WO2025191534A1 - Solid state forms of zasocitinib and process for preparation thereof - Google Patents

Abstract

Solid state forms of Zasocitinib, processes for the preparation thereof, and pharmaceutical compositions thereof.

Description

SOLID STATE FORMS OF ZASOCITINIB AND PROCESS FOR PREPARATION THEREOF

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63/565,072, filed March 14, 2024, U.S. Provisional Application No. 63/570,906, filed March 28, 2024, and U.S. Provisional Application No. 63/650,435, filed May 22, 2024. The entire disclosures of the foregoing applications are incorporated by reference herein.

FIELD OF THE DISCLOSURE

[0002] The present disclosure encompasses solid state forms of Zasocitinib, in embodiments crystalline polymorphs or salts or co-crystals of Zasocitinib, processes for preparation thereof, and pharmaceutical compositions thereof.

BACKGROUND OF THE DISCLOSURE

[0003] Zasocitinib, N-[(lR,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo[l(2H),2'- bipyridin]-3-yl)amino]-pyrazolo[l,5-a]pyrimidine-3-carboxamide, has the following chemical structure:

[0004] Zasocitinib, also known as NDI-034858, is an allosteric TYK2 inhibitor, and it is developed for the treatment of moderate-to-severe Plaque Psoriasis. [0005] The compound is described in U.S. Patent No. 10,577,373. Crystalline forms of Zasocitinib are described in International Publication No. WO 2023/183910.

[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 solid state forms (including solvated forms) of an active pharmaceutical ingredient may possess different properties. Such variations in the properties of different salts and solid state forms and solvates 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 in the properties of different salts and solid state forms may also offer improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different salts and solid state 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 Zasocitinib. SUMMARY OF THE DISCLOSURE

[0009] The present disclosure provides crystalline polymorphs of Zasocitinib or salts or cocrystals thereof, processes for preparation thereof, and pharmaceutical compositions thereof. These crystalline polymorphs can be used to prepare other solid state forms of Zasocitinib, Zasocitinib salts or Zasocitinib co-crystals and their solid state forms.

[0010] The present disclosure also provides uses of the said solid state forms of API in the preparation of other solid state forms of Zasocitinib or salts or co-crystals thereof.

[0011] The present disclosure provides crystalline polymorphs of Zasocitinib or salts or cocrystals thereof for use in medicine, including for the treatment of moderate-to-severe Plaque Psoriasis.

[0012] The present disclosure also encompasses the use of crystalline polymorphs of Zasocitinib or salts or co-crystals 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 Zasocitinib or salts or co-crystals thereof according to the present disclosure.

[0014] The present disclosure includes processes for preparing the above mentioned pharmaceutical compositions. The processes include combining any one or a combination of the crystalline polymorphs of Zasocitinib or salts or co-crystals thereof with at least one pharmaceutically acceptable excipient.

[0015] The crystalline polymorph of Zasocitinib or salts or co-crystals thereof as defined herein and the pharmaceutical compositions or formulations of the crystalline polymorph of Zasocitinib or salts or co-crystals thereof may be used as medicaments, such as for the treatment of moderate-to-severe Plaque Psoriasis.

[0016] The present disclosure also provides methods of treating moderate-to-severe Plaque Psoriasis, by administering a therapeutically effective amount of any one or a combination of the crystalline polymorphs of Zasocitinib or salts or co-crystals of the present disclosure, or at least one of the above pharmaceutical compositions, to a subject suffering from moderate-to-severe Plaque Psoriasis, or otherwise in need of the treatment.

[0017] The present disclosure also provides uses of crystalline polymorphs of Zasocitinib or salts or co-crystals of the present disclosure, or at least one of the above pharmaceutical compositions, for the manufacture of medicaments for treating e.g. moderate-to-severe Plaque Psoriasis.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 shows a characteristic X-ray powder diffraction pattern (“XRPD”) of Zasocitinib Form 1 ;

[0019] Figure 2 shows a characteristic XRPD of Zasocitinib Form 2;

[0020] Figure 3 shows a characteristic XRPD of Zasocitinib and L-ascorbic acid Form Al;

[0021] Figure 4 shows a characteristic XRPD of Zasocitinib and benzoic acid Form B 1 ;

[0022] Figure 5 shows a characteristic XRPD of Zasocitinib Form 3 ;

[0023] Figure 6 shows a characteristic XRPD of Zasocitinib Form 4;

[0024] Figure 7 shows a characteristic XRPD of Zasocitinib and L-malic acid Form Ml ; and

[0025] Figure 8 shows a characteristic XRPD of Zasocitinib and citric acid Form LI.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0026] The present disclosure encompasses solid state forms of Zasocitinib or salts or cocrystals thereof, including crystalline polymorphs of Zasocitinib or salts or co-crystals thereof, processes for preparation thereof, and pharmaceutical compositions thereof.

[0027] Solid state properties of Zasocitinib or salts or co-crystals thereof and crystalline polymorphs thereof can be influenced by controlling the conditions under which Zasocitinib or salts or co-crystals thereof and crystalline polymorphs thereof are obtained in solid form.

[0028] 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. Thus, a crystalline polymorph of Zasocitinib 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 Zasocitinib. In some embodiments of the disclosure, the described crystalline polymorph of Zasocitinib 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 Zasocitinib.

[0029] 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 Zasocitinib or Zasocitinib salt 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 Zasocitinib. In some embodiments of the disclosure, the described pure or purified Zasocitinib 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.

[0030] In specific embodiments, the above described pure or purified Zasocitinib may relate to enantiomeric purity, i.e., pure or purified Zasocitinib refers to Zasocitinib that is substantially free of enantiomers of Zasocitinib.

[0031] The solid state form may be referred to herein as “Zasocitinib Form 1” or “Crystalline Form 1 of Zasocitinib” or “Crystalline Zasocitinib Form 1” or “Crystalline Form 1 of Zasocitinib “ or “Crystalline Zasocitinib polymorph Form 1” or “ Zasocitinib polymorph Form 1” . For example, crystalline Form 1 of Zasocitinib may be interchangeably referred to herein as Zasocitinib Form 1 or as Crystalline Zasocitinib Form 1 or as Crystalline polymorph 1 of Zasocitinib or as Crystalline Zasocitinib polymorph 1 or Zasocitinib polymorph 1.

[0032] Depending on which other crystalline polymorphs a comparison is made, the crystalline polymorphs of Zasocitinib 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. [0033] A solid state form, such as a crystal form or an amorphous 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, variations 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 Zasocitinib 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 Zasocitinib characterized with the graphical data having such small variations, as are well known to the skilled person, in comparison with the Figure.

[0034] As used herein, and unless stated otherwise, the term “anhydrous” in relation to crystalline forms of Zasocitinib, relates to a crystalline form of Zasocitinib 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.

[0035] 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.

[0036] “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 (Zasocitinib) and the coformer (L-ascorbic acid or benzoic acid) is between 1: 1.5 and 1.5: 1, preferably between 1: 1.25 and 1.25: 1, in other embodiments about 1: 1.

[0037] As used herein, crystalline Zasocitinib: L-ascorbic acid is a distinct molecular species. Crystalline Zasocitinib: L-ascorbic acid may be a co-crystal of Zasocitinib and L- ascorbic acid. Alternatively crystalline Zasocitinib: L-ascorbic acid may be a salt.

[0038] As used herein, crystalline Zasocitinib: benzoic acid is a distinct molecular species. Crystalline Zasocitinib: benzoic acid may be a co-crystal of Zasocitinib and benzoic acid Alternatively crystalline Zasocitinib: benzoic acid may be a salt.

[0039] As used herein, the term “isolated” in reference to crystalline polymorph of Zasocitinib of the present disclosure corresponds to a crystalline polymorph of Zasocitinib that is physically separated from the reaction mixture in which it is formed.

[0040] As used herein, unless stated otherwise, the XRPD measurements are taken using copper Koi radiation wavelength 1.5418 A. XRPD peaks reported herein are measured using CuK a radiation, X = 1.5418 A, typically at a temperature of 25 ± 3°C.

[0041] As used herein, unless stated otherwise, ¹³C NMR reported herein are measured at 125 MHz at a magic angle spinning frequency tit/27c = 11 kHz, preferably at a temperature of at 293 K ± 3°C.

[0042] 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.

[0043] 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. [0044] 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.

[0045] 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.

[0046] As used herein and unless indicated otherwise, the term “ambient conditions” refer to atmospheric pressure and a temperature of 22-24°C.

[0047] The present disclosure includes a crystalline polymorph of Zasocitinib, designated Form 1. The crystalline Form 1 of Zasocitinib may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 1; an X-ray powder diffraction pattern having peaks at 3.6, 7.0, 10.7, 12.5 and 17.5 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0048] Crystalline Form 1 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having peaks at 3.6, 7.0, 10.7, 12.5 and 17.5 degrees 2-theta ± 0.2 degrees 2- theta, and also having any one, two, three, four or five additional peaks selected from 6.2, 12.9, 18.4, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta.

[0049] Crystalline Form 1 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having peaks at 3.6, 6.2, 7.0, 10.7, 12.5, 12.9, 17.5, 18.4, 18.9 and 19.9 degrees 2-theta ± 0.2 degrees 2-theta.

[0050] In one embodiment of the present disclosure, crystalline Form 1 of Zasocitinib is isolated.

[0051] Crystalline Form 1 of Zasocitinib may be characterized by each of the above characteristics alone/or by all possible combinations, e.g., an XRPD pattern having peaks at 3.6, 7.0, 10.7, 12.5 and 17.5 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 1 , and combinations thereof.

[0052] The present disclosure includes a crystalline polymorph of Zasocitinib, designated Form 2. The crystalline Form 2 of Zasocitinib may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 2; an X-ray powder diffraction pattern having peaks at 14.6, 16.5, 20.5 and 24.8 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0053] Crystalline Form 2 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having peaks at 14.6, 16.5, 20.5 and 24.8 degrees 2-theta ± 0.2 degrees 2- theta, and also having any one, two, three, four or five additional peaks selected from 4.6, 5.7,

7.6, 9.3 and 12.9 degrees 2-theta ± 0.2 degrees 2-theta.

[0054] Crystalline Form 2 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having peaks at 4.6, 5.7, 7.6, 9.3, 12.9, 14.6, 16.5, 20.5 and 24.8 degrees 2- theta ± 0.2 degrees 2-theta,

[0055] In one embodiment of the present disclosure, crystalline Form 2 of Zasocitinib is isolated.

[0056] Crystalline Form 2 of Zasocitinib may be characterized by each of the above characteristics alone/or by all possible combinations, e.g., an XRPD pattern having peaks at

14.6, 16.5, 20.5 and 24.8 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 2, and combinations thereof.

[0057] The present disclosure includes a crystalline polymorph of Zasocitinib, designated Form 3. The crystalline Form 3 of Zasocitinib may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 5; an X-ray powder diffraction pattern having a peak at 9.7 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0058] Crystalline Form 3 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having a peak at 9.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having any one, two, three, four or five additional peaks selected from 4.9, 6.7, 7.0, 7.6 and 12.4 degrees 2- theta ± 0.2 degrees 2-theta.

[0059] Crystalline Form 3 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having peaks at 4.9, 6.7, 7.0, 7.6, 9.7 and 12.4 degrees 2-theta ± 0.2 degrees 2- theta.

[0060] In one embodiment of the present disclosure, crystalline Form 3 of Zasocitinib is isolated.

[0061] Crystalline Form 3 of Zasocitinib may be characterized by each of the above characteristics alone/or by all possible combinations, e.g., an XRPD pattern having a peak at 9.7 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 5, and combinations thereof.

[0062] The present disclosure further encompasses crystalline Zasocitinib : L-ascorbic acid. Crystalline Zasocitinib : L-ascorbic acid may be a co-crystal of Zasocitinib and L-ascorbic acid. Alternatively, crystalline Zasocitinib : L-ascorbic acid may be a salt, i.e., Zasocitinib L- ascorbate.

[0063] The disclosure further encompasses a crystalline form of Zasocitinib : L-ascorbic acid, designated form AL Crystalline Form Al of Zasocitinib : L-ascorbic acid may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 3; an X-ray powder diffraction pattern having peaks at 6.4, 12.9 and 21.2 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0064] Crystalline Form Al of Zasocitinib : L-ascorbic acid may be further characterized by an X-ray powder diffraction pattern having peaks at 6.4, 12.9 and 21.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having any one, two, three, four or five additional peaks selected from 5.6, 14.0, 16.8, 19.6 and 20.5 degrees 2-theta ± 0.2 degrees 2-theta.

[0065] In embodiments of the present disclosure, crystalline Form Al of Zasocitinib : L- ascorbic acid is isolated.

[0066] Crystalline Form Al of Zasocitinib : L-ascorbic acid may be characterized by each of the above characteristics alone or by all possible combinations, e.g., an XRPD pattern having peaks at 6.4, 12.9 and 21.2 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 3 and combinations thereof.

[0067] The present disclosure further encompasses crystalline Zasocitinib : benzoic acid. Crystalline Zasocitinib : benzoic acid, may be a co-crystal of Zasocitinib and benzoic acid. Alternatively, crystalline Zasocitinib : benzoic acid, may be a salt, i.e., Zasocitinib benzoate. [0068] The disclosure further encompasses a crystalline form of Zasocitinib benzoic acid., designated form BL Crystalline Form Bl of Zasocitinib: benzoic acid, may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 4 an X-ray powder diffraction pattern having peaks at 8.9 and 13.4 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0069] Crystalline Form B 1 of Zasocitinib: benzoic acid may be further characterized by an X-ray powder diffraction pattern having peaks at 8.9 and 13.4 degrees 2-theta ± 0.2 degrees 2- theta, and also having any one, two, three, four or five additional peaks selected from 5.8, 6.8, 11.7, 15.4 and 18.5 degrees 2-theta ± 0.2 degrees 2-theta.

[0070] In embodiments of the present disclosure, crystalline Form Bl of Zasocitinib: benzoic acid is isolated.

[0071] Crystalline Form B 1 of Zasocitinib: benzoic acid may be characterized by each of the above characteristics alone or by all possible combinations, e.g., an XRPD pattern having peaks at 8.9 and 13.4 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 4 and combinations thereof.

[0072] The present disclosure includes a crystalline polymorph of Zasocitinib, designated Form 4. The crystalline Form 4 of Zasocitinib may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 6; an X-ray powder diffraction pattern having peaks at 5.2, 7.2 and 8.4 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0073] Crystalline Form 4 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having peaks at 5.2, 7.2 and 8.4degrees 2-theta ± 0.2 degrees 2-theta, and also having any one, two, three, or four additional peaks selected from 6.3, 12.7, 15.6 and 18.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0074] Crystalline Form 4 of Zasocitinib may be further characterized by an X-ray powder diffraction pattern having peaks at 5.2, 6.3, 7.2, 8.4, 12.7, 15.6 and 18.1 degrees 2-theta ± 0.2 degrees 2-theta.

[0075] In one embodiment of the present disclosure, crystalline Form 4 of Zasocitinib is isolated.

[0076] Crystalline Form 4 of Zasocitinib may be characterized by each of the above characteristics alone/or by all possible combinations, e.g., an XRPD pattern having peaks at 5.2, 7.2 and 8.4 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 6, and combinations thereof.

[0077] The present disclosure further encompasses crystalline Zasocitinib : L-malic acid. Crystalline Zasocitinib : L-malic acid may be a co-crystal of Zasocitinib and L-malic acid. Alternatively, crystalline Zasocitinib : L-malic acid may be a salt, i.e., Zasocitinib L-malate. [0078] The disclosure further encompasses a crystalline form of Zasocitinib : L-malic acid, designated Form ML Crystalline Form Ml of Zasocitinib : L-malic acid may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 7; an X-ray powder diffraction pattern having peaks at 6.4 and 6.8 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0079] Crystalline Form Ml of Zasocitinib : L-malic acid may be further characterized by an X-ray powder diffraction pattern having peaks at 6.4 and 6.8 degrees 2-theta ± 0.2 degrees 2- theta, and also having any one, or two additional peaks selected from 9.1 and 17.5 degrees 2- theta ± 0.2 degrees 2-theta.

[0080] Crystalline Form Ml of Zasocitinib : L-malic acid may be further characterized by an X-ray powder diffraction pattern having peaks at 6.4, 6.8, 9.1 and 17.5 degrees 2-theta ± 0.2 degrees 2-theta.

[0081] In embodiments of the present disclosure, crystalline Form Ml of Zasocitinib : L- malic acid is isolated.

[0082] Crystalline Form Ml of Zasocitinib : L-malic acid may be characterized by each of the above characteristics alone or by all possible combinations, e.g., an XRPD pattern having peaks at 6.4 and 6.8 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 7 ; and combinations thereof.

[0083] The present disclosure further encompasses crystalline Zasocitinib : citric acid.. Crystalline Zasocitinib : citric acid may be a co-crystal of Zasocitinib and citric acid. Alternatively, crystalline Zasocitinib : citric acid may be a salt, i.e., Zasocitinib citrate.

[0084] The disclosure further encompasses a crystalline form of Zasocitinib : citric acid, designated Form LI. Crystalline Form LI of Zasocitinib : citric acid may be characterized by data selected from one or more of the following: an X-ray powder diffraction pattern substantially as depicted in Figure 8 an X-ray powder diffraction pattern having peaks at 4.3 and 8.5 degrees 2-theta ± 0.2 degrees 2-theta; and combinations of these data.

[0085] Crystalline Form LI of Zasocitinib : citric acid may be further characterized by an X- ray powder diffraction pattern having peaks at 4.3 and 8.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having any one, two, three, four or five additional peaks selected from 6.4, 9.7, 13.7, 16.9 and 17.6 degrees 2-theta ± 0.2 degrees 2-theta.

[0086] Crystalline Form LI of Zasocitinib : citric acid may be further characterized by an X- ray powder diffraction pattern having peaks at 4.3, 6.4, 8.5, 9.7, 13.7, 16.9 and 17.6degrees 2- theta ± 0.2 degrees 2-theta . [0087] In embodiments of the present disclosure, crystalline Form LI of Zasocitinib : citric acid is isolated.

[0088] Crystalline Form LI of Zasocitinib : citric acid may be characterized by each of the above characteristics alone or by all possible combinations, e.g., an XRPD pattern having peaks at 4.3 and 8.5 degrees 2-theta ± 0.2 degrees 2-theta; an XRPD pattern as depicted in Figure 8; and combinations thereof.

[0089] The above crystalline polymorphs can be used to prepare other crystalline polymorphs of Zasocitinib, Zasocitinib salts or Zasocitinib co-crystals and their solid state forms. [0090] The present disclosure encompasses a process for preparing other solid state forms of Zasocitinib, Zasocitinib salts or Zasocitinib co-crystals and their solid state forms thereof. The process includes preparing any one of the Zasocitinib and solid state forms of Zasocitinib by the processes of the present disclosure and converting that salt to said other Zasocitinib salt or cocrystal. The conversion can be done, for example, by a process including acidifying any one or a combination of the above described Zasocitinib (salts) and/or solid state forms thereof and reacting the obtained Zasocitinib base with an appropriate acid, to obtain the corresponding salt. Alternatively, the conversion can be done by salt switching, i.e., reacting a Zasocitinib base addition salt, with an acid having a pKa which is lower than the pKa of the acid of the first Zasocitinib acid addition salt (or, for base addition salts: reacting a Zasocitinib base addition salt, with a base having a pKa which is higher than the pKa of the base of the first Zasocitinib base addition salt).

[0091] The present disclosure provides the above described crystalline polymorphs of Zasocitinib or salts or co-crystals thereof for use in the preparation of pharmaceutical compositions comprising Zasocitinib or salts or co-crystals thereof and/or crystalline polymorphs thereof.

[0092] The present disclosure also encompasses the use of crystalline polymorphs of Zasocitinib or salts or co-crystals thereof of the present disclosure for the preparation of pharmaceutical compositions of crystalline polymorph Zasocitinib or salts or co-crystals thereof and/or crystalline polymorphs thereof.

[0093] The present disclosure includes processes for preparing the above mentioned pharmaceutical compositions. The processes include combining any one or a combination of the crystalline polymorphs of Zasocitinib or salts or co-crystals thereof of the present disclosure with at least one pharmaceutically acceptable excipient.

[0094] Pharmaceutical combinations or formulations of the present disclosure contain any one or a combination of the solid state forms of Zasocitinib or salts or co-crystals thereof of the present disclosure. In addition to the active ingredient, the pharmaceutical formulations of the present disclosure can contain one or more excipients. Excipients are added to the formulation for a variety of purposes.

[0095] Diluents increase the bulk of a solid pharmaceutical composition and can make a pharmaceutical dosage form containing the composition easier for the patient and caregiver to handle. Diluents for solid compositions include, for example, microcrystalline cellulose (e.g. Avicel®), microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylates (e.g. Eudragit®), potassium chloride, powdered cellulose, sodium chloride, sorbitol, and talc.

[0096] Solid pharmaceutical compositions that are compacted into a dosage form, such as a tablet, can include excipients whose functions include helping to bind the active ingredient and other excipients together after compression. Binders for solid pharmaceutical compositions include acacia, alginic acid, carbomer (e.g. carbopol), carboxymethylcellulose sodium, dextrin, ethyl cellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose (e.g. Klucel®), hydroxypropyl methyl cellulose (e.g. Methocel®), liquid glucose, magnesium aluminum silicate, maltodextrin, methylcellulose, polymethacrylates, povidone (e.g. Kollidon®, Plasdone®), pregelatinized starch, sodium alginate, and starch.

[0097] The dissolution rate of a compacted solid pharmaceutical composition in the patient's stomach can be increased by the addition of a disintegrant to the composition. Disintegrants include alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium (e.g. Ac- Di-Sol®, Primellose®), colloidal silicon dioxide, croscarmellose sodium, crospovidone (e.g. Kollidon®, Polyplasdone®), guar gum, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate (e.g. Explotab®), and starch. [0098] Glidants can be added to improve the flowability of a non-compacted solid composition and to improve the accuracy of dosing. Excipients that can function as glidants include colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc, and tribasic calcium phosphate.

[0099] When a dosage form such as a tablet is made by the compaction of a powdered composition, the composition is subjected to pressure from a punch and dye. Some excipients and active ingredients have a tendency to adhere to the surfaces of the punch and dye, which can cause the product to have pitting and other surface irregularities. A lubricant can be added to the composition to reduce adhesion and ease the release of the product from the dye. Lubricants include magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc, and zinc stearate. [00100] Flavoring agents and flavor enhancers make the dosage form more palatable to the patient. Common flavoring agents and flavor enhancers for pharmaceutical products that can be included in the composition of the present disclosure include maltol, vanillin, ethyl vanillin, menthol, citric acid, fumaric acid, ethyl maltol, and tartaric acid.

[00101] Solid and liquid compositions can also be dyed using any pharmaceutically acceptable colorant to improve their appearance and/or facilitate patient identification of the product and unit dosage level.

[00102] In liquid pharmaceutical compositions of the present invention, Zasocitinib or salts or co-crystals thereof and any other solid excipients can be dissolved or suspended in a liquid carrier such as water, vegetable oil, alcohol, polyethylene glycol, propylene glycol, or glycerin. [00103] Liquid pharmaceutical compositions can contain emulsifying agents to disperse uniformly throughout the composition an active ingredient or other excipient that is not soluble in the liquid carrier. Emulsifying agents that can be useful in liquid compositions of the present invention include, for example, gelatin, egg yolk, casein, cholesterol, acacia, tragacanth, chondrus, pectin, methyl cellulose, carbomer, cetostearyl alcohol, and cetyl alcohol.

[00104] Liquid pharmaceutical compositions of the present invention can also contain a viscosity enhancing agent to improve the mouthfeel of the product and/or coat the lining of the gastrointestinal tract. Such agents include acacia, alginic acid bentonite, carbomer, carboxymethylcellulose calcium or sodium, cetostearyl alcohol, methyl cellulose, ethylcellulose, gelatin guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, maltodextrin, polyvinyl alcohol, povidone, propylene carbonate, propylene glycol alginate, sodium alginate, sodium starch glycolate, starch tragacanth, xanthan gum and combinations thereof.

[00105] Sweetening agents such as sorbitol, saccharin, sodium saccharin, sucrose, aspartame, fructose, mannitol, and invert sugar can be added to improve the taste.

[00106] Preservatives and chelating agents such as alcohol, sodium benzoate, butylated hydroxyl toluene, butylated hydroxyanisole, and ethylenediamine tetraacetic acid can be added at levels safe for ingestion to improve storage stability.

[00107] According to the present disclosure, a liquid composition can also contain a buffer such as gluconic acid, lactic acid, citric acid, or acetic acid, sodium gluconate, sodium lactate, sodium citrate, or sodium acetate. Selection of excipients and the amounts used can be readily determined by the formulation scientist based upon experience and consideration of standard procedures and reference works in the field.

[00108] The solid compositions of the present disclosure include powders, granulates, aggregates, and compacted compositions. The dosages include dosages suitable for oral, buccal, rectal, parenteral (including subcutaneous, intramuscular, and intravenous), inhalant, and ophthalmic administration. Although the most suitable administration in any given case will depend on the nature and severity of the condition being treated, in embodiments the route of administration is oral. The dosages can be conveniently presented in unit dosage form and prepared by any of the methods well-known in the pharmaceutical arts.

[00109] Dosage forms include solid dosage forms like tablets, powders, capsules, suppositories, sachets, troches, and lozenges, as well as liquid syrups, suspensions, and elixirs. [00110] The dosage form of the present disclosure can be a capsule containing the composition, such as a powdered or granulated solid composition of the disclosure, within either a hard or soft shell. The shell can be made from gelatin and optionally contain a plasticizer such as glycerin and/or sorbitol, an opacifying agent and/or colorant.

[00111] The active ingredient and excipients can be formulated into compositions and dosage forms according to methods known in the art.

[00112] A composition for tableting or capsule filling can be prepared by wet granulation. In wet granulation, some or all of the active ingredients and excipients in powder form are blended and then further mixed in the presence of a liquid, typically water, that causes the powders to clump into granules. The granulate is screened and/or milled, dried, and then screened and/or milled to the desired particle size. The granulate can then be tableted, or other excipients can be added prior to tableting, such as a glidant and/or a lubricant.

[00113] A tableting composition can be prepared conventionally by dry blending. For example, the blended composition of the actives and excipients can be compacted into a slug or a sheet and then comminuted into compacted granules. The compacted granules can subsequently be compressed into a tablet.

[00114] As an alternative to dry granulation, a blended composition can be compressed directly into a compacted dosage form using direct compression techniques. Direct compression produces a more uniform tablet without granules. Excipients that are particularly well suited for direct compression tableting include microcrystalline cellulose, spray dried lactose, dicalcium phosphate dihydrate, and colloidal silica. The proper use of these and other excipients in direct compression tableting is known to those in the art with experience and skill in particular formulation challenges of direct compression tableting.

[00115] A capsule filling of the present disclosure can include any of the aforementioned blends and granulates that were described with reference to tableting, but they are not subjected to a final tableting step.

[00116] A pharmaceutical formulation of Zasocitinib or salts or co-crystals thereof can be administered. Zasocitinib or salts or co-crystals thereof may be formulated for administration to a mammal, in embodiments to a human, by injection. Zasocitinib or salts or co-crystals thereof can be formulated, for example, as a viscous liquid solution or suspension, such as a clear solution, for injection. The formulation can contain one or more solvents. A suitable solvent can be selected by considering the solvent's physical and chemical stability at various pH levels, viscosity (which would allow for syringeability), fluidity, boiling point, miscibility, and purity. Suitable solvents include alcohol USP, benzyl alcohol NF, benzyl benzoate USP, and Castor oil USP. Additional substances can be added to the formulation such as buffers, solubilizers, and antioxidants, among others. Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th ed.

[00117] The crystalline polymorphs of Zasocitinib or salts or co-crystals thereof and the pharmaceutical compositions and/or formulations of Zasocitinib or salts or co-crystals thereof of the present disclosure can be used as medicaments, in embodiments in the treatment of moderate to severe Plaque Psoriasis.

[00118] The present disclosure also provides methods of treating moderate to severe Plaque Psoriasis, by administering a therapeutically effective amount of any one or a combination of the crystalline polymorphs of Zasocitinib or salts or co-crystals thereof of the present disclosure, or at least one of the above pharmaceutical compositions and/or formulations, to a subject in need of the treatment.

[00119] 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.

Powder X-ray Diffraction (“XRPD”) method

[00120] 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. Peak positions were determined without using silicon powder as an internal standard.

EXAMPLES

Preparation of starting materials

[00121] Zasocitinib can be prepared according to methods known from the literature, for example, U.S. Patent No. 10,577,373 or WO 2023/183910.

Example 1: Preparation of Zasocitinib Form 1

[00122] Zasocitinib base (1 gram) was suspended in 1 ,4-dioxane/water (11:1, 10 mL) and heated to reflux. A clear solution was obtained. Heating was turned off and the solution was left to cool in an oil bath. Crystallization occurred and the suspension was left to stir overnight at room temperature (around 25 °C). Then it was filtrated off over blue ribbon filter paper under vacuum, and washed with 4 mL of dioxane/water (10: 1). The obtained solid was analyzed by XRPD. Zasocitinib base Form 1 was obtained. Example 2: Preparation of Zasocitinib Form 2

[00123] Zasocitinib base (200 mg) was suspended in trifluoroethanol/water (1:3, 2 mL) at room temperature (around 25 °C). The suspension was left to stir for 2 days. Then it was filtrated off over blue ribbon filter paper under vacuum. The obtained solid was analyzed by XRPD and Zasocitinib base Form B2 was obtained.

Example 3: Preparation of Zasocitinib : L-ascorbic acid Form Al

[00124] Zasocitinib base (800 mg) and L-ascorbic acid (400 mg) were suspended in acetonitrile (9 mL) at temperature of 50°C. The suspension was left to stir for 12 days. Then it was filtrated off over blue ribbon filter paper under vacuum. The obtained solid was dried at 50°C for 2 hours and analyzed by XRPD and Zasocitinib : L-ascorbic acid Form Al was obtained.

Example 4: Preparation of Zasocitinib : benzoic acid Form Bl

[00125] Zasocitinib base (395 mg) and benzoic acid (816 mg) were suspended in 2-propanol (7 mL) at temperature of 50°C. The suspension was heated to reflux. Then heating was turned off and it was left to cool to room temperature in oil bath. It was left to stir overnight at room temperature (around 25 °C). Then it was filtrated off over blue ribbon filter paper under vacuum. The obtained solid was analyzed by XRPD and Zasocitinib : benzoic acid Form B 1 was obtained.

Example 5: Preparation of Zasocitinib Form 3

[00126] Zasocitinib base (1 gram) was suspended in THF/water (2: 1) and heated to reflux. A clear solution was obtained. Heating was turned off and the solution was left to cool in an oil bath. Crystallization occurred and the suspension was left to stir overnight at room temperature (around 25 °C). Then it was filtrated off over blue ribbon filter paper under vacuum. The obtained solid was dried in a drying oven at 80 °C under vacuum for 4 hours. The obtained solid was analyzed by XRPD and Zasocitinib base Form 3 was obtained. Example 6: Preparation of Zasocitinib Form 4

[00127] Zasocitinib base Form F (30 mg) was suspended in 0.3 mL of EtOH/water (10:1) at 5- 10°C. The suspension was stirred for 1 day, filtrated off and analyzed by XRPD. Zasocitinib base Form 4 was obtained.

Example 7: Preparation of Zasocitinib : L-malic acid Form Ml

[00128] Zasocitinib base Form C (866 mg) and L-malic acid (1134 mg, 4.5 eq.) were suspended in 15 mL of acetonitrile at room temperature. The suspension was stirred for 4 days at room temperature, then filtrated off and analyzed by XRPD, Zasocitinib and L-malic acid Eorm Ml was obtained.

Example 8: Preparation of Zasocitinib : citric acid Form LI

[00129] Zasocitinib base Form C (55 mg) and citric acid (23 mg, 1 eq.) were suspended in 1 mL of acetonitrile at room temperature. The suspension was stirred for 9 days at room temperature, then filtrated off and analyzed by XRPD, Zasocitinib and citric acid Form LI was obtained.

[00130] Further aspects and embodiments of the present disclosure are set out in the numbered clauses below:

1. Crystalline Zasocitinib: L-ascorbic acid

2. Crystalline Zasocitinib: L-ascorbic acid, which is a co-crystal.

3. Crystalline Zasocitinib: L-ascorbate.

4. A crystalline product according to Clause 1, 2, or 3, designated form Al, which is characterized by data selected from one or more of the following: a. an XRPD pattern having peaks at 6.4, 12.9 and 21.2 degrees 2-theta ± 0.2 degrees 2-theta; b. an XRPD pattern as depicted in Figure 3 ; and c. combinations of these data.

5. A crystalline product according to any of Clauses 1, 2, 3 or 4, designated form Al, characterized by the XRPD pattern having peaks at 6.4, 12.9 and 21.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 5.6, 14.0, 16.8, 19.6 and 20.5 degrees two theta ± 0.2 degrees two theta A crystalline product according to any of Clauses 1, 2, 3, 4, or 5, designated form Al, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of any other crystalline forms of Zasocitinib : L-ascorbic acid or crystalline Zasocitinib : L-ascorbate. A crystalline product according to any of Clauses 1, 2, 3, 4, 5 or 6, designated form Al, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of amorphous Zasocitinib: L-ascorbic acid or crystalline Zasocitinib : L-ascorbate. Crystalline Zasocitinib: benzoic acid Crystalline Zasocitinib: benzoic acid, which is a co-crystal. Crystalline Zasocitinib: benzoate. A crystalline product according to Clause 8, 9 or 10, designated form Bl, which is characterized by data selected from one or more of the following: d. an XRPD pattern having peaks at 8.9 and 13.4 degrees 2-theta ± 0.2 degrees 2-theta; e. an XRPD pattern as depicted in Figure 4; and f. combinations of these data. A crystalline product according to any of Clauses 8, 9 ,10 or 11, designated Form Bl, characterized by the XRPD pattern having peaks at 8.9 and 13.4 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 5.8, 6.8, 11.7, 15.4 and 18.5 degrees two theta ± 0.2 degrees two theta A crystalline product according to any of Clauses 8, 9, 10, 11 or 12, designated Form Bl, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of any other crystalline forms of Zasocitinib : benzoic acid or crystalline Zasocitinib : benzoate. A crystalline product according to any of Clauses 8, 9, 10, 11, 12 or 13, designated Form Bl, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of amorphous Zasocitinib: benzoic acid or crystalline Zasocitinib : benzoate. Crystalline Zasocitinib: L-malic acid Crystalline Zasocitinib: L-malic acid, which is a co-crystal. Crystalline Zasocitinib: malate. A crystalline product according to Clause 15, 16, or 17, designated Form Ml, which is characterized by data selected from one or more of the following: g. an XRPD pattern having peaks at 6.4 and 6.8 degrees 2-theta ± 0.2 degrees 2-theta; h. an XRPD pattern as depicted in Figure 5 ; and i. combinations of these data. A crystalline product according to any of Clauses 15, 16, 17, or 18, designated Form Ml, characterized by the XRPD pattern having peaks at 6.4 and 6.8 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, or two additional peaks selected from 9.1 and 17, .5 degrees two theta ± 0.2 degrees two theta A crystalline product according to any of Clauses 15, 16 ,17, 18, orl9, designated Form Ml, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of any other crystalline forms of Zasocitinib : L-malic or crystalline Zasocitinib : malate. A crystalline product according to any of 15, 16, 17, 18, 19, 20, or 21, designated form Bl, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of amorphous Zasocitinib: malic acid or crystalline Zasocitinib : L-malate. Crystalline Zasocitinib: citric acid Crystalline Zasocitinib: citric acid, which is a co-crystal. Crystalline Zasocitinib: citrate. A crystalline product according to Clause 22, 23, and 24, designated Form LI, which is characterized by data selected from one or more of the following: j. an XRPD pattern having peaks at 4.3 and 8.5 degrees 2-theta ± 0.2 degrees 2-theta; k. an XRPD pattern as depicted in Figure 8; and l. combinations of these data. A crystalline product according to any of Clauses 22, 23, and 24, designated Form LI, characterized by the XRPD pattern having peaks at 4.3 and 8.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, or two additional peaks selected from 6.4, 9.7, 13.7, 16.9 and 17.6 degrees two theta ± 0.2 degrees two theta A crystalline product according to any of Clauses 22, 23, 24, 25, or 26, designated Form LI, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of any other crystalline forms of Zasocitinib : citric acid or crystalline Zasocitinib : citrate. A crystalline product according to any of 22, 23, 24, 25, 26, or 27 , designated Form LI, which contains: no more than about 20%, no more than about 10%, no more than about 5%, no more than about 2%, no more than about 1% or about 0% of amorphous Zasocitinib: citric acid or crystalline Zasocitinib : citrate.

Claims

Claims

1. A crystalline product comprising a crystalline form of Zasocitinib, designated form 2, which is characterized by data selected from one or more of the following: a) an XRPD pattern having peaks at 14.6, 16.5, 20.5 and 24.8 degrees 2-theta ± 0.2 degrees 2-theta; b) an XRPD pattern as depicted in Figure 2; or combination of a) and b).

2. The crystalline product according to claim 1 , which is characterized by an XRPD pattern having peaks at 14.6, 16.5, 20.5 and 24.8 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 4.6, 5.7, 7.6, 9.3 and 12.9 degrees 2- theta ± 0.2 degrees 2-theta.

3. A crystalline product comprising a crystalline form of Zasocitinib, designated form 3, which is characterized by data selected from one or more of the following: a) an XRPD pattern having a peak at 9.7 degrees 2-theta ± 0.2 degrees 2-theta; b) an XRPD pattern as depicted in Figure 5; or combination of a) and b).

4. The crystalline product according to claim 3, which is characterized by an XRPD pattern having a peak at 9.7 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 4.9, 6.7, 7.0, 7.6 and 12.4 degrees 2-theta ± 0.2 degrees 2- theta.

5. A crystalline product comprising crystalline Zasocitinib: L-ascorbic acid.

6. The crystalline product according to claim 5, designated form Al, which is characterized by data selected from one or more of the following: a) an XRPD pattern having peaks at 6.4, 12.9 and 21.2 degrees 2-theta ± 0.2 degrees 2-theta; b) an XRPD pattern as depicted in Figure 3; or combination of a) and b).

7. A crystalline product according claim 5 or 6, designated form Al, characterized by the XRPD pattern having peaks at 6.4, 12.9 and 21.2 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 5.6, 14.0, 16.8, 19.6 and 20.5 degrees two theta ± 0.2 degrees two theta.

8. A crystalline product comprising crystalline Zasocitinib: benzoic acid.

9. The crystalline product according to claim 8, designated form Bl, which is characterized by data selected from one or more of the following: a) an XRPD pattern having peaks at 8.9 and 13.4 degrees 2-theta ± 0.2 degrees 2- theta; b) an XRPD pattern as depicted in Figure 4; or combination of a) and b).

10. The crystalline product according to claim 8 or 9, designated form Bl, characterized by the XRPD pattern having peaks at 8.9 and 13.4 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 5.8, 6.8, 11.7, 15.4 and 18.5 degrees two theta ± 0.2 degrees two theta.

11. A crystalline product comprising crystalline Zasocitinib: L-malic acid.

12. The crystalline product according to claim 11, designated form Ml, which is characterized by data selected from one or more of the following: a) an XRPD pattern having peaks at 6.4 and 6.8 degrees 2-theta ± 0.2 degrees 2- theta; b) an XRPD pattern as depicted in Figure 5; or combination of a) and b).

13. The crystalline product according to claim 11 or 12, designated form Ml, characterized by the XRPD pattern having peaks at 6.4 and 6.8 degrees 2-theta ± 0.2 degrees 2-theta, and having one, or two additional peaks selected from 9.1 and 17, .5 degrees two theta ± 0.2 degrees two theta.

14. A crystalline product comprising crystalline Zasocitinib: citric acid.

15. The crystalline product according to claim 14, designated form LI, which is characterized by data selected from one or more of the following: a) an XRPD pattern having peaks at 4.3 and 8.5 degrees 2-theta ± 0.2 degrees 2- theta; b) an XRPD pattern as depicted in Figure 8; or combination of a) and b).

16. The crystalline product according to claim 14 or 15, designated form LI, characterized by the XRPD pattern having peaks at 4.3 and 8.5 degrees 2-theta ± 0.2 degrees 2-theta, and also having one, two, three, four, or five additional peaks selected from 6.4, 9.7, 13.7, 16.9 and 17.6 degrees two theta ± 0.2 degrees two theta.

17. A pharmaceutical composition comprising the crystalline product according to any one of claims 1-16.

18. The pharmaceutical composition according to claim 17, further comprising at least one pharmaceutically acceptable excipient.

19. Use of the crystalline product according to any one of claims 1-16 in the preparation of a pharmaceutical composition and/or formulation.

20. A process for preparing a pharmaceutical composition comprising combining the crystalline product according to any of claims 1-16 with at least one pharmaceutically acceptable excipient.

21. The crystalline product according to any one of claims 1 to 16, the pharmaceutical composition according to claim 17 or 18, for use as a medicament.

22. The crystalline product according to any of claims 1-16, or the pharmaceutical composition according to claim 17 or 18, for use in the treatment of moderate-to-severe Plaque Psoriasis.

23. A method of treating moderate-to-severe Plaque Psoriasis, comprising administering a therapeutically effective amount of the crystalline product according to any of claims 1-16, or the pharmaceutical composition according to claim 17 or 18, to a subject in need of the treatment.

24. Use of the crystalline product according to any of claims 1-16, in the preparation of other crystalline polymorphs of Zasocitinib, Zasocitinib salts and their solid state forms or other cocrystals of Zasocitinib and their solid state forms.