Solid state forms of emrusolmin and process for preparation thereof

Abstract

Provided are solid state forms of emrusolmin, in embodiments crystalline polymorphs of emrusolmin, processes for preparation thereof, and pharmaceutical compositions thereof.

Description

Docket No: 102085.002661 - SMI095-W001SOLID STATE FORMS OF EMRUSOLMIN AND PROCESS FOR PREPARATION THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of the priority of U.S. Provisional Patent Application No. 63 / 756,603, filed February 10, 2025, the disclosure of which is incorporated by reference herein.FIELD OF THE DISCLOSURE

[0002] The present disclosure encompasses solid state forms of emrusolmin, in embodiments crystalline polymorphs of emrusolmin, processes for preparation thereof, and pharmaceutical compositions thereof.BACKGROUND OF THE DISCLOSURE

[0003] Emrusolmin has the chemical name 5-(l,3-benzodioxol-5-yl)-3-(3-bromophenyl)-lH-pyrazole and has the following chemical structure:

[0004] Emrusolmin also refers to any tautomers thereof, such as the following tautomer:

[0005] The compound is described in International Publication No. WO2010000372. Uses of Emrusolmin to treat Synucleinopathies like Parkinson's disease, Lewy body (LB) dementia and Multiple system atrophy (MSA) and additional diseases linked to protein aggregation and / or neurodegenerative diseases is also described in WO2010000372.Formulations comprising emrusolmin are described in International Publication No.WO2023166045.Docket No: 102085.002661 - SMI095-W001

[0006] Polymorphism, the occurrence of different crystalline forms, is a property of some molecules and molecular complexes. A single molecule may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g., measured by thermogravimetric analysis (“TGA”), or differential scanning calorimetry (“DSC”)), X-ray diffraction (XRD) pattern, infrared absorption fingerprint, and solid state (13C) NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.

[0007] Different salts and crystalline forms (including solvated forms) of an active pharmaceutical ingredient may possess different properties. Such variations may provide a basis for improving formulation, for example, by facilitating better processing or handling characteristics, changing the dissolution profile in a favorable direction, or improving stability (polymorph as well as chemical stability) and shelf-life. These variations may also offer improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different forms and solvates of an active pharmaceutical ingredient may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to assess variations in the properties and characteristics of a solid active pharmaceutical ingredient.

[0008] 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, including 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 (including solvated forms) of emrusolmin.SUMMARY OF THE DISCLOSURE

[0009] The present disclosure encompasses solid state forms of emrusolmin, processes for preparation thereof, and pharmaceutical compositions thereof. These crystalline polymorphsDocket No: 102085.002661 - SMI095-W001can be used to prepare other solid state forms of emrusolmin, other emrusolmin salts or cocrystals and their solid state forms.

[0010] The present disclosure also provides uses of said solid state forms of emrusolmin in the preparation of other solid state forms of emrusolmin or other salts or cocrystals and their solid state forms thereof.

[0011] The present disclosure provides crystalline polymorphs of emrusolmin for use in medicine, including for the treatment of Parkinson's disease, Alzheimer's disease, multiple system atrophy, Diffuse Lewy body disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localized amyloidosis, beta-2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, Finnish hereditary systemic amyloidosis, and prion disease including Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, genetic human prion disease, Bovine Spongiform Encephalopathy (BSE) and Scrapie.

[0012] The present disclosure also encompasses the use of crystalline polymorphs of emrusolmin of the present disclosure for the preparation of pharmaceutical compositions and / or formulations.

[0013] In another aspect, the present disclosure provides pharmaceutical compositions comprising crystalline polymorphs of emrusolmin according to the present disclosure.

[0014] The present disclosure includes processes for preparing the above mentioned pharmaceutical compositions. The processes include combining said crystalline polymorph of emrusolmin of the present disclosure with at least one pharmaceutically acceptable excipient.

[0015] The crystalline polymorph of emrusolmin as defined herein and the pharmaceutical compositions or formulations of the crystalline polymorph of emrusolmin may be used as medicaments, such as for the treatment of aggregation and / or neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, multiple system atrophy, Diffuse Lewy body disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localizedDocket No: 102085.002661 - SMI095-W001amyloidosis, beta-2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, Finnish hereditary systemic amyloidosis, and prion disease including Creutzfeldt-Jakob disease, variant Creutzfeldt- Jakob disease, genetic human prion disease, Bovine Spongiform Encephalopathy (BSE) and Scrapie.

[0016] The present disclosure also provides methods of treating aggregation and / or neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, multiple system atrophy, Diffuse Lewy body disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localized amyloidosis, beta-2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, Finnish hereditary systemic amyloidosis, and prion disease including Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, genetic human prion disease, Bovine Spongiform Encephalopathy (BSE) and Scrapie, by administering a therapeutically effective amount of emrusolmin present disclosure, or at least one of the above pharmaceutical compositions, to a subject suffering from said aggregation and / or neurodegenerative diseases, or otherwise in need of the treatment.

[0017] The present disclosure also provides uses of crystalline polymorphs of emrusolmin of the present disclosure, or at least one of the above pharmaceutical compositions, for the manufacture of medicaments for treating aggregation and / or neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, multiple system atrophy, Diffuse Lewy body disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localized amyloidosis, beta-2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, Finnish hereditary systemic amyloidosis, and prion disease including Creutzfeldt-Jakob disease, variant Creutzfeldt- Jakob disease, genetic human prion disease, Bovine Spongiform Encephalopathy (BSE) and Scrapie.

[0018] Other aspects and embodiments of the invention will be readily apparent from the following detailed description of the invention.BRIEF DESCRIPTION OF THE DRAWINGSDocket No: 102085.002661 - SMI095-W001

[0019] The present application is further understood when read in conjunction with the appended drawings. For the purpose of illustrating the subject matter, exemplary embodiments of the subject matter are shown in the drawings; however, the presently disclosed subject matter is not limited to the specific processes or methods disclosed. In addition, the drawings are not necessarily drawn to scale.

[0020] FIG. 1 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: HC1 Form Hl.

[0021] FIG. 2 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: HC1 Form H2.

[0022] FIG. 3 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: CSAForm Cl.

[0023] FIG. 4 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: TSAForm Tl.

[0024] FIG. 5 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: TSA Form T2.

[0025] FIG. 6 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: esylate Form El.

[0026] FIG. 7 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: esylate Form E2.

[0027] FIG. 8 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate Form ESI.

[0028] FIG. 9 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate Form ES2.

[0029] FIG. 10 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate Form ES 3.

[0030] FIG. 11 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate Form ES4.

[0031] FIG. 12 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate Form ES 5.

[0032] FIG. 13 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate Form ES 6.Docket No: 102085.002661 - SMI095-W001

[0033] FIG. 14 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate Form ES7.

[0034] FIG. 15 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: edisylate FormES8.

[0035] FIG. 16 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: tartarate Form TAI.

[0036] FIG. 17 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: mesylate Form MSI.

[0037] FIG. 18 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: mesylate Form MS2.

[0038] FIG. 19 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: bromide Form Bl.

[0039] FIG. 20 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: bromide Form B2.

[0040] FIG. 21 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: bromide Form B3.

[0041] FIG. 22 shows a characteristic X-ray powder diffraction pattern (XRPD) of emrusolmin: besylate Form BS1.

[0042] FIG. 23 shows the intrinsic dissolution of Emrusolmin Hydrochloride (Form Hl) vs Emrusolmin base.

[0043] FIG. 24 are optical micrographs. Left: Emrusolmin Hydrochloride crystals (Form Hl) at 20 x magnification; Right: Emrusolmin base crystals (Form 1) at 20 x magnification.

[0044] FIG. 25 shows the intrinsic dissolution of Emrusolmin Hydrobromide (Form Bl) vs Emrusolmin base (Form 1).

[0045] FIG. 26 are optical micrographs: Left Emrusolmin Hydrobromide crystals (Form Bl) at 20 x magnification; Right Emrusolmin base crystals (Form 1) at 20 x magnification.

[0046] FIG. 27 are DSC thermogram. Top: thermogram Emrusolmin Tosylate crystals (Form T4); Bottom: thermogram Emrusolmin base crystals (Form 1).Docket No: 102085.002661 - SMI095-W001

[0047] FIG. 28 are optical micrographs. Top: Emrusolmin Tosylate crystals (Form T4) at 20 x magnification; Bottom: Emrusolmin base crystals (Form 1) at 20 x magnification.

[0048] FIG. 29 shows the intrinsic dissolution of Emrusolmin Camsylate (Form Cl) vs Emrusolmin base (Form 1).

[0049] FIG. 30 are optical micrographs. Top: Emrusolmin Camsylate crystals (Form Cl) at 20 x magnification; Bottom: Emrusolmin base crystals (Form 1) at 20 x magnification.

[0050] FIG. 31 shows the intrinsic dissolution of Emrusolmin Mesylate (Form MSI) vs Emrusolmin base (Form 1).

[0051] FIG. 32 shows the DSC and TGA thermogram: Emrusolmin Esylate salt (Form E2)- upper thermogram and DSC thermogram of Emrusolmin base (Form 1) - lower image.

[0052] FIG. 33 shows the intrinsic dissolution of Emrusolmin Esylate (Form E2) vs Emrusolmin base (Form 1).

[0053] FIG. 34 are optical micrographs. Top: Emrusolmin Edisylate crystals (Form ESI) at 20 x magnification; Bottom: Emrusolmin base crystals (Form 1) at 20 x magnification.

[0054] FIG. 35 shows the intrinsic dissolution of Emrusolmin Edisylate (Form ESI) vs Emrusolmin base (Form 1).

[0055] FIG. 36 are optical micrographs. Top: Emrusolmin Hemiedisylate crystals (Form HE1) at 20 x magnification; Bottom: Emrusolmin base crystals (Form 1) at 20 x magnification.

[0056] FIG. 37 are optical micrographs. Top: Emrusolmin Besylate crystals (Form BS1) at 20 x magnification; Bottom: Emrusolmin base crystals (Form 1) at 20 x magnification.

[0057] FIG. 38 shows the intrinsic dissolution of Emrusolmin Besylate (Form BS1) vs Emrusolmin base (Form 1).

[0058] FIG. 39 shows the XRD pattern of Emrusolmin hemiedisylate pure form HE1.

[0059] FIG. 40 shows the XRD pattern of Emrusolmin camsylate form C2.

[0060] FIG. 41 shows the XRD pattern of Emrusolmin tosylate form T4.DETAILED DESCRIPTION OF THE DISCLOSURE

[0061] In the present disclosure the singular forms “a”, “an” and “the” include the plural reference, and reference to a particular numerical value includes at least that particular value, unless the context clearly indicates otherwise. Thus, for example, a reference to “aDocket No: 102085.002661 - SMI095-W001material” is a reference to at least one of such materials and equivalents thereof known to those skilled in the art, and so forth.

[0062] When a value is expressed as an approximation by use of the descriptor “about” it will be understood that the particular value forms another embodiment. In general, use of the term “about” indicates approximations that can vary depending on the desired properties sought to be obtained by the disclosed subject matter and is to be interpreted in the specific context in which it is used, based on its function. The person skilled in the art will be able to interpret this as a matter of routine. In some cases, the number of significant figures used for a particular value may be one non-limiting method of determining the extent of the word “about.” In other cases, the gradations used in a series of values may be used to determine the intended range available to the term “about” for each value. Where present, all ranges are inclusive and combinable. That is, references to values stated in ranges include every value within that range.

[0063] The present disclosure encompasses solid state forms of emrusolmin, processes for preparation thereof, and pharmaceutical compositions thereof.

[0064] Solid state properties of emrusolmin and crystalline polymorphs thereof can be influenced by controlling the conditions under which emrusolmin and crystalline polymorphs thereof are obtained in solid form.

[0065] A solid state form (or polymorph) may be referred to herein as “polymorphically pure” or as substantially free of any other solid state (or polymorphic) forms.

[0066] A solid state form (or polymorph) may be referred to herein as polymorphically pure or as substantially free of any other solid state (or polymorphic) forms. As used herein in this context, the expression “substantially free of any other forms” will be understood to mean that the solid state form contains about 20% (w / w) or less, about 10% (w / w) or less, about 5% (w / w) or less, about 2% (w / w) or less, about 1% (w / w) or less, or about 0% of any other forms of the subject compound as measured, for example, by XRPD. For example, polymorphically pure Emrusolmin Form Hl means that the solid state form is substantially free of other solid state forms of the same Emrusolmin. Thus, a crystalline polymorph of Emrusolmin described herein as substantially free of any other solid state forms would be understood to contain greater than about 80% (w / w), greater than about 90% (w / w), greater than about 95% (w / w), greater than about 98% (w / w), greater than about 99% (w / w), or about 100% of the subject crystalline polymorph of the emrusolmin. In some embodiments of the disclosure, the described crystallineDocket No: 102085.002661 - SMI095-W001polymorph of emrusolmin may contain from about 1% to about 20% (w / w), from about 5% to about 20% (w / w), or from about 5% to about 10% (w / w) of one or more other crystalline polymorph of the same emrusolmin.

[0067] A compound may be referred to herein as chemically pure or purified compound or as substantially free of any other compounds. As used herein in this context, the expression “substantially free of any other compounds” will be understood to mean that the pure compound contains about 20% (w / w) or less, about 10% (w / w) or less, about 5% (w / w) or less, about 2% (w / w) or less, about 1% (w / w) or less, or about 0% of any other compound as measured, for example, by HPLC. Thus, pure or purified emrusolmin herein as substantially free of any compounds would be understood to contain greater than about 80% (w / w), greater than about 90% (w / w), greater than about 95% (w / w), greater than about 98% (w / w), greater than about 99% (w / w), or about 100% of the subject emrusolmin. In some embodiments of the disclosure, the described pure or purified emrusolmin may contain from about 1% to about 20% (w / w), from about 5% to about 20% (w / w), or from about 5% to about 10% (w / w) of one or more other compounds.

[0068] Depending on which other crystalline polymorphs a comparison is made, the crystalline polymorphs of emrusolmin of the present disclosure may have advantageous properties selected from at least one of the following: chemical purity, flowability, solubility, dissolution rate, morphology or crystal habit, stability, such as chemical stability as well as thermal and mechanical stability with respect to polymorphic conversion, stability towards dehydration and / or storage stability, low content of residual solvent, a lower degree of hygroscopicity, flowability, and advantageous processing and handling characteristics such as compressibility and bulk density.

[0069] A crystal form may be referred to herein as being characterized by graphical data “as depicted in” or “as substantially depicted in” a Figure. Such data include, for example, powder X-ray diffractograms and solid state NMR spectra. As is well-known in the art, the graphical data potentially provides additional technical information to further define the respective solid state form (a so-called “fingerprint”) which cannot necessarily be described by reference to numerical values or peak positions alone. In any event, the skilled person will understand that such graphical representations of data may be subject to small variations, e.g., in peak relative intensities and peak positions due to certain factors such as, but not limited to,Docket No: 102085.002661 - SMI095-W001variations in instrument response and variations in sample concentration and purity, which are well known to the skilled person. Nonetheless, the skilled person would readily be capable of comparing the graphical data in the Figures herein with graphical data generated for an unknown crystal form and confirm whether the two sets of graphical data are characterizing the same crystal form or two different crystal forms. A crystal form of emrusolmin referred to herein as being characterized by graphical data “as depicted in” or “as substantially depicted in” a Figure will thus be understood to include any crystal forms of the emrusolmin characterized with the graphical data having such small variations, as are well known to the skilled person, in comparison with the Figure.

[0070] As used herein, and unless stated otherwise, the term “anhydrous” in relation to crystalline forms of emrusolmin, relates to a crystalline form of emrusolmin which does not include any crystalline water (or other solvents) in a defined, stoichiometric amount within the crystal. Moreover, an “anhydrous” form would generally not contain more than 1% (w / w), of either water or organic solvents as measured for example by TGA.

[0071] “ Co-Crystal” or “Co-crystal” as used herein is defined as a crystalline material including two or more molecules in the same crystalline lattice and associated by non-ionic and non-covalent bonds. In some embodiments, the co-crystal includes two molecules which are in natural state. In an embodiment, the molar ratio between the active pharmaceutical ingredient and the coformer is between 1: 1.5 and 1.5: 1, preferably between 1: 1.25 and 1.25: 1, in other embodiments about 1:1, or in other embodiments about 2:1.

[0072] The term “solvate,” as used herein and unless indicated otherwise, refers to a crystal form that incorporates a solvent in the crystal structure. When the solvent is water, the solvate is often referred to as a “hydrate.” The solvent in a solvate may be present in either a stoichiometric or in a non-stoichiometric amount.

[0073] As used herein, the term “isolated” in reference to crystalline polymorph of emrusolmin of the present disclosure corresponds to a crystalline polymorph of emrusolmin that is physically separated from the reaction mixture in which it is formed.

[0074] As used herein, unless stated otherwise, unit cell data were obtained by solving the crystal structure, unit cell data is preferably measured at 298K.Docket No: 102085.002661 - SMI095-W001

[0075] As used herein, unless stated otherwise, the XRPD measurements are taken using copper Ka radiation wavelength 1.5418 A. XRPD peaks reported herein are measured using CuK a radiation, A. = 1.5418 A, typically at a temperature of 25 ± 3°C.

[0076] As used herein, unless stated otherwise,13C NMR reported herein are measured at 125 MHz at a magic angle spinning frequency cor / n = 11 kHz, preferably at a temperature of at 293 K ± 3°C.

[0077] A thing, e.g., a reaction mixture, may be characterized herein as being at, or allowed to come to “room temperature” or “ambient temperature”, often abbreviated as “RT.” This means that the temperature of the thing is close to, or the same as, that of the space, e.g., the room or fume hood, in which the thing is located. Typically, room temperature is from about 20°C to about 30°C, or about 22°C to about 27°C, or about 25°C.

[0078] The amount of solvent employed in a chemical process, e.g., a reaction or crystallization, may be referred to herein as a number of “volumes” or “vol” or “V.” For example, a material may be referred to as being suspended in 10 volumes (or 10 vol or 10V) of a solvent. In this context, this expression would be understood to mean milliliters of the solvent per gram of the material being suspended, such that suspending a 5 grams of a material in 10 volumes of a solvent means that the solvent is used in an amount of 10 milliliters of the solvent per gram of the material that is being suspended or, in this example, 50 mL of the solvent. In another context, the term “v / v” may be used to indicate the number of volumes of a solvent that are added to a liquid mixture based on the volume of that mixture. For example, adding solvent X (1.5 v / v) to a 100 ml reaction mixture would indicate that 150 mL of solvent X was added.

[0079] A process or step may be referred to herein as being carried out “overnight.” This refers to a time interval, e.g., for the process or step, that spans the time during the night, when that process or step may not be actively observed. This time interval is from about 8 to about 20 hours, or about 10-18 hours, in some cases about 16 hours.

[0080] As used herein, the term “reduced pressure” refers to a pressure that is less than atmospheric pressure. For example, reduced pressure is about 10 mbar to about 50 mbar.

[0081] As used herein and unless indicated otherwise, the term “ambient conditions” refer to atmospheric pressure and a temperature of 22-24°C.

[0082] The solid state form of emrusolmin as described in any aspect or embodiment of the present disclosure may be chemically pure, or substantially free of any other compounds.Docket No: 102085.002661 - SMI095-W001

[0083] As used herein an “aggregation and / or neurodeg enerative diseases” includes but is not limited to Parkinson's disease, multiple system atrophy, Diffuse Lewy body disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localized amyloidosis, beta-2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, Finnish hereditary systemic amyloidosis, and prion disease including Creutzfeldt-Jakob disease, variant Creutzfeldt- Jakob disease, genetic human prion disease, Bovine Spongiform Encephalopathy (BSE) and Scrapie.

[0084] A compound may be referred to herein as chemically pure or purified compound or as substantially free of any other compounds. As used herein, the terms “chemically pure” or “purified” or “substantially free of any other compounds” refer to a compound that is substantially free of any impurities including enantiomers of the subject compound, or other isomers. A chemically pure or purified compound or a compound that is substantially free of any other compound will be understood to mean that it contains about 10% (w / w) or less, about 5% (w / w) or less, about 4% (w / w) or less, about 3% (w / w) or less, about 2% (w / w) or less, about 1.5% (w / w) or less, about 1% (w / w) or less, about 0.8% (w / w) or less, about 0.6% (w / w) or less, about 0.4% (w / w) or less, about 0.2% (w / w) or less, about 0.1% (w / w) or less, or about 0% of any other compound as measured, for example, by HPLC. Alternatively, A chemically pure or purified compound or a compound that is substantially free of any other compound will be understood to mean that it contains about 10% area percent or less, about 5% area percent or less, about 4% area percent or less, about 3% area percent or less, about 2% area percent or less, about 1.5% area percent or less, about 1% area percent or less, about 0.8% area percent or less, about 0.6% area percent or less, about 0.4% area percent or less, about 0.2% area percent or less, about 0.1% area percent or less, or about 0% of any other compound as measured by HPLC.

[0085] Thus, pure or purified emrusolmin described herein as substantially free of any compounds would be understood to contain greater than about 90% (w / w), greater than about 95% (w / w), greater than about 96% (w / w), greater than about 97% (w / w), greater than about 98% (w / w), greater than about 98.5% (w / w), greater than about 99% (w / w), greater than about 99.2% (w / w), greater than about 99.4% (w / w), greater than about 99.6% (w / w), greater thanDocket No: 102085.002661 - SMI095-W001about 99.8% (w / w), greater than about 99.9% (w / w), or about 100% of the subject emrusolmin. Alternatively, pure or purified emrusolmin, described herein as substantially free of any compounds would be understood to contain greater than about 90% area percent, greater than about 95% area percent, greater than about 96% area percent, greater than about 97% area percent, greater than about 98% area percent, greater than about 98.5% area percent, greater than about 99% area percent, greater than about 99.2% area percent, greater than about 99.4% area percent, greater than about 99.6% area percent, greater than about 99.8% area percent, greater than about 99.9% area percent, or about 100% of the subject emrusolmin.Hydrochloride (HCl) Forms

[0086] The present disclosure further encompasses solid state forms of emrusolmin: HCl. In some embodiments, Emrusolmin HCl compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In other embodiments, Emrusolmin HCl Form Hl compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In further embodiments, Emrusolmin HCl Form H2 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability.

[0087] In an embodiment, the solid state form of emrusolmin: HCl may be crystalline emrusolmin: HCl.

[0088] In an embodiment, crystalline emrusolmin: HCl may be emrusolmin HCl salt. Alternatively, crystalline emrusolmin: HCl may be a co-crystal of emrusolmin and HCl.

[0089] The present disclosure includes a crystalline polymorph of emrusolmin: HCl, designated emrusolmin Form Hl. Crystalline Form Hl of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 1; an X-ray powder diffraction having peaks at about 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0090] Crystalline Form Hl of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.5, 14.1, 17.4, 17.9 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta.

[0091] Crystalline Form Hl of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 11.5, 14.1, 17.4, 17.9, 18.9, 19.3, 22.6, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta.Docket No: 102085.002661 - SMI095-W001

[0092] Crystalline Form Hl of emrusolmin: HC1 may be a salt. Alternatively, crystalline Form Hl of emrusolmin: HC1 may be a co-crystal of emrusolmin and HC1.

[0093] The molar ratio between emrusolmin and HC1 in crystalline Form Hl may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0094] The present disclosure includes a crystalline polymorph of emrusolmin: HC1, designated emrusolmin Form H2. Crystalline Form H2 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 2; an X-ray powder diffraction having peaks at about 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0095] Crystalline Form H2 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 13.6, 16.9, 23.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta.

[0096] Crystalline Form H2 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 6.8, 9.5, 13.6, 14.9, 16.2, 16.9, 23.6, 26.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta.

[0097] Crystalline Form H2 of emrusolmin: HC1 may be a salt. Alternatively, crystalline Form H2 of emrusolmin: HC1 may be a co-crystal of emrusolmin and HC1.

[0098] The molar ratio between emrusolmin and HC1 in crystalline Form H2 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0099] According to the disclosure, solid state forms of emrusolmin hydrochloride are provided. In some embodiments, the solid state form of emrusolmin is isolated. In other embodiments, the solid state form of emrusolmin is polymorphically pure.

[0100] In some embodiments, the solid state form is crystalline emrusolmin hydrochloride. In some embodiments, the crystalline emrusolmin hydrochloride is isolated. In other embodiments, the crystalline emrusolmin hydrochloride is polymorphically pure.

[0101] In other embodiments, the solid state form is amorphous emrusolmin hydrochloride. In some embodiments, the amorphous emrusolmin hydrochloride is isolated. In other embodiments, the amorphous emrusolmin hydrochloride is polymorphically pure.Docket No: 102085.002661 - SMI095-W001

[0102] In further embodiments, the solid state form is a co-crystal of emrusolmin and hydrochloric acid. In some embodiments, the co-crystal of emrusolmin and hydrochloric acid is isolated. In other embodiments, the co-crystal of emrusolmin and hydrochloric acid is polymorphically pure.

[0103] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin hydrochloride designated as Form Hl. In some embodiments, Form Hl is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 1 ; an X-ray powder diffraction having peaks at about 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.5, 14.1, 17.4, 17.9 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 11.5, 14.1, 17.4, 17.9, 18.9, 19.3, 22.6, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form Hl is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 1. In some embodiments, Form Hl is characterized by an X-ray powder diffraction having peaks at about 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta. In further embodiments, Form Hl is characterized by an X-ray powder diffraction pattern having peaks at 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.5, 14.1, 17.4, 17.9 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta. In yet other embodiments, Form Hl is characterized by an X-ray powder diffraction pattern having peaks at 11.5, 14.1, 17.4, 17.9, 18.9, 19.3, 22.6, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form Hl is isolated. In other embodiments, the Form Hl is polymorphically pure.

[0104] In still further embodiments, the solid state form is a crystalline polymorph of emrusolmin hydrochloric acid, designated as Form H2. In some embodiments, Form H2 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 2; an X-ray powder diffraction having peaks at about 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 13.6, 16.9, 23.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 6.8,Docket No: 102085.002661 - SMI095-W0019.5, 13.6, 14.9, 16.2, 16.9, 23.6, 26.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form H2 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 2. In some embodiments, Form H2 is characterized by an X-ray powder diffraction having peaks at about 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form H2 is characterized by an X-ray powder diffraction pattern having peaks at 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 13.6, 16.9, 23.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form H2 is characterized by an X-ray powder diffraction pattern having peaks at 6.8, 9.5, 13.6, 14.9, 16.2, 16.9, 23.6, 26.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form H2 is isolated. In other embodiments, the Form H2 is polymorphically pure.

[0105] In some embodiments, the molar ratio between emrusolmin and the hydrochloric acid is between about 2: 1 to about 1:1; or about 1.5:1 to about 1 : 1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Camsylate (CSA) Forms

[0106] The present disclosure further encompasses solid state forms of emrusolmin:CSA.

[0107] In an embodiment, the solid state form of emrusolmin: CSA may be crystalline emrusolmin: CSA.

[0108] In an embodiment, crystalline emrusolmin: CSA may be emrusolmin CSA salt. Alternatively, crystalline emrusolmin: CSA may be a co-crystal of emrusolmin and CSA.

[0109] The present disclosure includes a crystalline polymorph of emrusolmin: CSA, designated Form Cl. Crystalline Form Cl of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 3; an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0110] Crystalline Form Cl of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 8.0, 20.2, 20.7, 21.1 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta.Docket No: 102085.002661 - SMI095-W001

[0111] Crystalline Form Cl of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 8.0, 13.4, 15.1, 16.0, 17.8, 20.2, 20.7, 21.1, 24.5 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta.

[0112] Crystalline Form Cl of emrusolmin: CSA may be a salt. Alternatively, crystalline Form Cl of emrusolmin: CSA may be a co-crystal of emrusolmin and CSA.

[0113] The molar ratio between emrusolmin and CSA in crystalline Form Cl may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0114] According to the disclosure, solid state forms of emrusolmin camsylate are provided. In some embodiments, the solid state form of emrusolmin camsylate is isolated. In other embodiments, the solid state form of emrusolmin camsylate is polymorphically pure.

[0115] In some embodiments, the solid state form is crystalline emrusolmin camsylate. In some embodiments, the crystalline emrusolmin camsylate is isolated. In other embodiments, the crystalline emrusolmin camsylate is polymorphically pure.

[0116] In other embodiments, the solid state form is amorphous emrusolmin camsylate. In some embodiments, the amorphous emrusolmin camsylate is isolated. In other embodiments, the amorphous emrusolmin camsylate is polymorphically pure.

[0117] In further embodiments, the solid state form is a co-crystal of emrusolmin and camphorsulfonic acid. In some embodiments, the co-crystal of emrusolmin and camphorsulfonic acid is isolated. In other embodiments, the co-crystal of emrusolmin and camphorsulfonic acid is polymorphically pure.

[0118] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin camsylate, designated Form Cl. Form Cl is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 3; an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 8.0, 20.2, 20.7, 21.1 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 8.0, 13.4, 15.1, 16.0, 17.8, 20.2, 20.7, 21.1, 24.5 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form Cl is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 3. In someDocket No: 102085.002661 - SMI095-W001embodiments, Form Cl is characterized by an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form Cl is characterized by an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 8.0, 20.2, 20.7, 21.1 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form Cl is characterized by an X-ray powder diffraction pattern having peaks at 8.0, 13.4, 15.1, 16.0, 17.8, 20.2, 20.7, 21.1, 24.5 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form Cl is isolated. In other embodiments, the Form Cl is polymorphically pure.

[0119] In still further embodiments, the solid state form is a crystalline polymorph of emrusolmin camsylate, designated Form C2. In some embodiments, Form C2 is characterized by data selected from one of more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 40; an X-ray powder diffraction having peaks at 5.3, 10.6, 13.8, 18.7 and 22.7 ± 0.2 degrees two-theta; an X-ray powder diffraction pattern having peaks at 5.3, 10.6, 13.8, 18.7 and 22.7 ± 0.2 degrees two-theta and also having one, two, three, or four additional peaks at 16.0, 21.3, 23.3 and 27.7 ± 0.2 degrees two-theta; or an X-ray powder diffraction pattern having peaks at 5.3, 10.6, 13.8, 16.0, 18.7, 21.3, 22.7, 23.3 and 27.7 ± 0.2 degrees two-theta. In some embodiments, Form C2 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 40. In some embodiments, Form C2 is characterized by an X-ray powder diffraction having peaks at 5.3, 10.6, 13.8, 18.7 and 22.7 ± 0.2 degrees two-theta; an X-ray powder diffraction pattern having peaks at 5.3, 10.6, 13.8, 18.7 and 22.7 ± 0.2 degrees two-theta and also having one, two, three, or four additional peaks at 16.0, 21.3, 23.3 and 27.7 ± 0.2 degrees two-theta. In some embodiments, Form C2 is characterized by an X-ray powder diffraction pattern having peaks at 5.3, 10.6, 13.8, 16.0, 18.7, 21.3, 22.7, 23.3 and 27.7 ± 0.2 degrees two-theta. In some embodiments, the Form C2 is isolated. In other embodiments, the Form C2 is polymorphically pure.

[0120] In some embodiments, the molar ratio between emrusolmin and the camphorsulfonic acid is between about 2: 1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Tosylate (TSA) FormsDocket No: 102085.002661 - SMI095-W001

[0121] The present disclosure further encompasses solid state forms of emrusolmin: TSA. In some embodiments, Emrusolmin TSA compared to Emrusolmin base exhibits higher melting point, better morphology and powder properties. In some embodiments, Emrusolmin toluenesulfonic acid (TSA) Form T1 compared to Emrusolmin base exhibits higher melting point, better morphology and powder properties. In some embodiments, Emrusolmin TSA Form T2 compared to Emrusolmin base exhibits higher melting point, better morphology and powder properties. In some embodiments, Emrusolmin TSA Form T4 compared to Emrusolmin base exhibits higher melting point, better morphology and powder properties.

[0122] In an embodiment, the solid state form of emrusolmin: TSA may be crystalline emrusolmin: TSA.

[0123] In an embodiment, crystalline emrusolmin: TSA may be emrusolmin TSA salt. Alternatively, crystalline emrusolmin: TSA may be a co-crystal of emrusolmin and TSA.

[0124] The present disclosure includes a crystalline polymorph of emrusolmin: TSA, designated Form Tl. Crystalline Form T1 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 4; an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0125] Crystalline Form Tl of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.1, 11.4, 15.5, 17.6 and 18.5 degrees 2-theta ± 0.2 degrees 2-theta.

[0126] Crystalline Form Tl of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 9.1, 11.4, 12.1, 13.7, 15.5, 17.6, 18.1, 18.5, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta.

[0127] Crystalline Form Tl of emrusolmin: TSA may be a salt. Alternatively, crystalline Form Tl of emrusolmin: TSA may be a co-crystal of emrusolmin and TSA.

[0128] The molar ratio between emrusolmin and TSA in crystalline Form Tl may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0129] The present disclosure includes a crystalline polymorph of emrusolmin: TSA, designated Form T2. Crystalline Form T2 of emrusolmin may be characterized by data selectedDocket No: 102085.002661 - SMI095-W001from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 5; an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0130] Crystalline Form T2 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.5, 10.2, 14.3, 19.8 and 21.7 degrees 2-theta ± 0.2 degrees 2-theta.

[0131] Crystalline Form T2 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 5.9, 9.5, 10.2, 14.3, 18.8, 19.8, 20.3, 21.7, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta.

[0132] Crystalline Form T2 of emrusolmin: TSA may be a salt. Alternatively, crystalline Form T2 of emrusolmin: TSA may be a co-crystal of emrusolmin and TSA.

[0133] The molar ratio between emrusolmin and TSA in crystalline Form T2 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0134] According to the disclosure, solid state forms of emrusolmin tosylate are provided. In some embodiments, the solid state form of emrusolmin tosylate is isolated. In other embodiments, the solid state form of emrusolmin tosylate is polymorphically pure.

[0135] In some embodiments, the solid state form is crystalline emrusolmin tosylate. In some embodiments, the crystalline emrusolmin tosylate is isolated. In other embodiments, the crystalline emrusolmin tosylate is polymorphically pure.

[0136] In other embodiments, the solid state form is amorphous emrusolmin tosylate. In some embodiments, the amorphous emrusolmin tosylate is isolated. In other embodiments, the amorphous emrusolmin tosylate is polymorphically pure.

[0137] In further embodiments, the solid state form is a co-crystal of emrusolmin and toluene sulfonic acid. In some embodiments, the co-crystal of emrusolmin and toluene sulfonic acid is isolated. In other embodiments, the co-crystal of emrusolmin and toluene sulfonic acid is polymorphically pure.

[0138] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin tosylate, designated Form Tl. In some embodiments, Form T1 is characterized by data selected from one or more of the following: an X-ray powder diffraction patternDocket No: 102085.002661 - SMI095-W001substantially as depicted in FIG. 4; an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.1, 11.4, 15.5, 17.6 and 18.5 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 9.1 , 11.4, 12.1, 13.7, 15.5, 17.6, 18.1, 18.5, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form T1 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 4. In some embodiments, Form T1 is characterized by an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form T1 is characterized by an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.1, 11.4, 15.5, 17.6 and 18.5 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form T1 is characterized by an X-ray powder diffraction pattern having peaks at 9.1 , 11.4, 12.1, 13.7, 15.5, 17.6, 18.1, 18.5, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form T1 is isolated. In other embodiments, the Form T1 is polymorphically pure.

[0139] In still further embodiments, the solid state form is a crystalline polymorph of emrusolmin tosylate, designated Form T2. Form T2 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 5; an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.5, 10.2, 14.3, 19.8 and 21.7 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 5.9, 9.5, 10.2, 14.3, 18.8, 19.8, 20.3, 21.7, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form T2 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 5. In some embodiments, Form T2 is characterized by an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form T2 is characterized by an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.5, 10.2, 14.3, 19.8 and 21.7 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form T2Docket No: 102085.002661 - SMI095-W001is characterized by an X-ray powder diffraction pattern having peaks at 5.9, 9.5, 10.2, 14.3, 18.8, 19.8, 20.3, 21.7, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form T2 is isolated. In other embodiments, the Form T2 is polymorphically pure.

[0140] In other embodiments, the solid state form is a crystalline polymorph of emrusolmin tosylate, designated Form T4. Form T4 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 41; an X-ray powder diffraction pattern having peaks at 13.4, 16.9, 21.9 and 27.5 ± 0.2 degrees two-theta; an X-ray powder diffraction pattern having peaks at 13.4, 16.9, 21.9 and 27.5 ± 0.2 degrees two-theta and also having one, two, three, or four additional peaks at about 9.1, 18.2, 19.4 and 22.6 ± 0.2 degrees two-theta; or an X-ray powder diffraction pattern having peaks at 9.1, 13.4, 16.9, 18.2, 19.4, 21.9, 22.6 and 27.5 ± 0.2 degrees two-theta. In some embodiments, Form T4 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG.41. In some embodiments, Form T4 is characterized by an X-ray powder diffraction pattern having peaks at 13.4, 16.9, 21.9 and 27.5 ± 0.2 degrees two-theta. In some embodiments, Form T4 is characterized by an X-ray powder diffraction pattern having peaks at 13.4, 16.9, 21.9 and 27.5 ± 0.2 degrees two-theta and also having one, two, three, or four additional peaks at about 9.1, 18.2, 19.4 and 22.6 ± 0.2 degrees two-theta. In some embodiments, Form T4 is characterized by or an X-ray powder diffraction pattern having peaks at 9.1, 13.4, 16.9, 18.2, 19.4, 21.9, 22.6 and 27.5 ± 0.2 degrees two-theta. In some embodiments, the Form T4 is isolated. In other embodiments, the Form T4 is polymorphically pure.

[0141] In some embodiments, the molar ratio between emrusolmin and the toluene sulfonic acid is between about 2: 1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Esylate Forms

[0142] The present disclosure further encompasses solid state forms of emrusolmin: esylate. In some embodiments, Emrusolmin Esylate compared to Emrusolmin base exhibits higher melting point and higher water solubility. In some embodiments, Emrusolmin Esylate Form El compared to Emrusolmin base exhibits higher melting point and higher water solubility. In some embodiments, Emrusolmin Esylate Form E2 compared to Emrusolmin base exhibits higher melting point and higher water solubility.Docket No: 102085.002661 - SMI095-W001

[0143] In an embodiment, the solid state form of emrusolmin: esylate may be crystalline emrusolmin: esylate.

[0144] In an embodiment, crystalline emrusolmin: esylate may be emrusolmin esylate salt. Alternatively, crystalline emrusolmin: esylate may be a co-crystal of emrusolmin and esylate.

[0145] The present disclosure includes a crystalline polymorph of emrusolmin: esylate, designated Form El. Crystalline Form El of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 6; an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0100] Crystalline Form El of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 7.3, 10.8, 15.8, 20.2 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta.

[0101] Crystalline Form El of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 7.3, 10.8, 14.9, 15.8, 18.4, 19.8, 20.2, 21.2, 25.0 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta.

[0102] Crystalline Form El of emrusolmin: esylate may be a salt. Alternatively, crystalline Form El of emrusolmin: esylate may be a co-crystal of emrusolmin and esylate.

[0103] The molar ratio between emrusolmin and esylate in crystalline Form El may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0104] The present disclosure includes a crystalline polymorph of emrusolmin: esylate, designated Form E2. Crystalline Form E2 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 7; an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0105] Crystalline Form E2 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.5, 12.0, 18.5, 22.5 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta.Docket No: 102085.002661 - SMI095-W001

[0106] Crystalline Form E2 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 9.9, 10.5, 12.0, 17.7, 18.5, 19.3, 22.5, 24.7, 26.6 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta.

[0107] Crystalline Form E2 of emrusolmin: esylate may be a salt. Alternatively, crystalline Form E2 of emrusolmin: esylate may be a co-crystal of emrusolmin and esylate.

[0108] The molar ratio between emrusolmin and esylate in crystalline Form E2 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0109] According to the disclosure, solid state forms of emrusolmin esylate are provided. In some embodiments, the solid state form of emrusolmin esylate is isolated. In other embodiments, the solid state form of emrusolmin esylate is polymorphically pure.

[0110] In some embodiments, the solid state form of emrusolmin esylate is crystalline emrusolmin esylate. In some embodiments, the crystalline emrusolmin esylate is isolated. In other embodiments, the crystalline emrusolmin esylate is polymorphically pure.

[0111] In other embodiments, the solid state form of emrusolmin esylate is amorphous emrusolmin esylate. In some embodiments, the amorphous emrusolmin esylate is isolated. In other embodiments, the amorphous emrusolmin esylate is polymorphically pure.

[0112] In further embodiments, the solid state form of emrusolmin esylate is a cocrystal of emrusolmin and ethanesulfonic acid. In some embodiments, the co-crystal of emrusolmin and ethanesulfonic acid is isolated. In other embodiments, the co-crystal of emrusolmin and ethanesulfonic acid is polymorphically pure.

[0113] In yet other embodiments, the solid state form of emrusolmin esylate is a crystalline polymorph of emrusolmin esylate, designated Form El. Form El is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 6; an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 7.3, 10.8, 15.8, 20.2 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.3, 10.8, 14.9, 15.8, 18.4, 19.8, 20.2, 21.2, 25.0 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form El is characterized by an X-ray powder diffraction pattern substantially asDocket No: 102085.002661 - SMI095-W001depicted in FIG. 6. In some embodiments, Form El is characterized by an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form El is characterized by an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 7.3, 10.8, 15.8, 20.2 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form El is characterized by an X-ray powder diffraction pattern having peaks at 7.3, 10.8, 14.9, 15.8, 18.4, 19.8, 20.2, 21.2, 25.0 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form El is isolated. In other embodiments, the Form El is polymorphically pure.

[0114] In yet further embodiments, the solid state form of emrusolmin esylate is a crystalline polymorph of emrusolmin esylate, designated Form E2. Form E2 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 7; an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.5, 12.0, 18.5, 22.5 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 9.9, 10.5, 12.0, 17.7, 18.5, 19.3, 22.5, 24.7, 26.6 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form E2 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 7. In some embodiments, Form E2 is characterized by an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form E2 is characterized by an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.5, 12.0, 18.5, 22.5 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form E2 is characterized by an X-ray powder diffraction pattern having peaks at 9.9, 10.5, 12.0, 17.7, 18.5, 19.3, 22.5, 24.7, 26.6 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form E2 is isolated. In other embodiments, the Form E2 is polymorphically pure.

[0146] In some embodiments, the molar ratio between emrusolmin and the ethanesulfonic acid is between about 2: 1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Docket No: 102085.002661 - SMI095-W001Edisylate Forms

[0115] The present disclosure further encompasses solid state forms of emrusolmin: edisylate. In some embodiments, Emrusolmin Edisylate compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In some embodiments, Emrusolmin Edisylate Form ESI compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In other embodiments, Emrusolmin Edisylate Form ES2 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In further embodiments, Emrusolmin Edisylate Form ES3 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In yet other embodiments, Emrusolmin Edisylate Form ES4 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In still further embodiments, Emrusolmin Edisylate Form ES5 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In other embodiments, Emrusolmin Edisylate Form ES6 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In further embodiments, Emrusolmin Edisylate Form ES7 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In yet other embodiments, Emrusolmin Edisylate Form ES8 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability.

[0116] In an embodiment, the solid state form of emrusolmin: edisylate may be crystalline emrusolmin: edisylate.

[0117] In an embodiment, crystalline emrusolmin: edisylate may be emrusolmin edisylate salt. Alternatively, crystalline emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0118] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ESI. Crystalline Form ESI of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 8; an X-ray powder diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0119] Crystalline Form ESI of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2Docket No: 102085.002661 - SMI095-W001degrees 2-theta, and also having one, two, three, four or five additional peaks at 15.7, 18.5, 20.6, 22.6 and 23.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0120] Crystalline Form ESI of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 11.8, 15.7, 16.5, 18.5, 20.6, 21.0, 22.6, 23.1, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta.

[0121] Crystalline Form ESI of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ESI of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0122] The molar ratio between emrusolmin and edisylate in crystalline Form ESI may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0123] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ES2. Crystalline Form ES2 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 9; an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0124] Crystalline Form ES2 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.1, 14.5, 14.9, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0125] Crystalline Form ES2 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 8.0, 11.1, 13.5, 14.5, 14.9, 17.9, 18.5, 24.2, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0126] Crystalline Form ES2 of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ES2 of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0127] The molar ratio between emrusolmin and edisylate in crystalline Form ES2 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0128] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ES3. Crystalline Form ES3 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction patternDocket No: 102085.002661 - SMI095-W001substantially as depicted in FIG. 10; an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0129] Crystalline Form ES3 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 12.7, 20.0, 20.4, 21.4 and 28.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0130] Crystalline Form ES3 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 10.0, 12.7, 14.0, 15.7, 17.2, 20.0, 20.4, 21.4, 23.7 and 28.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0131] Crystalline Form ES3 of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ES3 of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0132] The molar ratio between emrusolmin and edisylate in crystalline Form ES3 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0133] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ES4. Crystalline Form ES4 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 11; an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0134] Crystalline Form ES4 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 13.6, 25.2 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta.

[0135] Crystalline Form ES4 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 13.6, 17.6, 24.0, 25.2, 26.7 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta.

[0136] Crystalline Form ES4 of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ES4 of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0137] The molar ratio between emrusolmin and edisylate in crystalline Form ES4 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Docket No: 102085.002661 - SMI095-W001

[0138] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ES5. Crystalline Form ES5 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 12; an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0139] Crystalline Form ES5 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 7.6, 18.3, 20.7, 22.9 degrees 2-theta ± 0.2 degrees 2-theta.

[0140] Crystalline Form ES5 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 7.6, 10.4, 18.3, 20.7, 21.5, 22.4, 22.9 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta.

[0141] Crystalline Form ES5 of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ES5 of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0142] The molar ratio between emrusolmin and edisylate in crystalline Form ES5 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0143] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ES6. Crystalline Form ES6 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 13; an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0144] Crystalline Form ES6 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 15.2, 18.0 and 19.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0145] Crystalline Form ES6 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 7.4, 11.5 14.2, 15.2, 18.0 and 19.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0146] Crystalline Form ES6 of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ES6 of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.Docket No: 102085.002661 - SMI095-W001

[0147] The molar ratio between emrusolmin and edisylate in crystalline Form ES6 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0148] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ES7. Crystalline Form ES7 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 14; an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0149] Crystalline Form ES7 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one peak at 20.3 degrees 2-theta ± 0.2 degrees 2-theta.

[0150] Crystalline Form ES7 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 20.3, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta.

[0151] Crystalline Form ES7 of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ES7 of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0152] The molar ratio between emrusolmin and edisylate in crystalline Form ES7 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0153] The present disclosure includes a crystalline polymorph of emrusolmin: edisylate, designated Form ES8. Crystalline Form ES8 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 15; an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0154] Crystalline Form ES8 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 10.8, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2-theta.

[0155] Crystalline Form ES8 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 10.8, 17.4, 18.3, 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta.Docket No: 102085.002661 - SMI095-W001

[0156] Crystalline Form ES8 of emrusolmin: edisylate may be a salt. Alternatively, crystalline Form ES8 of emrusolmin: edisylate may be a co-crystal of emrusolmin and edisylate.

[0157] The molar ratio between emrusolmin and edisylate in crystalline Form ES8 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0158] According to the disclosure, solid state forms of emrusolmin edisylate are provided. In some embodiments, the solid state form of emrusolmin edisylate is isolated. In other embodiments, the solid state form of emrusolmin edisylate is polymorphically pure.

[0159] In some embodiments, the solid state form is crystalline emrusolmin edisylate. In some embodiments, the crystalline emrusolmin edisylate is isolated. In other embodiments, the crystalline emrusolmin edisylate is polymorphically pure.

[0160] In other embodiments, the solid state form is amorphous emrusolmin edisylate. In some embodiments, the amorphous emrusolmin edisylate is isolated. In other embodiments, the amorphous emrusolmin edisylate is polymorphically pure.

[0161] In further embodiments, the solid state form is a co-crystal of emrusolmin and ethanedisulfonic acid. In some embodiments, the co-crystal of emrusolmin and ethanedisulfonic acid is isolated. In other embodiments, the co-crystal of emrusolmin and ethanedisulfonic acid is polymorphically pure.

[0162] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ESI. In some embodiments, Form ESI is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 8; an X-ray powder diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 15.7, 18.5, 20.6, 22.6 and 23.1 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 11.8, 15.7, 16.5, 18.5, 20.6, 21.0, 22.6, 23.1, 23.8 and 25.9 degrees 2-theta± 0.2 degrees 2-theta. In some embodiments, Form ESI is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 8. In some embodiments, Form ESI is characterized by an X-ray powder diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ESI is characterized by an X-ray powderDocket No: 102085.002661 - SMI095-W001diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 15.7, 18.5, 20.6, 22.6 and 23.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ESI is characterized by an X-ray powder diffraction pattern having peaks at 11.8, 15.7, 16.5, 18.5, 20.6, 21.0, 22.6, 23.1, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ESI is isolated. In other embodiments, the ESI is polymorphically pure.

[0163] In still further embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ES2. In some embodiments, Form ES2 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 9; an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.1, 14.5, 14.9, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 8.0, 11.1, 13.5, 14.5, 14.9, 17.9, 18.5, 24.2, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES2 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 9. In some embodiments, Form ES2 is characterized by an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.1, 14.5, 14.9, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES2 is characterized by an X-ray powder diffraction pattern having peaks at 8.0, 11.1, 13.5, 14.5, 14.9, 17.9, 18.5, 24.2, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ES2 is isolated. In other embodiments, the ES2 is polymorphically pure.

[0164] In other embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ES3. In some embodiments, Form ES3 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 10; an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 12.7, 20.0, 20.4, 21.4 and 28.1Docket No: 102085.002661 - SMI095-W001degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 10.0, 12.7, 14.0, 15.7, 17.2, 20.0, 20.4, 21.4, 23.7 and 28.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES3 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 10. In some embodiments, Form ES3 is characterized by an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES3 is characterized by an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 12.7, 20.0, 20.4, 21.4 and 28.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES3 is characterized by an X-ray powder diffraction pattern having peaks at 10.0, 12.7, 14.0, 15.7, 17.2, 20.0, 20.4, 21.4, 23.7 and 28.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ES3 is isolated. In other embodiments, the ES3 is polymorphically pure.

[0165] In further embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ES4. In some embodiments, Form ES4 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 11; an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 13.6, 25.2 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 13.6, 17.6, 24.0, 25.2, 26.7 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, form ES4 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 11. In some embodiments, Form ES4 is characterized by an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES4 is characterized by an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 13.6, 25.2 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES4 is characterized by an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 13.6, 17.6, 24.0, 25.2, 26.7 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ES4 is isolated. In other embodiments, the ES4 is polymorphically pure.DocketNo: 102085.002661 - SMI095-W001

[0166] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ES5. In some embodiments, Form ES5 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 12; an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 7.6, 18.3, 20.7, 22.9 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.6, 10.4, 18.3, 20.7, 21.5, 22.4, 22.9 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES5 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 12. In some embodiments, Form ES5 is characterized by an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES5 is characterized by an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 7.6, 18.3, 20.7, 22.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES5 is characterized by an X-ray powder diffraction pattern having peaks at 7.6, 10.4, 18.3, 20.7, 21.5, 22.4, 22.9 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ES5 is isolated. In other embodiments, the ES5 is polymorphically pure.

[0167] In still further embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ES6. In some embodiments, Form ES6 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 13; an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 15.2, 18.0 and 19.1 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.4, 11.5 14.2, 15.2, 18.0 and 19.1 degrees 2-theta± 0.2 degrees 2-theta. In some embodiments, Form ES6 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 13. In some embodiments, Form ES6 is characterized by an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES6 is characterized by an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-Docket No: 102085.002661 - SMI095-W001theta, and also having one, two or three additional peaks at 15.2, 18.0 and 19.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES6 is characterized by an X-ray powder diffraction pattern having peaks at 7.4, 11.5 14.2, 15.2, 18.0 and 19.1 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ES6 is isolated. In other embodiments, the ES6 is polymorphically pure.

[0168] In other embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ES7. In some embodiments, Form ES7 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 14; an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one peak at 20.3 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 20.3, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES7 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 14. In some embodiments, Form ES7 is characterized by an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES7 is characterized by an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one peak at 20.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES7 is characterized by an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 20.3, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ES7 is isolated. In other embodiments, the ES7 is polymorphically pure.

[0169] In further embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form ES8. In some embodiments, Form ES8 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 15; an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 10.8, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 10.8, 17.4, 18.3, 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES8Docket No: 102085.002661 - SMI095-W001is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 15. In some embodiments, Form ES8 is characterized by an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES8 is characterized by an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 10.8, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form ES8 is characterized by an X-ray powder diffraction pattern having peaks at 10.8, 17.4, 18.3, 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the ES8 is isolated. In other embodiments, the ES8 is polymorphically pure.

[0170] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin edisylate, designated Form HE1. Form HE1 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 39; an X-ray powder diffraction pattern having peaks at 13.6, 17.6, 24.0, 25.4 and 26.7 ± 0.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 13.6, 17.6, 24.0, 25.4 and 26.7 ± 0.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four, or five additional peaks at 16.7, 20.4, 21.7, 22.5 and 27.3 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 13.6, 16.7, 17.6, 20.4, 21.7, 22.5, 24.0, 25.4, 26.7, and 27.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form HE1 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 39. In some embodiments, Form HE1 is characterized by an X-ray powder diffraction pattern having peaks at 13.6, 17.6, 24.0, 25.4 and 26.7 ± 0.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form HE1 is characterized by an X-ray powder diffraction pattern having peaks at 13.6, 17.6, 24.0, 25.4 and 26.7 ± 0.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four, or five additional peaks at 16.7, 20.4, 21.7, 22.5 and 27.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form HE1 is characterized by an X-ray powder diffraction pattern having peaks at 13.6, 16.7, 17.6, 20.4, 21.7, 22.5, 24.0, 25.4, 26.7, and 27.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form HE1 is isolated. In other embodiments, the Form HE1 is polymorphically pure.

[0147] In some embodiments, the molar ratio between emrusolmin and the ethanedisulfonic acid is between about 2: 1 to about 1 : 1 ; or about 1.5:1 to about 1 : 1.5 or about 1.1:1 to about 1:1.1, such as about 1:1, or such as about 2:1.Docket No: 102085.002661 - SMI095-W001Tartarate Forms

[0171] The present disclosure further encompasses solid state forms of emrusolmin: tartarate.

[0172] In an embodiment, the solid state form of emrusolmin: tartarate may be crystalline emrusolmin: tartarate.

[0173] In an embodiment, crystalline emrusolmin: tartarate may be emrusolmin tartarate salt. Alternatively, crystalline emrusolmin: tartarate may be a co-crystal of emrusolmin and tartarate.

[0174] The present disclosure includes a crystalline polymorph of emrusolmin: tartarate, designated Form TAI. Crystalline Form TAI of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 16; an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0175] Crystalline Form TAI of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 9.2, 13.2, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2-theta.

[0176] Crystalline Form TAI of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 9.2, 13.2, 17.1, 17.4 and 18.3, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta.

[0177] Crystalline Form TAI of emrusolmin: tartarate may be a salt. Alternatively, crystalline Form TAI of emrusolmin: tartarate may be a co-crystal of emrusolmin and tartarate.

[0178] The molar ratio between emrusolmin and tartarate in crystalline Form TAI may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0179] According to the disclosure, solid state forms of emrusolmin tartarate are provided. In some embodiments, the solid state form of emrusolmin tartarate is isolated. In other embodiments, the solid state form of emrusolmin tartarate is polymorphically pure.

[0180] In some embodiments, solid state form is crystalline emrusolmin tartarate. In some embodiments, the crystalline emrusolmin tartarate is isolated. In other embodiments, the crystalline emrusolmin tartarate is polymorphically pure.Docket No: 102085.002661 - SMI095-W001

[0181] In other embodiments, the solid state form is amorphous emrusolmin tartarate. In some embodiments, the amorphous emrusolmin tartarate is isolated. In other embodiments, the amorphous emrusolmin tartarate is polymorphically pure.

[0182] In further embodiments, the solid state form is a co-crystal of emrusolmin and tartaric acid. In some embodiments, the co-crystal of emrusolmin and tartaric acid is isolated. In other embodiments, the co-crystal of emrusolmin and tartaric acid is polymorphically pure.

[0183] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin tartarate, designated Form TAI. In some embodiments, Form TAI is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 16; an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 9.2, 13.2, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 9.2, 13.2, 17.1, 17.4 and 18.3, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form TAI is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 16. In some embodiments, Form TAI is characterized by an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form TAI is characterized by an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 9.2, 13.2, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form TAI is characterized by an X-ray powder diffraction pattern having peaks at 9.2, 13.2, 17.1, 17.4 and 18.3, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the TAI is isolated. In other embodiments, the TAI is polymorphically pure.

[0148] In some embodiments, the molar ratio between emrusolmin and the tartaric acid is between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Mesylate Forms

[0184] The present disclosure further encompasses solid state forms of emrusolmin: mesylate. In some embodiments, Emrusolmin Mesylate compared to Emrusolmin base exhibits higher water solubility. In some embodiments, Emrusolmin Mesylate Form MSI compared toDocket No: 102085.002661 - SMI095-W001Emrusolmin base exhibits higher water solubility. In some embodiments, Emrusolmin Mesylate Form MS2 compared to Emrusolmin base exhibits higher water solubility.

[0185] In an embodiment, the solid state form of emrusolmin: mesylate may be crystalline emrusolmin: mesylate.

[0186] In an embodiment, crystalline emrusolmin: mesylate may be emrusolmin mesylate salt. Alternatively, crystalline emrusolmin: mesylate may be a co-crystal of emrusolmin and mesylate.

[0187] The present disclosure includes a crystalline polymorph of emrusolmin: mesylate, designated Form MSI. Crystalline Form MSI of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 17; an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0188] Crystalline Form MSI of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.1, 16.1, 20.8, 22.2 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta.

[0189] Crystalline Form MSI of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 6.7, 10.1, 11.2, 13.9, 16.1, 20.2, 20.8, 22.2, 24.0 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta.

[0190] Crystalline Form MSI of emrusolmin: mesylate may be a salt. Alternatively, crystalline Form MSI of emrusolmin: mesylate may be a co-crystal of emrusolmin and mesylate.

[0191] The molar ratio between emrusolmin and mesylate in crystalline Form MSI may be between about 2: 1 to about 1:1; or about 1.5:1 to about 1 : 1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0192] The present disclosure includes a crystalline polymorph of emrusolmin: mesylate, designated Form MS2. Crystalline Form MS2 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 18; an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0193] Crystalline Form MS2 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2Docket No: 102085.002661 - SMI095-W001degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.7, 19.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta.

[0194] Crystalline Form MS2 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7, 17.7, 19.6, 20.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta.

[0195] Crystalline Form MS2 of emrusolmin: mesylate may be a salt. Alternatively, crystalline Form MS2 of emrusolmin: mesylate may be a co-crystal of emrusolmin and mesylate.

[0196] The molar ratio between emrusolmin and mesylate in crystalline Form MS2 may be between about 2: 1 to about 1:1; or about 1.5:1 to about 1 : 1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0197] According to the disclosure, solid state forms of emrusolmin mesylate are provided. In some embodiments, the solid state form of emrusolmin mesylate is isolated. In other embodiments, the solid state for of emrusolmin mesylate is polymorphically pure.

[0198] In some embodiments, the solid state form is crystalline emrusolmin mesylate. In some embodiments, the crystalline emrusolmin mesylate is isolated. In other embodiments, the crystalline emrusolmin mesylate is polymorphically pure.

[0199] In other embodiments, the solid state form is amorphous emrusolmin mesylate. In some embodiments, the amorphous emrusolmin mesylate is isolated. In other embodiments, the amorphous emrusolmin mesylate is polymorphically pure.

[0200] In further embodiments, the solid state form is a co-crystal of emrusolmin and methansulfonic acid. In some embodiments, the co-crystal of emrusolmin and methansulfonic acid is isolated. In other embodiments, the co-crystal of emrusolmin and methansulfonic acid is polymorphically pure.

[0201] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin mesylate, designated Form MSI. In some embodiments, Form MSI is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 17; an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.1, 16.1, 20.8, 22.2 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 6.7,Docket No: 102085.002661 - SMI095-W00110.1, 11.2, 13.9, 16.1, 20.2, 20.8, 22.2, 24.0 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form MSI is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 17. In some embodiments, Form MSI is characterized by an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form MSI is characterized by an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.1, 16.1, 20.8, 22.2 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form MSI is characterized by an X-ray powder diffraction pattern having peaks at 6.7, 10.1, 11.2, 13.9, 16.1, 20.2, 20.8, 22.2, 24.0 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the MSI is isolated. In other embodiments, the MSI is polymorphically pure.

[0202] In still further embodiments, the solid state form is a crystalline polymorph of emrusolmin mesylate, designated Form MS2. In some embodiments, Form MS2 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 18; an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.7, 19.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7, 17.7, 19.6, 20.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form MS2 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 18. In some embodiments, Form MS2 is characterized by an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form MS2 is characterized by an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.7, 19.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form MS2 is characterized by an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7, 17.7, 19.6, 20.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the MS2 is isolated. In other embodiments, the MS2 is polymorphically pure.Docket No: 102085.002661 - SMI095-W001

[0149] In some embodiments, the molar ratio between emrusolmin and the methanesulfonic acid is between about 2: 1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Bromide Forms

[0203] The present disclosure further encompasses solid state forms of emrusolmin: hydrobromide. In some embodiments, Emrusolmin Hydrobromide compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In some embodiments, Emrusolmin Hydrobromide Form Bl compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In some embodiments, Emrusolmin Hydrobromide Form B2 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In some embodiments, Emrusolmin Hydrobromide Form B3 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability.

[0204] In an embodiment, the solid state form of emrusolmin: bromide may be crystalline emrusolmin: bromide.

[0205] In an embodiment, crystalline emrusolmin: bromide may be emrusolmin hydrobromide bromide salt. Alternatively, crystalline emrusolmin: bromide may be a co-crystal of emrusolmin and bromide.

[0206] The present disclosure includes a crystalline polymorph of emrusolmin: hydrobromide, designated Form Bl. Crystalline Form Bl of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 19; an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0207] Crystalline Form Bl of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 6.6, 13.6, 19.2, 24.0 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta.

[0208] Crystalline Form Bl of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 6.6, 12.8, 13.6, 19.2, 19.9, 20.9, 21.7, 24.0, 25.8 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta.Docket No: 102085.002661 - SMI095-W001

[0209] Crystalline Form Bl of emrusolmin: hydrobromide may be a salt. Alternatively, crystalline Form Bl of emrusolmin: hydrobromide may be a co-crystal of emrusolmin and bromide.

[0210] The molar ratio between emrusolmin and bromide in crystalline Form Bl may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0211] The present disclosure includes a crystalline polymorph of emrusolmin: hydrobromide, designated Form B2. Crystalline Form B2 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 20; an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0212] Crystalline Form B2 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.2, 19.2, 23.7, 24.5 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta.

[0213] Crystalline Form B2 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 17.2, 19.2, 21.2, 22.8, 23.7, 24.5, 25.4 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta.

[0214] Crystalline Form B2 of emrusolmin: hydrobromide may be a salt. Alternatively, crystalline Form B2 of emrusolmin: bromide may be a co-crystal of emrusolmin and bromide.

[0215] The molar ratio between emrusolmin and bromide in crystalline Form B2 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0216] The present disclosure includes a crystalline polymorph of emrusolmin: hydrobromide, designated Form B3. Crystalline Form B3 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 21; an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0217] Crystalline Form B3 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2Docket No: 102085.002661 - SMI095-W001degrees 2-theta, and also having one, two or three additional peaks at 12.2, 23.4 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta.

[0218] Crystalline Form B3 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 12.2, 14.8, 16.9, 20.4, 23.023.4, 30.5 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta.

[0219] Crystalline Form B3 of emrusolmin: hydrobromide may be a salt. Alternatively, crystalline Form B3 of emrusolmin: hydrobromide may be a co-crystal of emrusolmin and bromide.

[0220] The molar ratio between emrusolmin and hydrobromide in crystalline Form B3 may be between about 2: 1 to about 1:1; or about 1.5:1 to about 1 : 1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0221] According to the disclosure, solid state forms of emrusolmin hydrobromide are provided. In some embodiments, the solid state form of emrusolmin hydrobromide is isolated. In other embodiments, the solid state form of emrusolmin hydrobromide is polymorphically pure.

[0222] In some embodiments, the solid state form is crystalline emrusolmin. hydrobromide. In some embodiments, the crystalline emrusolmin hydrobromide is isolated. In other embodiments, the crystalline emrusolmin hydrobromide is polymorphically pure.

[0223] In other embodiments, the solid state form is amorphous emrusolmin hydrobromide. In some embodiments, the amorphous emrusolmin hydrobromide is isolated. In other embodiments, the amorphous emrusolmin hydrobromide is polymorphically pure.

[0224] In further embodiments, the solid state form is a co-crystal of emrusolmin and hydrobromic acid. In some embodiments, the co-crystal of emrusolmin and hydrobromic acid is isolated. In other embodiments, the co-crystal of emrusolmin and hydrobromic acid is polymorphically pure.

[0225] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin hydrobromide, designated Form Bl. In some embodiments, Form Bl is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 19; an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 6.6, 13.6, 19.2, 24.0 and 27.2 degreesDocket No: 102085.002661 - SMI095-W0012-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 6.6, 12.8, 13.6, 19.2, 19.9, 20.9, 21.7, 24.0, 25.8 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form Bl is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 19. In some embodiments, Form Bl is characterized by an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form Bl is characterized by an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 6.6, 13.6, 19.2, 24.0 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form Bl is characterized by an X-ray powder diffraction pattern having peaks at 6.6, 12.8, 13.6, 19.2, 19.9, 20.9, 21.7, 24.0, 25.8 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form Bl is isolated. In other embodiments, the Form Bl is polymorphically pure.

[0226] In still further embodiments, the solid state form is a crystalline polymorph of emrusolmin hydrobromide, designated Form B2. In some embodiments, Form B2 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 20; an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.2, 19.2, 23.7, 24.5 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 17.2, 19.2, 21.2, 22.8, 23.7, 24.5, 25.4 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form B2 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 20. In some embodiments, Form B2 is characterized by an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form B2 is characterized by an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.2, 19.2, 23.7, 24.5 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form B2 is characterized by an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 17.2, 19.2, 21.2, 22.8, 23.7, 24.5, 25.4 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form B2 is isolated. In other embodiments, the Form B2 is polymorphically pure.Docket No: 102085.002661 - SMI095-W001

[0227] In other embodiments, the solid state form is a crystalline polymorph of emrusolmin hydrobromide, designated Form B3. In some embodiments, Form B3 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 21; an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 12.2, 23.4 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 12.2, 14.8, 16.9, 20.4, 23.023.4, 30.5 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form B3 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 21. In some embodiments, Form B3 is characterized by an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form B3 is characterized by an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 12.2, 23.4 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form B3 is characterized by an X-ray powder diffraction pattern having peaks at 12.2, 14.8, 16.9, 20.4, 23.023.4, 30.5 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, the Form B3 is isolated. In other embodiments, the Form B3 is polymorphically pure.

[0150] In some embodiments, the molar ratio between emrusolmin and the hydrobromic acid is between about 2: 1 to about 1:1; or about 1.5:1 to about 1 : 1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.Besylate Salts

[0228] The present disclosure further encompasses solid state forms of emrusolmin: besylate. In some embodiments, Emrusolmin Besylate compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability. In some embodiments, Emrusolmin Besylate Form BS1 compared to Emrusolmin base exhibits higher water solubility, better morphology and better filterability.

[0229] In an embodiment, the solid state form of emrusolmin: besylate may be crystalline emrusolmin: besylate.Docket No: 102085.002661 - SMI095-W001

[0230] In an embodiment, crystalline emrusolmin: besylate may be emrusolmin besylate salt. Alternatively, crystalline emrusolmin: besylate may be a co-crystal of emrusolmin and besylate.

[0231] The present disclosure includes a crystalline polymorph of emrusolmin: besylate, designated Form BS1. The crystalline Form BS1 of emrusolmin may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 22; an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0232] Crystalline Form BS1 of emrusolmin may be further characterized by an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 8.6, 10.5, 21.5 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta.

[0233] Crystalline Form BS1 of emrusolmin may be alternatively characterized by an X-ray powder diffraction pattern having peaks at 8.6, 10.5, 11.3, 18.7, 21.5, 22.6, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta.

[0234] Crystalline Form BS1 of emrusolmin: besylate may be a salt. Alternatively, crystalline Form BS1 of emrusolmin: besylate may be a co-crystal of emrusolmin and besylate.

[0235] The molar ratio between emrusolmin and besylate in crystalline Form BS1 may be between about 2:1 to about 1:1; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0236] According to the disclosure, solid state forms of emrusolmin besylate are provided. In some embodiments, the solid state form of emrusolmin besylate is isolated. In other embodiments, the solid state form of emrusolmin besylate is polymorphically pure.

[0237] In some embodiments, the solid state form is crystalline emrusolmin besylate. In some embodiments, the crystalline emrusolmin besylate is isolated. In other embodiments, the crystalline emrusolmin besylate is polymorphically pure.

[0238] In other embodiments, the solid state form is amorphous emrusolmin besylate. In some embodiments, the amorphous emrusolmin besylate is isolated. In other embodiments, the amorphous emrusolmin besylate is polymorphically pure.

[0239] In further embodiments, the solid state form is a co-crystal of emrusolmin and benzenesulfonic acid. In some embodiments, the co-crystal of emrusolmin and benzenesulfonicDocket No: 102085.002661 - SMI095-W001acid is isolated. In other embodiments, the co-crystal of emrusolmin and benzenesulfonic acid is polymorphically pure.

[0240] In yet other embodiments, the solid state form is a crystalline polymorph of emrusolmin besylate, designated Form BS1. In some embodiments, Form BS1 is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 22; an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 8.6, 10.5, 21.5 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 8.6, 10.5, 11.3, 18.7, 21.5, 22.6, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form BS1 is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 22. In some embodiments, Form BS1 is characterized by an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form BS1 is characterized by an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 8.6, 10.5, 21.5 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta. In some embodiments, Form BS1 is characterized by an X-ray powder diffraction pattern having peaks at 8.6, 10.5, 11.3, 18.7, 21.5, 22.6, 24.1, 25.9 and 26.9 degrees 2-theta± 0.2 degrees 2-theta. In some embodiments, the Form BS1 is isolated. In other embodiments, the Form BS1 is polymorphically pure.

[0151] In some embodiments, the molar ratio between emrusolmin and the benzenesulfonic acid is between about 2: 1 to about 1:1; or about 1.5:1 to about 1 : 1.5 or about 1.1:1 to about 1:1.1, and preferably 1:1.

[0241] In any aspect or embodiment of the present disclosure, crystalline Form Hl of emrusolmin may be isolated. Particularly, crystalline Form Hl of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0242] In any aspect or embodiment crystalline Form Hl of emrusolmin may be polymorphically pure.Docket No: 102085.002661 - SMI095-W001

[0243] In any aspect or embodiment crystalline Form Hl of emrusolmin may be anhydrous.

[0244] Alternatively, in any aspect or embodiment crystalline Form Hl of emrusolmin may be a hydrate.

[0245] In any aspect or embodiment of the present disclosure, crystalline Form H2 of emrusolmin may be isolated. Particularly, crystalline Form H2 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0246] In any aspect or embodiment crystalline Form H2 of emrusolmin may be polymorphically pure.

[0247] In any aspect or embodiment of the present disclosure, crystalline Form Cl of emrusolmin may be isolated. Particularly, crystalline Form Cl of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0248] In any aspect or embodiment crystalline Form Cl of emrusolmin may be polymorphically pure.

[0249] In any aspect or embodiment crystalline Form Cl of emrusolmin may be a hydrate.

[0250] In any aspect or embodiment of the present disclosure, crystalline Form C2 of emrusolmin may be isolated. Particularly, crystalline Form C2 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0251] In any aspect or embodiment crystalline Form C2 of emrusolmin may be polymorphically pure.

[0252] In any aspect or embodiment crystalline Form C2 of emrusolmin may be a hydrate.

[0253] In any aspect or embodiment of the present disclosure, crystalline Form T1 of emrusolmin may be isolated. Particularly, crystalline Form T1 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0254] In any aspect or embodiment crystalline Form T1 of emrusolmin may be polymorphically pure.

[0255] In any aspect or embodiment of the present disclosure, crystalline Form T2 of emrusolmin may be isolated. Particularly, crystalline Form T2 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.Docket No: 102085.002661 - SMI095-W001

[0256] In any aspect or embodiment crystalline Form T2 of emrusolmin may be polymorphically pure.

[0257] In any aspect or embodiment crystalline Form T2 of emrusolmin may be anhydrous.

[0258] In any aspect or embodiment of the present disclosure, crystalline Form T4 of emrusolmin may be isolated. Particularly, crystalline Form T4 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0259] In any aspect or embodiment crystalline Form T4 of emrusolmin may be polymorphically pure.

[0260] In any aspect or embodiment crystalline Form T4 of emrusolmin may be anhydrous.

[0261] In any aspect or embodiment of the present disclosure, crystalline Form El of emrusolmin may be isolated. Particularly, crystalline Form El of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0262] In any aspect or embodiment crystalline Form El of emrusolmin may be polymorphically pure.

[0263] In any aspect or embodiment crystalline Form El of emrusolmin may be anhydrous.

[0264] In any aspect or embodiment of the present disclosure, crystalline Form E2 of emrusolmin may be isolated. Particularly, crystalline Form E2 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0265] In any aspect or embodiment crystalline Form E2 of emrusolmin may be polymorphically pure.

[0266] In any aspect or embodiment of the present disclosure, crystalline Form ESI of emrusolmin may be isolated. Particularly, crystalline Form ESI of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0267] In any aspect or embodiment crystalline Form ESI of emrusolmin may be polymorphically pure.

[0268] In any aspect or embodiment crystalline Form ESI of emrusolmin may be a hydrate.Docket No: 102085.002661 - SMI095-W001

[0269] In any aspect or embodiment of the present disclosure, crystalline Form ES2 of emrusolmin may be isolated. Particularly, crystalline Form ES2 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0270] In any aspect or embodiment crystalline Form ES2 of emrusolmin may be polymorphically pure.

[0271] In any aspect or embodiment of the present disclosure, crystalline Form ES3 of emrusolmin may be isolated. Particularly, crystalline Form ES3 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0272] In any aspect or embodiment crystalline Form ES3 of emrusolmin may be polymorphically pure.

[0273] In any aspect or embodiment of the present disclosure, crystalline Form ES4 of emrusolmin may be isolated. Particularly, crystalline Form ES4 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0274] In any aspect or embodiment crystalline Form ES4 of emrusolmin may be polymorphically pure.

[0275] In any aspect or embodiment of the present disclosure, crystalline Form ES5 of emrusolmin may be isolated. Particularly, crystalline Form ES5 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0276] In any aspect or embodiment crystalline Form ES5 of emrusolmin may be polymorphically pure.

[0277] In any aspect or embodiment of the present disclosure, crystalline Form ES6 of emrusolmin may be isolated. Particularly, crystalline Form ES6 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0278] In any aspect or embodiment crystalline Form ES6 of emrusolmin may be polymorphically pure.

[0279] In any aspect or embodiment of the present disclosure, crystalline Form ES7 of emrusolmin may be isolated. Particularly, crystalline Form ES7 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0280] In any aspect or embodiment crystalline Form ES7 of emrusolmin may be polymorphically pure.Docket No: 102085.002661 - SMI095-W001

[0281] In any aspect or embodiment crystalline Form ES7 of emrusolmin may be anhydrous.

[0282] In any aspect or embodiment of the present disclosure, crystalline Form ES8 of emrusolmin may be isolated. Particularly, crystalline Form ES8 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0283] In any aspect or embodiment crystalline Form ES8 of emrusolmin may be polymorphically pure.

[0284] In any aspect or embodiment of the present disclosure, crystalline Form TAI of emrusolmin may be isolated. Particularly, crystalline Form TAI of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0285] In any aspect or embodiment crystalline Form TAI of emrusolmin may be polymorphically pure.

[0286] In any aspect or embodiment of the present disclosure, crystalline Form MSI of emrusolmin may be isolated. Particularly, crystalline Form MSI of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0287] In any aspect or embodiment crystalline Form MSI of emrusolmin may be polymorphically pure.

[0288] In any aspect or embodiment crystalline Form MSI of emrusolmin may be anhydrous.

[0289] In any aspect or embodiment of the present disclosure, crystalline Form MS2 of emrusolmin may be isolated. Particularly, crystalline Form MS2 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0290] In any aspect or embodiment crystalline Form MS2 of emrusolmin may be polymorphically pure.

[0291] In any aspect or embodiment of the present disclosure, crystalline Form Bl of emrusolmin may be isolated. Particularly, crystalline Form Bl of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0292] In any aspect or embodiment crystalline Form Bl of emrusolmin may be polymorphically pure.

[0293] In any aspect or embodiment crystalline Form Bl of emrusolmin may be anhydrous.Docket No: 102085.002661 - SMI095-W001

[0294] In any aspect or embodiment of the present disclosure, crystalline Form B2 of emrusolmin may be isolated. Particularly, crystalline Form B2 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0295] In any aspect or embodiment crystalline Form B2 of emrusolmin may be polymorphically pure.

[0296] In any aspect or embodiment of the present disclosure, crystalline Form B3 of emrusolmin may be isolated. Particularly, crystalline Form B3 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0297] In any aspect or embodiment crystalline Form B3 of emrusolmin may be polymorphically pure.

[0298] In any aspect or embodiment of the present disclosure, crystalline Form BS1 of emrusolmin may be isolated. Particularly, crystalline Form BS1 of emrusolmin according to any aspect or embodiment of the disclosure may be isolated.

[0299] In any aspect or embodiment crystalline Form BS1 of emrusolmin may be polymorphically pure.

[0300] In any aspect or embodiment crystalline Form BS1 of emrusolmin may be a hydrate.

[0301] The present disclosure provides the above-described crystalline polymorphs of emrusolmin for use in the preparation of pharmaceutical compositions comprising emrusolmin and / or crystalline polymorphs thereof.

[0302] The present disclosure provides the above-described crystalline polymorphs of emrusolmin for use in the preparation of pharmaceutical compositions comprising emrusolmin and / or crystalline polymorphs thereof and at least one pharmaceutically acceptable excipient.

[0303] The present disclosure includes processes for preparing the above-mentioned pharmaceutical compositions. The processes include combining any one or a combination of the crystalline polymorph of emrusolmin of the present disclosure with at least one pharmaceutically acceptable excipient.

[0304] The active ingredient and excipients can be formulated into compositions and dosage forms according to methods known in the art.

[0305] - A pharmaceutical formulation of a solid state form of emrusolmin can be administered, e.g. by oral administration.Docket No: 102085.002661 - SMI095-W001

[0306] The crystalline polymorphs of emrusolmin and the pharmaceutical compositions and / or formulations of emrusolmin of the present disclosure can be used as medicaments, in embodiments in the treatment of synucleinopathies such as MSA.

[0307] The present disclosure also provides methods of treating synucleinopathies such as MSA by administering a therapeutically effective amount of any one of the crystalline polymorphs of emrusolmin of the present disclosure, or at least one of the above pharmaceutical compositions and / or formulations, to a subject in need of the treatment.

[0308] Having thus described the disclosure with reference to particular preferred embodiments and illustrative examples, those in the art can appreciate modifications to the disclosure as described and illustrated that do not depart from the spirit and scope of the disclosure as disclosed in the specification. The Examples are set forth to aid in understanding the disclosure but are not intended to, and should not be construed to limit its scope in any way.

[0152] Powder X-ray Diffraction (“XRPD”) method

[0153] Sample after being powdered in a mortar and pestle is applied directly on a silicon plate holder. The X-ray powder diffraction pattern was measured with Philips X'Pert PRO X-ray powder diffractometer, equipped with Cu irradiation source =1.54184 A (Angstrom), X’Celerator (2.022° 20) detector. Scanning parameters: angle range: 3-40 deg., step size 0.0167, time per step 37 s, continuous scan. The described peak positions were determined without using silicon powder as an internal standard in an admixture with the sample measured.

[0154] EXAMPLES

[0155] Preparation of starting materials

[0156] Emrusolmin starting material was prepared as described in the literature, for example the procedure described in International Publication No. WO2010000372.

[0157] Example 1. Preparation of emrusolmin: HC1 form Hl

[0158] Emrusolmin starting material (152 mg) and 46 pL of HC1 (12M, molar ratio 1:3) were suspended in 2 ml of THF at room temperature. Suspension was partially dissolved and crystallized during 2 hours. After 1 day of mixing at room temperature, suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: HC1 form Hl was obtained. According to analytical results, the Emrusolmin to HC1 ratio was 1:1.

[0159] Example 2. Preparation of emrusolmin: HC1 form HlDocket No: 102085.002661 - SMI095-W001

[0160] 2587.6 mg of emrusolmin starting material and 3.93 ml of 12 M HC1 (ratio 1:1.5) were suspended in 25 ml of THF at room temperature. Suspension was partially dissolved after HC1 addition and crystallized during one hour. After one day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: HC1 form Hl was obtained. According to analytical results, the Emrusolmin to HC1 ratio was 1:1.

[0161] Example 3. Preparation of emrusolmin: HC1 form H2

[0162] 150 mg of emrusolmin: HC1 form Hl material prepared as detailed in example 2 was suspended in 15 ml of methyl acetate at room temperature. Suspension was heated to the temperature of reflux. Sample did not dissolve. After one day of sitting without mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: HC1 form H2 was obtained. According to analytical results ratio is 1:1.

[0163] Example 4. Preparation of emrusolmin: HC1 form H2

[0164] 20 mg of emrusolmin: HC1 form Hl material prepared as detailed in example 2 was suspended in 2 ml of methyl acetate at room temperature. Suspension was heated to the temperature of reflux. Sample did not dissolve. After one day of sitting without mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: HC1 form H2 was obtained. According to analytical results, the Emrusolmin to HC1 ratio was 1:1.

[0165] Example 5. Preparation of emrusolmin: CSA form Cl

[0166] 33 mg of emrusolmin starting material and 67 mg of camphor- 10-sulfonic acid (molar ratio 1:3) were suspended in 1 ml of THF at room temperature. After one day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: CSA form Cl was obtained. According to analytical results molar ratio is 1:1.

[0167] Example 6. Preparation of emrusolmin: CSA form Cl

[0168] 1655 mg of emrusolmin starting material and 1345 mg of camphor- 10-sulfonic acid (1:1.1) were suspended in 25 ml of acetone at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: CSA form Cl was obtained. According to analytical results ratio is 1:1.

[0169] Example 7. Preparation of emrusolmin: TSA form T1

[0170] 37.6 mg of emrusolmin starting material and 62.4 mg of p-toluenesulfonic acid monohydrate (molar ratio 1 :3) were suspended in 1 ml of THF at room temperature. After 1 dayDocket No: 102085.002661 - SMI095-W001of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin TSA form T1 was obtained. According to analytical results ratio is 1:1.

[0171] Example 8. Preparation of emrusolmin: TSA form T2

[0172] 37.6 mg of emrusolmin starting material and 62.4 mg of p-toluenesulfonic acid monohydrate (molar ratio 1 :3) were suspended in 1 ml of ethyl acetate at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: TSA form T2 was obtained. According to analytical results ratio is 1:1.

[0173] Example 9. Preparation of emrusolmin: TSA form T2

[0174] 1802 mg of emrusolmin starting material and 1198 mg of p-toluenesulfonic acid monohydrate (molar process ratio 1:1.1) were suspended in 25 ml of ethyl acetate at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. EMRUSOLMIN TSA form T2 was obtained. According to analytical results ratio is 1:1.

[0175] Example 10. Preparation of emrusolmin: esylate form El

[0176] 50.9 mg of emrusolmin starting material and 36.3 pL of ethanesulfonic acid (molar ratio 1:3) were suspended in 1 ml of acetone at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: esylate form El was obtained. According to analytical results ratio is 1:1.

[0177] Example 11. Preparation of emrusolmin: esylate form E2

[0178] 50.9 mg of emrusolmin starting material and 36.3 pL of ethanesulfonic acid (molar ratio 1:3) were suspended in 1 ml of ethyl acetate at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: esylate form E2 was obtained. According to analytical results ratio is 1:1.

[0179] Example 12. Preparation of emrusolmin: esylate form El

[0180] 2166 mg of emrusolmin starting material and 0.85 ml of ethanesulfonic acid (molar ratio 1:1.1) were suspended in 20 ml of acetone at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: esylate form El was obtained. According to analytical results ratio is 1:1.

[0181] Example 13. Preparation of emrusolmin: edisylate form ESI

[0182] 37.6 mg of emrusolmin starting material and 62.4 mg of 1 ,2-ethanedisulfonic acid (molar ratio 1:3) were suspended in 1 ml of ethyl acetate at room temperature. After 1 dayDocket No: 102085.002661 - SMI095-W001of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ESI was obtained. According to analytical results ratio is 1:1.

[0183] Example 14. Preparation of emrusolmin: edisylate form ES2

[0184] 37.6 mg of emrusolmin starting material and 62.4 mg of 1 ,2-ethanedisulfonic acid (molar ratio 1:3) were suspended in 1 ml of methanol at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES2 was obtained. According to analytical results ratio is 1:1.

[0185] Example 15. Preparation of emrusolmin: edisylate form ES3

[0186] 37.6 mg of emrusolmin starting material and 62.4 mg of 1 ,2-ethanedisulfonic acid (molar ratio 1:3) were suspended in 1 ml of acetonitrile at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES3 was obtained. According to analytical results ratio is 1:1.

[0187] Example 16. Preparation of emrusolmin: edisylate ESI

[0188] 1802 mg of emrusolmin starting material and 1198 mg of 1,2-ethanedisulfonic acid (molar ratio 1:1.1) were suspended in 25 ml of acetone at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ESI was obtained. According to analytical results ratio is 1:1.

[0189] Example 17. Preparation of emrusolmin: edisylate form ES4

[0190] 150 mg of emrusolmin: edisylate form ESI material prepared as detailed in example 16 was suspended in 7.5 ml of 1-buthanol at room temperature. Mixture was heated to 89 °C when dissolving occurred. Temperature was lowered to room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES4 was obtained. According to analytical results molar ratio is 1:1.

[0191] Example 18. Preparation of emrusolmin: edisylate form ES5

[0192] 150 mg of emrusolmin: edisylate form ESI prepared as detailed in example 16 was suspended in 15 ml of 2-buthanol at room temperature. Mixture was heated to the temperature of reflux. Sample did not dissolve. Temperature was lowered to room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES5 was obtained. According to analytical results molar ratio is 1:1.

[0193] Example 19. Preparation of emrusolmin: edisylate form ES6Docket No: 102085.002661 - SMI095-W001

[0194] 150 mg of emrusolmin: edisylate form ESI prepared as detailed in example 16 was suspended in 15 ml of ethanol at room temperature. Mixture was heated to the temperature of reflux. Sample did not dissolve. Temperature was lowered to room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES6 was obtained. According to analytical results molar ratio is 1:1.

[0195] Example 20. Preparation of emrusolmin: edisylate form ES6

[0196] 20 mg of emrusolmin: edisylate form ESI prepared as detailed in example 16 was suspended in 2 ml of ethanol at room temperature. Mixture was heated to the temperature of reflux. Sample did not dissolve. Temperature was lowered to room temperature. After 1 day of sitting without mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES6 was obtained. According to analytical results molar ratio is 1:1.

[0197] Example 21. Preparation of emrusolmin: edisylate form ES7

[0198] 3 mg of emrusolmin: edisylate form ES6 material provided in Example 20 was isothermally heated for 20 minutes at the temperature of 175°C. Sample was analyzed by XRPD. Emrusolmin: edisylate form ES7 was obtained. According to analytical results molar ratio is 1:1.

[0199] Example 22. Preparation of emrusolmin: edisylate form ES8

[0200] 150 mg of emrusolmin: edisylate form ESI prepared as detailed in example 16 was suspended in 15 ml of 1 -propanol at room temperature. Mixture was heated to 84 °C when dissolving occurred. Temperature was lowered to room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES8 was obtained. According to analytical results molar ratio is 1:1.

[0201] Example 23. Preparation of emrusolmin: edisylate form ES8

[0202] 2 mg of emrusolmin: edisylate form ESI prepared as detailed in example 16 was suspended in 2 ml of 1 -propanol at room temperature. Mixture was heated to 84 °C when dissolving occurred. Temperature was lowered to room temperature. After 1 day of sitting without mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: edisylate form ES8 was obtained. According to analytical results molar ratio is 1:1.

[0203] Example 24. Preparation of emrusolmin: tartarate form TAI

[0204] 43.2 mg of Emrusolmin starting material and 56.8 mg of L-tartaric acid (molar ratio 1:3) were suspended in 1 ml of acetonitrile at room temperature. After 1 day of mixingDocket No: 102085.002661 - SMI095-W001suspension was vacuum filtered and analyzed by XRPD. Emrusolmin-tartarate form TAI was obtained. According to analytical results ratio is 1:1.

[0205] Example 25. Preparation of emrusolmin: tartarate form TAI

[0206] 1312 mg of Emrusolmin starting material and 688 mg of L-tartaric acid (molar ratio 1:3) were suspended in 7 ml of acetone at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: tartarate form TAI was obtained. According to analytical results ratio is 1:1.

[0207] Example 26. Preparation of emrusolmin: tartarate form TAI

[0208] 1312 mg of emrusolmin starting material and 688 mg of L-tartaric acid (molar ratio 1:3) were suspended in 7 ml of THF at room temperature. Suspension was dissolved after 30 minutes and evaporated on rotavapour (50 °C, 0 mbar). Crystallization occurred and obtained solid was analyzed by XRPD. Emrusolmin: tartarate form TAI was obtained. According to analytical results molar ratio is 1:1.

[0209] Example 27. Preparation of emrusolmin: mesylate form MSI

[0210] 54 mg of emrusolmin starting material and 31 pL of methanesulfonic acid (molar ratio 1:3) were suspended in 1 ml of methanol at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: mesylate form MSI was obtained. According to analytical results ratio is 1:1.

[0211] Example 28. Preparation of emrusolmin: mesylate form MS2

[0212] 54 mg of emrusolmin starting material and 31 pL of methanesulfonic acid (molar ratio 1:3) were suspended in 1 ml of ethyl acetate at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: mesylate form MS2 was obtained. According to analytical results ratio is 1:1.

[0213] Example 29. Preparation of emrusolmin: mesylate form MS2

[0214] 2994 mg of emrusolmin starting material and 0.68 ml of methanesulfonic acid (molar ratio 1:1.1) were suspended in 25 ml of ethyl acetate or acetone at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: mesylate form MS2 was obtained. According to analytical results ratio is 1:1.

[0215] Example 30. Preparation of emrusolmin: bromide form Bl

[0216] 59 mg of emrusolmin starting material and 28 pL of HBr acid (molar ratio 1 :3) were suspended in 1 ml of acetone at room temperature. After 1 day of mixing suspension wasDocket No: 102085.002661 - SMI095-W001vacuum filtered and analyzed by XRPD. Emrusolmin: bromide form Bl was obtained.According to analytical results ratio is 1:1.

[0217] Example 31. Preparation of emrusolmin: bromide form B2

[0218] 59 mg of emrusolmin starting material and 28 pL of HBr acid (molar ratio 1 :3) were suspended in 1 ml of THF at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: bromide form B2 was obtained.According to analytical results ratio is 1:1.

[0219] Example 32. Preparation of emrusolmin: bromide form Bl

[0220] 1757 mg of emrusolmin starting material and 0.497 mL of HBr acid (molar ratio 1:1.1) were suspended in 20 ml of MEK at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: bromide form Bl was obtained. According to analytical results ratio is 1:1.

[0221] Example 33. Preparation of emrusolmin: bromide form B3

[0222] 20 mg of emrusolmin: bromide form Bl material prepared as detailed in example 32 material was suspended in 2 ml of methyl acetate at room temperature. Suspension was heated to the temperature of reflux. Sample did not dissolve. After one day of sitting without mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: bromide form B3 was obtained. According to analytical results molar ratio is 1:1.

[0223] Example 34. Preparation of emrusolmin: bromide form B3

[0224] 150 mg of emrusolmin: bromide form Bl material prepared as detailed in example 32 was suspended in 15 ml of methyl acetate at room temperature. Suspension was heated to the temperature of reflux. Sample did not dissolve. After one day of sitting without mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: bromide form B3 was obtained. According to analytical results ratio is 1:1.

[0225] Example 35. Preparation of emrusolmin: besylate form BS1

[0226] 42 mg of emrusolmin starting material and 58 mg of benzenesulfonic acid (molar ratio 1:3) were suspended in 1 ml of MEK at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: besylate form BS1 was obtained. According to analytical results ratio is 1:1.

[0227] Example 36. Preparation of emrusolmin: besylate form BS1Docket No: 102085.002661 - SMI095-W001

[0228] 1932 mg of Emrusolmin starting material and 1068 mg of benzenesulfonic (molar ratio 1:1.1) were suspended in 25 ml of ethyl acetate at room temperature. After 1 day of mixing suspension was vacuum filtered and analyzed by XRPD. Emrusolmin: besylate form BS1 was obtained. According to analytical results ratio is 1:1.

[0229] Example 37. Preparation of Emrusolmin Hydrochloride Form Hl

[0230] Emrusolmin (15.0 g; 43.3 mmol) and acetone (375.0 ml) were charged into 1 Liter reactor and heated to 50-55 °C. Hydrochloric Acid diluted in acetone (3.85 ml 37 % HC1 aq; 30.0 ml acetone) was added dropwise to Emrusolmin solution at 50-55 °C. The obtained suspension was stirred at 50-55 °C for 30 min. and then was cooled down to 20-25 °C and stirred for additional 2 hours. Crystals were filtered off and washed with acetone (2 x 45 ml). Obtained wet crystals were dried at 50 °C, vacuum for 10 hours yielding Emrusolmin Hydrochloride form Hl as white powder (16.3 g; Y = 99 %, Chrom. purity 99.93 %).

[0231] Example 38. Preparation of Emrusolmin Hydrobromide Form Bl

[0232] To a mixture of 7.0 g of Emrusolmin and 140.0 mL of EtOAc at 70 - 75 °C, 2,59 mL of 47% HBr (aq.) was added dropwise. Obtained reaction mixture was stirred at 70 -75 °C for about 1 h, slowly cooled to 20 - 25 °C and stirred at 20 - 25 °C for about 20 h.Crystals were filtered off, washed with 2x 15.0 mL of EtOAc and dried at 60 °C / 20 mbar for about 16 h. Emrusolmin Hydrobromide Form Bl was obtained (8.53 g; Chrom. purity 99.94 %).

[0233] Example 39. Preparation of Emrusolmin Tosylate form T4

[0234] Emrusolmin (15.0 g; 43.3 mmol) and acetone (375.0 ml) were charged into 1 Liter reactor and heated to 50-55 °C. p-Toluenesulfonic Acid monohydrate (8.71 g; 45.5 mmol) was dissolved in acetone (35.0 ml) and the solution was added drop wise to Emrusolmin solution at 50-55 °C. The obtained suspension was stirred at 50-55 °C for 30 min. and then was cooled down to 20-25 °C and stirred for additional 2 hours. Crystals were filtered off and washed with acetone (3 x 45 ml). Obtained wet crystals were dried at 50 °C, vacuum for 10 hours yielding Emrusolmin Tosylate form T4 as white powder (21.4 g; Y = 91 %, Chrom. purity 99.94 %).

[0235] Example 40. Preparation of Emrusolmin Camsylate form Cl

[0236] Emrusolmin (15.0 g; 43.3 mmol) and acetone (375.0 ml) were charged into 1 Liter reactor and heated to 50-55 °C. Camphorsulfonic Acid (10.59 g; 45.5 mmol) was dissolved in acetone (50.0 ml) and the solution was added dropwise to Emrusolmin solution at 50-55 °C. The obtained suspension was stirred at 50-55 °C for 30 min. and then was cooled down to 20-25Docket No: 102085.002661 - SMI095-W001°C and stirred for additional 2 hours. Crystals were filtered off and washed with acetone (2 x 45 ml). Obtained wet crystals were dried at 50 °C, vacuum for 10 hours. Dried crystals were additionally slurried in acetone- water mixture yielding Emrusolmin Camsylate form Cl as white powder (Y = 87 %, Chrom. purity 99.87 %).

[0237] Example 41. Preparation of Emrusolmin Mesylate form MSI

[0238] To a mixture of 7.0 g of Emrusolmin and 140.0 mL of EtOAc at 20 - 25 °C, 1.46 mL of Methanesulfonic acid was added dropwise. Obtained reaction mixture was stirred at 20 - 25 °C for about 98 h. Crystals were filtered off, washed with 2 x 15.0 mL of EtOAc and dried at 60 °C / 20 mbar for about 16 h. Emrusolmin Mesylate Form MSI was obtained (8.74 g; Chrom purity 99.89 %).

[0239] Example 42. Preparation of Emrusolmin Esylate form El

[0240] To a mixture of 6.0 g of Emrusolmin and 120.0 mL of EtOAc at 70 - 75 °C, solution of 1.5 mL of Ethanesulfonic acid and 12.0 mL of EtOAc was added dropwise. Obtained reaction mixture was stirred at 70 - 75 °C for about 0.5 h, slowly cooled to 20 - 25 °C and stirred at 20 - 25 °C for about 22 h. Crystals were filtered off, washed with 2 x 20.0 mL of EtOAc and dried at 50 °C / 20 mbar for about 16 h. Emrusolmin Esylate salt Form El was obtained (7.73 g; Chrom purity 99.92 %).

[0241] Example 43. Preparation of Emrusolmin Edisylate form ESI

[0242] To a mixture of 6.0 g of Emrusolmin, 150.0 mL of acetone and 1.5 mL of water at 50 - 55 °C, solution of 4.05 g of 1 ,2-ethanedisulfonic acid dihydrate and 21.0 mL of acetone was added dropwise. Obtained reaction mixture was stirred at 50 - 55 °C for about 1.0 h, slowly cooled to 20 - 25 °C and stirred at 20 - 25 °C for about 20 h. Crystals were filtered off, washed with 2 x 15.0 mL of acetone / water 100 / 1 and dried at 50 °C / 20 mbar for about 16 h. Emrusolmin Edisylate Form ESI was obtained (9.73 g; Chrom purity 99.91 %).

[0243] Example 44. Preparation of Emrusolmin Besylate form BS1

[0244] To a mixture of 6.0 g of Emrusolmin, 150.0 mL of acetone and 1.5 mL of water at 50 - 55 °C, solution of 3.25 g of Benzenesulfonic acid monohydrate in 15.0 mL of acetone was added dropwise. Obtained reaction mixture was stirred at 50 - 55 °C for about 0.5 h, slowly cooled to 20 - 25 °C and stirred at 20 - 25 °C for about 22 h. Crystals were filtered off, washed with 2 x 15.0 mL of acetone / water 100 / 1 and dried at 50 °C / 20 mbar for about 16 h. Emrusolmin Besylate Form BS1 was obtained (8.87 g; Chrom. purity 99.91 %).DocketNo: 102085.002661 - SMI095-W001

[0245] Example 45. Preparation of Emrusolmin Hemiedisylate form HE 1

[0246] 5.9466 g of Emrusolmin crude material and 3.927 g of 1,2-ethanedisulfonic acid were suspended in 82.5 ml of acetone at room temperature. Suspension was partially dissolved and crystallized during 2 hours. After 1 day of mixing at room temperature, suspension was vacuum filtered and analyzed by XRPD.

[0247] 5 g of obtained sample of Emrusolmin edisylate form ESI was suspended in 250 mL of 1-buthanol and heated to 90 °C. Suspension was partially dissolved and mixed for 1 hour at that temperature. After 1 hour suspension was cooled down to room temperature and mixed for 24 h. After 24 hours suspension was vacuum filtered and sample of form HE1 was obtained and analyzed by XRPD.

[0248] Example 46. Preparation of Emrusolmin Edisylate pure form ES4

[0249] 1.802 g of Emrusolmin crude material and 1.190 g of 1,2-ethanedisulfonic acid were suspended in 25 ml of acetone at room temperature. Suspension was partially dissolved and crystallized during 2 hours. After 1 day of mixing at room temperature, suspension was vacuum filtered and analyzed by XRPD.

[0250] 1 g of obtained sample of Emrusolmin edisylate form ESI was suspended in 50 mL of 1-buthanol and heated to 90 °C. Suspension was partially dissolved and mixed for 1 hour at that temperature. After 1 hour suspension was cooled down to room temperature and mixed for 24 h. After 24 hours suspension was vacuum filtered and sample of form HE1 was obtained and analyzed by XRPD.

[0251] Example 47. Preparation of Emrusolmin camsylate form C2

[0252] Emrusolmin (5.0 g; 14.4 mmol) and THF (35.0 ml) were charged into 250 ml flask and heated to 60-65 °C. (±)-10-Camphorsulfonic Acid (3.58 g; 15.11 mmol) was dissolved in THF (15.0 ml) and the solution was added to Emrusolmin solution at 60-65 °C. The solution was cooled down to 20-25 °C and stirred for additional 2 hours. Crystals were filtered off and washed with THF (2 x 10 ml). Obtained wet crystals were dried at 50 °C, vacuum for 10 hours yielding Emrusolmin camsylate form C2 as white powder (7.27 g; Y = 88 %).

[0253] Example 48. Preparation of Emrusolmin tosylate form T4

[0254] Emrusolmin (5.0 g; 14.4 mmol) and THF (35.0 ml) were charged into 250 ml flask and heated to 60-65 °C. p-Toluenesulfonic Acid monohydrate (2.89 g; 15.11 mmol) was dissolved in THF (15.0 ml) and the solution was added dropwise to Emrusolmin solution at 60-Docket No: 102085.002661 - SMI095-W00165 °C. The obtained suspension was stirred at 60-65 °C for 25 min. and then was cooled down to 20-25 °C and stirred for additional 2 hours. Crystals were filtered off and washed with THF (2 x 10 ml). Obtained wet crystals were dried at 50 °C, vacuum for 10 hours yielding Emrusolmin tosylate form T4 as white powder (6.61 g; Y = 85 %).

[0255] Example 49: Salt Analyses

[0256] A. XRPD

[0257] Instruments: Panalytical X'Pert PRO X-ray powder diffractometer, equipped with Cu irradiation source =1.54184 A (Angstrom), X’Celerator (2.022 °20)

[0258] Samples after being powdered in a mortar and pestle are applied directly into a Panalytical’ original silicon plate PW1817-32

[0259] Scanning parametersRange: 3-40 degrees two-thetaScan mode: Continuous scanStep size: 0.0167Time per step: 37 s

[0260] B. DSC

[0261] Instruments: Discovery DSC, TA Instruments

[0262] Method: Ramp 10 °C / min up to 300 °C

[0263] C. TGA

[0264] Instruments: Discovery TGA, TA Instrument

[0265] Method: Ramp 10 °C / min up to 300 °C

[0266] D. Microscope analysis

[0267] Equipment: Olympus Microscope BX53; Digital camera DP23-CU

[0268] E. Solubility determination

[0269] USP 2, Intrinsic dissolution, 100 rpm

[0270] Medium: PBS pH 7.4 + 0.5% CTAB (cetyltrimethylammonium bromide), 900 mL

[0271] Temp: 37 °C

[0272] Samples: Around 100 mg of API placed into intrinsic dissolution vessel, pressed for 90 s, 3 t

[0273] Sampling with replacementDocket No: 102085.002661 - SMI095-W001

[0274] Filter: RC 0.2 um

[0275] Sampling points: 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300 min

[0276] HPLC (264 nm)

[0277] E. Results

[0278] (i) Emrusolmin Hydrochloride

[0279] The aqueous solubility as well as dissolution rate of Emrusolmin Hydrochloride was determined to be higher than that of Emrusolmin base as presented on FIG.23. This increase in solubility is of considerable importance for active pharmaceutical ingredients (APIs) with inherently low aqueous solubility, as improved solubility can positively affect dissolution rate, bioavailability, and ultimately therapeutic performance. Consequently, Emrusolmin Hydrochloride salt is more favorable choice for pharmaceutical development.

[0280] In addition, Emrusolmin Hydrochloride has better morphology in comparison to Emrusolmin base resulting with better filterability since thin needles of free base are prone to agglomeration. Optical micrographs of Emrusolmin base and Emrusolmin Hydrochloride side by side are presented in FIG. 24.

[0281] (ii) Emrusolmin Hydrobromide

[0282] The aqueous solubility as well as dissolution rate of Emrusolmin Hydrobromide was determined to be higher than that of Emrusolmin base as presented on FIG.25. Enhanced aqueous solubility of the active pharmaceutical ingredient makes up a technical advantage, leading to improved bioavailability and reduced variability in drug absorption.Consequently, Emrusolmin Hydrobromide salt is more favorable possibility for pharmaceutical development.

[0283] Emrusolmin Hydrobromide has better morphology in comparison to Emrusolmin base. Defined and uniform morphology of the active pharmaceutical ingredient provides improved batch-to-batch consistency and reproducibility during manufacture.Advantageous morphology allows the active substance to be incorporated into a wider range of formulations without compromising performance. Optical micrographs of Emrusolmin base and Emrusolmin Hydrobromide side by side are presented in FIG. 26.

[0284] (iii) Emrusolmin Tosylate

[0285] Emrusolmin Tosylate has melting point higher than that of Emrusolmin base Form 1 (thermodynamically most stable form of free base) as presented in FIG. 27. MeltingDocket No: 102085.002661 - SMI095-W001point of Emrusolmin Tosylate (Crystal Form T4) is Tonset = 218 °C in comparison to Tonset = 198 °C for Emrusolmin base (Form 1). Higher melting point indicates improved thermal and physicochemical stability and lower the risk of degradation during manufacturing, processing and storage.

[0286] Emrusolmin Tosylate exhibits better morphology in comparison to Emrusolmin base resulting with better filterability. While Emrusolmin Tosylate crystallizes in form of plate-shaped crystals, Emrusolmin base (Form 1) forms very thin needles prone to aggregation. The unfavorable morphology of Emrusolmin base results in poor filterability, with aggregated crystals tending to entrap residual solvents, thereby complicating drying and downstream processing. Emrusolmin Tosylate crystals in contrast have good flowability and powder properties.

[0287] Optical micrographs of Emrusolmin Tosylate and Emrusolmin base side by side are presented in FIG. 28.

[0288] (iv) Emrusolmin Camsylate

[0289] The aqueous solubility as well as dissolution rate of Emrusolmin Camsylate was determined to be higher than that of Emrusolmin base as presented in FIG. 29. Emrusolmin base is API with inherently low aqueous solubility, so any improved solubility can positively affect dissolution rate, bioavailability, and ultimately therapeutic performance. Consequently, Emrusolmin Camsylate salt is more advantageous option for pharmaceutical development. In addition, morphology of the Camsylate salt is shown in FIG. 30, in comparison to Emrusolmin base. It has rod-like particles, thicker in comparison to Emrusolmin base needles. Consequently, filterability and ease of operation with the material is much better with the salt.

[0290] (v) Emrusolmin Mesylate

[0291] Emrusolmin Mesylate is a salt with higher aqueous solubility as well as higher dissolution rate in comparison to Emrusolmin base (FIG. 31) which provides a significant advantage by improving bioavailability and enabling more consistent therapeutic performance.

[0292] (vi) Emrusolmin Esylate

[0293] The higher melting point of the Emrusolmin Esylate salt compared to Emrusolmin free base provides advantages in manufacturing, including improved process robustness and reduced risk of melting or phase transformation. The Tonset temperature of theDocket No: 102085.002661 - SMI095-W001Esylate salt is 228 °C (FIG. 32) which is much higher in comparison to free base Tonset of 198 °C (for thermodynamically most stable Form 1).

[0294] Intrinsic dissolution in phosphate buffer at pH 7.4 shows that Emrusolmin Esylate salt is more soluble than free base (FIG. 33). The improved solubility of the salt in buffer at pH 7.4 is a significant advantage, enhancing dissolution under physiological conditions and improving bioavailability.

[0295] (vii) Emrusolmin Edisylate

[0296] Emrusolmin Edisylate exhibits rod-like morphology which makes it easy for handling during manufacturing and formulation development. The improved morphology is advantageous for manufacturing operations such as stirring and filtration. Such morphology results in good flowability and powder characteristics, which is particularly advantageous in pharmaceutical technology. Optical micrographs of Emrusolmin Edisylate crystals versus free Emrusolmin base are shown in FIG. 34.

[0297] Emrusolmin Edisylate salt shows superior solubility as well as dissolution rate in pH 7.4 buffer in comparison to Emrusolmin base, which is advantageous for enhancing dissolution under physiological conditions and improving bioavailability (FIG. 35).

[0298] (viii) Emrusolmin Hemiedisylate

[0299] Emrusolmin Hemiedisylate exhibits markedly improved filterability compared to Emrusolmin base, which is a direct consequence of its favorable crystal morphology (FIG. 36). Efficient filterability is a critical attribute in pharmaceutical manufacturing, as it enables rapid and effective solid-liquid separation during isolation. The superior filtration behavior eases more efficient removal of residual solvents, leading to improved chemical purity of the final product. In contrast, the poor filterability of free base can result in solvent entrapment and processing challenges. Accordingly, the enhanced filtration and isolation characteristics make Emrusolmin Hemiedisylate salt a more advantageous than Emrusolmin free base for pharmaceutical production.

[0300] (ix) Emrusolmin Besylate

[0301] Emrusolmin Besylate morphology shown on FIG. 37 shows significant improvement in comparison to thin needles of Emrusolmin base, resulting in good flowability and improved handling during formulation and processing. The favorable morphology andDocket No: 102085.002661 - SMI095-W001associated good flowability of the substance is advantage in pharmaceutical processing, including blending, granulation, and tableting.

[0302] In addition, Emrusolmin Besylate has higher solubility as well as dissolution rate in buffer at pH 7.4 than Emrusolmin base (FIG. 38) thereby providing advantage under physiological conditions.

[0303] The disclosures of each patent, patent application, and publication cited or described in this document are hereby incorporated herein by reference, each in its entirety, for all purposes.

Claims

Docket No: 102085.002661 - SMI095-W001What is Claimed Is:

1. A solid state form of emrusolmin hydrochloride.

2. The solid state form of claim 1, that is:crystalline emrusolmin hydrochloride;amorphous emrusolmin hydrochloride;a crystalline polymorph of emrusolmin hydrochloric acid designated as Form Hl, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 1 ; an X-ray powder diffraction having peaks at about 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 18.9, 19.3, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.5, 14.1, 17.4, 17.9 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 11.5, 14.1, 17.4, 17.9, 18.9, 19.3, 22.6, 23.0, 24.2 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta; ora crystalline polymorph of emrusolmin hydrochloric acid, designated as Form H2, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 2; an X-ray powder diffraction having peaks at about 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 6.8, 9.5, 14.9, 16.2 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 13.6, 16.9, 23.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 6.8, 9.5, 13.6, 14.9, 16.2, 16.9, 23.6, 26.6, 27.1 and 27.4 degrees 2-theta ± 0.2 degrees 2-theta.

3. A solid state form of emrusolmin camsylate.

4. The solid state form of claim 3, that is:Docket No: 102085.002661 - SMI095-W001crystalline emrusolmin camsylate;amorphous emrusolmin camsylate;a co-crystal of emrusolmin and camphorsulfonic acid;a crystalline polymorph of emrusolmin camsylate, designated Form Cl that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 3; an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 13.4, 15.1, 16.0, 17.8 and 24.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 8.0, 20.2, 20.7, 21.1 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 8.0, 13.4, 15.1, 16.0, 17.8, 20.2, 20.7, 21.1, 24.5 and 25.0 degrees 2-theta ± 0.2 degrees 2-theta; ora crystalline polymorph of emrusolmin camsylate, designated Form C2, that is characterized by data selected from one of more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 40; an X-ray powder diffraction having peaks at 5.3, 10.6, 13.8, 18.7 and 22.7 ± 0.2 degrees two-theta; an X-ray powder diffraction pattern having peaks at 5.3, 10.6, 13.8, 18.7 and 22.7 ± 0.2 degrees two-theta and also having one, two, three, or four additional peaks at 16.0, 21.3, 23.3 and 27.7 ± 0.2 degrees two-theta; or an X-ray powder diffraction pattern having peaks at 5.3, 10.6, 13.8, 16.0, 18.7, 21.3, 22.7, 23.3 and 27.7 ± 0.2 degrees two-theta.

5. A solid state form of emrusolmin tosylate.

6. The solid state form of claim 5, that is:crystalline emrusolmin tosylate;amorphous emrusolmin tosylate;a co-crystal of emrusolmin and toluene sulfonic acid;Docket No: 102085.002661 - SMI095-W001a crystalline polymorph of emrusolmin tosylate, designated Form Tl, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 4; an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 12.1, 13.7, 18.1, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.1, 11.4, 15.5, 17.6 and 18.5 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 9.1, 11.4, 12.1, 13.7, 15.5, 17.6, 18.1, 18.5, 19.9 and 26.5 degrees 2-theta ± 0.2 degrees 2-theta;a crystalline polymorph of emrusolmin tosylate, designated Form T2, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 5; an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 5.9, 18.8, 20.3, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 9.5, 10.2, 14.3, 19.8 and 21.7 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 5.9, 9.5, 10.2, 14.3, 18.8, 19.8, 20.3, 21.7, 24.7 and 26.2 degrees 2-theta ± 0.2 degrees 2-theta; ora crystalline polymorph of emrusolmin tosylate, designated Form T4, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 41; an X-ray powder diffraction pattern having peaks at 13.4, 16.9, 21.9 and 27.5 ± 0.2 degrees two- theta; an X-ray powder diffraction pattern having peaks at 13.4, 16.9, 21.9 and 27.5 ± 0.2 degrees two-theta and also having one, two, three, or four additional peaks at about 9.1, 18.2, 19.4 and 22.6 ± 0.2 degrees two-theta; or an X-ray powder diffraction pattern having peaks at 9.1, 13.4, 16.9, 18.2, 19.4, 21.9, 22.6 and 27.5 ± 0.2 degrees two-theta.

7. A solid state form of emrusolmin esylate.Docket No: 102085.002661 - SMI095-W0018. The solid state form of emrusolmin esylate of claim 7, that is:crystalline emrusolmin esylate;amorphous emrusolmin esylate;a co-crystal of emrusolmin and ethanesulfonic acid;a crystalline polymorph of emrusolmin esylate, designated Form El, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 6; an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 14.9, 18.4, 19.8, 21.2, and 25.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 7.3, 10.8, 15.8, 20.2 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.3, 10.8, 14.9, 15.8, 18.4, 19.8, 20.2, 21.2, 25.0 and 27.8 degrees 2-theta ± 0.2 degrees 2-theta;a crystalline polymorph of emrusolmin esylate, designated Form E2, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 7; an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 9.9, 17.7, 19.3, 24.7 and 26.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.5, 12.0, 18.5, 22.5 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 9.9, 10.5, 12.0, 17.7, 18.5, 19.3, 22.5, 24.7, 26.6 and 27.7 degrees 2-theta ± 0.2 degrees 2-theta.

9. A solid state form of emrusolmin edisylate.

10. The solid state form of claim 9, that is:crystalline emrusolmin edisylate;Docket No: 102085.002661 - SMI095-W001amorphous emrusolmin edisylate;a co-crystal of emrusolmin and ethanedisulfonic acid;a crystalline polymorph of emrusolmin edisylate, designated Form ESI, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 8; an X-ray powder diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 11.8, 16.5, 21.0, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 15.7, 18.5, 20.6, 22.6 and 23.1 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 11.8, 15.7, 16.5, 18.5, 20.6, 21.0, 22.6, 23.1, 23.8 and 25.9 degrees 2-theta ± 0.2 degrees 2-theta;a crystalline polymorph of emrusolmin edisylate, designated Form ES2, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 9; an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 8.0, 13.5, 17.9, 18.5 and 24.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 11.1, 14.5, 14.9, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 8.0, 11.1, 13.5, 14.5, 14.9, 17.9, 18.5, 24.2, 25.3 and 26.1 degrees 2-theta ± 0.2 degrees 2-theta;a crystalline polymorph of emrusolmin edisylate, designated Form ES3, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 10; an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 10.0, 14.0, 15.7, 17.2 and 23.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 12.7, 20.0, 20.4, 21.4 and 28.1 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction patternDocket No: 102085.002661 - SMI095-W001having peaks at 10.0, 12.7, 14.0, 15.7, 17.2, 20.0, 20.4, 21.4, 23.7 and 28.1 degrees 2-theta ± 0.2 degrees 2-theta;a crystalline polymorph of emrusolmin edisylate, designated Form ES4, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 11 ; an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 17.6, 24.0 and 26.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 13.6, 25.2 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.1, 8.6, 13.6, 17.6, 24.0, 25.2, 26.7 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta; a crystalline polymorph of emrusolmin edisylate, designated Form ES5, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 12; an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 10.4, 21.5, 22.4 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 7.6, 18.3, 20.7, 22.9 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.6, 10.4, 18.3, 20.7, 21.5, 22.4, 22.9 and 26.0 degrees 2-theta ± 0.2 degrees 2-theta; a crystalline polymorph of emrusolmin edisylate, designated Form ES6, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 13; an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 7.4, 11.5 and 14.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 15.2, 18.0 and 19.1 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 7.4, 11.5 14.2, 15.2, 18.0 and 19.1 degrees 2-theta ± 0.2 degrees 2-theta;Docket No: 102085.002661 - SMI095-W001a crystalline polymorph of emrusolmin edisylate, designated Form ES7, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 14; an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one peak at 20.3 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 16.9, 18.8, 20.3, 24.9 and 26.3 degrees 2-theta ± 0.2 degrees 2- theta;a crystalline polymorph of emrusolmin edisylate, designated Form ES8, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 15; an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 10.8, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 10.8, 17.4, 18.3, 19.4, 22.2, 28.5, 29.6 and 32.9 degrees 2-theta ± 0.2 degrees 2-theta; or a crystalline polymorph of emrusolmin edisylate, designated Form HE1, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 39; an X-ray powder diffraction pattern having peaks at 13.6, 17.6, 24.0, 25.4 and 26.7 ± 0.2 degrees 2- theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 13.6, 17.6, 24.0, 25.4 and 26.7 ± 0.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four, or five additional peaks at 16.7, 20.4, 21.7, 22.5 and 27.3 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 13.6, 16.7, 17.6, 20.4, 21.7, 22.5, 24.0, 25.4, 26.7, and 27.3 degrees 2-theta ± 0.2 degrees 2-theta.

11. A solid state form of emrusolmin tartarate.Docket No: 102085.002661 - SMI095-W00112. The solid state form of emrusolmin tartarate, that is:crystalline emrusolmin tartarate;amorphous emrusolmin tartarate;a co-crystal of emrusolmin and tartaric acid; ora crystalline polymorph of emrusolmin tartarate, designated Form TAI, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 16; an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 17.1, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 9.2, 13.2, 17.4 and 18.3 degrees 2-theta ± 0.2 degrees 2- theta; or an X-ray powder diffraction pattern having peaks at 9.2, 13.2, 17.1, 17.4 and 18.3, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta.

13. A solid state form of emrusolmin mesylate.

14. The solid state form of claim 13, that is:crystalline emrusolmin mesylate;amorphous emrusolmin mesylate;a co-crystal of emrusolmin and methansulfonic acid;a crystalline polymorph of emrusolmin mesylate, designated Form MSI, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 17; an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 6.7, 11.2, 13.9, 20.2 and 24.0 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 10.1, 16.1, 20.8, 22.2 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaksDocket No: 102085.002661 - SMI095-W001at 6.7, 10.1, 11.2, 13.9, 16.1, 20.2, 20.8, 22.2, 24.0 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta; ora crystalline polymorph of emrusolmin mesylate, designated Form MS2, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 18; an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7 and 20.6 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.7, 19.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 4.7, 9.4, 13.3, 15.7, 17.7, 19.6, 20.6, 21.7, 23.1 and 23.8 degrees 2-theta ± 0.2 degrees 2-theta.

15. A solid state form of emrusolmin hydrobromide.

16. The solid state form of claim 15, that is:crystalline emrusolmin hydrobromide;amorphous emrusolmin hydrobromide;a co-crystal of emrusolmin and hydrobromic acid;a crystalline polymorph of emrusolmin hydrobromide, designated Form Bl, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 19; an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 12.8, 19.9, 20.9, 21.7 and 25.8 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 6.6, 13.6, 19.2, 24.0 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 6.6, 12.8, 13.6, 19.2, 19.9, 20.9, 21.7, 24.0, 25.8 and 27.2 degrees 2-theta ± 0.2 degrees 2-theta;Docket No: 102085.002661 - SMI095-W001a crystalline polymorph of emrusolmin hydrobromide, designated Form B2, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 20; an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 21.2, 22.8, and 26.3 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks at 17.2, 19.2, 23.7, 24.5 and 25.4 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 10.9, 16.0, 17.2, 19.2, 21.2, 22.8, 23.7, 24.5, 25.4 and 26.3 degrees 2-theta ± 0.2 degrees 2-theta; ora crystalline polymorph of emrusolmin hydrobromide, designated Form B3, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 21; an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 14.8, 16.9, 20.4, 23.0 and 30.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two or three additional peaks at 12.2, 23.4 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 12.2, 14.8, 16.9, 20.4, 23.023.4, 30.5 and 34.0 degrees 2-theta ± 0.2 degrees 2-theta.

17. A solid state form of emrusolmin besylate.

18. The solid state form of claim 17, that iscrystalline emrusolmin besylate;amorphous emrusolmin besylate;a co-crystal of emrusolmin and benzenesulfonic acid;a crystalline polymorph of emrusolmin besylate, designated Form BS1, that is characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in FIG. 22; an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-thetaDocket No: 102085.002661 - SMI095-W001± 0.2 degrees 2-theta; an X-ray powder diffraction pattern having peaks at 11.3, 18.7, 24.1, 25.9 and 26.9 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three or four additional peaks at 8.6, 10.5, 21.5 and 22.6 degrees 2-theta ± 0.2 degrees 2-theta; or an X-ray powder diffraction pattern having peaks at 8.6, 10.5, 11.3, 18.7, 21.5, 22.6, 24.1, 25.9 and 26.9 degrees 2-theta± 0.2 degrees 2- theta.

19. The solid state form of any one of the preceding claims, wherein the molar ratio between emrusolmin and the acid is between about 2: 1 to about 1 : 1 ; or about 1.5:1 to about 1:1.5 or about 1.1:1 to about 1:1.1, such as about 1:1, or such as about 2:1.

20. The solid state form of any one of the preceding claims, that is isolated.

21. The solid state form of any one of the preceding claims that is polymorphically pure.

22. A pharmaceutical composition comprising one or more solid state forms of any one of the preceding claims, optionally comprising at least one pharmaceutically acceptable excipient.

23. A process for preparing the pharmaceutical composition of claim 22 comprising combining one or more solid state forms of any one of claims 1-21, with at least one pharmaceutical acceptable excipient.

24. A dosage form comprising one or more solid state forms of any one of claims 1-21 or the pharmaceutical composition of claim 22.

25. The solid state form of any one of claims 1-21, the pharmaceutical composition of claim 22, or the dosage form of claim 23, for use in preparing pharmaceutical compositions comprising emrusolmin, emrusolmin salts, and / or crystalline polymorphs thereof.

26. The solid state form of any one of claims 1-21, the pharmaceutical composition of claim 22, or the dosage form of claim 23, for use as a medicament for treating a synucleinopathy, such as a neurodegenerative disease, such as Parkinson's disease, Alzheimer's disease, multiple system atrophy (MSA), Diffuse Lewy body disease,Docket No: 102085.002661 - SMI095-W001frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localized amyloidosis, beta-2 microglobulin amyloidosis, hereditary non- neuropathic amyloidosis, or Finnish hereditary systemic amyloidosis.

27. The solid state form of any one of claims 1-21, the pharmaceutical composition of claim 22, or the dosage form of claim 23, for use in treating a synucleinopathy, such as a neurodegenerative disease, such as Parkinson's disease, Alzheimer's disease, multiple system atrophy (MSA), Diffuse Lewy body disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localized amyloidosis, beta- 2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, Finnish hereditary systemic amyloidosis.

28. A method of treating a synucleinopathy in a subject in need thereof, a neurodegenerative disease, such as Parkinson's disease, Alzheimer's disease, multiple system atrophy (MSA), Diffuse Lewy body disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease's, spinocerebellar ataxias and other Poly-Q diseases, hereditary cerebral amyloid angiopathy, familial amyloid polyneuropathy, primary systemic amyloidosis (AL amyloidosis), reactive systemic amyloidosis (AA amyloidosis), type II diabetes, injection-localized amyloidosis, beta- 2 microglobulin amyloidosis, hereditary non-neuropathic amyloidosis, or Finnish hereditary systemic amyloidosis, comprising administering a therapeutically effective amount of any one of the solid state forms of claims 1-21, the pharmaceutical composition of claim 22, or the dosage form of claim 23, to the subject.

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