: The formulation of any one of the preceding Embodiments, wherein the filler comprises silicified microcrystalline cellulose.

[0867] Embodiment No. A36: The formulation of any one of the preceding Embodiments, comprising: about 40.4% w / w of silicified microcrystalline cellulose; about 70.7 mg of silicified microcrystalline cellulose; about 282.5 mg of silicified microcrystalline cellulose; about 35.4% w / w of silicified microcrystalline cellulose; about 5.0% w / w of silicified microcrystalline cellulose; about 61.9 mg of silicified microcrystalline cellulose; about 8.8 mg of silicified microcrystalline cellulose; about 247.5 mg of silicified microcrystalline cellulose; or about 35.0 mg of silicified microcrystalline cellulose.

[0868] Embodiment No. A > . The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 35.4% w / w of silicified microcrystalline cellulose; about 61.9 mg of silicified microcrystalline cellulose; or about 247.5 mg of silicified microcrystalline cellulose.

[0869] Embodiment No. A38: The formulation of any one of the preceding Embodiments, wherein the extragranular mixture comprises: about 5.0% w / w of silicified microcrystalline cellulose; about 8.8 mg of silicified microcrystalline cellulose; or about 35.0 mg of silicified microcrystalline cellulose.294245842 91Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0870] Embodiment No. A39: The formulation of any one of the preceding Embodiments, wherein the disintegrant comprises crospovidone, hydroxypropyl cellulose, sodium starch glycolate, chitosan hydrochloride, methylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, or any combination thereof.

[0871] Embodiment No. A40: The formulation of any one of the preceding Embodiments, wherein the disintegrant comprises croscarmellose sodium.

[0872] Embodiment No. A41 : The formulation of any one of the preceding Embodiments, comprising: about 1.0% w / w of croscarmellose sodium; about 1.8 mg of croscarmellose sodium; or about 7.0 mg of croscarmellose sodium.

[0873] Embodiment No. A42: The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 1.0% w / w of croscarmellose sodium; about 1.8 mg of croscarmellose sodium; or about 7.0 mg of croscarmellose sodium.

[0874] Embodiment No. A43 : The formulation of any one of the preceding Embodiments, wherein the glidant comprises talc, tribasic calcium phosphate, calcium silicate, cellulose, powdered, magnesium oxide, sodium stearate, magnesium silicate, silicon dioxide, or any combination thereof.

[0875] Embodiment No. A44: The formulation of any one of the preceding Embodiments, wherein the glidant comprises colloidal silicon dioxide.

[0876] Embodiment No. A45: The formulation of any one of the preceding Embodiments, comprising: about 0.5% w / w of colloidal silicon dioxide; about 0.9 mg of colloidal silicon dioxide; or about 3.5 mg of colloidal silicon dioxide.

[0877] Embodiment No. A46: The formulation of any one of the preceding Embodiments, wherein the extragranular mixture comprises: about 0.5% w / w of colloidal silicon dioxide; about 0.9 mg of colloidal silicon dioxide; or about 3.5 mg of colloidal silicon dioxide.

[0878] Embodiment No. A47: The formulation of any one of the preceding Embodiments, wherein the lubricant comprises sodium lauryl sulphate, sodium stearyl fumarate, magnesium294245842 92Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) silicate, calcium stearate, lauric acid, poloxamer, magnesium stearate, or any combination thereof.

[0879] Embodiment No. A48: The formulation of any one of the preceding Embodiments, wherein the lubricant comprises magnesium stearate.

[0880] Embodiment No. A49: The formulation of any one of the preceding Embodiments, comprising: about 1.0% w / w of magnesium stearate; about 1.8 mg of magnesium stearate; about 7.0 mg of magnesium stearate; about 0.5% w / w of magnesium stearate; about 0.9 mg of magnesium stearate; or about 3.5 mg of magnesium stearate.

[0881] Embodiment No. A50: The formulation of any one of the preceding Embodiments, wherein the intragranular mixture comprises: about 0.5% w / w of magnesium stearate; about 0.9 mg of magnesium stearate; or about 3.5 mg of magnesium stearate.

[0882] Embodiment No. A51 : The formulation of any one of the preceding Embodiments, wherein the extragranular mixture comprises: about 0.5% w / w of magnesium stearate; about 0.9 mg of magnesium stearate; or about 3.5 mg of magnesium stearate.

[0883] Embodiment No. A52: The formulation of any one of the preceding Embodiments, comprising one or more of the ingredients described in Tables B1-B3.

[0884] Embodiment No. A53: The formulation of any one of the preceding Embodiments, being selected from the formulations described in Table 2.

[0885] Embodiment No. A54: A method for preparing the formulation of any one of the preceding Embodiments.

[0886] Embodiment No. A55: A method of inhibiting an oncogenic mutant B-Raf protein, comprising administering to the subject the formulation of any one of the preceding Embodiments.

[0887] Embodiment No. A56: The formulation of any one of the preceding Embodiments for use in inhibiting an oncogenic mutant B-Raf protein.294245842 93Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0888] Embodiment No. A57: The formulation of any one of the preceding Embodiments for use in treating or preventing cancer in a subject.

[0889] Embodiment No. A58: The method or formulation of any one of the preceding Embodiments, wherein the subject is a human.

[0890] Embodiment No. A59. The method or formulation of any one of the preceding Embodiments, wherein the subject is a mouse.

[0891] Embodiment No. A60: The method or formulation of any one of the preceding Embodiments, wherein the cancer is a solid tumor.

[0892] Embodiment No. A61 : The method or formulation of any one of the preceding Embodiments, wherein the cancer is a carcinoma, a lymphoma, a blastoma, a sarcoma, a leukemia, a brain cancer, a breast cancer, a blood cancer, a bone cancer, a lung cancer, a skin cancer, a liver cancer, an ovarian cancer, a bladder cancer, a renal cancer, a kidney cancer, a gastric cancer, a thyroid cancer, a pancreatic cancer, an esophageal cancer, a prostate cancer, a cervical cancer, a uterine cancer, a stomach cancer, a soft tissue cancer, a laryngeal cancer, a small intestine cancer, a testicular cancer, an anal cancer, a vulvar cancer, a joint cancer, an oral cancer, a pharynx cancer or a colorectal cancer.

[0893] Embodiment No. A62: The method or formulation of any one of the preceding Embodiments, wherein the cancer is the cancer is non-small cell lung cancer (NSCLC), colorectal cancer, melanoma, thyroid cancer, histiocytosis, small bowel cancer, gastrointestinal neuroendocrine cancer, carcinoma of unknown primary, non-melanoma skin cancer, prostate cancer, gastric cancer, non-Hodgkin's lymphoma, papillary thyroid carcinoma or glioblastoma.

[0894] Embodiment No. A63 : The method or formulation of any one of the preceding Embodiments, wherein the cancer is glioma.

[0895] Embodiment No. A64: The method or formulation of any one of the preceding Embodiments, wherein the cancer is low-grade glioma.

[0896] Embodiment No. A65: The method or formulation of any one of the preceding Embodiments, wherein the cancer is glioblastoma.EXAMPLES

[0897] It is understood that the values described in the examples are approximate and subject to experimental and instrumental variations.Example Al. Synthesis of Compound No. 1 Form A294245842 94Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0898] Form A of Compound No. 1 was prepared as described in PCT Application No. PCT / US2025 / 025980. About 300 mg of Compound No. 1 was weighed into a 4 mL glass vial. 0.8 mL of methanol was added into the vial under stirring at 50°C to obtain a suspension. The suspension was stirred at 50°C for 3 days. Solids were collected by centrifugation at 4000 rpm and then dried at 50°C under vacuum for about 2 hours. About 267 mg (89% yield) of Compound No. 1 Form A was obtained as a yellow solid (Table 1-1).Table 1-1. Characterization of Form AExample 1. Preparation of Capsules Comprising Compound 1.

[0899] Form A of Compound No. 1 was prepared as described in Example Al and used as the starting material for preparing a solid dispersion of Compound No. 1. The solid dispersion may be prepared as described in PCT Application No. PCT / US2025 / 025980.

[0900] Hydroxypropyl methylcellulose acetate succinate MG grade (HPMC ASMG) was used as the polymer to prepare a solid dispersion of Compound No. 1 :HPMC ASMG (1 :4, w / w). DCM / MeOH = 4 / 1 (v / v) was used as the spray drying solution with the concentration of Compound No. 1 at 10 mg / mL. After spray drying, the dispersion was dried at 40 °C under vacuum.Preparation of 3 mg Capsules

[0901] 3 mg capsules comprising Compound No. 1 were prepared following the procedures described in FIG. 1A.

[0902] Capsule shells (size “4” white opaque HPMC capsule shell), microcrystalline cellulose (PH-102), pregelatinized starch (2003 -NEC white), croscarmellose sodium (SD- 711), colloidal silicon dioxide (Aerosil 200 Pharma), magnesium stearate, and solid dispersion of Compound No. 1 : HPMC ASMG (1 :4, w / w) were each weighed and dispensed separately (FIG. 1A, Step 1).294245842 95Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0903] The pregelatinized starch was sieved through a 30 mesh screen. The sieved material was loaded into a 20 L bin blender and blended for 5 minutes at 15 rpm (FIG. 1A, Step 2).

[0904] The material from Step 2 was then unloaded and co-sieved with the Compound No. 1 solid dispersion through a 30 mesh screen and blended for 5 minutes at 15 rpm in a 20 L bin blender (FIG. 1 A, Step 3).

[0905] The material from Step 3 was then unloaded and co-sieved with microcrystalline cellulose, croscarmellose, and colloidal silicon dioxide through a 30 mesh screen and blended for 5 minutes at 15 rpm in a 20 L bin blender (FIG. 1A, Step 4).

[0906] The material from Step 4 was then unloaded and sieved through a 30 mesh screen, followed by blending for 15 minutes at 15 rpm in a 20 L bin blender (FIG. 1A, Step 5).

[0907] Blend uniformity (BU) sampling was performed using a Sample Thief from 10 different locations in the bin blender, with a target weight of 178.2 mg from each location (FIG. 1A, Step 6). The average BU was 101.3% with a relative standard deviation of 0.5.

[0908] Magnesium stearate was sieved through a 60 mesh screen, added into the mixture from Step 6, and blended for 5 minutes at 15 rpm in a 20 L bin blender to provide a bulk formulation (FIG. 1 A, Step 7).

[0909] The bulk density / tapped density of the bulk formulation was tested using a Tap Density Tester (FIG. 1 A, Step 8).

[0910] The bulk formulation was encapsulated using an automatic capsule filing machine (IN-CAP Module 4), with a filling weight of 90 mg (FIG. 1 A, Step 9).

[0911] The capsules were then polished, sorted by weight, underwent metal detection, and finally bottled (FIG. 1A, Steps 10-13).Preparation of 25 mg Capsules

[0912] 25 mg capsules comprising Compound No. 1 were prepared following the procedures described in FIG. IB.

[0913] Capsule shells (size “0” white opaque HPMC capsule shell), silicified microcrystalline cellulose (PROSOLV SMCC HD90), croscarmellose sodium (SD-711), magnesium stearate, and solid dispersion of Compound No. 1 : HPMC ASMG (1 :4, w / w) were each weighed and dispensed separately (FIG. IB, Step 1).

[0914] The silicified microcrystalline cellulose was sieved through a 30 mesh screen. The sieved material was loaded into a 100 L bin blender and blended for 5 minutes at 15 rpm (FIG. IB, Step 2).294245842 96Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0915] The material from Step 2 was then unloaded and co-sieved with the Compound No. 1 solid dispersion and croscarmellose sodium through a 30 mesh screen and blended for 10 minutes at 15 rpm in a 100 L bin blender (FIG. IB, Step 3).

[0916] The material from Step 3 was then unloaded and sieved through a 30 mesh screen and blended for 10 minutes at 15 rpm in a 100 L bin blender (FIG. IB, Step 4).

[0917] Blend uniformity (BU) sampling was performed using a Sample Thief from 10 different locations in the bin blender, with a target weight of 633.6 mg from each location (FIG. IB, Step 5). The average BU was 101.2% with a relative standard deviation of 0.3.

[0918] Magnesium stearate (intragranular) was sieved through a 60 mesh screen, added into the mixture from Step 5, and blended for 5 minutes at 15 rpm (FIG. IB, Step 6). The average BU after dry granulation was 100.3% with a relative standard deviation of 2.3.

[0919] The material from Step 6 was then dry granulated using an Alexanderwerk WP120 Roller Compactor with 40 mm knurled rolls (FIG. IB, Step 7)

[0920] Magnesium stearate (extragranular) was sieved through a 60 mesh screen, added into the mixture from Step 7, and blended for 5 minutes at 15 rpm in a 50 L bin blender to provide a bulk formulation (FIG. IB, Step 8).

[0921] The bulk density / tapped density of the bulk formulation was tested using a Tap Density Tester (FIG. IB, Step 9).

[0922] The bulk formulation was encapsulated using an automatic capsule filing machine (IN-CAP Module 0), with a filling weight of 320 mg (FIG. IB, Step 10).

[0923] The capsules were then polished, sorted by weight, underwent metal detection, and finally bottled (FIG. IB, Steps 11-14).

[0924] During the manufacturing development process, bulk formulations prepared utilizing 50% w / w Compound No. 1 + HPMC ASMG (1 :4, w / w) solid dispersion had a mixture that was sticky and interfered with the blending process as compared to preparations utilizing 40% w / w Compound No. 1 + HPMC ASMG (1 :4, w / w) solid dispersion.

[0925] During the manufacturing development process, bulk formulations prepared utilizing 0.5% w / w magnesium stearate had a mixture that was sticky and interfered with the blending process as compared to preparations utilizing 1% w / w magnesium stearate.

[0926] The compositions of the capsules are summarized in Tables 1A (3mg capsule) & IB (25 mg capsule).Table 1A294245842 97Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)Table IBExample 2. Preparation of Tablets Comprising Compound 1.

[0927] Form A of Compound No. 1 was prepared as described in Example Al and used as the starting material for preparing a solid dispersion of Compound No. 1. The solid dispersion may be prepared as described in PCT Application No. PCT / US2025 / 025980.

[0928] Hydroxypropyl methylcellulose acetate succinate MG grade (HPMC ASMG) was used as the polymer to prepare a solid dispersion of Compound No. 1 :HPMC ASMG (1 : 1, w / w) at a 20 kg scale (10 kg Compound No. 1 and 10 kg HPMC ASMG). DCM / MeOH = 4 / 1 (v / v) was used as the spray drying solution with the concentration of Compound No. 1 at 25 mg / mL. The spray drying parameters were as shown below in Table 1-2.Table 1-2. Spray drying parameters294245842 98Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0929] Following spray drying, the dispersion was dried under vacuum at 40 °C for 24 hours.Preparation of Bulk Tablet Formulation

[0930] A bulk formulation comprising Compound No. 1 was prepared following the procedures described in FIG. 2A.

[0931] Silicified microcrystalline cellulose (PROSOLV SMCC HD90), croscarmellose sodium (SD-711), magnesium stearate (5712), colloidal silicon dioxide (Aerosil 200 Pharma), and solid dispersion of Compound No. 1 : HPMC ASMG (1 : 1, w / w) were each weighed and dispensed separately (FIG. 2A, Step 1).

[0932] The silicified microcrystalline cellulose was subdivided into approximately two equal portions. The first portion of silicified microcrystalline cellulose was sieved through a 20 mesh screen, loaded into a 200 L bin blender, and blended for 10 minutes at 10 rpm (FIG.2A, Steps 2-3).

[0933] The croscarmellose sodium was sifted through a 40 mesh screen and loaded into the bin blender of Step 3 (FIG. 2A, Step 4).

[0934] The Compound No. 1 solid dispersion and second portion of silicified microcrystalline cellulose were co-sifted through a 20 mesh screen and loaded into the bin blender of Step 4 (FIG. 2A, Step 5)

[0935] The materials from Step 5 were blended for 50 minutes at 10 rpm (FIG. 2A, Step 6).

[0936] Magnesium stearate (intragranular) was sifted through a 40 mesh screen, added into the mixture from Step 6, and blended for 8 minutes at 10 rpm (FIG. 2 A, Step 7).

[0937] Blend uniformity (BU) sampling was performed using a Sample Thief from 10 different locations in the bin blender, with a target weight of 329.0 mg from each location (FIG. 2A, Step 8). The average BU was 102.6% with a relative standard deviation of 0.6.

[0938] The material from Step 8 was then dry granulated using an Alexanderwerk WP120 Roller Compactor with 40 mm knurled rolls (FIG. 2A, Step 9) The average BU after dry granulation was 102.4% with a relative standard deviation of 1.1.

[0939] Silicified microcrystalline cellulose was sifted through a 20 mesh screen, and colloidal silica dioxide was sifted through a 40 mesh screen. The combined mixture was then blended with the dry granules from Step 9 for 26 minutes at 10 rpm (FIG. 2 A, Step 10).294245842 99Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0940] Magnesium stearate (extragranular) was sifted through a 40 mesh screen, added into the mixture from Step 10, and blended for 8 minutes at 10 rpm to yield a bulk formulation (FIG. 2A, Step 11).

[0941] Blend uniformity (BU) sampling was performed using a Sample Thief from 10 different locations in the bin blender, with a target weight of 350.0 mg from each location (FIG. 2A, Step 12).

[0942] The bulk density / tapped density and particle size distribution of the bulk formulation was tested using a density tester and a vibratory sieve shaker (FIG. 2 A, Step 13).Preparation of 50 mg Tablets

[0943] 50 mg tablets comprising Compound No. 1 were prepared following the procedures described in FIG. 2B.

[0944] The bulk formulation comprising Compound No. 1 and film coating system (Opadry ® II, 85F520105-CN Yellow) were each weighed and dispensed separately (FIG. 2B, Step 1).

[0945] The bulk formulation was compressed using a Korsch XL 100 rotary tablet press with a target weight of 175.0 mg (FIG. 2B, Step 2).

[0946] The resulting tablets were then coated using a Glatt GMPC II coating machine at 4% target weight gain (FIG. 2B, Step 3).

[0947] The tablets were then polished, underwent metal detection, and bottled (FIG. 2B, Steps 4-6).Preparation of 200 mg Tablets

[0948] 200 mg tablets comprising Compound No. 1 were prepared following the procedures described in FIG. 2C.

[0949] The bulk formulation comprising Compound No. 1 and film coating system (Opadry ® II, 85F520105-CN Yellow) were each weighed and dispensed separately (FIG. 2C, Step 1).

[0950] The bulk formulation was compressed using a Korsch XL 100 rotary tablet press with a target weight of 700.0 mg (FIG. 2C, Step 2).

[0951] The resulting tablets were then coated using a Glatt GMPC II coating machine at 4% target weight gain (FIG. 2C, Step 3).

[0952] The tablets were then polished, underwent metal detection, and bottled (FIG. 2C, Steps 4-6).294245842 100Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)

[0953] During the prototype manufacturing process, tablets prepared using a combination of mannitol and silicified microcrystalline cellulose at 19.2% w / w and 14.2% w / w, respectively, as the diluent, exhibited an intragranular blend that was sticky and interfered with the blending process. Higher amounts of silicified microcrystalline cellulose as a standalone diluent was found to be effective at reducing the stickiness of the blend for preparing the formulation.

[0954] Additionally, a pre-blending step (FIG. 2A, Step 3) reduced the tendency of the blend to stick to the surface of the container by coating the bin surface with the silicified microcrystalline cellulose.

[0955] The compositions are summarized in Table 2 for both 50 mg and 200 mg tablets.Table 2EQUIVALENTS

[0956] The details of one or more embodiments of the disclosure are set forth in the accompanying description above. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms include plural referents unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the294245842 101Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO) art to which this disclosure belongs. All patents and publications cited in this specification are incorporated by reference.

[0957] The foregoing description has been presented only for the purposes of illustration and is not intended to limit the disclosure to the precise form disclosed, but by the claims appended hereto.294245842 102

Claims

1. Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)CLAIMSWhat is claimed is:

1. A formulation comprising:(i) Compound No. 1 :(Compound No. 1), or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a glidant; and(v) a lubricant.

2. A tablet comprising:(i) Compound No. 1 :(Compound No. 1), or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a glidant; and(v) a lubricant.294245842 103Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)3. A capsule comprising:(i) Compound No. 1 :(Compound No. 1), or a pharmaceutically acceptable salt thereof;(ii) a filler;(iii) a disintegrant;(iv) a glidant; and(v) a lubricant.

4. The formulation, tablet, or capsule of any one of the preceding claims, comprising an intragranular mixture and an extragranular mixture.

5. The formulation, tablet, or capsule of any one of the preceding claims, comprising Compound No. 1.

6. The formulation, tablet, or capsule of any one of the preceding claims, comprising an amorphous solid dispersion comprising Compound No. 1 or a pharmaceutically acceptable salt thereof.

7. The formulation, tablet, or capsule of any one of the preceding claims, comprising an amorphous solid dispersion comprising Compound No. 1.

8. The formulation, tablet, or capsule of claim 6 or 7, wherein the amorphous solid dispersion comprises HPMC ASMG.294245842 104Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)9 The formulation, tablet, or capsule of any one of claims 6-8, wherein the amorphous solid dispersion comprises Compound No. 1 and HPMC ASMG at about a 1 :1 w / w, about a 1 :2 w / w, about a 1 :3 w / w, about a 1 :4 w / w, or about a 1 :5 w / w ratio of Compound No. 1 to HPMC ASMG.

10. The formulation, tablet, or capsule of any one of the preceding claims, wherein the filler is silicified microcrystalline cellulose.

11. The formulation, tablet, or capsule of any one of the preceding claims, wherein the disintegrant is croscarmellose sodium.

12. The formulation, tablet, or capsule of any one of the preceding claims, wherein the lubricant is magnesium stearate.

13. The formulation, tablet, or capsule of any one of the preceding claims, wherein the glidant is colloidal silicon dioxide.

14. The formulation, tablet, or capsule of any one of the preceding claims, wherein the formulation, tablet, or capsule comprises about 35% w / w to about 60% w / w of the filler.

15. The formulation, tablet, or capsule of any one of the preceding claims, wherein the formulation, tablet, or capsule comprises about 0.5% w / w to about 5% w / w of the disintegrant.

16. The formulation, tablet, or capsule of any one of the preceding claims, wherein the formulation, tablet, or capsule comprises about 0.5% w / w to about 3% w / w of the lubricant.

17. The formulation, tablet, or capsule of any one of the preceding claims, wherein the formulation, tablet, or capsule comprises about 0.1% w / w to about 3% w / w of the glidant.

18. A method for preparing the formulation, tablet, or capsule of any one of the preceding claims.294245842 105Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)19. A method of inhibiting an oncogenic mutant of a B-Raf protein, comprising administering to a subject the formulation, tablet, or capsule of any one of claims 1-17.

20. A method of treating or preventing cancer in a subject, comprising administering to the subject the formulation, tablet, or capsule of any one of claims 1-17.

21. The method of claim 19 or 20, wherein the subject is a human.

22. The method of claim 20 or 21, wherein the cancer is a carcinoma, a lymphoma, a blastoma, a sarcoma, a leukemia, a brain cancer, a breast cancer, a blood cancer, a bone cancer, a lung cancer, a skin cancer, a liver cancer, an ovarian cancer, a bladder cancer, a renal cancer, a kidney cancer, a gastric cancer, a thyroid cancer, a pancreatic cancer, an esophageal cancer, a prostate cancer, a cervical cancer, a uterine cancer, a stomach cancer, a soft tissue cancer, a laryngeal cancer, a small intestine cancer, a testicular cancer, an anal cancer, a vulvar cancer, a joint cancer, an oral cancer, a pharynx cancer or a colorectal cancer.

23. The method of any one of claims 20-22, wherein the cancer is a hematological cancer.

24. The method of claim 23, wherein the hematological cancer is acute myeloid leukemia.

25. The method of any one of claims 20-22, wherein the cancer is a solid cancer.

26. The method of claim 25, wherein the solid cancer is a carcinoma.

27. The method of claim 26, wherein the carcinoma is pancreatic adenocarcinoma.

28. The method of claim 25 or 26, wherein the solid cancer is non-small cell lung cancer (NSCLC), brain cancer, colorectal cancer, melanoma, thyroid cancer, histiocytosis, small bowel cancer, gastrointestinal neuroendocrine cancer, carcinoma of unknown primary, nonmelanoma skin cancer, prostate cancer, gastric cancer, non-Hodgkin's lymphoma, papillary thyroid carcinoma, or glioblastoma.

29. The method of claim 28, wherein the solid cancer is NSCLC.294245842 106Attorney Docket No.: 43905-02077 (ASET-047 / 001 WO)30. The method of claim 28, wherein the solid cancer is brain cancer.

31. The method of claim 28, wherein the solid cancer is thyroid carcinoma, colorectal carcinoma, melanoma, or a histiocytic neoplasm.

32. The method of claim 31, wherein the solid cancer is colorectal carcinoma.

33. The method of any one of claims 20-32, wherein the cancer is characterized by at least one oncogenic mutation in the BRAF gene.

34. The method of any one of claims 20-33, wherein the cancer is characterized by at least one oncogenic variant of a RAS GTPase.

35. The method of any one of claims 20-34, wherein the cancer is characterized by at least one oncogenic mutation in the KRAS gene.

36. The method of claim 35, wherein the oncogenic mutation is not KRAS G12C.

37. The method of any one of claims 20-36, wherein the cancer is characterized by at least one oncogenic mutation in the NRAS gene.

38. The method of any one of claims 20-37, wherein the cancer is advanced or metastatic.294245842 107

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