WO2021195206A1

WO2021195206A1 - Polymorphic forms and related uses

Info

Publication number: WO2021195206A1
Application number: PCT/US2021/023876
Authority: WO
Inventors: Alexander Flohr
Original assignee: Black Diamond Therapeutics, Inc.
Priority date: 2020-03-24
Filing date: 2021-03-24
Publication date: 2021-09-30

Abstract

The present disclosure relates to polymorphic forms of the receptor tyrosine kinases inhibitor compound of formula (I), pharmaceutical compositions comprising the polymorphic forms, methods of making the polymorphic forms, and methods of using the polymorphic forms and pharmaceutical compositions thereof as a medicament, e.g., in the treatment of cancer.

Description

POLYMORPHIC FORMS AND RELATED USES RELATED APPLICATIONS This application claims priority to, and the benefit of, U.S. Application No. 62/994,104, filed March 24, 2020, the entire contents of which is incorporated herein by reference FIELD OF THE DISCLOSURE The present disclosure relates to polymorphic forms of the receptor tyrosine kinases inhibitor compound of formula I, pharmaceutical compositions comprising the polymorphic forms, methods of making the polymorphic forms, and methods of using the polymorphic forms and pharmaceutical compositions thereof as a medicament, e.g., in the treatment of cancer. BACKGROUND OF THE DISCLOSURE Controlling polymorphism, the occurrence of amorphous and crystalline form(s), is a critical aspect in the development into a pharmaceutical product. Polymorphic forms affect not only developmental tasks such as purification and formulation of a drug, but even the efficacy of a drug can be dependent on the final polymorphic form. Ways for obtaining specific forms suitable for a specific administration are manifold and vary from one drug to another. A single compound may give rise to a variety of polymorphic forms with distinct crystal structures showing different physical properties including thermal behaviours, which can be characterized (and distinguished) by one or more of x-ray diffraction pattern, infrared absorption fingerprint, Raman and NMR spectra, thermogravimetric analysis (optionally coupled with Fourier transformed infrared spectroscopy), differential scanning calorimetry, dynamic vapour sorption and other techniques. Due to the distinct physical properties of a particular polymorphic form, it may have advantages over other forms with regard to stability, solubility, bioavailability, as well as processing properties, such as handling, processing, shelve life, purification or as desirable intermediate crystal forms that facilitate conversion to other polymorphic forms, and the like. Thus, new polymorphic forms of a pharmaceutically useful compound can provide an opportunity for formulation optimization and to improve the performance characteristics of a pharmaceutical product. Compound of formula I is a new receptor tyrosine kinases inhibitor, which may be used for the prevention and treatment of cancer. It has been found that specific polymorphic forms of the disclosure show improved properties such as stability, solubility, bioavailability and/or ease of handling, and thus are specifically suitable for the manufacture of specific dosage forms. SUMMARY OF THE DISCLOSURE The present disclosure provides polymorphic forms of the receptor tyrosine kinases inhibitor compound of formula I.

The present disclosure also provides characterization of the identified polymorphic forms, pharmaceutical compositions comprising the polymorphic forms, methods of making the polymorphic forms, and methods of using the polymorphic forms and pharmaceutical compositions thereof as a medicament, e.g., in the prevention and treatment of cancer. In some embodiments, the polymorphic forms of the disclosure are crystalline, in some embodiments the polymorphic forms of the disclosure are amorphous. In some embodiments, the polymorphic forms of the disclosure are anhydrous, in some embodiments the polymorphic forms of the disclosure are hydrates, such as a monohydrate, or solvates. In some embodiments, the polymorphic forms of the disclosure include the monohydrate crystalline form designated Form 1, the anhydrous crystalline form designated Form 2, the non- solvated crystalline forms designated Form 4 or Form 5, and the solvated forms designated Form A or Form B or Form C or Form D or Form E or Form F. In some embodiments, the polymorphic forms of the disclosure include the amorphous Form G In some embodiments, the polymorphic forms are at least 90, 95, 96, 97, 98, or 99% pure. In some embodiments, the crystalline forms are at least 90, 95, 96, 97, 98, or 99% pure. In some embodiments, the disclosure provides a monohydrate crystalline form of polymorphic form (or Form 1). In some embodiments, the monohydrate crystalline form is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 1A. In some embodiments, the monohydrate crystalline Form 1 is characterized by a DSC thermogram comprising dehydration endothermic peak at about 105-135 °C. In some embodiments the monohydrate crystalline Form 1 is characterized by a DSC thermogram comprising a melting endothermic peak at about 166.0 °C In some embodiments, the monohydrate crystalline Form 1 is characterized by a DVS curve exhibiting a weight increase of about 0.25% or less. In some embodiments, the monohydrate crystalline Form 1 is characterized by a Raman spectrum comprising at least one peak, e.g., one or two or three or more peaks at wavenumbers (cm^-1) selected from a Raman spectrum substantially in accordance with Figure 1E. In some embodiments, the monohydrate crystalline Form 1 is characterized by a FTIR spectrum comprising at least one peak, e.g., one or two or three or more peaks at wavenumbers (cm^-1) selected from a FTIR spectrum substantially in accordance with Figure 1F. In some embodiments, the monohydrate crystalline Form 1 is characterized by a TG-FTIR curve showing changes in mass substantially in accordance with a TG-FTIR shown in Figure 1G. In another aspect, the disclosure provides an anhydrous crystalline form of the compound of formula I (or Form 2). In some embodiments, the anhydrous crystalline Form 2 is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 2A. In some embodiments the anhydrous crystalline Form 2 is characterized by a DSC thermogram comprising a melting endothermic peak at about 177.0 °C. In some embodiments, the anhydrous crystalline Form 2 is characterized by a DVS curve exhibiting a weight increase of about 0.25% or less (Figure 2B). In some embodiments, the anhydrous crystalline Form 2 is characterized by a Raman spectrum comprising at least one peak, e.g., one or two or three or more peaks at wavenumbers (cm^-1) selected from a Raman spectrum substantially in accordance with Figure 2C. In some embodiments, the anhydrous crystalline Form 2 is characterized by a TG-FTIR curve showing changes in mass substantially in accordance with a TG-FTIR curve shown in Figure 2D. In another aspect, the disclosure provides a non-solvated crystalline form of the compound of formula I (or Form 3). In some embodiments, the non-solvated crystalline Form 3 is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 3A. In another aspect, the disclosure provides a non-solvated crystalline form of the compound of formula I (or Form 4). In some embodiments, the non-solvated crystalline Form 4 is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 4A. In another aspect, the disclosure provides a solvated crystalline form of the compound of formula I (a crystalline ethanol solvate or Form A). In some embodiments, the solvated crystalline Form A is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 5A. In another aspect, the disclosure provides a solvated crystalline form of the compound of formula I (a crystalline dimethylsulfoxide solvate or Form B). In some embodiments, the solvated crystalline Form B is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 6A. In another aspect, the disclosure provides a solvated crystalline form of the compound of formula I (a crystalline dimethylformamide solvate or Form C). In some embodiments, the solvated crystalline Form C is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 7A. In another aspect, the disclosure provides a solvated crystalline form of the compound of formula I (a crystalline methanol solvate or Form D). In some embodiments, the anhydrous solvated Form D is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 8A. In another aspect, the disclosure provides a solvated crystalline form of the compound of formula I (a crystalline 2-propanol solvate or Form E). In some embodiments, the solvated crystalline Form E is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 9A. In another aspect, the disclosure provides a solvated crystalline form of the compound of formula I (a crystalline acetone solvate or Form F). In some embodiments, the anhydrous solvated Form F is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 10A. In another aspect, the disclosure provides an amorphous form of the compound of formula I (or Form G). In some embodiments, the amorphous Form G is characterized by a powder x-ray diffraction (XRPD) pattern comprising at least one peak, e.g., one or two or three or more peaks at diffraction angles (2-theta) selected from a XRPD pattern substantially in accordance with Figure 11A. In other aspects, the present disclosure provides a process for preparing a polymorphic form of the disclosure. The new polymorphic forms may be prepared by any method for preparing solid state forms known in the prior art, including various crystallization methods, suspension equilibrium methods, desolvation and dehydration methods of solvates and hydrates, respectively, solution mediated polymorphic transformation (slurry conversion method), solid-state polymorphic transformation, and others. In some aspects, the present disclosure provides a pharmaceutical composition comprising any one, or combination, of the polymorphic forms of the disclosure. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. In some embodiments, the composition further comprises a second therapeutically active agent. In some embodiments, the second therapeutically active agent comprises a non-Type I inhibitor. In some embodiments, the non-Type I inhibitor comprises a small molecule Type II inhibitor. In some embodiments the compositions are in solid form. In some embodiments the compositions are in liquid form. In some aspects, the present disclosure provides a method of inhibiting an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR), comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of inhibiting an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR), comprising administering to the subject in need thereof a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in the subject; and ii) administering to the subject in need of the treatment a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in the subject; and ii) administering to the subject in need of the treatment a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject; and ii) administering to the subject in need of the treatment a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject; and ii) administering to the subject in need of the treatment a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in the subject. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a polymorphic form described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in the subject. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in a biological sample from the subject. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a composition described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in a biological sample from the subject. In some aspects, the present disclosure provides a polymorphic form described herein for use in the inhibition of an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR). In some aspects, the present disclosure provides a composition described herein for use in the inhibition of an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR). In some aspects, the present disclosure provides a polymorphic form described herein for use in the prevention or treatment of cancer. In some aspects, the present disclosure provides a composition described herein for use in the prevention or treatment of cancer. In some aspects, the present disclosure provides a polymorphic form described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in the subject. In some aspects, the present disclosure provides a composition described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in the subject. In some aspects, the present disclosure provides a polymorphic form described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject. In some aspects, the present disclosure provides a composition described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject. In some aspects, the present disclosure provides use of a polymorphic form described herein in the manufacture of a medicament for inhibiting an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR). In some aspects, the present disclosure provides use of a polymorphic form described herein in the manufacture of a medicament for preventing or treating cancer. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods and examples are illustrative only and are not intended to be limiting. In the case of conflict between the chemical structures and names of the compounds disclosed herein, the chemical structures will control. Other features and advantages of the disclosure will be apparent from the following detailed description and claims. BRIEF DESCRIPTION OF THE FIGURES Figure 1A is a XRPD pattern of the crystalline monohydrate Form 1 at room temperature. Figure 1B is a DSC thermogram of the crystalline monohydrate Form 1 at room temperature showing a dehydration endothermic peak at about 105-135 °C and a melting endothermic peak at about 166.0 °C. Figure 1C is a DVS curve for the crystalline monohydrate Form 1 at room temperature showing relative humidity (in %) and the change in mass (sample wt %). Figure 1D is a further DVS curve for the crystalline monohydrate Form 1 at room temperature showing sample wt % against relative humidity. Figure 1E shows a FT-Raman spectrum of the crystalline monohydrate Form 1. The most pronounced Raman peaks are labelled in the figure. Figure 1F is a TG-FTIR spectrum of the crystalline monohydrate Form 1. Figure 1G is a FTIR spectrum of the crystalline monohydrate Form 1 at room temperature. Figure 1H shows XRPD patterns of crystalline monohydrate Form 1 (1H-a) and the crystalline non-solvated Form 4 (1H-b) used in competitive slurry experiments to give at equilibrium the monohydrate Form 1 (1H-c). Figure 2A is a XRPD pattern of the crystalline anhydrous Form 2 at room temperature. Figure.2B is a DSC thermogram of the crystalline anhydrous Form 2 at room temperature showing a melting enthalpy of about 60 J/g and a melting point of about 172 °C. Figure 2C shows a FT-Raman spectrum of the crystalline anhydrous Form 2. The most pronounced Raman peaks are labelled in the figure. Figure 2D is a TG-FTIR spectrum of the crystalline anhydrous Form 2 showing a mass loss of 0.75 wt. % of water and a mass loss of 0.26 wt. % of bound dichloromethane. Figure 3A is a XRPD pattern of the crystalline non-solvated Form 3 at room temperature. Figure 3B is a DSC thermogram of the crystalline non-solvated Form 3. Figure 4A is a XRPD pattern of the crystalline non-solvated Form 4 at room temperature. Figure 4B is a DSC thermogram of the crystalline non-solvated Form 4. Figure 4C is a TG-FTIR spectrum of the crystalline non-solvated Form 4. Figure 5A is a XRPD pattern of the crystalline solvated Form A at room temperature. Figure 5B shows a FT-Raman spectrum of the crystalline solvated Form A. The most pronounced Raman peaks are labelled in the figure. Figure 5C is a TG-FTIR spectrum of the crystalline solvated Form A showing a mass loss of 7 wt. % ethanol. Figure 6A is a XRPD pattern of the crystalline solvated Form B at room temperature. Figure 6B is a TG-FTIR spectrum of the crystalline solvated Form B showing a mass loss of first 34.5 wt. % and subsequently 40.1 wt. % of DMSO at room temperature. Figure 7A is a XRPD pattern of the crystalline solvated Form C at room temperature. Figure 7B shows a FT-Raman spectrum of the crystalline solvated Form C. The most pronounced Raman peaks are labelled in the figure. Figure 7C is a TG-FTIR spectrum of the crystalline solvated Form C showing a mass loss of 9.2 wt. % of DMF. Figure 8A is a XRPD pattern of the crystalline solvated Form D at room temperature. Figure 8B is a TG-FTIR spectrum of the crystalline solvated Form D showing a mass loss of 7 wt. % of methanol. Figure 9A is a XRPD pattern of the crystalline solvated Form E at room temperature. Figure 9B is a TG-FTIR spectrum of the crystalline solvated Form E showing a mass loss of 7.9 wt. % of 2-propanol. Figure 10A is a XRPD pattern of the crystalline solvated Form F at room temperature. Figure 10B is a TG-FTIR spectrum of the crystalline solvated Form F showing a mass loss of 4.1 wt. % of acetone. Figure 11A is a XRPD pattern of the amorphous Form G of the compound of formula I at room temperature. Figure 11B shows a FT-Raman spectrum of the amorphous Form G of the compound of formula I. The most pronounced Raman peaks are labelled in the figure. DETAILED DESCRIPTION OF THE DISCLOSURE Definitions The following definitions apply to any embodiment of the disclosure: The terms “polymorphic form(s) of the disclosure” and “polymorphic form(s) of the compound of formula I” are used interchangeably. Polymorphic forms refer to the occurrence of different crystalline and amorphous forms. The term "crystalline form" or "crystalline" refers to any solid substance that has a short or long range order of molecules, atoms or ions in a fixed structural lattice. The term "amorphous" form refers to solids of disordered molecules that do not have a distinguishable crystal lattice. In some embodiments the polymorphic forms refer to an amorphous form of the compound of formula I (also referred to as “amorphous form of the disclosure”). The term “(polymorphic) form(s) of the invention” refers to all amorphous and crystalline forms of the compound of formula I described herein. In some embodiments the polymorphic forms refer to crystalline forms of the compound of formula I (also referred to as “crystalline form(s) of the disclosure”). In some embodiments, the crystalline forms of the disclosure are in hydrated or solvated form. In some embodiments, the crystalline forms of the disclosure are in dry, i.e. anhydrous or non-solvated form. In some embodiments, the crystalline form(s) of the disclosure refer in particular to the monohydrate crystalline form designated Form 1. In some embodiments, the crystalline form(s) of the disclosure refer in particular to the anhydrous crystalline form designated Form 2. In some embodiments, the crystalline form(s) of the disclosure refer in particular to the non-solvated crystalline forms designated Form 4 or Form 5. In some embodiments, the crystalline form(s) of the disclosure refer in particular to the solvated forms designated Form A or Form B or Form C or Form D or Form E or Form F. In some embodiments the polymorphic forms refer to amorphous forms of the compound of formula I (also referred to as “amorphous form(s) of the disclosure”). In some embodiments, the amorphous form(s) of the disclosure are in hydrated or solvated form. In some embodiments, the amorphous form(s) of the disclosure are in dry, i.e. anhydrous or non-solvated form. In some embodiments, the amorphous form(s) of the disclosure refer in particular to the amorphous form designated Form G. The new polymorphic forms may be prepared by any method for preparing solid state forms known in the prior art. Typical methods used to obtain crystalline polymorphic forms include for example various crystallization methods, e.g., from a single solvent or a mixture of solvents, from the melt, on a substrate, by seeding, etc.; suspension equilibrium methods; desolvation and dehydration methods of solvates and hydrates, respectively, e.g., by evaporation, drying, slurrying in a solvent with poor solubility; solution mediated polymorphic transformation (slurry conversion method); solid-state polymorphic transformation, and others. Typical methods and physical processes used to obtain amorphous polymorphic forms include for example desolvation and dehydration methods of solvates and hydrates, respectively, e.g., by evaporation, drying, slurrying in a solvent with poor solubility; solution mediated polymorphic transformation (slurry conversion method); solid-state polymorphic transformation including e.g., by vitriﬁcation, grinding, freeze-drying, spray drying, rapid precipitation from a solution; and others. The term "anhydrous" or “non-solvated” in relation to polymorphic forms as used herein, unless stated otherwise, refers to a polymorphic form of the disclosure, which contains not more than 1.5% (w/w), or not more than 1% (w/w) of water or organic solvents, respectively, as measured by e.g., DSC. Anhydrous (or non-solvated) forms may be obtained by solvent evaporation in a solvent evaporation step or a drying step from the corresponding hydrated (or solvated) polymorphic forms. Solvent evaporation may be carried out, for example by placing the appropriate hydrated, polymorphic form in a volume of a suitable solvent or solvent mixture which is sufficient to cause dissolution, followed by evaporation of the resulting solution at room temperature or elevated temperatures. Examples of suitable pharmaceutically acceptable solvents include C1C4 alcohol solvents, such as methanol, ethanol, propanol; acetone; dimethylsulfoxide (DMSO); dimethylformamide (DMF); dichloromethane (DCM); tetrahydrofuran (THF), and other solvents. The resulting solution is then subjected to evaporation at room temperature in a nitrogen flow, optionally followed by a drying step. The drying can take place at room temperature or elevated temperature, such as up to 60°C, under atmospheric or reduced pressure, such as less than 1 atmosphere, for example, about 10 mbar to about 100 mbar, for a period of time ranging from hours to weeks. The term “solvate” or "solvated" as used herein in relation to the polymorphic forms, unless stated otherwise, refers to the formation of a complex of variable stoichiometry comprising the compound of Formula I and (organic) solvent molecules. Typically, the solvent used is a pharmaceutically acceptable solvent (and may not interfere with the biological activity of the compound). Examples of suitable pharmaceutically acceptable solvents include C1C4 alcohol solvents, such as methanol, ethanol, propanol; acetone; dimethylsulfoxide (DMSO); dimethylformamide (DMF); dichloromethane (DCM); tetrahydrofuran (THF), and other solvents. The solvent(s) used may be pre-dried to contain water of e.g., less than 1%. A solvate can be isolated either in anhydrous form or hydrated form and either as an amorphous form or a crystalline form, preferably a crystalline form. As indicated above, the term "non-solvated" as used herein in relation to the polymorphic forms, refers to polymorphic forms which are substantially free of solvent. The term "hydrate" or “hydrated” as used herein in relation to the polymorphic forms, unless stated otherwise, refers to the formation of a complex of variable stoichiometry comprising the compound of Formula I and one or more water molecules. The water molecules may be absorbed, adsorbed or contained within a crystal lattice of the solid compound, usually in defined stoichiometric ratio. For example, in a hemihydrate, one water molecule per 2 compound molecules is present; in a monohydrate one water molecule per compound molecule is present; in a dihydrate, two water molecules per compound molecule are present. Hydrates or solvates of a polymorphic form with a given solvent (system) may be prepared for example by suspension equilibration. Typically, the starting material is suspended in an appropriate amount of the designated solvent or solvent mixture. The suspensions are stirred with a magnetic stirrer for a specific time at room temperature or elevated temperature and subsequently subjected to filtration. The samples obtained after filtration may be air dried at room temperature for a short time only to avoid a possible de-solvation of the obtained hydrates or solvates. The crystallinity or morphology of the polymorphic forms of the disclosure can be determined by various methods, including, but not limited to, one or more of x-ray powder diffraction (XRPD), x-ray diffraction analysis of a single crystal, Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, etc. The study of solvates or hydrates or the determination of their absence can be performed using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS) thermogravimetric analysis (TGA) or thermogravimetry coupled with Fourier transformed IR spectroscopy (TG-FTIR) and competitive slurry experiments. The data is typically represented graphically and the skilled person will understand that such graphical representations of data may be subject to small variations. For example, data collected of a given sample (such as XRPD patterns, Raman spectra, FTIR spectra, DSC thermograms, DVS curves, TG-FTIR curves, etc.) may vary somewhat depending on the instrument used, the time and temperature of the sample during measurement, and standard experimental errors. Therefore, the values of temperature and 2-theta angles, interatomic distance d values, heights and relative peak intensities given herein may be subject to some deviation. As used herein, unless stated otherwise, the XRPD measurements are taken using copper Kα radiation wavelength 1.541 Å. XRPD patterns of a polymorphic form of the disclosure can be identified by characteristic peaks, e.g., by at least three characteristic peaks, or at least five peaks characterized by specific positions and intensities. 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. The term "substantially free" or “predominantly” or “substantially completely in one form” means that a polymorphic form of the present disclosure contains 20% (w/w) or less, 10% (w/w) or less, 5% (w/w) or less, 2% (w/w) or less, 1% (w/w) or less, 0.5% (w/w) or less, particularly less than 0.2% (w/w), more particularly less than about 0.1%, most particularly less than about 0.01% by weight of any other polymorph or of a specified polymorph. The term "essentially the same" with reference to XRPD means that variability in peak positions and relative intensities of the peaks are to be taken into account. For example, a typical precision of the 2-theta values is in the range of ± 0.2° 2-theta. Thus, a diffraction peak that usually appears at 25.56° 2-Theta for example can appear between 25.36° and 25.76° 2-theta on most x-ray diffractometers under standard conditions. Furthermore, one skilled in the art will appreciate that relative peak intensities will show inter-apparatus variability as well as variability due to degree of crystallinity, preferred orientation, sample preparation and other factors known to those skilled in the art and should be taken as qualitative measure only. Typically, XRPD measurements are done at a temperature of 20°C, preferably also at a relative humidity of 40%. The term "water activity" as used herein means the ratio of vapour pressure exerted by water in a substance to the vapour pressure of pure water, at the same temperature. The critical water activity describes the amount of water needed in a liquid system to obtain a hydrated form from a given anhydrous form. As used herein the term "room temperature" relates to temperatures between about 15 and 30 °C or about 22°C to about 27°C, or about 25°C. The present disclosure addresses a need in the art by providing new polymorphic forms of the compound of formula I showing favourable properties and thus are highly suitable for formulation into a pharmaceutical composition and for use as a medicament,. In particular, the new solid state forms of the present disclosure can have improved characteristics such as: crystallinity, solubility, dissolution rate, morphology, thermal and mechanical stability to e.g., polymorphic conversion and/or to dehydration, 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. In some embodiments, the present application relates to crystalline polymorphic forms of the compound of formula I, such as crystalline forms in form of a hydrate, such as Form 1, or in anhydrous/non-solvated form, such as Forms 2, 3 and 4, or in solvated form, such as Forms A, B, C, D, E, and F. In some embodiments, the present application relates to the amorphous polymorphic form of the compound of formula I, such as Form G.. In some embodiments, the polymorphic forms of the disclosure are substantially free of any other polymorphic form (or of a specified polymorphic form). In other embodiments, the polymorphic forms of the disclosure contain from 1% to 20% (w/w), from 5% to 20% (w/w), or from 5% to 10% (w/w) of any other polymorphic form (or of a specified polymorphic form). For crystalline polymorphic forms of the disclosure the degree of crystallinity (%) may be determined by the skilled person using XRPD. Other techniques, such as solid state NMR, Raman spectroscopy, FTIR, may also be used. For polymorphic forms of the current disclosure, it has been found to be possible to produce forms, which are greater than 80 % crystalline, either anhydrous or in hydrate form, or amorphous. Several of the polymorphic forms, in particular some of the crystalline polymorphic forms demonstrated stability sufficient to establish their promise in the production of pharmaceutical preparations. Such stability can be demonstrated in a variety of ways including by analysis of thermodynamic properties using thermogravimetric analysis (TGA), thermogravimetry coupled with FTIR (TG-FTIR), differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), competitive slurry experiments, and the like. According to the methods of the disclosure, exemplary subjects are mammals. In some embodiments, exemplary subjects are human. Exemplary subjects may be male or female. Exemplary subjects may be of any age (fetal, neonatal, child, adolescent, or adult) In some embodiments, the subject is an adult. Exemplary subjects may be healthy, for example, healthy subjects of the disclosure may participate in a clinical trial in which one or more steps of the methods of the disclosure are performed. In certain embodiments, exemplary subjects may have at least one benign or malignant tumor. In some embodiments, exemplary subjects have at least one form or type of cancer. Subjects of the methods of the disclosure may be patients diagnosed with cancer, patients undergoing treatment for cancer, potential participants in a research and/or clinical study, and/or participants selected for inclusion in or exclusion from a research and/or clinical study. According to the methods of the disclosure, the term “mammal” refers to any mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, cats, cattle, horses, sheep, pigs, goats, rabbits, etc. (e.g., human). The term "prevention" or “preventing” refers to reducing or eliminating the onset of the symptoms or complications of a disease (e.g., cancer). In some embodiments, such prevention comprises the step of administering a therapeutically effective amount of a polymorphic form disclosed herein) or a pharmaceutical composition disclosed herein to a subject in need thereof (e.g., a mammal (e.g., a human). The term "treatment" or “treating” is intended to encompass therapy and cure. In some embodiments, such treatment comprises the step of administering a therapeutically effective amount of a polymorphic form disclosed herein or a pharmaceutical composition disclosed herein to a subject in need thereof (e.g., a mammal (e.g., a human). In some embodiments, the term “treating” or “treatment” refers to therapeutic treatment measures; wherein the object is to slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder. For example, when treating cancer according to a method of the disclosure, a subject or mammal is successfully “treated” for cancer if, after receiving a therapeutic amount of an ErbB inhibitor according to the methods of the present disclosure, the patient shows observable and/or measurable reduction in or absence of one or more of the following: reduction in the number of cancer cells or absence of the cancer cells; reduction in the proliferation or survival of cancer cells; and/or relief to some extent, one or more of the symptoms associated with the specific infection; reduced morbidity and mortality, and improvement in quality of life issues. The above parameters for assessing successful treatment and improvement in the disease are readily measurable by routine procedures familiar to a physician. According to the methods of the disclosure, subjects having a mutation of the disclosure may be treated for cancer by administering a therapeutically-effective amount of a composition of the disclosure, a Type II ErbB inhibitor, an EGFR-Viii selective agent/inhibitor or the NT-113 Type I inhibitor. The term “therapeutically effective amount” refers to an amount of a composition of the disclosure, a Type II ErbB inhibitor, an EGFR-Viii selective agent/inhibitor or the NT-113 Type I inhibitor effective to “treat” a disease or disorder (e.g., cancer) in a subject or mammal. See preceding definition of “treating.” According to the methods of the disclosure, a Type II ErbB inhibitor may include a small molecule. A “small molecule” is defined herein to have a molecular weight below about 1500 Daltons. According to the methods of the disclosure, mutations may be detected by analyzing either nucleic acid or amino acid sequences from a subject. Nucleic acid and/or amino acid sequences may be isolated prior to sequence analysis. The terms “nucleic acid” and “polynucleotide” are used interchangeably herein to refer to single- or double-stranded RNA, DNA, or mixed polymers. Polynucleotides may include genomic sequences, extra-genomic and plasmid sequences, and smaller engineered gene segments that express, or may be adapted to express polypeptides. An “isolated nucleic acid” is a nucleic acid that is substantially separated from other genome DNA sequences as well as proteins or complexes such as ribosomes and polymerases, which naturally accompany a native sequence. The term embraces a nucleic acid sequence that has been removed from its naturally occurring environment, and includes recombinant or cloned DNA isolates and chemically synthesized analogues or analogues biologically synthesized by heterologous systems. A substantially pure nucleic acid includes isolated forms of the nucleic acid. This refers to the nucleic acid as originally isolated and does not exclude genes or sequences later added to the isolated nucleic acid. The term “polypeptide” is used in its conventional meaning, i.e., as a sequence of amino acids. The polypeptides are not limited to a specific length of the product. Peptides, oligopeptides, and proteins are included within the definition of polypeptide, and such terms may be used interchangeably herein unless indicated otherwise. This term also does not refer to or exclude post-expression modifications of the polypeptide, for example, glycosylations, acetylations, phosphorylations and the like, as well as other modifications known in the art, both naturally occurring and non-naturally occurring. A polypeptide may be an entire protein, or a subsequence thereof. An “isolated polypeptide” is one that has been identified and separated and/or recovered from a component of its natural environment. In some embodiments, the isolated polypeptide will be purified (1) to greater than 95% by weight of polypeptide as determined by the Lowry method (e.g., more than 99% by weight), (2) to a degree sufficient to obtain at least 15 residues of N- terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or non-reducing conditions using Coomassie blue or silver stain. Isolated polypeptide includes the polypeptide in situ within recombinant cells since at least one component of the polypeptide's natural environment will not be present. In some embodiments, the isolated polypeptide will be prepared by at least one purification step. A “native sequence” polynucleotide is one that has the same nucleotide sequence as a polynucleotide derived from nature. A “native sequence” polypeptide is one that has the same amino acid sequence as a polypeptide (e.g., EGFR) derived from nature (e.g., from any species). Such native sequence polynucleotides and polypeptides can be isolated from nature or can be produced by recombinant or synthetic means. A polynucleotide “variant,” as the term is used herein, is a polynucleotide that differs from a disclosed polynucleotide herein in one or more substitutions, deletions, additions and/or insertions. A polypeptide “variant,” as the term is used herein, is a polypeptide that differs from a disclosed polypeptide herein in one or more substitutions, deletions, additions and/or insertions, or inversions. Such variants may be naturally occurring, non-naturally occurring, or may be synthetically generated. EGFR mutations (or variants) of the disclosure may comprise one or more substitutions, deletions, additions and/or insertions, or inversions of the amino acid sequence that are alter the function of the resultant protein. Mutations may be detected, for example, by comparison or alignment of a nucleic or amino acid sequence with a wild type sequence. When comparing polynucleotide and polypeptide sequences, two sequences are said to be “identical” if the sequence of nucleotides or amino acids in the two sequences is the same when aligned for maximum correspondence, as described below. Comparisons between two sequences are performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A “comparison window” as used herein, refers to a segment of at least about 20 contiguous positions, (e.g., 30 to about 75 or 40 to about 50), in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Optimal alignment of sequences for comparison may be conducted using the Megalign program in the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, WI), using default parameters. This program embodies several alignment schemes described in the following references: Dayhoff, M.O. (1978) A model of evolutionary change in proteins – Matrices for detecting distant relationships. In Dayhoff, M.O. (ed.) Atlas of Protein Sequence and Structure, National Biomedical Research Foundation, Washington DC Vol.5, Suppl.3, pp.345-358; Hein J. (1990) Unified Approach to Alignment and Phylogenes pp.626-645 Methods in Enzymology vol. 183, Academic Press, Inc., San Diego, CA; Higgins, D.G. and Sharp, P.M. (1989) CABIOS 5:151- 153; Myers, E.W. and Muller W. (1988) CABIOS 4:11-17; Robinson, E.D. (1971) Comb. Theor 11:105; Santou, N. Nes, M. (1987) Mol. Biol. Evol. 4:406-425; Sneath, P.H.A. and Sokal, R.R. (1973) Numerical Taxonomy – the Principles and Practice of Numerical Taxonomy, Freeman Press, San Francisco, CA; Wilbur, W.J. and Lipman, D.J. (1983) Proc. Natl. Acad., Sci. USA 80:726-730. Optimal alignment of sequences for comparison may be conducted by the local identity algorithm of Smith and Waterman (1981) Add. APL. Math 2:482, by the identity alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443, by the search for similarity methods of Pearson and Lipman (1988) Proc. Natl. Acad. Sci. USA 85: 2444, by computerized implementations of these algorithms (GAP, BESTFIT, BLAST, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group (GCG), 575 Science Dr., Madison, WI), or by inspection. One example of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1977) Nucl. Acids Res.25:3389-3402 and Altschul et al. (1990) J. Mol. Biol.215:403-410, respectively. BLAST and BLAST 2.0 can be used, for example, with the parameters described herein, to determine percent sequence identity for the polynucleotides and polypeptides of the present disclosure. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. In some embodiments, cumulative scores can be calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1989) Proc. Natl. Acad. Sci. USA 89:10915) alignments, (B) of 50, expectation (E) of 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, a scoring matrix can be used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T and X determine the sensitivity and speed of the alignment. In one approach, the “percentage of sequence identity” is determined by comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) of 20 percent or less (e.g., 5 to 15 percent, or 10 to 12 percent), as compared to the reference sequences (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid bases or amino acid residues occur in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e., the window size) and multiplying the results by 100 to yield the percentage of sequence identity. Sequences A wild type EGFR sequence of the disclosure may comprise or consist of the amino acid sequence of:

Based on the definitions given throughout the application the skilled person knows which combinations are synthetically feasible and realistic, e.g., typically combinations of groups leading to heteroatoms directly linked to each other are not contemplated. All percentages and ratios used herein, unless otherwise indicated, are by weight. Other features and advantages of the present disclosure are apparent from the different examples. The provided examples illustrate different components and methodology useful in practicing the present disclosure. The examples do not limit the claimed disclosure. Based on the present disclosure the skilled artisan can identify and employ other components and methodology useful for practicing the present disclosure. All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference. Citation of publications and patent documents is not intended as an admission that any is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description and examples below are for purposes of illustration and not limitation of the claims that follow. Polymorphic Forms of the Disclosure Form 1: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is a monohydrate, designated herein as Form 1. Form 1 of the compound of formula I may be prepared by crystallizing the compound of formula I from a suitable solvent system comprising water for hydration (the compound of formula I of the disclosure may be prepared as described (Example 1A) and/or as disclosed in US application 62/736293 or corresponding co-pending international application claiming priority from US application 62/736293). The crystallization process of Form 1 may comprise dissolving Form 1 in suitable solvent mixture, e.g., at elevated temperatures; adding water for hydration of the compound of formula I and concentrating the obtained suspension at elevated temperatures. Upon cooling to below ambient temperatures, monohydrate Form 1 is isolated. The process steps may comprise heating; cooling; and optionally maintaining the mixture to achieve completion of the crystallization. The heating may be done to about reflux temperature and the cooling may be done to a temperature of about 25°C to about 0°C. The maintaining is typically done at a temperature of about room temperature or below temperature, e.g., 15 to 25 °C, for a time of about 1 to about 24 hours, or for about 1 to about 12 hours, for example, for about 1.5 hours. The isolation of the precipitate may be done by filtration, optionally including a washing step with a suitable solvent. Optionally, the isolated Form 1 is dried, e.g., under reduced pressure, e.g., at temperatures below 50 °C. Form 1 can be characterized by a powder XRPD pattern with at least one, e.g., at least two, e.g., all peaks selected from the group consisting of 15.44°± 0.2°, 24.56°± 0.2°, 25.56° ± 0.2° 2-theta, e.g., 15.44°± 0.1°, 25,56°± 0.1°, 25.56°± 0.1°, e.g., 15.44°, 25,56°, 25.56° ; a powder XRPD pattern with at least one, e.g., at least two, e.g., at least three, e.g., at least four, e.g., all peaks at 10.02°± 0.2°, 15.44°± 0.2°, 20.62°± 0.2°, 24.56°± 0.2°, 25.56° ± 0.2° 2-theta, e.g., 10.02°± 0.1°, 15.44°± 0.1°, 20.62°± 0.1°, 24.56°± 0.1°, 25.56° ± 0.1° 2-theta, e.g., 10.02°, 15.44°, 20.62°, 24.56°, 25.56° 2-theta . Form 1 may be further characterized by XRPD pattern having at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least seven peaks, e.g., all peaks selected from: 7.4°± 0.2°, 10.02°± 0.2°, 12.32°± 0.2°, 15.44°± 0.2°, 16.38°± 0.2°, 20.62°± 0.2°, 24.56°± 0.2°, 25.56° ± 0.2° 2-theta, e.g., .4°± 0.1°, 10.02°± 0.1°, 12.32°± 0.1°, 15.44°± 0.1°, 16.38°± 0.1°, 20.62°± 0.1°, 24.56°± 0.1°, 25.56° ± 0.1° 2-theta, e.g., 7.4°, 10.02°, 12.32°, 15.44°, 16.38°, 20.62°, 24.56°, 25.56° 2-theta. Form 1 can also be characterized by a powder XRPD pattern with peaks as shown in Table 1. Table 1: XRPD data for Form 1 (cps indicates counts per second)

Form 1 may further be characterized by an XRPD pattern substantially as depicted in Figure 1. Typically, Form 1 is substantially free of another polymorphic form, particularly, a powder XRPD pattern of Form 1 does not have any of the peaks at 15.44°, 24.56°, 25.56° ± 0.2° 2-theta. Form 1 can also be characterized by a Raman spectrum having at least one peak, e.g., at least two peaks, e.g., all peaks selected from at 1608 ± 2 cm^-1, 1394 ± 2 cm^-1, 1343 ± 2 cm^-1 e.g., 1608 ± 1 cm^-1, 1394 ± 1 cm^-1, 1343 ± 1 cm^-1, e.g., 1608 cm^-1, 1394 cm^-1, 1343 cm^-1. Form 1 can be further characterized by a Raman spectrum having at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., all peaks selected from 1608 ± 2 cm^-1, 1498 ± 2 cm^-1, 1430 ± 2 cm^-1, 1394 ± 2 cm^-1, 1343 ± 2 cm^-1, 1251 ± 2 cm^-1, 1209 ± 2 cm^-1, e.g., 1608 ± 1 cm^-1, 1498 ± 1 cm^-1, 1430 ± 1 cm^-1, 1394 ± 1 cm^-1, 1343 ± 1 cm^-1, 1251 ± 1 cm^-1, 1209 ± 1 cm^-1, e.g., 1608 cm^-1, 1498 cm^-1, 1430 cm^-1, 1394 cm^-1, 1343 cm^-1, 1251 cm^-1, 1209 cm^-1 Form 1 can also be characterized by a Raman spectrum having at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least 7 e.g., at least eight peaks, e.g., at least nine peaks, e.g., all peaks selected from1608 ± 2 cm^-1, 1498 ± 2 cm^-1, 1430 ± 2 cm^-1, 1394 ± 2 cm^-1, 1343 ± 2 cm- ¹, 1308 ± 2 cm^-1, 1251 ± 2 cm^-1, 1209 ± 2 cm^-1, 995 ± 2 cm^-1, 795 ± 2 cm^-1, e.g., 1608 ± 1 cm^-1, 1498 ± 1 cm^-1, 1430 ± 1 cm^-1, 1394 ± 1 cm^-1, 1343 ± 1 cm^-1, 1308 ± 1 cm^-1, 1251 ± 1 cm^-1, 1209 ± 1 cm^-1, 995 ± 1 cm^-1, 795 ± 1 cm^-1, 1608 cm^-1, 1498 cm^-1, 1430 cm^-1, 1394 cm^-1, 1343 cm^-1, 1308 cm^-1, 1251 cm^-1, 1209 cm^-1, 995 cm^-1, 795 cm^-1 Form 1 may further be characterized by a Raman spectrum substantially as depicted in Figure 1E. Form 1 can also be characterized by an FTIR spectrum having at least one absorption frequency, e.g., at least two absorption frequencies, e.g., at least three absorption frequencies, e.g., all absorption frequencies selected from at 1495 ± 2 cm^-1, 1425 ± 2 cm^-1, 1216 ± 2 cm^-1, 753 ± 2 cm- ¹, e.g., 1495 ± 1 cm^-1, 1425 ± 1 cm^-1, 1216 ± 1 cm^-1, 753 ± 1 cm^-1, e.g., 1495 cm^-1, 1425 cm^-1, 1216 cm^-1, 753 cm^-1. Form 1 can be further characterized by an FTIR spectrum having at least one absorption frequency, e.g., at least two absorption frequencies, e.g., at least three absorption frequencies, e.g., at least four absorption frequencies, e.g., at least five absorption frequencies, e.g., at least six absorption frequencies, e.g., all absorption frequencies selected from at 1545 ± 2 cm^-1, 1495 ± 2 cm^-1, 1425 ± 2 cm^-1, 1216 ± 2 cm^-1, 1113 ± 2 cm^-1, 941 ± 2 cm^-1, 753 ± 2 cm^-1, e.g., 1545 ± 1 cm^-1, 1495 ± 1 cm^-1, 1425 ± 1 cm^-1, 1216 ± 1 cm^-1, 1113 ± 1 cm^-1, 941 ± 1 cm^-1, 753 ± 1 cm^-1, e.g., 1545 cm^-1, 1495 cm^-1, 1425 cm^-1, 1216 cm^-1, 1113 cm^-1, 941 cm^-1, 753 cm^-1 Form 1 can also be characterized by an FTIR spectrum having at least one absorption frequency, e.g., at least two absorption frequencies, e.g., at least three absorption frequencies, e.g., at least four absorption frequencies, e.g., at least five absorption frequencies, e.g., at least six absorption frequencies, e.g., at least seven absorption frequencies, e.g., at least eight absorption frequencies, e.g., at least nine absorption frequencies, e.g., at least 10 absorption frequencies, e.g., at least 11 absorption frequencies, e.g., at least 12 absorption frequencies, e.g., at least 13 absorption frequencies, e.g., at least 14 absorption frequencies, e.g., at least 15 absorption frequencies, e.g., at least 16 absorption frequencies, e.g., at least 17 absorption frequencies, e.g., all absorption frequencies selected from at 1667 ± 2 cm^-1, 1626 ± 2 cm^-1, 1545 ± 2 cm^-1, 1495 ± 2 cm^-1, 1425 ± 2 cm^-1, 1336 ± 2 cm^-1, 1283 ± 2 cm^-1, 1241 ± 2 cm^-1, 1216 ± 2 cm^-1, 1137 ± 2 cm^-1, 1113 ± 2 cm^-1, 1063 ± 2 cm- ¹, 1031 ± 2 cm^-1, 986 ± 2 cm^-1, 941 ± 2 cm^-1, 854 ± 2 cm^-1, 753 ± 2 cm^-1, 618 ± 2 cm^-1, e.g., 1667 ± 1 cm^-1, 1626 ± 1 cm^-1, 1545 ± 1 cm^-1, 1495 ± 1 cm^-1, 1425 ± 1 cm^-1, 1336 ± 1 cm^-1, 1283 ± 1 cm- ¹, 1241 ± 1 cm^-1, 1216 ± 1 cm^-1, 1137 ± 1 cm^-1, 1113 ± 1 cm^-1, 1063 ± 1 cm^-1, 1031 ± 1 cm^-1, 986 ± 1 cm^-1, 941 ± 1 cm^-1, 854 ± 1 cm^-1, 753 ± 1 cm^-1, 618 ± 1 cm^-1, e.g., 1667 cm^-1, 1626 cm^-1, 1545 cm^-1, 1495 cm^-1, 1425 cm^-1, cm^-1, 1283 cm^-1, 1241 cm^-1, 1216 cm^-1, 1137 cm^-1, 1113 cm^-1, 1063 cm^-1, 1031 cm^-1, 986 cm^-1, 941 cm^-1, 854 cm^-1, 753 cm^-1, 618 cm^-1 Form 1 may further be characterized by an FTIR spectrum substantially as depicted in Figure 1G. The thermal behaviour of Form 1 may be characterized by TG-FTIR analysis, DVS analysis and DSC analysis. The TG-FTIR curve of Form 1 shows a content of 3.09 wt. % of water confirming that Form 1 is the monohydrate form of compound of formula I (Figure 1F). Form 1 may further be characterized by a TG-FTIR curve substantially as depicted in Figure 1F. Likewise, the DVS curve of Form 1 shows a weight increase of at most 0.25%, based on the weight of Form 1 as determined in the range of from 0% to 95% relative humidity at a temperature of (25.0 ± 0.1 °C). Form 1 may also be characterized by a DVS curve substantially as depicted in Figures 1B and 1C. The minimal (and reversible) increase in weight indicates the superior non- hygroscopicity of Form 1 and thus its superior stability and suitability for formulation as a pharmaceutical composition. Form 1 may also be characterized by a dehydration endothermic peak at about 105-135 °C as shown in the DSC thermogram of Form 1 (Figure 1B). Form 1 may also be characterized by a melting endothermic peak at about 166.0 °C (onset temperature) as shown in the DSC thermogram of Form 1 (Figure 1B). Form 1 may further be characterized by a DSC thermogram substantially as depicted in Figure 1B. The thermodynamic properties of Form 1 compared to other polymorphic forms of the disclosure may also be characterized through solvent-mediated solid phase transformations. The critical water activity was determined in competitive slurry conversion experiments containing a mixture of monohydrate Form 1 and the most stable non-solvated form (Form 4 as described hereinafter) in a 1,4-dioxane/water (99/1, v/v) solvent system. Monohydrate Form 1 and non-solvated Form 4 were suspended in a 1:1 ratio in the solvent mixture (1,4-dioxane was pre-dried over molecular sieves). The 99/1 (v/v) solvent system had a water activity of about 0.2. The Karl-Fischer titration of the filtrate after the experiment showed a water content of 1% (v/v). After seven days of equilibration the sample converted completely into the monohydrate Form 1. Thus, the critical water activity must be below 0.2 in an aqueous system. The overlay of the XRPD patterns of starting materials and conversion product is depicted in Figure 1H. Form 1 may further be characterized by its solubility characteristics. Approximate solubilities for Form 1 were determined at room temperature by addition of small aliquots of solvent to ca.10 mg of solid and shaking/sonicating the mixture for a short period of time at ambient conditions. Form 1 was observed to be freely soluble (> 100 mg/mL) in aqueous acids (e.g., acetic acid), NMP; show good solubility (between 5-55 mg/mL) in DCM, DMF, dioxane, DMSO, MeOH, THF and be slightly soluble (1-5 mg/mL) in acetone, MEK, EtOH, EtOAc, MIBK. In acetonitrile, anisole, EtOH, heptane, TBME, water, Form 1 was less soluble (< 1 mg/mL) (see Example 12). The data collected shows that Form 1 has advantageous properties selected from at least one of chemical purity, flowability, solubility, morphology or crystal habit, stability - such as storage stability, stability to dehydration, stability to polymorphic conversion, and minimal hygroscopicity. Form 2: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is an anhydrous form, designated herein as Form 2. Form 2 of the compound of formula I may be prepared as described above and in the Examples. Form 2 can be characterized by data selected from: a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., all peaks selected from at 12.02°± 0.2°, 17.62°± 0.2°, 24.7° ± 0.2° 2- theta, e.g., 12.02°± 0.1°, 17.62°± 0.1°, 24.7° ± 0.1° 2-theta, e.g., 12.02°, 17.62°, 24.7° 2-theta ; a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., all peaks selected from at 5.94°± 0.2°, 12.02°± 0.2°, 17.62°± 0.2°, 24.7°± 0.2°, 26.8° ± 0.2° 2-theta, e.g., 5.94°± 0.1°, 12.02°± 0.1°, 17.62°± 0.1°, 24.7°± 0.1°, 26.8° ± 0.1° 2-theta, e.g., 5.94°, 12.02°, 17.62°, 24.7°, 26.8° 2-theta . Form 2 may be further characterized by XRPD pattern having additionally at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least seven peaks, e.g., at least eight peaks, e.g., all peaks selected from at: 5.94°± 0.2°, 6.36°± 0.2°, 8.62°± 0.2°, 12.02°± 0.2°, 17.62°± 0.2°, 21.24°± 0.2°, 22.18°± 0.2°, 24.7°± 0.2°, 26.8° ± 0.2° 2-theta, e.g., .94°± 0.1°, 6.36°± 0.1°, 8.62°± 0.1°, 12.02°± 0.1°, 17.62°± 0.1°, 21.24°± 0.1°, 22.18°± 0.1°, 24.7°± 0.1°, 26.8° ± 0.1° 2-theta. Form 2 can also be characterized by a powder XRPD pattern with peaks as shown in Table 2. Table 2: XRPD data for Form 2 (cps indicates counts per second)

Form 2 may further be characterized by an XRPD pattern substantially as depicted in Figure 2A. Typically, Form 2 is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form 2 mays not have any of the peaks at 4.3°, 5.6°, 15.3° ± 0.2° 2-theta. Form 2 can also be characterized by a Raman spectrum having one or more peaks at wavelengths (cm^-1) selected from a Raman spectrum substantially in accordance with Figure 2C. The thermal behaviour of Form 2 may be characterized by TG-FTIR analysis and DSC analysis. TG-FTIR analyses confirmed that Form 2 (prepared in different ways) is the anhydrous form of the free base. The TG-FTIR curve of Form 2, prepared by repeated evaporation under nitrogen flow of a solution of Form 1 in dichloromethane (see Example 2), shows a mass loss of 0.29 wt. % water (in a range of 25°C – 105°C) and a subsequent mass loss of 0.43 % of bound DCM (in the range of 105°C – 170°C) (Figure 2D). The TG-FTIR curve of Form 2, prepared by extensive drying of Form E (see Example 2), shows a mass loss of 0.56 wt. % 2-propanol (in a range of 25°C – 160°C) (Figure 2D). Form 2 may also be characterized by a melting endothermic peak at about 172 °C as shown in the DSC thermogram of Form 2 (Figure 2B). The calculated melting enthalpy was about 60 J/g. Form 3: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is a non-solvated form, designated herein as Form 3. Form 3 of the compound of formula I may be prepared as described above and in the Examples (see Example 3). Form 3 can be characterized by a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., all peaks selected from at 4.3°± 0.2°, 5.6°± 0.2°, 6.4° ± 0.2° 2-theta, e.g., 4.3°± 0.1°, 5.6°± 0.1°, 6.4° ± 0.1° 2-theta, e.g., 4.3°, 5.6°, 6.4° 2-theta; a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., all peaks selected from at 4.3°± 0.2°, 5.6°± 0.2°, 6.4°± 0.2°, 12.9°± 0.2°, 25.7° ± 0.2° 2-theta, e.g., 4.3°± 0.1°, 5.6°± 0.1°, 6.4°± 0.1°, 12.9°± 0.1°, 25.7° ± 0.1° 2-theta, e.g., 4.3°, 5.6°, 6.4°, 12.9°, 25.7° 2- theta. Form 3 can also be characterized by a powder XRPD pattern with peaks as shown in Table 3. Table 3: XRPD data for Form 3 (cps indicates counts per second)

Form 3 may further be characterized by an XRPD pattern substantially as depicted in Figure 3A. Typically, Form 3 is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form 3 may not have any of the peaks at 17.6°, 24.7°, 26.6° ± 0.2° 2- theta. The DSC thermogram of Form 3 shows two thermal events (Figure 3B). First, Form 3 may also be characterized by a solid-solid transformation of Form 3 to Form 2 at about 154 °C (onset temperature) with a melting temperature of Form 3 of about 165 °C. The second thermal event is the melting of Form 2 at about 174° C (onset temperature). The melting enthalpy of Form 3 is about 67 J/g (integral from 140 °C to 190 °C). Form 4: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is a non-solvated form, designated herein as Form 4. Form 4 of the compound of formula I may be prepared as described above and in the Examples. Competitive slurry experiments have shown that of the three non-solvated forms disclosed herein (Forms, 2, 3, 4), Form 4 seems to be the most stable non-solvated form. Form 4 can be characterized by a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., all peaks selected from at 15.3°± 0.2°, 24.7°± 0.2°, 26.6° ± 0.2° 2-theta, e.g., 15.3°± 0.1°, 24.7°± 0.1°, 26.6° ± 0.1° 2-theta, e.g., 15.3°, 24.7°, 26.6° 2-theta; a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., all peaks selected from at 4.1°± 0.2°, 6.5°± 0.2°, 15.3°± 0.2°, 24.7°± 0.2°, 26.6° ± 0.2° 2- theta, e.g., 4.1°± 0.1°, 6.5°± 0.1°, 15.3°± 0.1°, 24.7°± 0.1°, 26.6° ± 0.1° 2-theta, e.g., 4.1°, 6.5°, 15.3°, 24.7°, 26.6° 2-theta. Form 4 may be further characterized by XRPD pattern having additionally least 1, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., all peaks selected from at: 4.1°± 0.2°, 6.5°± 0.2°, 15.3°± 0.2°, 21.2°± 0.2°, 21.9°± 0.2°, 24.7°± 0.2°, 26.6° ± 0.2° 2-theta, e.g., 4.1°± 0.1°, 6.5°± 0.1°, 15.3°± 0.1°, 21.2°± 0.1°, 21.9°± 0.1°, 24.7°± 0.1°, 26.6° ± 0.1° 2-theta; e.g., 4.1°, 6.5°, 15.3°, 21.2°, 21.9°, 24.7°, 26.6° 2-theta. Form 4 can also be characterized by a powder XRPD pattern with peaks as shown in Table 4. Table 4: XRPD data for Form 4 (cps indicates counts per second)

Form 4 may further be characterized by an XRPD pattern substantially as depicted in Figure 4A. Typically, Form 4 is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form 4 may not have any of the peaks at 5.6°, 12°, 17.6° ± 0.2° 2-theta. The thermal behaviour of Form 4 may be characterized by TG-FTIR analysis, DSC analysis, and DVS analysis. TG-FTIR analyses confirmed that Form 4 (prepared in different ways) is the non- solvated form of the free base. The TG-FTIR curve of Form 4, prepared by drying Form D (see hereinafter) at room temperature and under vacuum shows a completely dry material (Figure 4C, see Example 4. The TG-FTIR curve of Form 4, prepared by suspension equilibrium in pre-dried methanol followed by drying shows a mass loss of 0.19 wt% water (in a range of 25°C – 100°C) (see Example 4). The DSC thermogram of Form 4 shows three thermal events (Figure 4B). First, Form 4 may also be characterized by a melting endothermic peak at about 150 °C (onset temperature), which is followed by a recrystallization and solid-solid conversion at about 165 °C to Form 4. The third thermal event is the melting endothermic peak of Form 4 at about 172 °C (onset temperature) corresponding to the DSC thermogram of Form 4 (Figure 4B). The calculated melting enthalpy over a temperature range of from 140 °C to 185 °C (i.e. the sum of all endothermal enthalpies and subtraction of the exothermal enthalpy of the recrystallization) was about 82 J/g. Form A: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is an ethanol solvate form, designated herein as Form A. Form A of the compound of formula I may be prepared as described above and in the Examples. Form A can be characterized by a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., all peaks selected from at 5.96°± 0.2°, 23.92°± 0.2°, 26.66° ± 0.2° 2-theta, e.g., 5.96°± 0.1°, 23.92°± 0.1°, 26.66° ± 0.1° 2-theta, e.g., 5.96°, 23.92°, 26.66°2-theta; Form A may also be characterized a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., all peaks selected from at 5.96°± 0.2°, 23.72°± 0.2°, 23.92°± 0.2°, 26.66°± 0.2°, 27.3° ± 0.2° 2-theta, e.g., 5.96°± 0.1°, 23.72°± 0.1°, 23.92°± 0.1°, 26.66°± 0.1°, 27.3° ± 0.1° 2-theta, e.g., 5.96°, 23.72°, 23.92°, 26.66°, 27.3°2-theta. Form A may further be characterized by XRPD pattern having additionally least 1, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least seven peaks, e.g., all peaks at: 5.96°± 0.2°, 17.94°± 0.2°, 19.1°± 0.2°, 21.5°± 0.2°, 23.72°± 0.2°, 23.92°± 0.2°, 26.66°± 0.2°, 27.3° ± 0.2° 2-theta, 5.96°± 0.1°, 17.94°± 0.1°, 19.1°± 0.1°, 21.5°± 0.1°, 23.72°± 0.1°, 23.92°± 0.1°, 26.66°± 0.1°, 27.3° ± 0.1° 2-theta, e.g., 5.96°, 17.94°, 19.1°, 21.5°, 23.72°, 23.92°, 26.66°, 27.3°2-theta. Form A can also be characterized by a powder XRPD pattern with peaks as shown in Table 5. Table 5: XRPD data for Form A (cps indicates counts per second)

Form A may further be characterized by an XRPD pattern substantially as depicted in Figure 5A. Typically, Form A is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form A may not have any of the peaks of relevant intensity at 3°, 5.2°, 9.4° 2-theta. Form A can also be characterized by a Raman spectrum having one or more peaks at wavelengths (cm^-1) selected from a Raman spectrum substantially in accordance with Figure 5B. The thermal behaviour of Form A may be characterized by TG-FTIR analysis, which confirmed that Form A is an ethanol mono-solvate form of the compound of formula I. The TG-FTIR curve of Form A, prepared by suspension equilibration of Form 1 in ethanol, showed a mass loss of 7 % of ethanol in a temperature range of 25°C – 150°C (Figure 5C, see Example 5). Form B: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is a DMSO solvate form, designated herein as Form B. Form B of the compound of formula I may be prepared as described above and in the Examples. Form B can be characterized by a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., all peaks selected from at 6.92°± 0.2°, 23.68°± 0.2°, 26.7° ± 0.2° 2-theta, e.g., 6.92°± 0.1°, 23.68°± 0.1°, 26.7° ± 0.1° 2-theta, e.g., 6.92°, 23.68°, 26.7°2-theta; Form B may also be characterized a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., all peaks selected from at 6.92°± 0.2°, 21.72°± 0.2°, 22.12°± 0.2°, 23.68°± 0.2°, 24.88°± 0.2°, 26.7° ± 0.2° 2-theta, e.g., 6.92°± 0.1°, 21.72°± 0.1°, 22.12°± 0.1°, 23.68°± 0.1°, 24.88°± 0.1°, 26.7° ± 0.1° 2-theta, e.g., 6.92°, 21.72°, 22.12°, 23.68°, 24.88°, 26.7° 2-theta. Form B may further be characterized by XRPD pattern having additionally at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least seven peaks, e.g., at least eight peaks, e.g., all peaks selected from at: 5.16°± 0.2°, 6.92°± 0.2°, 23.68°± 0.2°, 20.5°± 0.2°, 21.72°± 0.2°, 22.12°± 0.2°, 24.88°± 0.2°, 26.7°± 0.2°, 27.12° ± 0.2° 2-theta, e.g., 5.16°± 0.1°, 6.92°± 0.1°, 23.68°± 0.1°, 20.5°± 0.1°, 21.72°± 0.1°, 22.12°± 0.1°, 24.88°± 0.1°, 26.7°± 0.1°, 27.12° ± 0.1° 2-theta, e.g., 5.16°, 6.92°, 23.68°, 20.5°, 21.72°, 22.12°, 24.88°, 26.7°, 27.12° 2- theta. Form B can also be characterized by a powder XRPD pattern with peaks as shown in Table 6. Table 6: XRPD data for Form B (cps indicates counts per second)

Form B may further be characterized by an XRPD pattern substantially as depicted in Figure 6A. Typically, Form B is substantially free of another polymorphic form, particularly. In some embodiments, a powder XRPD pattern of Form B may not have any of the peaks of relevant intensity at 3°, 6°, 9.4° 2-theta. The thermal behaviour of Form B may be characterized by TG-FTIR analysis, which confirmed that Form B is a DMSO solvate form of the compound of formula I. The TG-FTIR curve of Form B, prepared by suspension equilibration of Form 1 in DMSO, showed in a first step in a temperature range of 25°C – 150°C a mass loss of 34.5 % of DMSO and in a second step in a temperature range of 150°C – 250°C a mass loss of 40.11 % of DMSO (Figure 6B, see Example 6). Form C: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is a DMF solvate form, designated herein as Form C. Form C of the compound of formula I may be prepared as described above and in the Examples. Form C can be characterized by a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., all peaks selected from at 5.2°± 0.2°, 6°± 0.2°, 23.82° ± 0.2° 2-theta, e.g., .2°± 0.1°, 6°± 0.1°, 23.82° ± 0.1° 2-theta, e.g., 5.2°, 6°, 23.82° 2-theta; Form C may also be characterized a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., all peaks at 5.2°± 0.2°, 6°± 0.2°, 7.8°± 0.2°, 15.66°± 0.2°, 23.82°± 0.2°, 26.74° ± 0.2° 2-theta, e.g., 5.1°± 0.1°, 6°± 0.1°, 7.8°± 0.1°, 15.66°± 0.1°, 23.82°± 0.1°, 26.74° ± 0.1° 2-theta, e.g., 5.2°, 6°, 7.8°, 15.66°, 23.82°, 26.74° 2-theta. Form C may further be characterized by XRPD pattern having additionally at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least seven peaks, e.g., at least eight peaks, e.g., at least nine peaks, e.g., all peaks at: 5.2°± 0.2°, 6°± 0.2°, 7.8°± 0.2°, 10.42°± 0.2°, 15.66°± 0.2°, 21.96°± 0.2°, 23.82°± 0.2°, 25°± 0.2°, 26.74° ± 0.2° 2-theta, 5.1°± 0.1°, 6°± 0.1°, 7.8°± 0.1°, 10.42°± 0.1°, 15.66°± 0.1°, 21.96°± 0.1°, 23.82°± 0.1°, 25°± 0.1°, 26.74° ± 0.1° 2-theta, e.g., 5.2°, 6°, 7.8°, 10.42°, 15.66°, 21.96°, 23.82°, 25°, 26.74°2-theta. Form C can also be characterized by a powder XRPD pattern with peaks as shown in Table 7. Table 7: XRPD data for Form C (cps indicates counts per second)

Form C may further be characterized by an XRPD pattern substantially as depicted in Figure 7A. Typically, Form C is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form C may not have any of the peaks of relevant intensity at 3°, 6.9°, 9.4° 2-theta. Form C can also be characterized by a Raman spectrum having one or more peaks at wavelengths (cm^-1) selected from a Raman spectrum substantially in accordance with Figure 7B. The thermal behaviour of Form C may be characterized by TG-FTIR analysis, which confirmed that Form C is an DMF solvate form of the compound of formula I. The TG-FTIR curve of Form C, prepared by suspension equilibration of Form 1 in DMF, showed a mass loss of 9.15 % of DMF in a temperature range of 25°C – 190°C (Figure 7C, see Example 7). Form D: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is a methanol solvate form, designated herein as Form D. Form D of the compound of formula I may be prepared as described above and in the Examples. Form D can be characterized by a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., all peaks at 2.98°± 0.2°, 9.36°± 0.2°, 25.58° ± 0.2° 2-theta, e.g., 2.98°± 0.1°, 9.36°± 0.1°, 25.58° ± 0.1° 2-theta, e.g., 2.98°, 9.36°, 25.58°2-theta; Form D may also be characterized a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., all peaks selected from at 2.98°± 0.2°, 7.78°± 0.2°, 9.36°± 0.2°, 25.58°± 0.2°, 26.7° ± 0.2° 2-theta, e.g., 2.98°± 0.1°, 7.78°± 0.1°, 9.36°± 0.1°, 25.58°± 0.1°, 26.7° ± 0.1° 2-theta, e.g., 2.98°, 7.78°, 9.36°, 25.58°, 26.7°2-theta. Form D may further be characterized by XRPD pattern having additionally at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, at least six peaks, e.g., all peaks selected from at: 2.98°± 0.2°, 7.78°± 0.2°, 9.36°± 0.2°, 20.74°± 0.2°, 24.8°± 0.2°, 25.58°± 0.2°, 26.7° ± 0.2° 2-theta, e.g., 2.98°± 0.1°, 7.78°± 0.1°, 9.36°± 0.1°, 20.74°± 0.1°, 24.8°± 0.1°, 25.58°± 0.1°, 26.7° ± 0.1° 2-theta, e.g., 2.98°, 7.78°, 9.36°, 20.74°, 24.8°, 25.58°, 26.7°2-theta. Form D can also be characterized by a powder XRPD pattern with peaks as shown in Table 8. Table 8 XRPD data for Form D (cps indicates counts per second)

Form D may further be characterized by an XRPD pattern substantially as depicted in Figure 8A. Typically, Form D is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form D may not have any of the peaks of relevant intensity at 5.2°, 21.7°, 23.9° 2-theta. The thermal behaviour of Form D may be characterized by TG-FTIR analysis, which confirmed that Form D is a methanol solvate form of the compound of formula I. The TG-FTIR curve of Form D, prepared by suspension equilibration of Form 1 in pre-dried methanol, showed a mass loss of 7 % of methanol (and water) in a temperature range of 25°C – 120°C (Figure 8B, see Example 8). Form E: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is a 2-propanol solvate form, designated herein as Form E. Form E of the compound of formula I may be prepared as described above and in the Examples. Form E can be characterized by a powder XRPD pattern with at least one peak, e.g., with at least two peaks, e.g., with at least three peaks, e.g., with at least four peaks, e.g., all peaks selected from at 5.9°± 0.2°, 16.1°± 0.2°, 18.6°± 0.2°, 23.7°± 0.2°, 26.5° ± 0.2° 2-theta, e.g., 5.9°± 0.1°, 16.1°± 0.1°, 18.6°± 0.1°, 23.7°± 0.1°, 26.5° ± 0.1° 2-theta, e.g., 5.9°, 16.1°, 18.6°, 23.7°, 26.5°2-theta; Form E may also be characterized a powder XRPD pattern with at least one peak, e.g., with at least two peaks, e.g., with at least three peaks, e.g., with at least four peaks, e.g., with at least five peaks, e.g., with at least six peaks, e.g., with at least seven peaks, e.g., with at least eight peaks, e.g., all peaks at 5.3°± 0.2°, 5.9°± 0.2°, 16.1°± 0.2°, 18.6°± 0.2°, 17.9°± 0.2°, 23.7°± 0.2°, 26.5°± 0.2°, 27.2° ± 0.2° 2-theta, e.g., 5.3°± 0.1°, 5.9°± 0.1°, 16.1°± 0.1°, 18.6°± 0.1°, 17.9°± 0.1°, 23.7°± 0.1°, 26.5°± 0.1°, 27.1° ± 0.1° 2-theta, e.g., 5.3°, 5.9°, 16.1°, 18.6°, 17.9°, 23.7°, 26.5°, 27.2°2-theta. Form E may further be characterized by XRPD pattern having additionally at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least seven peaks, e.g., at least eight peaks, at least nine peaks, at least 10 ,e.g., all peaks at: 5.3°± 0.2°, 5.9°± 0.2°, 8.02°± 0.2°, 16.1°± 0.2°, 18.6°± 0.2°, 17.9°± 0.2°, 21.8°± 0.2°, 23.7°± 0.2°, 24.6°± 0.2°, 26.5°± 0.2°, 27.2° ± 0.2° 2-theta, 5.3°± 0.1°, 5.9°± 0.1°, 8.02°± 0.1°, 16.1°± 0.1°, 18.6°± 0.1°, 17.9°± 0.1°, 21.8°± 0.1°, 23.7°± 0.1°, 24.6°± 0.1°, 26.5°± 0.1°, 27.1° ± 0.1° 2-theta, e.g., 5.3°, 5.9°, 8.02°, 16.1°, 18.6°, 17.9°, 21.8°, 23.7°, 24.6°, 26.5°, 27.2°2- theta. Form E can also be characterized by a powder XRPD pattern with peaks as shown in Table 9. Table 9 XRPD data for Form E (cps indicates counts per second)

Form E may further be characterized by an XRPD pattern substantially as depicted in Figure 9A. Typically, Form E is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form E may not have any of the peaks of relevant intensity at 3°, 6.9°, 9.4° 2-theta. The thermal behaviour of Form E may be characterized by TG-FTIR analysis, which confirmed that Form E is a 2-propanol solvate form of the compound of formula I. The TG-FTIR curve of Form E, prepared by suspension equilibration of Form 1 in pre-dried 2-propanol, showed a mass loss of 7.9 % of methanol (and water) in a temperature range of 25°C – 160°C (Figure 9B, see Example 9). Form F: In some embodiments, the present disclosure provides a crystalline polymorphic form of the disclosure, which is an acetone solvate form, designated herein as Form F. Form F of the compound of formula I may be prepared as described above and in the Examples. Form F can be characterized by a powder XRPD pattern with at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., all peaks selected from at 5.9°± 0.2°, 16.4°± 0.2°, 18.8°± 0.2°, 23.8°± 0.2°, 26.5° ± 0.2° 2-theta, 5.9°± 0.1°, 16.4°± 0.1°, 18.8°± 0.1°, 23.8°± 0.1°, 26.5° ± 0.1° 2-theta, e.g., 5.9°, 16.4°, 18.8°, 23.8°, 26.5° 2-theta; Form F may also be characterized a powder XRPD pattern with at least one peak, e.g., with at least two peaks, e.g., with at least three peaks, e.g., with at least four peaks, e.g., with at least five peaks, e.g., with at least six peaks, e.g., with at least seven peaks, e.g., e.g., all peaks at 5.3°± 0.2°, 5.9°± 0.2°, 8.1°± 0.2°, 16.4°± 0.2°, 18.8°± 0.2°, 23.8°± 0.2°, 26.5°± 0.2°, 27.2° ± 0.2° 2-theta, 5.3°± 0.1°, 5.9°± 0.1°, 8.1°± 0.1°, 16.4°± 0.1°, 18.8°± 0.1°, 23.8°± 0.1°, 26.5°± 0.1°, 27.1° ± 0.1° 2-theta, e.g., 5.3°, 5.9°, 8.1°, 16.4°, 18.8°, 23.8°, 26.5°, 27.2°2-theta. Form F may further be characterized by XRPD pattern having additionally at least one peak, e.g., at least two peaks, e.g., at least three peaks, e.g., at least four peaks, e.g., at least five peaks, e.g., at least six peaks, e.g., at least seven peaks, e.g., at least eight peaks, at least nine peaks, at least 10 peaks, e.g., all peaks selected from at: 5.3°± 0.2°, 5.9°± 0.2°, 8.1°± 0.2°, 9.4°± 0.2°, 16.4°± 0.2°, 18.8°± 0.2°, 23.8°± 0.2°, 24.6°± 0.2°, 25.2°± 0.2°, 26.5°± 0.2°, 27.2 ± 0.2° 2-theta, 5.3°± 0.1°, 5.9°± 0.1°, 8.1°± 0.1°, 9.4°± 0.1°, 16.4°± 0.1°, 18.8°± 0.1°, 23.8°± 0.1°, 24.6°± 0.1°, 25.1°± 0.1°, 26.5°± 0.1°, 27.2 ± 0.1° 2-theta, e.g., 5.3°, 5.9°, 8.1°, 9.4°, 16.4°, 18.8°, 23.8°, 24.6°, 25.2°, 26.5°, 27.2° 2-theta. Form F can also be characterized by a powder XRPD pattern with peaks as shown in Table 10. Table 10 XRPD data for Form F (cps indicates counts per second)

Form F may further be characterized by an XRPD pattern substantially as depicted in Figure 10A. Typically, Form F is substantially free of another polymorphic form. In some embodiments, a powder XRPD pattern of Form F may not have any of the peaks of relevant intensity at 3°, 6.9°, 9.4° 2-theta. The thermal behaviour of Form F may be characterized by TG-FTIR analysis, which confirmed that Form F is an acetone solvate form of the compound of formula I. The TG-FTIR curve of Form F, prepared by suspension equilibration of Form 1 in acetone, showed a mass loss of 4.1 % of acetone (and water) in a temperature range of 25°C – 160°C (Figure 10B, see Example 10). Amorphous Form G In some embodiments, the present disclosure also provides an amorphous form of the compound of formula I, which is an acetic acid solvate form, designated herein as Form G. Form G of the compound of formula I may be prepared by evaporation of an acetic acid solution, as described above and in the Examples. Both XRPD and Raman spectroscopy show patterns that are clearly distinct from any of the above crystalline Forms (Figure 11A, Figure 11B, see Example 11). Form G may be characterized by a Raman spectrum having peaks at 2936 ± 2 cm^-1, 1356 ± 2 cm- ¹, 883 ± 2 cm^-1. Form 1 may further be characterized by a Raman spectrum substantially as depicted in Figure 11B. Form G may further be characterized by an XRPD pattern substantially as depicted in Figure 11A. Typically, Form G is substantially free of another polymorphic form. Pharmaceutical Compositions The above polymorphic forms of the compound of formula I can be used in the preparation of a pharmaceutical composition comprising any one, or combinations of, the polymorphic forms of the compound of formula I described above, and at least one pharmaceutically acceptable carrier and/or excipient (also referred to as diluent). Thus, in some embodiments, the present disclosure further provides a pharmaceutical composition comprising any one, or combination, of the polymorphic forms of the compound of formula I described above and a pharmaceutically acceptable carrier and/or excipient. The excipients are acceptable in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof (i.e., the patient). The term "therapeutically- effective amount" as used herein refers to the amount of a polymorphic form (as such or in form of a pharmaceutical composition) of the present disclosure which is effective for producing some desired therapeutic effect. Pharmaceutical compositions may be in unit dose form containing a predetermined amount of a polymorphic form of the compound of formula I per unit dose. Such a unit may contain a therapeutically effective dose of a polymorphic form of the compound of formula I or a fraction of a therapeutically effective dose such that multiple unit dosage forms might be administered at a given time to achieve the desired therapeutically effective dose. In some embodiments, unit dosage formulations are those containing a daily dose or sub-dose, or an appropriate fraction thereof, of a polymorphic form of the present disclosure or salt thereof. The pharmaceutical compositions may be administered by any acceptable means in solid or liquid form, including (1) oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), tablets, e.g., those targeted for buccal, sublingual, and systemic absorption, boluses, powders, granules, pastes for application to the tongue; (2) parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation; (3) topical application, for example, as a cream, ointment, or a controlled-release patch or spray applied to the skin; (4) intravaginally or intrarectally, for example, as a pessary, cream or foam; (5) sublingually; (6) ocularly; (7) transdermally; (8) nasally; (9) pulmonary; or (10) intrathecally. If the pharmaceutical composition is in a liquid form, the one, or combination, of the above polymorphic forms of the compound of formula I with lower solubility characteristics may be retained as solid(s) in the liquid pharmaceutical composition, e.g., as a suspension, while, the one, or combination, of the above polymorphic forms of the compound of formula I with higher solubility characteristics may be fully solubilized in the liquid pharmaceutical composition, e.g., as a solution The phrase "pharmaceutically-acceptable carrier" as used herein means a pharmaceutically- acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, talc magnesium, calcium or zinc stearate, or steric acid), or solvent encapsulating material, involved in carrying or transporting the subject polymorphic form from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically- acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) pH buffered solutions; (21) polyesters, polycarbonates and/or polyanhydrides; and (22) other non-toxic compatible substances employed in pharmaceutical compositions. Such compositions may contain components conventional in pharmaceutical preparations, e.g., wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants, pH modifiers, bulking agents, and additional active agents. Examples of pharmaceutically-acceptable antioxidants include: (1) water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha- tocopherol, and the like; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. Such compositions may be prepared by any method known in the art, for example, by bringing into association the polymorphic form of the disclosure with one or more carriers and/or excipients. Different compositions and examples of carriers and/or excipients are well known to the skilled person and are described in detail in, e.g., Remington: The Science and Practice of Pharmacy. Pharmaceutical Press, 2013; Rowe, Sheskey, Quinn: Handbook of Pharmaceutical Excipients.Pharmaceutical Press, 2009. Excipients that may be used in the preparation of the pharmaceutical compositions may include one or more of buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants, sweeteners, perfuming agents, flavoring agents, diluents and other known additives to provide a composition suitable for an administration of choice. As indicated above, the polymorphic form(s) of the present disclosure may be in solid or liquid form and administered by various routes in any convenient administrative form, e.g., tablets, powders, capsules, solutions, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. In solid dosage forms of the disclosure for oral administration (capsules, tablets, pills, dragees, powders, granules, trouches and the like), a polymorphic form is mixed with one or more pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds and surfactants, such as poloxamer and sodium lauryl sulfate; (7) wetting agents, such as, for example, cetyl alcohol, glycerol monostearate, and non- ionic surfactants; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, zinc stearate, sodium stearate, stearic acid, and mixtures thereof; (10) coloring agents; and (11) controlled release agents such as crospovidone or ethyl cellulose. In the case of capsules, tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-shelled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface-active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets, and other solid dosage forms of the pharmaceutical compositions of the present invention, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be formulated for rapid release, e.g., freeze-dried. They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The polymorphic form can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients. Liquid dosage forms for oral administration of the polymorphic form(s) of the disclosure include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3Butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. An oral composition can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents. In form of suspensions, a polymorphic form of the disclosure may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof. Dosage forms for rectal or vaginal administration of a polymorphic form of the disclosure include a suppository, which may be prepared by mixing one or more compounds of the invention with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active compound. Other suitable forms include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate. Dosage forms for the topical or transdermal administration of a polymorphic form of the disclosure include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active polymorphic form may be mixed under sterile conditions with a pharmaceutically- acceptable carrier, and with any preservatives, buffers, or propellants which may be required. Such ointments, pastes, creams and gels may contain, in addition to a polymorphic form of the disclosure, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Dosage forms such as powders and sprays for administration of a polymorphic form of the disclosure, may contain excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane. Dosage forms such as transdermal patches for administration of a polymorphic form of the disclosure may include absorption enhancers or retarders to increase or decrease the flux of the compound across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the compound in a polymer matrix or gel. Other dosage forms contemplated include ophthalmic formulations, eye ointments, powders, solutions and the like. It is understood that all contemplated compositions must be stable under the conditions of manufacture and storage, and preserved against the contaminating action of microorganisms, such as bacteria and fungi. The dosage levels of a polymorphic form of the present disclosure in the pharmaceutical compositions of the present disclosure may be adjusted in order to obtain an amount of a polymorphic form of the present disclosure which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being deleterious to the patient. The dosage of choice will depend upon a variety of factors including the nature of the particular polymorphic form of the present disclosure used, the route of administration, the time of administration, the rate of excretion or metabolism of the particular polymorphic form used, the rate and extent of absorption, the duration of the treatment, other drugs, polymorphic forms and/or materials used in combination with the particular polymorphic form, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A medical practitioner having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required. In some embodiments, a suitable daily dose of a polymorphic form of the present disclosure will be that amount of the polymorphic form which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. In some embodiments, oral, intravenous, intracerebroventricular and subcutaneous doses of the polymorphic form(s) of the present disclosure for a patient, when used for the indicated analgesic effects, will range from about 0.0001 to about 100 mg, more usual 0.1 to 100 mg/kg per kilogram of body weight of recipient (patient, mammal) per day. In some embodiments, daily dosages may be from about 1 to about 1000 mg/day, and for example, from about 50 to about 500 mg/day. The effective dose of a polymorphic form of the present disclosure may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout a specified period (per day or per week or per month), optionally, in unit dosage forms. In some embodiments, dosing also depends on factors as indicated above, e.g., on the administration, and can be readily arrived at by one skilled in medicine or the pharmacy art. The polymorphic form(s) of the present disclosure inhibit or modulate the activity of a receptor tyrosine kinase, in particular extracellular mutants of ErbB-receptors, such as, but not limited to, EGFR-Viii (also EGFR-V3) and HER2-S310F. Thus, the polymorphic form(s) and compositions of the present disclosure can be useful as a medicament, i.e. as a medicament in therapy, for the treatment of cancer, as detailed below. In some embodiments, the present disclosure provides a method of treatment of a mammal, for example, a human, suffering from cancer, as detailed below. According to the methods of the disclosure, subjects having a mutation of the disclosure may be treated for cancer by administering a therapeutically-effective amount of a composition of the disclosure, a Type II ErbB inhibitor, an EGFR-Viii selective agent/inhibitor or the NT-113 Type I inhibitor. The term “therapeutically effective amount” refers to an amount of a composition of the disclosrue, a Type II ErbB inhibitor, an EGFR-Viii selective agent/inhibitor or the NT-113 Type I inhibitor effective to “treat” a disease or disorder (e.g., cancer) in a subject or mammal. Thus, the present disclosure is directed towards the use of the polymorphic form(s) of the present disclosure or a pharmaceutical composition thereof for the treatment of cancer, as detailed below, in a mammal, for example a human. In some aspects, the present disclosure provides a pharmaceutical composition comprising any one, or combination, of the polymorphic forms of the disclosure. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. In some embodiments, the composition further comprises a second therapeutically active agent. In some embodiments, the second therapeutically active agent comprises a non-Type I inhibitor. In some embodiments, the non-Type I inhibitor comprises a small molecule Type II inhibitor. In some embodiments, the present disclosure contemplates administration of a polymorphic form of the invention alone or in combination with one or more additional therapeutic agents, such as other Tyrosine kinase inhibitors: Erlotinib hydrochloride (e.g., Tarceva(R) by Genentech/Roche), Linifanib (or ABT 869, by Genentech), sunitinib malate (e.g., Sutent(R) by Pfizer), bosutinib (or SKI-606, described in US 6,780,996), dasatinib (e.g., Sprycel(R) by Bristol-Myers Squibb), armala (e.g., pazopanib, e.g., Votrient(R) by GlaxoSmithKline), imatinib and imatinib mesylate (e.g., Gilvec(R) and Gleevec(R) by Novartis); Vascular Endothelial Growth Factor (VEG) receptor inhibitors (Bevacizumab, or Avastin(R) by Genentech/Roche), axitinib, (or AG013736, described in WO 01/002369), Brivanib Alaninate (or BMS-582664), motesanib (or AMG-706, described in PCT WO 02/066470), pasireotide (e.g., SOM230, described in WO 02/010192), sorafenib (e.g., Nexavar(R)); HER2 receptor inhibitors: Trastuzumab (e.g., Herceptin(R) by Genentech/Roche), neratinib (or HKI-272, described WO 05/028443), lapatinib or lapatinib ditosylate (e.g., Tykerb(R) by GlaxoSmithKline); CD20 antibodies: Rituximab (e.g., Riuxan(R) and MabThera(R) by Genentech/Roche), tositumomab (e.g., Bexxar(R) by GlaxoSmithKline), ofatumumab (e.g., Arzerra(R) by GlaxoSmithKline); Bcr/Abl kinase inhibitors: nilotinib hydrochloride (e.g., Tasigna(R) by Novartis); DNA Synthesis inhibitors: Capecitabine (e.g., Xeloda(R) by Roche), gemcitabine hydrochloride (e.g., Gemzar(R) by Eli Lilly and Company), nelarabine (or Arranon(R) and Atriance(R) by GlaxoSmithKline); Antineoplastic agents: oxaliplatin (e.g., Eloxatin(R) ay Sanofi-Aventis described in US 4,169,846 ); Epidermal growth factor receptor (EGFR) inhibitors: Gefitinib (or Iressa(R)), Afatinib (or Tovok(R) by Boehringer Ingelheim), cetuximab (e.g., Erbitux(R) by Bristol-Myers Squibb), panitumumab (e.g., Vectibix(R) by Amgen); HER dimerization inhibitors: Pertuzumab (e.g., Omnitarg(R), by Genentech); Human Granulocyte colony-stimulatingfactor (G-CSF) modulators: Filgrastim (e.g., Neupogen(R) by Amgen); Immunomodulators: Afutuzumab (by Roche(R)), pegfilgrastim (e.g., Neulasta(R) by Amgen), lenalidomide (e.g., CC-5013, e.g., Revlimid(R)), thalidomide (e.g., Thalomid(R)); (m) CD40 inhibitors: Dacetuzumab (e.g., SGN-40 or huS2C6, by Seattle Genetics, Inc); Pro-apoptotic receptor agonists (PARAs): Dulanermin (e.g., AMG-951, by Amgen/Genentech); Hedgehog antagonists: Vismodegib (or GDC-0449, described in WO 06/028958); PI3K inhibitors: Pictilisib (or GDC-0941 described in WO 09/036082 and WO 09/055730 ), Dactolisib (or BEZ 235 or NVP- BEZ 235, described in WO 06/122806); Phospholipase A2 inhibitors: Anagrelide (e.g., Agrylin(R)); BCL-2 inhibitors: Navitoclax (or ABT-263, described in WO 09/155386); Mitogen- activated protein kinase kinase (MEK) inhibitors: XL-518 (Cas No. 1029872-29-4, by ACC Corp.); Aromatase inhibitors: Exemestane (e.g., Aromasin(R) by Pfizer), letrozole (e.g., Femara(R) by Novartis), anastrozole (e.g., Arimidex(R)); Topoisomerase I inhibitors: Irinotecan (e.g., Camptosar(R) by Pfizer), topotecan hydrochloride (e.g., Hycamtin(R) by GlaxoSmithKline); Topoisomerase II inhibitors: etoposide (e.g., VP-16 and Etoposide phosphate, e.g., Toposar(R), VePesid(R) and Etopophos(R)), teniposide (e.g., VM-26, e.g., Vumon(R)); mTOR inhibitors: Temsirolimus (e.g., Torisel(R) by Pfizer), ridaforolimus (formally known as deferolimus, (or AP23573 and MK8669, described in WO 03/064383), everolimus (e.g., Afinitor(R) by Novartis); Osteoclastic bone resorption inhibitors: zoledronic acid (or Zometa(R) by Novartis); CD33 Antibody Drug Conjugates: Gemtuzumab ozogamicin (e.g., Mylotarg(R) by Pfizer/Wyeth); CD22 Antibody Drug Conjugates: Inotuzumab ozogamicin (also referred to as CMC-544 and WAY- 207294, by Hangzhou Sage Chemical Co., Ltd.); CD20 Antibody Drug Conjugates: Ibritumomab tiuxetan (e.g., Zevalin(R)); Somatostain analogs: octreotide (e.g., octreotide acetate, e.g., Sandostatin(R) and Sandostatin LAR(R)); Synthetic Interleukin-11 (IL-11): oprelvekin (e.g., Neumega(R) by Pfizer/Wyeth); Synthetic erythropoietin: Darbepoetin alfa (e.g., Aranesp(R) by Amgen); Receptor Activator for Nuclear Factor kappa B (RANK) inhibitors: Denosumab (e.g., Prolia(R) by Amgen); Thrombopoietin mimetic peptibodies: Romiplostim (e.g., Nplate(R) by Amgen; Cell growth stimulators: Palifermin (e.g., Kepivance(R) by Amgen); Anti-Insulin-like Growth Factor-1 receptor (IGF-1R) antibodies: Figitumumab (e.g., CP-751,871, by ACC Corp), robatumumab (CAS No. 934235-44-6); Anti-CS1 antibodies: Elotuzumab (HuLuc63, CAS No. 915296-00-3); CD52 antibodies: Alemtuzumab (e.g., Campath(R)); CTLA-4 inhibitors: Tremelimumab (IgG2 monoclonal antibody by Pfizer, formerly known as ticilimumab, CP- 675,206), ipilimumab (CTLA-4 antibody, e.g., MDX-010, CAS No. 477202-00-9); Histone deacetylase inhibitors (HDI): Voninostat (e.g., Zolinza(R) by Merck); Alkylating agents: Temozolomide (e.g., Temodar(R) and Temodal(R) by Schering-Plough/Merck), dactinomycin (e.g., actinomycin-D and e.g., Cosmegen(R)), melphalan (e.g., L-PAM, L-sarcolysin, and phenylalanine mustard, e.g., Alkeran(R)), altretamine (e.g., hexamethylmelamine (HMM), e.g., Hexalen(R)), carmustine (e.g., BiCNU(R)), bendamustine (e.g., Treanda(R)), busulfan (e.g., Busulfex(R) and Myleran(R)), carboplatin (e.g., Paraplatin(R)), lomustine (e.g., CCNU, e.g., CeeNU(R)), cisplatin (e.g., CDDP, e.g., Platinol(R) and Platinol(R)-AQ), chlorambucil (e.g., Leukeran(R)), cyclophosphamide (e.g., Cytoxan(R) and Neosar(R)), dacarbazine (e.g., DTIC, DIC and imidazole carboxamide, e.g., DTIC-Dome(R)), altretamine (e.g., hexamethylmelamine (HMM) e.g., Hexalen(R)), ifosfamide (e.g., Ifex(R)), procarbazine (e.g., Matulane(R)), mechlorethamine (e.g., nitrogen mustard, mustine and mechloroethamine hydrochloride, e.g., Mustargen(R)), streptozocin (e.g., Zanosar(R)), thiotepa (e.g., thiophosphoamide, TESPA and TSPA, e.g., Thioplex(R); Biologic response modifiers: bacillus calmette-guerin (e.g., theraCys(R) and TICE(R) BCG), denileukin diftitox (e.g., Ontak(R)); Anti-tumor antibiotics: doxorubicin (e.g., Adriamycin(R) and Rubex(R)), bleomycin (e.g., lenoxane(R)), daunorubicin (e.g., dauorubicin hydrochloride, daunomycin, and rubidomycin hydrochloride, e.g., Cerubidine(R)), daunorubicin liposomal (daunorubicin citrate liposome, e.g., DaunoXome(R)), mitoxantrone (e.g., DHAD, e.g., Novantrone(R)), epirubicin (e.g., Ellence™), idarubicin (e.g., Idamycin(R), Idamycin PFS(R)), mitomycin C (e.g., Mutamycin(R)); Anti-microtubule agents: Estramustine (e.g., Emcyl(R)); Cathepsin K inhibitors: Odanacatib (or MK-0822, by Lanzhou Chon Chemicals, ACC Corp., and ChemieTek, described in WO 03/075836); Epothilone B analogs: Ixabepilone (e.g., Lxempra(R) by Bristol-Myers Squibb); Heat Shock Protein (HSP) inhibitors: Tanespimycin (17Allylamino-17- demethoxygeldanamycin, e.g., KOS-953 and 17AAG, by SIGMA, described in US 4,261,989); TpoR agonists: Eltrombopag (e.g., Promacta(R) and Revolade(R) by GlaxoSmithKline); Anti- mitotic agents: Docetaxel (e.g., Taxotere(R) by Sanofi-Aventis); Adrenal steroid inhibitors: aminoglutethimide (e.g., Cytadren(R)); Anti-androgens: Nilutamide (e.g., Nilandron(R) and Anandron(R)), bicalutamide (sold under tradename Casodex(R)), flutamide (e.g., Fulexin™); Androgens: Fluoxymesterone (e.g., halotestin(R)); Proteasome inhibitors: Bortezomib (e.g., Velcade(R)); CDK1 inhibitors: Alvocidib (e.g., flovopirdol or HMR-1275, described in US 5,621,002); Gonadotropin-releasing hormone (GnRH) receptor agonists: Leuprolide or leuprolide acetate (e.g., Viadure(R) by Bayer AG, Eligard(R) by Sanofi-Aventis and Lupron(R) by Abbott Lab); Taxane anti-neoplastic agents: Cabazitaxel, larotaxel; 5HT1a receptor agonists: Xaliproden (or SR57746, described in US 5,266,573); HPC vaccines: Cervarix(R) sold by GlaxoSmithKline, Gardasil(R) sold by Merck; Iron Chelating agents: Deferasinox (e.g., Exjade(R) by Novartis); Anti-metabolites: Claribine (2Chlorodeoxyadenosine, e.g., leustatin(R)), 5-fluorouracil (e.g., Adrucil(R)), 6-thioguanine (e.g., Purinethol(R)), pemetrexed (e.g., Alimta(R)), cytarabine (e.g., arabinosylcytosine (Ara-C), e.g., Cytosar-U(R)), cytarabine liposomal (e.g., Liposomal Ara-C, e.g., DepoCyt™), decitabine (e.g., Dacogen(R)), hydroxyurea (e.g., Hydrea(R), Droxia™ and Mylocel™), fludarabine (e.g., Fludara(R)), floxuridine (e.g., FUDR(R)), cladribine (e.g., 2Chlorodeoxyadenosine (2CdA) e.g., Leustatin™), methotrexate (e.g., amethopterin, methotrexate sodim (MTX), e.g., Rheumatrex(R) and Trexall™), pentostatin (e.g., Nipent(R)); Bisphosphonates: Pamidronate (e.g., Aredia(R)), zoledronic acid (e.g., Zometa(R)); Demethylating agents: 5Azacitidine (e.g., Vidaza(R)), decitabine (e.g., Dacogen(R)); Plant Alkaloids: Paclitaxel protein-bound (e.g., Abraxane(R)), vinblastine (e.g., vinblastine sulfate, vincaleukoblastine and VLB, e.g., Alkaban-AQ(R) and Velban(R)), vincristine (e.g., vincristine sulfate, LCR, and VCR, e.g., Oncovin(R) and Vincasar Pfs(R)), vinorelbine (e.g., Navelbine(R)), paclitaxel (e.g., Taxol and Onxal™); Retinoids: Alitretinoin (e.g., Panretin(R)), tretinoin (all-trans retinoic acid, e.g., ATRA, e.g., Vesanoid(R)), Isotretinoin (13-cis-retinoic acid, e.g., Accutane(R), Amnesteem(R), Claravis(R), Clarus(R), Decutan(R), Isotane(R), Izotech(R), Oratane(R), Isotret(R), and Sotret(R)), bexarotene (e.g., Targretin(R)); Glucocorticosteroids: Hydrocortisone (e.g., cortisone, hydrocortisone sodium succinate, hydrocortisone sodium phosphate, and e.g., Ala- Cort(R), Hydrocortisone Phosphate, Solu-Cortef(R), Hydrocort Acetate(R) and Lanacort(R)), dexamethasone, prednisolone (e.g., Delta-Cortel(R), Orapred(R), Pediapred(R) and Prelone(R)), prednisone (e.g., Deltasone(R), Liquid Red(R), Meticorten(R) and Orasone(R)), methylprednisolone (e.g., 6-Methylprednisolone, Methylprednisolone Acetate, Methylprednisolone Sodium Succinate, e.g., Duralone(R), Medralone(R), Medrol(R), M- Prednisol(R) and Solu-Medrol(R)); Cytokines: interleukin-2 (e.g., aldesleukin and IL-2, e.g., Proleukin(R)), interleukin-11 (e.g., oprevelkin, e.g., Neumega(R)), alpha interferon alfa (e.g., IFN- alpha, e.g., Intron(R) A, and Roferon-A(R)); Lutinizing hormone releasing hormone (LHRH) agonists: Goserelin (e.g., Zoladex(R)); Progesterones: megestrol (e.g., megestrol acetate, e.g., Megace(R)); Miscellaneous cytotoxic agents: Arsenic trioxide (e.g., Trisenox(R)), asparaginase (e.g., L-asparaginase, Erwinia L-asparaginase, e.g., Elspar(R) and Kidrolase(R)); Anti-nausea drugs: NK-1 receptor antagonists: Casopitant (e.g., Rezonic(R) and Zunrisa(R) by GlaxoSmithKline); and Cytoprotective agents: Amifostine (e.g., Ethyol(R)), leucovorin (e.g., calcium leucovorin, citrovorum factor and folinic acid).

Uses of Polymorphic Forms and Compositions In some aspects, the present disclosure provides a method of inhibiting an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR), comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of inhibiting an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR), comprising administering to the subject in need thereof a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in the subject; and ii) administering to the subject in need of the treatment a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in the subject; and ii) administering to the subject in need of the treatment a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject; and ii) administering to the subject in need of the treatment a therapeutically effective amount of a polymorphic form described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject; and ii) administering to the subject in need of the treatment a composition described herein. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in the subject. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a polymorphic form described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in the subject. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of a polymorphic form described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in a biological sample from the subject. In some aspects, the present disclosure provides a method of preventing or treating cancer, comprising administering to the subject in need thereof a composition described herein when that at least one oncogenic variant of an ErbB receptor described herein is identified as being present in a biological sample from the subject. In some aspects, the present disclosure provides a polymorphic form described herein for use in the inhibition of an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR). In some aspects, the present disclosure provides a composition described herein for use in the inhibition of an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR). In some aspects, the present disclosure provides a polymorphic form described herein for use in the prevention or treatment of cancer. In some aspects, the present disclosure provides a composition described herein for use in the prevention or treatment of cancer. In some aspects, the present disclosure provides a polymorphic form described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in the subject. In some aspects, the present disclosure provides a composition described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in the subject. In some aspects, the present disclosure provides a polymorphic form described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject. In some aspects, the present disclosure provides a composition described herein for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor described herein is present in a biological sample from the subject. In some aspects, the present disclosure provides use of a polymorphic form described herein in the manufacture of a medicament for inhibiting an oncogenic variant of an ErbB receptor (e.g., an oncogenic variant of an EGFR). In some aspects, the present disclosure provides use of a polymorphic form described herein in the manufacture of a medicament for preventing or treating cancer. In some embodiments, cancer is a solid tumor. In some embodiments, the cancer is a bladder cancer, a breast cancer, a cervical cancer, a colorectal cancer, an endometrial cancer, a gastric cancer, a glioblastoma (GBM), a head and neck cancer, a lung cancer, a non-small cell lung cancer (NSCLC), or any subtype thereof. In some embodiments, the cancer is glioblastoma (GBM) or any subtype thereof. In some embodiments, the cancer is glioblastoma. In some embodiments, the cancer or a tumor or a cell thereof expresses an oncogenic variant of an epidermal growth factor receptor (EGFR). In some embodiments, the oncogenic variant is an oncogenic variant in an ErbB receptor. In some embodiments, the oncogenic variant in the ErbB receptor is an allosteric variant. In some embodiments, the ErbB receptor is an epidermal growth factor receptor (EGFR) or a human epidermal growth factor receptor 2 (HER2) receptor. In some embodiments, the ErbB receptor is an epidermal growth factor receptor (EGFR). In some embodiments, the ErbB receptor is a HER2 receptor. In some embodiments, the oncogenic variant is an oncogenic variant in an epidermal growth factor receptor (EGFR). In some embodiments, the oncogenic variant in the EGFR is an allosteric variant. In some embodiments, the oncogenic variant is an oncogenic variant of a HER2 receptor. In some embodiments, the oncogenic variant in the HER2 receptor is an allosteric variant. In some embodiments, the oncogenic variant in the EGFR is an EGFR variant III (EGFR-Viii) variant. In some embodiments, the oncogenic variant in the EGFR is a substitution of a valine (V) for an alanine (A) at position 289 of SEQ ID NO: 1. In some embodiments, the oncogenic variant is an oncogenic variant in an EGFR and wherein the oncogenic variant in the EGFR is an allosteric variant in the EGFR, the oncogenic variant in the EGFR is a modification of a structure of the EGFR, wherein the oncogenic variant in the EGFR is capable of forming a covalently linked dimer, wherein the covalently linked dimer is constitutively active and wherein the covalently linked dimer enhances an activity of EGFR when contacted to a Type I ErbB inhibitor. In some embodiments, the modification of the structure of the EGFR comprises a modification of one or more of a nucleic acid sequence, an amino acid sequence, a secondary structure, a tertiary structure, and a quaternary structure. In some embodiments, the modification of the structure of the EGFR occurs within a first cysteine rich (CR1) and/or second cysteine rich (CR2) region of EGFR. In some embodiments, the first cysteine rich (CR1) and/or second cysteine rich (CR2) region of EGFR comprises amino acid residues T211-R334 and/or C526-S645 of SEQ ID NO: 1, respectively. In some embodiments, the oncogenic variant in the EGFR generates a physical barrier to formation of a disulfide bond within the CR1 and/or the CR2 region. In some embodiments, the oncogenic variant in the EGFR removes a physical barrier to formation of a disulfide bond within the CR1 and/or the CR2 region. In some embodiments, the oncogenic variant in the EGFR results into one or more free or unpaired Cysteine (C) residues located at a dimer interface of the EGFR. In some embodiments, the oncogenic variant in the EGFR results into one or more free or unpaired Cysteine (C) residues at a site selected from the group consisting of

according to SEQ ID NO: 1. In some embodiments, the modification occurs within 10 angstroms or less of an intramolecular disulfide bond at a site selected from the group consisting of C

according to SEQ ID NO: 1. In some embodiments, the oncogenic variant is an oncogenic variant in an EGFR and wherein the oncogenic variant in the EGFR is an allosteric variant in the EGFR, wherein a nucleotide sequence encoding the EGFR having the oncogenic variant comprises a deletion or the substitution comprises one or more amino acids that encode an adenosine triphosphate (ATP) binding site. In some embodiments, the ATP binding site comprises amino acids E746 to A750 of SEQ ID NO: 1. In some embodiments, the ATP binding site or the deletion or substitution thereof comprises K858 of SEQ ID NO: 1. In some embodiments, the deletion comprises K858 of SEQ ID NO: 1. In some embodiments, an arginine (R) is substituted for the lysine (K) at position 858 (K858R) of SEQ ID NO: 1. In some embodiments, an arginine (R) is substituted for the leucine (L) at position 858 (L858R) of SEQ ID NO: 1. In some embodiments, the oncogenic variant is an oncogenic variant in an EGFR and wherein the oncogenic variant in the EGFR is an allosteric variant in the EGFR, wherein a nucleotide sequence encoding the EGFR having the oncogenic variant comprises an insertion within a sequence encoding exon 20 or a portion thereof. In some embodiments, the sequence encoding exon 20 or a portion thereof comprises a sequence encoding KEILDEAYVMASVDNPHVCAR (SEQ ID NO: 7). In some embodiments, the sequence encoding exon 20 or a portion thereof comprises a sequence encoding a C-helix, a terminal end of the C-helix or a loop following the C-helix. In some embodiments, the insertion comprises the amino acid sequence of ASV, SVD, NPH, or FQEA. In some embodiments, the sequence encoding exon 20 or a portion thereof comprises one or more of: (a) an insertion of the amino acid sequence ASV between positions V769 and D770 of SEQ ID NO: 1; (b) an insertion of the amino acid sequence SVD between positions D770 and N771 of SEQ ID NO: 1; (c) an insertion of the amino acid sequence NPH between positions H773 and V774 of SEQ ID NO: 1; (d) an insertion of the amino acid sequence FQEA between positions A763 and Y764 of SEQ ID NO: 1; (e) an insertion of the amino acid sequence PH between positions H773 and V774 of SEQ ID NO: 1; (f) an insertion of the amino acid G between positions D770 and N771 of SEQ ID NO: 1; (g) an insertion of the amino acid H between positions H773 and V774 of SEQ ID NO: 1; (h) an insertion of the amino acid sequence HV between positions V774 and C775 of SEQ ID NO: 1; (i) an insertion of the amino acid sequence AH between positions H773 and V774 of SEQ ID NO: 1; (j) an insertion of the amino acid sequence SVA between positions A767 and S768 of SEQ ID NO: 1; (k) a substitution of the amino acid sequence GYN for the DN between positions 770 and 771 of SEQ ID NO: 1; (l) an insertion of the amino acid H between positions N771 and P772 of SEQ ID NO: 1; (m) an insertion of the amino acid Y between positions H773 and V774 of SEQ ID NO: 1; (n) an insertion of the amino acid sequence PHVC between positions C775 and R776 of SEQ ID NO: 1; (o) a substitution of the amino acid sequence YNPY for the H at position 773 of SEQ ID NO: 1; (p) an insertion of the amino acid sequence DNP between positions P772 and H773 of SEQ ID NO: 1; (q) an insertion of the amino acid sequence VDS between positions S768 and V769 of SEQ ID NO: 1; (r) an insertion of the amino acid H between positions D770 and N771 of SEQ ID NO: 1; (s) an insertion of the amino acid N between positions N771 and P772 of SEQ ID NO: 1; (t) an insertion of the amino acid sequence PNP between positions P772 and H773 of SEQ ID NO: 1; (u) a substitution of the amino acid sequence GSVDN for the DN between positions 770 and 771 of SEQ ID NO: 1; (v) a substitution of the amino acid sequence GYP for the NP between positions 771 and 772 of SEQ ID NO: 1; (w) an insertion of the amino acid G between positions N771 and P772 of SEQ ID NO: 1; (x) an insertion of the amino acid sequence GNP between positions P772 and H773 of SEQ ID NO: 1; (y) an insertion of the amino acid sequence GSV between positions V769 and D770 of SEQ ID NO: 1; (z) a substitution of the amino acid sequence GNPHVC for the VC between positions 774 and 775 of SEQ ID NO: 1; (aa) an insertion of the amino acid sequence LQEA between positions A763 and Y764 of SEQ ID NO: 1; (bb) an insertion of the amino acid sequence GL between positions D770 and N771 of SEQ ID NO: 1; (cc) an insertion of the amino acid Y between positions D770 and N771 of SEQ ID NO: 1; (dd) an insertion of the amino acid sequence NPY between positions H773 and V774 of SEQ ID NO: 1; (ee) an insertion of the amino acid sequence TH between positions H773 and V774 of SEQ ID NO: 1; (ff) a substitution of the amino acid sequence KGP for the NP between positions 771 and 772 of SEQ ID NO: 1; (gg) a substitution of the amino acid sequence SVDNP for the NP between positions 771 and 772 of SEQ ID NO: 1; (hh) an insertion of the amino acid sequence NN between positions N771 and P772 of SEQ ID NO: 1; (ii) an insertion of the amino acid T between positions N771 and P772 of SEQ ID NO: 1; and (jj) a substitution of the amino acid sequence STLASV for the SV between positions 768 and 769 of SEQ ID NO: 1. In some embodiments, the oncogenic variant is an oncogenic variant in an EGFR and wherein the oncogenic variant in the EGFR is an allosteric variant in the EGFR, the EGFR having the oncogenic variant comprises

, , , ,

or any combination thereof. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor, the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of a phenylalanine (F) for a serine (S) at position 310 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of a tyrosine (Y) for a serine (S) at position 310 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of a glutamine (Q) for an arginine (R) at position 678 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of a leucine (L) for a valine (V) at position 777 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of a methionine (M) for a valine (V) at position 777 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of an isoleucine (I) for a valine (V) at position 842 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of an alanine (A) for a leucine (L) at position 755 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of a proline (P) for a leucine (L) at position 755 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the oncogenic mutatin in the HER2 receptor comprises a substitution of a serine (S) for a leucine (L) at position 755 of SEQ ID NO: 2 or 5. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, wherein a nucleotide sequence encoding the HER2 receptor having the oncogenic variant comprises an insertion within a sequence encoding exon 20 or a portion thereof. In some embodiments, the sequence encoding exon 20 or a portion thereof comprises a sequence encoding KEILDEAYVMAGVGSPYVSR(SEQ ID NO: 8). In some embodiments, the sequence encoding exon 20 or a portion thereof comprises a sequence encoding a C-helix, a terminal end of the C- helix or a loop following the C-helix. In some embodiments, the insertion comprises the amino acid sequence of GSP or YVMA. In some embodiments, the sequence encoding exon 20 or a portion thereof comprises one or more of: (a) an insertion of the amino acid sequence YVMA between positions A775 and G776 of SEQ ID NO: 2; (b) an insertion of the amino acid sequence GSP between positions P780 and Y781 of SEQ ID NO: 2; (c) an insertion of the amino acid sequence YVMA between positions A771 and Y772 of SEQ ID NO: 2; (d) an insertion of the amino acid sequence YVMA between positions A775 and G776 of SEQ ID NO: 2; (e) an insertion of the amino acid V between positions V777 and G778 of SEQ ID NO: 2; (f) an insertion of the amino acid V between positions V777 and G778 of SEQ ID NO: 2; (g) a substitution of the amino acid sequence AVGCV for the GV between positions 776 and 777 of SEQ ID NO: 2; (h) a substitution of the amino acid sequence LC for the G between position 776 of SEQ ID NO: 2; (i) a substitution of the amino acid sequence LCV for the G between position 776 of SEQ ID NO: 2; (j) an insertion of the amino acid sequence GSP between positions V777 and G778 of SEQ ID NO: 2; (k) a substitution of the amino acid sequence PS for the LRE between positions 755 and 757 of SEQ ID NO: 2; (l) a substitution of the amino acid sequence CPGSP for the SP between positions 779 and 780 of SEQ ID NO: 2; (m) an insertion of the amino acid C between positions V777 and G778 of SEQ ID NO: 2; (n) a substitution of the amino acid sequence VVMA for the AG between positions 775 and 776 of SEQ ID NO: 2; (o) a substitution of the amino acid sequence VV for the G at position 776 of SEQ ID NO: 2; (p) a substitution of the amino acid sequence AVCV for the GV between positions 776 and 777 of SEQ ID NO: 2; (q) a substitution of the amino acid sequence VCV for the GV between positions 776 and 777 of SEQ ID NO: 2; (r) an insertion of the amino acid G between positions G778 and S779 of SEQ ID NO: 2; (s) a substitution of the amino acid sequence PK for the LRE between positions 755 and 757 of SEQ ID NO: 2; (t) an insertion of the amino acid V between positions A775 and G776 of SEQ ID NO: 2; (u) an insertion of the amino acid sequenceYAMA between positions A775 and G776 of SEQ ID NO: 2; (v) a substitution of the amino acid sequence CV for the G at position 776 of SEQ ID NO: 2; (w) a substitution of the amino acid sequence AVCGG for the GVG between positions 776 and 778 of SEQ ID NO: 2; (x) a substitution of the amino acid sequence CVCG for the GVG between positions 776 and 778 of SEQ ID NO: 2; (y) a substitution of the amino acid sequence VVVG for the GVG between positions 776 and 778 of SEQ ID NO: 2; (z) a substitution of the amino acid sequence SVGG for the GVGS between positions 776 and 779 of SEQ ID NO: 2; (aa) a substitution of the amino acid sequence VVGES for the GVGS between positions 776 and 779 of SEQ ID NO: 2; (bb) a substitution of the amino acid sequence AVGSGV for the GV between positions 776 and 777 of SEQ ID NO: 2; (cc) a substitution of the amino acid sequence CVC for the GV between positions 776 and 777 of SEQ ID NO: 2; (dd) a substitution of the amino acid sequence HVC for the GV between positions 776 and 777 of SEQ ID NO: 2; (ee) a substitution of the amino acid sequence VAAGV for the GV between positions 776 and 777 of SEQ ID NO: 2; (ff) a substitution of the amino acid sequence VAGV for the GV between positions 776 and 777 of SEQ ID NO: 2; (gg) a substitution of the amino acid sequence VVV for the GV between positions 776 and 777 of SEQ ID NO: 2; (hh) an insertion of the amino acid sequence FPG between positions G778 and S779 of SEQ ID NO: 2; (ii) an insertion of the amino acid sequence GS between positions S779 and P780 of SEQ ID NO: 2; (jj) a substitution of the amino acid sequence VPS for the VLRE between positions 754 and 757 of SEQ ID NO: 2; (kk) an insertion of the amino acid E between positions V777 and G778 of SEQ ID NO: 2; (ll) an insertion of the amino acid sequence MAGV between positions V777 and G778 of SEQ ID NO: 2; (mm) an insertion of the amino acid S between positions V777 and G778 of SEQ ID NO: 2; (nn) an insertion of the amino acid sequence SCV between positions V777 and G778 of SEQ ID NO: 2; and (oo) an insertion of the amino acid sequence LMAY between positions Y772 and V773 of SEQ ID NO: 2. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-2 receptor and wherein the oncogenic variant in the HER2 receptor is an allosteric variant in the HER2 receptor, the HER2 receptor having the oncogenic variant comprises HER2- ^16, HER2C311R, HER2- S310F, p95-HER2-M611 or any combination thereof. In some embodiments, the oncogenic variant is an oncogenic variant in a HER-4 receptor. In some embodiments, the oncogenic variant in the HER-4 receptor is an allosteric variant in the HER4 receptor. In some embodiments, the oncogenic variant in the HER4 receptor results into the deletion of exon 16 (HER4-Δ16). In some embodiments, the subject or the cancer is insensitive or resistant to treatment with one or more of gefinitinib, erlotinib, afatinib, osimertinib, and necitunumab. In some embodiments, the subject or the cancer is insensitive or resistant to treatment with one or more of crixotinib, alectinib, and ceritinib. In some embodiments, the subject or the cancer is insensitive or resistant to treatment with one or more of dabrafenib and trametinib. In some embodiments, the subject or the cancer is insensitive or resistant to treatment with crizotinib. In some embodiments, the sequence encoding the oncogenic variant of the EGFR comprises a deletion of exon 20 or a portion thereof and wherein the cancer, tumor or cell thereof does not comprise an oncogenic variation in a sequence encoding one or more of an EGFR kinase domain (KD), BRAF, NTRK, and KRAS or wherein. In some embodiments, the sequence encoding the oncogenic variant of the EGFR comprises a deletion of exon 20 or a portion thereof and wherein the cancer, tumor or cell thereof does not comprise a marker indicating responsiveness to immunotherapy. In some embodiments, the oncogenic variant (e.g., allosteric variant) or the oncogenic mutation (e.g., allosteric mutation) is detected by a Food and Drug Aministration (FDA)-approved diagnosis. In some embodiments, the subject has an adverse reaction to treatment with a therapeutic agent different from the polymorphic form of the present disclosure. In some embodiments, the subject has an adverse reaction to treatment with a Type I inhibitor. In some embodiments, the subject has an adverse reaction to treatment with one or more of gefinitinib, erlotinib, afatinib, osimertinib, necitunumab, crizotinib, alectinib, ceritinib, dabrafenib, trametinib, afatinib, sapitinib, dacomitinib, canertinib, pelitinib,

In some embodiments, the adverse reaction is an activation of the oncogenic variant of an EGFR and wherein the oncogenic variant comprises a mutation in an extracellular domain of the receptor. In some embodiments, the adverse reaction is an activation of the oncogenic variant of a HER-2 Receptor and wherein the oncogenic variant comprises a mutation in an extracellular domain of the receptor. In some embodiments, the polymorphic form is used in combination with a second therapeutically active agent. In some embodiments, the composition comprises a second therapeutically active agent. In some embodiments, the second therapeutically active agent comprises a second polymorphic form of the disclosure. In some embodiments, the second therapeutically active agent comprises a non-Type I inhibitor. In some embodiments, the non-Type I inhibitor comprises a Type II inhibitor. In some embodiments, the Type II inhibitor comprises a small molecule inhibitor. In some embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a non-Type I inhibitor. In some embodiments, the non-Type I inhibitor comprises a small molecule Type II inhibitor. In some embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a non-Type I inhibitor. In some embodiments, the non-Type I inhibitor comprises a small molecule Type II inhibitor. In some embodiments, the polymorphic form is used in combination with a therapeutically effective amount of a non-Type I inhibitor. In some embodiments, the non-Type I inhibitor comprises a small molecule Type II inhibitor. In some embodiments, the composition comprises a non-Type I inhibitor. In some embodiments, the non-Type I inhibitor comprises a small molecule Type II inhibitor. In some embodiments, the cancer comprises a solid tumor. In some embodiments, the cancer comprises a bladder cancer, a breast cancer, a cervical cancer, a colorectal cancer, an endometrial cancer, a gastric cancer, a glioblastoma (GBM), a head and neck cancer, a lung cancer, a non-small cell lung cancer (NSCLC) or any subtype thereof. In some embodiments, the cancer comrprises a glioblastoma (GBM). In some embodiments, the cancer comprises a breast cancer. In some embodiments, the cancer comprises a lung cancer. In some embodiments, the therapeutically effective amount reduces a severity of a sign or symptom of the cancer. In some embodiments, the sign of the cancer comprises a tumor grade and wherein a reduction of the severity of the sign comprises a decrease of the tumor grade. In some embodiments, the sign of the cancer comprises a tumor metastasis and wherein a reduction of the severity of the sign comprises an elimination of the metastasis or a reduction in the rate or extent the metastasis. In some embodiments, the sign of the cancer comprises a tumor volume and wherein a reduction of the severity of the sign comprises an elimination of the tumor or a reduction in the volume. In some embodiments, the symptom of the cancer comprises pain and wherein a reduction of the severity of the sign comprises an elimination or a reduction in the pain. In some embodiments, the therapeutically effective amount induces a period of remission. In some embodiments, the therapeutically effective amount improves a prognosis of the subject. In some embodiments, the subject is a participant or a candidate for participation in in a clinical trial or protocol thereof. In some embodiments, the subject is excluded from treatment with a Type I inhibitor. In some embodiments, the Type I inhibitor comprises gefinitinib, erlotinib, afatinib, osimertinib, necitunumab, crizotinib, alectinib, ceritinib, dabrafenib, trametinib, afatinib, sapitinib, dacomitinib, canertinib, pelitinib, W

In some embodiments, the use comprises treating the subject with a Non-Type I inhibitor. In some embodiments, the composition comprises a Non-Type I inhibitor. In some embodiments, the Non-Type I inhibitor comprises a Type II small molecule inhibitor. In some embodiments, the Type II small molecule inhibitor comprises neratinib, AST-1306, HKI- 357, or lapatinib. Having described the disclosure with reference to certain preferred embodiments, other embodiments will become apparent to one skilled in the art from consideration of the specification. The disclosure is further defined by reference to the following examples describing the preparation, characterization and uses of the polymorphic forms of the disclosure. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the scope of the disclosure.

EXAMPLES Instrumentation and experimental protocols for characterization of polymorphs of the disclosure Solvents: For all experiments, Merck and Sigma analytical grade solvents were used. Solubility measurements: Approximate solubilities were determined at room temperature by addition of small aliquots of solvent to approximately 10 mg of solid and shaking/sonicating for a short period of time at ambient conditions. X-Ray Powder Diffraction (XRPD) XRPD patterns were collected on a Stoe Stadi P diffractometer at 40KV and 40mA using CuKa radiation of 1.541 A wavelength and a Mythen1K detector. Data were collected at 2-theta from 4 to 40 ° with a 2-theta step size of 0.02 ° and a scanning speed of 12s/step. Sample preparation: Typically, the sample would be exposed to the x-ray beam for 840 seconds. Samples were prepared as flat plate specimens using powder as received without grinding. For a typical sample preparation about 10 mg of sample was placed between two acetate foils and mounted into a Stoe transmission sample holder. The sample was rotated during the measurement (1 Rps). The Instrument is daily checked with a NIST SRM1976 Alumina standard to ensure the correct peak positions and sufficient signal intensity. Differential Scanning Calorimetry (DSC): DSC data were collected on a TA Instruments Q2000 equipped with a 50 position auto-sampler. The instrument was calibrated for energy and temperature calibration using certified indium. Typically, 0.5-1.5 mg of each sample, in a pin- holed aluminium pan, was heated at 10 °C/min from 25 °C to 175-220 °C A nitrogen purge at 50 mL/min was maintained over the sample. When two heating scans were carried out, the sample was rapidly cooled to -50 °C between the scans. Dynamic Vapor Sorption (DVS) Sorption isotherms were determined using a SPS11-100n “Sorptions Prüfsystem” (ProUmid) instrument. The sample temperature was maintained at 25 °C, the humidity was controlled by mixing streams of dry and wet nitrogen, with a total flow rate of 200 mL/min. The relative humidity was measured by a calibrated Rotronic probe (dynamic range of 1.0-100 % relative humidity), located near the sample. The weight change, (mass relaxation) of the sample as a function of % relative humidity was constantly monitored by the microbalance (accuracy ± 0.005 mg). Typically, a 5-20 mg sample was placed aluminum sample pan under ambient conditions. The sample was loaded and unloaded at 40 % relative humidity and 25 °C (typical ambient conditions) and two cycles were run at 25 °C, in which the relative humidity was stepwise increased from 0 % to 95 % and subsequently decreased again to 0 % and the weight of the sample measured. Samples were recovered after completion of the isotherm and re-analyzed by XRPD. Fourier Transformed (FT)-Raman spectroscopy: FT-Raman spectra were recorded on a Bruker MultiRAM FT-Raman system with a near infrared Nd:YAG laser operating at 1064 nm and a liquid nitrogen-cooled germanium detector. For each sample, a minimum of 64 scans with a resolution of 2 cm^-1 were accumulated. 300 mW laser power was used. The FT-Raman data are shown in the region between 3500 to 100 cm^-1. Below 100 cm^-1 the data are meaningless due to the filter cut-off. Thermogravimety-Fourier Transformed Infrared (TG-FTIR) analysis: TG-FTIR measurements were carried out with a Netzsch Thermo-Microbalance TG 209 coupled to a Bruker FTIR Spectrometer Vector 22 or IFS 28 Samples: sample pans with a pinhole, N2 atmosphere, heating rate 10 °C/min, heating range 25 °C up to 250 °C. Fourier Transform infrared (FTIR) spectroscopy: FTIR experiments were conducted on a Bruker ATR platinum Diamond single reflection instrument Samples: the samples (approx.1-2 mg) were placed directly on the diamond surface of the ATR unit and analysed in the wave number region 4000 - 600 cm^-1. Slurry conversion experiments of Form 1: The critical water activity was determined in a 1,4- dioxane/water (99/1, v/v) solvent mixture. Monohydrate Form 1 and a non-solvated form were suspended in a 1:1 ratio in the solvent mixture (1,4-dioxane was pre-dried over molecular sieves). The 99/1 (v/v) solvent system had a water activity of about 0.2. The Karl-Fischer titration of the filtrate after the experiment showed a water content of 1% (v/v). After seven days of equilibration the sample converted completely into the monohydrate Form 1. Thus, the critical water activity must be below 0.2 in an aqueous system. The overlay of the XRPD patterns of starting materials and conversion product is depicted in Figure 1H. Example 1A: Preparation of a polymorphic form of the compound of formula I Step 1: Chlorination: A solution of 7-fluoro-6-nitro-quinazolin-4-ol 1 (5.00 g, 23.9 mmol, 1.00 eq) in thionyl chloride (20.0 mL) was added dimethyl formamide (174 mg, 2.39 mmol, 183 uL, 0.10 eq). The reaction was stirred at 80 °C for 10 h. The reaction mixture was concentrated under reduced pressure to give 4Chloro-7-fluoro-6-nitroquinazoline 2 (6.00 g, crude) as an off-white solid. The product was taken to next step without purification. Step 2: Coupling to free amine: A mixture of 4Chloro-7-fluoro-6-nitroquinazoline 2 (2.4 g, 10.55 mmol, 1 eq) and the free amine 3-chloro-4-(pyridin-2-ylmethoxy)aniline (3.50 g, 14.9 mmol) in isopropyl alcohol was heated at 80 °C for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was triturated with ethyl acetate to give the corresponding secondary amine 3. Step 3: Nucleophilic displacement of the 7-fluoro-substituent: To a solution of the secondary amine 3 (1 eq) and 2-morpholinoethanol (179 mg, 1.37 mmol) in acetonitrile was added cesium carbonate (2eq) or DBU (2eq) and optionally potassium iodide (1 eq). Then the mixture was stirred at 80-110 °C for 12 h to achieve nucleophilic displacement of the 7-fluoro-substituent. The reaction mixture was quenched by addition of water and then extracted with ethyl acetate. The combined organic layers were washed with brine dried over sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography to give the corresponding coupling product 4. Step 4: Reduction of nitro-group: A mixture of 4 (1 eq) and nickel(II) chloride hexahydrate (2 eq) in dichloromethane and methanol (1:1) was added sodium borohydride (4 eq) at 0 °C and then the mixture was stirred at 0 °C for 12 h. The reaction mixture was filtered and the filtrate was concentrated to give a residue. The residue was purified by reversed phase column chromatography to give the corresponding free amine 5. Step 5: The free amine 5 (100 mg) was reacted in DMF (0.75 mL) with acrylic anhydride (270 mg) in the presence of triethylamine (260 mg) at 25-30°C. After completed reaction, the mixture was diluted with water and the compound of formula I was isolated by filtration. ¹H NMR (400MHz, DMSO-d6) δ = 9.69 (s, 1H), 9.62 (s, 1H), 8.83 (s, 1H), 8.60 (d, J = 4.8 Hz, 1H), 8.49 (s, 1H), 7.99 (d, J = 2.4 Hz, 1H), 7.88 (dt, J = 1.2, 7.6 Hz, 1H), 7.69 (dd, J = 2.4, 9.0 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.41 - 7.34 (m, 1H), 7.31 (s, 1H), 7.25 (d, J = 9.2 Hz, 1H), 6.68 (br dd, J = 10.8, 17.2 Hz, 1H), 6.31 (dd, J = 16.8, 1.2 Hz, 1H), 5.82 (br d, J = 11.6 Hz, 1H), 5.29 (s, 2H), 4.34 (t, J = 5.6 Hz, 2H), 3.57 (t, J = 4.4 Hz, 4H), 3.32 (br s, 4H), 2.82 (t, J = 5.6 Hz, 2H). MS (ESI) m/z 561.4 [M+H]⁺ Example 1B: Preparation of crystalline monohydrate Form 1 The compound of formula I was purified on silica gel and eluted with ethyl acetate /methanol. The eluate was concentrated to 100 mL, water (100 mL) was added at 50°C to initiate the hydrate formation. The suspension was further concentrated at 70-80°C to ca 130 mL, cooled to 15-25°C, isolated by filtration and dried under reduced pressure keeping the temperature below 50°C to give crystalline monohydrate Form 1 of the compound of formula I. Example 2: Preparation of anhydrous crystalline Form 2 (a) Crystalline monohydrate Form 1 (62.0 mg) was dissolved in dichloromethane (13 ml). The resulting solution was filtered through a 0.2-µm PTFE syringe filter and then evaporated at room temperature in a nitrogen flow to obtain a white, pale yellow solid. (b) Crystalline solvate Form E was dried for three days at room temperature under vacuum. Subsequently, it was dried for another day at room temperature before the temperature was increased to 40°C for one day. (c) Crystalline monohydrate Form 1 (142.7 mg) was dissolved in 30 mL dichloromethane. The resulting solution was evaporated at room temperature in a nitrogen flow to give a white, pale yellow solid. Subsequently, the whole sample was re-dissolved in 16 mL dichloromethane and evaporated under nitrogen flow to give a white, pale yellow solid. Example 3: Preparation of non-solvated crystalline Form 3 (a) Crystalline monohydrate Form 1 (58.5 mg) was heated to 110°C. The polymorph turned pale yellow. Then the temperature was increased for 10°C every 10 minutes until a temperature of 140°C were reached. This temperature was held for 15 minutes before the obtained yellow solid was cooled to room temperature. (b) Crystalline monohydrate Form 1 (131 mg) was heated to 140°C. The polymorph turned pale yellow. It was held at this temperature for 30 min before the obtained yellow solid was cooled to room temperature. Example 4: Preparation of non-solvated crystalline Form 4 (a) Crystalline solvated Form D was dried for two days at room temperature under vacuum to give a completely dry product. (b) Crystalline monohydrate Form 1 (145.2 mg) was suspended in 1 mL of pre-dried methanol. The resulting yellowish suspension was stirred for 3 days at room temperature, before it was filter- centrifuged through a 0.2-µm PVDF filter. The resulting solid was dried for one day at room temperature under vacuum to give a yellowish solid. Example 5: Preparation of solvated crystalline Form A Crystalline monohydrate Form 1 (63.9 mg) was suspended in 2 mL of ethanol. The resulting white suspension was stirred for 14 days at room temperature. Subsequently, this white suspension was filter-centrifuged through a 0.2-µm PVDF filter to give a wet white solid. Example 6: Preparation of solvated crystalline Form B Crystalline monohydrate Form 1 (61.1 mg) was suspended in 1 mL of DMSO. The resulting white suspension was stirred for 14 days at room temperature. Subsequently, this white suspension was filter-centrifuged through a 0.2-µm PVDF filter to give a wet white solid. Example 7: Preparation of solvated crystalline Form C (a) Crystalline monohydrate Form 1 (65.9 mg) was suspended in 1 mL of DMF. The resulting white suspension was stirred for 14 days at room temperature. Subsequently, this white suspension was filter-centrifuged through a 0.2-µm PVDF filter to give a wet white solid. (b) Crystalline monohydrate Form 1 (62.5 mg) was suspended in 13 mL of DMF. The resulting colourless solution was filter-centrifuged through a 0.2-µm PVDF filter and then evaporated at room temperature in a nitrogen flow to give a white, pale yellow solid. Example 8: Preparation of solvated crystalline Form D Crystalline monohydrate Form 1 (60.7 mg) was suspended in 0.5 mL of pre-dried methanol. The resulting yellowish suspension was stirred for 7 days at room temperature (at 22-25°C). Subsequently, this yellowish suspension was filter-centrifuged through a 0.2-µm PVDF filter to give a yellowish solid. Example 9: Preparation of solvated crystalline Form E Crystalline monohydrate Form 1 (62.4 mg) was suspended in 0.5 mL of pre-dried 2-propanol. The resulting yellowish suspension was stirred at 40 °C. After one day 1 mL of 2-propanol (pre-dried) were added. Subsequently, this white/beige suspension was filter-centrifuged through a 0.2-µm PVDF filter to give a white solid. Example 10: Preparation of solvated crystalline Form F A mixture of the crystalline anhydrous/non-solvated forms Form 2 (11.4 mg), Form 3 (10.9 mg) and Form 4 (10.6 mg) was suspended in 1 mL of acetone. The beige suspension was stirred at room temperature for three days C. Subsequently, this white/beige suspension was filter-centrifuged through a 0.2-µm PVDF filter to give a white, pale beige solid. Example 11: Preparation of amorphous Form G Crystalline monohydrate Form 1 (64.8 mg) was dissolved in 0.5 mL acetic acid. The resulting light yellow solution was evaporated at room temperature in a nitrogen flow to give a yellow, glass-like solid. Example 12: Solubility measurements of Form 1 Form 1 may further be characterized by its solubility characteristics. Approximate solubilities for Form 1 were determined at room temperature by addition of small aliquots of solvent to ca.10 mg of solid and shaking/sonicating the mixture for a short period of time at ambient conditions. The solubility characteristics for Form 1 are provided in the following table:

Example 13: Activity of compound of formula I for Inhibiting EGFR and HER2 The polymorphic forms and compositions of the disclosure are potent inhibitors of one or more oncogenic variants of an EGFR. Alternatively, or in addition, polymorphic forms and compositions of the disclosure are potent inhibitors of one or more of a wild type HER-2 receptor or an oncogenic variant of a HER-2 receptor. In some embodiments, the oncogenic variant of a HER-2 receptor is an allosteric variant of a HER-2 receptor. Table A indicates the activity of polymorphic Form 1 as an inhibitor of EGFR and HER2. Methods Various in vitro or in vivo biological assays may be suitable for detecting the effect of the compounds of the present disclosure. These in vitro or in vivo biological assays can include, but are not limited to, enzymatic activity assays, electrophoretic mobility shift assays, reporter gene assays, in vitro cell viability assays, and the like. Retroviral Production: EGFR mutants were subcloned into pMXs-IRES-Blasticidin (RTV-016, Cell Biolabs, San Diego, CA). Retroviral expression vector retrovirus was produced by transient transfection of HEK 293T cells with the retroviral EGFR mutant expression vector pMXs-IRES- Blasticidin (RTV-016, Cell Biolabs), pCMV-Gag-Pol vector and pCMV-VSV-G-Envelope vector. Briefly, HEK 293T/17 cells were plated in 100mm collagen coated plate (354450, Corning Life Sciences, Tewksbury, MA) (4 10⁵ per plate) and incubated overnight. The next day, retroviral plasmids (3 ^g of EGFR mutant, 1.0 ^g of pCMV-Gag-Pol and 0.5 ^g pCMV-VSV-G) were mixed in 500 ^l of Optimem (31985, Life Technologies). The mixture was incubated at room temperature for 5 min and then added to Optimem containing transfection reagent Lipofectamine (11668, Invitrogen) and incubated for 20 minutes. Mixture was then added dropwise to HEK 293T cells. The next day the medium was replaced with fresh culture medium and retrovirus was harvested @ 24 and 48 hrs. Generation of EGFR mutant stable cell lines: BaF3 cells (1.5E5 cells) were infected with 1 ml of viral supernatant supplemented with 8 ^g/ml polybrene by centrifuging for 30 min at 1000 rpm. Cells were placed in a 37°C incubator overnight. Cells were then spun for 5 minutes to pellet the cells. Supernatant was removed and cells re-infected a fresh 1 ml of viral supernatant supplemented with 8 ^g/ml polybrene by centrifuging for 30 min at 1000 rpm. Cells were placed in 37°C incubator overnight. Cells were then maintained in RPMI containing 10% Heat Inactivated FBS, 2% L-glutamine containing 10 ng/ml IL-3. After 48 hours cells were selected for retroviral infection in 10 ^g/ml Blasticidin for one week. Blasticidin resistant populations were washed twice in phosphate buffered saline before plating in media lacking IL-3 to select for IL-3 independent growth. Assay for cell proliferation: BaF3 cell lines were resuspended at 1.3E5 c/ml in RPMI containing 10% Heat Inactivated FBS, 2% L-glutamine and 1% Pen/Strep and dispensed in triplicate (17.5E4 c/well) into 96 well plates. To determine the effect of drug on cell proliferation, cells incubated for 3 days in the presence of vehicle control or test drug at varying concentrations. Inhibition of cell growth was determined by luminescent quantification of intracellular ATP content using CellTiterGlo (Promega), according to the protocol provided by the manufacturer. Comparison of cell number on day 0 versus 72 hours post drug treatment was used to plot dose-response curves. The number of viable cells was determined and normalized to vehicle-treated controls. Inhibition of proliferation, relative to vehicle-treated controls was expressed as a fraction of 1 and graphed using PRISM^® software (Graphpad Software, San Diego, CA). EC₅₀ values were determined with the same application. Cellular protein analysis: Cell extracts were prepared by detergent lysis (RIPA, R0278, Sigma, St Louis, MO) containing 10 mM Iodoacetamide (786-228, G-Biosciences, St, Louis, MO), protease inhibitor (P8340, Sigma, St. Louis, MO) and phosphatase inhibitors (P5726, P0044, Sigma, St. Louis, MO) cocktails. The soluble protein concentration was determined by micro-BSA assay (Pierce, Rockford IL). Protein immunodetection was performed by electrophoretic transfer of SDS-PAGE separated proteins to nitrocellulose, incubation with antibody, and chemiluminescent second step detection. Nitrocellulose membranes were blocked with 5% nonfat dry milk in TBS and incubated overnight with primary antibody in 5% bovine serum albumin. The following primary antibodies from Cell Signaling Technology were used at 1:1000 dilution: phospho- EGFR[Y1173] and total EGFR. β-Actin antibody, used as a control for protein loading, was purchased from Sigma Chemicals. Horseradish peroxidase-conjugated secondary antibodies were obtained from Cell Signaling Technology and used at 1:5000 dilution. Horseradish peroxidase- conjugated secondary antibodies were incubated in nonfat dry milk for 1 hour. SuperSignal chemiluminescent reagent (Pierce Biotechnology) was used according to the manufacturer's directions and blots were imaged using the Alpha Innotech image analyzer and AlphaEaseFC software (Alpha Innotech, San Leandro CA). Table A. Activity of compound of formula I for Inhibiting EGFR and HER2

EQUIVALENTS It is understood that the invention can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

Claims 1. A polymorphic form of the compound of formula I

2. The polymorphic form of claim 1which is a crystalline form.

3. The polymorphic form of claim 1which is an amorphous form.

4. The polymorphic form of claims 1 or 2 which is a monohydrate crystalline form (or Form 1).

5. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a powder X-ray diffraction (XRPD) pattern comprising one or two or three peaks at diffraction angles selected from the group consisting of 15.44°, 24.56°, 25.56° ± 0.2° 2-theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha1 X-rays at a wavelength of 1.541 Angstroms).

6. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a powder X-ray diffraction (XRPD) pattern comprising one or more peaks at diffraction angles selected from the group consisting of 10.02°, 15.44°, 20.62°, 24.56°, 25.56° ± 0.2° 2-theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha₁ X- rays at a wavelength of 1.541 Angstroms).

7. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by one or more peaks at angles (2-theta) selected from a powder X-ray diffraction (XRPD) pattern substantially as shown in Figure 1A.

8. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a DSC thermogram comprising a melting endothermic peak at about 166.0 °C.

9. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a DSC thermogram comprising a dehydration endothermic peak at about 105- 135 °C.

10. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a DSC thermogram substantially in accordance with Figure 1B.

11. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a DVS curve showing a weight gain of at most 0.25 wt %- based on the weight of the monohydrate crystalline form.

12. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a DVS curve substantially in accordance with Figure 1C, 1D.

13. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a Raman spectrum having peaks at 1608 ± 2 cm^-1, 1394 ± 2 cm^-1, 1343 ± 2 cm^-1.

14. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a Raman spectrum having peaks at 1608 ± 2 cm^-1, 1498 ± 2 cm^-1, 1430 ± 2 cm^-1, 1394 ± 2 cm^-1, 1343 ± 2 cm^-1, 1251 ± 2 cm^-1, 1209 ± 2 cm^-1.

15. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a Raman spectrum having peaks at 1608 ± 2 cm^-1, 1498 ± 2 cm^-1, 1430 ± 2 cm^-1, 1394 ± 2 cm^-1, 1343 ± 2 cm^-1, 1308 ± 2 cm^-1, 1251 ± 2 cm^-1, 1209 ± 2 cm^-1, 995 ± 2 cm^-1, 795 ± 2 cm^-1.

16. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a Raman spectrum substantially in accordance with Figure 1E.

17. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a FTIR spectrum having characteristic absorptions at about 1495 ± 2 cm^-1, 1425 ± 2 cm^-1, 1216 ± 2 cm^-1, 753 ± 2 cm^-1.

18. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a FTIR spectrum having characteristic absorptions at about 1545 ± 2 cm^-1, 1495 ± 2 cm^-1, 1425 ± 2 cm^-1, 1216 ± 2 cm^-1, 1113 ± 2 cm^-1, 941 ± 2 cm^-1, 753 ± 2 cm^-1.

19. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a FTIR spectrum substantially in accordance with Figure 1F.

20. The monohydrate crystalline form of claim 4, wherein the monohydrate crystalline form is characterized by a powder X-ray diffraction pattern comprising one or two or three peaks at diffraction angles selected from the group consisting of 15.44°, 24.56°, 25.56° ± 0.2° 2-theta; a Raman spectrum having peaks at 1608 ± 2 cm^-1, 1394 ± 2 cm^-1, 1343 ± 2 cm^-1, and a DSC thermogram comprising dehydration endothermic peak at about 105-135°C and/or a melting endothermic peak at about 166.0 °C.

21. A process for the preparation of a monohydrate crystalline form of claim 4 comprising: dissolving the compound of formula I in a suitable solvent or mixture of solvents, and evaporating the solvent or mixture of solvents.

22. The polymorphic form of claims 1 or 2, which is an anhydrous crystalline form or Form 2.

23. The anhydrous crystalline form of claim 20, wherein the anhydrous crystalline form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 12.02°, 17.62°, 24.7 ± 0.2° 2-theta (wherein said powder X- ray diffraction pattern is obtained using copper K-alpha1 X-rays at a wavelength of 1.541 Angstroms).

24. The anhydrous crystalline form of claim 20, wherein the anhydrous crystalline form is characterized by a DSC thermogram comprising melting endothermic peak at about 172 °C.

25. The polymorphic form of claims 1 or 2 which is a non-solvated crystalline form or Form 3.

26. The non-solvated crystalline form of claim 23, wherein the non-solvated crystalline form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 4.3, 5.6°, 6.4 ± 0.2° 2-theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha₁ X-rays at a wavelength of 1.541 Angstroms).

27. The polymorphic form of claims 1 or 2 which is a non-solvated crystalline form or Form 4.

28. The non-solvated crystalline form of claim 25, wherein the non-solvated crystalline form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 15.3°, 24.7°, 26.6° ± 0.2° 2-theta (wherein said powder X- ray diffraction pattern is obtained using copper K-alpha1 X-rays at a wavelength of 1.541 Angstroms).

29. The polymorphic form of claims 1 or 2 which is a crystalline solvate form.

30. The polymorphic form of claims 1 or 2 which is a crystalline ethanol solvate form or Form A.

31. The crystalline ethanol solvate form of claim 30, wherein the crystalline ethanol solvate form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 5.96°, 23.92°, 26.66° ± 0.2° 2-theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha₁ X-rays at a wavelength of 1.541 Angstroms).

32. The polymorphic form of claims 1 or 2 which is a crystalline DMSO solvate form or Form B.

33. The crystalline DMSO solvate form of claim 32, wherein the crystalline DMSO solvate form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of at 6.92°, 23.68°, 26.7° ± 0.2° 2-theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha₁ X-rays at a wavelength of 1.541 Angstroms).

34. The polymorphic form of claims 1 or 2 which is a crystalline DMF solvate form or Form C.

35. The crystalline DMF solvate form of claim 34, wherein the crystalline DMF solvate form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 5.2°, 6°, 23.82° ± 0.2° 2-theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha1 X-rays at a wavelength of 1.541 Angstroms).

36. The polymorphic form of claims 1 or 2 which is a crystalline methanol solvate form or Form D.

37. The crystalline methanol solvate form of claim 36, wherein the crystalline methanol solvate form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 2.98°, 9.36°, 25.58° 2-theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha1 X-rays at a wavelength of 1.541 Angstroms).

38. The polymorphic form of claims 1 or 2 which is a crystalline 2-propanol solvate form or Form E.

39. The crystalline 2-propanol solvate form of claim 38, wherein the crystalline 2-propanol solvate form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 5.9°, 16.1°, 18.6°, 23.7°, 26.5° ± 0.2° 2- theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha₁ X-rays at a wavelength of 1.541 Angstroms).

40. The polymorphic form of claims 1 or 2 which is a crystalline acetone solvate form or Form F.

41. The crystalline acetone solvate form of claim 40, wherein the crystalline acetone solvate form is characterized by a powder X-ray diffraction (XRPD) pattern comprising peaks at diffraction angles selected from the group consisting of 5.9°, 16.4°, 18.8°, 23.8°, 26.5° ± 0.2° 2- theta (wherein said powder X-ray diffraction pattern is obtained using copper K-alpha1 X-rays at a wavelength of 1.541 Angstroms).

42. The polymorphic form of claims 1 or 3 which is an amorphous acetic acid solvate form (or Form G).

43. The amorphous acetic acid solvate form of claim 42, wherein the amorphous acetic acid solvate form is characterized by a Raman spectrum having peaks at 2936 ± 2 cm^-1, 1356 ± 2 cm^-1, 883 ± 2 cm^-1.

44. The amorphous acetic acid solvate form of claim 42, wherein the amorphous acetic acid solvate form is characterized by one or more peaks at angles (2-theta) selected from a powder X- ray diffraction (XRPD) pattern substantially as shown in Figure 11A.

45. The polymorphic form of any preceding claim, which is at least 90, 95, 96, 97, 98, or 99% pure.

46. A pharmaceutical composition comprising a therapeutically effective amount of any one, or combination, of the polymorphic forms of any preceding claim and a pharmaceutically acceptable excipient.

47. The pharmaceutical composition of claim 46, wherein the polymorphic form is present in an amount of at least about 90%, 91%, 92% , 93%, 94%, 95%, 96%, 97%, 98%, or 99% by weight.

48. The pharmaceutical composition of claim 41, wherein the composition is in a solid or liquid dosage form.

49. The pharmaceutical composition of claim 41, wherein the composition is in a solid dosage form.

50. A method of inhibiting an oncogenic variant of an ErbB receptor, comprising administering to the subject in need thereof a therapeutically effective amount of the polymorphic form of any one of the preceding claims.

51. A method of inhibiting an oncogenic variant of an ErbB receptor, comprising administering to the subject in need thereof the pharmaceutical composition of any one of the preceding claims.

52. A method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of the polymorphic form of any one of the preceding claims.

53. A method of preventing or treating cancer, comprising administering to the subject in need thereof the pharmaceutical composition of any one of the preceding claims.

54. A method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor is present in the subject; and ii) administering to the subject in need of the treatment a therapeutically effective amount of the polymorphic form of any one of the preceding claims.

55. A method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor is present in the subject; and ii) administering to the subject in need of the treatment the pharmaceutical composition of any one of the preceding claims.

56. A method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor is present in a biological sample from the subject; and ii) administering to the subject in need of the treatment a therapeutically effective amount of the polymorphic form of any one of the preceding claims.

57. A method of preventing or treating cancer, comprising: i) identifying a subject candidate as the subject in need of the treatment when that at least one oncogenic variant of an ErbB receptor is present in a biological sample from the subject; and ii) administering to the subject in need of the treatment the pharmaceutical composition of any one of the preceding claims.

58. A method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of the polymorphic form of any one of the preceding claims when that at least one oncogenic variant of an ErbB receptor is identified as being present in the subject.

59. A method of preventing or treating cancer, comprising administering to the subject in need thereof the polymorphic form of any one of the preceding claims when that at least one oncogenic variant of an ErbB receptor is identified as being present in the subject.

60. A method of preventing or treating cancer, comprising administering to the subject in need thereof a therapeutically effective amount of the polymorphic form of any one of the preceding claims when that at least one oncogenic variant of an ErbB receptor is identified as being present in a biological sample from the subject.

61. A method of preventing or treating cancer, comprising administering to the subject in need thereof the pharmaceutical composition of any one of the preceding claims when that at least one oncogenic variant of an ErbB receptor is identified as being present in a biological sample from the subject.

62. The polymorphic form of any one of the preceding claims for use in the inhibition of an oncogenic variant of an ErbB receptor.

63. The pharmaceutical composition of any one of the preceding claims for use in the inhibition of an oncogenic variant of an ErbB receptor.

64. The polymorphic form of any one of the preceding claims for use in the prevention or treatment of cancer.

65. The pharmaceutical composition of any one of the preceding claims for use in the prevention or treatment of cancer.

66. The polymorphic form of any one of the preceding claims for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor is present in the subject.

67. The pharmaceutical composition of any one of the preceding claims for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor is present in the subject.

68. The polymorphic form of any one of the preceding claims for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor is present in a biological sample from the subject.

69. The pharmaceutical composition of any one of the preceding claims for use in the prevention or treatment of cancer in a subject, wherein at least one oncogenic variant of an ErbB receptor is present in a biological sample from the subject.

70. Use of the polymorphic form of any one of the preceding claims in the manufacture of a medicament for inhibiting an oncogenic variant of an ErbB receptor.

71. Use of the polymorphic form of any one of the preceding claims in the manufacture of a medicament for preventing or treating cancer.

72. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the cancer is a solid tumor.

73. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the cancer is a bladder cancer, a breast cancer, a cervical cancer, a colorectal cancer, an endometrial cancer, a gastric cancer, a glioblastoma (GBM), a head and neck cancer, a lung cancer, a non-small cell lung cancer (NSCLC), or any subtype thereof.

74. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the cancer is glioblastoma (GBM) or any subtype thereof.

75. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the cancer is glioblastoma.

76. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the cancer or a tumor or a cell thereof expresses an oncogenic variant of an epidermal growth factor receptor (EGFR).

77. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant is an oncogenic variant in an ErbB receptor.

78. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant in the ErbB receptor is an allosteric variant.

79. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant is an oncogenic variant in an epidermal growth factor receptor (EGFR).

80. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant in the EGFR is an allosteric variant.

81. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant is an oncogenic variant of a HER2 receptor.

82. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant in the HER2 receptor is an allosteric variant.

83. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant is an oncogenic variant in a HER-4 receptor.

84. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the subject or the cancer is insensitive or resistant to treatment with one or more of gefinitinib, erlotinib, afatinib, osimertinib, and necitunumab.

85. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the sequence encoding the oncogenic variant of the EGFR comprises a deletion of exon 20 or a portion thereof and wherein the cancer, tumor or cell thereof does not comprise an oncogenic variation in a sequence encoding one or more of an EGFR kinase domain (KD), BRAF, NTRK, and KRAS or wherein.

86. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the sequence encoding the oncogenic variant of the EGFR comprises a deletion of exon 20 or a portion thereof and wherein the cancer, tumor or cell thereof does not comprise a marker indicating responsiveness to immunotherapy.

87. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the oncogenic variant or the oncogenic mutation is detected by a Food and Drug Aministration (FDA)-approved diagnosis.

88. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the subject has an adverse reaction to treatment with a Type I inhibitor.

89. The polymorphic form, pharmaceutical composition, method, or use of any one of the preceding claims, wherein the subject has an adverse reaction to treatment with one or more of gefinitinib, erlotinib, afatinib, osimertinib, necitunumab, crizotinib, alectinib, ceritinib, dabrafenib, trametinib, afatinib, sapitinib, dacomitinib, canertinib, pelitinib, WZ4002, WZ8040, WZ3146, CO-1686 and AZD9291.