Pharmaceutical compositions of 3-fluoro-5-(((LS,2ar)-l,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1h-cyclopenta[CD]inden-7-YL)OXY)-benzonitrile

Abstract

Disclosed herein are compositions and formulations of 3-fluoro-5-(((1S,2aR)-1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]inden-7-yl)oxy)benzonitrile (Compound (I)), wherein Compound (I) has the structure (I) and methods of making and using such compositions and formulations.

Description

[0001] Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT PHARMACEUTICAL COMPOSITIONS OF 3-FLUORO-5-(((1S,2AR)-1,3,3,4,4- PENTAFLUORO-2A-HYDROXY-2,2A,3,4-TETRAHYDRO-1H- CYCLOPENTA[CD]INDEN-7-YL)OXY)-BENZONITRILE This application claims the benefit of priority of U.S. Provisional Application No. 63 / 642,141, filed on May 3, 2024, the contents of which is incorporated herein by reference in its entirety. Field of the disclosure Disclosed herein are pharmaceutical compositions comprising 3-fluoro-5-(((1S,2aR)- 1,3,3,4,4-pentafluoro-2a-hydroxy-2,2a,3,4-tetrahydro-1H-cyclopenta[cd]inden-7- yl)oxy)benzonitrile (hereinafter Compound (I)), wherein Compound (I) has the structure: and processes of making and using formulations. Compound (I) is also referred to as NKT2152. Background Although pharmaceuticals may be administered in a variety of ways, solid oral dosage forms are preferred since these offer greater drug stability, more accurate dosing, and ease of administration. For an oral dosage form to be effective, it must readily release the drug for its absorption. A number of pharmaceutical drug substances are poorly water soluble and are, therefore, not well-absorbed after oral administration. Moreover, absorption of most drugs takes place in the upper small intestine and is greatly reduced after the ileum, meaning that the absorption window is small. One of the current challenges in the pharmaceutical industry is the development of strategies that improve drug bioavailability, for example, through the development of fast release formulations which ensure that the drug is released in the short timeframe required for its uptake, or by enhancing drug solubility. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Accordingly, it is desirable to identify a solid oral formulation that has good blend uniformity, and which can achieve consistent release and dissolution profiles, and, moreover, has desirable bioavailability. It is also desirable to provide a formulation wherein the risk of product degradation is reduced. It is further desirable to provide a process which can easily be adapted to provide immediate or modified release of the active agent. The present invention achieves one or more of these objectives. Compound (I) is a HIF-2α inhibitor and is useful for treating diseases mediated by aberrant activity of HIF-2α, including cancer such as renal cancer, glioblastoma, neuroblastoma, pheochromocytomas and paragangliomas, somatostatinomas, hemangioblastomas, gastrointestinal stromal tumors (GIST), pituitary tumors, leiomyomas, leiomyosarcomas, polycythaemia, and retinal tumors) and non-cancer diseases (such as pulmonary artery hypertension (PAH), reflux esophagitis, hepatic steatosis, and nonalcoholic steatohepatitis (NASH)), inflammatory disease (such as inflammatory bowel disease), autoimmune disease (such as Graft-versus-Host-Disease), and iron overload. Compound (I) and a crystalline form of Compound (I), designated as Form A polymorph, having an X-ray powder diffraction (XRPD) pattern comprising peaks at angular positions 15.8 and 18.6, wherein the angular positions may vary by + 0.2o2θ as measured by X- ray powder diffraction using an X-ray wavelength of 1.5418 Å are disclosed in U.S. Patent No. 11,267,782 and PCT Application Publication No. WO / 2023 / 064305, respectively, the entire contents of each of which are incorporated herein by reference. Compound (I) Form A is in Phase 1 / 2 study in patients with clear cell renal cell carcinoma (ccRCC) as a monotherapy and combination therapy. Summary Compound (I) Form A is in Phase 1 / 2 study in patients with ccRCC as a monotherapy and is administered to the patients as immediate-release capsules. Compound (I) Form A has poor solubility in water (<1 mg / mL at 25°C) and therefore presented significant challenges to develop a solid oral immediate release formulation of Compound (I) Form A having desirable bioavailability. It has been surprisingly discovered that a solid oral immediate release formulation of micronized Compound (I) Form A containing sprayed sodium lauryl sulfate (SLS), provides desirable bioavailability of the compound. Accordingly, provided herein, in a first aspect, is a wet granulated pharmaceutical composition comprising: Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (a) micronized Compound (I) Form A having an X-ray powder diffraction (XRPD) pattern comprising peaks at angular positions 15.8 and 18.6, wherein the angular positions may vary by + 0.2o2θ as measured by X-ray powder diffraction using an X-ray wavelength of 1.5418 Å; (b) a sprayed surfactant; and (c) a non-sprayed surfactant; wherein the sprayed and non-sprayed surfactants are the same or different. In a second aspect, provided is a method of treating a disease mediated by HIF-2α comprising administering to a patient in need thereof a wet granulated pharmaceutical composition of the first aspect (or any one of the embodiments thereof disclosed herein). In a third aspect, provided is a process of making a wet granulated pharmaceutical composition of the first aspect (or any one of the embodiments thereof disclosed herein) by a wet granulating process, comprising: (1a) preparing a mixture comprising micronized Compound (I) Form A and a non-sprayed surfactant; (1b) spraying on to the mixture of step (1a) a granulating amount of water comprising a sprayed surfactant to form wet granules; (1c) drying the wet granulates of step (1b) to remove water; (1d) milling the granules from step (1c) to produce milled granules; (1e) sieving the milled granules from step (1d) to remove lumps or agglomerates; and (1f) optionally encapsulating granules obtained from step (1e) in immediate release capsules. In a fourth aspect, provided is micronized Compound (I) Form A having an X-ray powder diffraction (XRPD) pattern comprising peaks at angular positions 15.8 and 18.6 (or any embodiments thereof disclosed herein), wherein the angular positions may vary by + 0.2o2θ as measured by X-ray powder diffraction using an X-ray wavelength of 1.5418 Å and wherein the micronized Compound (I) Form A has a D90 value of about 14 µm (or any embodiments thereof disclosed herein). In a fifth aspect, provided is an immediate release capsule comprising the wet granulated pharmaceutical composition of the first aspect (or any embodiments thereof disclosed herein). Brief Description of the Drawings Figure 1 depicts the non-sink dissolution of 100 mg capsules of non-micronized (F1) and micronized (F2) Compound (I) Form A in SGF media. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Figure 2 depicts the non-sink dissolution of 100 mg capsules of non-micronized Compound (I) Form A in SGF media without surfactant (F1), micronized Compound (I) Form A in SGF media without surfactant (F2), micronized Compound (I) Form A in SGF media comprising sodium lauryl sulfate (F3), and micronized Compound (I) Form A in SGF media comprising Soluplus® (BASF) (F4). Figure 3 depicts 200 mg capsule dissolution of dry granulated formulations of micronized Compound (I) Form A (F5) and (F6).in SGF media. Figure 4 depicts the granules only manufacturing process. Figure 5 depicts bioavailability of 10 mg, 25 mg, and 50 mg of micronized Compound (I) Form A in Beagle Dogs. Figure 6 depicts a Compound (I) Form A X-ray powder diffraction pattern. Detailed Description Definitions: Unless otherwise stated, the following terms used in the specification and claims are defined for the purposes of this application and have the following meaning: As used herein, “a” and “an” mean one or more, unless the context clearly dictates otherwise. As used herein, “about” means + 10%. In one embodiment, about is + 5%. In another embodiment, about is + 4%. In another embodiment, about is + 3%. In another embodiment, about is + 2% or + 1%, of a listed value. For example, a reaction carried out at about 10 °C includes 9 °C, 11 °C, and all temperatures contained in between 9 °C and 11 °C. As used herein, “AUC” means area under the concentration-time curve and is the definite integral of the concentration of an administered compound found in blood plasma, after a dose is given, as a function of time, as measured using liquid chromatography–mass spectrometry. As used herein, “AUClast” means area under the concentration-time curve up to the last measurable concentration. As used herein, “Cmax” means the maximum (peak) concentration of an administered compound found in blood plasma, after a dose is given and reflects the rate and extent of absorption, as measured using liquid chromatography–mass spectrometry. The formulations of Compound (I) Form A disclosed herein are prepared from micronized Compound (I) Form A unless otherwise noted. Compound (I) Form A can be prepared by the method disclosed in PCT Applications Publication Nos. WO / 2023 / 064305 or WO 2023 / 060431. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Micronized Compound (I) Form A can be prepared by methods well known in the art, including the method disclosed in the Working Example below. Particle size can be determined by methods known in the art, such as laser light diffaction, dynamic light scattering, or sieve analysis. In one embodiment the micronized Compound (I) Form A has a D90 value of < 25 µm. In one embodiment, the micronized Compound (I) Form A has a D90 value of < 20 µm. In one embodiment, the micronized Compound (I) Form A has a D90 value of < 15 µm. In one embodiment, the micronized Compound (I) Form A has a D90 value of about 14 µm. In one embodiment, the micronized Compound (I) Form A has a D90 value of 14 ± 4 µm. In one embodiment, the micronized Compound (I) Form A has a D90 value of 14 ± 2 µm. In another embodiment, the micronized Compound (I) Form A has a D90 value of about 13.6 µm. In one embodiment, the micronized Compound (I) Form A has a D50 value of < 10 µm. In one embodiment, the micronized Compound (I) Form A has a D50 value of < 6 µm. In one embodiment, the micronized Compound (I) Form A has a D50 value of about 6 µm. In one embodiment, the micronized Compound (I) Form A has a D50 value of 6 ± 3 µm. In one embodiment, the micronized Compound (I) Form A has a D50 value of 6 ± 2 µm. In one embodiment, the micronized Compound (I) Form A has a D50 value of 6 ± 1 µm. In another embodiment, the micronized Compound (I) Form A has a D50 value of about 5.9 µm. In one embodiment, the micronized Compound (I) Form A has a D10 value of < 3 µm. In one embodiment, the micronized Compound (I) Form A has a D10 value of about 3 µm. In one embodiment, the micronized Compound (I) Form A has a D10 value of 3 ± 2 µm. In one embodiment, the micronized Compound (I) Form A has a D10 value of 3 ± 1 µm. In one embodiment, the micronized Compound (I) Form A has a D10 value of 3 ± 0.5 µm. In another embodiment, the micronized Compound (I) Form A has a D10 value of 2.6 µm. In another embodiment, the micronized Compound (I) Form A has a D10 value of about 3 µm, a D50 value of about 6 µm, and a D90 value of about 14 µm. In another embodiment, the micronized Compound (I) Form A has a D10 value of 3 ± 2 µm, a D50 value of 6 ± 3 µm, and a D90 value of 14 ± 4 µm. In another embodiment, the micronized Compound (I) Form A has a D10 value of 3 ± 1 µm, a D50 value of 6 ± 2 µm, and a D90 value of 14 ± 3 µm. In another embodiment, the micronized Compound (I) Form A has a D10 value of 3 ± 0.5 µm, a D50 value of 6 ± 1 µm, and a D90 value of 14 ± 2 µm. In another embodiment, the micronized Compound (I) Form A has a D10 value of 2.6 µm, a D50 value of 5.9 µm, and a D90 value of 13.6 µm. The terms D10, D50, and D90 are well known in the art, i.e, D50 indicates size under which 50% by weight of the particles in the sample exist. For example, the D10 value of 2.6 µm means that 10% by weight of the Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT particles in the sample have a size below 2.6 µm. It is understood that the particle sizes given herein are subject to variations depending on the apparatuses and methods used. “XRPD” means X-ray powder diffraction, an analytical technique which measures the diffraction of X-rays in the presence of a solid component. Materials which are crystalline and have regular repeating arrays of atoms generate a distinctive powder pattern. The terms “pharmaceutical composition(s)” is being used herein interchangeably with “formulation(s)” unless stated otherwise. A “pharmaceutically acceptable carrier or excipient” means a carrier or an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable, and includes a carrier or an excipient that is acceptable for veterinary use as well as human pharmaceutical use. “A pharmaceutically acceptable carrier / excipient” as used in the specification and claims includes both one and more than one such excipient. The term “disease” as used herein is intended to be generally synonymous, and is used interchangeably with, the terms “disorder,” “syndrome,” and “condition” (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, is typically manifested by distinguishing signs and symptoms, and causes the human or animal to have a reduced duration or quality of life. The term “combination therapy” means the administration of two or more therapeutic agents to treat a disease or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses the use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein. The term “patient” is generally synonymous with the term “subject” and includes all mammals including humans. Examples of patients include humans, livestock such as cows, goats, sheep, pigs, and rabbits, and companion animals, such as dogs, cats, rabbits, and horses. Preferably, the patient is a human. “Treating” or “treatment” of a disease includes: Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (1) preventing the disease, i.e., causing the clinical symptoms of the disease not to develop in a mammal that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease; (2) inhibiting the disease, i.e., arresting or reducing the development of the disease (i.e., stabilizing) or its clinical symptoms; or (3) relieving the disease, i.e., causing regression of the disease or its clinical symptoms. A “therapeutically effective amount” means the amount of Compound (I) or Compound (I) Form A that, when administered to a patient for treating a disease, is sufficient to affect such treatment for the disease. The “therapeutically effective amount” will vary depending on the compound, the disease and its severity, and the age, weight, etc., of the subject to be treated. The formulations disclosed herein comprise one or more surfactants. Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid, and include e.g., such compounds as sodium lauryl sulfate, sodium docusate, Tween 60 or 80, triacetin, vitamin E TPGS, sorbitan monooleate, polyoxyethylene sorbitan monooleate, polysorbates, polaxomers, bile salts, glyceryl monostearate, copolymers of ethylene oxide and propylene oxide, e.g., Pluronic® (BASF), and the like. Some other surfactants include polyoxyethylene fatty acid glycerides and vegetable oils, e.g., polyoxyethylene (60) hydrogenated castor oil, and polyoxyethylene alkylethers and alkylphenyl ethers, e.g. octoxynol 10, octoxynol 40. In certain embodiments, the formulations disclosed herein may also include one or more binders. Binders impart cohesive qualities and include, e.g., alginic acid and salts thereof; cellulose derivatives, such as carboxymethylcellulose, methylcellulose (e.g., Methocel®), ydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose (e.g., Klucel®), ethylcellulose (e.g., Ethocel®), and microcrystalline cellulose (e.g., Avicel®); microcrystalline dextrose; amylose; magnesium aluminum silicate; polysaccharide acids; bentonites; gelatin; polyvinyl-pyrrolidone / vinyl acetate copolymer, crosspovidone; povidone; starch; pregelatinized starch; tragacanth, dextrin, a sugar, such as sucrose (e.g., Dipac®), glucose, dextrose, molasses, mannitol, sorbitol, xylitol (e.g., Xylitab®), and lactose; a natural or synthetic gum, such as acacia, tragacanth, ghatti gum mucilage of isapol husks, polyvinylpyrrolidone (e.g., Polyvidone® CL, Kollidon® CL, Polyplasdone® XL-10), larch arabogalactan, Veegum®, polyethylene glycol, polyethylene oxide, waxes, sodium alginate, and the like. In certain embodiments, the formulations disclosed herein may also include one or more “diluents”, which refers to chemical compounds that are used to dilute a therapeutically active Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT compound prior to delivery. Diluents can also be used to stabilize compounds because they can provide a more stable environment. Salts dissolved in buffered solutions (which also can provide pH control or maintenance) are utilized as diluents in the art, including, but not limited to a phosphate buffered saline solution. In certain embodiments, diluents increase bulk of a composition to facilitate compression or create sufficient bulk for a homogenous blend for capsule filling. Such compounds include, e.g., lactose, starch, mannitol, sorbitol, dextrose, microcrystalline cellulose such as Avicel®, dibasic calcium phosphate, dicalcium phosphate dihydrate, tricalcium phosphate, calcium phosphate, anhydrous lactose, spray-dried lactose, pregelatinized starch, compressible sugar, such as Di-Pac® (Amstar), hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate stearate, sucrose-based diluents, confectioner's sugar, monobasic calcium sulfate monohydrate, calcium sulfate dihydrate, calcium lactate trihydrate, dextrates, hydrolyzed cereal solids, amylose, powdered cellulose, calcium carbonate, glycine, kaolin, mannitol, sodium chloride; inositol, bentonite, and the like. In certain embodiments, the formulations disclosed herein may also include one or more “disintegrants” which include both the dissolution and dispersion of the dosage form when contacted with gastrointestinal fluid. “Disintegration agents or disintegrants” facilitate the breakup or disintegration of a substance. Examples of disintegration agents include a starch, e.g., a natural starch such as corn starch or potato starch, a pregelatinized starch, such as National 1551 or sodium starch glycolate, such as Promogel® or Explotab®, a cellulose, such as a wood product, methylcrystalline cellulose, e.g., Avicel®, Avicel® PH101, Avicel® PH 102, Avicel® PH105, Elceme® P100, Emcocel®, Vivacel®, and Solka-Floc®, methylcellulose, croscarmellose, or a cross-linked cellulose, such as cross-linked sodium carboxymethylcellulose (Ac-Di-Sol®), cross- linked carboxymethylcellulose, or cross-linked croscarmellose, a cross-linked starch, such as sodium starch glycolate, a cross-linked polymer, such as crosspovidone, a cross-linked polyvinylpyrrolidone, alginate, such as alginic acid or a salt of alginic acid, such as sodium alginate, a clay, such as Veegum® HV (magnesium aluminum silicate), a gum, such as agar, guar, locust bean, Karaya, pectin, or tragacanth, sodium starch glycolate, bentonite, a natural sponge, a surfactant, a resin, such as a cation-exchange resin, citrus pulp, sodium lauryl sulfate, sodium lauryl sulfate in combination with a starch, and the like. It should be appreciated that there is considerable overlap between excipients used in the solid dosage forms described herein. Thus, the above-listed additives should be taken as merely exemplary, and not limiting, of the types of excipients that can be included in formulations Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT described herein. The types and amounts of such excipients can be readily determined by one skilled in the art, according to the particular properties desired. Embodiments: 1. Embodiment 1 comprises a wet granulated pharmaceutical composition comprising: (a) micronized Compound (I) Form A having an X-ray powder diffraction peaks at angular positions 15.8 and 18.6, wherein the angular positions may vary by + 0.2o2θ as measured by X-ray powder diffraction using an X-ray wavelength of 1.5418 Å; (b) a sprayed surfactant; and (c) a non-sprayed surfactant; wherein the sprayed and non-sprayed surfactants are the same or different. 2. Embodiment 2 comprises the wet granulated pharmaceutical composition of embodment 1, further comprising a binder. 3. Embodiment 3 comprises the wet granulated pharmaceutical composition of embodment 1 or 2, further comprising a disintegrant. 4A. Embodiment 4A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 3, further comprising a diluent. 4B. Embodiment 4B comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4A, wherein the micronized Compound (I) Form A has a D90 value of < 25 µm. 4. Embodiment 4 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4B, wherein the micronized Compound (I) Form A has a D90 value of < 20 µm. 5A. Embodiment 5A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4, wherein the micronized Compound (I) Form A has a D90 value of 14 ± 4 µm. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 5B. Embodiment 5B comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4, wherein the micronized Compound (I) Form A has a D90 value of 14 ± 3 µm. 5C. Embodiment 5C comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4, wherein the micronized Compound (I) Form A has a D90 value of 14 ± 2 µm. 5D. Embodiment 5D comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4, wherein the micronized Compound (I) Form A has a D90 value of less than about 14 µm. 5. Embodiment 5 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4, wherein the micronized Compound (I) Form A has a D90 value of about 14 µm. 6A. Embodiment 6A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 5, wherein the micronized Compound (I) Form A has a D50 value of less than about 10 µm. 6B. Embodiment 6B comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 5, wherein the micronized Compound (I) Form A has a D50 value of about 10 µm. 6C. Embodiment 6C comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 5, wherein the micronized Compound (I) Form A has a D50 value of 6 ± 3 µm. 6D. Embodiment 6D comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 5, wherein the micronized Compound (I) Form A has a D50 value of 6 ± 2 µm. 6E. Embodiment 6E comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 5, wherein the micronized Compound (I) Form A has a D50 value of 6 ± 1 µm. 6F. Embodiment 6F comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 5, wherein the micronized Compound (I) Form A has a D50 value of less than about 6 µm. 6. Embodiment 6 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 5, wherein the micronized Compound (I) Form A has a D50 value of about 6 µm. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 7A. Embodiment 7A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 6, wherein the micronized Compound (I) Form A has a D10 value of 3 ± 2 µm. 7B. Embodiment 7B comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 6, wherein the micronized Compound (I) Form A has a D10 value of about 3 ± 1 µm. 7C. Embodiment 7C comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 6, wherein the micronized Compound (I) Form A has a D10 value of about 3 ± 0.5 µm. 7D. Embodiment 7D comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 6, wherein the micronized Compound (I) Form A has a D10 value less than about 3 µm. 7. Embodiment 7 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 6, wherein the micronized Compound (I) Form A has a D10 value of about 3 µm. 8A Embodiment 8A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4A, wherein the micronized Compound (I) Form A has a D10 value of 3 ± 2 µm, a D50 value of 6 ± 3 µm, and a D90 value of 14 ± 4 µm. 8B Embodiment 8B comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4A, wherein the micronized Compound (I) Form A has a D10 value of 3 ± 1 µm, a D50 value of 6 ± 2 µm, and a D90 value of 14 ± 3 µm. 8C Embodiment 8C comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4A, wherein the micronized Compound (I) Form A has a D10 value of 3 ± 0.5 µm, a D50 value of 6 ± 1 µm, and a D90 value of 14 ± 2 µm. 8. Embodiment 8 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 4A, wherein the micronized Compound (I) Form A has a D10 value of 2.6 µm, a D50 value of 5.9 µm, and a D90 value of 13.6 µm. 9. Embodiment 9 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 8, wherein the dry wt / wt % ratio of micronized Compound (I) Form A to combined weight of the sprayed and non-sprayed surfactants is 4:1. 10. Embodiment 10 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 9, wherein the percentage of the sprayed surfactant is about 3.0 % by weight of the total dry weight of the pharmaceutical composition. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 11. Embodiment 11 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 9, wherein the weight of the sprayed surfactant is about 2.45 % of the total dry weight of the pharmaceutical composition. 12. Embodiment 12 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 9 and 11, wherein the weight of the sprayed surfactant is 2.43 % by weight of the total dry weight of the pharmaceutical composition. 13A. Embodiment 13A comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 12, where the weight of the binder is about 6.0 % by weight of the total dry weight of the pharmaceutical composition. 13. Embodiment 13 comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 12, where the weight of the binder is about 5.0 % by weight of the total dry weight of the pharmaceutical composition. 14. Embodiment 14 comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 13A, where the binder comprises sprayed and non-sprayed binders which may be the same or different. 14A. Embodiment 14A comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 12 and 13, where the binder comprises sprayed and non-sprayed binders which may be the same or different. 15A. Embodiment 15A comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 13A and 14, where the weight of sprayed binder is about 0.7 % by weight of the total dry weight of the pharmaceutical composition. 15. Embodiment 15 comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 12, 13, and 14A, where the weight of sprayed binder is about 0.65 % by weight of the total dry weight of the pharmaceutical composition. 16. Embodiment 16 comprises the wet granulated pharmaceutical composition of any one of embodiments 14A, 14, and 15, where the weight of sprayed binder is 0.61 % by weight of the total dry weight of the pharmaceutical composition. 17. Embodiment 17 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12 and 16, where the binder comprises sprayed and non-sprayed binders which may be the same or different and the weight of non-sprayed binder is about 5.30 % by weight of the total dry weight of the pharmaceutical composition. 18A. Embodiment 18A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12 and 16, where the binder comprises sprayed and non-sprayed binders Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT which may be the same or different and the weight of non-sprayed binder is about 4.80 % by weight of the total dry weight of the pharmaceutical composition. 18. Embodiment 18 comprises the wet granulated pharmaceutical composition of any one of embodiments 14A, 15, and 16 where the weight of non-sprayed binder is about 4.50 % by weight of the total dry weight of the pharmaceutical composition 19. Embodiment 19 comprises the wet granulated pharmaceutical composition of any one of embodiments 14A, 15, 16, 18A, and 18, where the weight of non-sprayed binder is 4.77 % by weight of the total dry weight of the pharmaceutical composition. 20. Embodiment 20 comprises the wet granulated pharmaceutical composition of any one of embodiments 14A, 15, 16, and 18, where the weight of non-sprayed binder is about 4.30 % by weight of the total dry weight of the pharmaceutical composition. 21. Embodiment 21A comprises the wet granulated pharmaceutical composition of any one of embodiments 14A, 15, 16, 18, and 20, where the weight of non-sprayed binder is 4.25 % by weight of the total dry weight of the pharmaceutical composition. 22. Embodiment 21 comprises the wet granulated pharmaceutical composition of any one of embodiments 14A, 15, 16, 18A and 18, where the weight of non-sprayed binder is 4.56 % by weight of the total dry weight of the pharmaceutical composition. 23. Embodiment 23 comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 22, where the binder is selected from polyvinylpyrrolidinone, microcrystalline cellulose, and copovidone. 24. Embodiment 24 comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 23, where the binder is copovidone. 25. Embodiment 25 comprises the wet granulated pharmaceutical composition of any one of embodiments 3 to 24, where the weight of disintegrant is about 5.0 % by weight of the total dry weight of the pharmaceutical composition. 26. Embodiment 25 comprises the wet granulated pharmaceutical composition of any one of embodiments 3 to 24, where the weight of disintegrant is about 4.50 % by weight of the total dry weight of the pharmaceutical composition. 27. Embodiment 27 comprises the wet granulated pharmaceutical composition of any one of embodiments 3 to 24, and 26, where the weight of disintegrant is 4.37% by weight of the total dry weight of the pharmaceutical composition. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 28. Embodiment 28A comprises the wet granulated pharmaceutical composition of any one of embodments 3 to 26, where the weight of disintegrant is 4.84 % by weight of the total dry weight of the pharmaceutical composition. 29. Embodiment 29 comprises the wet granulated pharmaceutical composition of any one of embodiments 3 to 26, where the weight of disintegrant is 4.65 % by weight of the total dry weight of the pharmaceutical composition. 30. Embodiment 30 comprises the wet granulated pharmaceutical composition of any one of embodiments 3 to 29, where the disintegrant is selected from sodium starch glycolate, croscarmellose sodium, and crospovidone. 31. Embodiment 31 comprises the wet granulated pharmaceutical composition of any one of embodiments 2 to 30, where the disintegrant is crospovidone. 32. Embodiment 32 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A to 19, 23 to 26, 28, 30, and 31, wherein the weight of the non-sprayed surfactant is about 0.30 % by weight of the total dry weight of the pharmaceutical composition. 33. Embodiment 33 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A to 19, 23 to 26, 28, 30, and 31, wherein the weight of the non-sprayed surfactant is about 0.26 % by weight of the total dry weight of the pharmaceutical composition. 34. Embodiment 34 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A to 19, 23 to 26, 28, 30, 31, and 33, wherein the weight of the non-sprayed surfactant is 0.26 % by weight of the total dry weight of the pharmaceutical composition. 34A. Embodiment 34A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, and 31, wherein the weight of the non-sprayed surfactant is about 10.0 % by weight of the total dry weight of the pharmaceutical composition. 35. Embodiment 35 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, and 31, wherein the weight of the non-sprayed surfactant is about 9.70 % by weight of the total dry weight of the pharmaceutical composition. 35A. Embodiment 35A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, 31, and 35, wherein Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT the weight of the non-sprayed surfactant is 9.71 % by weight of the total dry weight of the pharmaceutical composition. 36A. Embodiment 36A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A,18, 22 to 26, and 29 to 31, wherein the weight of the non-sprayed surfactant is about 4.0 % by weight of the total dry weight of the pharmaceutical composition. 36. Embodiment 36 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A,18, 22 to 26, 29 to 31, and 36A, wherein the weight of the non-sprayed surfactant is 4.03 % by weight of the total dry weight of the pharmaceutical composition. 37. Embodiment 37 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 36, wherein the sprayed and the non-sprayed surfactants are independently selected from Polyoxyl 40 stearate, Cremophor RH40, Polysorbate 80, Tocophersolan, Soluplus, poloxamer 188, poloxamer 457, linoeoyl polyoxyl-6-gylcerides (Labrafil M2125), lauroyl polyoxyl-32 glycerides, and sodium lauryl sulfate. 38. Embodiment 38 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 37, wherein the sprayed and non-sprayed surfactants are both sodium lauryl sulfate. 39. Embodiment 39 comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18A to 19, 23 to 26, 28, 30 to 34, 37, and 38 where the weight of diluent is about 75 % by weight of the total dry weight of the pharmaceutical composition. 40. Embodiment 40 comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18A to 19, 23 to 26, 28, 30 to 34, 37, and 38, where the weight of diluent is about 76.34 % by weight of the total weight of the pharmaceutical composition. 40A. Embodiment 40A comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18A,18, 22 to 26, 29 to 31, 36A, 36, 37, and 38 where the weight of diluent is about 60 % by weight of the total dry weight of the pharmaceutical composition. 40B. Embodiment 40B comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18A,18, 22 to 26, 29 to 31, 36A, 36, 37, and 38, Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT where the weight of diluent is about 57.88% by weight of the total weight of the pharmaceutical composition. 40C. Embodiment 40C comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18A,18, 22 to 26, 29 to 31, 36A, 36, 37, 38, and 40B, where the weight of diluent is 57.88% by weight of the total weight of the pharmaceutical composition. 41. Embodiment 41 comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, 31, 34A, 35, 35A, 37, and 38 where the weight of diluent is about 35 % by weight of the total dry weight of the pharmaceutical composition. 41A. Embodiment 41A comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, 31, 34A, 35, 35A, 37, and 38 where the weight of diluent is about 31 % by weight of the total dry weight of the pharmaceutical composition. 42A. Embodiment 42 comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, 3134A, 35, 35A, 37, 38 and 41A, where the weight of diluent is about 30.09 % by weight of the total dry weight of the pharmaceutical composition. 42. Embodiment 42 comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, 31, 34A, 35, 35A, 37, 38, 41A, and 42A, where the weight of diluent is 30.10 % by weight of the total dry weight of the pharmaceutical composition. 43. Embodiment 43 comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 42, wherein the diluent is selected from lactose, pregelatinized starch, corn starch, microcrystalline cellulose and mannitol. 44. Embodiment 44 comprises the wet granulated pharmaceutical composition of any one of embodiments 4 to 43, wherein the diluent is mannitol. 45. Embodiment 45 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A to 19, 23 to 26, 28, 30 to 34, and 37 to 40, , 43, and 44, wherein the weight of Compound (I) Form A is about 11.0 % by weight of the total dry weight of the pharmaceutical composition. 46. Embodiment 46 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A to 19, 23 to 26, 28, 30 to 34, 37 to 40, 43, 44 Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT and 45, wherein the weight of Compound (I) Form A is about 10.75 % by weight of the total dry weight of the pharmaceutical composition. 47. Embodiment 47 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, 31, 34A, 35, 35A, 37, 38, and 41A to 44, wherein the weight of Compound (I) Form A is about 50.0 % by weight of the total dry weight of the pharmaceutical composition. 48. Embodiment 48 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18, 20, 21, 23, 24, 26, 27, 30, 31, 34A, 35, 35A, 37, 38, 41A to 44 and 47, wherein the weight of Compound (I) Form A is about 48.54 % by weight of the total dry weight of the pharmaceutical composition. 48A. Embodiment 48A comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A,18, 22 to 26, 29 to 31, 36A, 36, 37, 38, 40A, 40B, 40C, 43, and 44 wherein the weight of Compound (I) Form A is about 25.0 % by weight of the total dry weight of the pharmaceutical composition. 48B. Embodiment 48B comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 12, 13, 14A, 15, 16, 18A,18, 22 to 26, 29 to 31, 36A, 36, 37, 38, 40A, 40B, 40C, 43, 44, 41 to 44, and 48A, wherein the weight of Compound (I) Form A is about 25.84 % by weight of the total dry weight of the pharmaceutical composition. 49. Embodiment 49 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 48B, wherein the granules of wet granulated pharmaceutical composition do not comprise an extragranular layer of pharmaceutically acceptable excipients. 50. Embodiment 50 comprises the wet granulated pharmaceutical composition of any one of embodiments 1 to 48B, wherein the granules of wet granulated pharmaceutical composition further comprise an extragranular layer comprising one or more pharmaceuticall acceptable excipients. 51. Embodiment 51 comprises the wet granulated pharmaceutical composition of embodiment 50, wherein the extragranular layer comprises a diluent. 52. Embodiment 52 comprises the wet granulated pharmaceutical composition of any one of embodiments 50 and 51, wherein the extragranular layer comprises a disintegrant. 53. Embodiment 53 comprises the wet granulated pharmaceutical composition of any one of embodiments 50 to 52, wherein the extragranular layer comprises a glidant. 54. Embodiment 54 comprises a wet granulated pharmaceutical composition comprising: Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (a) micronized Compound (I) Form A selected from any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of a sprayed surfactant selected from any one of embodiments 1, 37 and 38; and (c) a non-sprayed surfactant of any one of embodiments 1, 37 and 38; wherein the sprayed and non-sprayed surfactants are the same or different and wherein the dry wt / wt% ratio of Compound (I) Form A to combined weight of the sprayed and non-sprayed surfactants is 4:1. 55. Embodiment 55 comprises a wet granulated pharmaceutical composition comprising: (a) 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 1, 37, and 38; and (c) 9.71 wt % of the non-sprayed surfactant; of any one of embodiments 1, 37, and 38 wherein the sprayed and non-sprayed surfactants are the same or different and the dry wt / wt% ratio of Compound (I) Form A to combined weight of the sprayed and non-sprayed surfactants is 4:1. 55A. Embodiment 55A comprises a wet granulated pharmaceutical composition comprising: (a) about 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of a sprayed surfactant; (c) about 9.71 wt % of a non-sprayed surfactant; (d) about 30.1 wt % of a diluent; (e) about 4.86 wt % of a binder; and (f) about 4.37 wt % of a disintegrant; wherein the sprayed and non-sprayed surfactants are the same or different; and the wt % is based on total dry weight of the pharmaceutical composition. 56. Embodiment 56 comprises a wet granulated pharmaceutical composition comprising: (a) about 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (c) about 9.71 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 30.1 wt % of the diluent of any one of embodiments 43 and 44; (e) about 4.86 wt % of the binder of any one of embodiments 23 and 24, wherein about 4.25 wt% is a non-sprayed binder and about 0.61 wt % is a sprayed binder; and (f) about 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 57. Embodiment 57 comprises a wet granulated pharmaceutical composition comprising: (a) 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 9.71 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 30.1 wt % of the diluent of any one of embodiments 43 and 44; (e) 4.86 wt % of the binder of any one of embodiments 23 and 24, wherein about 4.25 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 58. Embodiment 58 comprises a wet granulated pharmaceutical composition consisting essentially of: (a) 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 9.71 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 30.1 wt % of the diluent of any one of embodiments 43 and 44; (e) 4.85 wt % of the binder of any one of embodiments 23 and 24, wherein about 4.25 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 58A. Embodiment 58A comprises a wet granulated pharmaceutical composition consisting essentially of: Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (a) about 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 9.71 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 30.1 wt % of the diluent of any one of embodiments 43 and 44; (e) about 4.85 wt % of the binder of any one of embodiments 23 and 24, wherein about 4.25 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) about 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 59. Embodiment 59 comprises a wet granulated pharmaceutical composition consisting of: (a) 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of a sprayed surfactant of any one of embodiments 37 and 38; (c) 9.71 wt % of a non-sprayed surfactant of any one of embodiments 37 and 38; (d) 30.1 wt % of a diluent of any one of embodiments 43 and 44; (e) 4.85 wt % of a binder of any one of embodiments 23 and 24, wherein about 4.25 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.37 wt % of a disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 59A. Embodiment 59A comprises a wet granulated pharmaceutical composition consisting of: (a) about 48.54 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 9.71 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 30.1 wt % of the diluent of any one of embodiments 43 and 44; (e) about 4.85 wt % of the binder of any one of embodiments 23 and 24, wherein about 4.25 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) about 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT wt % is based on total dry weight of the pharmaceutical composition. 60. Embodiment 60 comprises a wet granulated pharmaceutical composition comprising: (a) 10.75 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 1, 37, and 38; and (c) 0.26 wt % of the non-sprayed surfactant; of any one of embodiments 1, 37, and 38 wherein the sprayed and non-sprayed surfactants are the same or different and the dry wt / wt% ratio of Compound (I) Form A to combined weight of the sprayed and non-sprayed surfactants is 4:1. 61. Embodiment 61 comprises a wet granulated pharmaceutical composition comprising: (a) about 10.75 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of a sprayed surfactant; (c) about 0.26 wt % of a non-sprayed surfactant; (d) about 76.34 wt % of a diluent; (e) about 5.38 wt % of a binder; and (f) about 4.84 wt % of a disintegrant; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 62. Embodiment 62 comprises a wet granulated pharmaceutical composition comprising: (a) about 10.75 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 0.26 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 76.34 wt % of the diluent of any one of embodiments 43 and 44; (e) about 5.38 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.84 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) about 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 63. Embodiment 63 comprises a wet granulated pharmaceutical composition comprising: (a) 10.75 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 0.26 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 76.34 wt % of the diluent of any one of embodiments 43 and 44; (e) 5.38 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.84 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.37 wt % of the disintegrant of any one of embodments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 64. Embodiment 64 comprises a wet granulated pharmaceutical composition consisting essentially of: (a) 10.75 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 0.26 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 76.34 wt % of the diluent of any one of embodiments 43 and 44; (e) 5.38 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.84 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 64A. Embodiment 64A comprises a wet granulated pharmaceutical composition consisting essentially of: (a) about 10.75 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 0.26 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 76.34 wt % of the diluent of any one of embodiments 43 and 44; (e) about 5.38 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.84 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (f) about 4.37 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65. Embodiment 65 comprises a wet granulation pharmaceutical composition consisting of: (a) 10.75 wt % of the micronized Compound (I) Form A of any one of embodments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 0.26 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 76.34 wt % of the diluent of any one of embodiments 43 and 44; (e) 5.38 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.84 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.37 wt % of a disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65A. Embodiment 65A comprises a wet granulation pharmaceutical composition consisting of: (a) about 10.75 wt % of the micronized Compound (I) Form A of any one of embodments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 0.26 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 76.34 wt % of the diluent of any one of embodiments 43 and 44; (e) about 5.38 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.84 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) about 4.37 wt % of a disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65B. Embodiment 65B comprises a wet granulated pharmaceutical composition comprising: (a) 25.84 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 1, 37, and 38; and (c) 4.03 wt % of the non-sprayed surfactant; of any one of embodiments 1, 37, and 38 Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT wherein the sprayed and non-sprayed surfactants are the same or different and the dry wt / wt% ratio of Compound (I) Form A to combined weight of the sprayed and non-sprayed surfactants is 4:1. 65C. Embodiment 65C comprises a wet granulated pharmaceutical composition comprising: (a) about 25.84 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of a sprayed surfactant; (c) about 4.03 wt % of a non-sprayed surfactant; (d) about 57.88 wt % of a diluent; (e) about 5.17 wt % of a binder; and (f) about 4.65 wt % of a disintegrant; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65D. Embodiment 65D comprises a wet granulated pharmaceutical composition comprising: (a) about 25.84 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 4.03 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 57.88 wt % of the diluent of any one of embodiments 43 and 44; (e) about 5.17 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.56 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) about 4.65 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65E. Embodiment 65E comprises a wet granulated pharmaceutical composition comprising: (a) 25.84 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 4.03 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 57.88 wt % of the diluent of any one of embodiments 43 and 44; Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (e) 5.17 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.56 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.65 wt % of the disintegrant of any one of embodments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65F. Embodiment 65F comprises a wet granulated pharmaceutical composition consisting essentially of: (a) 25.84 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 4.03 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 57.88 wt % of the diluent of any one of embodiments 43 and 44; (e) 5.17 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.56 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.65 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65G. Embodiment 65G comprises a wet granulated pharmaceutical composition consisting essentially of: (a) about 25.84 wt % of the micronized Compound (I) Form A of any one of embodiments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 4.03 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 57.88 wt % of the diluent of any one of embodiments 43 and 44; (e) about 5.17 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.56 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) about 4.65 wt % of the disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65H. Embodiment 65H comprises a wet granulation pharmaceutical composition consisting of: (a) 25.84 wt % of the micronized Compound (I) Form A of any one of embodments 1 and 4B to 8; Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT (b) 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) 4.03 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) 57.88 wt % of the diluent of any one of embodiments 43 and 44; (e) 5.17 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.56 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) 4.65 wt % of a disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65I. Embodiment 65I comprises a wet granulation pharmaceutical composition consisting of: (a) about 25.84 wt % of the micronized Compound (I) Form A of any one of embodments 1 and 4B to 8; (b) about 2.43 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 4.03 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 57.88 wt % of the diluent of any one of embodiments 43 and 44; (e) about 5.17 wt % of the binder of any one of embodiments 23, and 24, wherein about 4.56 wt% is non-sprayed binder and about 0.61 wt % is sprayed binder; and (f) about 4.65 wt % of a disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. 65J. Embodiment 65J comprises a wet granulation pharmaceutical composition comprising, or consisting essentially of, or consisting of: (a) about 5 to 55 wt % of the micronized Compound (I) Form A of any one of embodments 1 and 4B to 8; (b) about 1 to 4 wt % of the sprayed surfactant of any one of embodiments 37 and 38; (c) about 0.1 to 15 wt % of the non-sprayed surfactant of any one of embodiments 37 and 38; (d) about 25 to 80 wt % of the diluent of any one of embodiments 43 and 44; (e) about 3.1 to 7 wt % of the binder of any one of embodiments 23, and 24, wherein about 3 to 6 wt% is non-sprayed binder and about 0.1 to 1 wt % is sprayed binder; and (f) about 3 to 6 wt % of a disintegrant of any one of embodiments 30 and 31; wherein the sprayed and non-sprayed surfactants are the same or different; and wt % is based on total dry weight of the pharmaceutical composition. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 66. Embodiment 66 comprises the pharmaceutical composition of any one of embodiments 1 to 65J, wherein the micronized Compound (I) Form A X-ray powder diffraction pattern comprises peaks at angular positions 15.8, 18.6, and 20.1, wherein the angular positions may vary by + 0.2o2θ. 67. Embodiment 67 comprises the pharmaceutical composition of any one of embodiments 1 to 65J, wherein the micronized Compound (I) Form A X-ray powder diffraction pattern comprises peaks at angular positions 12.9, 15.8, 18.6, and 20.1, wherein the angular positions may vary by + 0.2o2θ. 68. Embodiment 68 comprises the pharmaceutical composition of any one of embodiments 1 to 65J, wherein the micronized Compound (I) Form A X-ray powder diffraction pattern comprises peaks at angular positions 11.4, 12.9, 15.8, 18.6, and 20.1, wherein the angular positions may vary by + 0.2oθ. 69. Embodiment 69 comprises the pharmaceutical composition of any one of embodiments 1 to 65J, wherein the micronized Compound (I) Form A exhibits an X-ray powder diffraction pattern comprising at least one peak, at least two peaks, at least three peaks, at least four peaks, or at least five peaks, at least six peaks, or at least seven peaks, at angular positions shown in Table 1 below, wherein the angular positions may vary by + / - 0.2oθ in addition to those recited in such embodiments. For sake of clarity, peaks other than those always recited in the embodiments will be selected from the table below. Table 1 Angle (2-Theta °) d value (Å) Intensity % 92 959 69 Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 70. Embodiment 70 comprises the pharmaceutical composition of any one of embodiments 1 to 65J, wherein the micronized Compound (I) Form A comprises at least two, at least three, at least four, at least five, or at least six peaks selected from 10.1, 11.4, 12.9, 13.7, 15.8, 18.6, 19.6, 20.1, 21.4, 21.7, 25.0, and 26.0, wherein the angular positions may vary by + 0.2o2θ. 71. Embodiment 71 comprises the pharmaceutical composition of any one of embodiments 1 to 65J, wherein the micronized Compound (I) Form A X-ray powder diffraction pattern comprises peaks at angular positions substantially as shown in Fig.6. 72. Embodiment 72 comprises the pharmaceutical composition of any one of the embodiments 1 to 71, wherein the angular positions of the X-ray diffraction peaks denoted therein may vary by + 0.1o2θ. 73. Embodiment 73 comprises a 10 mg or 20 mg immediate release capsule comprising a wet granulated pharmaceutical composition of any one of embodiments 1 to 19, 23 to 25, 28 to 34, 38 to 40, 45, 46, 49 to 54, and 60 to 72 74. Embodiment 74 comprises a 50 mg to 300 mg immediate release capsule comprising a wet granulated pharmaceutical composition of any one of embodiments 1 to 18, 20 to to 27, 30, 31, 34a, 35 to 38, 41 to 44, 47 to 59, and 66 to 72. 75. Embodiment 75 comprises a method of treating a disease mediated by HIF-2α, comprising administering to a patient in need thereof the pharmaceutical composition of any one of embodiments 1 to 73 or the immediate release capsule of embodiments 73 or 74. 76. Embodiment 76 comprises the process of wet granulated composition of any one of embodiments 1 to 73, comprising: (1a) preparing a mixture of micronized Compound (I) Form A (or an embodiment thereof disclosed herein), a non-sprayed surfactant (or an embodiment thereof disclosed herein), a diluent (or an embodiment thereof disclosed herein), when present, a non-sprayed binder (or an embodiment thereof disclosed herein), when present, and a disintegrant, when present; (1b) spraying onto the mixture of step (1a) a granulating amount of water comprising a sprayed surfactant and a sprayed binder to form wet granules; (1c) drying the wet granulates of step (1b) to remove water; (1d) milling the granules from step (1c) to produce milled granules; (1e) sieving the milled granules from step (1d) to remove lumps or agglomerates; and (1f) optionally encapsulating granules obtained from step (1e). Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Utility Compound (I) and its Form A are useful for the treatment of HIF-2α mediated diseases, which include, but are not limited to, various types of cancers such as acanthoma, acinic cell carcinoma, acoustic neuroma, acral lentiginous melanoma, acrospiroma, acute eosinophilic leukemia, acute lymphoblastic leukemia, acute megakaryoblastic leukemia, acute monocytic leukemia, acute myeloblastic leukemia with maturation, acute myeloid dendritic cell leukemia, acute myeloid leukemia, acute promyelocytic leukemia, adamantinoma, adenocarcinoma, adenoid cystic carcinoma, adenoma, adenomatoid odontogenic tumor, adrenocortical carcinoma, adult T- cell leukemia, aggressive NK-cell leukemia, AIDS-related cancers, AIDS-related lymphoma, alveolar soft part sarcoma, ameloblastic fibroma, anal cancer, anaplastic large cell lymphoma, anaplastic thyroid cancer, angioimmunoblastic T-cell lymphoma, angiomyolipoma, angiosarcoma, appendix cancer, astrocytoma, atypical teratoid rhabdoid tumor, basal cell carcinoma, basal-like carcinoma, B-cell leukemia, B-cell lymphoma, bellini duct carcinoma, biliary tract cancer, bladder cancer, blastoma, bone cancer, bone tumor, brain stem glioma, brain tumor, breast cancer, brenner tumor, bronchial tumor, bronchioloalveolar carcinoma, brown tumor, Burkitt's lymphoma, carcinoid tumor, carcinoma, carcinosarcoma, Castleman's disease, central nervous system embryonal tumor, cerebellar astrocytoma, cerebral astrocytoma, cervical cancer, cholangiocarcinoma, chondroma, chondrosarcoma, chordoma, choriocarcinoma, choroid plexus papilloma, chronic lymphocytic leukemia, chronic monocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorder, chronic neutrophilic leukemia, clear cell renal cell carcinoma, clear-cell tumor, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, dermatofibrosarcoma protuberans, dermoid cyst, desmoplastic small round cell tumor, diffuse large B cell lymphoma, dysembryoplastic neuroepithelial tumor, embryonal carcinoma, endodermal sinus tumor, endometrial cancer, endometrial uterine cancer, endometrioid tumor, enteropathy -associated T-cell lymphoma, ependymoblastoma, ependymoma, epithelioid sarcoma, erythroleukemia, esophageal cancer, esthesioneuroblastoma, Ewing's sarcoma, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic bile duct cancer, extramammary Paget's disease, fallopian tube cancer, fibroma, fibrosarcoma, follicular lymphoma, follicular thyroid cancer, gallbladder cancer, ganglioglioma, ganglioneuroma, gastric cancer, gastric lymphoma, gastrointestinal cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, germ cell tumor, germinoma, gestational choriocarcinoma, gestational trophoblastic tumor, giant cell tumor of bone, glioblastoma multiforme, glioma, gliomatosis cerebri, glomus tumor, glucagonoma, Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT gonadoblastoma, granulosa cell tumor, hairy cell leukemia, head and neck cancer, heart cancer, hemangioblastoma, hemangiopericytoma, hemangiosarcoma, hematological malignancy, hepatocellular carcinoma, hepatosplenic T-cell lymphoma, Hodgkin lymphoma, hypopharyngeal cancer, hypothalamic glioma, inflammatory breast cancer, intraocular melanoma, islet cell carcinoma, juvenile myelomonocytic leukemia, Kaposi's sarcoma, kidney cancer, klatskin tumor, krukenberg tumor, laryngeal cancer, lentigo maligna melanoma, leukemia, lip and oral cavity cancer, liposarcoma, lung cancer, luteoma, lymphangioma, lymphangiosarcoma, lymphoepithelioma, lymphoid leukemia, lymphoma, macroglobulinemia, malignant fibrous histiocytoma, malignant glioma, malignant mesothelioma, malignant peripheral nerve sheath tumor, malignant rhabdoid tumor, malignant triton tumor, malt lymphoma, mantle cell lymphoma, mast cell leukemia, mediastinal germ cell tumor, mediastinal tumor, medullary thyroid cancer, medulloblastoma, medulloepithelioma, melanoma, meningioma, merkel cell carcinoma, mesothelioma, metastatic squamous neck cancer with occult primary, urothelial carcinoma, mixed mullerian tumor, monocytic leukemia, mouth cancer, mucinous tumor, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic disease, myeloid leukemia, myeloid sarcoma, myeloproliferative disease, myxoma, nasal cavity cancer, nasopharyngeal cancer, neoplasm, neurinoma, neuroblastoma, neurofibroma, neuroma, nodular melanoma, non-Hodgkin lymphoma, nonmelanoma skin cancer, non-small cell lung cancer, ocular oncology, oligoastrocytoma, oligodendroglioma, oncocytoma, optic nerve sheath meningioma, oral cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, ovarian epithelial cancer, ovarian germ cell tumor, ovarian low malignant potential tumor, pancoast tumor, pancreatic cancer, papillary thyroid cancer, papillomatosis, paraganglioma, paranasal sinus cancer, parathyroid cancer, penile cancer, perivascular epithelioid cell tumor, pharyngeal cancer, pheochromocytoma, pineal parenchymal tumor of intermediate differentiation, pineoblastoma, pituicytoma, pituitary adenoma, pituitary tumor, plasma cell neoplasm, pleuropulmonary blastoma, polyembryoma, precursor T-lymphoblastic lymphoma, primitive neuroectodermal tumor, prostate cancer, pseudomyxoma peritonei, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyoma, rhabdomyosarcoma, Richter's transformation, sacrococcygeal teratoma, salivary gland cancer, sarcoma, Schwann omatosis, sebaceous gland carcinoma, secondary neoplasm, seminoma, serous tumor, Sertoli-Leydig cell tumor, sex cord-stromal tumor, sezary syndrome, signet ring cell carcinoma, skin cancer, small blue round cell tumor, small cell carcinoma, small cell lung cancer, small cell lymphoma, small intestine cancer, soft tissue sarcoma, somatostatinoma, soot wart, spinal tumor, splenic marginal zone lymphoma, squamous Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT cell carcinoma, stomach cancer, superficial spreading melanoma, supratentorial primitive neuroectodermal tumor, surface epithelial-stromal tumor, synovial sarcoma, T-cell acute lymphoblastic leukemia, T-cell large granular lymphocyte leukemia, T-cell leukemia, T-cell lymphoma, T-cell prolymphocytic leukemia, teratoma, terminal lymphatic cancer, testicular cancer, thecoma, throat cancer, thymic carcinoma, thymoma, thyroid cancer, transitional cell cancer of renal pelvis and ureter, transitional cell carcinoma, urachal cancer, urethral cancer, urogenital neoplasm, uterine sarcoma, uveal melanoma, vaginal cancer, verner morrison syndrome, verrucous carcinoma, visual pathway glioma, vulvar cancer, Waldenstrom's macroglobulinemia, Warthin's tumor, Wilms' tumor, or any combination thereof. In some embodiments, the methods comprising administering a HIF-2a inhibitor disclosed herein and an immunotherapeutic agent described herein are applied to the treatment of cancers of the adrenal glands, blood, bone marrow, brain, breast, cervix, colon, head and neck, kidney (e.g., ccRCC), liver (e.g., hepatocellular carcinoma), bladder (e..g, muscle invasive bladder cancer), lung, ovary, pancreas, plasma cells, rectum, retina, skin, spine, throat, or any combination thereof. Combinations and Combination Therapies Compound (I) or Compound (I) Form A may be used in combination with one or more other drugs in the treatment of diseases or conditions for which Compound (I) or Compound (I) Form A or the other drugs may have utility. Such other drug(s) may be administered by a route and in an amount commonly used therefore, contemporaneously, or sequentially, with Compound (I) or Compound (I) Form A. When Compound (I) or Compound (I) Form A is used contemporaneously with the one or more other drugs, a pharmaceutical composition in unit dosage form containing such other drugs and Compound (I) or Compound (I) Form A is preferred. However, the combination therapy may also include therapies in which Compound (I) or Compound (I) Form A and the one or more other drugs are administered on different overlapping schedules. It is also contemplated that, when used in combination with one or more other active ingredients, Compound (I) or Compound (I) Form A and the other active ingredients may be used in lower doses than when each is used singly. Accordingly, the pharmaceutical compositions of the present disclosure also include those that contain one or more other drugs, in addition to Compound (I) or Compound (I) Form A. The above combinations include combinations of Compound (I) or Compound (I) Form A not only with one other drug, but also with two or more other active drugs. Likewise, Compound (I) or Compound (I) Form A may be used in combination with other drugs that are used in the prevention, treatment, control, amelioration, or reduction of risk of the diseases or conditions for Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT which a compound of this disclosure is useful. Such other drugs may be administered by a route and in an amount commonly used therefore, contemporaneously, or sequentially, with Compound (I) or Compound (I) Form A. When Compound (I) or Compound (I) Form A is used contemporaneously with one or more other drugs, a pharmaceutical composition containing such other drugs in addition to Compound (I) or Compound (I) Form A can be used. Accordingly, the pharmaceutical compositions of the present disclosure also include those that also contain one or more other active ingredients, in addition to Compound (I) or Compound (I) Form A. The weight ratio of Compound (I) or Compound (I) Form A to the second active ingredient may be varied and will depend upon the effective dose of each ingredient. Generally, an effective dose of each ingredient will be used. Where the subject in need is suffering from or at risk of suffering from cancer, the subject may be treated with Compound (I) or Compound (I) Form A in any combination with one or more other anti-cancer agents. In some embodiments, one or more of the anti-cancer agents are proapoptotic agents. Examples of anti-cancer agents include, but are not limited to, any of the following: gossyphol, genasense, polyphenol E, Chlorofusin, all trans-retinoic acid (ATRA), bryostatin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), 5-aza-2’- deoxycytidine, all trans retinoic acid, doxorubicin, vincristine, etoposide, gemcitabine, imatinib (GleevecTM), geldanamycin, 17-N-Allylamino-17-Demethoxygeldanamycin (17-AAG), flavopiridol, LY294002, bortezomib, trastuzumab, BAY 11-7082, PKC412, or PD184352, TaxolTM, also referred to as “paclitaxel”, which is a well-known anti-cancer drug that acts by enhancing and stabilizing microtubule formation, and analogs of TaxolTM, such as TaxotereTM. Compounds that have the basic taxane skeleton as a common structure feature have also been shown to have the ability to arrest cells in the G2-M phases by stabilizing microtubules and may be useful for treating cancer in combination with the compounds described herein. Suitable anti-cancer agents also include inhibitors of kinase-associated cell proliferative disorders. These kinases include, but are not limited to, Aurora-A, BTK, CDK1, CDK2, CDK3, CDK4, CDK6, CDK5, CDK7, CDK8, CDK9, ephrin receptor kinases, CHK1, CHK2, SRC, Yes, Fyn, Lck, Fer, Fes, Syk, Itk, Bmx, GSK3, JNK, MEK, PAK1, PAK2, PAK3, PAK4, PDK1, PKA, PKC, RAF, Rsk and SGK. In particular, inhibitors of CDK4 / 6, including abemaciclib (Verzenio), palbociclib (Ibrance), dalpiciclib, and ribociclib (Kisqali), have the potential to be synergistic with HIF-2α inhibitors and reverse the resistance to HIF-2α inhibition; mitogen-activated protein kinase signaling, e.g., U0126, PD98059, PD184352, PD0325901, ARRY-142886, SB239063, SP600125, BAY 43-9006, wortmannin, or LY294002; Syk inhibitors; antibodies (e.g., rituxan); Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT MET inhibitors, such as foretinib, carbozantinib, or crizotinib; VEGFR inhibitors, such as sunitinib, sorafenib, regorafinib, lenvatinib, vandetanib, carbozantinib, axitinib; EGFR inhibitors, such as afatinib, brivanib, carbozatinib, erlotinib, gefitinib, neratinib, lapatinib; PI3K inhibitors, such as XL147, XL765, BKM120 (buparlisib), GDC-0941, BYL719, IPI145, BAY80-6946. BEX235 (dactolisib), CAL101 (idelalisib), GSK2636771, TG100-115; MTOR inhibitor such as rapamycin (sirolimus), temsirolimus, everolimus, XL388, XL765, AZD2013, PF04691502, PKI- 587, BEZ235, GDC0349; MEK inhibitors, such as AZD6244, trametinib, PD184352, pimasertinib, GDC-0973, AZD8330; CSF1R inhibitors (PLX3397, LY3022855, etc.) and CSF1R antibodies (IMC-054, RG7155, etc); TGF beta receptor kinase inhibitors, such as LY2157299; and BTK inhibitor, such as ibrutinib. Other anti-cancer agents include proteasome inhibitors, such as carfilzomib, MLN9708, delanzomib, and bortezomib; BET inhibitors, such as INCB054329, OTX015, CPI-0610; LSD1 inhibitors, such as GSK2979552, INCB059872; HDAC inhibitors, such as panobinostat, vorinostat; DNA methyl transferase inhibitors, such as azacytidine, decitabine, and other epigenetic modulators; SHP-2 inhibitors, such as TNO155; Bcl2 inhibitor ABT-199, and other Bcl-2 family protein inhibitors; Beta catenin pathway inhibitors, notch pathway inhibitors, and hedgehog pathway inhibitors; and antibodies or other therapeutic proteins against VEGF, including bevacizumab and aflibercept. Other anti-cancer agents / drugs that may be used in combination with the compounds of the disclosure include, but are not limited to, liver X receptor (LXR) modulators, including LXR agonists and LXR beta-selective agonists; and aryl hydrocarbon receptor (AhR) inhibitors. Other anti-cancer agents that may be employed in combination with Compound (I) or Compound (I) Form A include, but are not limited to, Adriamycin; Dactinomycin; Bleomycin; Vinblastine; Cisplatin; acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin; aldesleukin; altretamine; ambomycin; ametantrone acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacitidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin; bleomycin sulfate; brequinar sodium; bropirimine; busulfan; cactinomycin; calusterone; caracemide; carbetimer; carboplatin; carmustine; carubicin hydrochloride; carzelesin; cedefingol; chlorambucil; cirolemycin; cladribine; crisnatol mesylate; cyclophosphamide; cytarabine; dacarbazine; daunorubicin hydrochloride; decitabine; dexormaplatin; dezaguanine; dezaguanine mesylate; diaziquone; doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone propionate; duazomycin; edatrexate; eflornithine hydrochloride; elsamitrucin; Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT enloplatin; enpromate; epipropidine; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride; estramustine; estramustine phosphate sodium; etanidazole; etoposide; etoposide phosphate; etoprine; fadrozole hydrochloride; fazarabine; fenretinide; floxuridine; fludarabine phosphate; fluorouracil; flurocitabine; fosquidone; fostriecin sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamide; ilmofosine; interleukin II (including recombinant interleukin II, or Ril2), interferon alfa-2a; interferon alfa-2b; interferon alfa-n1; interferon alfa-n3; interferon beta-1a; interferon gamma-1 b; iproplatin; irinotecan hydrochloride; lanreotide acetate; letrozole; leuprolide acetate; liarozole hydrochloride; lometrexol sodium; lomustine; losoxantrone hydrochloride; masoprocol; maytansine; mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate; melphalan; menogaril; mercaptopurine; methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide; mitocarcin; mitocromin; mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone hydrochloride; mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxisuran; pegaspargase; peliomycin; pentamustine; peplomycin sulfate; perfosfamide; pipobroman; piposulfan; piroxantrone hydrochloride; plicamycin; plomestane; porfimer sodium; porfiromycin; prednimustine; procarbazine hydrochloride; puromycin; puromycin hydrochloride; pyrazofurin; riboprine; rogletimide; safingol; safingol hydrochloride; semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulofenur; talisomycin; tecogalan sodium; tegafur; teloxantrone hydrochloride; temoporfin; teniposide; teroxirone; testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; toremifene citrate; trestolone acetate; triciribine phosphate; trimetrexate; trimetrexate glucuronate; triptorelin; tubulozole hydrochloride; uracil mustard; uredepa; vapreotide; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate; vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin; zinostatin; and zorubicin hydrochloride. Other anti-cancer agents that may be employed in combination with Compound (I) or Compound (I) Form A include, but are not limited, 20-epi-1, 25 dihydroxyvitamin D3; 5- ethynyluracil; abiraterone; aclarubicin; acylfulvene; adecypenol; adozelesin; aldesleukin; ALL-TK antagonists; altretamine; ambamustine; amidox; amifostine; aminolevulinic acid; amrubicin; amsacrine; anagrelide; anastrozole; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-dorsalizing morphogenetic protein-1; antiandrogen, prostatic carcinoma; antiestrogen; antineoplaston; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators; apurinic acid; ara-CDP-DL-PTBA; arginine Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT deaminase; asulacrine; atamestane; atrimustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin; azatyrosine; baccatin III derivatives; balanol; batimastat; BCR / ABL antagonists; benzochlorins; benzoylstaurosporine; beta lactam derivatives; beta-alethine; betaclamycin B; betulinic acid; Bfgf inhibitor; bicalutamide; bisantrene; bisaziridinylspermine; bisnafide; bistratene A; bizelesin; breflate; bropirimine; budotitane; buthionine sulfoximine; calcipotriol; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carboxamide- amino-triazole; carboxyamidotriazole; CaRest M3; CARN 700; cartilage derived inhibitor; carzelesin; casein kinase inhibitors (ICOS); castanospermine; cecropin B; cetrorelix; chlorlns; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrin; cladribine; clomifene analogues; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogue; conagenin; crambescidin 816; crisnatol; cryptophycin 8; cryptophycin A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfate; cytolytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin; dexamethasone; dexifosfamide; dexrazoxane; dexverapamil; diaziquone; didemnin B; didox; diethylnorspermine; dihydro-5-azacytidine; 9-dioxamycin; diphenyl spiromustine; docosanol; dolasetron; doxifluridine; droloxifene; dronabinol; duocarmycin SA; ebselen; ecomustine; edelfosine; edrecolomab; eflomithine; elemene; emitefur; epirubicin; epristeride; estramustine analogue; estrogen agonists; estrogen antagonists; etanidazole; etoposide phosphate; exemestane; fadrozole; fazarabine; fenretinide; filgrastim; fmasteride; flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunorunicin hydrochloride; forfenimex; formestane; fostriecin; fotemustine; gadolinium texaphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitors; gemcitabine; glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; hypericin; ibandronic acid; idarubicin; idoxifene; idramantone; ilmofosine; ilomastat; imidazoacridones; imiquimod; immunostimulant peptides; insulin-like growth factor-1 receptor inhibitor; interferon agonists; interferons; interleukins; iobenguane; iododoxorubicin; ipomeanol, 4-; iroplact; irsogladine; isobengazole; isohomohalicondrin B; itasetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; lenograstim; lentinan sulfate; leptolstatin; letrozole; leukemia inhibiting factor; leukocyte alpha interferon; leuprolide+estrogen+progesterone; leuprorelin; levamisole; liarozole; linear polyamine analogue; lipophilic disaccharide peptide; lipophilic platinum compounds; lissoclinamide 7; lobaplatin; lombricine; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lurtotecan; lutetium texaphyrin; lysofylline; lytic peptides; maitansine; mannostatin A; marimastat; masoprocol; maspin; matrilysin inhibitors; matrix metalloproteinase inhibitors; menogaril; merbarone; meterelin; methioninase; metoclopramide; Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT MIF inhibitor; mifepristone; miltefosine; mirimostim; mismatched double stranded RNA; mitoguazone; mitolactol; mitomycin analogues; mitonafide; mitotoxin fibroblast growth factor- saporin; mitoxantrone; mofarotene; molgramostim; monoclonal antibody, human chorionic gonadotrophin; mopidamol; multiple drug resistance gene inhibitor; multiple tumor suppressor 1- based therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall extract; myriaporone; N-acetyldinaline; N-substituted benzamides; nafarelin; nagrestip; naloxone+pentazocine; napavin; naphterpin; nartograstim; nedaplatin; nemorubicin; neridronic acid; neutral endopeptidase; nilutamide; nisamycin; nitric oxide modulators; nitroxide antioxidant; nitrullyn; O6-benzylguanine; octreotide; okicenone; oligonucleotides; onapristone; ondansetron; ondansetron; oracin; oral cytokine inducer; ormaplatin; osaterone; oxaliplatin; oxaunomycin; palauamine; palmitoylrhizoxin; pamidronic acid; panaxytriol; panomifene; parabactin; pazelliptine; pegaspargase; peldesine; pentosan polysulfate sodium; pentostatin; pentrozole; perflubron; perfosfamide; perillyl alcohol; phenazinomycin; phenylacetate; phosphatase inhibitors; picibanil; pilocarpine hydrochloride; pirarubicin; piritrexim; placetin A; placetin B; plasminogen activator inhibitor; platinum complex; platinum compounds; platinum-triamine complex; porfimer sodium; porfiromycin; prednisone; propyl bis-acridone; prostaglandin J2; proteasome inhibitors; protein A-based immune modulator; protein kinase C inhibitors, microalgal; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; purpurins; pyrazoloacridine; pyridoxylated hemoglobin polyoxyethylerie conjugate; raf antagonists; raltitrexed; ramosetron; ras farnesyl protein transferase inhibitors; ras inhibitors; ras- GAP inhibitor; retelliptine demethylated; rhenium Re 186 etidronate; rhizoxin; ribozymes; R.sub.11 retinamide; rogletimide; rohitukine; romurtide; roquinimex; rubiginone B1; ruboxyl; safingol; saintopin; SarCNU; sarcophytol A; sargramostim; SDI 1 mimetics; semustine; senescence derived 1; sense oligonucleotides; signal transduction inhibitors; signal transduction modulators; single chain antigen-binding protein; sizofuran; sobuzoxane; sodium borocaptate; sodium phenylacetate; solverol; somatomedin binding protein; sonermin; sparfosic acid; spicamycin D; spiromustine; splenopentin; spongistatin 1; squalamine; stem cell inhibitor; stem- cell division inhibitors; stipiamide; stromelysin inhibitors; sulfinosine; superactive vasoactive intestinal peptide antagonist; suradista; suramin; swainsonine; synthetic glycosaminoglycans; tallimustine; tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; temoporfin; temozolomide; teniposide; tetrachlorodecaoxide; tetrazomine; thaliblastine; thiocoraline; thrombopoietin; thrombopoietin mimetic; thymalfasin; thymopoietin receptor agonist; thymotrinan; thyroid stimulating hormone; Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT tin ethyl etiopurpurin; tirapazamine; titanocene bichloride; topsentin; toremifene; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; trimetrexate; triptorelin; tropisetron; turosteride; tyrosine kinase inhibitors; tyrphostins; UBC inhibitors; ubenimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonists; vapreotide; variolin B; vector system, erythrocyte gene therapy; velaresol; veramine; verdins; verteporfin; vinorelbine; vinxaltine; vitaxin; vorozole; zanoterone; zeniplatin; zilascorb; and zinostatin stimalamer. Yet other anticancer agents that may be employed in combination with Compound (I) or Compound (I) Form A include alkylating agents, antimetabolites, natural products, or hormones, e.g., nitrogen mustards (e.g., mechloroethamine, cyclophosphamide, chlorambucil, etc.), alkyl sulfonates (e.g., busulfan), nitrosoureas (e.g., carmustine, lomusitne, etc.), or triazenes (decarbazine, etc.). Examples of antimetabolites include, but are not limited to, folic acid analogs (e.g., methotrexate) pyrimidine analogs (e.g., cytarabine), and purine analogs (e.g., mercaptopurine, thioguanine, pentostatin). Examples of natural products useful in combination with Compound (I) or Compound (I) Form A include, but are not limited to, vinca alkaloids (e.g., vincristine), epipodophyllotoxins (e.g., etoposide), antibiotics (e.g., daunorubicin, doxorubicin, bleomycin), enzymes (e.g., L- asparaginase), and biological response modifiers (e.g., interferon alpha). Examples of alkylating agents that may be employed in combination with Compound (I) or Compound (I) Form A include, but are not limited to, nitrogen mustards (e.g., mechloroethamine, cyclophosphamide, chlorambucil, melphalan, etc.), ethylenimine and methylmelamines (e.g., hexamethlymelamine, thiotepa), alkyl sulfonates (e.g., busulfan), nitrosoureas (e.g., carmustine, lomusitne, semustine, streptozocin, etc.), and triazenes (decarbazine, etc.). Examples of antimetabolites include, but are not limited to, folic acid analogs (e.g., methotrexate), pyrimidine analogs (e.g., fluorouracil, floxuridine, cytarabine), purine analogs (e.g., mercaptopurine, thioguanine, pentostatin). Examples of hormones and antagonists useful in combination with Compound (I) or Compound (I) Form A include, but are not limited to, adrenocorticosteroids (e.g., prednisone), progestins (e.g., hydroxyprogesterone caproate, megestrol acetate, medroxyprogesterone acetate), estrogens (e.g., diethylstilbestrol, ethinyl estradiol), antiestrogens (e.g., tamoxifen), androgens (e.g., testosterone propionate, fluoxymesterone), antiandrogens (e.g., flutamide), and gonadotropin releasing hormone analogs (e.g., leuprolide). Other agents that may be used in the methods and compositions described herein for the treatment or prevention of cancer include, but are not Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT limited to, platinum coordination complexes (e.g., cisplatin, carboblatin), anthracenediones (e.g., mitoxantrone), substituted urea (e.g., hydroxyurea), methyl hydrazine derivatives (e.g., procarbazine), and adrenocortical suppressants (e.g., mitotane, aminoglutethimide). Other anti-cancer agents that may be employed in combination with Compound (I) or Compound (I) Form A include, but are not limited anti-cancer agents which act by arresting cells in the G2-M phases by stabilizing microtubules and include Erbulozole (also known as R-55104), Dolastatin 10 (also known as DLS-10 and NSC-376128), Mivobulin isethionate (also known as CI-980), Vincristine, NSC-639829, Discodermolide (also known as NVP-XX-A-296), ABT-751 (Abbott, also known as E-7010), Altorhyrtins (such as Altorhyrtin A and Altorhyrtin C), Spongistatins (such as Spongistatin 1, Spongistatin 2, Spongistatin 3, Spongistatin 4, Spongistatin 5, Spongistatin 6, Spongistatin 7, Spongistatin 8, and Spongistatin 9), Cemadotin hydrochloride (also known as LU-103793 and NSC-D-669356), Epothilones (such as Epothilone A, Epothilone B, Epothilone C (also known as desoxyepothilone A or dEpoA), Epothilone D (also referred to as KOS-862, dEpoB, and desoxyepothilone B), Epothilone E, Epothilone F, Epothilone B N-oxide, Epothilone A N-oxide, 16-aza-epothilone B, 21-aminoepothilone B (also known as BMS-310705), 21-hydroxyepothilone D (also known as Desoxyepothilone F and dEpoF), 26-fluoroepothilone), Auristatin PE (also known as NSC-654663), Soblidotin (also known as TZT-1027), LS-4559-P (Pharmacia, also known as LS-4577), LS-4578 (Pharmacia, also known as LS-477-P), LS-4477 (Pharmacia), LS-4559 (Pharmacia), RPR-112378 (Aventis), Vincristine sulfate, DZ-3358 (Daiichi), FR-182877 (Fujisawa, also known as WS-9885B), GS-164 (Takeda), GS-198 (Takeda), KAR-2 (Hungarian Academy of Sciences), BSF-223651 (BASF, also known as ILX-651 and LU- 223651), SAH-49960 (Lilly / Novartis), SDZ-268970 (Lilly / Novartis), AM-97 (Armad / Kyowa Hakko), AM-132 (Armad), AM-138 (Armad / Kyowa Hakko), IDN-5005 (Indena), Cryptophycin 52 (also known as LY-355703), AC-7739 (Ajinomoto, also known as AVE-8063A and CS- 39.HCl), AC-7700 (Ajinomoto, also known as AVE-8062, AVE-8062A, CS-39-L-Ser.HCl, and RPR-258062A), Vitilevuamide, Tubulysin A, Canadensol, Centaureidin (also known as NSC- 106969), T-138067 (Tularik, also known as T-67, TL-138067 and TI-138067), COBRA-1 (Parker Hughes Institute, also known as DDE-261 and WHI-261), H10 (Kansas State University), H16 (Kansas State University), Oncocidin A1 (also known as BTO-956 and DIME), DDE-313 (Parker Hughes Institute), Fijianolide B. Laulimalide, SPA-2 (Parker Hughes Institute), SPA-1 (Parker Hughes Institute, also known as SPIKET-P), 3-IAABU (Cytoskeleton / Mt. Sinai School of Medicine, also known as MF-569), Narcosine (also known as NSC-5366), Nascapine, D-24851 (Asta Medica), A-105972 (Abbott), Hemiasterlin, 3-BAABU (Cytoskeleton / Mt. Sinai School of Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Medicine, also known as MF-191), TMPN (Arizona State University), Vanadocene acetylacetonate, T-138026 (Tularik), Monsatrol, Inanocine (also known as NSC-698666), 3-1AABE (Cytoskeleton / Mt. Sinai School of Medicine), A-204197 (Abbott), T-607 (Tuiarik, also known as T-900607), RPR-115781 (Aventis), Eleutherobins (such as Desmethyleleutherobin, Desaetyleleutherobin, Isoeleutherobin A, and Z-Eleutherobin), Caribaeoside, Caribaeolin, Halichondrin B, D-64131 (Asta Medica), D-68144 (Asta Medica), Diazonamide A, A-293620 (Abbott), NPI-2350 (Nereus), Taccalonolide A, TUB-245 (Aventis), A-259754 (Abbott), Diozostatin, (-)-Phenylahistin (also known as NSCL-96F037), D-68838 (Asta Medica), D-68836 (Asta Medica), Myoseverin B, D-43411 (Zentaris, also known as D-81862), A-289099 (Abbott), A-318315 (Abbott), HTI-286 (also known as SPA-110, trifluoroacetate salt) (Wyeth), D-82317 (Zentaris), D-82318 (Zentaris), SC-12983 (NCI), Resverastatin phosphate sodium, BPR-OY-007 (National Health Research Institutes), and SSR-250411 (Sanofi). One or more additional immune checkpoint inhibitors may be used in combination with Compound (I) or Compound (I) Form A for treatment of HIF-2α-associated diseases, disorders, or conditions. Exemplary immune checkpoint inhibitors include, but are not limited, inhibitors (smack molecules or biologics) against immune checkpoint molecules such as CD27, CD28, CD40, CD122, CD96, CD73, CD39, CD47, OX40, GITR, CSF1R, JAK, PI3K delta, PI3K gamma, TAM, arginase, CD137 (also known as 4-1BB), ICOS, A2AR, A2BR, SHP-2, B7-H3, B7-H4, BTLA, CTLA-4, LAG3, TIM3, VISTA, CD96, TIGIT, PD-1, PD-L1, and PD-L2. In some embodiments, the immune checkpoint molecule is a stimulatory checkpoint molecule selected from CD27, CD28, CD40, ICOS, OX40, GITR, CD137, and STING. In some embodiments, the immune checkpoint molecule is an inhibitory checkpoint molecule selected from B7-H3, B7-H4, BTLA, CTLA-4, IDO, TDO, Arginase, KIR, LAG3, PD-1, TIM3, CD96, TIGIT, and VISTA. In some embodiments, the compounds provided herein can be used in combination with one or more agents selected from KIR inhibitors, TIGIT inhibitors, LAIR1 inhibitors, CD160 inhibitors, 2B4 inhibitors, and TGFR beta inhibitors. In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-1, e.g., an anti-PD-1 monoclonal antibody. In some embodiments, the anti-PD-1 monoclonal antibody is nivolumab, pembrolizumab (also known as MK-3475), pidilizumab, SHR-1210, PDR001, or AMP-224. In some embodiments, the anti-PD-1 monoclonal antibody is nivolumab, or pembrolizumab or PDR001. In some embodiments, the anti-PD1 antibody is pembrolizumab. In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-L1, e.g., an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT monoclonal antibody is BMS-935559, MEDI4736, MPDL3280A (also known as RG7446), or MSB0010718C. In some embodiments, the anti-PD-L1 monoclonal antibody is MPDL3280A (atezolizumab) or MEDI4736 (durvalumab). In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CTLA-4, e.g., an anti-CTLA-4 antibody. In some embodiments, the anti-CTLA-4 antibody is ipilimumab or tremelimumab. In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of LAG3, e.g., an anti-LAG3 antibody. In some embodiments, the anti- LAG3 antibody is BMS-986016 or LAG525. In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of GITR, e.g., an anti-GITR antibody. In some embodiments, the anti-GITR antibody is TRX518, MK-4166, INCAGN01876, or MK-1248. In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of OX40, e.g., an anti-OX40 antibody or OX40L fusion protein. In some embodiments, the anti-OX40 antibody is MEDI0562, INCAGN01949, GSK2831781, GSK-3174998, MOXR-0916, PF-04518600, or LAG525. In some embodiments, the OX40L fusion protein is MEDI6383. In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-1, e.g. an anti-PD-1 antibody. In some embodiments, the anti-PD-1 antibody is sasanlimab, cemiplimab-rwlc, nivolumab, pembrolizumab, dostarlimab, vopratelimab, spartalizumab, camrelizumab, sintilimab, tislelizumab (BGB-A287), toripalimab, INCMGA00012 (MGA012), AMP-224, AMP-514 (MEDI0680), acrixolimab (YBL-006) atezolizumab, durvalumab, avelumab, KN035, Cosibelimab, AUNP12, CA-170, or BMS-986189. Compound (I) or Compound (I) Form A may also be used to increase or enhance an immune response, including increasing the immune response to (1) an antigen, (2) to improve immunization, such as, for example, by enhancing vaccine efficacy, or (3) to increase inflammation. In some embodiments, Compound (I) or Compound (I) Form A may be ued to enhance the immune response to vaccines including, but are not limited to, Listeria vaccines, oncolytic viral vaccines, and cancer vaccines, such as GVAX® (granulocyte-macrophage colony- stimulating factor (GM-CF) gene-transfected tumor cell vaccine). Anti-cancer vaccines include, but are not limited to, dendritic cells, synthetic peptides, DNA vaccines, and recombinant viruses. Other immune-modulatory agents may also include those that block immune cell migration, such as antagonists to chemokine receptors, including CCR2 and CCR4, Sting agonists, and Toll receptor agonists. Other anti-cancer agents may also include those that augment the immune system, such as adjuvants or adoptive T cell transfer. Compounds of this application may be effective in Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT combination with CAR (Chimeric antigen receptor) T cell treatment as a booster for T cell activation. Examples The following examples are merely illustrative of the disclosure and should not be considered to limit the scope of the invention in any way, as these examples and equivalents thereof will become apparent to those skilled in the art in light of the present disclosure and the accompanying claims. Example 1 Micronization of Compound (I) Form A After turning on the stainless-steel Jet Mill (Make: DEC group; Model: MC-150), the nitrogen valve and Ventrui pressure and ring pressure were set according to parameters in Table 2 below and run idly for about 3 min. The feeder hopper was turned on and the feed rate was set as disclosed in Table 2. Solid Compound (I) Form A was placed in feeder hopper and then charged into the micronization chamber under a preset speed of 50.00 gr / min. After all of Compound (I) Form A was charged, the feeder was switched off and the circulating load of micronized Compound (I) Form A in the micronization chamber urged with nitrogen for 5 min. Particle size distribution (PSD) analysis on micronized batches of Compound (I) Form A was done as described in Example 2 below. The PSD resulting from several representative batches of micronized Compound (I) Form A are shown in Table 2. Table 2 Batch No.Micronization ParametersPSD (µm) after micronizationBatch #1Venturi pressure: 80 bar; ring pressure:D10: 2 D50: 5 D90: 10 Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Example 2 Determiantion of Particle size distribution (PSD) determination of Micronized Compound (I) Form A Particle size distribution (PSD) of micronized Compound (I) Form A was determined as follows: 1. Instruments and Equipments Malvern Mastersizer 3000 and Hydro MV Vortex mixer Ultrasonic Bath Analytical balance (capable of reading to 0.01mg) 50 mL volumetric flask or equivalent volumetric 100 mL volumetric flask or equivalent volumetric 2. Reagents and samples Dispersant: Lecithin, AR or equivalent (Purchased from TCI, Catalog #：L0023) Isopar G (Purchased from Heyuan City Sheng Xing Xing Co., Ltd.) Micronized Compound (I) Form A 3. Test Procedure (wet dispersion) Dispersant Isopar G Pre-dispersant [0.1% (m / v) lecithin-Isopar G] For example, weigh 100 mg of lecithin to a 100-mL volumetric flask containing about 20 mL of Isopar G, sonicate, if necessary, dissolve and dilute to volume with Isopar G. 4. Operating Procedure and Sample Preparation Table 2A Mastersizer 3000 Setting Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Before measurement, the background should be clean and stable. SOP with parameters were set as disclosed in Table 2A above. Dispersant was added into a sample cell. The detector was aligned and, the background (blank) was measured with dispersant in the cell with the control speed set. Approximately 200 mg of micronized Compound (I) Form A was transferred into a 50 mL volumetric flask.10 mL Isopar G and 200 μL pre-dispersant were added, rinsing all micronized Compound (I) Form A to the bottom of the flask. The slurry was vortexed for 1 min and sonicated externally (50W, 100%) for 1 min. The sample slurry was added into the sample cell slowly while avoiding bubbles. The sample was analyzed by pressing “Measurement” after the obscuration level reached a target of 20%. After waiting 120 sec, the obscuration was stable at around 15% because the sample was slightly soluble in Isopar G. Formulations of Compound (I) Form A For all Capsule formulations, equipment listed in Table 3 was used: Table 3 Example 3 Effect of Micronization of Compound (I) Form A on its Dissolution in Simulated Gastric Fluid (SGF) To test the effect of micronization of Compound (I) A on its dissolution profile in SGF, the Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT following study was conducted. 1. Preparation of Capsule containing formulations comprising unmicronized or micronized Compound (I) Form a. Composition of formulations containing unmicronized Compound (I) Form A (F1) and micronized Compound (I) Form A (F2) are disclosed in Table 4 below: Table 4 Dry blend, without surfactants mg per Capsule 1. Weighed Lactose was added into a mortar and mixed with pestle for 2 min and ensuring that the inner wall of mortar was coated with excipient. 2. Weighed micronized or unmicronized Compound (I) Form A was added into the mortar. 3. Weighed Crospovidone was added into the mortar and the mixture and mixed with Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT pestle for 2 min. 4. The blend was screened through #40 mesh. 5. The blend from Step 4 was compressed into slugs with 1400 psi and hardness of slugs was recorded. 6. The slugs were crushed gently in a mortar and pestle to give intra-granule mixture. 7. The intra-granule mixture was screened through #40 mesh. 8. The screened intra-granule mixture was weighed and theoretical weight for extra granular excipients was adjusted. 9. Weighed MCC were added into a mortar and mixed with pestle for 1 min. 10. Weighed silica was added into the blend of Step 9 and mixed for 1 min. 11. The blend was passed through #40 mesh to give extra-granular blend. 12. Intra-granular blend was added to extra-granular blend and mixed for 2 min. 13. Weighed Magnesium Stearate was screened through #40 mesh, added to the blend of Step 12 and mixed for 2 min. 14. Final blend was filled into 3 size 0 capsules. 2. Dissolution Test and Profile of F1 and F2 in SGF One capsule of each F1 and F2 was tested in simulated gastric fluid media without enzyme (SGF, pH 1.6; Figure 1) under dissolution parameters described in Table 5 below. Table 5 Dissolution Parameters Media Modified SGF (without enzyme) pH 1.6 Volume 900 mL Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Result: As seen in Fig 1., micronization of the Compound (I) Form A provided almost 4X increase in release of Compound (I) relative to unmicronized Compound (I) Form (F1). Based on results of Example 3, micronized Compound (I) Form A was used in the formulations below. Example 4 Effect of Surfactant on Dissolution of Micronized Compound (I) Form A in Simulation Gastric Fluid (SGF) Surfactants sodium lauryl sulfate and Soluplus (Polyvinyl caprolactam–polyvinyl acetate– polyethylene glycol graft copolymer) were tested to determine effects of surfactants on dissolution of micronized Compound (I) Form A as follows. 1. Preparation of Capsule containing formulations comprising micronized Compound (I) Form A and sodium lauryl sulfate (F3) or Soluplus (F4) a. Composition of Capsule formulations comprising micronized Compound (I) Form A with SLS (F3) or Soluplus (F4) are disclosed in Table 6 below: Table 6 Dry Blend with Surfactant mg per Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT b. Preparation of Formulations (F3) and (F4): 1. Weighed MCC, Lactose monohydrate and and SLS or Soluplus were added into a mortar and mixed with pestle for 2 min, making sure the inner wall of mortar was coated with excipients. Weighed micronized Compound (I) Form A was added, followed by addition of weighed Crospovidone. The mixture was mixted with pestle for 2 min and then screened through #40 mesh. 2. The blend was compressed into slugs and the slugs were crushed in a mortar and pestle. 3. The blend was screened through #40 mesh to give intra-granule mixture which was weighed. Theoretical weight of extragranular excipients was adjusted. 4. Weighed Crospovidone was added into mortar. Mix with pestle for 1 min. 5. Weighed Silica was added to the blend from Step 4, mixed for 1 min, and then screened through #40 mesh to give extra-granular blend. 6. Intra-granular blend was added to the extra-granular blend and then mixed for 2 min. 7. Weighed Magnesium Stearate was screened through #40 mesh and added to the blend of Step 6 and the blend was mixed for 2 min. 8. 360 mg of the final blend was filled into 3 size 0 capsules. 2. Dissolution Test and Profile of F3 and F4 in SGF One capsule each of F3 and F4 formulations was tested in a simulated gastric fluid media without enzyme (SGF, pH 1.6). The capsules were simultaneously tested in SGF media containing 0.1% polysorbate 80 (see figure 2) and compared against the F1 and F2 formulations. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Dissolution Parameters Result: As seen in Fig.2, formulation containing micronized Compound (I) Form A and sodium lauryl sulfate (SLS) surfactant gave better release of Compound (I) than formulations containing (i) micronized Compound (I) Form A and Soluplus® and (ii) micronized and unmicronized Compound (I) Form A alone. Dissolution curves of F1 and F2 from Fig 1 above were overlaid here. Example 5 Effect of Dry and Wet Granulation formulations with Intra and Extra granular components and varying amounts of SLS on Dissolution of Micronized Compound (I) Form A in Simulated Gastric Fluid (SGF) A. Dry Granulation formulations with varying amounts of SLS: 1. Composition of Dry Granulation formulations containing 11.3% (F5) and 5.6% (F6) of SLS are disclosed in Table 7 below. Table 7 Dry Granulation formulation

[0002] Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT % % % In dry granulation formulation, the dry intragranular excipients, listed in Table 7 above, were mixed, then granulation was performed using the slugging technique, involving preparation of an intermediate intra-granular phase blend of Compound (I) Form A, sodium lauryl sulfate, and diluent excipient, followed by compression into a compacted slug. The slug was then crushed, and the material was screened to produce densified granules. The granules were blended with extragranular excipients, listed in Table 7 above, to provide the final blend, which was filled into capsules. Both F5 and F6 dry blend formulations were filled into size #0 HPMC capsules. 3. Dissolution Test and Profile of F5 and F6 in SGF Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Result: As seen in Fig 3, dry granulation formulations F5 and F6 gave poor bioavailability of Compound (I) Form A. B, Wet Blend Granulation Formulations: A series of wet granulation tablets and capsules, F9, F13, F16, F17, F19, and F20, were formulated and tested in canine (beagle) bioavailability studies to determine relative bioavailability of above solid dosage formulations containing SLS vs. an aqueous suspension formulation used in GLP tox. 1. Preparation of Aqueous Suspension of micronized Compound (I) Form A: a. Micronized Compound (I) Form A was added to a glass beaker and 400 mL of deionized water was added. b. The mixture was heated to approximately 80 ℃. c. 2.0 g of Methylcellulose (4000 cps) was slowly added to the hot water while stirring until it was well dispersed. d. The beaker was placed into an ice bath and stirring was continued until a solution was obtained. e. 0.4 mL Tween-80 was added and stirring was continued 1 hour. 2. Preparation of Wet Granulation Formulations F9, F13, F16, F17, F19, and F20 A. Composition of Wet Blend formulations F9, F13, F16, F17, F19, and F20 are disclosed in Table 8 below: Table 8 Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT n Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT n Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT B. Preparation of Wet granulation Formulations: a1. Wet granulation tablets F9 and F16: 1. Copovidone was dissolved in water in a small beaker with a stir bar (for F16, SLS was also dissolved; see Table 8). 2. Weighed Pearlitol (Mannitol) and Sodium Lauryl Sulfate were mixted in a mortar with a pestle and the inside surface of the mortar was with covered by Pearlitol and Sodium Lauryl Sulfate. 3. Weighed micronized Compound (I) Form A was added and the dry blend was screened from #2 through #40 mesh. 4. Weighed Crospovidone and Copovidone were screened through #40 mesh and added to the mortar containing to the blend from Step 3 and the mixture was mixed for 3 min. 5. Granulation media (see Table 8; F9 is without SLS and F16 was with SLS)) was slowly added to the blend while mixing. After all solution was added, the blend was continued to mix for about 2 min to form wet granules. 6. The wet granules were transferred into a large weighing bowl and spread on the bowl evenly, and big lumps, if present, were broken up. 7. The weighing bowl was placed into an oven and dried at 50 °C for 2 h. 8. Large dried granules were gently broken in mortar if needed. 9. Weight of extra-granular excipients was adjusted based on the mass recovery yield of the intra-granules to keep the w / w % consistent per the formulation (outlined in Table 8). 10. Weighed Pearlitol, Crospovidone, and Silica were screened through #40 mesh, added to the dried intra-granules and mixed for 2 min. 11. Weighed and screened (#40 screen) Magnesium Stearate was added to the blend and mixed for 2 min. 12. Flowability of the final blend was visually assessed and manually compressed into tablet with tooling: Natoli 0.4062 with round bevel edge. a2. Wet granulation tablets F13 and F17: 1. Weighed Lactose or Mannitol (see Table 8) and SLS were added into a mortar and mixed with pestle for 2 min, making sure the inner wall of mortar was coated with the excipients. 2. Weighed micronized Compound (I) Form was added to the blend and the resulting Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT dry blend was screened from #2 through #40 mesch. 3. Weighed Copovidone was screened through #40 mesh and then added to the mortar containing the blend and mixed with pestle for 3 min. 4. Granulation media (water only / see table 8) was slowly added to the blend while mixing. After all the solution was added, the blend was continued to mix for about 2 min to form wet granules. 5. The wet granules were transferred into a large weighing bowl and spread on the bowl evenly, and big lumps, if present, were broken up. 6. The weighing bowl was placed into an oven and dried at 50 °C for 2 h. 7. Large dried granules were gently broken in mortar if needed. 8. Weighed extra-granular excipients was adjusted based on the mass recovery yield of the intra- granules to keep the w / w % consistent per the formulation (outlined in Table 8). 9. Microcrystalline cellulose (MCC PH-102), Crospovidone and Silica were weighed and were screened through #40 mesh, then added to the dried intra-granules and mixed for 2 min. 10. Magnesium Stearate was weighed and screened (#40 screen) and added to the blend and mixed for 2 min. 11. Flowability of the final blend was visually assessed and the blend was manually compressed into tablet with tooling: Natoli 0.4062 with round bevel edge. a3. Wet granulation capsules F19 and F21: 1. Copovidone and SLS were dissolved in water in a small beaker with stir bar. 2. Weighed Pearlitol (Mannitol) and Sodium Lauryl Sulfate were mixted in a mortar with pestle and the inside surface of mortar was covered with Pearlitol and Sodium Lauryl Sulfate. 3. Weighed micronized Compound (I) Form A was added and the dry blend was screened through #40 mesh. 4. Weighed Crospovidone and Copovidone were screened through #40 mesh and added to the mortar containing to the blend from Step 3 and the mixture was mixed for 3 min. 5. For F19, granulation media was slowly sprayed to the blend of Step 4 while mixing. After all solution was added, the blend was continued to mix for about 2 min to form wet granules. For F21, granulation media (containing SLS) was sprayed into the blend of Step 4, followed by granulation. 6. The wet granules were transferred into a large weighing bowl and spread on the bowl evenly, and big lumps, if present, were broken up. Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 7. The weighing bowl was placed into an oven and dried at 50 °C for 2 h. 8. Large, dried granules were gently broken in mortar if needed. 9. Weight of extra-granular excipients was adjusted based on the mass recovery yield of the intra-granules to keep the w / w % consistent per the formulation (outlined in Table 8). 10. Weighed Pearlitol, Crospovidone, and Silica were screened through #40 mesh, added to the dried intra-granules and mixed for 2 min. 11. Weighed and screened (40 screen) Magnesium Stearate was added to the blend and mixed for 2 min. 12. The granules were manually filled into size 0 Gelatin capsules. 3. Dog PK studies with Wet granulation formulations a. Dog BA studies were done as crossover studies to evaluate pharmacokinetics of F9, F13, F16, F17, F19, and F20 formulations, following oral (PO) administration to male beagle dogs. Male beagle dogs were 8 month to 3 years old with body weights of 10.00-14.00 kg on the dosing date. The animals were housed in a 12-hour light / 12-hour dark cycle environment. The animals for PO administrations were food fasted overnight prior to dosing and were fed approximately 4 hours after dosing. All the animals had free access to water. A total of five male beagle dogs were dosed via the design as shown in Table 9. A single PO dose was administered to each dog for each of the different formulations in order by Group numbers. The washout period between any two consecutive dose groups was ≥ 10 days. Blood samples (1.5 mL) were collected from each animal that was administered with F9, F13, F16, F17, F19, and F20 formulations at pre-dose, 15, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h and 72 h post dose via peripheral veins. The blood samples were placed into tubes containing EDTA-K3, and then centrifuged at 2000 g for 10 minutes at 4 °C to produce plasma. All samples were stored at -75±15°C until analysis. Table 9 Dog BA Study Dosing information Dose Group Level Volume Conc. No. of ls s s Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT s s s s s b. Results of the dog BA studies are disclosed in Table 10 below: Table 10 AUC(0-72h) AUC(0-72h) 2 ) Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 2 ) In the dog oral fasted BA studies, the wet granulation capsules F19 and F21 had 73% and 92% bioavailability, respectively, compared to the SLS / suspension liquid formulation POC2 used in preclinical studies. F19 and F21 formulations were similar except that the F21 formulation had SLS dissolved into the granulation media that was sprayed on the intragranular blend while for F19, all SLS was added as a powder to the intragranular blend (and water with Copovidone (and no SLS) was used as the granulation media. The increase in bioavailabilty is attributed to the dissolved / sprayed SLS during granulation. From these results, wet granulation formulation of capsule F21 was chosen to move forward into the clinical studies. Example 6 Large Scale 50 and 200 mg Compound (I) Form A Formulations Using the wet granulation / SLS spray approach, granules only and granules with extragranular excepients (Extragranular) formualtions were prepared and their dissolution profiles were compared as described below. 1. Granules only Formulations: 50 mg and 200 mg strength capsules: a. Equipment Used for Scale-up of Granules Only Formulations is disclosed in Table 11 below: Table 11 Equipment Key Technical Process Model Manufacturer Name Parameters Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT b. Composition of 50 mg and 200 mg Granules only formulation are disclosed in Table 12 below: Table^12 Ingredients mg / unit mg / unit Theo Wt. (g) w / w % Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT c. Preparation of Granules: Sieved (30 mesh) micronized Compound (I) Form A, Pearlitol (Mannitol), sodium lauryl sulfate, crospovidone, and copovidone were transferred to a granulator and mixed to prepare a dry blend. Granulation media was prepared by mixing sodium lauryl sulfate and copovidone in water until dissolved. Wet granules were prepared by spraying the granulation media onto the dry blend and granulating at 300RPM. The resulting wet granules were dried and milled. The milled dry blend was transferred, sieved (0.6mm / #30 mesh), and encapsulated to generate 50 mg and 200 mg dose strength capsules. 2. Extragranular formulations: 50 mg and 200 mg strength capsules: a. Components of intragranular plus extragranular formulation are dsclosed in Table 13 and its sevieving and flowability analyses are disclosed in Tables 14 and 15. Table 13 50 mg 200 mg 50 mg 200 mg h t e Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT h t e Formulations using extragranular excipients (in addition to the granules) were trialed and scaled up. The manufacturing process was similar for granules alone, but with extra processing steps to include blending of granules with extragranular excipients before capsule fill. c. Extragranular Formulation: Sieving Analysis Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Table 14 of d. Extragranular Formulation: Flowability Analysis Table 15 50 mg Capsule Final blend 200 mg Capsule Final blend 1 3 0 3. Di lations in SGF (see Table 5 for conditions): a. Granules only: Dissolution profile of 50 mg and 200 mg capsules with granules only formulations are disclosed in Table 16 below: Table 16 Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT b. Extragranular Formulation: Dissolution profile of 50 mg and 200mg capsules with Dissolution profile of 50 mg and 200 mg capsules with extragranular formulations are disclosed in Table 17 below: Table 17 50 mg Dissolution, Extragranular formulation % Release Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT The extragranular formulation flowability (Hausner ratio) was similar to the granules only formulation, and the granules only formulation was determined to be superior to the extrangranular formulation based on dissolution RSD. The granules only formulation was chosen as the capsule fill. Example 7 10 mg and 25 mg Granule Only Capsule Formulations 1. Components of 10 and 25 mg granule only formulation are dsclosed in Table 18: Table 18 50 mg and h n ll Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT Preparation of 10 mg and 25 mg granule only capsule formulations: The above formulations were prepared using the same manufacturing process and equipment as the 50 / 200 mg common granule but varying the amounts of micronized form A and diluent while maintaining a SLS to micronized form A weight / weight ratio of 0.25 (see Table 18). After final drying, the 10 mg granules were analyzed by sieving, compared against the 50 / 200 mg common blend and the results are shown in Table 19 below. 2. 10 mg granule only capsule formulation: Sieving and Flowability Analysis Table 19 10 mg Granules Sieving and Flowability Analysis 50 / 200mg Formulation 10mg Formulation Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT It was found to have similar particle size distribution, bulk and tapped density, and slightly lower compressibility 3. Dissolution Profile of 10 mg granules only Capsule formulation: Dissolution profile of capsules containing 10 mg blend is disclosed in Table 20 below. Table 20 Dissolution Profile (n=12) for Compound (I) Form A 10 mg Capsules 15 30 45 60 90 Batch Aspect Disso 0mg common blend. 4. Dog PK study with 10 mg, 25 mg and 50 mg granule only Capsule formulations The 10 mg, 25 mg and 50 mg granule only formulations were dosed sequentially in a single dose beagle bioavailability study (n=5) and found to be dose proportional (see Figure 5). Table 21 Dog PK Study Study Group mg dose Dogs / group Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT h Example 8 Preparation of Large Scale 50mg / 200mg Granules Only formulation 1. Components of 20 and 200 mg granules only Capsule formulation are dsclosed in Table 22: Table 22 50 mg and g e ty Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 2. Preparation of Formulation: 1. Sieved (#30 mesh sieve) micronized Compound (I) Form A (999.9g), mannitol (620.1g), sodium lauryl sulfate (200.0g), crospovidone (90.02g), and copovidone (87.55g) were transfered to the high-shear granulator. 2. Granulation media was prepared by mixing sodium lauryl sulfate (50.06g) and copovidone (12.57g) in sufficient water to dissolve and stir until a solution was obtained. 3. The dry ingredients of Step 1 were blended. 4. Wet granulation was performed in the high shear granulator by spraying the granulation media at approximately 60g / minute onto the dry ingedients while blending with impellers at 250RPM (choppers off). 5. The wet granulation was dried to achieve final LOD of not more that 2.0%. 6. The wet granulated material (Quadro Comil) was milled at 750RPM / 032R screen. 7. Encapsulation was performed using an encapsulator with appropriate tooling. 8. Capsule weight was checked (+ / - 7%) and the polished. 3. Dissolution Profile of 200 mg capsule is provided in Table 23. Table 23 Dissolution Profile (n=12) for 200 mg granule only capsule formulation 15 30 45 60 90 Batch Aspect min min min min min 0

Claims

Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT What is Claimed:

1. A wet granulated pharmaceutical composition comprising: (a) micronized Compound (I) Form A: having an X-ray powder diffraction peaks at angular positions 15.8and 18.6, wherein the angular 2θ as measured by X-ray powder diffraction using an X-ray wavelength of 1.5418 Å; (b) a sprayed surfactant; and (c) a non-sprayed surfactant; wherein the sprayed and non-sprayed surfactants are the same or different.

2. The wet granulated pharmaceutical composition of claim 1, wherein the micronized Compound (I) Form A has a D90 value less than about 25 µm.

3. The wet granulated pharmaceutical composition of claim 1 or 2, wherein the micronized Compound (I) Form A has D90 value less than about 14 µm.

4. The wet granulated pharmaceutical composition of any one of claims 1 to 3, wherein the micronized Compound (I) Form A has D50 value less than about 10 µm.

5. The wet granulated pharmaceutical composition of any one of claims 1 to 4, wherein the micronized Compound (I) Form A has a D50 value less than about 6 µm.

6. The wet granulated pharmaceutical composition of any one of claims 1 to 5, wherein the micronized Compound (I) Form A has a D10 value less than about 3 µm.

7. The wet granulated pharmaceutical composition of claim 1, wherein the micronized Compound (I) Form A has a D10 value of 3 ± 2 µm, a D50 value of 6 ± 3 µm, and a D90 value of 14 ± 4 µm.Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 8. The wet granulated pharmaceutical composition of claim 1, wherein the micronized Compound (I) Form A has a D10 value of 2.6 µm, a D50 value of 5.9 µm, and a D90 value of 13.6 µm.

9. The wet granulated pharmaceutical composition of any one of claims 1 to 8, wherein the dry wt / wt % ratio of micronized Compound (I) Form A to combined weight of the sprayed and non-sprayed surfactants is 4:

1.

10. The wet granulated pharmaceutical composition of any one of claims 1 to 9, wherein the weight of the sprayed surfactant is about 2.45 % of the total dry weight of the pharmaceutical composition.

11. The wet granulated pharmaceutical composition of any one of claims 1 to 10, wherein the weight of the sprayed surfactant is 2.43 % by weight of the total dry weight of the pharmaceutical composition.

12. The wet granulated pharmaceutical composition of any one of claims 1 to 11, further comprising a binder.

13. The wet granulated pharmaceutical composition of claim 12, where the weight of the binder is about 5.0 % by weight of the total dry weight of the pharmaceutical composition.

14. The wet granulated pharmaceutical composition of claim 12 or 13, where the binder comprises sprayed and non-sprayed binders which may be the same or different.

15. The wet granulated pharmaceutical composition of claim 14, where the weight of sprayed binder is about 0.65 % by weight of the total dry weight of the pharmaceutical composition.

16. The wet granulated pharmaceutical composition of claim 14 or 15, where the weight of sprayed binder is about 0.61 % by weight of the total dry weight of the pharmaceutical composition.

17. The wet granulated pharmaceutical composition of any one of claims 14 to 16, where the weight of non-sprayed binder is about 4.50 % by weight of the total dry weight of the pharmaceutical composition.Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 18. The wet granulated pharmaceutical composition of any one of claims 14 to 17, where the weight of non-sprayed binder is 4.77 % by weight of the total dry weight of the pharmaceutical composition.

19. The wet granulated pharmaceutical composition of any one of claims 14 to 17, where the weight of non-sprayed binder is about 4.30 % by weight of the total dry weight of the pharmaceutical composition.

20. The wet granulated pharmaceutical composition of any one of claims 14 to 17, and 19, where the weight of non-sprayed binder is 4.25 % by weight of the total dry weight of the pharmaceutical composition.

21. The wet granulated pharmaceutical composition of any one of claims 14 to 17, where the weight of non-sprayed binder is 4.56 % by weight of the total dry weight of the pharmaceutical composition.

22. The wet granulated pharmaceutical composition of any one of claims 12 to 21, where the binder is selected from polyvinylpyrrolidinone, microcrystalline cellulose, and copovidone.

23. The wet granulated pharmaceutical composition of any one of claims 1 to 22, further comprising a disintegrant.

24. The wet granulated pharmaceutical composition of any one of claims 23, where the weight of disintegrant is about 4.50 % by weight of the total dry weight of the pharmaceutical composition.

25. The wet granulated pharmaceutical composition of any one of claims 23 and 24, where the weight of disintegrant is 4.37% by weight of the total dry weight of the pharmaceutical composition.

26. The wet granulated pharmaceutical composition of any one of claims 23 and 24, where the weight of disintegrant is 4.84 % by weight of the total dry weight of the pharmaceutical composition.Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 27. The wet granulated pharmaceutical composition of any one of claims 23 and 24, where the weight of disintegrant is 4.65 % by weight of the total dry weight of the pharmaceutical composition.

28. The wet granulated pharmaceutical composition of any one of claims 23 to 27, where the disintegrant is selected from sodium starch glycolate, croscarmellose sodium, and crospovidone.

29. The wet granulated pharmaceutical composition of any one of claims 1 to 18, 22 to 24, 26, and 28, wherein the weight of the non-sprayed surfactant is about 0.30 % by weight of the total dry weight of the pharmaceutical composition.

30. The wet granulated pharmaceutical composition of any one of claims 1 to 18, 22 to 24, 26, 28, and 29, wherein the weight of the non-sprayed surfactant is 0.26 % by weight of the total dry weight of the pharmaceutical composition.

31. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 19, 20, 22 to 25, and 28, wherein the weight of the non-sprayed surfactant is about 9.70 % by weight of the total dry weight of the pharmaceutical composition.

32. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 19, 20, 22 to 25, 28, and 31, wherein the weight of the non-sprayed surfactant is 9.71 % by weight of the total dry weight of the pharmaceutical composition.

33. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 21 to 23, 27, and 28, wherein the weight of the non-sprayed surfactant is about 4.0 % by weight of the total dry weight of the pharmaceutical composition.

34. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 21 to 23, 27, 28, and 33, wherein the weight of the non-sprayed surfactant is 4.03 % by weight of the total dry weight of the pharmaceutical composition.

35. The wet granulated pharmaceutical composition of any one of claims 1 to 34, wherein the sprayed and the non-sprayed surfactants are independently selected from Polyoxyl 40 stearate, Cremophor RH40, Polysorbate 80, Tocophersolan, Soluplus, poloxamer 188, poloxamerAttorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 457, linoeoyl polyoxyl-6-gylcerides (Labrafil M2125), lauroyl polyoxyl-32 glycerides, and sodium lauryl sulfate.

36. The wet granulated pharmaceutical composition of any one of claims 1 to 35, further comprising a diluent.

37. The wet granulated pharmaceutical composition of any one of claims 1 to 18, 22 to 24, 26, 28 to 30, and 35, further comprising a diluent where the weight of diluent is about 76.34 % by weight of the total weight of the pharmaceutical composition.

38. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 21 to 23, 27, 28, 33, 34, and 35, further comprising a diluent where the weight of diluent is about 57.88% by weight of the total weight of the pharmaceutical composition.

39. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 19, 20, 22 to 25, 28, 31, 32, and 35, further comprising a diluent where the weight of diluent is about 31 % by weight of the total dry weight of the pharmaceutical composition.

40. The wet granulated pharmaceutical composition of any one of claims 36 to 39, wherein the diluent is selected from lactose, pregelatinized starch, corn starch, microcrystalline cellulose and mannitol.

41. The wet granulated pharmaceutical composition of any one of claims 1 to 18, 22 to 24, 26, 28 to 30, 35, 37, and 40, wherein the weight of the micronized Compound (I) Form A is about 11.0 % by weight of the total dry weight of the pharmaceutical composition.

42. The wet granulated pharmaceutical composition of any one of claims 1 to 18, 22 to 24, 26, 28 to 30, 35, 37, 40, and 41, wherein the weight of the micronized Compound (I) Form A is about 10.75 % by weight of the total dry weight of the pharmaceutical composition.

43. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 19, 20, 22 to 25, 28, 31, 32, 35, 39, and 40, wherein the weight of the micronized Compound (I) Form A is about 50.0 % by weight of the total dry weight of the pharmaceutical composition.

44. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 19, 20, 22 to 25, 28, 31, 32, 35, 39, 40, and 43, wherein the weight of the micronized Compound (I) Form A is about 48.54 % by weight of the total dry weight of the pharmaceutical composition.Attorney Docket No.16036.0008-00304 Client Ref. No: NKT-24-006PCT 45. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 21 to 23, 27, 28, 33, 34, 35, 38, and 40, wherein the weight of the micronized Compound (I) Form A is about 25.0 % by weight of the total dry weight of the pharmaceutical composition.

46. The wet granulated pharmaceutical composition of any one of claims 1 to 17, 21 to 23, 27, 28, 33, 34, 35, 38, 40, and 45, wherein the weight of the micronized Compound (I) Form A is about 25.84 % by weight of the total dry weight of the pharmaceutical composition.

47. A method of treating a disease mediated by HIF-2α, comprising administering to a patient in need thereof the pharmaceutical composition of any one of claims 1 to 46 wherein the disease is a cancer.

48. The process of making the wet granulated pharmaceutical composition of any one of claims 1 to 46, comprising: (1a) preparing a mixture of micronized Compound (I) Form A, a non-sprayed surfactant, a diluent, when present, a non-sprayed binder, when present, and a disintegrant, when present; (1b) spraying onto the mixture of step (1a) a granulating amount of water comprising a sprayed surfactant and a sprayed binder to form wet granules; (1c) drying the wet granulates of step (1b) to remove water; (1d) milling the granules from step (1c) to produce milled granules; (1e) sieving the milled granules from step (1d) to remove lumps or agglomerates; and (1f) optionally encapsulating granules obtained from step (1e).

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