Oral liquid suspension of a pan-RAF kinase inhibitor

Abstract

Disclosed herein is a solid formulation of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof for preparing a liquid suspension. In another aspect, the application provides a method of preparing a liquid suspension and a kit of a solid formulation comprising Compound A. In another aspect, the application provides a method of treating cancer with a formulation of Compound A. Additionally, the disclosure provides a method of treating a pediatric cancer patient by administering a formulation of Compound A.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 342,533, filed May 16, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] background In 2018, there were 18.1 million new cases and 9.5 million cancer-related deaths worldwide. By 2040, the number of new cancer cases and cancer-related deaths per year is expected to rise to 29.5 million and 16.4 million, respectively. In 2020, an estimated 1.8 million new cancer cases were diagnosed in the United States, and there were 606,520 cancer deaths. Cancer remains the second most common cause of death in the United States, accounting for nearly 1 in 24 deaths.

[0003] Approximately 15,500 children under the age of 18 in the United States and 300,000 worldwide are diagnosed with cancer each year. Cancer also remains the most common cause of death from disease in children in the United States, accounting for more than 1,700 deaths per year. Despite the need for safer and more effective treatments for childhood cancer, new drugs for pediatric patients are rare. (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide ("Compound A") (also known as toborafenib, DAY101, DOT101, TAK-580, BIIB024, or MLN 2480) is a class II pan-Raf kinase inhibitor useful for the treatment of Raf-mediated diseases, such as cancer. Compound A is currently administered in the form of an oral tablet. Therefore, there is an unmet need to develop new and useful formulations of Compound A as an effective treatment for pediatric cancer patients. Summary of the Invention [Means for solving the problem]

[0004] overview In certain aspects, the present disclosure provides a method for producing a method for treating a cancer cell comprising: (a) an amorphous solid dispersion comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof; and (b) one or more pharma- ceutically acceptable excipients, including flow-aids and surfactants; The present invention provides a pharmaceutical powder comprising:

[0005] In some embodiments, the one or more pharma- ceutically acceptable excipients stabilize and / or aid in solubilizing Compound A in an amorphous state.

[0006] In some embodiments, the pharmaceutical powder is reconstituted into an oral liquid suspension. In some embodiments, the amorphous solid dispersion comprises one or more polymers. In some embodiments, the one or more polymers include polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymer (PVP-VA), cross-linked polyvinyl N-pyrrolidone, polyvinyl alcohol (PVA), polysaccharides, hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutylether-β-cyclodextrin (Captisol), γ-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyethylene glycol (PEG), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG), polysaccharides, poly(methacrylic acid-co-methyl methacrylate) (Eudragit), poloxamer, silica gel, aluminosilicate, or combinations thereof. In some embodiments, the one or more polymers include PVP-VA or HPMCAS.

[0007] In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 90 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 90 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the weight ratio of Compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2:1 to 1:2. In some embodiments, the amorphous solid dispersion comprises Compound A. In some embodiments, the amorphous solid dispersion is a hot melt extrudate (HME). In some embodiments, the amorphous solid dispersion is prepared by dissolving Compound A or a pharma- ceutically acceptable salt thereof in a solvent and then removing at least a portion of the solvent. In some embodiments, Compound A or a pharma- ceutically acceptable salt thereof is amorphous. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 500 μm. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the pharmaceutical powder comprises about 20 wt% to about 60 wt% of the amorphous solid dispersion. In some embodiments, one or more pharma- ceutically acceptable additives are in admixture with the amorphous solid dispersion in the pharmaceutical powder. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 80 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the one or more pharma- ceutically acceptable additives include an antifoam, a bulking agent, a colorant, a preservative, a flavoring agent, a sweetener, or a combination thereof. In some embodiments, the antifoaming agent comprises simethicone. In some embodiments, the antifoaming agent is present in the pharmaceutical powder at about 0.1 wt% to about 10 wt%. In some embodiments, the bulking agent comprises a polysaccharide, a sugar or derivative thereof, or both. In some embodiments, the bulking agent comprises cellulose, starch, synthetic soluble fiber, sugar alcohol, or a combination thereof. In some embodiments, the bulking agent comprises mannitol. In some embodiments, the bulking agent comprises microcrystalline cellulose, polydextrose, sodium carboxymethylcellulose (CMC sodium), or a combination thereof. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 80 wt% of the bulking agent.In some embodiments, the flow aid is selected from silicon dioxide, magnesium stearate, talc, starch, magnesium silicate, hydrated sodium sulfoaluminate, and combinations thereof. In some embodiments, the silicon dioxide comprises fumed silica, colloidal silicon dioxide (CSD), or both. In some embodiments, the pharmaceutical powder comprises about 0.25 wt% to about 10 wt% of the flow aid. In some embodiments, the surfactant comprises a cationic surfactant, an anionic surfactant, a nonionic surfactant, or a combination thereof. In some embodiments, the surfactant comprises sodium lauryl sulfate (SLS). In some embodiments, the surfactant comprises a poloxamer. In some embodiments, the pharmaceutical powder comprises about 0.01 wt% to about 10 wt% of the surfactant. In some embodiments, the pharmaceutical powder comprises. a) about 10 wt% to about 60 wt% amorphous solid dispersion comprising (i) about 40 wt% to about 60 wt% Compound A and (ii) about 40 wt% to about 60 wt% PVP-VA, which is a hot melt extrudate; b) about 30 wt % to about 70 wt % of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; c) about 0.1 wt % to 5 wt % of a surfactant, the surfactant being SLS; d) about 0.25 wt% to 6 wt% of a flow aid, the flow aid being a CSD; and e) about 0.5 wt% to 5 wt% of an antifoaming agent, which is simethicone or dimethicone; Includes.

[0008] In certain aspects, the present disclosure provides oral liquid suspensions comprising a solid formulation, e.g., a powder formulation as described herein, and an aqueous solution in the kit disclosed herein. In some embodiments, the oral liquid suspension is produced by contacting a solid formulation, e.g., a powder formulation as described herein, in the kit disclosed herein with an aqueous solution. In some embodiments, the oral liquid suspension comprises a pharmaceutical powder, e.g., a powder formulation as described herein, and an aqueous solution. In some embodiments, the oral liquid suspension is produced by contacting a pharmaceutical powder, e.g., a powder formulation as described herein, disclosed herein, with an aqueous solution. In some embodiments, the powder is reconstituted with water, and the resulting suspension is administered orally or enterally via a nasogastric or gastric feeding tube equipped with a syringe for administration. In certain aspects, the present disclosure provides an oral liquid suspension comprising: (a) (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof; (b) one or more pharma- ceutically acceptable excipients; and (c) water. In some embodiments, Compound A or a pharma- ceutically acceptable salt thereof is in the form of an amorphous solid dispersion. In some embodiments, the amorphous solid dispersion comprises one or more polymers.In some embodiments, the one or more polymers comprise polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymer (PVP-VA), cross-linked polyvinyl N-pyrrolidone, polyvinyl alcohol (PVA), polysaccharides, hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutylether-β-cyclodextrin (Captisol), cyclodextrins (e.g., -cyclodextrin), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyethylene glycol (PEG), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG), polysaccharides, poly(methacrylic acid-co-methyl methacrylate) (Eudragit), poloxamer, silica gel, aluminosilicate, or combinations thereof. In some embodiments, the one or more pharma- ceutically acceptable additives are selected from antifoaming agents, flow aids, surfactants, bulking agents, colorants, preservatives, flavoring agents, sweeteners, and combinations thereof. In some embodiments, the oral liquid suspension is prepared by adding water to a powder formulation of Compound A. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 10 mg / mL to about 125 mg / mL in the oral liquid suspension. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 10 to about 50 mg / mL in the oral liquid suspension. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 to about 50 mg / mL in the oral liquid suspension. In some embodiments, the aqueous solution is water. In some embodiments, the pH value of the liquid suspension is about 2 to 7. In some embodiments, the suspension is administered by oral syringe for at least 30 minutes. In some embodiments, the suspension retains syringeability for at least 15 minutes after contacting the powder formulation with the aqueous solution. In some embodiments, the suspension remains injectable for at least 30 minutes after contacting the powder formulation with an aqueous solution.The term injectable refers to the ability of the oral suspension to be drawn into the barrel of a syringe for administration, e.g., oral administration, to a subject, e.g., a child or infant. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 200 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 30 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 300 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 125 mg / mL to about 200 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 1 mg / mL to about 2.5 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 5 mg / mL to about 15 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 10 mg / mL to about 15 mg / mL. In some embodiments, the concentration of the antifoam in the suspension is about 1 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the antifoam in the suspension is about 1 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the antifoam in the suspension is about 3 mg / mL to about 8 mg / mL. In some embodiments, the suspension is based on the weight of the solids. (a) an amorphous solid dispersion comprising (i) about 40 wt % to about 60 wt % of Compound A and (ii) about 40 wt % to about 60 wt % of PVP-VA, the amorphous solid dispersion being a hot melt extrudate; (b) about 40 wt % to about 70 wt % of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; (c) about 0.25 wt % to about 1 wt % of a surfactant, the surfactant being SLS; (d) about 1 wt % to about 6 wt % of a flow aid, the flow aid being colloidal silicon dioxide (CSD); (e) about 1 wt % to about 5 wt % of an antifoaming agent, the antifoaming agent being simethicone; and (f) Where appropriate, a preservative, flavouring agent, sweetener, or combination thereof. Includes.

[0009] In some embodiments, the suspension comprises, based on the weight of solids, (a) about 10 wt.% amorphous solid dispersion comprising (i) about 40 wt.% Compound A and (ii) about 60 wt.% copovidone, wherein the amorphous solid dispersion is a hot melt extrudate; (b) about 30 wt% to 32 wt% mannitol; (c) about 30 wt% to 32 wt% microcrystalline cellulose; (d) about 0.5 wt% to 1 wt% SLS; (e) about 4 wt%–5 wt% CSD; (f) about 2 wt% to 3 wt% simethicone; and (g) Where appropriate, a preservative, flavouring agent, sweetener, or combination thereof. Includes.

[0010] In some embodiments, the oral liquid suspension is bioequivalent to a tablet formulation of Compound A, the tablet composition comprising: (i) about 40 wt% Compound A and (ii) about 60 wt% copovidone, the amorphous solid dispersion being a hot melt extrudate; and one or more pharma- ceutically acceptable excipients. In some embodiments, the oral liquid suspension is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A of at least about 100 ng / mL in a human subject when administered to a human subject in an amount equivalent to about 100 mg of Compound A. In some embodiments, the oral liquid suspension is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A of at least about 100 ng / mL in a human subject when administered to a human subject in an amount equivalent to about 100 mg of Compound A.

[0011] In certain aspects, the disclosure provides a method of treating cancer comprising administering to a subject an oral liquid suspension comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A), or a pharma- ceutically acceptable salt thereof, in an amount sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A of at least 2000 ng / mL in the subject. In some aspects, the disclosure provides a method of treating cancer in a subject comprising administering to the subject a pharmaceutical powder as disclosed herein or a reconstituted oral liquid formulation as disclosed herein. In some aspects, the disclosure provides a method of treating cancer in a subject comprising reconstituting a solid formulation in a kit as disclosed herein and administering to the subject the reconstituted formulation. In some embodiments, the subject is 18 years of age or younger. In some embodiments, the cancer is low-grade glioma. In some aspects, the present disclosure provides a method for treating a subject with pediatric low-grade glioma (pLGG), comprising reconstituting an amorphous solid dispersion of compound A or a salt thereof in an aqueous solution, and administering a pharma- ceutically acceptable dosage of the reconstituted compound A or a salt thereof to a subject in need thereof. In some embodiments, the method is administered with food, before eating food, or after eating food.

[0012] In certain aspects, the present disclosure provides a kit comprising: (a) a solid formulation of an amorphous solid dispersion of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof, the solid formulation comprising one or more pharma- ceutically acceptable excipients; and (b) instructions for aqueous reconstitution of the solid formulation. In some embodiments, the solid formulation is in the form of a powder, granules, or pellets. In some embodiments, the solid formulation is in the form of a powder. In some embodiments, the amorphous solid dispersion comprises one or more polymers. In some embodiments, the one or more polymers comprise polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymer (PVP-VA), cross-linked polyvinyl N-pyrrolidone, polyvinyl alcohol (PVA), polysaccharides, hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutylether-β-cyclodextrin (Captisol), cyclodextrins (e.g., γ-cyclodextrin), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyethylene glycol (PEG), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG), polysaccharides, poly(methacrylic acid-co-methyl methacrylate) (Eudragit), poloxamer, silica gel, aluminosilicate, or combinations thereof. In some embodiments, the one or more polymers include PVP-VA or HPMCAS. In some embodiments, the one or more polymers include HPMCAS. In some embodiments, the one or more polymers include PVP-VA. In some embodiments, the one or more polymers include copovidone. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 90 wt% of the one or more polymers.In some embodiments, the amorphous solid dispersion comprises about 40 wt% to about 80 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 55 wt% to about 65 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 90 wt% of compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 60 wt% of compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 35 wt% to about 45 wt% of compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2:1 to 1:2. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is about 1:1 to 1:2. In some embodiments, the amorphous solid dispersion comprises compound A. In some embodiments, the amorphous solid dispersion is a hot melt extrudate (HME). In some embodiments, the amorphous solid dispersion is prepared by dissolving Compound A or a pharma- ceutically acceptable salt thereof in a solvent and then removing at least a portion of the solvent. In some embodiments, the amorphous solid dispersion is prepared by dissolving Compound A or a pharma- ceutically acceptable salt thereof in a solvent and then removing at least a portion of the solvent. In some embodiments, the particles in the amorphous solid dispersion have a D50 value of about 10 μm to about 500 μm. In some embodiments, the particles in the amorphous solid dispersion have a D50 value of about 100 μm to about 400 μm. In some embodiments, the solid formulation comprises about 10 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 40 wt% to about 60 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 15 wt% to about 35 wt% of the amorphous solid dispersion. In some embodiments, the one or more pharma- ceutically acceptable excipients are in admixture with the amorphous solid dispersion in the solid formulation. In some embodiments, the amorphous solid dispersion comprises one or more pharma-ceutically acceptable excipients.In some embodiments, the solid formulation comprises about 5 wt% to about 80 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 40 wt% to about 60 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the one or more pharma- ceutically acceptable additives are selected from antifoaming agents, flow aids, surfactants, bulking agents, colorants, preservatives, flavoring agents, sweeteners, and combinations thereof. In some embodiments, the one or more pharma- ceutical acceptable additives are selected from antifoaming agents, flow aids, surfactants, bulking agents, and combinations thereof. In some embodiments, the antifoaming agent comprises simethicone. In some embodiments, the solid formulation comprises about 0.1 wt% to about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 1 wt% to about 8 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 3 wt% to about 8 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.5 wt% to about 3 wt% simethicone. In some embodiments, the flow aid is selected from silicon dioxide, magnesium stearate, talc, starch, magnesium silicate, hydrated sodium sulfoaluminate, and combinations thereof. In some embodiments, the silicon dioxide comprises fumed silica, colloidal silicon dioxide (CSD), or both. In some embodiments, the solid formulation comprises about 0.25 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 1 wt% to about 5 wt% of the flow aid. In some embodiments, the surfactant comprises a cationic surfactant, an anionic surfactant, a nonionic surfactant, or a combination thereof. In some embodiments, the surfactant comprises sodium lauryl sulfate (SLS). In some embodiments, the solid formulation comprises about 0.01 wt% to about 10 wt% of the surfactant. In some embodiments, the solid formulation comprises about 0.1 wt% to about 2 wt% of the surfactant. In some embodiments, the bulking agent comprises a polysaccharide, a sugar or derivative thereof, or both. In some embodiments, the bulking agent comprises a cellulose, a starch, a synthetic soluble fiber, a sugar alcohol, or a combination thereof. In some embodiments, the bulking agent comprises mannitol.In some embodiments, the bulking agent comprises microcrystalline cellulose, polydextrose, sodium carboxymethylcellulose (CMC sodium), or a combination thereof. In some embodiments, the solid formulation comprises about 5 wt% to about 80 wt% of the bulking agent. In some embodiments, the solid formulation comprises about 30 wt% to about 75 wt% of the bulking agent. In some embodiments, the instructions for aqueous reconstitution are in the form of a reference document referring to the instructions.

[0013] In some embodiments, the solid formulation in the kit comprises: (a) about 10 wt% to about 60 wt% amorphous solid dispersion comprising (i) about 40 wt% to about 60 wt% Compound A and (ii) about 40 wt% to about 60 wt% PVP-VA, wherein the amorphous solid dispersion is a hot melt extrudate; (b) about 30 wt%-70 wt% of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; (c) about 0.1 wt % to 5 wt % of a surfactant, the surfactant being SLS; (d) about 0.25 wt % to 6 wt % of a flow aid, the flow aid being a CSD; and (e) about 0.5 wt% to 5 wt% of an antifoaming agent, the antifoaming agent being simethicone; Includes.

[0014] In some embodiments, the kit comprises one or more doses of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the kit comprises 1-5 unit doses of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the kit comprises a single unit dose of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the dose is a pediatric dose. In some embodiments, each dose comprises about 50 mg to about 800 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each dose comprises about 300 mg or about 600 mg of Compound A. In some embodiments, the kit further comprises one or more containers, optionally including markings representing volume measurements. In certain aspects, the present disclosure provides kits comprising the pharmaceutical powders disclosed herein for reconstitution.

[0015] In certain aspects, the disclosure provides a unit dose composition for a powder formulation of Compound A, wherein the powder formulation comprises Compound A and, optionally, one or more of the following: one or more polymers, one or more bulking agents, surfactants, antifoaming agents, flow aids, sweeteners, and natural flavors. In certain embodiments, the disclosure provides a unit dose composition for a powder formulation of Compound A, wherein the powder formulation comprises Compound A, one or more polymers, one or more bulking agents, surfactants, antifoaming agents, flow aids, sweeteners, and natural flavors. In some embodiments, the one or more polymers can be polymers described herein. In some embodiments, the one or more polymers are copovidone. In some embodiments, the one or more bulking agents can be bulking agents described herein. In some embodiments, the one or more bulking agents are microcrystalline cellulose, mannitol, maltodextrin, or a combination thereof. In some embodiments, the surfactant can be a surfactant described herein. In some embodiments, the surfactant is sodium lauryl sulfate. In some embodiments, the antifoaming agent can be an antifoaming agent described herein. In some embodiments, the antifoaming agent is simethicone. In some embodiments, the flow aid can be a flow aid described herein. In some embodiments, the flow aid is colloidal silicon dioxide. In some embodiments, the sweetener can be a sweetener described herein. In some embodiments, the sweetener is sucralose powder. In some embodiments, the natural flavor can be a natural flavor described herein. In some embodiments, the natural flavor is artificial strawberry powder.

[0016] In some embodiments, the powder formulation of Formula A comprises about 5% to about 15% w / w of Compound A, and optionally one or more of the following: one or more polymers, one or more bulking agents, surfactants, antifoaming agents, flow aids, sweeteners, and natural flavors. In certain embodiments, the powder formulation of Formula A comprises about 5% to about 20% w / w of one or more polymers, about 50% to about 70% w / w of one or more bulking agents, about 0.1% to about 1% w / w of a surfactant, about 0.5% to about 2.5% w / w of an antifoaming agent, about 1% to about 5% w / w of a flow aid, about 0.1% to about 1% w / w of a sweetener, and about 0.5% to 1.5% w / w of a natural flavor. In some embodiments, the powder formulation of Formula A comprises about 9% to about 15% w / w of Compound A, about 10% to about 20% w / w of one or more polymers, about 60% to about 70% w / w of one or more bulking agents, about 0.5% to about 1% w / w of a surfactant, about 1.5% to about 2.5% w / w of an antifoaming agent, about 4% to about 5% w / w of a flow aid, about 0.5% to about 1% w / w of a sweetener, and about 1.0% to 1.5% w / w of a natural flavor. In some embodiments, the powder formulation of Formula A comprises about 14% to about 15% w / w of Compound A, about 14% to about 15% w / w of one or more polymers, about 66% to about 67% w / w of one or more bulking agents, about 0.7% to about 0.8% w / w of a surfactant, about 2.2% to about 2.3% w / w of an antifoaming agent, about 4.4% to about 4.5% w / w of a flow aid, about 0.5% to about 0.6% w / w of a sweetener, and about 1.5% to 1.6% w / w of a natural flavor.

[0017] In some embodiments, the powder formulation of Formula A contains about 5% to about 15% w / w Compound A, about 5% to about 20% w / w copovidone, about 50% to about 70% w / w of bulking agents including microcrystalline cellulose, mannitol, and maltodextrin, about 0.1% to about 1% w / w sodium lauryl sulfate, about 0.5% to about 2.5% w / w simethicone, about 1% to about 5% w / w colloidal silicon dioxide, about 0.1% to about 1% w / w sucralose powder, and about 0.5% to 1.5% w / w artificial strawberry flavor. In some embodiments, the powder formulation of Formula A contains about 9% to about 15% w / w Compound A, about 10% to about 20% w / w copovidone, about 60% to about 70% w / w microcrystalline cellulose, mannitol, and maltodextrin, about 0.5% to about 1% w / w sodium lauryl sulfate, about 1.5% to about 2.5% w / w simethicone, about 4% to about 5% w / w colloidal silicon dioxide, about 0.5% to about 1% w / w sucralose powder, and about 1.0% to 1.5% w / w artificial strawberry flavor. In some embodiments, the powder formulation of Formula A contains about 14% to about 15% w / w Compound A, about 14% to about 15% w / w copovidone, about 66% to about 67% w / w microcrystalline cellulose, mannitol, and maltodextrin, about 0.7% to about 0.8% w / w sodium lauryl sulfate, about 2.2% to about 2.3% w / w simethicone, about 4.4% to about 4.5% w / w colloidal silicon dioxide, about 0.5% to about 0.6% w / w sucralose powder, and about 1.5% to 1.6% w / w artificial flavor, e.g., strawberry flavor.

[0018] In some embodiments, the powder formulation of Formula A comprises about 5% to about 15% w / w Compound A, about 5% to about 20% w / w copovidone, about 25% to about 35% w / w microcrystalline cellulose, about 25% to about 35% w / w mannitol, and about 2% to about 8% w / w maltodextrin, about 0.1% to about 1% w / w sodium lauryl sulfate, about 0.5% to about 2.5% w / w simethicone, about 1% to about 5% w / w colloidal silicon dioxide, about 0.1% to about 1% w / w sucralose powder, and about 0.5% to 1.5% w / w artificial strawberry flavor. In some embodiments, the powder formulation of Formula A comprises about 9% to about 15% w / w Compound A, about 10% to about 20% w / w copovidone, about 30% to about 35% w / w microcrystalline cellulose, about 30% to about 35% w / w mannitol, and about 4% to about 6% w / w maltodextrin, about 0.5% to about 1% w / w sodium lauryl sulfate, about 1.5% to about 2.5% w / w simethicone, about 4% to about 5% w / w colloidal silicon dioxide, about 0.5% to about 1% w / w sucralose powder, and about 1.0% to 1.5% w / w artificial flavor, e.g., strawberry flavor. In some embodiments, the powder formulation of Formula A contains about 14% to about 15% w / w Compound A, about 14% to about 15% w / w copovidone, about 30% to about 31% w / w microcrystalline cellulose, about 30% to about 31% w / w mannitol, and about 5% to about 6% w / w maltodextrin, about 0.7% to about 0.8% w / w sodium lauryl sulfate, about 2.2% to about 2.3% w / w simethicone, about 4.4% to about 4.5% w / w colloidal silicon dioxide, about 0.5% to about 0.6% w / w sucralose powder, and about 1.5% to 1.6% w / w artificial flavor, e.g., strawberry flavor.

[0019] In some embodiments, the powder formulation of Formulation A comprises about 350 mg to about 450 mg of Compound A, about 600 mg to about 700 mg of one or more polymers, about 2500 mg to about 3500 mg of one or more bulking agents, about 25 mg to about 50 mg of a surfactant, about 75 mg to about 150 mg of an antifoaming agent, about 150 mg to about 250 mg of a flow aid, about 10 mg to about 75 mg of a sweetener, and about 50 mg to 100 mg of a natural flavor. In some embodiments, the powder formulation of Formulation A comprises about 400 mg to about 450 mg of Compound A, about 600 mg to about 650 mg of one or more polymers, about 2500 mg to about 3000 mg of one or more bulking agents, about 30 mg to about 40 mg of a surfactant, about 75 mg to about 100 mg of an antifoaming agent, about 150 mg to about 200 mg of a flow aid, about 10 mg to about 30 mg of a sweetener, and about 50 mg to 75 mg of a natural flavor. In some embodiments, the powder formulation of Formulation A comprises about 420 mg to about 430 mg of Compound A, about 640 mg to about 650 mg of one or more polymers, about 2850 mg to about 3000 mg of one or more bulking agents, about 30 mg to about 35 mg of a surfactant, about 90 mg to about 100 mg of an antifoaming agent, about 190 mg to about 200 mg of a flow aid, about 20 mg to about 30 mg of a sweetener, and about 60 mg to 70 mg of a natural or artificial flavor.

[0020] In some embodiments, the powder formulation of Formula A contains about 350 mg to about 450 mg of Compound A, about 600 mg to about 700 mg of copovidone, about 2500 mg to about 3500 mg of microcrystalline cellulose, mannitol, and maltodextrin, about 25 mg to about 50 mg of sodium lauryl sulfate, about 75 mg to about 150 mg of simethicone, about 150 mg to about 250 mg of colloidal silicon dioxide, about 10 mg to about 75 mg of sucralose powder, and about 50 mg to 100 mg of artificial strawberry flavor. In some embodiments, the powder formulation of Formula A contains about 400 mg to about 450 mg of Compound A, about 600 mg to about 650 mg of copovidone, about 2500 mg to about 3000 mg of microcrystalline cellulose, mannitol, and maltodextrin, about 30 mg to about 40 mg of sodium lauryl sulfate, about 75 mg to about 100 mg of simethicone, about 150 mg to about 200 mg of colloidal silicon dioxide, about 10 mg to about 30 mg of sucralose powder, and about 50 mg to 75 mg of artificial strawberry flavor. In some embodiments, the powder formulation of Formula A contains about 420 mg to about 430 mg of Compound A, about 640 mg to about 650 mg of copovidone, about 2850 mg to about 3000 mg of microcrystalline cellulose, mannitol, and maltodextrin, about 30 mg to about 35 mg of sodium lauryl sulfate, about 90 mg to about 100 mg of simethicone, about 190 mg to about 200 mg of colloidal silicon dioxide, about 20 mg to about 30 mg of sucralose powder, and about 60 mg to 70 mg of an artificial flavor, e.g., strawberry flavor.

[0021] In some embodiments, the powder formulation of Formula A includes about 350 mg to about 450 mg of Compound A, about 600 mg to about 700 mg of copovidone, about 1000 mg to about 1500 mg of microcrystalline cellulose, about 1000 mg to about 1500 mg of mannitol, about 175 mg to about 250 mg of maltodextrin, about 25 mg to about 50 mg of sodium lauryl sulfate, about 75 mg to about 150 mg of simethicone, about 150 mg to about 250 mg of colloidal silicon dioxide, about 10 mg to about 75 mg of sucralose powder, and about 50 mg to 100 mg of artificial strawberry flavor. In some embodiments, the powder formulation of Formula A includes about 400 mg to about 450 mg of Compound A, about 600 mg to about 650 mg of copovidone, about 1200 mg to about 1500 mg of microcrystalline cellulose, about 1200 mg to about 1500 mg of mannitol, about 200 mg to about 250 mg of maltodextrin, about 30 mg to about 40 mg of sodium lauryl sulfate, about 75 mg to about 100 mg of simethicone, about 150 mg to about 200 mg of colloidal silicon dioxide, about 10 mg to about 30 mg of sucralose powder, and about 50 mg to 75 mg of artificial strawberry flavor. In some embodiments, the powder formulation of Formula A contains about 420 mg to about 430 mg of Compound A, about 640 mg to about 650 mg of copovidone, about 1300 mg to about 1400 mg of microcrystalline cellulose, about 1300 mg to about 1400 mg of mannitol, about 200 mg to about 240 mg of maltodextrin, about 30 mg to about 35 mg of sodium lauryl sulfate, about 90 mg to about 100 mg of simethicone, about 190 mg to about 200 mg of colloidal silicon dioxide, about 20 mg to about 30 mg of sucralose powder, and about 60 mg to 70 mg of an artificial flavor, e.g., strawberry flavor.

[0022] In certain aspects, the disclosure provides a method of preparing an aqueous formulation, comprising the steps of: (a) providing a solid formulation of an amorphous solid dispersion, the amorphous solid dispersion comprising (i) (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof and (ii) one or more polymers; and (b) contacting the solid formulation with an aqueous solution. In some embodiments, the contacting comprises mixing the solid formulation with the aqueous solution. In some embodiments, the mixing comprises shaking the solid formulation and the aqueous solution. In certain aspects, the disclosure provides a method of preparing an oral liquid suspension of Compound A or a salt thereof, comprising reconstituting a solid formulation in a kit disclosed herein in an aqueous solution. In certain aspects, the present disclosure provides a method for preparing an oral liquid suspension of Compound A or a salt thereof, comprising reconstituting a pharmaceutical powder as disclosed herein in an aqueous solution. In some embodiments, the kit comprises a pharmaceutical powder as disclosed herein for reconstitution. Incorporation by Reference

[0023] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0024] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings. [Brief description of the drawings]

[0025] [Figure 1-1] FIG. 1 illustrates exemplary mixing instructions (steps 1 through 12). [Figure 1-2] Same as above.

[0026] [Diagram 2] FIG. 2 illustrates a plot of mean plasma concentration (Cmax) (ng / mL) versus time (hours) following PO administration of DAY101 to male CD-1 mice.

[0027] [Diagram 3] Figures 3A-3D illustrate the relative bioavailability of HME tablets and PfR (powder for reconstitution) by geometric mean plasma concentration of suspension (ng / mL) versus nominal time post-dose (hours) following administration of 300 mg DAY101 in Regimen G1 and Regimen H1 (Figures 3A-B) and 100 mg DAY101 in Regimen G2 and Regimen H2 (Figures 3C-3D).

[0028] [Figure 4] Figures 4A-4D illustrate the relative bioavailability comparing fed and fasted states by geometric mean plasma concentration (ng / mL) versus nominal time post-dose (hours) following administration of 300 mg on DAY101 in Regimen G1 and Regimen I1 (Figures 4A-4B) and 100 mg on DAY101 in Regimen G2 and Regimen I2 (Figures 4C-4D).

[0029] [Diagram 5] FIG. 5 illustrates the overall taste / preference ratings in a stacked bar graph: Taste / preference analysis set (part 1) (subjects taste 5 mL of Day101 HME PfR oral suspension in six different formulations (regimens A-F = formulations 1-6); legend for grades: 1=extremely dislike, 2=extremely dislike, 3=dislike moderately, 4=slightly dislike, 5=neither like nor dislike, 6=slightly like, 7=like moderately, 8=like extremely, 9=like extremely; outcome: dislike (grades 1-3), neutral (grades 4-6), like (grades 7-9)).

[0030] [Figure 6] FIG. 6 illustrates the geometric mean (× / ÷geometric SD) plasma concentrations (ng / mL) of DAY101 following a single oral dose of 300 mg of DAY101 administered as tablet and suspension formulations in the fasted state to healthy male and female subjects: Regimen H1 and Regimen G1 (Log10 / Linear).

[0031] [Figure 7] FIG. 7 illustrates the geometric mean (× / ÷geometric SD) plasma concentrations (ng / mL) of DAY101 following a single oral dose of 100 mg of DAY101 administered as tablet and suspension formulations in the fasted state to healthy male and female subjects: Regimen H2 and Regimen G2 (Log10 / Linear).

[0032] [Figure 8] FIG. 8 illustrates the geometric mean (× / ÷ geometric SD) plasma concentrations (ng / mL) of DAY101 following a single oral dose of 300 mg of DAY101 administered as a tablet formulation to healthy male and female subjects in the fed and fasted states: Regimen I1 and Regimen G1 (Log10 / Linear).

[0033] [Figure 9] FIG. 9 illustrates the geometric mean (× / ÷ geometric SD) plasma concentrations (ng / mL) of DAY101 following a single oral dose of 100 mg of DAY101 administered as a tablet formulation to healthy male and female subjects in the fed and fasted states: Regimen I2 and Regimen G2 (Log10 / Linear).

[0034] [Figure 10-1] FIG. 10 illustrates exemplary mixing instructions (Section A: Steps 1 through 17). [Figure 10-2] Same as above. [Figure 10-3] Same as above. [Figure 10-4] Same as above.

[0035] [Figure 11]FIG. 11 illustrates exemplary instructions for administering a dose of the disclosed liquid suspension via a feeding tube (Section B: Steps 19 through 23). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] Detailed Description While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in the practice of the invention. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims, and their equivalents, be covered thereby. definition

[0037] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications referenced herein are incorporated herein by reference.

[0038] As used in this specification and the claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0039] The term "solid dispersion" or "solid formulation" as used herein refers to an amorphous dispersion comprising Compound A or a pharma- ceutically acceptable salt thereof in the solid state, optionally prepared by hot melt extrusion.

[0040] The term "amorphous," as used herein, refers to a solid dispersion or solid formulation comprising a solid form of Compound A or a salt thereof that lacks the long-range order characteristic of a crystal, i.e., the solid is non-crystalline.

[0041] The term "micron" or "μm" as used herein means 1×10 -6 It refers to "micrometer", which is a unit of metre.

[0042] The term "in vivo" is used to describe events that take place within the body of a subject.

[0043] The term "ex vivo" is used to describe events that take place outside the subject's body. An ex vivo assay is not performed in a subject. Rather, it is performed on a sample that is separated from the subject. An example of an ex vivo assay that is performed on a sample is an "in vitro" assay.

[0044] The term "in vitro" is used to describe events that take place in a container for holding a test reagent such that it is separate from the biological source from which the material is obtained. In vitro assays can include cell-based assays in which living or dead cells are used. In vitro assays can also include cell-free assays in which no intact cells are used.

[0045] The terms "subject," "individual," and "patient" may be used interchangeably and refer to humans as well as non-human mammals (e.g., non-human primates, dogs, horses, cats, pigs, cattle, ungulates, lagomorphs, etc.). In various embodiments, a subject may be a human (e.g., adult male, adult female, adolescent male, adolescent female, boy, girl) under the care of a physician or other health worker in a hospital, as an outpatient, or other clinical setting. In certain embodiments, a subject may not be under the care or prescription of a physician or other health worker.

[0046] As used herein, the phrase "a subject in need thereof" refers to a subject, as described below, suffering from or at risk of a condition to be treated prophylactically or therapeutically with a compound or salt described herein.

[0047] The terms "determining," "measuring," "evaluating," "assessing," "assaying," and "analyzing" are often used interchangeably herein to refer to forms of measurement. The terms include determining whether an element is present or absent (e.g., detecting). These terms can include quantitative, qualitative, or quantitative and qualitative determinations. Evaluating can be relative or absolute. "Detecting the presence of" can include determining the amount of something present in addition to determining whether it is present or absent, depending on the context.

[0048] The terms "administer", "administered", "administers" and "administering" are defined as providing a composition to a subject by a route known in the art, including, but not limited to, intravenous, intraarterial, oral, parenteral, enteral, nasal, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In certain embodiments, an oral route of administering a composition can be used. The terms "administer", "administered", "administers" and "administering" a compound should be understood to mean providing a compound of the present disclosure or a prodrug of a compound of the present disclosure to an individual in need thereof.

[0049] The term "effective amount" or "therapeutically effective amount" refers to an amount of a solid dispersion, liquid formulation, or solid formulation containing Compound A or a salt thereof sufficient to treat one or more symptoms of cancer or cause regression of cancer. For example, in one embodiment, a therapeutically effective amount refers to an amount of Compound A that reduces the rate of tumor growth, reduces tumor burden, reduces the number of metastases, increases the time to tumor progression, or increases survival time by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100%.

[0050] The term "pharmaceutically acceptable salts" as used herein refers to salts suitable for use in contact with human tissues without undue toxicity, irritation, allergic response, etc., commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. See Berge et al., J. Pharmaceutical Sciences, 1977, 66, 1-19.

[0051] The term "pharmaceutically acceptable excipient" or "excipient" as used herein refers to any component in the composition of the present disclosure other than the solid dispersion of Compound A or its salt. An excipient is typically an inert substance added to a composition to facilitate processing, handling, administration, etc. of the composition. Useful excipients include, but are not limited to, adjuvants, anti-adherents, binders, carriers, disintegrants, bulking agents, flavors, colorants, diluents, lubricants, glidants, preservatives, adsorbents, solvents, surfactants, and sweeteners.

[0052] Conventional pharmaceutical additives are well known to those skilled in the art.In particular, those skilled in the art will recognize that a wide variety of pharma-ceutically acceptable additives can be used in the blending of Compound 1 and vinylpyrrolidone-vinyl acetate copolymer solid dispersion, including those listed in Handbook of Pharmaceutical Excipients, Pharmaceutical Press 4th Ed. (2003) and Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins, 21st Ed. (2005).

[0053] As used herein, "treatment" or "treating" refers to an approach to obtain beneficial or desired results with respect to a disease, disorder, or medical condition, including, but not limited to, therapeutic benefit. In certain embodiments, treating or treating includes administering a compound or composition disclosed herein to a subject. Therapeutic benefit may include eradication or amelioration of the underlying disorder being treated. Therapeutic benefit may also be achieved with eradication or amelioration of one or more physiological symptoms associated with the underlying disorder, such as observing an improvement in a subject, even though the subject may still suffer from the underlying disorder. Treating may include, for example, reducing, delaying, or alleviating the severity of one or more symptoms of a disease or condition, or reducing the frequency with which a patient experiences a symptom, such as a disease, defect, disorder, or adverse condition. Treating may be used herein to refer to a method that results in some level of treatment or amelioration of a disease or condition, and may contemplate a variety of outcomes toward that end.

[0054] In certain embodiments, the term "prevent" or "preventing" in relation to a disease or disorder may refer to a compound that reduces the appearance of a disorder or condition in a treated sample compared to an untreated control sample in a statistical sample, or delays the onset or reduces the severity of one or more symptoms of a disorder or condition compared to an untreated control sample. In certain embodiments, "prevent" or "preventing" includes administering a compound or composition to a subject at risk of developing a particular disease or to a subject reporting one or more physiological symptoms of a disease, even if the diagnosis of the disease may not have been made.

[0055] The term "vinylpyrrolidone-vinyl acetate copolymer" as used herein refers to a polymer containing vinylpyrrolidone and vinyl acetate. Names and abbreviations for vinylpyrrolidone-vinyl acetate copolymer include, but are not limited to, copovidone, copovidonum, copolyvidone, copovidone, PVP-VAc-copolymer. Copovidone is a vinylpyrrolidone-vinyl acetate copolymer, such as CAS 25086-89-9, composed of 6 parts vinylpyrrolidone and 4 parts vinyl acetate. Examples of commercial products of copovidone are Kollidon® VA 64 and Kollidon® 64 Fine. Another example is "Plasdone S-630", a 60:40 random copolymer of N-vinylpyrrolidone and vinyl acetate.

[0056] "HPMCAS" refers to hypromellose acetate succinate, a polymer containing acetyl and succinoyl groups. There are different types and grades of HPMCAS (e.g., HPMCAS-LG, HPMCAS-MG, HPMCAS-HG), which dissolve at different pH due to different compositions and ratios of their functional groups (e.g., acetyl, succinoyl). HPMCAS has L, M, and H grades depending on the wt% of acetyl and succinoyl content. The particle sizes for HPMCAS are fine (F) and granular (G).

[0057] "HPMCP" refers to hydroxypropyl methylcellulose phthalate polymer. There are different types and grades of HPMCP (e.g., HP-55s, HP-50, HP-55), which dissolve at different pHs due to different compositions and ratios of their functional groups (e.g., phthalyl).

[0058] "HPC" refers to hydroxypropyl cellulose. There are different types and grades of HPC (e.g., HPC-SSL, HPC-SL, HOC-SLT).

[0059] The term "w / w" means by weight. For example, 50% w / w means that the mass of a substance is 50% of the total mass of the solution or mixture.

[0060] As used herein, "mass median diameter" or "D 50 The term "equivalent diameter" describes the diameter at which 50% by weight of the particles in a powder dispersion have a larger equivalent diameter and the other 50% by weight have a smaller equivalent diameter, as determined by laser diffraction in a Malvern Master Sizer Microplus instrument or equivalent, or other suitable technique. For example, the D 50 If D is 105 μm, then 50% of the particles are larger than 105 μm and 50% of the particles are smaller than 105 μm. 90The term "D" describes the diameter at which 90% by weight of the particles in a powder dispersion have a smaller equivalent diameter and the other 10% by weight have a larger equivalent diameter. 10 " describes the diameter at which 10% by weight of the particles in a powder dispersion have a smaller equivalent diameter and the other 90% by weight have a larger equivalent diameter.

[0061] It is intended that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification includes every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification includes every narrower numerical range that is within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

[0062] While various embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be used.

[0063] Whenever the terms "at least," "greater than," or "greater than or equal to" precede a first number in a series of two or more numbers, the terms "at least," "greater than," or "greater than or equal to" apply to each and every number in the series. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0064] Whenever the terms "less than," "at most," "less than," or "less than or equal to" precede the first number in a series of two or more numbers, the terms "less than," "at most," "less than," or "less than or equal to" apply to each and every number in the series. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0065] The term "about" as used herein includes the recited number ±10%. Thus, "about 10" means 9 to 11. The term "about" may also refer to a value within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, e.g., the limits of the measurement system. In some instances, "about" may mean within 1 standard deviation, as is customary for a given value.

[0066] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0067] Any aspect or embodiment described herein may be combined with any other aspect or embodiment disclosed herein. Pharmaceutical powders and other solid forms of pharmaceutical compositions, liquid formulations

[0068] In certain aspects, the present disclosure provides a pharmaceutical composition in solid form comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A). In some embodiments, the pharmaceutical composition in solid form is in the form of a powder, granule, flake, or pellet. In some embodiments, the pharmaceutical composition in solid form is in the form of a tablet or capsule.

[0069] In certain aspects, the present disclosure provides a pharmaceutical powder. In some embodiments, the pharmaceutical powder comprises an amorphous solid dispersion of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof, wherein the solid formulation comprises one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises (a) an amorphous solid dispersion comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof; and (b) one or more pharma- ceutically acceptable additives, including flow aids and surfactants. In some embodiments, the pharmaceutical powder is configured to be reconstituted into an oral liquid suspension. In some embodiments, the powder for oral suspension contains 25 mg / mL of tovorafenib after reconstitution with water, and the following inactive ingredients: microcrystalline cellulose, copovidone, colloidal silicon dioxide, mannitol, sodium lauryl sulfate, simethicone, maltodextrin, sucralose, and strawberry flavor.

[0070] In some embodiments, each Compound A tablet contains 100 mg of toborafenib and the following inactive ingredients: microcrystalline cellulose, copovidone, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, and OPADRY® Orange.

[0071] In certain aspects, the present disclosure provides oral liquid suspensions. In some embodiments, the oral liquid suspensions comprise a pharmaceutical powder or other solid formulation disclosed herein and an aqueous solution. In some embodiments, the oral liquid suspensions are produced by contacting a pharmaceutical powder disclosed herein with an aqueous solution. In some embodiments, the aqueous solution is water. In some embodiments, the oral liquid suspensions are reconstituted. In some embodiments, the oral liquid suspensions comprise a solid formulation in a kit disclosed herein and an aqueous solution. In some embodiments, the oral liquid suspensions are produced by contacting a solid formulation in a kit disclosed herein with an aqueous solution. In some embodiments, tablets and powders for oral suspensions can be used interchangeably.

[0072] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise about 10 wt% to about 80 wt% of an amorphous solid dispersion comprising Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise about 15 wt% to about 80 wt% of an amorphous solid dispersion. In some embodiments, the solid formulations comprise about 20 wt% to about 80 wt% of an amorphous solid dispersion. In some embodiments, the solid formulations comprise about 25 wt% to about 80 wt% of an amorphous solid dispersion. In some embodiments, the solid formulations comprise about 30 wt% to about 80 wt% of an amorphous solid dispersion. In some embodiments, the solid formulations comprise about 35 wt% to about 80 wt% of an amorphous solid dispersion. In some embodiments, the solid formulations comprise about 40 wt% to about 80 wt% of an amorphous solid dispersion. In some embodiments, the solid formulation comprises about 45 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 50 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 55 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 60 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 65 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 70 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 75 wt% to about 80 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 75 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 70 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 65 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 60 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 55 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 50 wt% of the amorphous solid dispersion.In some embodiments, the solid formulation comprises about 20 wt% to about 45 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 40 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 35 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 30 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 20 wt% to about 25 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 75 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 70 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 65 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 60 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 55 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 50 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 45 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 40 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 35 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 30 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation comprises about 10 wt% to about 25 wt% of the amorphous solid dispersion. In some embodiments, the solid formulation is a powder. In some embodiments, the solid formulation is in the form of granules or pellets.

[0073] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% amorphous solid dispersion. In some embodiments, the solid formulation comprises at least 5 wt%, at least 10 wt%, at least 15 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, at least 40 wt%, at least 45 wt%, at least 50 wt%, at least 55 wt%, at least 60 wt%, at least 65 wt%, at least 70 wt%, at least 75 wt%, at least 80 wt%, at least 85 wt%, at least 90 wt%, or at least 95 wt% amorphous solid dispersion. In some embodiments, the solid formulation comprises at most 5wt%, at most 10wt%, at most 15wt%, at most 20wt%, at most 25wt%, at most 30wt%, at most 35wt%, at most 40wt%, at most 45wt%, at most 50wt%, at most 55wt%, at most 60wt%, at most 65wt%, at most 70wt%, at most 75wt%, at most 80wt%, at most 85wt%, at most 90wt%, or at most 95wt% of the amorphous solid dispersion.In some embodiments, the solid formulation is a powder.In some embodiments, the solid formulation is in the form of granules or pellets. Amorphous solid dispersions

[0074] In one aspect, an amorphous solid dispersion comprising Compound A or a pharma- ceutically acceptable salt thereof is described herein. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 100 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 150 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 200 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 250 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 300 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 350 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 400 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 450 μm to about 500 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 450 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 400 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 350 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 300 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 250 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 200 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 150 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 100 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 50 μm to about 100 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 450 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 400 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 350 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 300 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 250 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 200 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 150 μm. In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 100 μm.In some embodiments, the amorphous solid dispersion has a D50 value of about 10 μm to about 100 μm.

[0075] In some embodiments, the amorphous solid dispersion has a diameter of about 10 μm, about 15 μm, about 20 μm, about 25 μm, about 30 μm, about 35 μm, about 40 μm, about 45 μm, about 50 μm, about 55 μm, about 60 μm, about 65 μm, about 70 μm, about 75 μm, about 80 μm, about 85 μm, about 90 μm, about 95 μm, about 100 μm, about 105 μm, about 110 μm, about 115 μm, about 120 μm, about 125 μm, about 130 μm, about 135 μm, about 140 μm, about 145 μm, about 150 μm, about 155 μm, about 160 μm, about 165 μm, about 170 μm, about 175 μm, about 180 μm, about 185 μm, Approximately 190μm, approximately 195μm, approximately 200μm, approximately 205μm, approximately 210μm, approximately 220μm, approximately 220μm, approximately 230μm, approximately 240μm, approximately 250μm, about 260μm, about 270μm, about 280μm, about 290μm, about 300μm, about 310μm, about 320μm, about 330μm, about 3 and having a D50 value of about 40 μm, about 350 μm, about 360 μm, about 370 μm, about 380 μm, about 390 μm, about 400 μm, about 410 μm, about 420 μm, about 430 μm, about 440 μm, about 450 μm, about 460 μm, about 470 μm, about 480 μm, about 490 μm, or about 500 μm. In some embodiments, the solid dispersion has a diameter of at least 10 μm, at least 15 μm, at least 20 μm, at least 25 μm, at least 30 μm, at least 35 μm, at least 40 μm, at least 45 μm, at least 50 μm, at least 75 μm, at least 80 μm, at least 85 μm, at least 90 μm, at least 95 μm, at least 100 μm, at least 110 μm, at least 120 μm, at least 125 μm, at least 150 μm, at least 175 μm , having a D50 value of at least 200 μm, at least 250 μm, at least 300 μm, at least 350 μm, at least 360 μm, at least 370 μm, at least 380 μm, at least 390 μm, at least 400 μm, at least 410 μm, at least 420 μm, at least 430 μm, at least 440 μm, at least 450 μm, at least 460 μm, at least 470 μm, at least 480 μm, at least 490 μm, or at least 500 μm.In some embodiments, the solid dispersion has a diameter of at most 10 μm, at most 15 μm, at most 20 μm, at most 25 μm, at most 30 μm, at most 35 μm, at most 40 μm, at most 45 μm, at most 50 μm, at most 75 μm, at most 80 μm, at most 85 μm, at most 90 μm, at most 95 μm, at most 100 μm, at most 110 μm, at most 120 μm, at most 125 μm, at most 150 μm, at most 175 μm, The D50 value may be up to 200 μm, up to 250 μm, up to 300 μm, up to 350 μm, up to 360 μm, up to 370 μm, up to 380 μm, up to 390 μm, up to 400 μm, up to 410 μm, up to 420 μm, up to 430 μm, up to 440 μm, up to 450 μm, up to 460 μm, up to 470 μm, up to 480 μm, up to 490 μm, or up to 500 μm. In some embodiments, the D50 is determined by sieve particle size analysis.

[0076] Amorphous solid dispersion can be produced by any suitable method known in the art.In some embodiments, the amorphous solid dispersion of the present disclosure is produced by hot melt extrusion.In some embodiments, the amorphous solid dispersion of the present disclosure is produced by spray drying.In some embodiments, the amorphous solid dispersion of the present disclosure is produced by dissolving compound A or its salt and polymer in a solution, and then removing the solvent. Amorphous Solid Dispersion - Polymer

[0077] In one aspect, described herein is an amorphous solid dispersion comprising Compound A, or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises one or more polymers. In some embodiments, the one or more polymers comprise polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymer (PVP-VA), cross-linked polyvinyl N-pyrrolidone, polyvinyl alcohol (PVA), polysaccharides, hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutylether-β-cyclodextrin (Captisol), cyclodextrins (e.g., γ-cyclodextrin), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyethylene glycol (PEG), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG), polysaccharides, poly(methacrylic acid-co-methyl methacrylate) (Eudragit), poloxamer, silica gel, aluminosilicate, or combinations thereof. In some embodiments, the one or more polymers include vinylpyrrolidone-vinyl acetate copolymer (PVP-VA) or HPMCAS. In some embodiments, the one or more polymers include HPMCAS. In some embodiments, the one or more polymers include vinylpyrrolidone-vinyl acetate copolymer (PVP-VA).

[0078] In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 90 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 80 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 70 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 60 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 50 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 40 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 30 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 20 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 90 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 80 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 70 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 60 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 50 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 40 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 30 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 30 wt% to about 90 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 40 wt% to about 80 wt% of one or more polymers, hi some embodiments, the amorphous solid dispersion comprises about 50 wt% to about 70 wt% of one or more polymers.In some embodiments, the amorphous solid dispersion comprises about 40 wt% to about 70 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 40 wt% to about 60 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 90 wt% of one or more polymers.

[0079] In some embodiments, the amorphous solid dispersion comprises about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% of one or more polymers. In some embodiments, the amorphous solid dispersion comprises at least 5 wt%, at least 10 wt%, at least 15 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, at least 40 wt%, at least 45 wt%, at least 50 wt%, at least 55 wt%, at least 60 wt%, at least 65 wt%, at least 70 wt%, at least 75 wt%, at least 80 wt%, at least 85 wt%, at least 90 wt%, or at least 95 wt% of one or more polymers. up to 5wt%, up to 10wt%, up to 15wt%, up to 20wt%, up to 25wt%, up to 30wt%, up to 35wt%, up to 40wt%, up to 45wt%, up to 50wt%, up to 55wt%, up to 60wt%, up to 65wt%, up to 70wt%, up to 75wt%, up to 80wt%, up to 85wt%, up to 90wt%, or up to 95wt% of one or more polymers.

[0080] In some embodiments, the suspension described herein comprises one or more polymers disclosed herein. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 200 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 150 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL to about 25 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 20 mg / mL to about 200 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 20 mg / mL to about 150 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 20 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 20 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 20 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 20 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 20 mg / mL to about 25 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 40 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is from about 40 mg / mL to about 125 mg / mL.In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 70 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 80 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 90 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 100 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 60 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 90 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 110 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 120 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 30 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 60 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 80 mg / mL.In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 90 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 110 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 120 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 50 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 90 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 110 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is about 60 mg / mL to about 125 mg / mL.

[0081] In some embodiments, the concentration of the one or more polymers in the suspension is about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about 40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 55 mg / mL, about 60 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 100 mg / mL, about 115 mg / mL, about 120 mg / mL or about 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is at least 10 mg / mL, at least 15 mg / mL, at least 20 mg / mL, at least 25 mg / mL, at least 25 mg / mL, at least 30 mg / mL, at least 35 mg / mL, at least 40 mg / mL, at least 45 mg / mL, at least 50 mg / mL, at least 55 mg / mL, at least 60 mg / mL, at least 65 mg / mL, at least 70 mg / mL, at least 75 mg / mL, at least 80 mg / mL, at least 85 mg / mL, at least 90 mg / mL, at least 95 mg / mL, at least 100 mg / mL, at least 105 mg / mL, at least 100 mg / mL, at least 115 mg / mL, at least 120 mg / mL or at least 125 mg / mL. In some embodiments, the concentration of the one or more polymers in the suspension is at most 10 mg / mL, at most 15 mg / mL, at most 20 mg / mL, at most 25 mg / mL, at most 25 mg / mL, at most 30 mg / mL, at most 35 mg / mL, at most 40 mg / mL, at most 45 mg / mL, at most 50 mg / mL, at most 55 mg / mL, at most 60 mg / mL, at most 65 mg / mL, at most 70 mg / mL, at most 75 mg / mL, at most 80 mg / mL, at most 85 mg / mL, at most 90 mg / mL, at most 95 mg / mL, at most 100 mg / mL, at most 105 mg / mL, at most 100 mg / mL, at most 115 mg / mL, at most 120 mg / mL or at most 125 mg / mL. Amorphous solid dispersion - Compound A

[0082] In some embodiments, the amorphous solid dispersion disclosed herein comprises Compound A. In some embodiments, the amorphous solid dispersion comprises (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide. In some embodiments, the amorphous solid dispersion comprises [ka] In some embodiments, the amorphous solid dispersion is a hot melt extrudate (HME). In some embodiments, the amorphous solid dispersion is prepared by dissolving Compound A or a pharma- ceutically acceptable salt thereof in a solvent and then removing at least a portion of the solvent. In some embodiments, Compound A or a pharma- ceutically acceptable salt thereof is amorphous.

[0083] In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 90 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 80 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 70 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 60 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 50 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 40 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 30 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 10 wt% to about 20 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 90 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 80 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 70 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 60 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 50 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 40 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 30 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 35 wt% to about 45 wt% of Compound A or a pharma- ceutically acceptable salt thereof.In some embodiments, the amorphous solid dispersion comprises about 30 wt% to about 90 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 40 wt% to about 80 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 50 wt% to about 70 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 40 wt% to about 70 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 40 wt% to about 60 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises about 20 wt% to about 90 wt% of Compound A or a pharma- ceutically acceptable salt thereof.

[0084] In some embodiments, the amorphous solid dispersion comprises about 10 wt%, about 20 wt%, about 30 wt%, about 40 wt%, about 50 wt%, about 60 wt%, about 70 wt%, about 80 wt%, about 90 wt%, or about 95 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises at least 10 wt%, at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, at least 60 wt%, at least 70 wt%, at least 80 wt%, at least 90 wt%, or at least 95 wt% of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the amorphous solid dispersion comprises up to 10 wt%, up to 20 wt%, up to 30 wt%, up to 40 wt%, up to 50 wt%, up to 60 wt%, up to 70 wt%, up to 80 wt%, up to 90 wt%, or up to 95 wt% Compound A or a pharma- ceutically acceptable salt thereof.

[0085] In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 10:1 to 1:10 or 5:1 to 1:5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2:1 to 1:2. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is about 1:1 to 1:2. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2 to 0.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2 to 0.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2 to 0.75. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2 to 1. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2 to 1.25. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2 to 1.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 2 to 1.75. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 1.75 to 0.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 1.50 to 0.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 1.25 to 0.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 1 to 0.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 0.75 to 0.5. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to one or more polymers is 1 to 1.

[0086] In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to the one or more polymers is about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2.0. In some embodiments, the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to the one or more polymers is at least 0.5, at least 0.6, at least 0.7, at least 0.8, at least 0.9, at least 1.0, at least 1.1, at least 1.2, at least 1.3, at least 1.4, at least 1.5, at least 1.6, at least 1.7, at least 1.8, at least 1.9, or at least 2.0. In some embodiments, the weight ratio of compound A, or a pharma- ceutically acceptable salt thereof, to the one or more polymers is at most 0.5, at most 0.6, at most 0.7, at most 0.8, at most 0.9, at most 1.0, at most 1.1, at most 1.2, at most 1.3, at most 1.4, at most 1.5, at most 1.6, at most 1.7, at most 1.8, at most 1.9, or at most 2.0.

[0087] In some embodiments, compound A or a pharma- ceutically acceptable salt thereof is in the form of an amorphous solid dispersion. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof is about 10 mg / mL to about 125 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof is about 10 mg / mL to about 100 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof is about 10 mg / mL to about 75 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof is about 10 to about 50 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof is about 10 to about 30 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof is about 10 to about 35 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 10 to about 40 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 10 to about 45 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 mg / mL to about 100 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 mg / mL to about 75 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 to about 50 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 to about 30 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 to about 35 mg / mL in the oral liquid suspensions described herein.In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 to about 40 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 25 to about 45 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 50 to about 125 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 50 to about 100 mg / mL in the oral liquid suspension described herein. In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is about 50 to about 75 mg / mL in the oral liquid suspension described herein.

[0088] In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof in the oral liquid suspension is about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, about 30 mg / mL, about 35 mg / mL, about 40 mg / mL, about 45 mg / mL, about 50 mg / mL, about 55 mg / mL, about 65 mg / mL, about 70 mg / mL, about 75 mg / mL, about 80 mg / mL, about 85 mg / mL, about 90 mg / mL, about 95 mg / mL, about 100 mg / mL, about 105 mg / mL, about 110 mg / mL, about 115 mg / mL, about 120 mg / mL, or about 125 mg / mL. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof in the oral liquid suspension is about 10 mg / mL. In some embodiments, the concentration of compound A or a pharma- ceutically acceptable salt thereof in the oral liquid suspension is about 25 mg / mL. In some embodiments, the concentration of compound A or its pharma- ceutically acceptable salt is about 50mg / mL in oral liquid suspension.In some embodiments, the concentration of compound A or its pharma- ceutically acceptable salt is at least 10mg / mL, at least 15mg / mL, at least 20mg / mL, at least 25mg / mL, at least 30mg / mL, at least 35mg / mL, at least 40mg / mL, at least 45mg / mL, at least 50mg / mL, at least 55mg / mL, at least 65mg / mL, at least 70mg / mL, at least 75mg / mL, at least 80mg / mL, at least 85mg / mL, at least 90mg / mL, at least 95mg / mL, at least 100mg / mL, at least 105mg / mL, at least 110mg / mL, at least 115mg / mL, at least 120mg / mL, or at least 125mg / mL in oral liquid suspension.In some embodiments, the concentration of Compound A or a pharma- ceutically acceptable salt thereof is at most 10 mg / mL, at most 15 mg / mL, at most 20 mg / mL, at most 25 mg / mL, at most 30 mg / mL, at most 35 mg / mL, at most 40 mg / mL, at most 45 mg / mL, at most 50 mg / mL, at most 55 mg / mL, at most 65 mg / mL, at most 70 mg / mL, at most 75 mg / mL, at most 80 mg / mL, at most 85 mg / mL, at most 90 mg / mL, at most 95 mg / mL, at most 100 mg / mL, at most 105 mg / mL, at most 110 mg / mL, at most 115 mg / mL, at most 120 mg / mL, or at most 125 mg / mL in the oral liquid suspension. Pharmaceutically acceptable excipients

[0089] The pharmaceutical compositions described herein, for example, pharmaceutical compositions in solid form (e.g., pharmaceutical powders) and suspensions, can include one or more pharma- ceutically acceptable additives. In some embodiments, the one or more pharma- ceutically acceptable additives are in a mixture with the amorphous solid dispersion in the pharmaceutical powder. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 90 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 80 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 60 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 50 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 40 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 30 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 20 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 90 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 80 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 60 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 50 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 40 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 10 wt% to about 30 wt% of one or more pharma- ceutically acceptable excipients, hi some embodiments, the pharmaceutical powder comprises about 40 wt% to about 80 wt% of one or more pharma- ceutically acceptable excipients.In some embodiments, the pharmaceutical powder comprises about 50 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 40 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 40 wt% to about 60 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 20 wt% to about 90 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 25 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 20 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 15 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the pharmaceutical powder comprises about 5 wt% to about 10 wt% of one or more pharma- ceutically acceptable additives.

[0090] In some embodiments, the pharmaceutical powder comprises about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% of one or more pharma- ceutically acceptable excipients. In some embodiments, the pharmaceutical powder comprises at least 10 wt%, at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, at least 60 wt%, at least 70 wt%, at least 80 wt%, at least 90 wt%, or at least 95 wt% of one or more pharma- ceutically acceptable excipients. In some embodiments, the pharmaceutical powder comprises up to 5 wt%, up to 10 wt%, up to 15 wt%, up to 20 wt%, up to 25 wt%, up to 30 wt%, up to 35 wt%, up to 40 wt%, up to 45 wt%, up to 50 wt%, up to 55 wt%, up to 60 wt%, up to 65 wt%, up to 70 wt%, up to 75 wt%, up to 80 wt%, up to 85 wt%, up to 90 wt%, or up to 95 wt% of one or more pharma- ceutically acceptable excipients.

[0091] In some embodiments, the solid formulations described herein comprise one or more pharma- ceutically acceptable additives and an amorphous solid dispersion. In some embodiments, the solid formulation comprises from about 5 wt% to about 90 wt% of one or more pharma- ceutically acceptable additives (i.e., one or more pharma- ceutically acceptable additives are present in the solid formulation at about 5 wt% to about 90 wt%). In some embodiments, the solid formulation comprises from about 5 wt% to about 80 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises from about 5 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises from about 5 wt% to about 60 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises from about 5 wt% to about 50 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises from about 5 wt% to about 40 wt% of one or more pharma- ceutical acceptable additives. In some embodiments, the solid formulation comprises about 5 wt% to about 30 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 5 wt% to about 20 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 10 wt% to about 90 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 10 wt% to about 80 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 10 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 10 wt% to about 60 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 10 wt% to about 50 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 10 wt% to about 40 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises from about 10 wt% to about 30 wt% of one or more pharma- ceutically acceptable excipients, hi some embodiments, the solid formulation comprises from about 40 wt% to about 80 wt% of one or more pharma- ceutically acceptable excipients.In some embodiments, the solid formulation comprises about 50 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 40 wt% to about 70 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 40 wt% to about 60 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 20 wt% to about 90 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 5 wt% to about 25 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 5 wt% to about 20 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 5 wt% to about 15 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 5 wt% to about 10 wt% of one or more pharma- ceutically acceptable additives. In some embodiments, the solid formulation comprises about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% of one or more pharma- ceutically acceptable excipients. In some embodiments, the solid formulation comprises at least 10 wt%, at least 20 wt%, at least 30 wt%, at least 40 wt%, at least 50 wt%, at least 60 wt%, at least 70 wt%, at least 80 wt%, at least 90 wt%, or at least 95 wt% of one or more pharma- ceutically acceptable excipients. In some embodiments, the solid formulation comprises up to 5 wt%, up to 10 wt%, up to 15 wt%, up to 20 wt%, up to 25 wt%, up to 30 wt%, up to 35 wt%, up to 40 wt%, up to 45 wt%, up to 50 wt%, up to 55 wt%, up to 60 wt%, up to 65 wt%, up to 70 wt%, up to 75 wt%, up to 80 wt%, up to 85 wt%, up to 90 wt%, or up to 95 wt% of one or more pharma- ceutically acceptable excipients. In some embodiments, the solid formulation is a powder.In some embodiments, the solid formulation is in the form of granules or pellets.

[0092] In some embodiments, the one or more pharma- ceutically acceptable additives include an antifoaming agent, a bulking agent, a colorant, a preservative, a flavoring agent, a sweetener, or a combination thereof. In some embodiments, the one or more pharma- ceutically acceptable additives include a colorant, a preservative, a flavoring agent, a sweetener, or a combination thereof. In some embodiments, the one or more pharma- ceutically acceptable additives include a colorant. In some embodiments, the one or more pharma- ceutical acceptable additives include a preservative. In some embodiments, the one or more pharma- ceutical acceptable additives include a flavoring agent. In some embodiments, the one or more pharma- ceutical acceptable additives include a sweetener.

[0093] Some pharma- ceutically acceptable excipients are well known in the pharmaceutical art and are described, for example, in Rowe et al., Handbook of Pharmaceutical Excipients: A Comprehensive Guide to Uses, Properties, and Safety, 5 th Ed., 2006, and Remington: The Science and Practice of Pharmacy (Gennaro, 21 stEd. Mack Pub. Co., Easton, PA (2005)). Exemplary pharma- ceutical acceptable additives include sterile saline and phosphate-buffered saline at physiological pH. Preservatives, stabilizers, dyes, buffers, and the like may be provided in the pharmaceutical composition. In addition, antioxidants and suspending agents may also be used. In general, the type of additive is selected based on the mode of administration and the chemical composition of the active ingredient(s). Alternatively, the compositions described herein may be formulated as a lyophilizate. The compositions described herein may be lyophilized or otherwise formulated as a lyophilized product using one or more suitable additive solutions to solubilize and / or dilute the pharmaceutical agent(s) of the composition upon administration. In other embodiments, the pharmaceutical agent may be encapsulated in liposomes using techniques known and practiced in the art. In certain particular embodiments, the pharmaceutical agent is not formulated in liposomes for application to stents used to treat arteries that are not completely occluded but are highly occluded. The pharmaceutical compositions may be formulated for any suitable mode of administration as described herein and in the art. Defoamer

[0094] In some embodiments, one or more of the pharma- ceutically acceptable additives described herein comprises an antifoaming agent. In some embodiments, the antifoaming agent comprises simethicone or dimethicone. In some embodiments, the antifoaming agent comprises simethicone. The antifoaming agent can be in the form of a powder in a solid carrier (e.g., antifoaming agent and maltodextrin, e.g., 30% simethicone / 70% maltodextrin). In some embodiments, the antifoaming agent is held by a solid carrier. In some embodiments, the solid carrier is maltodextrin, microcrystalline cellulose, or calcium carbonate. In some embodiments, the antifoaming agent is in liquid form. In some embodiments, the antifoaming agent is a suspension.

[0095] In some embodiments, the solid formulation, e.g., pharmaceutical powder, comprises from about 0.1 wt% to about 15 wt% of an antifoaming agent, hi some embodiments, the solid formulation comprises from about 0.1 wt% to about 14 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 13 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 12 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 11 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 10 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 9 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 8 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 5 wt% to about 8 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 7 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 6 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 5 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 4 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 3 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 2 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 1 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.9 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.8 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.7 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.6 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.5 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.4 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.3 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.25 wt% of the antifoaming agent. In some embodiments, the solid formulation is a powder. In some embodiments, the solid formulation is in the form of flakes, granules, or pellets. In some embodiments, the antifoaming agent comprises simethicone and a carrier, such as maltodextrin. In some embodiments, the carrier is starch. In some embodiments, the antifoaming agent comprises simethicone and maltodextrin.In some embodiments, the antifoaming agent comprises simethicone (about 30 wt%) and maltodextrin (about 70 wt%). In some embodiments, the antifoaming agent comprises simethicone (30 wt%) and maltodextrin (70 wt%). In some embodiments, the antifoaming agent comprises simethicone (20-40 wt%) and maltodextrin (60-80 wt%).

[0096] In some embodiments, the solid formulation, e.g., pharmaceutical powder, comprises about 0.1 wt% to about 0.2 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 0.15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.15 wt% to about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.2 wt% to about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.25 wt% to about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.3 wt% to about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.4 wt% to about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.5 wt% to about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises about 0.6 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.7 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.8 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.9 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 1 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 2 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 3 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 4 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 5 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 6 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 7 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 8 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 9 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 10 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 11 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 12 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 13 wt% to about 15 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 14 wt% to about 15 wt% of the antifoaming agent.In some embodiments, the solid formulation comprises about 2 wt% to about 10 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 3 wt% to about 10 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 3 wt% to about 9 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 3 wt% to about 8 wt% of the antifoaming agent. In some embodiments, the solid formulation comprises about 0.1 wt% to about 15 wt% of simethicone. In some embodiments, the solid formulation comprises about 3 wt% to about 8 wt% of simethicone. In some embodiments, the solid formulation comprises about 0.5 wt% to about 3 wt% of simethicone. In some embodiments, the solid formulation is a powder. In some embodiments, the solid formulation is in the form of flakes, granules, or pellets.

[0097] In some embodiments, the solid formulation, e.g., pharmaceutical powder, is about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, %, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, or about 15 wt% of an antifoaming agent. In some embodiments, the solid formulation comprises at least 0.1 wt%, at least 0.2 wt%, at least 0.3 wt%, at least 0.4 wt%, at least 0.5 wt%, at least 0.6 wt%, at least 0.7 wt%, at least 0.8 wt%, at least 0.9 wt%, at least 1 wt%, at least 1.1 wt%, at least 1.2 wt%, at least 1.3 wt%, at least 1.4 wt%, at least 1.5 wt%, at least 2 wt%, at least 2.5 wt%, at least 3 wt%, at least 3.5 wt%, at least 4 wt%, at least 4.5 wt%, at least 5 wt%, at least 6 wt%, at least 7 wt%, at least 8 wt%, at least 9 wt%, at least 10 wt%, at least 11 wt%, at least 12 wt%, at least 13 wt%, at least 14 wt%, or at least 15 wt% antifoaming agent. In some embodiments, the solid formulation comprises at most 0.1 wt%, at most 0.2 wt%, at most 0.3 wt%, at most 0.4 wt%, at most 0.5 wt%, at most 0.6 wt%, at most 0.7 wt%, at most 0.8 wt%, at most 0.9 wt%, at most 1 wt%, at most 1.1 wt%, at most 1.2 wt%, at most 1.3 wt%, at most 1.4 wt%, at most 1.5 wt%, at most 1.6 wt%, at most 1.8 wt%, at most 1.9 wt%, at most 2.0 wt%, at most 2.2 wt%, at most 2.4 wt%, at most 2.5 wt%, at most 2.6 wt%, at most 2.7 wt%, at most 2.8 wt%, at most 2.9 wt%, at most 3.0 wt%, at most 3.1 wt%, at most 3.2 wt%, at most 3.3 wt%, at most 3.4 wt%, at most 3.5 wt%, at most 3.6 wt%, at most 3.7 wt%, at most 3.8 wt%, at most 3.9 ...5 wt%, at most 3.6 wt%, at t%, up to 2 wt%, up to 2.5 wt%, up to 3 wt%, up to 3.5 wt%, up to 4 wt%, up to 4.5 wt%, up to 5 wt%, up to 6 wt%, up to 7 wt%, up to 8 wt%, up to 9 wt%, up to 10 wt%, up to 11 wt%, up to 12 wt%, up to 13 wt%, up to 14 wt%, or up to 15 wt% of antifoaming agent. In some embodiments, the solid formulation is a powder.In some embodiments, the solid formulation is in the form of flakes, granules, or pellets.

[0098] In some embodiments, the suspension described herein comprises one or more pharma- ceutically acceptable additives disclosed herein. In some embodiments, the one or more pharma- ceutically acceptable additives comprise an antifoaming agent. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 25 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 20 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 15 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 9 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 8 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 7 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 6 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 5 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 4 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 3 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 2 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 5 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 10 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 15 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 20 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 25 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 1 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the antifoaming agent in the suspension is about 3 mg / mL to about 8 mg / mL.In some embodiments, the concentration of the antifoam agent in the suspension is about 1 mg / mL, about 2 mg / mL, about 3 mg / mL, about 4 mg / mL, about 5 mg / mL, about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, or about 30 mg / mL. In some embodiments, the concentration of the antifoam agent in the suspension is at least 1 mg / mL, at least 2 mg / mL, at least 3 mg / mL, at least 4 mg / mL, at least 5 mg / mL, at least 10 mg / mL, at least 15 mg / mL, at least 20 mg / mL, at least 25 mg / mL, or at least 30 mg / mL. In some embodiments, the concentration of the antifoam agent in the suspension is at most 1 mg / mL, at most 2 mg / mL, at most 3 mg / mL, at most 4 mg / mL, at most 5 mg / mL, at most 10 mg / mL, at most 15 mg / mL, at most 20 mg / mL, at most 25 mg / mL, or at most 30 mg / mL. Bulking Agent

[0099] In some embodiments, one or more of the pharma- ceutically acceptable excipients described herein comprises a bulking agent. In some embodiments, the bulking agent comprises a polysaccharide, a sugar or derivative thereof, or both. In some embodiments, the bulking agent comprises a polysaccharide. In some embodiments, the bulking agent is a sugar. In some embodiments, the bulking agent comprises a cellulose, a starch, a synthetic soluble fiber, a sugar alcohol, or a combination thereof. In some embodiments, the bulking agent comprises a cellulose. In some embodiments, the bulking agent comprises a starch. In some embodiments, the bulking agent comprises a maltodextrin. In some embodiments, the bulking agent comprises HPMC. In some embodiments, the bulking agent comprises dicalcium phosphate dihydrate (DCP). In some embodiments, the bulking agent comprises a synthetic soluble fiber. In some embodiments, the bulking agent comprises a sugar alcohol. In some embodiments, the bulking agent comprises mannitol. In some embodiments, the bulking agent comprises microcrystalline cellulose, polydextrose, sodium carboxymethylcellulose (sodium CMC), or a combination thereof. In some embodiments, the bulking agent comprises microcrystalline cellulose. In some embodiments, the bulking agent comprises polydextrose, hi some embodiments, the bulking agent comprises sodium carboxymethylcellulose.

[0100] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise about 5 wt% to about 90 wt% of the filler (i.e., the filler is present in the solid formulation at about 5 wt% to about 90 wt%). In some embodiments, the solid formulations comprise about 5 wt% to about 80 wt% of the filler. In some embodiments, the solid formulations comprise about 5 wt% to about 70 wt% of the filler. In some embodiments, the solid formulations comprise about 5 wt% to about 60 wt% of the filler. In some embodiments, the solid formulations comprise about 5 wt% to about 50 wt% of the filler. In some embodiments, the solid formulations comprise about 5 wt% to about 40 wt% of the filler. In some embodiments, the solid formulations comprise about 5 wt% to about 30 wt% of the filler. In some embodiments, the solid formulations comprise about 5 wt% to about 20 wt% of the filler. In some embodiments, the solid formulation comprises about 10 wt% to about 90 wt% of the filler. In some embodiments, the solid formulation comprises about 10 wt% to about 80 wt% of the filler. In some embodiments, the solid formulation comprises about 10 wt% to about 70 wt% of the filler. In some embodiments, the solid formulation comprises about 10 wt% to about 60 wt% of the filler. In some embodiments, the solid formulation comprises about 10 wt% to about 50 wt% of the filler. In some embodiments, the solid formulation comprises about 10 wt% to about 40 wt% of the filler. In some embodiments, the solid formulation comprises about 10 wt% to about 30 wt% of the filler. In some embodiments, the solid formulation comprises about 40 wt% to about 80 wt% of the filler. In some embodiments, the solid formulation comprises about 50 wt% to about 70 wt% of the filler. In some embodiments, the solid formulation comprises about 40 wt% to about 70 wt% of the filler. In some embodiments, the solid formulation comprises about 40 wt% to about 60 wt% of the filler. In some embodiments, the solid formulation comprises about 20 wt% to about 90 wt% of the filler. In some embodiments, the solid formulation comprises about 5 wt% to about 25 wt% of the filler. In some embodiments, the solid formulation comprises about 5 wt% to about 20 wt% of the filler. In some embodiments, the solid formulation comprises about 5 wt% to about 15 wt% of the filler. In some embodiments, the solid formulation comprises about 5 wt% to about 10 wt% of the filler. In some embodiments, the solid formulation is a powder. In some embodiments, the solid formulation is in the form of flakes, granules, or pellets.

[0101] In some embodiments, the solid formulation, e.g., pharmaceutical powder, comprises about 5 wt%, about 10 wt%, about 15 wt%, about 20 wt%, about 25 wt%, about 30 wt%, about 35 wt%, about 40 wt%, about 45 wt%, about 50 wt%, about 55 wt%, about 60 wt%, about 65 wt%, about 70 wt%, about 75 wt%, about 80 wt%, about 85 wt%, about 90 wt%, or about 95 wt% of a bulking agent. In some embodiments, the solid formulation comprises at least 5 wt%, at least 10 wt%, at least 15 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, at least 40 wt%, at least 45 wt%, at least 50 wt%, at least 55 wt%, at least 60 wt%, at least 65 wt%, at least 70 wt%, at least 75 wt%, at least 80 wt%, at least 85 wt%, at least 90 wt%, or at least 95 wt% of filler. In some embodiments, the solid formulation comprises up to 5wt%, up to 10wt%, up to 15wt%, up to 20wt%, up to 25wt%, up to 30wt%, up to 35wt%, up to 40wt%, up to 45wt%, up to 50wt%, up to 55wt%, up to 60wt%, up to 65wt%, up to 70wt%, up to 75wt%, up to 80wt%, up to 85wt%, up to 90wt%, or up to 95wt% of filler.In some embodiments, the solid formulation is a powder.In some embodiments, the solid formulation is in the form of flakes, granules, or pellets.

[0102] In some embodiments, the suspension comprises one or more pharma- ceutically acceptable excipients disclosed herein.

[0103] In some embodiments, the concentration of the bulking agent in the suspension is about 30 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 40 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 60 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 70 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 80 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 90 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 100 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 125 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 150 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 175 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 200 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 250 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 300 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 350 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 400 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 450 mg / mL to about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 450 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 400 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 350 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 300 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 250 mg / mL.In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 200 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 150 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 100 mg / mL to about 250 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 125 mg / mL to about 200 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL to about 150 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is about 50 mg / mL, about 75 mg / mL, about 100 mg / mL, about 125 mg / mL, about 150 mg / mL, about 175 mg / mL, about 200 mg / mL, about 250 mg / mL, about 300 mg / mL, about 350 mg / mL, about 400 mg / mL, about 450 mg / mL, or about 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is at least 50 mg / mL, at least 75 mg / mL, at least 100 mg / mL, at least 125 mg / mL, at least 150 mg / mL, at least 175 mg / mL, at least 200 mg / mL, at least 250 mg / mL, at least 300 mg / mL, at least 350 mg / mL, at least 400 mg / mL, at least 450 mg / mL, or at least 500 mg / mL. In some embodiments, the concentration of the bulking agent in the suspension is up to 50 mg / mL, up to 75 mg / mL, up to 100 mg / mL, up to 125 mg / mL, up to 150 mg / mL, up to 175 mg / mL, up to 200 mg / mL, up to 250 mg / mL, up to 300 mg / mL, up to 350 mg / mL, up to 400 mg / mL, up to 450 mg / mL, or up to 500 mg / mL. Flow aid

[0104] In some embodiments, one or more of the pharma- ceutically acceptable excipients described herein comprises a flow aid. In some embodiments, the flow aid is a glidant. In some embodiments, the flow aid is selected from silicon dioxide, magnesium stearate, talc, starch, magnesium silicate, hydrated sodium sulfoaluminate, and combinations thereof. In some embodiments, the flow aid is selected from magnesium stearate, talc, starch, magnesium silicate, hydrated sodium sulfoaluminate, and combinations thereof. In some embodiments, the flow aid is silicon dioxide. In some embodiments, the silicon dioxide comprises fumed silica, colloidal silicon dioxide (CSD), or both. In some embodiments, the flow aid is porous silica. In some embodiments, the flow aid is non-porous silica.

[0105] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise about 0.25 wt% to about 10 wt% of the flow aid (i.e., the flow aid is present in the solid formulation at about 0.25 wt% to about 10 wt%). In some embodiments, the solid formulations comprise about 0.5 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulations comprise about 1 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulations comprise about 1.5 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulations comprise about 2 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulations comprise about 2.5 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulations comprise about 3 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 3.5 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 4 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 4.5 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 5 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 6 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 7 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 8 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 9 wt% to about 10 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 9 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 8 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 7 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 6 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 5 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 4.5 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 4 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 3.5 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 3 wt% of the flow aid.In some embodiments, the solid formulation comprises about 0.5 wt% to about 2.5 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 2 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 1.5 wt% of the flow aid. In some embodiments, the solid formulation comprises about 0.5 wt% to about 1 wt% of the flow aid. In some embodiments, the solid formulation is a powder. In some embodiments, the solid formulation is in the form of flakes, granules, or pellets.

[0106] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of a flow aid. In some embodiments, the solid formulation comprises at least 0.5 wt%, at least 0.6 wt%, at least 0.7 wt%, at least 0.8 wt%, at least 0.9 wt%, at least 1 wt%, at least 1.1 wt%, at least 1.2 wt%, at least 1.3 wt%, at least 1.4 wt%, at least 1.5 wt%, at least 2 wt%, at least 2.5 wt%, at least 3 wt%, at least 3.5 wt%, at least 4 wt%, at least 4.5 wt%, at least 5 wt%, at least 6 wt%, at least 7 wt%, at least 8 wt%, at least 9 wt%, or at least 10 wt% of a flow aid. In some embodiments, the pharmaceutical composition comprises up to 0.5 wt%, up to 0.6 wt%, up to 0.7 wt%, up to 0.8 wt%, up to 0.9 wt%, up to 1 wt%, up to 1.1 wt%, up to 1.2 wt%, up to 1.3 wt%, up to 1.4 wt%, up to 1.5 wt%, up to 2 wt%, up to 2.5 wt%, up to 3 wt%, up to 3.5 wt%, up to 4 wt%, up to 4.5 wt%, up to 5 wt%, up to 6 wt%, up to 7 wt%, up to 8 wt%, up to 9 wt%, or up to 10 wt% of a flow aid.

[0107] In some embodiments, the suspension described herein comprises one or more pharma- ceutically acceptable additives disclosed herein. In some embodiments, the one or more pharma- ceutically acceptable additives comprise a flow aid. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL to about 25 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL to about 20 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL to about 15 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL to about 5 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 5 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 10 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 15 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 20 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 25 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 5 mg / mL to about 15 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 10 mg / mL to about 15 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is about 3 mg / mL, about 5 mg / mL, about 10 mg / mL, about 15 mg / mL, about 20 mg / mL, about 25 mg / mL, or about 30 mg / mL. In some embodiments, the concentration of the flow aid in the suspension is at least 3 mg / mL, at least 5 mg / mL, at least 10 mg / mL, at least 15 mg / mL, at least 20 mg / mL, at least 25 mg / mL, or at least 30 mg / mL.In some embodiments, the concentration of the flow aid in the suspension is at most 3 mg / mL, at most 5 mg / mL, at most 10 mg / mL, at most 15 mg / mL, at most 20 mg / mL, at most 25 mg / mL, or at most 30 mg / mL. Surfactants

[0108] The solid formulation and / or liquid formulation described herein may include one or more surfactants. In some embodiments, one or more of the pharma- ceutically acceptable additives described herein include a surfactant. In some embodiments, the surfactant includes a cationic surfactant, an anionic surfactant, a nonionic surfactant, or a combination thereof. In some embodiments, the surfactant is a cationic surfactant. In some embodiments, the surfactant is an anionic surfactant. In some embodiments, the surfactant is nonionic. A nonionic surfactant does not have a charged group at its head. Exemplary nonionic surfactants include, but are not limited to, fatty alcohols, cetyl alcohol, stearyl alcohol, cetostearyl alcohol, and oleyl alcohol. Exemplary non-ionic surfactants include, but are not limited to, polyethylene glycol alkyl ethers (e.g., octaethylene glycol monododecyl ether, pentaethylene glycol monododecyl ether), polypropylene glycol alkyl ethers, glucoside alkyl ethers (e.g., decyl glucoside, lauryl glucoside, octyl glucoside), polyethylene glycol octyl phenyl ethers (e.g., Triton® X-100), polyethylene glycol alkyl phenyl ethers (e.g., nonoxynol-9), glycerol alkyl esters (e.g., glyceryl laurate), polyoxyethylene glycol sorbitan alkyl esters (e.g., polysorbates), sorbitan alkyl esters (e.g., Spans®), cocamide MEA, cocamide DEA, dodecyl dimethylamine oxide, Tocofersolan (TPGS), block copolymers of polyethylene glycol and polypropylene glycol (e.g., poloxamers), and polyethoxylated tallow amine (POEA). In some embodiments, the surfactant is a non-ionic surfactant comprising polyethylene glycol. In some embodiments, the surfactant is a block copolymer of polyethylene glycol and polypropylene glycol, hi some embodiments, the surfactant comprises a poloxamer.

[0109] In some embodiments, the nonionic surfactant has a number average molecular weight of about 1000 to about 100,000 Da, about 2000 to about 20,000 Da, about 4000 to about 15,000 Da, about 6000 to about 12,000 Da, or about 7000 to about 10,000 Da. In some embodiments, the nonionic surfactant has a number average molecular weight of about 7000 to about 10,000 Da. In some embodiments, the nonionic surfactant has an ethylene glycol content of about 30 wt% to about 99 wt%, about 50 wt% to about 95 wt%, about 60 wt% to about 95 wt%, about 75 wt% to about 90 wt%, or about 80 wt% to about 85 wt%. In some embodiments, the nonionic surfactant has an ethylene glycol content of about 80 wt% to about 85 wt%.

[0110] The surfactant used in the present disclosure can include cationic surfactant.Cationic surfactant includes pH-dependent primary, secondary or tertiary amine, such as octenidine dihydrochloride; and permanently charged quaternary ammonium salt, such as cetrimonium bromide (CTAB), cetylpyridinium chloride (CPC), benzalkonium chloride (BAC), benzethonium chloride (BZT), dimethyldioctadecylammonium chloride and dioctadecyldimethylammonium bromide (DODAB).

[0111] The surfactant used in the present disclosure can include anionic surfactants. Anionic surfactants contain anionic functional groups at their head, such as sulfate, sulfonate, phosphate, and carboxylate. Exemplary anionic surfactants include, but are not limited to, ammonium lauryl sulfate, sodium lauryl sulfate (sodium dodecyl sulfate, SLS, or SDS), and related alkyl ether sulfates sodium laureth sulfate (sodium lauryl ether sulfate or SLES), sodium myreth sulfate, docusate (sodium dioctyl sulfosuccinate), perfluorooctane sulfonate (PFOS), perfluorobutane sulfonate, docusate sodium, alkylaryl ether phosphate, and alkyl ether phosphate. In some embodiments, the surfactant includes sodium lauryl sulfate (SLS).

[0112] The surfactant used in the present disclosure can be a zwitterionic surfactant. Zwitterionic (amphoteric) surfactant refers to those that have cationic and anionic centers bound to the same molecule. Exemplary zwitterionic surfactants include, but are not limited to, the phospholipids phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin.

[0113] In some embodiments, the surfactant comprises a cationic surfactant, an anionic surfactant, a non-ionic surfactant, or a combination thereof. In some embodiments, the surfactant comprises sodium lauryl sulfate (SLS). In some embodiments, the surfactant comprises a poloxamer.

[0114] In some embodiments, one or more pharma- ceutically acceptable additives described herein include CTAB. In some embodiments, one or more pharma- ceutically acceptable additives described herein include SLS. In some embodiments, one or more pharma- ceutically acceptable additives described herein include sodium docusate. In some embodiments, one or more pharma- ceutically acceptable additives described herein include Tween® 80. In some embodiments, one or more pharma- ceutically acceptable additives described herein include Tween® 20. In some embodiments, one or more pharma- ceutically acceptable additives described herein include poloxamer.

[0115] In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 0.02 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 0.03 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 0.04 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 0.05 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 0.1 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 0.25 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 0.5 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulations comprise from about 1 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 2 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 3 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 4 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 5 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 6 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 7 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 8 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises about 9 wt% to about 10 wt% of a surfactant. In some embodiments, the solid formulation described herein comprises about 0.01 wt% to about 9 wt% of a surfactant. In some embodiments, the solid formulation described herein comprises about 0.01 wt% to about 8 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 7 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 6 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 5 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 4 wt% of a surfactant.In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 3 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 2 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 1 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 0.5 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 0.25 wt% of a surfactant. In some embodiments, the solid formulations described herein comprise from about 0.01 wt% to about 0.1 wt% of a surfactant. In some embodiments, the solid formulation is a powder. In some embodiments, the solid formulation is in the form of a flake, granule, or pellet.

[0116] In some embodiments, the solid formulation, e.g., pharmaceutical powder, is about 0.01 wt%, about 0.02 wt%, about 0.03 wt%, about 0.04 wt%, about 0.05 wt%, 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 10 wt%, about 15 ... %, about 1 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt% of a surfactant. In some embodiments, the solid formulation comprises at least 0.01 wt%, at least 0.02 wt%, at least 0.03 wt%, at least 0.04 wt%, at least 0.05 wt%, at least 0.1 wt%, at least 0.2 wt%, at least 0.3 wt%, at least 0.4 wt%, at least 0.5 wt%, at least 0.6 wt%, at least 0.7 wt%, at least 0.8 wt%, at least 0.9 wt%, at least 1 wt%, at least 1.1 wt%, at least 1.2 wt%, at least 1.3 wt%, at least 1.4 wt%, at least 1.5 wt%, at least 2 wt%, at least 2.5 wt%, at least 3 wt%, at least 3.5 wt%, at least 4 wt%, at least 4.5 wt%, at least 5 wt%, at least 6 wt%, at least 7 wt%, at least 8 wt%, at least 9 wt%, or at least 10 wt% surfactant.In some embodiments, the solid formulation comprises at most 0.01 wt%, at most 0.02 wt%, at most 0.03 wt%, at most 0.04 wt%, at most 0.05 wt%, at most 0.1 wt%, at most 0.2 wt%, at most 0.3 wt%, at most 0.4 wt%, at most 0.5 wt%, at most 0.6 wt%, at most 0.7 wt%, at most 0.8 wt%, at most 0.9 wt%, at most 1 ...1 wt%, at most 0.1 wt%, at most 0.1 wt%, at most 0.1 wt%, at most 0.1 wt%, at most 0.1 wt%, at most 0.1 wt%, at most 0.1 wt%, at most %, up to 1.1 wt%, up to 1.2 wt%, up to 1.3 wt%, up to 1.4 wt%, up to 1.5 wt%, up to 2 wt%, up to 2.5 wt%, up to 3 wt%, up to 3.5 wt%, up to 4 wt%, up to 4.5 wt%, up to 5 wt%, up to 6 wt%, up to 7 wt%, up to 8 wt%, up to 9 wt%, or up to 10 wt% of surfactant. In some embodiments, the solid formulation is a powder. In some embodiments, the solid formulation is in the form of flakes, granules, or pellets.

[0117] In some embodiments, the suspension described herein comprises one or more pharma- ceutically acceptable additives disclosed herein. In some embodiments, the one or more pharma- ceutically acceptable additives comprise a surfactant. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 1 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 1.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 2 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 2.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 3 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 3.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 4 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 4.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 6 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 7 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 8 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 9 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 9 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 8 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 7 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 6 mg / mL.In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 5 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 4.5 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 4 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 3.5 mg / mL to about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 3 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 1 mg / mL to about 2.5 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 2.5 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 2 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL to about 1 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is about 0.5 mg / mL, about 1 mg / mL, about 1.5 mg / mL, about 2 mg / mL, about 2.5 mg / mL, about 3 mg / mL, about 3.5 mg / mL, about 4 mg / mL, about 4.5 mg / mL, about 5 mg / mL, about 6 mg / mL, about 7 mg / mL, about 8 mg / mL, about 9 mg / mL, or about 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is at least 0.5 mg / mL, at least 1 mg / mL, at least 1.5 mg / mL, at least 2 mg / mL, at least 2.5 mg / mL, at least 3 mg / mL, at least 3.5 mg / mL, at least 4 mg / mL, at least 4.5 mg / mL, at least 5 mg / mL, at least 6 mg / mL, at least 7 mg / mL, at least 8 mg / mL, at least 9 mg / mL, or at least 10 mg / mL. In some embodiments, the concentration of the surfactant in the suspension is at most 0.5 mg / mL, at most 1 mg / mL, at most 1.5 mg / mL, at most 2 mg / mL, at most 2.5 mg / mL, at most 3 mg / mL, at most 3.5 mg / mL, at most 4 mg / mL, at most 4.5 mg / mL, at most 5 mg / mL, at most 6 mg / mL, at most 7 mg / mL, at most 8 mg / mL, at most 9 mg / mL, or at most 10 mg / mL.

[0118] In some embodiments, the pharmaceutical powder of the present disclosure comprises: (i) about 40 wt % to about 60 wt % of Compound A and (ii) about 40 wt % to about 60 wt % of PVP-VA, the amorphous solid dispersion being a hot melt extrudate; about 30 wt% to about 70 wt% of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; about 0.1 wt % to 5 wt % of a surfactant, the surfactant being SLS; about 0.25 wt% to 6 wt% of a flow aid, the flow aid being a CSD; and About 0.5 wt% to 5 wt% of an antifoaming agent, which is simethicone or dimethicone; Includes.

[0119] In some embodiments, the solid formulation comprises: (a) an amorphous solid dispersion comprising about 40 wt% to about 60 wt% of Compound A and about 40 wt% to about 60 wt% of PVP-VA, which is a hot melt extrudate and is present in the solid formulation at about 40 wt% to about 60 wt%; (b) about 30 wt%-70 wt% of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; (c) about 0.1 wt % to 5 wt % of a surfactant, the surfactant being SLS; (d) about 0.25 wt % to 6 wt % of a flow aid, the flow aid being a CSD; and (e) about 0.5 wt% to 5 wt% of an antifoaming agent, the antifoaming agent being simethicone; Includes. Sweeteners and flavourings

[0120] The solid formulation and / or liquid formulation described herein can include one or more sweeteners, one or more flavoring agents, or both.In some embodiments, one or more pharma-ceutically acceptable additives described herein include a sweetener.In some embodiments, one or more pharma-ceutically acceptable additives described herein include a flavoring agent.

[0121] Sweeteners or sweetening agents may include any compound that provides sweetness that enhances the palatability of the formulation, including natural and synthetic sugars and natural and synthetic non-sugar sweeteners.These may include glucose, fructose, sucrose, or other pharma-ceutically acceptable monosaccharides and disaccharides, or sugar alcohols, such as xylitol.Sweeteners may also include maltodextrin, polydextrose, etc.Other sweeteners may include glycerin, inulin, maltol, acesulfame salts, alitame, aspartame, neotame, cyclamate salts, sucralose, sorbitol liquid, saccharin and its salts, and other artificial and naturally occurring agents that provide sweetness, either alone or in combination.

[0122] Exemplary sweeteners include, but are not limited to, glucose, fructose, sucrose, xylitol, tagatose, sucralose, maltitol, isomaltulose, hydrogenated isomaltulose sold under the trade name Isomalt™, lactitol, sorbitol, erythritol, trehalose, maltodextrin, polydextrose, etc. Other sweeteners illustratively include glycerin, inulin, maltol, acesulfame and its salts, such as potassium acesulfame, alitame, aspartame, neotame, sodium cyclamate, saccharin and its salts, such as sodium saccharin or calcium saccharin, neohesperidin dihydrochalcone, stevioside, thaumatin, etc.Sweetening agents may be available in the form of crude or refined products, such as, for example, hydrogenated starch hydrolysates, maltitol syrup, high fructose corn syrup, and the like, as well as in trademarked products, such as, for example, a combination of propylene glycol, ethyl alcohol, and a proprietary artificial flavor sold under the trade name Sweet Am™ liquid by Flavors of North America, a combination of maltodextrin, sorbitol, and fructose sold under the trade name Sweet Am™ powder, product code 918.005, a combination of water, propylene glycol, sorbitol, fructose, and a proprietary combination of natural and artificial flavors sold under the trade name Sweet Am™ powder by Flavors of North America, product code 918.010, a combination of water, propylene glycol, sorbitol, fructose, and a proprietary combination of natural and artificial flavors sold under the trade name Sweet Am™ powder by Virginia Such sweeteners may be used as a combination of 1-10% proprietary plant / vegetable extract and 90-99% dextrose sold by Dare under the trade name ProSweet™, maltitol liquid sold by Ingredion under the trade name Maltisweet™, sorbitol and sorbitol / xylitol liquid sold by SPI Polyols under the trade name Sorbo™, high fructose corn syrup sold by Ingredion under the trade name Invertose™, sucralose and maltodextrin combinations sold by Tate and Lyle under the trade names Rebalance M60 and X60, and sugar-containing and sugar-free flavored syrups sold by Paddock Laboratories, Inc. under the trade names Ora-Sweet™ and Ora-Sweet-SF™, respectively. The sweeteners may be used alone or in combination of two or more. Suitable concentrations of different sweetening agents can be selected based on published information, manufacturer data sheets, and by routine testing.

[0123] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, contain about 0.01 wt% to about 10 wt% sweetener(s). In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, optionally contain about 0.01 wt% to about 10 wt% sweetener(s). In some embodiments, the solid formulations contain about 0.01 wt% to about 5 wt% sweetener. In some embodiments, the solid formulations contain about 0.01 wt% to about 1 wt% sweetener. In some embodiments, the solid formulations contain about 0.1 wt% to about 0.5 wt% sweetener. In some embodiments, the solid formulations contain about 0.2 wt% to about 0.8 wt% sweetener. In some embodiments, the solid formulations contain about 0.5 wt% to about 0.6 wt% sweetener. In some embodiments, the solid formulations contain about 0.6 wt% sweetener.

[0124] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise from about 0.01 wt% to about 2 wt% of a flavoring agent(s). In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, optionally comprise from about 0.01 wt% to about 2 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.01 wt% to about 2 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.001 wt% to about 1 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.01 wt% to about 0.5 wt% of a flavoring agent.

[0125] In some embodiments of the present disclosure, the pharmaceutical compositions, e.g., pharmaceutical powders and suspensions described herein, comprise one or more sweeteners (e.g., sucralose and sorbitol liquid). In some embodiments, the suspensions described herein comprise a sweetener present at about 0.01% w / v to about 30% w / v of the liquid formulation. In some embodiments, the sweetener comprises a mixture of two or more sweeteners. In some embodiments, the sweetener comprises sucralose. In some embodiments, the sweetener comprises sorbitol. In some embodiments, the sweetener comprises sucrose. In some embodiments, the suspensions described herein may be 0.1% to 14%, 0.2% to 7%, 0.3% to 5%, 0.35% to 0.5%, 0.35% to 1.0%, 0.35% to 1.5%, 0.35% to 2.0%, 0.35% to 2.5%, 0.35% to 3.0%, 0.35% to 3.5%, 0.5% to 1.0%, 0.5% to 1.5%, 0.5% to 2.0%, 0.5% to 2.5%, 0.5% to 3.0%, 0.5% to 3.5%, 1.0% to 1.5%, 1.0% to 2.0%, 1.0% to 2.0%, 1.0% to 2.0%, 1.0% to 3.5 ... % to 2.5%, 1.0% to 3.0%, 1.0% to 3.5%, 1.5% to 2.0%, 1.5% to 2.5%, 1.5% to 3.0%, 1.5% to 3.5%, 1.5% to 4.0%, 2.0% to 2.5%, 2.0% to 3.0%, 2.0% to 3.5%, 2.0% to 4.0%, 2.5% to 3.0%, 2.5% to 3.5%, 2.5% to 4.0%, 3.0% to 3.5%, 3.0% to 4.0%, 3.5% to 4.0% w / v sweetener, or any range or value contemplated therein. In some embodiments, the suspensions described herein contain 0.1% to 1% w / v sweetener. In some embodiments, the suspensions described herein contain between 0.05% and 0.5% w / v sweetener. In some embodiments, the suspensions described herein contain between 0.2% and 0.8% w / v sweetener. In some embodiments, the sweetener or combination of sweeteners is present at about 0.35% w / v to about 3.5% w / v.In some embodiments, the sweetener or combination of sweeteners is present in the suspension at about 0.35% w / v to about 3.5% w / v, about 0.2% w / v to about 7.0% w / v, about 0.1% w / v to about 10% w / v, about 1% w / v to about 10% w / v, about 1% w / v to about 15% w / v, about 0.5% w / v to about 12% w / v, or about 0.1% w / v to about 15% w / v.

[0126] In some embodiments, the suspensions described herein comprise between 0.1% and 14% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.2% and 7% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.35% and 3.5% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.05% and 0.5% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.15% and 0.35% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.3% and 5% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.35% and 3.5% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.35% and 3.0% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.5% and 1.0% w / v sweetener. In some embodiments, the suspensions described herein comprise between 1.0% and 2.5% w / v sweetener. In some embodiments, the suspensions described herein comprise between 1.0% and 2.5% w / v sweetener. In some embodiments, the suspensions described herein comprise between 2.0% and 4.0% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.1% and 5% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.1% and 15% w / v sweetener. In some embodiments, the suspensions described herein comprise between 0.1% and 10% w / v sweetener. In some embodiments, the suspensions described herein comprise between 5% and 15% w / v sweetener. In some embodiments, the suspensions described herein comprise between 5% and 25% w / v sweetener. In some embodiments, the sweetener comprises sucralose. In some embodiments, the sweetener comprises sorbitol. In some embodiments, the sweetener comprises sucrose. In some embodiments, the sweetener comprises glycyrrhizin.

[0127] In some embodiments, the pharmaceutical compositions described herein, such as pharmaceutical powders and suspensions, contain flavorings or fragrances that enhance the flavor or aroma of the dose, improve the overall palatability of the dose, and thus help mask the flavor of active ingredients that patients may find unpleasant. This can provide an improved experience for patients and better compliance with the drug regimen desired by clinicians. Suitable natural or artificial flavors can be selected from pharmacologic acceptable options listed in standard pharmaceutical references known to those skilled in the art. Suitable natural or synthetic flavors can be selected from standard reference books, such as Remington: The Science and Practice of Pharmacy (2000) and Fenaroli's Handbook of Flavor Ingredients (1994).

[0128] Non-limiting examples of suitable natural flavors include almond, anise, apple, apricot, banana, blackberry, blackcurrant, blueberry, caramel, cherry, chocolate, cinnamon, cranberry, grape, lemon, lime, orange, peppermint, pineapple, raspberry, spearmint, strawberry, vanilla, and the like, some of which can be easily simulated using synthetic agents or combinations thereof. In some embodiments, flavors include those that can be easily simulated using synthetic agents or combinations thereof, including fat, poultry, fish, beef, and other meats. In some embodiments, vanilla flavor is used. In some embodiments, mint flavor is used. In some embodiments, strawberry flavor (e.g., Strawberry Flavor CW08) is used. In other embodiments, other pharma- ceutically acceptable flavors can be used to mask the flavors of other ingredients, e.g., other APIs, to enhance palatability, and thus compliance, in a range of patient populations. In some embodiments, the natural flavors can be natural or synthetic. In some embodiments, the synthetic flavors are artificial flavors, e.g., artificial strawberry flavor. Natural and synthetic flavors can be used to accommodate the tastes of diverse patient populations, including, but not limited to, age- and culturally-related flavor preferences (e.g., bubble gum flavor for pediatric patients).

[0129] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, comprise from about 0.01 wt% to about 10 wt% of a flavoring agent. In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, optionally comprise from about 0.01 wt% to about 10 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.01 wt% to about 5 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.01 wt% to about 1 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.1 wt% to about 0.5 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 1 wt% to about 2 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.5 wt% to about 2.5 wt% of a flavoring agent. In some embodiments, the solid formulations comprise from about 0.01 wt% to about 2 wt% of a flavoring agent. In some embodiments, the solid formulation comprises from about 0.001 wt% to about 1 wt% of the flavoring agent. In some embodiments, the solid formulation comprises from about 0.01 wt% to about 0.5 wt% of the flavoring agent.

[0130] In some embodiments of the present disclosure, the pharmaceutical compositions described herein, e.g., pharmaceutical powders and suspensions, comprise one or more flavoring agents. In some embodiments, the suspensions described herein comprise a flavoring agent present at about 0.01% w / v to about 30% w / v of the liquid formulation. In some embodiments, the suspensions described herein may be 0.1% to 14%, 0.2% to 7%, 0.3% to 5%, 0.35% to 0.5%, 0.35% to 1.0%, 0.35% to 1.5%, 0.35% to 2.0%, 0.35% to 2.5%, 0.35% to 3.0%, 0.35% to 3.5%, 0.5% to 1.0%, 0.5% to 1.5%, 0.5% to 2.0%, 0.5% to 2.5%, 0.5% to 3.0%, 0.5% to 3.5%, 1.0% to 1.5%, 1.0% to 2.0%, 1.0% to 2.0%, 1.0% to 2.0%, 1.0% to 3.5 ... In some embodiments, the suspensions described herein comprise 0.1% to 1% w / v flavoring agent. In some embodiments, the suspensions described herein comprise between 0.05% and 0.5% w / v of a flavoring agent. In some embodiments, the suspensions described herein comprise between 0.2% and 2% w / v of a flavoring agent. In some embodiments, the flavoring agent or combination of flavoring agents is present in the suspension at between about 0.35% w / v and about 3.5% w / v, between about 0.2% w / v and about 7.0% w / v, between about 0.1% w / v and about 10% w / v, between about 1% w / v and about 10% w / v, between about 1% w / v and about 15% w / v, between about 0.5% w / v and about 12% w / v, or between about 0.1% w / v and about 15% w / v. Coloring agent

[0131] The solid formulation and / or liquid formulation described herein can include one or more coloring agents.Many such agents are approved for use by the United States Food and Drug Administration and are well known to those skilled in the art of compounding pharmacy.Suitable coloring agents approved by the United States Food and Drug Administration (FDA) include FD&C Red No. 3, FD&C Red No. 20, FD&C Red No. 40, FD&C Yellow No. 6, FD&C Blue No. 2, D&C Green No. 5, D&C Orange No. 5, D&C Yellow No. 10, caramel, iron oxide, and mixtures thereof.

[0132] The use of color can enhance the aesthetic appearance of the dosage, as well as provide confirmation of drug identity in situations where more than one oral dosage form is prepared, stored, transported, or used. Enhancing the aesthetic appearance of the dosage increases the overall palatability of the dosage, which can provide benefits to patients and clinicians in terms of improved patient experience and improved compliance with drug regimens. The ability to clearly identify medications in pharmaceutical, clinical, and patient contexts provides benefits to patients by reducing the scope for errors in the preparation, storage, handling, transport, and use of medications.

[0133] In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, optionally contain from about 0.0001 wt% to about 1 wt% of a colorant. In some embodiments, the solid formulations described herein, e.g., pharmaceutical powders, optionally contain from about 0.0001 wt% to about 1 wt% of a colorant.

[0134] In some embodiments of the present disclosure, the colorant comprises FD&C Red No. 40. However, any FDA approved colorant is contemplated herein. In some embodiments, the concentration of the colorant is 0.001%-0.1% w / v in the suspension, or any range or value therein. In some embodiments, the concentration of the colorant in the suspension is 0.001%-1%, 0.01%-2%, 0.002%-0.005%, 0.002%-0.004%, 0.002%-0.003% w / v, or any range or value therein. In some embodiments, the concentration of the colorant in the suspension or pharmaceutical powder is less than 0.002%. In some embodiments, the concentration of the colorant in the suspension or pharmaceutical powder is greater than 0.005%. In some embodiments, the liquid suspensions described herein comprise about 0.001%-1% w / v of the colorant. In some embodiments, the liquid suspensions described herein comprise about 0.01%-2% w / v colorant. In some embodiments, the liquid suspensions described herein comprise about 0.002%-0.005% w / v colorant. In some embodiments, the liquid suspensions described herein comprise about 0.002%-0.003% w / v colorant. In some embodiments, the liquid suspensions described herein comprise about 0.002%-0.004% w / v colorant.

[0135] In some embodiments, the solid formulations described herein do not contain any colorants.

[0136] In some embodiments, the pH value of the liquid suspensions described herein is about 2 to 7. In certain aspects, the present disclosure provides oral liquid suspensions comprising: (a) (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof; (b) one or more pharma- ceutically acceptable excipients; and (c) water.

[0137] In some embodiments, the suspension comprises, based on the weight of solids, (a)(i) about 40 wt % to about 60 wt % of compound A, and (ii) About 40wt% to about 60wt% PVP-VA % to about 50 wt % of an amorphous solid dispersion comprising: (b) about 40 wt % to about 70 wt % of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; (c) about 0.25 wt % to about 1 wt % of a surfactant, the surfactant being SLS; (d) about 1 wt % to about 6 wt % of a flow aid, the flow aid being colloidal silicon dioxide (CSD); (e) about 1 wt % to about 10 wt % of an antifoaming agent (e.g., about 1 wt % to about 5 wt % of an antifoaming agent), the antifoaming agent comprising or being simethicone; and (f) Where appropriate, a preservative, flavouring agent, sweetener, or combination thereof. Includes.

[0138] In some embodiments, the anti-foaming agent comprises simethicone and maltodextrin. In some embodiments, the anti-foaming agent comprises simethicone (about 30 wt%) and maltodextrin (about 70 wt%).

[0139] In some embodiments, the suspension comprises a flavoring agent, hi some embodiments, the suspension comprises a strawberry flavor.

[0140] In some embodiments, the suspension comprises a sweetener. In some embodiments, the suspension comprises sucralose.

[0141] In some embodiments, the suspension comprises about 25 mg / mL of Compound A or a salt thereof. In some embodiments, the suspension comprises about 25 mg / mL of Compound A.

[0142] In some embodiments, the suspension comprises, based on the weight of solids, (a)(i) about 40 wt % of Compound A; and (ii) about 60 wt% copovidone about 10 wt% to 30 wt% (e.g., about 25 wt%) of an amorphous solid dispersion comprising (b) about 30 wt% to 32 wt% mannitol; (c) about 30 wt% to 32 wt% microcrystalline cellulose; (d) about 0.5 wt% to 1 wt% SLS; (e) about 4 wt%–5 wt% CSD; (f) about 2 wt% to 3 wt% of a defoamer; If necessary, a carrier for the defoamer; and optionally a preservative, flavoring agent, sweetener, or combination thereof. Includes.

[0143] In some embodiments, the suspension comprises, based on the weight of solids, (a)(i) about 40 wt % of Compound A; and (ii) about 60 wt% copovidone about 10 wt% to 30 wt% (e.g., about 25 wt%) of an amorphous solid dispersion comprising (b) about 30 wt% to 32 wt% mannitol; (c) about 30 wt% to 32 wt% microcrystalline cellulose; (d) about 0.5 wt% to 1 wt% SLS; (e) about 4 wt%–5 wt% CSD; (f) about 2 wt% to 3 wt% simethicone; If necessary, a carrier for the defoamer; and optionally a preservative, flavoring agent, sweetener, or combination thereof. Includes.

[0144] In some embodiments, the suspension comprises the following components, based on weight of solids: (a)(i) about 40 wt % of Compound A; and (ii) about 60 wt% copovidone about 10 wt % to 30 wt % (e.g., about 25 wt %) of an amorphous solid dispersion comprising (b) about 20 wt% to 40 wt% mannitol; (c) about 20 wt% to 40 wt% microcrystalline cellulose; (d) about 0.1 wt% to 2 wt% SLS; (e) about 1 wt%–10 wt% CSD; (f) about 1 wt% to 5 wt% simethicone; (g) about 1 wt% to 10 wt% maltodextrin; and optionally a preservative, flavoring agent, sweetener, or combination thereof. Includes one or more of:

[0145] In some embodiments, the suspension comprises the following components, based on weight of solids: (a)(i) about 40 wt % of Compound A; and (ii) about 60 wt% copovidone about 10 wt % to 30 wt % (e.g., about 25 wt %) of an amorphous solid dispersion comprising (b) about 20 wt% to 40 wt% mannitol; (c) about 20 wt% to 40 wt% microcrystalline cellulose; (d) about 0.1 wt% to 2 wt% SLS; (e) about 1 wt%–10 wt% CSD; (f) about 1 wt% to 5 wt% simethicone; (g) about 1 wt% to 10 wt% maltodextrin; (h) about 0.1 wt % to 5 wt % of a flavoring agent; and (i) about 0.1 wt% to 5 wt% of a sweetener Includes one or more of:

[0146] In some embodiments, the suspension comprises, based on the weight of solids, (a)(i) about 40 wt % of Compound A; and (ii) about 60 wt% copovidone about 10 wt % to 30 wt % (e.g., about 25 wt %) of an amorphous solid dispersion comprising (b) about 30 wt% to 32 wt% mannitol; (c) about 30 wt% to 32 wt% microcrystalline cellulose; (d) about 0.5 wt% to 1 wt% SLS; (e) about 4 wt%–5 wt% CSD; (f) about 2 wt% to 3 wt% simethicone; (g) about 3 wt% to 8 wt% maltodextrin; and optionally a preservative, flavoring agent, sweetener, or combination thereof. Includes.

[0147] In some embodiments, the oral liquid suspension includes a carrier for the antifoaming agent. In some embodiments, the oral liquid suspension includes a carrier for simethicone. In some embodiments, the carrier is a starch. In some embodiments, the carrier is a bulking agent. In some embodiments, the carrier is maltodextrin. In some embodiments, the carrier is present at about 1-15 wt% based on the weight of the solids. In some embodiments, the carrier is present at about 1-10 wt% based on the weight of the solids. In some embodiments, the carrier is present at about 2-8 wt% based on the weight of the solids. In some embodiments, the carrier is present at about 4-6 wt% based on the weight of the solids. In some embodiments, the carrier is present at about 5 wt% based on the weight of the solids. In some embodiments, the weight ratio of the carrier to the antifoaming agent is about 1:9 to 9:1. In some embodiments, the weight ratio of the carrier to the antifoaming agent is about 1:4 to 4:1. In some embodiments, the weight ratio of the carrier to the antifoaming agent is about 1:3 to 3:1. In some embodiments, the weight ratio of carrier to antifoaming agent is about 8:3 to 6:3. In some embodiments, the weight ratio of carrier to antifoaming agent is about 7:3.

[0148] In some embodiments, the oral liquid suspension is bioequivalent to a tablet formulation of Compound A or a pharma- ceutically acceptable salt thereof, wherein the tablet composition comprises: (i) an amorphous solid dispersion comprising about 40 wt. % Compound A and (ii) about 60 wt. % copovidone, wherein the amorphous solid dispersion is a hot melt extrudate; and one or more pharma- ceutically acceptable excipients disclosed herein.

[0149] Pharmaceutical compositions (including pharmaceutical powders and oral preparations derived therefrom) may be formulated using one or more physiologically acceptable carriers, including additives and adjuvants that facilitate the processing of pharmaceutical agents into pharmacopoeial preparations. The appropriate formulation depends on the route of administration selected. Overviews of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa., Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins, 1999).

[0150] Pharmaceutically acceptable additives can contain physiologically acceptable agents that act, for example, to stabilize, increase the solubility, or increase the absorption of a compound such as a pharmaceutical agent. Such physiologically acceptable agents include, for example, carbohydrates, such as glucose, sucrose, or dextran, antioxidants, such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, or other stabilizers or additives. The selection of pharma-ceutically acceptable additives, including physiologically acceptable agents, depends, for example, on the route of administration of the composition. The preparation or pharmaceutical composition can be a self-emulsifying drug delivery system or a self-microemulsifying drug delivery system. The pharmaceutical composition (preparation) can also be a liposome or other polymer matrix, into which, for example, the compound of the present invention can be incorporated. For example, liposomes containing phospholipids or other lipids are non-toxic, physiologically acceptable, and metabolizable carriers that are relatively simple to prepare and administer.

[0151] Pharmaceutical compositions (including pharmaceutical powders and oral formulations derived therefrom) may be sterile aqueous or non-aqueous solutions, suspensions, or emulsions, such as microemulsions. The additives described herein are examples and are in no way limiting. An effective amount or therapeutically effective amount refers to the amount of one or more pharmaceutical agents administered to a subject, either as a single dose or as part of a series of doses, that is effective to produce the desired therapeutic effect.

[0152] The dosage of the pharmaceutical powders and oral formulations derived therefrom described herein for treating a disease or disorder may depend on the condition of the subject, i.e., the stage of the disease, the severity of the symptoms caused by the disease, the general health condition, as well as age, sex, and weight, and other factors that are apparent to those skilled in the medical field. The pharmaceutical compositions may be administered in a manner appropriate to the disease being treated, as determined by those skilled in the medical field. In addition to the factors described herein and above regarding the use of pharmaceutical agents for treating a disease or disorder, the suitable duration and frequency of administration of the pharmaceutical agent may also be determined or adjusted by factors such as the condition of the patient, the type and severity of the patient's disease, the specific form of the active ingredient, and the method of administration. The optimal dosage of the drug may generally be determined using experimental models and / or clinical trials. The optimal dosage may depend on the subject's body mass, weight, or blood volume. The use of the minimum dosage that is sufficient to provide effective treatment is usually preferred. The design and execution of preclinical and clinical studies for pharmaceutical agents described herein, including those administered for prophylactic benefit, is well within the skill of those skilled in the relevant art. When two or more pharmaceutical agents are administered to treat a disease or condition, the optimal dose of each pharmaceutical agent may be different, e.g., less than when either agent is administered alone as a monotherapy. In certain particular embodiments, the two pharmaceutical agents in combination may act synergistically or additively, and either agent may be used in a lower amount than when administered alone. The amount of pharmaceutical agent that may be administered per day may be, for example, between about 0.01 mg / kg body weight and 100 mg / kg body weight, e.g., between about 0.1 and 1 mg / kg body weight, between about 1 and 10 mg / kg body weight, between about 10 and 50 mg / kg body weight, between about 50 and 100 mg / kg body weight. In other embodiments, the amount of pharmaceutical agent that may be administered per day is between about 0.01 mg / kg body weight and 1000 mg / kg body weight, between about 100 and 500 mg / kg body weight, or between about 500 and 1000 mg / kg body weight. The optimal dosage per day or course of treatment may vary for the disease or disorder being treated, and may also vary with the route of administration and therapeutic regimen. In-use and long-term stability

[0153] In one aspect, the present invention provides an oral liquid suspension that is stable during reconstitution and use.In some cases, the oral liquid suspension that comprises the amorphous solid dispersion of compound A and PVP-VA or its salt tends to aggregate and / or form viscous gel immediately after reconstitution, which makes it difficult for patients to measure and administer the liquid formulation accurately.Surprisingly, it has been found that certain pharmaceutical additives and their combinations reduce and slow down gel formation, thereby improving the stability of oral liquid suspension during use.

[0154] In some embodiments, the suspension retains injectability for at least 15 minutes. In some embodiments, the suspension retains injectability for at least 30 minutes. In some embodiments, the suspension retains injectability for at least 5 minutes. In some embodiments, the suspension retains injectability for at least 10 minutes. In some embodiments, the suspension retains injectability for at least 20 minutes. In some embodiments, the suspension retains injectability for at least 25 minutes. In some embodiments, injectability is tested at room temperature.

[0155] In one aspect, provided herein is a solid form pharmaceutical formulation (e.g., pharmaceutical powder) that is stable after long-term storage. In some embodiments, the solid form pharmaceutical formulation (e.g., pharmaceutical powder) described herein retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 3 months. In some embodiments, the solid form pharmaceutical formulation (e.g., pharmaceutical powder) described herein retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 6 months. In some embodiments, the solid form pharmaceutical formulation (e.g., pharmaceutical powder) described herein retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 12 months. In some embodiments, the solid form pharmaceutical formulation (e.g., pharmaceutical powder) described herein retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 18 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage for 24 months at 20±5° C. In some embodiments, the amount of Compound A or a pharma- ceutically acceptable salt thereof in the solid form of the pharmaceutical formulation is determined by HPLC.

[0156] In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 3 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 6 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 12 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 18 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 24 months.

[0157] In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 3 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 6 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 12 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 18 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 90% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 24 months.

[0158] In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 3 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 6 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 12 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 18 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 20±5°C for 24 months.

[0159] In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 3 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 6 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 12 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 18 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at 5±3°C for 24 months.

[0160] In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 3 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 6 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 12 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 18 months. In some embodiments, the solid form of the pharmaceutical formulation described herein (e.g., pharmaceutical powder) retains at least 95% of the initial amount of Compound A or a pharma- ceutically acceptable salt thereof after storage at about 40°C for 24 months. Method for preparing oral dosage forms

[0161] In certain aspects, the present disclosure provides a method of preparing an aqueous formulation, comprising: (a) providing a solid formulation of an amorphous solid dispersion, the amorphous solid dispersion comprising: (i) (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof, (ii) one or more polymers and (b) contacting the solid formulation with an aqueous solution The present invention provides a method comprising:

[0162] In some embodiments, the solid formulation is a pharmaceutical powder disclosed herein. In some embodiments, the contacting step comprises mixing the solid formulation with an aqueous solution to form a suspension. In some embodiments, the mixing step comprises shaking the solid formulation and the aqueous solution to form a suspension. In some embodiments, the mixing step comprises adding the solid formulation to a container containing an aqueous solution, and then shaking the container to form a suspension. In some embodiments, the container is a container described herein. In some embodiments, the container is shaken in all directions. In some embodiments, the mixing or shaking step continues until all of the solid formulation is dispersed in the aqueous solution.

[0163] In some embodiments, the mixing step lasts from about 10 seconds to about 240 seconds. The mixing step lasts from about 10 seconds to about 60 seconds, from about 60 seconds to about 120 seconds, from about 40 seconds to about 80 seconds, or from about 50 seconds to about 70 seconds. In some embodiments, the mixing step lasts from about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds, about 60 seconds, about 65 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 85 seconds, about 90 seconds, about 95 seconds, about 100 seconds, about 105 seconds, about 110 seconds, about 115 seconds, or about 120 seconds. In some embodiments, the mixing step lasts for at least 10 seconds, at least 15 seconds, at least 20 seconds, at least 25 seconds, at least 30 seconds, at least 35 seconds, at least 40 seconds, at least 45 seconds, at least 50 seconds, at least 55 seconds, at least 60 seconds, at least 65 seconds, at least 70 seconds, at least 75 seconds, at least 80 seconds, at least 85 seconds, at least 90 seconds, at least 95 seconds, at least 100 seconds, at least 105 seconds, at least 110 seconds, at least 115 seconds, or at least 120 seconds. In some embodiments, the mixing step lasts for up to 10 seconds, up to 15 seconds, up to 20 seconds, up to 25 seconds, up to 30 seconds, up to 35 seconds, up to 40 seconds, up to 45 seconds, up to 50 seconds, up to 55 seconds, up to 60 seconds, up to 65 seconds, up to 70 seconds, up to 75 seconds, up to 80 seconds, up to 85 seconds, up to 90 seconds, up to 95 seconds, up to 100 seconds, up to 105 seconds, up to 110 seconds, up to 115 seconds, or up to 120 seconds. In some embodiments, the mixing step lasts for 60 seconds. In some embodiments, the mixing step lasts no longer than about 120 seconds.

[0164] In some embodiments, the shaking step lasts from about 10 seconds to about 240 seconds. The mixing step lasts from about 10 seconds to about 60 seconds, from about 60 seconds to about 120 seconds, from about 40 seconds to about 80 seconds, or from about 50 seconds to about 70 seconds. In some embodiments, the shaking step lasts from about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds, about 60 seconds, about 65 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 85 seconds, about 90 seconds, about 95 seconds, about 100 seconds, about 105 seconds, about 110 seconds, about 115 seconds, or about 120 seconds. In some embodiments, the mixing step lasts for at least 10 seconds, at least 15 seconds, at least 20 seconds, at least 25 seconds, at least 30 seconds, at least 35 seconds, at least 40 seconds, at least 45 seconds, at least 50 seconds, at least 55 seconds, at least 60 seconds, at least 65 seconds, at least 70 seconds, at least 75 seconds, at least 80 seconds, at least 85 seconds, at least 90 seconds, at least 95 seconds, at least 100 seconds, at least 105 seconds, at least 110 seconds, at least 115 seconds, or at least 120 seconds. In some embodiments, the shaking step lasts for up to 10 seconds, up to 15 seconds, up to 20 seconds, up to 25 seconds, up to 30 seconds, up to 35 seconds, up to 40 seconds, up to 45 seconds, up to 50 seconds, up to 55 seconds, up to 60 seconds, up to 65 seconds, up to 70 seconds, up to 75 seconds, up to 80 seconds, up to 85 seconds, up to 90 seconds, up to 95 seconds, up to 100 seconds, up to 105 seconds, up to 110 seconds, up to 115 seconds, or up to 120 seconds. In some embodiments, the shaking step lasts for 60 seconds. In some embodiments, the shaking step lasts no longer than about 120 seconds.

[0165] In some embodiments, the mixing or shaking is performed gradually. In some embodiments, the mixing or shaking is performed in 5, 10, 15, 20, 25, or 30-second increments. In some embodiments, the mixing or shaking is performed in about 5, 10, 15, 20, 25, or 30-second increments. In some embodiments, the mixing or shaking is performed in 15-second increments.

[0166] In some embodiments, the method further comprises allowing the container to stand without mixing or shaking for a period of time, hi some embodiments, the period of time is about 1 minute, about 2 minutes, about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, or about 30 minutes.

[0167] In some embodiments, the method further comprises inverting the container and continuing to mix the suspension. In some embodiments, the method further comprises inverting the container and rotating for about 10 seconds to about 60 seconds, about 20 seconds to about 40 seconds, about 40 seconds to about 80 seconds, or about 15 seconds to about 45 seconds. In some embodiments, the rotating is for about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds, about 60 seconds, about 65 seconds, about 70 seconds, about 75 seconds, or about 80 seconds.

[0168] In some embodiments, the aqueous solution is at an elevated temperature or near room temperature. In some embodiments, the aqueous solution is near room temperature. In some embodiments, the aqueous solution has a temperature of about 15°C to about 80°C, about 20°C to about 60°C, or about 20°C to about 50°C. In some embodiments, the aqueous solution has a temperature of about 15°C, about 20°C, about 25°C, about 30°C, about 35°C, about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, about 65°C, about 70°C, about 75°C, about 80°C, or about 85°C. In some embodiments, the aqueous solution has a temperature of at least 15°C, at least 20°C, at least 25°C, at least 30°C, at least 35°C, at least 40°C, at least 45°C, at least 50°C, at least 55°C, at least 60°C, at least 65°C, at least 70°C, at least 75°C, at least 80°C, or at least 85°C. In some embodiments, the aqueous solution has a temperature of at most 15° C., at most 20° C., at most 25° C., at most 30° C., at most 35° C., at most 40° C., at most 45° C., at most 50° C., at most 55° C., at most 60° C., at most 65° C., at most 70° C., at most 75° C., at most 80° C., or at most 85° C. In some embodiments, the aqueous solution is hot water or room temperature water. In some embodiments, the aqueous solution is hot water. In some embodiments, the aqueous solution is room temperature water.

[0169] In some embodiments, the volume of the aqueous solution is about 5 mL to about 200 mL, about 5 mL to 100 mL, about 5 mL to 50 mL, about 5 mL to 25 mL, about 5 mL to 20 mL, about 10 mL to 50 mL, about 10 mL to 25 mL, about 25 mL to 50 mL, about 25 mL to 150 mL, or about 10 mL to about 20 mL. In some embodiments, the volume of the aqueous solution is about 5 mL, about 10 mL, about 15 mL, about 20 mL, about 25 mL, about 30 mL, about 35 mL, about 40 mL, about 45 mL, about 50 mL, about 60 mL, about 70 mL, about 80 mL, about 90 mL, about 100 mL, about 125 mL, about 150 mL, about 175 mL, or about 200 mL. In some embodiments, the volume of the aqueous solution is about 10 mL, about 11 mL, about 12 mL, about 13 mL, about 14 mL, about 15 mL, about 16 mL, about 17 mL, about 18 mL, about 19 mL, or about 20 mL. In some embodiments, the volume of the aqueous solution is about 14 mL.

[0170] In some embodiments, the method further comprises withdrawing the suspension from the container with a syringe. In some embodiments, the suspension is administered to the subject directly from the syringe.

[0171] In some embodiments, the aqueous formulation disclosed herein is administered with food, before eating food, or after eating food.In some embodiments, the aqueous formulation is administered with food.In some embodiments, the aqueous formulation is administered before the subject eats food.In some embodiments, the aqueous formulation is administered after the subject eats food. kit

[0172] In certain aspects, the present disclosure provides kits comprising the pharmaceutical powder or pharmaceutical composition disclosed herein for reconstitution. In some embodiments, the pharmaceutical powder or pharmaceutical composition in the kit is reconstituted using the preparation methods disclosed herein.

[0173] In certain aspects, the present disclosure provides a method of preparing an oral liquid suspension of Compound A or a salt thereof, comprising reconstituting a solid formulation in a kit disclosed herein in an aqueous solution.

[0174] In certain aspects, the present disclosure provides a method of preparing an oral liquid suspension of Compound A or a salt thereof, comprising reconstituting a pharmaceutical powder disclosed herein in an aqueous solution.

[0175] In another aspect, the present disclosure provides a method of treating cancer in a subject, comprising reconstituting a solid formulation in a kit disclosed herein and administering the reconstituted formulation to a subject in need thereof. Kits and articles of manufacture are also described for the compositions of Compound A or its pharma- ceutically acceptable salts, including the powder and liquid compositions described herein. Such kits can include a carrier, package, or container that is partitioned to receive one or more containers, such as vials, tubes, bottles, etc., each of the container(s) containing one of the separate elements used in the methods described herein, including solid or liquid formulations. Suitable containers include, for example, bottles, vials, syringes, and test tubes. The containers can be formed from a variety of materials, such as glass or plastic (e.g., HDPE).

[0176] In some embodiments, the kit includes one or more containers that optionally include markings that represent a volume measurement. In some embodiments, the kit includes one container that optionally includes markings that represent a volume measurement. In some embodiments, the kit includes 1-10 containers that optionally include markings that represent a volume measurement. In some embodiments, the kit includes 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 containers that optionally include markings that represent a volume measurement. In some embodiments, the containers are reusable after each use. In some embodiments, the containers are disposable after use.

[0177] The kits may each include one or more additional containers with one or more of the various materials (e.g., reagents, optionally in concentrated form, and / or devices) that are desirable from a commercial and user standpoint for the solid or liquid formulations described herein. Non-limiting examples of such materials include, but are not limited to, buffers, diluents, filters, needles, syringes; carriers, packages, containers, vials, and / or tube labels listing the contents and / or instructions for use, as well as inserts with instructions for use associated with the solid or liquid formulations. A set of instructions may also be included. In some embodiments, the kit includes a set of instructions as shown in FIG. 1. In some embodiments, the kit may include an administration syringe and / or a dispersion syringe. In some embodiments, the kit includes a bottle adaptor.

[0178] The label may be on or associated with the container. The label may be on the container when the letters, numbers, or other symbols forming the label are attached, molded, or etched on the container itself, and the label may be associated with the container when present in a receptacle or carrier that also holds the container, for example, as a package insert. The label may be used to indicate that the contents should be used for a particular therapeutic application. The label may also indicate instructions for the use of the contents, for example, in the methods described herein.

[0179] In some embodiments, the syringe in the kit is used to transfer a predetermined amount of the liquid formulation containing Compound A or a pharma- ceutically acceptable salt thereof from a container to form a suspension. The suspension can be prepared by dispersing a powder form of Compound A or a pharma- ceutically acceptable salt thereof in a predetermined volume of reconstitution medium in a bottle for single use or in a bottle for multiple use. The individual dose of the patient can be applied by using the administration syringe. The suspension in the syringe can be given directly to the child's mouth. In certain aspects, the disclosure provides kits that include: (a) a solid formulation of an amorphous solid dispersion of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof, comprising one or more pharma- ceutically acceptable excipients; and (b) instructions for aqueous reconstitution of the solid formulation. An example of the instructions is shown in FIG. 1. In some embodiments, the instructions for aqueous reconstitution are in the form of a reference material that refers to the instructions.

[0180] In some embodiments, the solid formulation is in the form of a powder, granules, or pellets. In some embodiments, the solid formulation is in the form of a powder. In some embodiments, the solid formulation is in the form of a granule. In some embodiments, the solid formulation is in the form of a pellet. In some embodiments, the solid formulation is a tablet, which is orange, film-coated, oval, and stamped with "100" on one side and "D101" on the other side. In some embodiments, the solid formulation is in powder form, which is white to off-white, and is further reconstituted with water to form a homogenous, flavored, white suspension at a concentration of 25 mg / mL.

[0181] In some embodiments, the kit of the present disclosure includes one or more of the following: a solid formulation of Compound A or a pharma- ceutically acceptable salt thereof, instructions for aqueous reconstitution of the solid formulation, a bottle, a bottle cap, a bottle adaptor, and / or a syringe. In some embodiments, the kit includes a solid formulation of Compound A or a pharma- ceutically acceptable salt thereof, instructions for aqueous reconstitution of the solid formulation, a bottle, a bottle cap, a bottle adaptor, and a syringe. The syringe may be an administration syringe with markings indicating the volume of liquid therein. The syringe may be individually wrapped, for example, in a plastic bag, as needed. In some embodiments, the solid formulation of Compound A or a pharma- ceutically acceptable salt thereof is contained in a bottle, which may be sealed by a bottle cap and / or seal. In some embodiments, the bottle is configured to contain a liquid volume of at least 25 mL, at least 50 mL, at least 75 mL, at least 100 mL, at least 125 mL, at least 150 mL, or at least 200 mL. In some embodiments, the bottle is configured to contain a liquid volume of about 25 mL to about 75 mL. In some embodiments, the bottle is configured to contain a liquid volume of about 15 mL to about 50 mL. In some embodiments, the bottle is configured to contain a liquid volume of about 50 mL to about 150 mL. In some embodiments, the bottle is configured to contain a liquid volume of about 100 mL to about 200 mL. In some embodiments, the bottle adapter is configured to fit the neck of the bottle and allow the tip of a syringe to be inserted into the hole of the bottle adapter. In some embodiments, the bottle adapter is configured to allow the syringe to withdraw liquid from the bottle without spilling or leaking. In some embodiments, the kit of the present disclosure includes 1 mg to 5000 mg of a solid formulation (e.g., pharmaceutical powder) of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the kit includes about 100 mg to about 1000 mg of a solid formulation (e.g., pharmaceutical powder) comprising Compound A. In some embodiments, the kit includes about 300 mg to about 600 mg of a solid formulation (e.g., pharmaceutical powder) comprising Compound A.In some embodiments, the kit includes about 100 mg to about 200 mg of a solid formulation (e.g., pharmaceutical powder) comprising compound A. In some embodiments, the kit includes about 500 mg to about 1500 mg of a solid formulation (e.g., pharmaceutical powder) comprising compound A. In some embodiments, the kit includes about 200 mg to about 800 mg of a solid formulation (e.g., pharmaceutical powder) comprising compound A. In some embodiments, the kit includes about 400 mg to about 450 mg of a solid formulation (e.g., pharmaceutical powder) comprising compound A. In some embodiments, the kit includes about 400 mg to about 500 mg of a solid formulation (e.g., pharmaceutical powder) comprising compound A. In some embodiments, the kit includes about 430 mg of a solid formulation (e.g., pharmaceutical powder) comprising compound A. In some embodiments, the kit comprises about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, or about 650 mg of a solid formulation (e.g., a pharmaceutical powder) comprising Compound A. Administration

[0182] Kits are provided that have one or more unit doses of the medicaments described herein, usually in oral or injection doses.Such kits can include a container that contains unit doses, an information package insert that describes the use of the drug in treating disease and the associated benefits, and, if necessary, the instrument or device for delivering the composition.

[0183] The solid and liquid formulations of Compound A or its pharmaceutically acceptable salt are described herein. In some embodiments, the solid and liquid formulations of Compound A or its pharmaceutically acceptable salt are used as unit doses.

[0184] The present disclosure provides kits having a unit dose or unit doses. A unit dose comprises an amount of a solid formulation (pharmaceutical powder) disclosed herein. In some embodiments, the kit comprises a plurality of unit doses, each of which comprises Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the kit comprises one unit dose, which comprises Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the kit comprises a single dose, which comprises Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the kit comprises two or more unit doses, which comprise Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the kit comprises 1-10 unit doses, each of which comprises Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the kit comprises 1-5 unit doses, each of which comprises Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the kit comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 unit doses, each of which comprises Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the unit dose is a pediatric dose.

[0185] In some embodiments, each unit dose contains about 25 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 900 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 800 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 700 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 600 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 500 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 400 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 300 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 200 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 25 mg to about 100 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 100 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 200 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 300 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 400 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 500 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 600 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 700 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 800 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 900 mg to about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 200 mg to about 900 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 300 mg to about 800 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 400 mg to about 700 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 500 mg to about 600 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 400 mg to about 600 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains about 300 mg to about 600 mg of Compound A or a pharma- ceutically acceptable salt thereof.

[0186] In some embodiments, each unit dose contains about 25 mg, about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, or about 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains at least 25, at least 50 mg, at least 100 mg, at least 150 mg, at least 200 mg, at least 250 mg, at least 300 mg, at least 350 mg, at least 400 mg, at least 450 mg, at least 500 mg, at least 600 mg, at least 700 mg, at least 800 mg, at least 900 mg, or at least 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, each unit dose contains up to 25 mg, up to 50 mg, up to 100 mg, up to 150 mg, up to 200 mg, up to 250 mg, up to 300 mg, up to 350 mg, up to 400 mg, up to 450 mg, up to 500 mg, up to 600 mg, up to 700 mg, up to 800 mg, up to 900 mg, or up to 1000 mg of Compound A or a pharma- ceutically acceptable salt thereof.

[0187] In some embodiments, if a weekly dose is missed by 3 days or less, the missed dose must be taken as soon as possible and the next dose must be taken on the usual day. In some embodiments, if a weekly dose is missed for more than 3 days, the missed dose must be skipped and the next dose must be taken on the usual day. In some embodiments, there must be a minimum of 4 days between doses.

[0188] In some embodiments, the dose is not co-administered with a strong or moderate CYP2C8 inhibitor. In some embodiments, the dose is not co-administered with a strong or moderate CYP2C8 inducer. In some embodiments, the dose is not co-administered with a sensitive CYP3A4 substrate. In some embodiments, the dose is not co-administered with a BCRP substrate. In some embodiments, the dose is not administered to a pregnant subject. In some embodiments, the dose is not administered to a lactating subject. In some embodiments, the dose is not administered to a subject with impaired liver function. Oral Formulations for the Treatment of Cancer

[0189] In certain aspects, the present disclosure provides a method of treating cancer in a subject, the method comprising administering to the subject a pharmaceutical powder disclosed herein or a reconstituted oral liquid formulation disclosed herein.

[0190] In certain aspects, the disclosure provides a method of treating cancer comprising administering to a subject an oral liquid suspension comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A), or a pharma- ceutically acceptable salt thereof, to achieve a defined pharmacokinetic profile. During or after administration of the oral liquid suspension, the plasma concentration of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A), or a pharma- ceutically acceptable salt thereof, can be determined using a validated bioanalytical assay. For example, the following pharmacokinetic (PK) parameters can be calculated, where appropriate: maximum observed plasma concentration (Cmax) and area under the concentration versus time curve from time 0 to t (AUC 0-t ).

[0191] In certain aspects, the disclosure provides a method of treating cancer, comprising administering to a subject an oral liquid suspension comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamide)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A), or a pharma- ceutically acceptable salt thereof, in an amount sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A of at least 2000 ng / mL in the subject. In some embodiments, the oral liquid suspension is reconstituted from a solid formulation, e.g., a pharmaceutical powder, described herein, comprising Compound A or a pharma- ceutically acceptable salt thereof. Pharmacokinetic parameters

[0192] In some embodiments, the oral liquid suspension comprising Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve a maximum observed plasma concentration (C) of Compound A in the subject of at least 100 ng / mL, at least 200 ng / mL, at least 300 ng / mL, at least 400 ng / mL, at least 500 ng / mL, at least 1000 ng / mL, at least 1500 ng / mL, at least 2000 ng / mL, at least 2500 ng / mL, at least 3000 ng / mL, at least 3500 ng / mL, at least 4000 ng / mL, at least 4500 ng / mL, at least 5000 ng / mL, at least 5500 ng / mL, at least 6000 ng / mL, at least 6500 ng / mL, at least 7000 ng / mL, at least 7500 ng / mL, or at least 8000 ng / mL. In some embodiments, an oral liquid suspension comprising Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve a maximum observed plasma concentration (C) of Compound A in a subject of at most 100 ng / mL, at most 200 ng / mL, at most 300 ng / mL, at most 400 ng / mL, at most 500 ng / mL, at most 1000 ng / mL, at most 1500 ng / mL, at most 2000 ng / mL, at most 2500 ng / mL, at most 3000 ng / mL, at most 3500 ng / mL, at most 4000 ng / mL, at most 4500 ng / mL, at most 5000 ng / mL, at most 5500 ng / mL, at most 6000 ng / mL, at most 6500 ng / mL, at most 7000 ng / mL, at most 7500 ng / mL, or at most 8000 ng / mL.

[0193] In some embodiments, an oral liquid suspension comprising Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve a maximum observed plasma concentration (C) of Compound A in the subject of about 100 ng / mL, about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 1000 ng / mL, about 1500 ng / mL, about 2000 ng / mL, about 2500 ng / mL, about 3000 ng / mL, about 3500 ng / mL, about 4000 ng / mL, about 4500 ng / mL, about 5000 ng / mL, about 5500 ng / mL, about 6000 ng / mL, about 6500 ng / mL, about 7000 ng / mL, about 7500 ng / mL, or about 8000 ng / mL. In some embodiments, the oral liquid suspension containing Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve a Cmax of Compound A in the subject that is within a suitable range. In some embodiments, the Cmax is about 100 ng / mL to about 8,000 ng / mL. In some embodiments, the Cmax is about 100 ng / mL to about 2,000 ng / mL. In some embodiments, the Cmax is about 2,000 ng / mL to about 8,000 ng / mL. In some embodiments, the Cmax is at least about 100 ng / mL. In some embodiments, the Cmax is at least about 200 ng / mL. In some embodiments, the Cmax is at least about 300 ng / mL. In some embodiments, the Cmax is at least about 400 ng / mL. In some embodiments, the Cmax is at least about 500 ng / mL. In some embodiments, the Cmax is at least about 1000 ng / mL. In some embodiments, the Cmax is at least about 2,000 ng / mL. In some embodiments, Cmax is at least about 3,000 ng / mL. In some embodiments, Cmax is at least about 4,000 ng / mL. In some embodiments, Cmax is at least about 5,000 ng / mL. In some embodiments, Cmax is at least about 6,000 ng / mL. In some embodiments, Cmax is at least about 7,000 ng / mL. In some embodiments, Cmax is up to about 8,000 ng / mL.

[0194] In some embodiments, the oral liquid suspension comprising compound A or a pharma- ceutical acceptable salt thereof has a concentration of about 100 ng / mL to about 300 ng / mL, about 100 ng / mL to about 500 ng / mL, about 100 ng / mL to about 1,000 ng / mL, about 100 ng / mL to about 1,500 ng / mL, about 100 ng / mL to about 2,000 ng / mL, about 100 ng / mL to about 2,500 ng / mL, about 100 ng / mL to about 3,000 ng / mL, about 100 ng / mL to about 3,500 ng / mL, about 100 ng / mL to about 4,000 ng / mL, about 100 ng / mL to about 4, 500ng / mL, approximately 100ng / mL to approximately 5,000ng / mL, approximately 100ng / mL to approximately 5,500ng / mL, approximately 100ng / mL to approximately 6,000ng / mL, approximately 100ng / mL to approximately 6,500ng / mL, approximately 100ng / mL to approximately 7,000ng / mL, approximately 100n g / mL~about 8,000ng / mL, about 2,000ng / mL~about 2,500ng / mL, about 2,000ng / mL~about 3,000ng / mL, about 2,000ng / mL~about 3,500ng / mL, about 2,000ng / mL~about 4,000ng / mL, about 2,000ng / mL ~4,500ng / mL, 2,000ng / mL~5,000ng / mL, 2,000ng / mL~5,500ng / mL, 2,000ng / mL~6,000ng / mL, 2,000ng / mL~6,500ng / mL, 2,000ng / mL~7, 000ng / mL, approximately 2,000ng / mL to approximately 8,000ng / mL, approximately 2,500ng / mL to approximately 3,000ng / mL, approximately 2,500ng / mL to approximately 3,500ng / mL, approximately 2,500ng / mL to approximately 4,000ng / mL, approximately 2,500ng / mL to approximately 4,500n g / mL, approximately 2,500ng / mL to approximately 5,000ng / mL, approximately 2,500ng / mL to approximately 5,500ng / mL, approximately 2,500ng / mL to approximately 6,000ng / mL, approximately 2,500ng / mL to approximately 6,500ng / mL, approximately 2,500ng / mL to approximately 7,000ng / mL , about 2,500ng / mL to about 8,000ng / mL, about 3,000ng / mL to about 3,500ng / mL, about 3,000ng / mL to about 4,000ng / mL, about 3,000ng / mL to about 4,500ng / mL, about 3,000ng / mL to about 5,000ng / mL, about 3,3,5 00ng / mL~about 4,000ng / mL, about 3,500ng / mL~about 4,500ng / mL, about 3,500ng / mL~about 5,000ng / mL, about 3,500ng / mL~about 5,500ng / mL, about 3,500ng / mL~about 6,000ng / mL, about 3,500 ng / mL~about 6,500ng / mL, about 3,500ng / mL~about 7,000ng / mL, about 3,500ng / mL~about 8,000ng / mL, about 4,000ng / mL~about 4,500ng / mL, about 4,000ng / mL~about 5,000ng / mL, about 4,000ng / mL ~ approx. 5,500ng / mL, approx. 4,000ng / mL ~ approx. 6,000ng / mL, approx. 4,000ng / mL ~ approx. 6,500ng / mL, approx. 4,000ng / mL ~ approx. 7,000ng / mL, approx. 4,000ng / mL ~ approx. 8,000ng / mL, approx. 4,500ng / m L~about 5,000ng / mL, about 4,500ng / mL~about 5,500ng / mL, about 4,500ng / mL~about 6,000ng / mL, about 4,500ng / mL~about 6,500ng / mL, about 4,500ng / mL~about 7,000ng / mL, about 4,500ng / mL~ Approximately 8,000ng / mL, approximately 5,000ng / mL to approximately 5,500ng / mL, approximately 5,000ng / mL to approximately 6,000ng / mL, approximately 5,000ng / mL to approximately 6,500ng / mL, approximately 5,000ng / mL to approximately 7,000ng / mL, approximately 5,000ng / mL to approximately 8 ,000ng / mL, about 5,500ng / mL to about 6,000ng / mL, about 5,500ng / mL to about 6,500ng / mL, about 5,500ng / mL to about 7,000ng / mL, about 5,500ng / mL to about 8,000ng / mL, about 6,000ng / mL to about 6,500ng / mL, about 6,000ng / mL to about 7,000ng / mL, about 6,000ng / mL to about 8,000ng / mL, about 6,500ng / mL to about 7,000ng / mL, about 6,500ng / mL to about 8,000ng / mL, or about 7,000ng / mL to about 8,The subject is administered an amount sufficient to achieve a Cmax of Compound A of 1,000 ng / mL.

[0195] In some embodiments, an oral liquid suspension comprising Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve a predefined AUC level of Compound A. In some embodiments, the area under the concentration versus time curve from time 0 to t (AUC 0-t ) or AUCss (steady state AUC) is measured in a subject administered Compound A, or a pharma- ceutically acceptable salt thereof. In some embodiments, AUC 0-t is the AUC 0-12 (or AUC0-12 hours), AUC 0-24 (or AUC0-24 hours), or AUC 0-48 (or AUC0-48 hours). In some embodiments, the AUC 0-t is the AUC 0-24 In some embodiments, the AUC is AUCss.

[0196] In some embodiments, the oral liquid suspension comprising Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve a prescribed steady-state AUC (AUCss) in the subject. In some embodiments, the oral liquid suspension comprising Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve an AUCss for Compound A in the subject that is at least about 100,000 ng·h / mL. In some embodiments, the AUCss is at least about 200,000 ng·h / mL. In some embodiments, the AUCss is at least about 300,000 ng·h / mL. In some embodiments, the oral liquid suspension comprising Compound A or a pharma- ceutically acceptable salt thereof is administered in an amount sufficient to achieve an AUCss for Compound A in the subject that is at least about 400,000 ng·h / mL. In some embodiments, the AUCss is at least about 500,000 ng·h / mL. In some embodiments, the AUCss is at least about 600,000 ng·h / mL. In some embodiments, the AUCss is at least about 400,000 ng·h / mL to at least about 800,000 ng·h / mL. In some embodiments, the AUCss is at least about 500,000 ng·h / mL to at least about 700,000 ng·h / mL. In some embodiments, the AUCss is at least about 300,000 ng·h / mL to at least about 800,000 ng·h / mL. In some embodiments, the AUCss is at least about 200,000 ng·h / mL to at least about 800,000 ng·h / mL. In some embodiments, the AUCss is about 100,000 ng·h / mL to about 800,000 ng·h / mL. In some embodiments, the AUCss is up to about 600,000 ng·h / mL. In some embodiments, the AUCss is up to about 800,000 ng·h / mL. In some embodiments, the AUCss is up to about 1,000,000 ng·h / mL. In some embodiments, the AUCss is up to about 1,200,000 ng·h / mL. In some embodiments, the AUCss is up to about 1,600,000 ng·h / mL.

[0197] In some embodiments, the oral liquid suspension comprising compound A or a pharma- ceutically acceptable salt thereof has a concentration of about 100,000 ng·h / mL to about 1,600,000 ng·h / mL, about 100,000 ng·h / mL to about 1,000,000 ng·h / mL, about 100,000 ng·h / mL to about 800,000 ng·h / mL, about 100,000 ng·h / mL to about 600,000 ng·h / mL, 200,000 ng·h / mL to about 1,600,000 ng·h / mL, about 200 ,000ng·h / mL~approx. 1,000,000ng·h / mL, approx. 200,000ng·h / mL~approx. 800,000ng·h / mL, approx. 200,000ng·h / mL~approx. 600,000ng·h / mL, 300,000ng·h / mL ~ approx. 1,600,000ng h / mL, approx. 300,000 ng h / mL ~ approx. 1,000,000 ng h / mL, approx. 300,000 ng h / mL ~ approx. 800,000 ng h / mL, approx. 600,000ng·h / mL, 400,000ng·h / mL~Approx. 1,600,000ng·h / mL, Approx. 400,000ng·h / mL~Approx. 1,000,000ng·h / mL, Approx. 400,000ng·h / mL~Approx. 0ng·h / mL, approximately 400,000ng·h / mL to approximately 600,000ng·h / mL, 500,000ng·h / mL to approximately 1,600,000ng·h / mL, approximately 500,000ng·h / mL to approximately 1,000,000ng·h / The subject is administered an amount sufficient to achieve an AUCss for Compound A in the subject that is about 500,000 ng·h / mL to about 800,000 ng·h / mL, about 500,000 ng·h / mL to about 600,000 ng·h / mL, 600,000 ng·h / mL to about 1,600,000 ng·h / mL, about 600,000 ng·h / mL to about 1,000,000 ng·h / mL, or about 600,000 ng·h / mL to about 800,000 ng·h / mL.

[0198] In some embodiments, the oral liquid suspension comprising compound A or a pharma- ceutically acceptable salt thereof has a concentration of about 300,000 ng·h / mL to about 450,000 ng·h / mL, about 300,000 ng·h / mL to about 500,000 ng·h / mL, about 300,000 ng·h / mL to about 550,000 ng·h / mL, about 300,000 ng·h / mL to about 650,000 ng·h / mL, about 350,000 ng·h / mL to about 750,000 ng·h / mL, about 40 The subject is administered an amount sufficient to achieve an AUCss for Compound A in the subject that is between 0,000 ng·h / mL and about 650,000 ng·h / mL, between about 400,000 ng·h / mL and about 750,000 ng·h / mL, between about 400,000 ng·h / mL and about 850,000 ng·h / mL, between about 400,000 ng·h / mL and about 950,000 ng·h / mL, or between about 400,000 ng·h / mL and about 1,000,000 ng·h / mL.

[0199] In some embodiments, an oral liquid suspension comprising Compound A or a pharma- ceutical acceptable salt thereof has a defined AUC 0-t In some embodiments, the subject is administered an amount sufficient to achieve an AUC 0-t is the AUC 0-24 In some embodiments, the oral liquid suspension comprising Compound A or a pharma- ceutical acceptable salt thereof has an AUC 0-24 In some embodiments, the oral liquid suspension comprising Compound A or a pharma- ceutical acceptable salt thereof is administered in an amount sufficient to achieve an AUC of Compound A of at least about 50,000 ng·h / mL. 0-24 In some embodiments, the oral liquid suspension comprising Compound A or a pharma- ceutical acceptable salt thereof is administered in an amount sufficient to achieve an AUC of Compound A of at least about 100,000 ng·h / mL. 0-24 In some embodiments, the subject is administered an amount sufficient to achieve an AUC 0-24is at least about 100,000 ng·h / mL to at least about 600,000 ng·h / mL. 0-24 In some embodiments, the AUC 0-24 is at least about 100,000 ng h / mL. 0-24 is up to approximately 600,000 ng·h / mL.

[0200] In some embodiments, the oral liquid suspension comprising compound A or a pharma- ceutical acceptable salt thereof has a concentration of about 100,000 ng·h / mL to about 150,000 ng·h / mL, about 100,000 ng·h / mL to about 200,000 ng·h / mL, about 100,000 ng·h / mL to about 250,000 ng·h / mL, about 100,000 ng·h / mL to about 300,000 ng·h / mL, about 100,000 ng·h / mL to about 350,000 ng·h / mL, about 100,000 ng·h / mL to about 400,000 ng·h / mL, about 100,000 ng·h / mL to about 500,000 ng·h / mL, about 100,000 ng·h / mL to about 600,000 ng·h / mL, about 100,000 ng·h / mL to about 700,000 ng·h / mL, about 100,000 ng·h / mL to about 800,000 ng·h / mL, about 100,000 ng·h / mL to about 900,000 ng·h / mL, about 100,000 ng·h / mL to about 1100,000 ng·h / mL, about 100,000 ng·h / mL to about 1200,000 ng·h / mL, about 100,000 ng·h / mL to about 1300,000 ng·h / mL, about 100,000 ng·h / mL to about 1400,000 ng·h / mL L ~ approx. 450,000ng h / mL, approx. 100,000 ng h / mL ~ approx. 500,000 ng h / mL, approx. 100,000 ng h / mL ~ approx. 550,000 ng h / mL, approx. 100,000 ng h / mL ~ approx. 600,000 ng h / mL, approx. 150,000 ng ·h / mL ~ approx. 200,000ng h / mL, approx. 150,000ng h / mL ~ approx. 250,000 ng h / mL, approx. 150,000 ng h / mL ~ approx. 300,000 ng h / mL, approx. 00ng·h / mL~approx. 400,000ng·h / mL, approx. 150,000ng·h / mL~approx. 450,000ng·h / mL, approx. 150,000ng·h / mL~approx. 500,000ng·h / mL, approx. 150,000ng·h / mL~approx. 150,000ng·h / mL~approx. 600,000ng·h / mL, approx. 200,000ng·h / mL~approx. 250,000ng·h / mL, approx. 200,000ng·h / mL~approx. 300,000ng·h / mL, approx. 200,000ng·h / mL~approx. 350,000ng·h / mL, approx. 200,000ng h / mL ~ approx. 400,000 ng h / mL, approx. 200,000 ng h / mL ~ approx. 450,000 ng h / mL, approx. 200,000 ng h / mL ~ approx. 500,000 ng h / mL, approx. 200,000 ng h / mL ~ approx. 550,000 n g h / mL, about 200,000 ng h / mL to about 600,000 ng h / mL, about 250,000 ng h / mL to about 300,000 ng h / mL, about 250,000 ng h / mL to about 350,000 ng h / mL, about 250,000 ng h / mL to about 400,000ng·h / mL, approximately 250,000ng·h / mL to approximately 450,000ng·h / mL, approximately 250,000ng·h / mL to approximately 500,000ng·h / mL, approximately 250,000ng·h / mL to approximately 550,000ng·h / mL, approx. 250,000ng h / mL ~ approx. 600,000 ng h / mL, approx. 300,000 ng h / mL ~ approx. 350,000 ng h / mL, approx. 300,000 ng h / mL ~ approx. 400,000 ng h / mL, approx. 30 0,000ng·h / mL~approx. 450,000ng·h / mL, approx. 300,000ng·h / mL~approx. 500,000ng·h / mL, approx. 300,000ng·h / mL~approx. 550,000ng·h / mL, approx. 300,000ng · h / mL ~ approx. 600,000 ng · h / mL, approx. 350,000 ng · h / mL ~ approx. 400,000 ng · h / mL, approx. 350,000 ng · h / mL ~ approx. 450,000 ng · h / mL, approx. 500,000ng·h / mL, approximately 350,000ng·h / mL to approximately 550,000ng·h / mL, approximately 350,000ng·h / mL to approximately 600,000ng·h / mL, approximately 400,000ng·h / mL to approximately 450,000 ng·h / mL, approximately 400,000ng·h / mL to approximately 500,000ng·h / mL, approximately 400,000ng·h / mL to approximately 550,000ng·h / mL, approximately 400,000ng·h / mL to approximately 600,000ng·h / mL , about 450,000ng·h / mL to about 500,000ng·h / mL, about 450,000ng·h / mL to about 550,000ng·h / mL, about 450,000ng·h / mL to about 600,000ng·h / mL, about 500,000ng·h / mL to about 550,000ng·h / mL, about 500,000ng·h / mL to about 600,000ng·h / mL, or about 550,000ng·h / mL to about 600,000ng·h / mL. 0-24 The therapeutic agent is administered in an amount sufficient to achieve in the subject.

[0201] In some embodiments, an oral liquid suspension comprising Compound A or a pharma- ceutical acceptable salt thereof has a defined AUC 0-∞In some embodiments, Compound A is administered in an amount sufficient to achieve an AUC 0-∞ In some embodiments, the AUC of Compound A ranges from about 250 μg·hr / L to about 1,600 μg·hr / L. 0-∞ comprises at least about 250 μg·hr / L. 0-∞ In some embodiments, the AUC of Compound A is at most about 1,600 μg·hr / L. 0-∞is about 250μg·h / L to about 350μg·h / L, about 250μg·h / L to about 450μg·h / L, about 250μg·h / L to about 550μg·h / L, about 250μg·h / L to about 650μg·h / L, about 250μg·h / L to about 750μg·h / L, about 250μg·h / L to about 850μg·h / L, about 250μg·h / L to about 950μg·h / L, about 250μg·h / L to about 1,000μg·h / L, about 250μg·h / L to about 1,250μg·h / L, about 250μg·h / L ~Approx. 1,500μg·hr / L, Approx. 250μg·hr / L ~Approx. 1,600μg·hr / L, Approx. 350μg·hr / L ~ Approx. 450μg·hr / L, Approx. 350μg·hr / L ~ Approx. 550μg·hr / L, Approx. 350μg·hr / L ~ Approx. 650μg·hr / L, Approx. 350 μg·hr / L~approx. 750μg·hr / L, approx. 350μg·hr / L~approx. 850μg·hr / L, approx. 350μg·hr / L~approx. 950μg·hr / L, approx. 350μg·hr / L~approx. 1,000μg·hr / L, approx. 350μg·hr / L~approx. 1,250μg·hr / L, approx. 350 μg · h / L ~ approx. 1,500 μg · h / L, approx. 350 μg · h / L ~ approx. 1,600 μg · h / L, approx. 450 μg · h / L ~ approx. 550 μg · h / L, approx. 450 μg · h / L ~ approx. 650 μg · h / L, approx. 50μg·hr / L, approx. 450μg·hr / L to approx. 850μg·hr / L, approx. 450μg·hr / L to approx. 950μg·hr / L, approx. 450μg·hr / L to approx. 1,000μg·hr / L, approx. 450μg·hr / L to approx. 1,250μg·hr / L, approx. 450μg·hr / L Time / L ~ approx. 1,500 μg · hour / L, approx. 450 μg · hour / L ~ approx. 1,600 μg · hour / L, approx. 550 μg · hour / L ~ approx. 650 μg · hour / L, approx. 550 μg · hour / L ~ approx. 750 μg · hour / L, approx. Approximately 550μg·hr / L to approximately 950μg·hr / L, approximately 550μg·hr / L to approximately 1,000μg·hr / L, approximately 550μg·hr / L to approximately 1,250μg·hr / L, approximately 550μg·hr / L to approximately 1,500μg·hr / L, approximately 550μg·hr / L to approximately 1,600μg·hr / L, approximately 650μg·hr / L~approx. 750μg·hr / L, approximately 650μg·hr / L~approximately 850μg·hr / L, approximately 650μg·hr / L~approximately 950μg·hr / L, approximately 650μg·hr / L ~ approx. 1,000 μg · h / L, approx. 650 μg · h / L ~ approx. 1,250 μg · h / L, approx. 650 μg · h / L ~ approx. 1,500 μg · h / L, approx. 650 μg · h / L ~ approx. 1,600 μg · h / L , about 750μg·hr / L to about 850μg·hr / L, about 750μg·hr / L to about 950μg·hr / L, about 750μg·hr / L to about 1,000μg·hr / L, about 750μg·hr / L to about 1,250 μg·hr / L, approx. 750 μg·hr / L to approx. 1,500 μg·hr / L, approx. 750 μg·hr / L to approx. 1,600 μg·hr / L, approx. 850 μg·hr / L to approx. 950 μg·hr / L, approx. 850 μg·hr / L ~ approx. 1,000 μg · h / L, approx. 850 μg · h / L ~ approx. 1,250 μg · h / L, approx. 850 μg · h / L ~ approx. 1,500 μg · h / L, approx. 850 μg · h / L ~ approx. L, approx. 950 μg · h / L ~ approx. 1,000 μg · h / L, approx. 950 μg · h / L ~ approx. 1,250 μg · h / L, approx. 950 μg · h / L ~ approx. 1,500 μg · h / L, approx. 950 μg · h / L ~ approx. 1,600μg·hr / L, about 1,000μg·hr / L to about 1,250μg·hr / L, about 1,000μg·hr / L to about 1,500μg·hr / L, about 1,000μg·hr / L to about 1,600μg·hr / L, about 1,250μg·hr / L to about 1,500μg·hr / L, about 1,250μg·hr / L to about 1,600μg·hr / L, or about 1,500μg·hr / L to about 1,600μg·hr / L.

[0202] In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 100 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least 100 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 100 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least 100 ng / mL, at least 200 ng / mL, at least 300 ng / mL, at least 400 ng / mL, at least 500 ng / mL, at least 1000 ng / mL, at least 1,500 ng / mL, at least 2000 ng / mL, at least 2500 ng / mL, at least 3000 ng / mL, at least 3500 ng / mL, at least 4000 ng / mL, at least 4500 ng / mL, at least 5000 ng / mL, at least 5500 ng / mL, at least 6000 ng / mL, at least 6500 ng / mL, at least 7000 ng / mL, at least 7500 ng / mL, or at least 8000 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 100 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at most 100 ng / mL, at most 200 ng / mL, at most 300 ng / mL, at most 400 ng / mL, at most 500 ng / mL, at most 1000 ng / mL, at most 1,500 ng / mL, at most 2000 ng / mL, at most 2500 ng / mL, at most 3000 ng / mL, at most 3500 ng / mL, at most 4000 ng / mL, at most 4500 ng / mL, at most 5000 ng / mL, at most 5500 ng / mL, at most 6000 ng / mL, at most 6500 ng / mL, at most 7000 ng / mL, at most 7500 ng / mL, or at most 8000 ng / mL.In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 100 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of about 100 ng / mL, about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 1000 ng / mL, about 1,500 ng / mL, about 2000 ng / mL, about 2500 ng / mL, about 3000 ng / mL, about 3500 ng / mL, about 4000 ng / mL, about 4500 ng / mL, about 5000 ng / mL, about 5500 ng / mL, about 6000 ng / mL, about 6500 ng / mL, about 7000 ng / mL, about 7500 ng / mL, or about 8000 ng / mL.

[0203] In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 75 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least 100 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 75 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least 100 ng / mL, at least 200 ng / mL, at least 300 ng / mL, at least 400 ng / mL, at least 500 ng / mL, at least 1000 ng / mL, at least 1,500 ng / mL, at least 2000 ng / mL, at least 2500 ng / mL, at least 3000 ng / mL, at least 3500 ng / mL, at least 4000 ng / mL, at least 4500 ng / mL, at least 5000 ng / mL, at least 5500 ng / mL, at least 6000 ng / mL, at least 6500 ng / mL, at least 7000 ng / mL, at least 7500 ng / mL, or at least 8000 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 75 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at most 100 ng / mL, at most 200 ng / mL, at most 300 ng / mL, at most 400 ng / mL, at most 500 ng / mL, at most 1000 ng / mL, at most 1,500 ng / mL, at most 2000 ng / mL, at most 2500 ng / mL, at most 3000 ng / mL, at most 3500 ng / mL, at most 4000 ng / mL, at most 4500 ng / mL, at most 5000 ng / mL, at most 5500 ng / mL, at most 6000 ng / mL, at most 6500 ng / mL, at most 7000 ng / mL, at most 7500 ng / mL, or at most 8000 ng / mL.In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 75 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of about 100 ng / mL, about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 1000 ng / mL, about 1,500 ng / mL, about 2000 ng / mL, about 2500 ng / mL, about 3000 ng / mL, about 3500 ng / mL, about 4000 ng / mL, about 4500 ng / mL, about 5000 ng / mL, about 5500 ng / mL, about 6000 ng / mL, about 6500 ng / mL, about 7000 ng / mL, about 7500 ng / mL, or about 8000 ng / mL.

[0204] In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 50 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least about at least 2000 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 50 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least 100 ng / mL, at least 200 ng / mL, at least 300 ng / mL, at least 400 ng / mL, at least 500 ng / mL, at least 1000 ng / mL, at least 1,500 ng / mL, at least 2000 ng / mL, at least 2500 ng / mL, at least 3000 ng / mL, at least 3500 ng / mL, at least 4000 ng / mL, at least 4500 ng / mL, at least 5000 ng / mL, at least 5500 ng / mL, at least 6000 ng / mL, at least 6500 ng / mL, at least 7000 ng / mL, at least 7500 ng / mL, or at least 8000 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 50 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at most 100 ng / mL, at most 200 ng / mL, at most 300 ng / mL, at most 400 ng / mL, at most 500 ng / mL, at most 1000 ng / mL, at most 1,500 ng / mL, at most 2000 ng / mL, at most 2500 ng / mL, at most 3000 ng / mL, at most 3500 ng / mL, at most 4000 ng / mL, at most 4500 ng / mL, at most 5000 ng / mL, at most 5500 ng / mL, at most 6000 ng / mL, at most 6500 ng / mL, at most 7000 ng / mL, at most 7500 ng / mL, or at most 8000 ng / mL.In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 50 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of about 100 ng / mL, about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 1000 ng / mL, about 1,500 ng / mL, about 2000 ng / mL, about 2500 ng / mL, about 3000 ng / mL, about 3500 ng / mL, about 4000 ng / mL, about 4500 ng / mL, about 5000 ng / mL, about 5500 ng / mL, about 6000 ng / mL, about 6500 ng / mL, about 7000 ng / mL, about 7500 ng / mL, or about 8000 ng / mL.

[0205] In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 25 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least about at least 100 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 25 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least 100 ng / mL, at least 200 ng / mL, at least 300 ng / mL, at least 400 ng / mL, at least 500 ng / mL, at least 1000 ng / mL, at least 1,500 ng / mL, at least 2000 ng / mL, at least 2500 ng / mL, at least 3000 ng / mL, at least 3500 ng / mL, at least 4000 ng / mL, at least 4500 ng / mL, at least 5000 ng / mL, at least 5500 ng / mL, at least 6000 ng / mL, at least 6500 ng / mL, at least 7000 ng / mL, at least 7500 ng / mL, or at least 8000 ng / mL. In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 25 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at most 100 ng / mL, at most 200 ng / mL, at most 300 ng / mL, at most 400 ng / mL, at most 500 ng / mL, at most 1000 ng / mL, at most 1,500 ng / mL, at most 2000 ng / mL, at most 2500 ng / mL, at most 3000 ng / mL, at most 3500 ng / mL, at most 4000 ng / mL, at most 4500 ng / mL, at most 5000 ng / mL, at most 5500 ng / mL, at most 6000 ng / mL, at most 6500 ng / mL, at most 7000 ng / mL, at most 7500 ng / mL, or at most 8000 ng / mL.In some embodiments, the oral liquid suspension, when administered to a human subject in an amount equivalent to about 25 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of about 100 ng / mL, about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 1000 ng / mL, about 1,500 ng / mL, about 2000 ng / mL, about 2500 ng / mL, about 3000 ng / mL, about 3500 ng / mL, about 4000 ng / mL, about 4500 ng / mL, about 5000 ng / mL, about 5500 ng / mL, about 6000 ng / mL, about 6500 ng / mL, about 7000 ng / mL, about 7500 ng / mL, or about 8000 ng / mL.

[0206] The subject may be, for example, a mammal, a human, a pregnant female, an elderly person, an adult, an adolescent, a pre-adolescent child, a child, an infant, a baby, a newborn, or a neonate. The subject may be a patient. In some cases, the subject may be a human. In some cases, the subject may be a child (e.g., a young human who is under the age of puberty). In some cases, the subject may be an infant. In some cases, the subject may be a bottle-fed infant. In some cases, the subject may be an individual enrolled in a clinical study. In some cases, the subject may be a laboratory animal, e.g., a mammal, or a rodent. In some cases, the subject may be a mouse. In some cases, the subject may be an obese or overweight subject. Age range

[0207] In some embodiments, the subjects described herein are younger than 18 years old. In some embodiments, the subjects described herein are 1 week to 6 months old. In some embodiments, the subjects described herein are 28 days to 6 months old. In some embodiments, the subjects described herein are at least 6 months old. In some embodiments, the subjects described herein are at most 6 months old. In some embodiments, the subjects described herein are at least 28 days, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months old. In some embodiments, the subjects described herein are at most 28 days, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months old. In some embodiments, the subjects described herein are at least 1 year old, 2 years old, 3 years old, 4 years old, 5 years old, 6 years old, 7 years old, 8 years old, 9 years old, 10 years old, 11 years old, 12 years old, 13 years old, 14 years old, 15 years old, 16 years old, 17 years old, or 18 years old. In some embodiments, the subjects described herein are at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 years old. In some embodiments, the subjects described herein are at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 years old. In some embodiments, the subjects described herein are at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 years old. In some embodiments, the subjects described herein are up to 28 days old, 1 month old, 2 months old, 3 months old, 4 months old, 5 months old, 6 months old, 7 months old, 8 months old, 9 months old, 10 months old, 11 months old, 12 months old, 24 months old, 48 months old, 60 months old, 72 months old, 84 months old, 96 months old, 108 months old, 120 months old, 132 months old, 144 months old, 156 months old, 168 months old, 180 months old, 192 months old, 204 months old, or 216 months old.In some embodiments, the subjects described herein are up to 28 days old, 1 month old, 2 months old, 3 months old, 4 months old, 5 months old, 6 months old, 7 months old, 8 months old, 9 months old, 10 months old, 11 months old, 12 months old, 2 years old, 3 years old, 4 years old, 5 years old, 6 years old, 7 years old, 8 years old, 9 years old, 10 years old, 11 years old, 12 years old, 13 years old, 14 years old, 15 years old, 16 years old, 17 years old, or 18 years old.

[0208] In some embodiments, the subject has been previously treated with one or more different cancer treatment modalities.In some embodiments, the subject has been previously treated with one or more of radiotherapy, chemotherapy, or immunotherapy.In some embodiments, the subject has been previously treated with 1, 2, 3, 4, or 5 lines of prior therapy.In some embodiments, the prior therapy is a cytotoxic therapy. Cancer and Tumors

[0209] In certain aspects, provided herein is a method of treating cancer, comprising administering a pharmaceutical powder or suspension disclosed herein comprising compound A or a pharma- ceutically acceptable salt thereof. In some embodiments, the cancer is selected from the group consisting of colorectal cancer, pancreatic cancer, lung cancer, ovarian cancer, liver cancer, breast cancer, kidney cancer, prostate cancer, gastrointestinal cancer, melanoma, cervical cancer, neuroendocrine cancer, bladder cancer, glioblastoma, and head and neck cancer. In certain embodiments, the cancer is pancreatic cancer. In certain embodiments, the cancer is ovarian cancer. In certain embodiments, the cancer is colorectal cancer. In certain embodiments, the cancer is breast cancer. In certain embodiments, the cancer is prostate cancer. In certain embodiments, the cancer is lung cancer. In certain embodiments, the cancer is melanoma. In some embodiments, the cancer is a solid cancer.

[0210] In some embodiments, the cancer is a blood cancer. In some embodiments, the cancer is selected from the group consisting of acute myeloid leukemia (AML), Hodgkin's lymphoma, multiple myeloma, T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia, chronic myelogenous leukemia (CML), non-Hodgkin's lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and cutaneous T-cell lymphoma (CTCL).

[0211] The method and pharmaceutical composition of compound A or its salt can be used to treat any suitable cancer known in the art. Non-limiting examples of cancers treated by the method of the present disclosure may include melanoma (e.g., metastatic malignant melanoma), renal cancer (e.g., clear cell carcinoma), prostate cancer (e.g., hormone-resistant prostate adenocarcinoma), pancreatic adenocarcinoma, breast cancer, colon cancer, lung cancer (e.g., non-small cell lung cancer), esophageal cancer, squamous cell carcinoma of the head and neck, liver cancer, ovarian cancer, cervical cancer, thyroid cancer, glioblastoma, glioma, leukemia, lymphoma, and other neoplastic malignancies. In some embodiments, the cancer is low-grade glioma (LGG), such as pediatric low-grade glioma (pLGG). In some embodiments, the pharmaceutical composition of compound A or its salt is used as a front-line treatment for treating cancer. In some embodiments, the subject has not previously been treated with any standard of care for treating cancer. In some embodiments, the pharmaceutical composition of Compound A or a salt thereof is used to treat a newly diagnosed cancer.

[0212] In some embodiments, the cancer is low-grade glioma. In some embodiments, the cancer is pLGG. In some embodiments, the pLGG is identified as having one or more of the following mutations: RAS positive mutation, RAF positive mutation, MEK positive mutation, and ERK positive mutation. In some embodiments, the pLGG has a BRAF mutation. In some embodiments, the BRAF mutation is a non-V600 BRAF mutation. In some embodiments, the BRAF mutation is a V600 BRAF mutation. In some embodiments, the presence of BRAF fusion or rearrangement or BRAF mutation in the subject is confirmed before treatment. In some embodiments, the subject is identified as having one or more of the following wild-type fusions: KIAA1549:BRAF, STARD3NL:BRAF, BCAS1:BRAF, KHDRBS2:BRAF, CCDC6:BRAF, FAM131B:BRAF, SRGAP:BRAF, CLCN6:BRAF, GNAI1:BRAF, MRKN1:BRAF, GIT2:BRAF, GTF21:BRAF, FXR1:BRAF, RNF130:BRAF, BRAF:MACF1, TMEM106B:BRAF, PPC1CC:BRAF, CUX1:BRAF, SRGAP3:RAF1, QK1:RAF1, FYCO:RAF1, ATG7:RAF1, and NFIA:RAF1. In some embodiments, the subject is identified as having a KIAA1549:BRAF wild-type fusion. In some embodiments, the pLGG has a gene fusion. In some embodiments, the cancer is pLGG with RIN2:BRAF gene fusion. In some embodiments, the subject has a cancer with any of the following gene fusions: KIAA1549:BRAF, AGK:BRAF, STARD3NL:BRAF, BCAS1:BRAF, KHDRBS2:BRAF, CCDC6:BRAF, FAM131B:BRAF, SRGAP:BRAF, CLCN6:BRAF, GNAI1:BRAF, MRKN1:BRAF, GIT2:BRAF, GTF2I:BRAF, FXR1:BRAF, RNF130:BRAF, MACF1:BRAF, TMEM106B:BRAF, PPC1CC:BRAF, CUX1:BRAF, CCD6:BRAF, PPP1CC:BRAF, SEPT7:BRAF, PDE10A:BRAF, EPB41L2:BRAF,OSBP:BRAF、DAAM1:BRAF、TEX41:BRAF、FOXN3:BRAF、TRIPP1:BRAF、TOM1L2:BRAF、TMEM106B:BRAF、SRGAP3:RAF1、QK1:RAF1、FYCO:RAF1、ATG7:RAF1、NF IA-RAF1、TMF1:RAF1、GOLGA3:RAF1、SOX6:RAF1、BMPR1A:RAF1、PDZRN3:RAF1、SLMAP:RAF1、MAP4:RAF1、BCL6-RAF1、SEPT17:BRAF、ZNF767:BRAF、CCDC9 1:BRAF、DYNC1 / 2:BRAF、ZKSCAN1:BRAF、GTF2I:BRAF、MZT1:BRAF、RAD18:BRAF、CUX1:BRAF、CUX1-RAF1、CUL1:BRAF、SLC12A7:BRAF、TRIM24:BRAF、AGAP 3:BRAF、AKAP9:BRAF、TAX1BP1:BRAF、CDC27:BRAF、FKBP15:BRAF、SKAP2:BRAF、TARDBP:BRAF、SEPT3:BRAF、ARMC10:BRAF、PAPSS1:BRAF、FCHSD1:BRAF、E RC1:BRAF、CDK5RAP2:BRAF、TMEM178B:BRAF、BAIAP2L1:BRAF、CEP89:BRAF、CNTNAP2:BRAF、EML4:BRAF、KCTD7:BRAF、LSM14A:BRAF、NFIC:BRAF、NUCD3 :BRAF、PHTF2:BRAF、PLIN3:BRAF、RP2:BRAF、SOX5:BRAF、SOX6:BRAF、TLK2:BRAF、ZKSCAN5:BRAF、KLC1-RAF1、DAAM1-RAF1、ZNF444-RAF1、LRCH3-RAF1、G OLGA4-RAF1、CTDSPL-RAF1、PRKAR2A-RAF1、CTNNA1-RAF1、MKRN1-RAF1、DYNC1H1-RAF1、GPHN-RAF1、KLHL7:BRAF、TANK:BRAF、RBMS3:BRAF、FAM114A2:B RAF、AGGF1-RAF1、EPS15:BRAF、NUP214:BRAF、BTF3L4:BRAF、GHR:BRAF、DOCK4:BRAF、ZC3HAV1:BRAF、MKRN1:BRAF、MYRIP:BRAF、SND1:BRAF、TNS3:BRAF、The subject has one or more of ATG7:BRAF, NUB1:BRAF, STRN3:BRAF, STK35:BRAF, ETFA:BRAF, SVOPL:BRAF, JHDM1D:BRAF, PPFIBP2:BRAF, SCL45A3:BRAF, ESRP1-RAF1, AGTRAP:BRAF, SVIP:BRAF, NRF1:BRAF, RAF1-CCDC176, RAF1-TRAK1, ESYT2:BRAF, PCBP2:BRAF, and SALL2:BRAF. In some embodiments, the subject has a TRIM33:BRAF gene fusion.

[0213] In some embodiments, the targets are the following gene fusions: AGK:BRAF, STARD3NL:BRAF, BCAS1:BRAF, KHDRBS2:BRAF, CCDC6:BRAF, FAM131B:BRAF, SRGAP:BRAF, CLCN6:BRAF, GNAI1:BRAF, MRKN1:BRAF, GIT2:BRAF, GTF2I:BRAF, FXR1:BRAF, RNF130:BRAF, MACF1:BRAF, TMEM106B:BRAF, PPC1CC:BRAF, CUX1:BRAF, CCD6:BRAF, PPP1CC:BRAF, SEPT7:BRAF, PDE10A:BRAF, EPB41L2:BRAF, OSBP:BRAF, DAAM1:BRAF, TEX41:BRAF, FOXN3:BRAF, TRIPP1:BRAF, TOM1L2:BRAF, TMEM106B:BRAF, QK1:RAF1, FYCO:RAF1, ATG7:RAF1, NFIA-RAF1, TMF1:RAF1, GOLGA3:RAF1, SOX6:RAF1, BMPR1A:RAF1, PDZRN3:RAF1, SLMAP:RAF1, MAP4:RAF1, BCL6-RAF1, SEPT17:BRAF, ZNF767:BRAF, CCDC91:BRAF, DYNC1 / 2:BRAF, ZKSCAN1:BRAF, GTF2I:BRAF, MZT1:BRAF, RAD18:BRAF, CUX1:BRAF, CUX1-RAF1, CUL1:BRAF, SLC12A7:BRAF, TRIM24:BRAF, AGAP3:BRAF, AKAP9:BRAF, TAX1BP1:BRAF, CDC27:BRAF, FKBP15:BRAF, SKAP2:BRAF, TARDBP:BRAF, SEPT3:BRAF, ARMC10:BRAF, PAPSS1:BRAF, FCHSD1:BRAF, ERC1:BRAF, CDK5RAP2:BRAF, TMEM178B:BRAF, BAIAP2L1:BRAF, CEP89:BRAF, CNTNAP2:BRAF, EML4:BRAF, KCTD7:BRAF, LSM14A:BRAF, NFIC:BRAF, NUDCD3:BRAF, PHTF2:BRAF, PLIN3:BRAF, RP2:BRAF, SOX5:BRAF, SOX6:BRAF, TLK2:BRAF, ZKSCAN5:BRAF, KLC1-RAF1, DAAM1-RAF1, ZNF444-RAF1, LRCH3-RAF1, GOLGA4-RAF1, CTDSPL-RAF1, PRKAR2A- RAF1, CTNNA1-RAF1, MKRN1-RAF1, DYNC1H1-RAF1, GPHN-RAF1, KLHL7:BRAF, TANK:BRAF, RBMS3:BRAF, FAM114A2:BRAF, AGGF1-RAF1, E PS15:BRAF, NUP214:BRAF, BTF3L4:BRAF, GHR:BRAF, DOCK4:BRAF, ZC3HAV1:BRAF, MKRN1:BRAF, MYRIP:BRAF, SND1:BRAF, TNS3:BRAF, and one or more of ATG7:BRAF, NUB1:BRAF, STRN3:BRAF, STK35:BRAF, ETFA:BRAF, SVOPL:BRAF, JHDM1D:BRAF, PPFIBP2:BRAF, SCL45A3:BRAF, ESRP1-RAF1, AGTRAP:BRAF, SVIP:BRAF, NRF1:BRAF, RAF1-CCDC176, RAF1-TRAK1, ESYT2:BRAF, PCBP2:BRAF, and SALL2:BRAF.

[0214] In some embodiments, the gene fusion is a BRAF fusion. In some embodiments, the BRAF fusion is AGK:BRAF, STARD3NL:BRAF, BCAS1:BRAF, KHDRBS2:BRAF, CCDC6:BRAF, FAM131B:BRAF, SRGAP:BRAF, CLCN6:BRAF, GNAI1:BRAF, MRKN1:BRAF, GIT2:BRAF, GTF2I:BRAF, FXR1:BRAF, RNF130:BRAF, MACF1:BRAF, TMEM106B:BRAF, PPC1CC:BRAF, CUX1:BRAF, CCD6:BRAF, PPP1CC:BRAF, SEPT7:BRAF, PDE10A:BRAF, EPB41L2:BRAF, OSBP:BRAF, DAAM1:BRAF, TEX41:BRAF, FOXN3:BRAF, TRIPP1:BRAF, TOM1L2:BRAF, 5 BRAFselected from fusions, TMEM106B:BRAF, SEPT17:BRAF, ZNF767:BRAF, CCDC91:BRAF, DYNC1 / 2:BRAF, ZKSCAN1:BRAF, GTF2I:BRAF, MZT1:BRAF, RAD18:BRAF, CUX1:BRAF, CUL1:BRAF, SLC12A7:BRAF, TRIM24:BRAF, AGAP3:BRAF, AKAP9:BRAF, TAX1BP1:BRAF, CDC27:BRAF, FKBP15:BRAF, SKAP2:BRAF, TARDBP:BRAF, SEPT3:BRAF, ARMC10:BRAF, PAPSS1:BRAF, FCHSD1:BRAF, ERC1:BRAF, CDK5RAP2:BRAF, TMEM178B:BRAF, BAIAP2L1:BRAF, CEP89:BRAF, CNTNAP2:BRAF, EML4:BRAF, KCTD7:BRAF, LSM14A:BRAF, NFIC:BRAF, NUDCD3:BRAF, PHTF2:BRAF, PLIN3:BRAF, RP2:BRAF, SOX5:BRAF, SOX6:BRAF, TLK2:BRAF, ZKSCAN5:BRAF, KLHL7:BRAF, TANK:BRAF, RBMS3:BRAF, FAM114A2:BRAF, EPS15:BRAF, NUP214:BRAF, BTF3L4:BRAF, GHR:BRAF, DOCK4:BRAF, ZC3HAV1:BRAF, MKRN1:BRAF, MYRIP:BRAF, SND1:BRAF, TNS3:BRAF, ATG7:BRAF, NUB1:BRAF, STRN3:BRAF, STK35:BRAF, ETFA:BRAF, SVOPL:BRAF, JHDM1D:BRAF, PPFIBP2:BRAF, SCL45A3:BRAF, AGTRAP:BRAF, SVIP:BRAF, NRF1:BRAF, ESYT2:BRAF, PCBP2:BRAF and SALL2:BRAF.

[0215] In some embodiments, the gene fusion is a RAF1 fusion. In some embodiments, the RAF1 fusion is SRGAP3:RAF1, QK1:RAF1, FYCO:RAF1, ATG7:RAF1, NFIA:RAF1, TMF1:RAF1, GOLGA3:RAF1, SOX6:RAF1, BMPR1A:RAF1, PDZRN3:RAF1, SLMAP:RAF1, MAP4:RAF1, BCL6:RAF1, CUX1:RAF1, KLC1:RAF1 1, DAAM1:RAF1, ZNF444:RAF1, LRCH3:RAF1, GOLGA4:RAF1, CTDSPL:RAF1, PRKAR2A:RAF1, CTNNA1:RAF1, MKRN1:RAF1, DYNC1H1:RAF1, AGGF1:RAF1, ESRP1:RAF1, GPHN:RAF1, RAF1-CCDC176 and RAF1-TRAK1.

[0216] In some embodiments, the subject has a CRAF gene fusion. In some embodiments, the CRAF gene fusion is selected from the group consisting of SRGAP3:RAF1, QK1:RAF1, FYCO:RAF1, ATG7:RAF1, NFIA:RAF1, TMF1:RAF1, GOLGA3:RAF1, SOX6:RAF1, BMPR1A:RAF1, PDZRN3:RAF1, SLMAP:RAF1, MAP4:RAF1, BCL6:RAF1, CUX1:RAF1, KLC1 :RAF1, DAAM1:RAF1, ZNF444:RAF1, LRCH3:RAF1, GOLGA4:RAF1, CTDSPL:RAF1, PRKAR2A:RAF1, CTNNA1:RAF1, MKRN1:RAF1, DYNC1H1:RAF1, AGGF1:RAF1, ESRP1:RAF1, GPHN:RAF1, RAF1-CCDC176 or RAF1-TRAK1.

[0217] Text AS1:BRAF、KHDRBS2:BRAF、CCDC6:BRAF、FAM131B:BRAF、SRGAP:BRAF、CLCN6: BRAF、GNAI1:BRAF、MRKN1:BRAF、GIT2:BRAF、GTF2I:BRAF、FXR1:BRAF、RNF130:BRAF、MACF1:BRAF、TMEM106B:BRAF、PPC1CC:BRAF、CUX1:BRAF、CCD6:BRA F、PPP1CC:BRAF、SEPT7:BRAF、PDE10A:BRAF、EPB41L2:BRAF、OSBP:BRAF、DAAM1:BRAF、TEX41:BRAF、FOXN3:BRAF、TRIPP1:BRAF、TOM1L2:BRAF、TMEM106B :BRAF、SRGAP3:RAF1、QK1:RAF1、FYCO:RAF1、ATG7:RAF1、NFIA-RAF1、TMF1: RAF1、GOLGA3:RAF1、SOX6:RAF1、BMPR1A:RAF1、PDZRN3:RAF1、SLMAP:RAF1、M AP4:RAF1、BCL6-RAF1、SEPT17:BRAF、ZNF767:BRAF、CCDC91:BRAF、DYNC1 / 2:BRAF、ZKSCAN1:BRAF、GTF2I:BRAF、MZT1:BRAF、RAD18:BRAF、CUX1:BRAF、CU x1-raf1 EPT3:BRAF、ARMC10:BRAF、PAPSS1:BRAF、FCHSD1:BRAF、ERC1:BRAF、CDK5RAP2:BRAF、TMEM178B:BRAF、BAIAP2L1:BRAF、CEP89:BRAF、CNTNAP2:BRAF、EML 4: BRAFKLC1-RAF1, DAAM1-RAF1, ZNF444-RAF1, LRCH3- RAF1, GOLGA4-RAF1, CTDSPL-RAF1, PRKAR2A-RAF1, CTNNA1-RAF1, MKRN1-RAF1, DYNC1H1-RAF1, GPHN-RAF1, KL HL7:BRAF, TANK:BRAF, RBMS3:BRAF, FAM114A2:BRAF, AGGF1-RAF1, EPS15:BRAF, NUP214:BRAF, BTF3L4:BRAF, G HR:BRAF, DOCK4:BRAF, ZC3HAV1:BRAF, MKRN1:BRAF, MYRIP:BRAF, SND1:BRAF, TNS3:BRAF, ATG7:BRAF, NUB1:BRAF, STRN3:BRAF, STK35:BRAF, ETFA:BRAF, SVOPL:BRAF, JHDM1D:BRAF, PPFIBP2:BRAF, SCL45A3:BRAF, ESRP1- RAF1, AGTRAP:BRAF, SVIP:BRAF, NRF1:BRAF, RAF1-CCDC176, RAF1-TRAK1, ESYT2:BRAF, PCBP2:BRAF, or SALL2:BRAF.

[0218] In some aspects, the disclosure provides a method of treating a subject having pediatric low-grade glioma (pLGG), comprising reconstituting an amorphous solid dispersion of Compound A or a salt thereof in an aqueous solution and administering a pharma- ceutically acceptable dosage of the reconstituted Compound A or a salt thereof to a subject in need thereof.

[0219] In addition, the diseases or conditions provided herein include refractory or recurrent malignant tumors whose growth can be inhibited using the methods of treatment of the present disclosure. In some embodiments, the cancer treated by the methods of treatment of the present disclosure is selected from the group consisting of carcinoma, squamous cell carcinoma, adenocarcinoma, sarcoma, endometrial cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, colon cancer, colorectal cancer, squamous cell carcinoma of the anogenital area, melanoma, renal cell carcinoma, lung cancer, non-small cell lung cancer, squamous cell carcinoma of the lung, gastric cancer, bladder cancer, gallbladder cancer, liver cancer, thyroid cancer, laryngeal cancer, salivary gland cancer, esophageal cancer, head and neck cancer, glioblastoma, glioma, squamous cell carcinoma of the head and neck, prostate cancer, pancreatic cancer, mesothelioma, sarcoma, blood cancer, leukemia, lymphoma, neuroma, and combinations thereof. In some embodiments, the cancers treated by the methods of the present disclosure include, for example, carcinoma, squamous cell carcinoma (e.g., cervix, eyelid, conjunctiva, vagina, lung, oral cavity, skin, bladder, tongue, larynx, and esophagus), and adenocarcinoma (e.g., prostate, small intestine, endometrium, cervix, large intestine, lung, pancreas, esophagus, rectum, uterus, stomach, breast, and ovary). In some embodiments, the cancers treated by the methods of the present disclosure further include sarcoma (e.g., myogenic sarcoma), leukemia, neuroma, melanoma, and lymphoma. In some embodiments, the cancer treated by the methods of the present disclosure is breast cancer. In some embodiments, the cancer treated by the methods of the present disclosure is triple-negative breast cancer (TNBC). In some embodiments, the cancer treated by the methods of the present disclosure is ovarian cancer. In some embodiments, the cancer treated by the methods of the present disclosure is colorectal cancer. In some embodiments, the cancer is non-spitzoid cutaneous melanoma. In some embodiments, the cancer is

[0220] Specific examples of cancers that may be prevented and / or treated in accordance with the present disclosure include, but are not limited to, renal cancer, kidney cancer, glioblastoma multiforme, metastatic breast cancer; breast cancer; breast sarcoma; neurofibroma; neurofibromatosis; childhood tumors; neuroblastoma; malignant melanoma; carcinoma of the epidermis; leukemias, including, but not limited to, acute leukemia, acute lymphocytic leukemia, acute myeloid leukemia, including myeloblastic leukemia, promyelocytic leukemia, myelomonocytic leukemia, monocytic leukemia, erythroleukemia, and myelodysplastic syndromes. syndrome), chronic leukemias, including but not limited to chronic myelocytic (granulocytic) leukemia, chronic lymphocytic leukemia, hairy cell leukemia; polycythemia vera; lymphomas, including but not limited to Hodgkin's disease, non-Hodgkin's disease; multiple myelomas, including but not limited to smoldering multiple myeloma, non-secretory myeloma, osteosclerotic myeloma, plasma cell leukemia, solitary plasmacytoma, and extramedullary plasmacytoma; Waldenstrom's macroglobulinemia; monoclonal gammopathy of undetermined significance; benign monoclonal gammopathy; heavy chain disease; bone cancer and connective tissue sarcomas, including but not limited to sarcoma of bone, myeloma bone disease, multiple myeloma, cholesteatoma-induced osteosarcoma of bone, Paget's disease of bone, osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant giant cell tumor, fibrosarcoma of bone sarcoma, chordoma, periosteal sarcoma, soft tissue sarcoma, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, schwannoma, rhabdomyosarcoma, and synovial sarcoma; brain tumors, including but not limited to glioma, astrocytoma, brain stem glioma, ependymoma, oligodendroglioma, non-glial tumors, acoustic neuroma, craniopharyngioma, myeloma, blastoma, meningioma, pineocytoma, pineoblastoma, and primary brain lymphoma; breast cancer, including but not limited to adenocarcinoma, lobular (small cell) carcinoma, intraductal carcinoma, medullary breast cancer, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget's disease (including juvenile Paget's disease) and inflammatory breast cancer; adrenal gland cancer, including but not limited to pheochromocytoma and adrenocortical carcinoma;thyroid cancer, including, but not limited to, papillary or follicular thyroid cancer, medullary thyroid cancer, and anaplastic thyroid cancer; pancreatic cancer, including, but not limited to, insulinoma, gastrinoma, glucagonoma, vipoma, somatostatin-secreting tumors, and carcinoid or islet cell tumors; pituitary cancer, including, but not limited to, Cushing's disease, prolactin-secreting tumors, acromegaly, and diabetes insipius; eye cancer, including, but not limited to, ocular melanoma, including, but not limited to, iris melanoma, choroidal melanoma, and cilliary body melanoma melanoma, and retinoblastoma; vaginal cancer, e.g., squamous cell carcinoma, adenocarcinoma, and melanoma; vulvar cancer, e.g., squamous cell carcinoma, melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, and Paget's disease; cervical cancer, e.g., but not limited to, squamous cell carcinoma, and adenocarcinoma; uterine cancer, e.g., but not limited to, endometrial carcinoma and uterine sarcoma; ovarian cancer, e.g., but not limited to, ovarian epithelial carcinoma, borderline tumor, germ cell tumor, and stromal tumor; cervical cancer; esophageal cancer, e.g., but not limited to, squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, carcinoma), mucoepidermoid carcinoma, adenosquamous carcinoma, sarcoma, melanoma, plasmacytoma, verrucous carcinoma, and oat cell (small cell) carcinoma; gastric cancer, including but not limited to, adenocarcinoma, fungiform (polypoid), ulcerative, superficial spreading, diffuse spreading, malignant lymphoma, liposarcoma, fibrosarcoma, and carcinosarcoma; colon cancer; colorectal cancer, KRAS mutant colorectal cancer; colon cancer; rectal cancer; liver cancer, including but not limited to, hepatocellular carcinoma and hepatoblastoma, gallbladder cancer, including adenocarcinoma; cholangiocarcinoma, including but not limited to, pappillary, nodular, and diffuse; lung cancer, including but not limited to, KRAS mutant non-small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large cell carcinoma, and small cell lung cancer; lung cancer;Testicular cancer, including, but not limited to, embryonal tumor, seminoma, undifferentiated, classical (typical), spermatocytic, nonseminoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma (yolk sac tumor); prostate cancer, including, but not limited to, androgen-independent prostate cancer, androgen-dependent prostate cancer, adenocarcinoma, leiomyosarcoma, and rhabdomyosarcoma; penile cancer, including, but not limited to, cancer); oral cancer, including but not limited to squamous cell carcinoma; basal carcinoma; salivary gland cancer, including but not limited to adenocarcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma; pharyngeal cancer, including but not limited to squamous cell carcinoma, and verrucous membrane; skin cancer, including but not limited to basal cell carcinoma, squamous cell carcinoma, and melanoma, superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, acral lentigo melanoma; kidney cancer, including but not limited to renal cell carcinoma, adenocarcinoma, adenocarcinoma, adrenal nephroma, fibrosarcoma, transitional cell carcinoma (renal pelvis and / or ureter); kidney cancer; Wilms' tumor; bladder cancer, including but not limited to transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, carcinosarcoma. In addition, cancers include myxosarcoma, osteogenic sarcoma, endothelial sarcoma, lymphangioendothelial sarcoma, mesothelioma, synovium, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, and papillary adenocarcinoma;

[0221] In some embodiments, the cancer is a tumor. In some embodiments, the tumor is a solid tumor. In certain embodiments, the tumor is a tumor selected from the group consisting of colorectal tumor, pancreatic tumor, lung tumor, ovarian tumor, liver tumor, breast tumor, kidney tumor, prostate tumor, neuroendocrine tumor, gastrointestinal tumor, melanoma, cervical tumor, bladder tumor, glioblastoma, and head and neck tumor. In certain embodiments, the tumor is a colorectal tumor. In certain embodiments, the tumor is an ovarian tumor. In some embodiments, the tumor is a breast tumor. In some embodiments, the tumor is a lung tumor. In certain embodiments, the tumor is a pancreatic tumor. In some embodiments, the tumor is a melanoma tumor. In some embodiments, the tumor is characterized as comprising or having a gene fusion. In some embodiments, the cancer is a cancerous tumor. In certain embodiments, the subject in need thereof has had the tumor at least partially removed.

[0222] In some embodiments, the patient or patient population treated with the pharmaceutical composition of the present disclosure has a solid tumor. In some embodiments, the solid tumor is melanoma, renal cell carcinoma, lung cancer, bladder cancer, breast cancer, cervical cancer, colon cancer, gallbladder cancer, pharyngeal cancer, liver cancer, thyroid cancer, stomach cancer, salivary gland cancer, prostate cancer, pancreatic cancer, or Merkel cell carcinoma. In some embodiments, the patient or patient population treated with the pharmaceutical composition of the present disclosure has a hematological cancer. In some embodiments, the patient has a hematological cancer, such as diffuse large B-cell lymphoma ("DLBCL"), Hodgkin's lymphoma ("HL"), non-Hodgkin's lymphoma ("NHL"), follicular lymphoma ("FL"), acute myeloid leukemia ("AML"), or multiple myeloma ("MM"). In some embodiments, the patient or patient population treated has a cancer selected from the group consisting of ovarian cancer, lung cancer, and melanoma.

[0223] In some embodiments, the patient or patient population treated with the pharmaceutical composition of the present disclosure has not been previously treated with a MEK inhibitor or MAPK inhibitor. In some embodiments, the pharmaceutical composition of the present disclosure is administered in combination with a MEK inhibitor or MAPK inhibitor. In some embodiments, the MEK inhibitor is selected from the group consisting of cobimetinib, selumetinib, pimasertib, PD0325901, refametinib, binimetinib, BI-847325, trametinib, GDC-0623, G-573, CH5126766, CIP-137401 and [ka] In some embodiments, the MEK inhibitor is selected from compounds having the structure: In some embodiments, the MEK inhibitor is selumetinib, binimetinib, or pimasertib. In some embodiments, the MEK inhibitor is pimasertib.

[0224] In some embodiments, the MEK inhibitor or a pharmaceutically acceptable salt thereof is selected from cobimetinib, selumetinib, pimasertib, PD0325901, refametinib, binimetinib, BI-847325, trametinib, GDC-0623, G-573, CH5126766, CI-1040, PD035901, and TAK-933. In some embodiments, the MEK inhibitor or a pharmaceutically acceptable salt thereof is selected from cobimetinib, selumetinib, pimasertib, PD0325901, refametinib, binimetinib, BI-847325, trametinib, GDC-0623, G-573, CH5126766, CI-1040, PD035901, TAK-933, and CIP-137401.

[0225] In some embodiments, the MEK inhibitor is a MEK inhibitor described in U.S. Patent No. 7,777,050, U.S. Patent No. 8,178,693, U.S. Patent No. 9,562,016, U.S. Patent No. 7,425,637, U.S. Patent No. 8,178,693, U.S. Patent No. 9,156,795, U.S. Patent No. 9,562,017, U.S. Patent No. 7,378,423, U.S. Patent No. 8,703,781, U.S. Patent No. 9,290,468, each of which is individually incorporated by reference herein in their entirety. EXAMPLES

[0226] The invention now being generally described, it will be more readily understood by reference to the following examples, which are included merely for the purpose of illustrating certain aspects and embodiments of the invention and are not intended to limit the invention in any way. Example 1 Patient Mixing Instructions (Figure 1; steps 1 to 12)

[0227] In step 1, open the bottle containing the powder formulation and remove the seal. Do not discard the child-resistant cap. Remove the oral syringe from the wrapper. In step 2, fill the cup with warm or room temperature water. Do not use cold water. In step 3, pull up on the plunger and draw water into the oral syringe up to the 14 mL mark. In step 4, remove the oral syringe from the cup. Gently push the plunger out of the tip to force any air bubbles out. Expel excess water so that the top of the plunger is at the 14 mL mark on the syringe. In step 5, inject 14 mL of water into the bottle. Replace the cap immediately and shake the bottle vigorously in all directions for 60 seconds. Continue shaking steps in 15 second increments until the powder is completely dispersed. Do not shake for a total of >2 minutes. Observe for complete dispersion of the powder in the liquid. In step 6, invert the bottle and rotate for 30 seconds. Remove the child-resistant cap and ensure that no solids are attached to the neck of the bottle. If solids are present in the neck of the bottle, recap the bottle, invert and swirl for an additional 15 seconds. The bottle is then allowed to sit for approximately 1 minute. In step 7, replace the cap with a bottle adapter. Attach it to the bottle by pushing it onto the neck of the bottle. In step 8, insert the tip of the oral syringe into the bottle adapter. The tip of the syringe should fit snugly into the hole in the bottle of the adapter. In step 9, with the syringe in place, swirl the suspension for 30 seconds, turn the bottle upside down and withdraw the prescribed volume plus 1 mL extra into the syringe. In step 10, remove the oral syringe from the bottle. Remove only air bubbles from the tip by gently pushing up on the plunger. In step 11, reinsert the syringe into the bottle and adjust to the prescribed volume. In step 12, gently remove the syringe from the bottle. Place the tip of the syringe into the child's mouth against the inside of the cheek. Slowly squirt the medicine into the mouth by depressing the plunger. Have the child swallow it. Example 2 Part 1 Taste / Preference Evaluation

[0228] The goal of this study was to assess the taste and palatability attributes (odor, sweetness, bitterness, flavor, mouthfeel / texture, and aftertaste) and overall acceptability of a hot melt extrusion (HME) powder for reconstitution (PfR) suspension formulation of Compound A.

[0229] Part 1 was a single-center, open-label, randomized, single-period, six-way crossover design to assess the taste and palatability attributes and overall palatability of several Compound A HME PfR suspension formulations with different flavors and sweetener levels in 12 volunteers using a sip-and-spit methodology. On the morning of Day 1, subjects were randomized into one of six rows (ABFCED, BCADFE, CDBEAF, DECFBA, EFDACB, and FAEBDC), with two subjects assigned to each row. Each subject received the following regimen in a randomized fashion: (Tables 1 and 2) Table 1. Description of regimens in part 1 [Table 1]

[0230] The Compound A drug product used in Part I was formulated as a powder for reconstitution (PfR) dosage form. This PfR formulation was used herein.

[0231] The drug product is packaged as 300 mg active strength (to be delivered) in a bottle with a child-resistant cap and induction seal liner. It is reconstituted to an active concentration of 25 mg / mL with water or aqueous diluent containing flavoring and / or sweeteners in Table 2b and administered using a syringe. In one example, the bottle is overfilled with 365 mg of Compound A to allow reproducible administration delivery of 300 mg of Compound A (i.e., 12 mL of 25 mg / mL Compound A concentration). The composition of the PfR dose of Compound A is provided below in Table 2a as the base formulation. Formulation A in Table 1 is the same as the base formulation in Table 2a, and formulations B-F in Table 1 contain the base formulation shown in Table 2a and the corresponding flavoring and / or sweeteners shown in Table 2b.

[0232] Flavors / sweeteners are mixed at the pharmacy with water as set forth in Table 2b below. Table 2a. Composition of Compound A reconstitution powder, 300 mg bottle [Table 2a] 1 Tested against USP Monograph for Simethicone and USP for Assay and Characterization. Table 2b. Description of flavors and sweetener levels for formulations [Table 2b] Example 3 Part 2 Relative Bioavailability and Food Effects

[0233] The goals of this study were: (1) to determine the relative bioavailability of the HME PfR suspension formulation of Compound A compared to that of the HME tablet formulation of Compound A in healthy subjects; (2) to assess the PK profiles of the HME tablet formulation of Compound A and the HME PfR suspension formulation of Compound A in healthy subjects; (3) to evaluate the effect of food on the PK profile of Compound A following a single dose of the HME tablet formulation of Compound A in fed healthy subjects; and (4) to provide information on the safety and tolerability of Compound A following oral administration.

[0234] Part 2 was a single-center, open-label, randomized, three-period crossover design to evaluate the relative bioavailability of selected HME PfR suspension formulations of Compound A compared to the HME tablet reference formulation in 12 volunteers. The effect of food on Compound A HME tablet exposure was also investigated. In Period 1, subjects were randomized to one of three regimen columns (GHI, HIG, and IGH) prior to the first dose of Compound A, with four subjects assigned to each regimen column. On Day 1 of each study period, subjects received the following regimens in Table 2: Table 2. Formulations used in Part 2 [Table 2]

[0235] Compound A drug product was formulated as a powder for reconstitution (PfR) dosage form for use in clinical studies. Drug product was packaged as 300 mg (active strength, to be delivered) in a glass bottle with a child-resistant cap and induction seal liner. It is reconstituted with water to an active concentration of 25 mg / mL and administered using a syringe. Bottles were overfilled with 430 mg of Compound A and reconstituted with 14 mL of water to allow reproducible administration delivery of 300 mg of Compound A (i.e., 12 mL of Compound A concentration of 25 mg / mL). The 100 mg dose utilized the same bottle and reconstitution procedure as the 300 mg dose. A 4 mL aliquot of 25 mg / mL was utilized to provide the 100 mg dose. The composition of the Compound A PfR dose is provided in Table 4 below. Table 4. Composition of Flavored Compound A Reconstitution Powder, 100 mg (H2 Regimen) and 300 mg Bottles (Regimen H1) [Table 4] 1 The 100 mg dose was supplied from a 300 mg bottle. After reconstitution to 25 mg / mL, a 4 mL aliquot for the 100 mg dose was administered instead of the 12 mL dose for the 300 mg dose.

[0236] Subjects underwent preliminary screening procedures at the screening visit (Day -28 to Day -2) to determine their eligibility for Part 2 of the study. Each period followed the same study design. Subjects were admitted to the hospital the morning before dosing (Day -1) for all regimens.

[0237] Subjects received a single dose of Compound A on the morning of Day 1 after a minimum of 10 hours of overnight fasting (Regimen G and H, fasting state) or 30 minutes after the start of a standard high-fat breakfast (Regimen I, fed state). Blood samples were collected at regular intervals for PK analysis from pre-dose to 120 hours post-dose. After administration of Regimen H (selected Compound A HME PfR suspension formulation in fasting state), subjects individually and confidentially completed a taste / preference questionnaire.

[0238] Subjects remained in the clinical unit until 96 hours post-dose (Day 5). Subjects returned to the clinic 120 hours post-dose (Day 6) for a final PK sample.

[0239] There was a minimum washout of 14 days between each dose of Compound A. Follow-up calls were conducted 7-10 days after the final dose to ensure the continued welfare of subjects.

[0240] Example 4 Taste / palatability and pharmacokinetic assessment

[0241] Taste / palatability results (Part 1 and Part 2 Regimen H only)

[0242] Taste was assessed for palatability attributes (odor, sweetness, bitterness, flavor, mouthfeel and aftertaste) and overall in a 9-grade system. The median (min-max) scores for each taste / palatability attribute for Regimen H in Part 1 and Part 2 are summarized in Table 5. Table 5. Median (min-max) scores of different taste / palatability attributes for evaluation of HME PfR suspension formulations of Compound A administered in different regimens: Taste / palatability analysis set (Part 1 and Part 2, Regimen H only) [Table 5]

[0243] The overall taste / liking ratings are presented in stacked bar graphs in FIG.

[0244] Taste / Preference Analysis (Part 1)

[0245] Median scores for the reference (regimen A) ranged from 3.0 to 5.0 for all taste attributes, including overall acceptability, indicating that subjects had a moderate dislike to neutral view of the product. Once sweetener was added, liking improved with median scores ranging from 4.0 to 6.0, indicating a near neutral view of the product. Flavoring combined with different sweetener levels increased to median scores of 5.0 to 7.0, indicating acceptability ranging from neutral to moderate liking.

[0246] Based on grouping (Grades 1-3: dislike, Grades 4-6: neutral, Grades 7-9: like), seven subjects indicated dislike for the reference product based on overall acceptability. This was reduced to two subjects for the sweetened product, and one subject or less for each flavored regimen. The regimen with the highest percentage of subjects scoring "like" was regimen C, with seven subjects choosing this rating.

[0247] The addition of sweetener alone to the HME PfR suspension formulation of Compound A provided a moderate improvement over the reference product, but was not significant in all cases. Each of the flavored Compound A formulations provided a more robust improvement over the reference product for each taste attribute, except bitterness. There did not appear to be a clear preference between the flavoring regimens, although Regimen F (vanilla, low sucralose) tended to show the least improvement.

[0248] With the exception of bitterness, Friedman's test was statistically significant at the 5% significance level for each taste aspect, including overall acceptability, indicating that at least one of the flavor / sweetener levels had a significantly different taste score versus the other regimens (p≦0.001, 0.013, <0.001, <0.001, 0.022, and 0.033 for overall acceptability, odor, sweetness, flavor, mouthfeel / texture, and aftertaste). For bitterness, the p-value was greater than 0.05 (p=0.650), suggesting that there was no significant difference between at least two of the regimens for bitterness scores.

[0249] For all pairwise comparisons, the median of the paired differences was positive, indicating that each flavor / sweetener combination showed improved acceptability for each taste aspect analyzed and overall acceptability when compared to the reference with no sweetener or flavor.

[0250] Statistical analysis of the taste / preference ratings using the Wilcoxon signed rank test for taste / preference is presented in Table 6. Table 6. Taste / preference rating results from Wilcoxon signed rank test: Taste / preference analysis set (part 1) [Table 6] (1) Median pairwise difference for each subject (test regimen - regimen A) (2) P-value from the Wilcoxon signed-rank test under the null hypothesis that the difference in medians is equal to 0 Subjects tasted 5 mL of Compound A HME PfR oral suspension, six different formulations (Regimens A-F = Formulations 1-6). Regimen A = 25 mg / mL Compound A (no sweetener / flavor), Regimen B-F = different flavors, sweetener levels (mg / mL)

[0251] In general, the least improvement from regimen A (no flavor or sucralose) was observed for regimen B (0.15% sucralose) across taste aspects, except for aftertaste, where the improvement was equal to the regimen with flavor.Regimens C (strawberry flavor and 0.15% sucralose), regimen D (strawberry flavor and 0.3% sucralose), and regimen E (vanilla flavor and 0.3% sucralose) all provided similar improvements across taste aspects and overall acceptability when compared to the reference regimen A, with generally greater improvements than regimen F (vanilla flavor and 0.15% sucralose).Regimen F provided the least improvement in aftertaste across regimens compared to regimen A, and the least improvement in sweetness in common with regimen B without flavor.

[0252] Taste / Preference Analysis (Part 2)

[0253] The overall taste profile scores for Regimen H were comparable to those for Regimen C in Part 1, which used the same flavor and sweetener (strawberry / 0.15%).

[0254] Statistical issues regarding taste / preference

[0255] For Friedman's test, subjects can only be included in the comparison of all regimens if they had a numerical score for each regimen. Some subjects scored the taste aspect as "NA" (not applicable) for at least one regimen, so they were not included, and therefore the number of subjects included was reduced for taste aspects (number of subjects included in analysis): smell (4), bitterness (4), sweetness (9), flavor (11) and aftertaste (9). Some caution must be exercised when interpreting results for regimens with significant missing data.

[0256] Taste / Preference Conclusions

[0257] For overall acceptability and all taste aspects, taste scores improved significantly for Compound A HME PfR suspension formulations containing the addition of the sweetener sucralose alone or additional flavor (strawberry or vanilla), with greater improvements seen with the addition of both sweetener and flavor.

[0258] Pharmacokinetic Results and Analysis (Part 2)

[0259] In Figures 3(A)-3(D) and the table, T after administration of Compound A as a reference HME tablet in the fasted state at dose levels of 300 mg and 100 mg. max was reached at 3.00 hours post-dose for all subjects in regimen G1 and between 2.00 and 5.00 hours post-dose for subjects in regimen G2, resulting in a T of 3.5 hours. max The median value was the geometric mean T 1 / 2 were 67.4 hours and 73.5 hours for the 300 mg and 100 mg dose levels, respectively. When Compound A was administered in a PfR suspension (regimen H1 and H2) formulation at the 300 mg and 100 mg dose levels, T max The median occurred at 3.000 hours for both regimens. Geometric mean T 1 / 2 The estimates were longer at 83.177 hours and 65.363 hours for the 300 mg and 100 mg dose levels, respectively.

[0260] In Figures 4(A)-4(D) and Table 7, following administration of Compound A as HME tablets in the fed state at dose levels of 300 mg (Regimen H1) and 100 mg (Regimen H2), T max The median values ​​were 6.5 hours and 5.0 for regimens I1 and I2, respectively. Geometric mean T 1 / 2 The estimates were longer, at 85.4 and 61.7 hours, for regimens I1 and I2, respectively. maxIntersubject variability for AUC(0-last) was low to moderate, with CVs of 26.5% and 11.7%, respectively, for the 300 mg tablet administered in the fed state (regimen I1) and 23.4% and 20.7%, respectively, for the 100 mg tablet administered in the fed state (regimen I2). Table 7. Geometric mean (geometric CV%) plasma pharmacokinetic parameters for Compound A following single oral doses of 100 mg and 300 mg of Compound A administered as tablet and suspension formulations to healthy male and female volunteers. [Table 7]

[0261] Long T compared to the sampling schedule 1 / 2 As a result, the area over which AUC(0-inf) was extrapolated was large (>20%) and therefore AUC(0 inf) was not reliably calculated for any subject.

[0262] The mean plasma concentration versus time profiles of Compound A are shown in Figures 6 to 9, respectively, in log 10 / On a linear scale, regimens (regimens H1 and G2, regimens H2 and G2, regimens I1 and G1, and regimens I2 and G2) are shown. Regimen G1 (300 mg HME tablet, fasting) and Regimen G2 (100 mg HME tablet, fasting)

[0263] Following single oral administration of Compound A to healthy male and female subjects as a reference HME tablet in the fasted state at 300 mg (regimen G1) and 100 mg (regimen G2) dose levels, quantifiable plasma concentrations of Compound A were observed from the first time point (0.5 hours post-dose) for Regimen G1 and at pre-dose (due to carryover from previous periods) for all subjects in Regimen G2. Subject 2005 had a pre-dose value (36.4 ng / mL) that was higher than its corresponding C maxThe peak plasma concentration of Compound A (C max ) was reached at 3.00 hours post-dose for all subjects in regimen G1 and between 2.00 and 5.00 hours post-dose for all subjects in regimen G2, with a T of 3.50 hours. max It was the median value.

[0264] C max After administration, plasma concentrations declined in a multiphasic manner in all subjects in both regimens G1 and G2 and remained quantifiable until the last sample collection time (120 hours post-dose). At the 300 mg dose level (regimen G1), T 1 / 2 was reliably calculated for all four subjects and ranged between 56.7 and 82.6 hours, with a geometric mean of 67.4 hours. At the 100 mg dose level (regimen G2), T 1 / 2 was reliably calculated for all six subjects included in the summary statistics, ranging between 58.3 and 113 hours, with a geometric mean of 73.5 hours.

[0265] At the 300 mg dose level (regimen G1), C max The AUC(0-last) ranged from 2040 ng / mL to 3240 ng / mL with a geometric mean (geometric CV%) of 2620 ng / mL (24.3%). The AUC(0-last) ranged from 103 000 ng·h / mL to 183 000 ng·h / mL with a geometric mean (geometric CV%) of 133 000 ng·h / mL (29.4%). At the 100 mg dose level (regimen G2), C max AUC(0-last) ranged from 1010 ng / mL to 1670 ng / mL with a geometric mean of 1180 ng / mL (21.6%) (geometric mean CV%). AUC(0-last) ranged from 44 000 ng·h / mL to 66 900 ng·h / mL with a geometric mean of 53 500 ng·h / mL (15.0%) (geometric mean CV%). In all subjects on both regimens, AUC(0-inf) could not be reliably calculated due to extrapolated portions of the curves representing >20% of the total area. Regimen H1 (300 mg of HME PfR suspension, fasted) and Regimen H2 (100 mg of HME PfR suspension, fasted)

[0266] Following single oral administration of Compound A as a suspension in HME PfR in the fasted state to healthy male and female subjects at 300 mg (Regimen H1) and 100 mg (Regimen H2) dose levels, quantifiable plasma concentrations of Compound A were observed from the earliest time point (0.5 hours post-dose) for Regimen H1, pre-dose for 7 of 8 subjects for Regimen H2 (due to carryover from previous periods), and from the earliest time point 0.5 hours post-dose for the remaining subjects. Subject 2010 had a pre-dose value (86.6 ng / mL) of 1.0 mg / mL, which was the same as the corresponding C max Regimen H2 was excluded from summary statistics and statistical analyses because it was >5% of the T value (1200 ng / mL). Peak plasma concentrations of Compound A were reached between 1.50 and 4.00 hours post-dose for all subjects in regimens H1 and H2, with a T of 3.00 hours for both regimens. max It was the median value.

[0267] C max Thereafter, plasma concentrations declined in a multiphasic manner in all subjects in both regimens and remained quantifiable until the last sample collection time (120 hours post-dose). At the 300 mg dose level (regimen H1), T 1 / 2 was reliably calculated for all four subjects, ranging between 71.9 and 114 hours, with a geometric mean of 83.2 hours. At the 100 mg dose level (regimen H2), T 1 / 2 was reliably calculated for six subjects, with a geometric mean of 65.4 hours, ranging between 57.3 and 77.5 hours. If the terminal slopes could not be determined reliably, this would result in an unacceptable coefficient of determination (i.e., R 2 <0.9).

[0268] At the 300 mg dose level (regimen H1), C maxThe AUC(0-last) ranged from 2300 ng / mL to 2940 ng / mL with a geometric mean (geometric CV%) of 2470 ng / mL (11.7%). The AUC(0-last) ranged from 127 000 ng·h / mL to 189 000 ng·h / mL with a geometric mean (geometric CV%) of 151 000 ng·h / mL (17.9%). At the 100 mg dose level (regimen H2), C max AUC(0-inf) ranged from 884 ng / mL to 1580 ng / mL with a geometric mean (geometric mean CV%) of 1110 ng / mL (22.0%). AUC(0-last) ranged from 42500 ng·hr / mL to 72500 ng·hr / mL with a geometric mean (geometric CV%) of 52400 ng·hr / mL (22.3%). In cases where AUC(0-inf) could not be reliably calculated, this was due to an extrapolated portion of the curve representing >20% of the total area and the result of an unacceptable coefficient of determination (i.e., R 2 <0.9). Regimen I1 (300 mg HME tablet, fed) and Regimen I2 (100 mg HME tablet, fed)

[0269] Following single oral administration of Compound A to healthy male and female subjects as HME tablets in the fed state at 300 mg (regimen I1) and 100 mg (regimen I2) dose levels, quantifiable plasma concentrations of Compound A were observed from the first time point (0.5 hours post-dose) for regimen I1, pre-dose for 7 of 8 subjects for regimen I2 (due to carryover from previous periods), and from 0.5 hours in the remaining subjects. Peak plasma concentrations of Compound A were reached between 4.00 and 24.00 hours post-dose for both regimens, with T of 6.50 and 5.00 hours for regimens I1 and I2, respectively. max It was the median value.

[0270] C max Thereafter, plasma concentrations declined in a multiphasic manner in all subjects in both regimens and remained quantifiable until the last sample collection time (120 hours post-dose). At the 300 mg dose level (regimen I1), T 1 / 2was reliably calculated for 3 of 4 subjects, ranging between 58.9 and 125 hours, with a geometric mean of 85.4 hours. At the 100 mg dose level (regimen I2), T1 / 2 was reliably calculated for 7 of 8 subjects, ranging between 51.3 and 77.2 hours, with a geometric mean of 61.7 hours. When the terminal slopes could not be determined reliably, this resulted in an unacceptable coefficient of determination (i.e., R 2 <0.9).

[0271] At the 300 mg dose level (regimen I1), C max The AUC(0-last) ranged from 1650 ng / mL to 2870 ng / mL with a geometric mean (geo...

Claims

1. a) a solid formulation of an amorphous solid dispersion of (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof, comprising one or more pharma- ceutically acceptable excipients; and b) Instructions for aqueous reconstitution of said solid formulation. Kit including:

2. 10. The kit of claim 1, wherein the solid formulation is in the form of a powder, granules, or pellets.

3. The kit of claim 1 , wherein the solid formulation is in the form of a powder.

4. The kit of any one of claims 1 to 3, wherein the amorphous solid dispersion comprises one or more polymers.

5. The one or more polymers may be selected from the group consisting of polyvinylpyrrolidone, polyvinylpyrrolidone-polyvinyl acetate copolymer (PVP-VA), cross-linked polyvinyl N-pyrrolidone, polyvinyl alcohol (PVA), polysaccharides, hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutyl ether-β-cyclodextrin (Ca 5. The kit of claim 4, comprising a polysaccharide, poly(methacrylic acid-co-methyl methacrylate) (Eudragit), a poloxamer, a silica gel, an aluminosilicate, or a combination thereof.

6. The kit of claim 5 , wherein the one or more polymers comprise PVP-VA or HPMCAS.

7. 7. The kit of any one of claims 4 to 6, wherein the amorphous solid dispersion comprises from about 10 wt% to about 90 wt% of the one or more polymers.

8. 8. The kit of claim 7, wherein the amorphous solid dispersion comprises from about 40 wt% to about 80 wt% of the one or more polymers.

9. 9. The kit of claim 8, wherein the amorphous solid dispersion comprises about 55 wt% to about 65 wt% of the one or more polymers.

10. 10. The kit of any one of claims 1 to 9, wherein the amorphous solid dispersion comprises about 10 wt% to about 90 wt% of Compound A or a pharma- ceutically acceptable salt thereof.

11. 11. The kit of claim 10, wherein the amorphous solid dispersion comprises about 20 wt% to about 60 wt% of Compound A or a pharma- ceutically acceptable salt thereof.

12. 12. The kit of claim 11, wherein the amorphous solid dispersion comprises about 35 wt% to about 45 wt% of Compound A or a pharma- ceutically acceptable salt thereof.

13. The kit according to any one of claims 4 to 12, wherein the weight ratio of compound A or a pharma- ceutically acceptable salt thereof to the one or more polymers is from 2:1 to 1:

2.

14. 14. The kit of claim 13, wherein the weight ratio of Compound A or a pharma- ceutically acceptable salt thereof to the one or more polymers is about 1:1 to 1:

2.

15. The kit of any one of claims 1 to 14, wherein the amorphous solid dispersion comprises Compound A.

16. The kit of any one of claims 1 to 15, wherein the amorphous solid dispersion is a hot melt extrudate (HME).

17. 16. The kit of any one of claims 1 to 15, wherein the amorphous solid dispersion is prepared by dissolving Compound A or a pharma- ceutically acceptable salt thereof in a solvent and then removing at least a portion of the solvent.

18. 18. The kit of any one of claims 1 to 17, wherein the particles in the amorphous solid dispersion have a D50 value of from about 10 μm to about 500 μm.

19. 20. The kit of claim 18, wherein the particles in the amorphous solid dispersion have a D50 value of about 100 μm to about 400 μm.

20. 20. The kit of any one of claims 1 to 19, wherein the solid formulation comprises from about 10 wt% to about 80 wt% of the amorphous solid dispersion.

21. 21. The kit of claim 20, wherein the solid formulation comprises about 40 wt% to about 60 wt% of the amorphous solid dispersion.

22. 21. The kit of claim 20, wherein the solid formulation comprises about 15 wt% to about 35 wt% of the amorphous solid dispersion.

23. 23. The kit of any one of claims 1 to 22, wherein the one or more pharma- ceutically acceptable excipients are in admixture with the amorphous solid dispersion in the solid formulation.

24. The kit of any one of claims 1 to 22, wherein the amorphous solid dispersion comprises one or more pharma- ceutically acceptable excipients.

25. 25. The kit of any one of claims 1 to 24, wherein the solid formulation comprises from about 5 wt% to about 80 wt% of the one or more pharma- ceutically acceptable excipients.

26. 26. The kit of claim 25, wherein the solid formulation comprises from about 40 wt% to about 60 wt% of the one or more pharma- ceutically acceptable excipients.

27. 27. The kit of any one of claims 1 to 26, wherein the one or more pharma- ceutically acceptable excipients are selected from antifoaming agents, flow aids, surfactants, bulking agents, colorants, preservatives, flavoring agents, sweetening agents, and combinations thereof.

28. 28. The kit of claim 27, wherein the one or more pharma- ceutically acceptable excipients are selected from antifoam agents, flow aids, surfactants, bulking agents, and combinations thereof.

29. 29. The kit of claim 28, wherein the anti-foaming agent comprises simethicone.

30. 30. The kit of any one of claims 27 to 29, wherein the solid formulation comprises from about 0.1 wt% to about 15 wt% of the antifoaming agent.

31. 31. The kit of claim 30, wherein the solid formulation comprises from about 1 wt % to about 8 wt % of the antifoaming agent.

32. 32. The kit of claim 31, wherein the solid formulation comprises from about 3 wt% to about 8 wt% of the antifoaming agent.

33. The kit of claim 30, wherein the solid formulation comprises from about 0.5 wt% to about 3 wt% simethicone.

34. 34. The kit of any one of claims 27 to 33, wherein the flow aid is selected from silicon dioxide, magnesium stearate, talc, starch, magnesium silicate, hydrated sodium sulfoaluminate, and combinations thereof.

35. 35. The kit of claim 34, wherein the silicon dioxide comprises fumed silica, colloidal silicon dioxide (CSD), or both.

36. 36. The kit of any one of claims 27 to 35, wherein the solid formulation comprises from about 0.25 wt% to about 10 wt% of the flow aid.

37. 37. The kit of claim 36, wherein the solid formulation comprises from about 1 wt% to about 5 wt% of the flow aid.

38. The kit of any one of claims 27 to 37, wherein the surfactant comprises a cationic surfactant, an anionic surfactant, a non-ionic surfactant, or a combination thereof.

39. 39. The kit of claim 38, wherein the surfactant comprises sodium lauryl sulfate (SLS).

40. 40. The kit of claim 38, wherein the surfactant comprises a poloxamer.

41. 41. The kit of any one of claims 27 to 40, wherein the solid formulation comprises from about 0.01 wt% to about 10 wt% of the surfactant.

42. 42. The kit of claim 41, wherein the solid formulation comprises from about 0.1 wt % to about 2 wt % of the surfactant.

43. The kit of any one of claims 27 to 42, wherein the bulking agent comprises a polysaccharide, a sugar or derivative thereof, or both.

44. 44. The kit of claim 43, wherein the bulking agent comprises cellulose, starch, synthetic soluble fiber, sugar alcohol, or a combination thereof.

45. The kit of any one of claims 27 to 44, wherein the bulking agent comprises mannitol.

46. 46. ​​The kit of any one of claims 27 to 45, wherein the bulking agent comprises microcrystalline cellulose, polydextrose, sodium carboxymethylcellulose (sodium CMC), or a combination thereof.

47. 47. The kit of any one of claims 27 to 46, wherein the solid formulation comprises from about 5 wt% to about 80 wt% of the bulking agent.

48. 48. The kit of claim 47, wherein the solid formulation comprises from about 30 wt% to about 75 wt% of the bulking agent.

49. A kit according to any one of claims 1 to 48, wherein the instructions for aqueous reconstitution are in the form of a reference material which refers to said instructions.

50. The solid formulation comprises: a) an amorphous solid dispersion comprising about 10 wt% to about 60 wt% Compound A and about 40 wt% to about 60 wt% PVP-VA, the amorphous solid dispersion being a hot melt extrudate and present in said solid dosage form at about 10 wt% to about 30 wt%; b) about 30 wt % to 70 wt % of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; c) about 0.1 wt % to 5 wt % of a surfactant, the surfactant being SLS; d) about 0.25 wt % to 6 wt % of a flow aid, the flow aid being a CSD; e) about 0.5 wt % to 5 wt % of an anti-foaming agent, which is simethicone; The kit of claim 1 , comprising:

51. The kit of any one of claims 1 to 50, wherein the solid formulation further comprises a carrier for the antifoam agent.

52. 52. The kit of claim 51, wherein the carrier of the antifoaming agent is present at about 4-6 wt%, 3-7 wt%, or 1-10 wt% of the solid formulation.

53. 53. The kit of any one of claims 1 to 52, comprising one or more doses of Compound A or a pharma- ceutically acceptable salt thereof.

54. 54. The kit of claim 53, comprising 1 to 5 unit doses of Compound A or a pharma- ceutically acceptable salt thereof.

55. 55. The kit of claim 54, comprising a single unit dose of Compound A or a pharma- ceutically acceptable salt thereof.

56. 56. The kit of any one of claims 53 to 55, wherein the dose is a pediatric dose.

57. 57. The kit of any one of claims 53 to 56, wherein each dose comprises from about 50 mg to about 800 mg of Compound A or a pharma- ceutically acceptable salt thereof.

58. 58. The kit of claim 57, wherein each dose contains about 300 mg or about 600 mg of Compound A.

59. 59. The kit of any one of claims 1 to 58, further comprising one or more containers optionally including markings indicating volume measurements.

60. a) an amorphous solid dispersion comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof; and b) one or more pharma- ceutically acceptable excipients, including flow aids and surfactants; 23. A pharmaceutical powder comprising:

61. 61. The pharmaceutical powder of claim 60, adapted to be reconstituted into an oral liquid suspension.

62. 62. The pharmaceutical powder of claim 60 or 61, wherein the amorphous solid dispersion comprises one or more polymers.

63. 63. The pharmaceutical powder of claim 62, wherein the one or more polymers comprise polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymer (PVP-VA), cross-linked polyvinyl N-pyrrolidone, polyvinyl alcohol (PVA), polysaccharides, hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutylether-β-cyclodextrin (Captisol), γ-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyethylene glycol (PEG), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG), polysaccharides, poly(methacrylic acid-co-methyl methacrylate) (Eudragit), poloxamer, silica gel, aluminosilicate, or combinations thereof.

64. 63. The pharmaceutical composition of claim 62, wherein the one or more polymers comprises PVP-VA or HPMCAS.

65. 65. The pharmaceutical powder of any one of claims 62-64, wherein said amorphous solid dispersion comprises from about 10 wt% to about 90 wt% of said one or more polymers.

66. 66. The pharmaceutical powder of any one of claims 60-65, wherein said amorphous solid dispersion comprises from about 10 wt% to about 90 wt% of Compound A or a pharma- ceutically acceptable salt thereof.

67. 67. The pharmaceutical powder of any one of claims 62 to 66, wherein the weight ratio of Compound A or a pharma- ceutically acceptable salt thereof to the one or more polymers is from 2:1 to 1:

2.

68. 68. The pharmaceutical powder of any one of claims 60 to 67, wherein the amorphous solid dispersion comprises Compound A.

69. 69. The pharmaceutical powder of any one of claims 60 to 68, wherein the amorphous solid dispersion is a hot melt extrudate (HME).

70. 69. The pharmaceutical powder of any one of claims 60-68, wherein the amorphous solid dispersion is prepared by dissolving Compound A or a pharma- ceutically acceptable salt thereof in a solvent and then removing at least a portion of the solvent.

71. 71. The pharmaceutical powder of any one of claims 60 to 70, wherein Compound A, or a pharma- ceutically acceptable salt thereof, is amorphous.

72. 72. The pharmaceutical powder of any one of claims 60-71, wherein the amorphous solid dispersion has a D50 value of from about 10 μm to about 500 μm.

73. 73. The pharmaceutical powder of any one of claims 60-72, comprising from about 10 wt% to about 80 wt% of said amorphous solid dispersion.

74. 74. The pharmaceutical powder of claim 73, comprising about 20 wt% to about 60 wt% of said amorphous solid dispersion.

75. 75. The pharmaceutical powder of any one of claims 60 to 74, wherein said one or more pharma- ceutically acceptable excipients are in admixture with said amorphous solid dispersion in said pharmaceutical powder.

76. 76. The pharmaceutical powder of any one of claims 60-75, comprising from about 5 wt% to about 80 wt% of said one or more pharma-ceutically acceptable excipients.

77. 77. The pharmaceutical powder of any one of claims 60-76, wherein the one or more pharma- ceutically acceptable excipients comprise an antifoaming agent, a bulking agent, a colorant, a preservative, a flavoring agent, a sweetener, or a combination thereof.

78. 78. The pharmaceutical powder of claim 77, wherein the antifoaming agent comprises simethicone.

79. 79. The pharmaceutical powder of claims 77 and 78, wherein the antifoaming agent is present in the pharmaceutical powder at about 0.1 wt % to about 10 wt %.

80. 80. The pharmaceutical powder of any one of claims 77 to 79, wherein the bulking agent comprises a polysaccharide, a sugar or derivative thereof, or both.

81. 81. The pharmaceutical powder of claim 80, wherein the bulking agent comprises cellulose, starch, synthetic soluble fiber, sugar alcohol, or combinations thereof.

82. 82. The pharmaceutical powder of any one of claims 77 to 81, wherein the bulking agent comprises mannitol.

83. 83. The pharmaceutical powder of any one of claims 77-82, wherein the bulking agent comprises microcrystalline cellulose, polydextrose, sodium carboxymethylcellulose (sodium CMC), or a combination thereof.

84. 84. The pharmaceutical powder of any one of claims 77 to 83, comprising from about 5 wt% to about 80 wt% of said bulking agent.

85. 85. The pharmaceutical powder of any one of claims 60 to 84, wherein the flow aid is selected from silicon dioxide, magnesium stearate, talc, starch, magnesium silicate, hydrated sodium sulfoaluminate, and combinations thereof.

86. 86. The pharmaceutical powder of claim 85, wherein the silicon dioxide comprises fumed silica, colloidal silicon dioxide (CSD), or both.

87. 87. The pharmaceutical powder of any one of claims 60 to 86, comprising from about 0.25 wt% to about 10 wt% of said flow aid.

88. 88. The pharmaceutical powder of any one of claims 60-87, wherein the surfactant comprises a cationic surfactant, an anionic surfactant, a non-ionic surfactant, or a combination thereof.

89. 89. The pharmaceutical powder of claim 88, wherein the surfactant comprises sodium lauryl sulfate (SLS).

90. 89. The pharmaceutical powder of claim 88, wherein the surfactant comprises a poloxamer.

91. 91. The pharmaceutical powder of any one of claims 60 to 90 comprising from about 0.01 wt% to about 10 wt% of said surfactant.

92. a) about 10 wt % to about 60 wt % amorphous solid dispersion comprising (i) about 40 wt % to about 60 wt % Compound A and (ii) about 40 wt % to about 60 wt % PVP-VA, wherein the amorphous solid dispersion is a hot melt extrudate; b) about 30 wt % to about 70 wt % of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; c) about 0.1 wt % to 5 wt % of a surfactant, the surfactant being SLS; d) about 0.25 wt % to 6 wt % of a flow aid, the flow aid being a CSD; and e) about 0.5 wt % to 5 wt % of an anti-foaming agent, which is simethicone or dimethicone; 61. The pharmaceutical powder of claim 60 comprising:

93. a) the solid formulation in a kit according to any one of claims 1 to 59, and b) aqueous solution 20. An oral liquid suspension comprising:

94. 60. An oral liquid suspension produced by contacting the solid formulation of the kit of any one of claims 1 to 59 with an aqueous solution.

95. a) a pharmaceutical powder according to any one of claims 60 to 92, and b) aqueous solution 20. An oral liquid suspension comprising:

96. 93. An oral liquid suspension produced by contacting the pharmaceutical powder of any one of claims 60 to 92 with an aqueous solution.

97. a) (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof; b) one or more pharma- ceutically acceptable excipients; and c) water 20. An oral liquid suspension comprising:

98. 98. The oral liquid suspension of claim 97, wherein Compound A, or a pharma- ceutically acceptable salt thereof, is in the form of an amorphous solid dispersion.

99. 99. The oral liquid suspension of claim 98, wherein the amorphous solid dispersion comprises one or more polymers.

100. 100. The oral liquid suspension of claim 99, wherein the one or more polymers comprise polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymer (PVP-VA), cross-linked polyvinyl N-pyrrolidone, polyvinyl alcohol (PVA), polysaccharides, hydroxypropyl methylcellulose (HPMC or hypromellose), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutylether-β-cyclodextrin (Captisol), γ-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyethylene glycol (PEG), polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG), polysaccharides, poly(methacrylic acid-co-methyl methacrylate) (Eudragit), poloxamer, silica gel, aluminosilicate, or combinations thereof.

101. 101. The oral liquid suspension of any one of claims 97-100, wherein the one or more pharma- ceutically acceptable excipients are selected from antifoaming agents, flow aids, surfactants, bulking agents, colorants, preservatives, flavoring agents, sweetening agents, and combinations thereof.

102. 102. The oral liquid suspension of any one of claims 93 to 101 which has been reconstituted.

103. 103. The oral liquid suspension of any one of claims 93-102, wherein the concentration of Compound A or a pharma- ceutically acceptable salt thereof is from about 10 mg / mL to about 125 mg / mL in the oral liquid suspension.

104. 103. The oral liquid suspension of any one of claims 93-102, wherein the concentration of Compound A or a pharma- ceutically acceptable salt thereof is from about 10 to about 50 mg / mL in the oral liquid suspension.

105. 97. An oral liquid suspension according to any one of claims 93 to 96, wherein the aqueous solution is water.

106. 106. Oral liquid suspension according to any one of claims 93 to 105, wherein the pH value of the liquid suspension is from about 2 to 7.

107. 107. An oral liquid suspension according to any one of claims 93 to 106, wherein the suspension retains injectability for at least 15 minutes.

108. 108. The oral liquid suspension of claim 107, wherein the suspension retains injectability for at least 30 minutes.

109. 109. The oral liquid suspension of any one of claims 93-108, wherein the concentration of the one or more polymers in the suspension is from about 10 mg / mL to about 200 mg / mL.

110. 110. The oral liquid suspension of claim 109, wherein the concentration of the one or more polymers in the suspension is from about 30 mg / mL to about 50 mg / mL.

111. 110. The oral liquid suspension of claim 109, wherein the concentration of the one or more polymers in the suspension is from about 60 mg / mL to about 80 mg / mL.

112. 112. The oral liquid suspension of any one of claims 93 to 111, wherein the concentration of the bulking agent in the suspension is from about 30 mg / mL to about 500 mg / mL.

113. 113. The oral liquid suspension of claim 112, wherein the concentration of the bulking agent in the suspension is from about 50 mg / mL to about 300 mg / mL.

114. 114. The oral liquid suspension of claim 113, wherein the concentration of the bulking agent in the suspension is from about 125 mg / mL to about 200 mg / mL.

115. 115. The oral liquid suspension of any one of claims 93 to 114, wherein the concentration of the surfactant in the suspension is from about 0.5 mg / mL to about 10 mg / mL.

116. 116. The oral liquid suspension of claim 115, wherein the concentration of the surfactant in the suspension is from about 1 mg / mL to about 2.5 mg / mL.

117. 117. An oral liquid suspension according to any one of claims 93 to 116, wherein the concentration of the flow aid in the suspension is from about 3 mg / mL to about 30 mg / mL.

118. 118. The oral liquid suspension of claim 117, wherein the concentration of the flow aid in the suspension is from about 5 mg / mL to about 15 mg / mL.

119. 119. The oral liquid suspension of claim 118, wherein the concentration of the flow aid in the suspension is from about 10 mg / mL to about 15 mg / mL.

120. 120. The oral liquid suspension of any one of claims 93-119, wherein the concentration of the antifoaming agent in the suspension is from about 1 mg / mL to about 30 mg / mL.

121. 121. The oral liquid suspension of claim 120, wherein the concentration of the antifoaming agent in the suspension is from about 1 mg / mL to about 10 mg / mL.

122. 122. The oral liquid suspension of claim 121, wherein the concentration of the antifoaming agent in the suspension is from about 3 mg / mL to about 8 mg / mL.

123. The suspension comprises, based on the weight of the individual, a) about 10 wt % to about 50 wt % amorphous solid dispersion comprising (i) about 40 wt % to about 60 wt % Compound A and (ii) about 40 wt % to about 60 wt % PVP-VA, wherein the amorphous solid dispersion is a hot melt extrudate; b) about 40 wt % to about 70 wt % of a bulking agent, the bulking agent comprising microcrystalline cellulose and mannitol; c) about 0.25 wt % to about 1 wt % of a surfactant, the surfactant being SLS; d) about 1 wt % to about 6 wt % of a flow aid, the flow aid being colloidal silicon dioxide (CSD); e) about 1 wt % to about 5 wt % of an anti-foaming agent, the anti-foaming agent comprising simethicone; and f) optionally, preservatives, flavoring agents, sweeteners, or combinations thereof; 109. An oral liquid suspension according to any one of claims 93 to 108 comprising:

124. The suspension comprises, based on the weight of the solids, a) about 20-30 wt % (e.g., 25 wt %, or 24%-25%) amorphous solid dispersion comprising (i) about 40 wt % Compound A and (ii) about 60 wt % copovidone, optionally a hot melt extrudate; b) about 30 wt % to 32 wt % mannitol; c) about 30 wt % to 32 wt % microcrystalline cellulose; d) about 0.5 wt% to 1 wt% SLS; e) about 4 wt% to 5 wt% CSD; f) about 1 wt% to 3 wt% simethicone; g) about 3% to about 8% wt % maltodextrin; h) optionally, preservatives, flavoring agents, sweeteners, or combinations thereof.

109. An oral liquid suspension according to any one of claims 93 to 108 comprising:

125. The suspension comprises, based on the weight of the solids, a) about 10 wt % amorphous solid dispersion comprising (i) about 40 wt % Compound A and (ii) about 60 wt % copovidone, wherein the amorphous solid dispersion is a hot melt extrudate; b) about 30 wt % to 32 wt % mannitol; c) about 30 wt % to 32 wt % microcrystalline cellulose; d) about 0.5 wt% to 1 wt% SLS; e) about 4 wt% to 5 wt% CSD; f) about 1 wt % to 3 wt % simethicone; and g) optionally, preservatives, flavoring agents, sweeteners, or combinations thereof; 109. An oral liquid suspension according to any one of claims 93 to 108 comprising:

126. 126. The oral liquid suspension of any one of claims 93 or 125, wherein the oral liquid suspension is bioequivalent to a tablet formulation of Compound A, and the tablet composition comprises an amorphous solid dispersion comprising (i) about 40 wt.% Compound A and (ii) about 60 wt.% copovidone, which is a hot melt extrudate; and one or more pharma- ceutically acceptable excipients.

127. 126. The oral liquid suspension of any one of claims 93 or 125, which, when administered to a human subject in an amount equivalent to about 100 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least about 100 ng / mL.

128. 128. The oral liquid suspension of claim 127, which, when administered to a human subject in an amount equivalent to about 100 mg of Compound A, is sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in the subject of at least about 100 ng / mL.

129. A kit comprising a pharmaceutical powder for reconstitution according to any one of claims 60 to 92.

130. 1. A method of treating cancer in a subject, comprising: administering to the subject an oral liquid suspension comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A), or a pharma- ceutically acceptable salt thereof, in an amount sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A of at least 2000 ng / mL in the subject. A method comprising:

131. 129. A method of treating cancer in a subject comprising administering to the subject a pharmaceutical powder of any one of claims 60-92 or a reconstituted oral liquid formulation of any one of claims 93-128.

132. 60. A method of treating cancer in a subject, comprising reconstituting the solid formulation in the kit of any one of claims 1-59 and administering the reconstituted formulation to the subject.

133. 133. The method of any one of claims 130 to 132, wherein the subject is 18 years of age or younger.

134. 134. The method of any one of claims 130 to 133, wherein the cancer is low-grade glioma.

135. 1. A method of treating a subject having pediatric low grade glioma (pLGG), comprising reconstituting an amorphous solid dispersion of Compound A or a salt thereof in an aqueous solution and administering a pharmacologic acceptable dosage of the reconstituted Compound A or a salt thereof to the subject in need thereof.

136. The method of any one of claims 130-135, wherein the subject has not previously been administered a MEK inhibitor or a MAPK inhibitor.

137. 137. The method of any one of claims 130 to 136, administered with food, before ingesting food, or after ingesting food.

138. 1. A method of preparing a liquid formulation comprising the steps of: a) providing a solid formulation of an amorphous solid dispersion, said amorphous solid dispersion comprising: (i) (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A) or a pharma- ceutically acceptable salt thereof; and (ii) one or more polymers and b) contacting said solid formulation with an aqueous solution A method comprising:

139. 139. The method of claim 138, wherein the contacting step comprises mixing the solid formulation with the aqueous solution to form a suspension.

140. 140. The method of claim 139, wherein the mixing step comprises shaking the solid formulation and the aqueous solution to form a suspension.

141. 140. The method of claim 139, wherein the mixing step comprises adding the aqueous solution to a container containing the solid formulation and then shaking the container to form a suspension.

142. 140. The method of claim 139, wherein the mixing step comprises adding the solid formulation to a container containing the aqueous solution and then shaking the container to form a suspension.

143. 143. The method of any one of claims 140-142, wherein the shaking step lasts from about 10 seconds to about 240 seconds.

144. 143. The method of any one of claims 140-142, wherein the shaking step lasts from about 10 seconds to about 60 seconds, from about 60 seconds to about 120 seconds, from about 40 seconds to about 80 seconds, or from about 50 seconds to about 70 seconds.

145. 143. The method of any one of claims 140 to 142, wherein the shaking step lasts for about 60 seconds.

146. 143. The method of any one of claims 140-142, wherein the shaking step lasts no longer than about 120 seconds in total.

147. The method of any one of claims 141 to 146, wherein the container is shaken in all directions.

148. 147. The method of any one of claims 139 to 146, wherein the mixing or shaking step is performed in 15 second increments.

149. 147. The method of any one of claims 139-146, wherein the mixing or shaking step is continued until all of the solid formulation is dispersed in the aqueous solution.

150. 150. The method of any one of claims 138-149, wherein the aqueous solution has a temperature of about 15°C to about 80°C, about 20°C to about 60°C, or about 20°C to about 50°C.

151. 150. The method of any one of claims 138 to 149, wherein the aqueous solution is hot water or room temperature water.

152. 152. The method of any one of claims 141-151, further comprising the steps of inverting the container and continuing to mix the suspension.

153. 153. The method of claim 152, comprising the steps of inverting the container and rotating for about 10 seconds to about 60 seconds, about 20 seconds to about 40 seconds, about 40 seconds to about 80 seconds, or about 15 seconds to about 45 seconds.

154. 154. The method of any one of claims 141 to 153, further comprising the step of leaving the container without mixing for a period of time.

155. 155. The method of any one of claims 138-154, wherein the volume of the aqueous solution is from about 5 mL to about 200 mL, from about 5 mL to 100 mL, from about 5 mL to 50 mL, from about 5 mL to 25 mL, from about 5 mL to 20 mL, from about 10 mL to 50 mL, from about 10 mL to 25 mL, from about 25 mL to 50 mL, from about 25 mL to 150 mL, or from about 10 mL to about 20 mL.

156. 155. The method of any one of claims 138-154, wherein the volume of the aqueous solution is about 10 mL, about 11 mL, about 12 mL, about 13 mL, about 14 mL, about 15 mL, about 16 mL, about 17 mL, about 18 mL, about 19 mL, or about 20 mL.

157. 152. The method of any one of claims 138 to 151, wherein the volume of the aqueous solution is about 14 mL.

158. 158. The method of any one of claims 141 to 157, further comprising withdrawing the suspension from the container using a syringe.

159. 159. The method of claim 158, further comprising administering the suspension directly from the syringe to a subject.

160. 160. The method of any one of claims 138 to 159, wherein the solid formulation is in the form of a pharmaceutical powder.

161. 60. A method for preparing an oral liquid suspension of Compound A or a salt thereof, comprising reconstituting the solid formulation in the kit of any one of claims 1 to 59 in an aqueous solution.

162. 93. A method for preparing an oral liquid suspension of Compound A or a salt thereof, comprising reconstituting a pharmaceutical powder according to any one of claims 60 to 92 in an aqueous solution.

163. 1. A method of treating pediatric low grade glioma (pLGG) in a subject, comprising:

1. A method comprising the step of administering to a subject an oral liquid suspension comprising (R)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (Compound A), or a pharma- ceutically acceptable salt thereof, in an amount sufficient to achieve a maximum observed plasma concentration (Cmax) of Compound A in said subject of at least 2000 ng / mL, wherein said subject has not previously been administered a MEK inhibitor, a MAPK inhibitor, or a combination thereof.

164. 129. A method of treating pediatric low grade glioma (pLGG), comprising administering to a subject the pharmaceutical powder of any one of claims 60-92 or the reconstituted oral liquid formulation of any one of claims 93-128, wherein the subject has not previously been administered a MEK inhibitor, a MAPK inhibitor, or a combination thereof.

165. 60. A method of treating pediatric low grade glioma (pLGG), comprising reconstituting the solid formulation in the kit of any one of claims 1-59 and administering the reconstituted formulation to the subject, wherein the subject has not previously been administered a MEK inhibitor, a MAPK inhibitor, or a combination thereof.

166. 166. The method of any one of claims 163-165, wherein the subject has not previously been administered a MEK inhibitor.

167. 166. The method of any one of claims 163-165, wherein the subject has not previously been administered a MAPK inhibitor.

168. The method of any one of claims 163-165, wherein the subject is 6 months of age and older with relapsed or refractory pLGG harboring a BRAF fusion or rearrangement, or a BRAF V600 mutation.

169. 166. The method of any one of claims 163 to 165, wherein the subject exhibits the presence of a BRAF fusion or rearrangement, or a BRAF mutation, prior to the initiation of treatment.

170. A method of treating pediatric low grade glioma (pLGG), comprising administering to a subject in need thereof a pharmaceutical powder according to any one of claims 60-92 or an oral liquid suspension according to any one of claims 93-128, the subject is a 6-month-old patient; The method, wherein the pLGG is a recurrent or pLGG with a BRAF fusion or rearrangement, or a BRAF V600 mutation.

171. 171. The method of claim 170, wherein the oral liquid suspension is administered orally or enterally via a nasal or gastric feeding tube equipped with an administration syringe.

172. Approximately 420 mg / m orally once weekly according to body surface area (BSA) ２ 172. The method of claim 170 or 171, comprising administering Compound A (not to exceed 600 mg).

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