DESC:FIELD OF THE INVENTION

The present invention relates to a solid dispersion of Aficamten. The present invention further relates to a composition comprising solid dispersions of Aficamten and pharmaceutical composition containing the same.

BACKGROUND OF THE INVENTION

Aficamten is a cardiac myosin inhibitor and is useful in the treatment of Obstructive HCM (oHCM), Non-Obstructive Hypertrophic Cardiomyopathy (nHCM) and Hypertrophic Cardiomyopathy (HCM). Aficamten is chemically known as (R)-N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide and is represented as Formula I.

Aficamten (Formula I)

The compound Aficamten was first described in PCT publication WO2019144041A1 and its use thereof as cardiac sarcomere inhibitors.

Crystalline forms of Aficamten Form I, Form II, Form III, Form IV, Form V and Form VI and its process for preparation thereof are described in PCT publication WO2021011807A1.

Crystalline Aficamten: maleic acid co-crystal Form M1 and its process for preparation thereof are described in PCT publication WO2024134498A1.

Co-crystal of Aficamten: tartaric acid Form CSI and its process for preparation thereof are described in PCT publication WO2024179422A1.

Discovering new solid state forms and solvates of a pharmaceutical product may yield materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms. New solid-state forms of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., a different crystal habit, higher crystallinity, or polymorphic stability, which may offer better processing or handling characteristics, improved dissolution profile, or improved shelf-life (chemical/physical stability). For at least these reasons, there is a need for additional solid-state forms of Aficamten, that can be used readily in pharmaceutical compositions suitable for use as therapeutics.

SUMMARY OF THE INVENTION

The present invention encompasses a solid dispersion comprising Aficamten and its pharmaceutical compositions thereof.

In accordance with one embodiment, the present invention provides an amorphous solid dispersion of Aficamten.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with Eudragit.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with Polyvinyl acetate Phthalate.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with PVP-K30.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with HPMC Phthalate.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with HPMCAS.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with HPMC.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with Copovidone.

In accordance with another embodiment, the present invention provides a pharmaceutical composition comprising an amorphous solid dispersion of Aficamten and at least one pharmaceutically acceptable excipient.

In accordance with another embodiment, the present invention provides use of amorphous solid dispersion of Aficamten prepared by the processes of the present invention for the treatment of Obstructive HCM (oHCM), Non-Obstructive Hypertrophic Cardiomyopathy (nHCM) and Hypertrophic Cardiomyopathy (HCM) with effective amount.

BRIEF DESCRIPTION OF THE DRAWING

Figure 1: PXRD pattern of amorphous solid dispersion of Aficamten with Eudragit (1:4).

Figure 2: PXRD pattern of amorphous solid dispersion of Aficamten with Polyvinyl acetate Phthalate (1:4).

Figure 3: PXRD pattern of amorphous solid dispersion of Aficamten with PVP-K30 (1:4).

Figure 4: PXRD pattern of amorphous solid dispersion of Aficamten with HPMC Phthalate (1:4).

Figure 5: PXRD pattern of amorphous solid dispersion of Aficamten with HPMCAS (1:4).
Figure 6: PXRD pattern of amorphous solid dispersion of Aficamten with HPMC (1:4).

Figure 7: PXRD pattern of amorphous solid dispersion of Aficamten with Copovidone (1:4).

Figure 8: PXRD overlay of amorphous solid dispersion of Aficamten with Eudragit (1:4), Initial with 3rd month at 25°C/60% RH and 40°C/75% RH (Closed condition).

Figure 9: PXRD overlay of amorphous solid dispersion of Aficamten with PVAP (1:4), Initial with 3rd month at 25°C/60% RH and 40°C/75% RH (Closed condition).

Figure 10: PXRD overlay of amorphous solid dispersion of Aficamten with PVPK-30 (1:4), Initial with 3rd month at 25°C/60% RH and 40°C/75% RH (Closed condition).

Figure 11: PXRD overlay of amorphous solid dispersion of Aficamten with HPMC Pthalate (1:4), Initial with 3rd month at 25°C/60% RH and 40°C/75% RH (Closed condition).

Figure 12: PXRD overlay of amorphous solid dispersion of Aficamten with HPMCAS (1:4), Initial with 3rd month at 25°C/60% RH and 40°C/75% RH (Closed condition).

Figure 13: PXRD overlay of amorphous solid dispersion of Aficamten with HPMC (1:4), Initial with 3rd month at 25°C/60% RH and 40°C/75% RH (Closed condition).

Figure 14: PXRD pattern of amorphous solid dispersion of Aficamten with HPMC (1:3).

Figure 15: PXRD overlay of amorphous solid dispersion of Aficamten with HPMC (1:3), Initial with 3rd month at 25°C/60% RH and 40°C/75% RH (Closed condition).

DETAILED DESCRIPTION OF THE INVENTION

In accordance with one embodiment, the present invention provides a solid form of Aficamten and the pharmaceutical compositions thereof. Specific aspect of present application relates to the amorphous solid dispersions (ASD’s) of Aficamten and their preparative processes.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from Methacrylic acid/ethyl acrylate, Carbopol copolymers, Caprylocaproyl polyoxyl-8 glycerides, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, cellulose acetate phthalate (CAP), hypromellose (HPMC), hydroxypropyl cellulose, hypromellose phthalate (HPMCP), hypromellose acetate succinate (HPMCAS, HPMCAS HG), polyethylene glycol methyl, poly-ethylene glycol vinyl acetate vinylcaprolactam (e.g., SOLUPLUS), polyethylene glycol 6000 (PEG 6000), polyvinylpyrrolidone (PVP, PVP-K30), polyvinylpyrrolidone vinyl acetate (PVP-VA), Polyvinyl acetate Pthalate, Poly (ethyl acrylate -co -methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) 1:2: 0.1 (Eudragit RS 100), methyacrylic acid copolymer type B (Eudragit S 100), Eudragit L-100, Sureteric, Pluronic F-68 and polyoxyethylene (20) sorbitan monooleate (Tween 80) and mixture thereof.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from Eudragit, optionally with one more pharmaceutically acceptable polymer.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with Eudragit, characterized by a powder X-ray diffraction pattern, as illustrated by Figure 1.
In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from Polyvinyl acetate Pthalate, optionally with one more pharmaceutically acceptable polymer.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with Polyvinyl acetate Pthalate, characterized by a powder X-ray diffraction pattern, as illustrated by Figure 2.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from PVP-K30, optionally with one more pharmaceutically acceptable polymer.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with PVP-K30, characterized by a powder X-ray diffraction pattern, as illustrated by Figure 3.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from HPMC Pthalate, optionally with one more pharmaceutically acceptable polymer.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with HPMC Pthalate, characterized by a powder X-ray diffraction pattern, as illustrated by Figure 4.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from HPMCAS, optionally with one more pharmaceutically acceptable polymer.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with HPMCAS, characterized by a powder X-ray diffraction pattern, as illustrated by Figure 5.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from HPMC, optionally with one more pharmaceutically acceptable polymer.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with HPMC (1:4), characterized by a powder X-ray diffraction pattern, as illustrated by Figure 6.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with HPMC (1:3), characterized by a powder X-ray diffraction pattern, as illustrated by Figure 14.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with pharmaceutically acceptable polymers selected from Copovidone, optionally with one more pharmaceutically acceptable polymer.

In accordance with another embodiment, the present invention provides an amorphous solid dispersion of Aficamten with Copovidone (1:4), characterized by a powder X-ray diffraction pattern, as illustrated by Figure 7.

In accordance with another embodiment, the present invention provides a general process for the preparation of amorphous solid dispersion of Aficamten comprising,
a) Dissolving Aficamten and one or more polymer in an organic solvent, and
b) Isolating the solid amorphous solid dispersion of Aficamten.

The polymers selected from the group comprising: Methacrylic acid/ethyl acrylate, Carbopol copolymers, Caprylocaproyl polyoxyl-8 glycerides, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, cellulose acetate phthalate (CAP), hypromellose (HPMC), hydroxypropyl cellulose, hypromellose phthalate (HPMCP), hypromellose acetate succinate (HPMCAS, HPMCAS HG), polyethylene glycol methyl, poly-ethylene glycol vinyl acetate vinylcaprolactam (e.g., SOLUPLUS), polyethylene glycol 6000 (PEG 6000), polyvinylpyrrolidone (PVP, PVP-K30), polyvinylpyrrolidone vinyl acetate (PVP-VA), Polyvinyl acetate Pthalate, Poly (ethyl acrylate -co -methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) 1:2: 0.1 (Eudragit RS 100), methyacrylic acid copolymer type B (Eudragit S 100), Eudragit L-100, Sureteric, Pluronic F-68 and polyoxyethylene (20) sorbitan monooleate (Tween 80) and optionally in presence of one or more polymer.

In accordance with another embodiment, the present invention provides isolation by conventional techniques such as precipitation by cooling the reaction mass, isolated by solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration, lyophilization or spray-drying; preferably by concentrated by subjecting the solution to heating or spray-drying.

In accordance with another embodiment, the present invention provides amorphous solid dispersion can also be achieved by melting technique, co-precipitation process, simple physical mixing and like.

In accordance with another embodiment, the present invention provides Aficamten used in this aspect may be obtained by any methods known in the art or a reaction mixture comprising Aficamten may be used directly.

In accordance with another embodiment, the present invention provides the isolated solid optionally dried under suitable drying conditions such as aerial drying, drying under vacuum or inert gas at a suitable temperature of about 25°C or above.

In accordance with another embodiment, the present invention provides the solid forms of the present application are stable under thermal, humid and stress conditions.
In accordance with another embodiment, the present invention provides the solid forms of the present application are stable under closed conditions at both 25°C/60% RH and 40°C/75%RH.

In accordance with another embodiment, the present invention provides Aficamten is present in an amount from 1% to 80% by weight of the solid dispersion. In some embodiments, the polymer is present in an amount from 80% to 99% by weight of the solid dispersion.

Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application.

Unless otherwise specified the term “organic solvent” used herein for the above embodiments is selected from but not limited to alcohols, amides, aliphatic or alicyclic hydrocarbons, sulfoxides, ketones, nitriles, ethers, esters, halogenated hydrocarbons, aromatic hydrocarbons and the like, water and mixtures thereof. The alcohols include, but are not limited to methanol, ethanol, propanol, butanol and the like; amides include, but are not limited to dimethylacetamide, dimethylformamide, N-methylpyrrolidone and the like; aliphatic or alicyclic hydrocarbons include, but are not limited to n-pentane, isopentane, neopentane, n-hexane, isohexane, 3-methylpentane, 2,3-dimethylbutane, neohexane, n-heptane, isoheptane, 3-methylhexane, neoheptane, 2,3-dimethylpentane, 2,4-dimethylpentane, 3,3-dimethylpentane, 3-ethylpentane, 2,2,3-trimethylbutane, n-octane, isooctane, 3-methylheptane, neooctane, cyclohexane, methylcyclohexane, cycloheptane, C5-C8 aliphatic hydrocarbons, petroleum ethers and the like; sulfoxides include, but are not limited to dimethyl sulfoxide, diethyl sulfoxide and the like; ketones include, but are not limited to acetone, methyl isobutyl ketone, methyl ethyl ketone and the like; nitriles include, but are not limited to acetonitrile, propionitrile and the like; ethers include, but are not limited to tetrahydrofuran, methyl tetrahydrofuran, diethyl ether, diisopropyl ether, methyl tert-butyl ether, 1,4-dioxane and the like; esters such as methyl acetate, ethyl acetate, isobutyl acetate and the like; halogenated hydrocarbons include, but are not limited to methylene chloride, chloroform and the like; aromatic hydrocarbons include, but are not limited to toluene, xylene and the like; water and mixture thereof; preferably methanol, ethanol, methylene chloride and mixture thereof.

As used herein the term "amorphous" refers to solid forms that consist of disordered arrangements of molecules and do not possess a distinguishable crystal lattice.

As used herein "crystalline" refers to compounds or compositions where the structural units are arranged in fixed geometric patterns or lattices, so that crystalline solids have rigid long-range order. The structural units that constitute the crystal structure can be atoms, molecules, or ions. Crystalline solids show definite melting points.

Unless otherwise specified, the term “solid dispersion” refers to a solid state which comprises at least two constituents, wherein one constituent is homogenously dispersed significantly evenly throughout the other constituent or constituents. It includes solid or glassy solutions, i.e., the dispersion of the constituents is in such a way that the composition is chemically and physically homogenous in nature. In one embodiment, the first constituent is an active pharmaceutical ingredient (API), such as a compound of Aficamten, and the second constituent is a matrix that comprises a polymer, wherein the API is dispersed significantly uniformly within the matrix (the polymer). The API may be present in an amorphous state or in fine crystalline dispersed form. Also, the API may be available as a mixture of amorphous and crystalline forms. A solid dispersion can comprise more than two constituents. For example, two or more API can be dispersed into the matrix, and the matrix can comprise two or more polymers. Without limitation, solid dispersions may be physically classified as a eutectic mixture, a solid solution, a glass solution or suspension, an amorphous precipitate in a glassy or crystalline carrier, a complex, a complexed formation or a combination of the different systems. In addition, solid dispersions may be prepared using various techniques known to those skilled in the art, such as by co-dissolving the API and polymer in a solvent, then spray-drying, spray-congealing, evaporating, curing or microwaving, blending and direct compression, mechanical admixture at an elevated but non-melting temperature, wet granulation, extrusion-spheronization, melt fusion, hot melt extrusion and the like. A “solid matrix” refers to a matrix that is solid.

The term “polymer” refers to a compound comprising repeating structural units (monomers) connected by covalent chemical bonds. Polymers may be further derivatized, crosslinked, grafted or end- capped. Non-limiting examples of polymers include copolymers, terpolymers, quaternary polymers, and homologues. The term “copolymer” refers to a polymer consisting essentially of two or more different types of repeating structural units (monomers).

The term “pharmaceutically acceptable excipient” includes, without limitation, any adjuvant, carrier, excipient, binder, filler, disintegrant, lubricant, glidant, sweetening agent, diluent, preservative, dye, colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier which has been approved by the United States Food and Drug Administration as being acceptable for use in humans or domestic animals.

The term “effective amount” or “therapeutically effective amount” refers to that amount of a compound described herein that is sufficient to affect the intended application, including but not limited to disease treatment, as defined below. The therapeutically effective amount may vary depending upon the intended treatment application (in vivo), or the subject and disease condition being treated, e.g., the weight and age of the subject, the severity of the disease condition, the manner of administration and the like, which can readily be determined by one of ordinary skill in the art. The term also applies to a dose that will induce a particular response in target cells, e.g., reduction of platelet adhesion and/or cell migration. The specific dose will vary depending on the particular compounds chosen, the dosing regimen to be followed, whether it is administered in combination with other compounds, timing of administration, the tissue to which it is administered, and the physical delivery system in which it is carried.

EXAMPLES

The following non limiting examples illustrate specific embodiments of the present invention. They are not intended to be limiting the scope of the present invention in any way.

EXAMPLE-1: Amorphous solid dispersion with Eudragit L-100 (API: Polymer - 1:4w/w)

In a round bottomed flask, Aficamten (200 mg) was dissolved in methanol (25 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol (5mL). In another round bottomed flask, Eudragit-L100 (800 mg) was dissolved in methanol (50 mL) at ambient temperature. Combined the above two solutions and distilled under vacuum at 60°C over rotavapour. Dried the compound under vacuum at 50°C for 20hrs. The PXRD of the resultant solid material is given in Fig.1.

EXAMPLE-2: Amorphous solid dispersion with Polyvinyl acetate Pthalate (API: Polymer - 1:4w/w)

In a round bottomed flask, Aficamten (200 mg) was dissolved in methanol (20 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol (5mL). In another round bottomed flask, Polyvinyl acetate Pthalate (800 mg) was dissolved in methanol (50 mL) at ambient temperature. Combined the above two solutions and distilled under vacuum at 60°C over rotavapour. Dried the compound under vacuum at 50°C for 20hrs. The PXRD of the resultant solid material is given in Fig.2.

EXAMPLE-3: Amorphous solid dispersion with PVP-K30 (API: Polymer -1:4w/w)

In a round bottomed flask, Aficamten (200 mg) was dissolved in methanol (20 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol (5mL). In another round bottomed flask, PVP-K30 (800 mg) was dissolved in methanol (30 mL) at ambient temperature. Combined the above two solutions and distilled under vacuum at 60°C over rotavapour. Dried the compound under vacuum at 50°C for 21hrs. The PXRD of the resultant solid material is given in Fig.3.

EXAMPLE-4: Amorphous solid dispersion with HPMC Pthalate (API: Polymer -1:4w/w)

In a round bottomed flask, Aficamten (200 mg) was dissolved in methanol (20 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol (5mL). In another round bottomed flask, HPMC Pthalate (800 mg) was dissolved in methanol (30 mL) at ambient temperature. Combined the above two solutions and distilled under vacuum at 60°C over rotavapour. Dried the compound under vacuum at 50°C for 21hrs. The PXRD of the resultant solid material is given in Fig.4.

EXAMPLE-5: Amorphous solid dispersion with HPMC AS HG (API: Polymer-1:4w/w)

In a round bottomed flask, Aficamten (200 mg) was dissolved in methanol (20 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol (5mL). In another round bottomed flask, HPMC AS HG (800 mg) was dissolved in methanol (35 mL) at ambient temperature. Combined the above two solutions and distilled under vacuum at 60°C over rotavapour. Dried the compound under vacuum at 50°C for 20hrs. The PXRD of the resultant solid material is given in Fig.5.

EXAMPLE-6: Amorphous solid dispersion with HPMC (API: Polymer - 1:4w/w)

In a round bottomed flask, Aficamten (200 mg) was dissolved in methanol (20 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol (5mL). In another round bottomed flask, HPMC (800 mg) was dissolved in methanol (35 mL) at ambient temperature. Combined the above two solutions and distilled under vacuum at 60°C over rotavapour. Dried the compound under vacuum at 50°C for 21hrs. The PXRD of the resultant solid material is given in Fig.6.

EXAMPLE-6A: Amorphous solid dispersion with HPMC (API: Polymer - 1:4w/w)

In a round bottomed flask, Aficamten (1 gm) was dissolved in methanol (70 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol. In another round bottomed flask, HPMC (4 gm) was dissolved in a mixture of methanol (250 mL) and methylene chloride (50 mL) at ambient temperature. Combined the above two solutions and Spray drying with below conditions: Pressure 2 bar; Inlet gas flow 0.40 m3/min; Inlet temp 70°C; Outlet temp 40°C; Nozzle size 0.8mm and Feed rate 8 g/min to obtain title compound. Dried the compound under vacuum at 50°C for 12hrs

EXAMPLE-7: Amorphous solid dispersion with Copovidone (API: Polymer - 1:4w/w)

Mixture of Aficamten (100mg) with Copovidone (400mg) are triturated using mortar and pestle. This mixture was heated to 162°C under vacuum, maintained for 30 min and cooled to room temperature to obtain title compound. The PXRD of the resultant solid material is given in Fig.7.

EXAMPLE-8: Amorphous solid dispersion with HPMC (API: Polymer - 1:3w/w)

In a round bottomed flask, Aficamten (50 mg) was dissolved in methanol (4 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol (2mL). In another round bottomed flask, HPMC (150 mg) was dissolved in methanol (10 mL) at ambient temperature. Combined the above two solutions and distilled under vacuum at 50°C over rotavapour.

EXAMPLE-9: Amorphous solid dispersion with HPMC (API: Polymer - 1:3w/w)

In a round bottomed flask, Aficamten (1 gm) was dissolved in methanol (70 mL) at ambient temperature and filtered the clear solution for particle free and washed with methanol. In another round bottomed flask, HPMC (3 gm) was dissolved in a mixture of methanol (250 mL) and methylene chloride (50 mL) at ambient temperature. Combined the above two solutions and Spray drying with below conditions: Pressure 2 bar; Inlet gas flow 0.40 m3/min; Inlet temp 70°C; Outlet temp 40°C; Nozzle size 0.8mm and Feed rate 8 g/min to obtain title compound. Dried the compound under vacuum at 50°C for 12hrs. The PXRD of the resultant solid material is given in Fig. 14.

It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be constructed as limiting, but merely as exemplifications of preferred embodiments. For example, the functions described above and implemented as the best mode for operating the present invention are for illustration purposes only. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of this invention. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the specification appended hereto. ,CLAIMS:We Claim:

1. An amorphous solid dispersion of Aficamten with one or more pharmaceutically acceptable polymers.

2. The amorphous solid dispersion of Aficamten according to claim 1, wherein the pharmaceutically acceptable polymers is selected from a group of Eudragit, Polyvinyl acetate Phthalate, PVP-K30, HPMC Phthalate, HPMCAS, HPMC, Copovidone and mixture thereof.

3. The amorphous solid dispersion of Aficamten of claim 1, wherein pharmaceutically acceptable polymer is PVP-K30.

4. The amorphous solid dispersion of Aficamten of claim 1, wherein pharmaceutically acceptable polymer is HPMC.

5. The amorphous solid dispersion of Aficamten according to claim 1, wherein the ratio of Aficamten and pharmaceutically acceptable polymer is range from about 1:2 to about 1:10.

6. A process for the preparation of amorphous solid dispersion of Aficamten comprising,
a) dissolving Aficamten and one or more polymer in an organic solvent, and
b) isolating the solid amorphous solid dispersion of Aficamten.

7. The process of claim 6, wherein the polymer is selected from the group comprising: Eudragit, Polyvinyl acetate Phthalate, PVP-K30, HPMC Phthalate, HPMCAS, HPMC, Copovidone and mixture thereof.

8. The process of claim 6, wherein the organic solvent is methanol or methylene chloride.
9. The pharmaceutical composition comprising amorphous solid dispersion of Aficamten as defined in any of claims 1 to 8 and one or more pharmaceutically acceptable excipients.

10. Use of a morphous solid dispersion of Aficamten as defined in any of Claims 1 to 9, for the preparation of other solid-state forms of Aficamten, Aficamten co-crystals, Aficamten salts and their solid-state forms.