Solid state forms of modulators of TNF-alpha activity and salts thereof

Abstract

The present disclosure relates to solid state forms of (7R,14R)-1-(difluoromethoxy)-11-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14-methanobenzo[f]benzo[4,5]imidazo[1,2-a][1,4]diazocin-5(14H)-one and salts thereof. Such solid state forms are useful in preparation of pharmaceutical compositions and dosage forms for the treatment of disease.

Description

WSGR Ref. No. 53699-722.601SOLID STATE FORMS OF MODULATORS OF TNF-ALPHA ACTIVITY AND SALTS THEREOFCROSS-REFERENCE

[0001] This application claims the benefit of US Provisional Application No. 63 / 683,662, filed August 15, 2024, which is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION

[0002] Tumor necrosis factor alpha (TNFa) is an inflammatory cytokine that is responsible for a wide range of signaling events within cells. Aberrant TNFa signaling gives rise to inflammatory conditions and is thought to be an important component of inflammatory disease, such as rheumatoid arthritis. One such modulator of TNFa is (7R,14R)-l-(difluoromethoxy)-l l-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one and pharmaceutically acceptable salts thereof.SUMMARY OF THE INVENTION

[0003] The present disclosure relates to crystalline forms I-IX of (7R,14R)-1- (difluoromethoxy)-l l-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7- dihydro-7, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one, herein after known as Compound 1. The molecular structure of Compound 1 is shown below:Compound 1(7R, 14R)- 1 -(difluoromethoxy)- 11 -(4-(dimethy Iphosphory l)-3 -fluorophenyl)- 10-fluoro-6-(methy l-d3)-6,7 -dihydro- 7,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one

[0004] Also disclosed herein are crystalline forms of (7R,14R)-l-(difluoromethoxy)-l l-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate, hereinafter known as Compound 2. The molecular structure of Compound 2 is shown below:WSGR Ref. No. 53699-722.601Compound 2(7R, 14R)- 1 -(difluoromethoxy)- 11 -(4-(dimethy Iphosphory l)-3 -fluorophenyl)- 10-fhioro-6-(methy l-d3)-6,7 -dihydro- 7,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate

[0005] Also disclosed herein are crystalline forms I-III of (7R, 14R)-1 -(difluoromethoxy)- 11 -(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(rnethyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one phosphate, hereinafter known as Compound 3. The molecular structure of Compound 3 is shown below:Compound 3(7R, 14R)- 1 -(difluoromethoxy)- 11 -(4-(dimethy Iphosphory l)-3 -fluorophenyl)- 10-fhioro-6-(methy l-d3)-6,7 -dihy dro- 7, 14-methanobenzo[f]benzo [4,5] imidazo [1 ,2-a] [ 1 ,4]diazocin-5( 14H)-one phosphate

[0006] Provided herein are pharmaceutical compositions comprising solid state forms of Compound 1, Compound 2, Compound 3, or any combinations thereof, and a pharmaceutically acceptable excipient.

[0007] Also described herein is a method of inhibiting tumor necrosis factor alpha (TNFa) comprising administering to the subject with a condition in need thereof, the solid form of Compound 1, Compound 2, Compound 3, or any combinations thereof.

[0008] One embodiment provides a solid form of (7R, 14R)-l-(difhrorom ethoxy)- 11 -(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one, depicted below as Compound 1,WSGR Ref. No. 53699-722.601Compound 1 wherein the solid form is crystalline.

[0009] One embodiment provides a solid form of (7R, 14R)-1 -(difluoromethoxy)- 11 -(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H) besylate, depicted below as Compound 2,Compound 2 wherein the solid form is crystalline.

[0010] One embodiment provides a solid form of (7R, 14R)-l-(difhrorom ethoxy)- 11 -(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one phosphate, depicted below as Compound 3,Compound 3 wherein the solid form is crystalline.WSGR Ref. No. 53699-722.601

[0011] One embodiment provides a pharmaceutically acceptable salt of (7R,14R)-1- (difluoromethoxy)-l l-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7- dihydro-7, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one wherein the salt is selected from the group consisting hydrochloride, sulfate, tosylate, mesylate, maleate, phosphate, and besylate.

[0012] One embodiment provides a compound (7R,14R)-l-(difhroromethoxy)-l l-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate.

[0013] One embodiment provides a compound (7R,14R)-l-(difhroromethoxy)-l l-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one phosphate.

[0014] One embodiment provides a pharmaceutical composition comprising a solid form of any one of the compounds provided herein, and a pharmaceutically acceptable excipient.

[0015] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a solid form of any one of the compounds provided herein, and a pharmaceutically acceptable carrier.

[0016] One embodiment provides a method of treating inflammatory or autoimmune disease or disorder in a patient in need thereof, comprising administering a solid form of any one of the compounds provided herein.

[0017] One embodiment provides a method of treating inflammatory or autoimmune disease or disorder in a patient in need thereof, comprising administering a solid form of any one of the compounds provided herein and a pharmaceutically acceptable excipient.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The features of the invention are set forth with particularity in the appended claims. A better understanding of the features of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0019] Figure 1 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form I;

[0020] Figure 2 shows a differential scanning calorimetry and therm ogravimetric analysis of crystalline Compound 1 Form I;

[0021] Figure 3 shows the Dynamic Vapor Sorption Isotherm Plot of Compound 1 Form I;

[0022] Figure 4 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form II;

[0023] Figure 5 shows a differential scanning calorimetry and therm ogravimetric analysis of crystalline Compound 1 Form II;WSGR Ref. No. 53699-722.601

[0024] Figure 6 shows the Dynamic Vapor Sorption Isotherm Plot of Compound 1 Form II;

[0025] Figure 7 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form III;

[0026] Figure 8 shows a differential scanning calorimetry and therm ogravimetric analysis of crystalline Compound 1 Form III;

[0027] Figure 9 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form IV;

[0028] Figure 10 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 1 Form IV;

[0029] Figure 11 shows the Dynamic Vapor Sorption Isotherm Plot of Compound 1 Form IV;

[0030] Figure 12 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form V;

[0031] Figure 13 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 1 Form V;

[0032] Figure 14 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form VI;

[0033] Figure 15 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 1 Form VI;

[0034] Figure 16 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form VII;

[0035] Figure 17 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 1 Form VII;

[0036] Figure 18 shows X-ray powder diffraction patterns of crystalline Compound 1 Form VIII;

[0037] Figure 19 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 1 Form VIII;

[0038] Figure 20 shows an X-ray powder diffraction pattern of crystalline Compound 1 Form IX;

[0039] Figure 21 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 1 Form IX;

[0040] Figure 22 shows an X-ray powder diffraction pattern of crystalline Compound 2 Form I;

[0041] Figure 23 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 2 Form I;

[0042] Figure 24 shows the Dynamic Vapor Sorption Isotherm Plot of Compound 2 Form I;

[0043] Figure 25 shows an X-ray powder diffraction pattern of crystalline Compound 3 Form I;

[0044] Figure 26 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 3 Form I;

[0045] Figure 27 shows an X-ray powder diffraction pattern of crystalline Compound 3 Form II;WSGR Ref. No. 53699-722.601

[0046] Figure 28 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 3 Form II;

[0047] Figure 29 shows an X-ray powder diffraction pattern of crystalline Compound 3 Form in;

[0048] Figure 30 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 3 Form III;

[0049] Figure 31 shows the Dynamic Vapor Sorption Isotherm Plot of Compound 3 Form III;

[0050] Figure 32 shows a differential scanning calorimetry and thermogravimetric analysis of crystalline Compound 2 Form I with extra diffraction peak.DETAILED DESCRIPTION OF THE INVENTION

[0051] Provided herein are compositions comprising solid state forms of Compound 1, Compound 2, Compound 3, or any combinations thereof.

[0052] Compound 1 was found to have a number of unexpected advantageous properties. Crystalline forms of Compound 1, such as Forms I and IV were determined to be stable. Of the Compound 1 crystalline forms, Compound 1 Form I showed increased solubility when compared to Compound 1 Form IV. Compound 1 Form I exhibited a propensity to gel in aqueous media.

[0053] Compound 2 was found to have a number of advantageous properties. Compound 2 Form I showed favorable solid-state properties. Compound 2 Form I is physically and chemically stable at 40 °C / 75% RH (open) and 60 °C (capped) for 6 weeks and showed acceptable mechanical stability. Compound 2 Form I also provided slower gelling tendency when compared to other salt forms disclosed herein. Based on the differential scanning calorimetry analysis studies provided herein, it appears that Compound 1 Form I is the more thermodynamically stable form of Compound 1.

[0054] Compound 3 showed advantageous properties. Compound 3 Form m showed acceptable solid-state properties. Compound 3 exhibited complex polymorphism during the salt screen.

[0055] Overall, Compound 1 Form I, Compound 2 Form I, and Compound 3 Form III all showed acceptable solid-state properties. The three solid forms were all physically and chemically stable at 40 °C / 75%RH (open) and 60 °C (capped) for 7 days. Compound 2 Form I and Compound 3 Form III showed approximately 2-fold higher solubility in FaSSIF at 0.5 hour than Compound 1 Form I, indicating Compound 2 Form I and Compound 3 Form III might provide rapid dissolution. In SGF and FeSSIF, Compound 2 Form I and Compound 3 Form III showed similar solubility with Compound 1 Form I.WSGR Ref. No. 53699-722.601Definitions

[0056] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference.

[0057] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.

[0058] The term “hydrate” and “solvate” are meant to describe crystalline forms (e.g., of any compounds described herein) that include an amount of water or solvent, as supported by data derived from differential scanning calorimetry (DSC) experiments, thermogravimetric analysis (TGA) experiments, X-ray powder diffraction experiments, and / or the procedure for generating the solid crystalline form. In some embodiments, a solvate crystalline form or hydrate crystalline form comprises at least 1.5%, 1.75%, 2.0%, 2.5%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 15.0%, or 20.0% of the total weight (w / w) of the sample as water, solvent, or a combination thereof, as determined by TGA. In some embodiments, a solvate crystalline form or hydrate crystalline form exhibits at least one DSC endotherm onset before or within 30 °C of the boiling point of water or the solvent(s) used in the generation of the crystalline form. For example, a hydrate crystalline form may have a DSC endotherm onset at 108 °C, with the endotherm peak positioned at 124 °C.

[0059] Crystalline solid forms termed a “solvate,” or “hydrate” are not meant to be limiting. For example, a solvate or hydrate can comprise a combination of water and solvent in the crystalline solid form.

[0060] The term “type,” “form,” and “pattern” are meant to be used interchangeably and are meant to refer to a particular crystalline material with properties described herein. For example, “crystalline hydrate Type A,” “crystalline hydrate Form A,” and “XRPD Pattern A” refer to the same crystalline matter.

[0061] The term "about" when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range, in some instances, will vary between 1% and 15% of the stated number or numerical range.

[0062] The term "substantially similar" as used herein means an analytical spectrum, such as XRPD pattern, DSC thermogram, or TGA thermogram, which resembles the reference spectrum to a great degree in both the peak locations and peak intensity.Characterization of Compounds and Solid State Forms

[0063] One embodiment provides a solid form of (7R,14R)-l-(difluoromethoxy)-l l-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14-WSGR Ref. No. 53699-722.601 methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one, depicted below asCompound 1,Compound 1 wherein the solid form is crystalline. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.1° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 10.3° ± 0.3 and 17.7° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2- theta value of 12.6° ± 0.3, 17.3° ± 0.3, and 24.0° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.5° ± 0.3, 21.0° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.5° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, and 24.3° ± 0.3. In some embodiments, the solid form exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form exhibits at least four X- ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid formWSGR Ref. No. 53699-722.601 exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form exhibits the X-ray powder diffraction pattern as shown in Figure 1. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 259.3 °C ± 5.0. In some embodiments, the solid form exhibits the differential scanning calorimetry thermogram as shown in Figure 2. In some embodiments, the solid form exhibits a weight loss of 0% ± 2.0 between 50 and 300 °C ± 10.0 as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 2. In some embodiments, the amount of other crystalline or amorphous forms is 10% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1% (w / w) or less. In some embodiments, the solid form has a chemical purity of 97% or more. In some embodiments, the solid form has a chemical purity of 98% or more. In some embodiments, the solid form has a chemical purity of 99% or more. In some embodiments, the solid form has a chemical purity of 99.5% or more.

[0064] One embodiment provides a solid form of (7R,14R)-l-(difluoromethoxy)-l l-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate, depicted below as Compound 2,Compound 2 wherein the solid form is crystalline. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.9° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 22.1° ± 0.3 and 27.8° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2- theta value of 16.9° ± 0.3, 17.6° ± 0.3, and 18.5° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.7° ± 0.3, 16.4° ± 0.3, andWSGR Ref. No. 53699-722.60119.4° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 8.4° ± 0.3, 9.4° ± 0.3, and 26.1° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 12.8° ± 0.3, 13.5° ± 0.3, 20.9° ± 0.3, and 24.8° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.7° ± 0.3, 18.9° ± 0.3, 23.5° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form exhibits at least seven X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3,WSGR Ref. No. 53699-722.60127.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form exhibits the X-ray powder diffraction pattern as shown in Figure 22. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 236.2 °C ± 5.0. In some embodiments, the solid form exhibits the differential scanning calorimetry thermogram as shown in Figure 23. In some embodiments, the solid form exhibits a weight loss of 0% ± 2.0 between 30 and 230 °C ± 10.0 as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 23. In some embodiments, the amount of other crystalline or amorphous forms is 10% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1% (w / w) or less. In some embodiments, the solid form has a chemical purity of 97% or more. In some embodiments, the solid form has a chemical purity of 98% or more. In some embodiments, the solid form has a chemical purity of 99% or more. In some embodiments, the solid form has a chemical purity of 99.5% or more.

[0065] One embodiment provides a solid form of (7R,14R)-l-(difluoromethoxy)-l l-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one phosphate, depicted below as Compound 3,Compound 3 wherein the solid form is crystalline. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.4 ° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 10.5° ± 0.3 and 20.1° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2- theta value of 14.0° ± 0.3, 20.4° ± 0.3, and 23.5° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.6 ° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form exhibits at least one X-ray powder diffraction reflection selectedWSGR Ref. No. 53699-722.601 from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form exhibits at least four X- ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form exhibits the X-ray powder diffraction pattern as shown in Figure 29. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 245.5 °C ± 5.0. In some embodiments, the solid form exhibits the differential scanning calorimetry thermogram as shown in Figure 30. In some embodiments, the solid form exhibits a weight loss of 0% ± 2.0 between 50 and 230 °C ± 10.0 as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 30. In some embodiments, the amount of other crystalline or amorphous forms is 10% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1% (w / w) or less. In some embodiments, the solid form has a chemical purity of 97% or more. In some embodiments, the solid form has a chemical purity of 98% or more. In some embodiments, the solid form has a chemical purity of 99% or more. In some embodiments, the solid form has a chemical purity of 99.5% or more.

[0066] One embodiment provides a pharmaceutically acceptable salt of (7R,14R)-1- (difluoromethoxy)-l l-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7- dihydro-7, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one wherein theWSGR Ref. No. 53699-722.601 salt is selected from the group consisting of hydrochloride, sulfate, tosylate, mesylate, maleate, phosphate, and besylate.

[0067] One embodiment provides a compound (7R,14R)-1 -(difluoromethoxy)- 11 -(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate.

[0068] One embodiment provides a compound (7R,14R)-l-(difhioromethoxy)-l l-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one phosphate.

[0069] In one embodiment, the present invention provides solid state forms of Compound 1, Compound 2, and Compound 3. In one embodiment, the crystalline forms are characterized by the interlattice plane intervals determined by an X-ray powder diffraction (XRPD) diffractogram. The diffractogram is typically represented by a diagram plotting the intensity of the peaks versus the location of the peaks, i.e., diffraction angle 20 (two-theta) in degrees. The characteristic peaks of a given compound can be selected according to the peak locations and their relative intensity to distinguish compounds and crystalline structures from others. Those skilled in the art recognize that the measurements of the XRPD peak locations and / or intensity for a given crystalline form of the same compound will vary within a margin of error. The values of degree 20 allow appropriate error margins. Typically, the error margins are represented by "±". For example, the degree 20 of "8.716±0.3" denotes a range from 8.716+0.3, i.e., 9.016, to 8.716-0.3, i.e., 8.416. Depending on the sample preparation techniques, the calibration techniques applied to the instruments, human operational variation, and etc., those skilled in the art recognize that the margin of error for a XRPD can be ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; ±0.05; or less. Additional details of the methods and equipment used for the XRPD analysis are described in the Examples section.

[0070] In one embodiment, the crystalline forms are characterized by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). The DSC thermogram is typically expressed by a diagram plotting the normalized heat flow in units of Watts / gram ("W / g") versus the measured sample temperature in degree C. The DSC thermogram is generally evaluated for extrapolated onset and end (outset) temperatures, peak temperature, and heat of fusion. The single maximum value of a DSV thermogram is often used as the characteristic peak to distinguish one crystalline form from another crystalline form. The TGA thermogram is typically expressed by a diagram plotting the weight loss percentage (%) versus the measured sample temperature in degree C. In the figures disclosed herein, DSC and TGA thermograms have been plotted sharing an X axis (temperature), but have distinct Y axes of weight % and heat flow corresponding respectively to TGA and DSC measurements.WSGR Ref. No. 53699-722.601

[0071] Those skilled in the art recognize that the measurements of the DSC and TGA thermograms for a given crystalline form of the same compound will vary within a margin of error. The values of a single maximum value, expressed in degree C, allow appropriate error margins. Typically, the error margins are represented by "±". For example, the single maximum value of "53.1 °C ±10.0" denotes a range from 53.1 °C + 10.0, i.e., 63.1 °C, to about 53.1 °C - 10.0, i.e., 43.1 °C. Depending on the sample preparation techniques, crystallization conditions, calibration techniques applied to the instruments, human operational variations, and etc., those skilled in the art recognize that the appropriate margin of error for a single maximum value can be ±10.0 °C; ±7.5 °C; ±5.0 °C; ±2.5 °C; ±2 °C; ±1.5 °C; ±1 °C; ±0.5 °C; or less for any of the powder diffraction reflections described herein.

[0072] Additional details of the methods and equipment used for the DSC and TGA thermogram analysis are described in the Examples section.Compound 1

[0073] In some embodiments, the present invention provides a crystalline solid state of (7R, 14R)- 1 -(difluoromethoxy)- 11 -(4-(dimethylphosphoryl)-3 -fluorophenyl)- 10-fluoro-6- (methyl-d3)-6,7-dihydro-7,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)- one, also known as Compound 1. In some embodiments, provided herein is crystalline Compound 1 Form I. In some embodiments, provided herein is crystalline Compound 1 Form II. In some embodiments, provided herein is crystalline Compound 1 Form III. In some embodiments, provided herein is crystalline Compound 1 Form IV. In some embodiments, provided herein is crystalline Compound 1 Form V. In some embodiments, provided herein is crystalline Compound 1 Form VI. In some embodiments, provided herein is crystalline Compound 1 Form VII. In some embodiments, provided herein is crystalline Compound 1 Form VIII. In some embodiments, provided herein is crystalline Compound 1 Form IX.Compound 1 Form I

[0074] In some embodiments, the present invention provides crystalline solid state Compound 1 Form I. In some embodiments, the solid form of Compound 1 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.1° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 10.3° ± 0.3 and 17.7° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits an X- ray powder diffraction reflection at a 2-theta value of 12.6° ± 0.3, 17.3° ± 0.3, and 24.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.5° ± 0.3, 21.0° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.5° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, and 24.3° ± 0.3.WSGR Ref. No. 53699-722.601

[0075] In some embodiments, the solid form Compound 1 Form I exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits at least six X- ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form I exhibits at least seven X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form I is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form I exhibits an X-ray powder diffraction pattern substantially similar to that shown in Figure 1. In some embodiments, Compound 1 Form I exhibits at least one of the X-ray powder diffraction pattern reflections in Table 1.Table 1. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form I.WSGRRef. No.53699-722.601WSGR Ref. No. 53699-722.601

[0076] In some embodiments, the crystalline solid state of Compound 1 Form I exhibits a DSC thermogram substantially similar to that shown in Figure 2. In some embodiments, the crystalline solid state of Compound 1 Form I exhibits a DSC endotherm at 234.6 °C ± 5.0. In some embodiments, the crystalline solid state of Compound 1 Form I exhibits a DSC endotherm at 259.3 °C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 1 Form I are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0077] In some embodiments, the crystalline solid state of Compound 1 Form I exhibits a TGA thermogram substantially similar to that shown in Figure 2. In some embodiments, the crystalline solid state of Compound 1 Form I exhibits a weight loss of 0% ± 2.0 (w / w) between 50 and 300 °C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 1 Form I is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0078] In some embodiments, the crystalline solid state of Compound 1 Form I exhibits a Dynamic Vapor Sorption Isotherm Plot substantially similar to that shown in Figure 3.

[0079] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form I is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0080] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 1 Form I has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form I has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form I has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form I has a chemical purity of 98% or more. In some embodiments, the crystalline solid state formWSGR Ref. No. 53699-722.601Compound 1 Form I has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form I has a chemical purity of 99.5% or more. Compound 1 Form II

[0081] In some embodiments, the present invention provides crystalline solid state form of Compound 1 Form II. In some embodiments, the solid form of Compound 1 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.2° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.1° ± 0.3 and 9.7° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 15.4° ± 0.3, 17.0° ± 0.3, and 18.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3.

[0082] In some embodiments, the solid form Compound 1 Form II exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 7.1° ± 0.3, 9.1° ± 0.3, 9.7° ± 0.3, 15.4° ± 0.3, 17.0° ± 0.3, 18.8° ± 0.3, 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 7.1° ± 0.3, 9.1° ± 0.3, 9.7° ± 0.3, 15.4° ± 0.3, 17.0° ± 0.3, 18.8° ± 0.3, 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 87.1° ± 0.3, 9.1° ± 0.3, 9.7° ± 0.3, 15.4° ± 0.3, 17.0° ± 0.3, 18.8° ± 0.3, 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 7.1° ± 0.3, 9.1° ± 0.3, 9.7° ± 0.3, 15.4° ± 0.3, 17.0° ± 0.3, 18.8° ± 0.3, 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 7.1° ± 0.3, 9.1° ± 0.3, 9.7° ± 0.3, 15.4° ± 0.3, 17.0° ± 0.3, 18.8° ± 0.3, 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 7.1° ± 0.3, 9.1° ± 0.3, 9.7° ± 0.3, 15.4° ± 0.3, 17.0° ± 0.3, 18.8° ± 0.3, 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form II exhibits at least seven X-ray powder diffraction reflections selected from the group consisting of 7.1° ± 0.3, 9.1° ± 0.3, 9.7° ± 0.3, 15.4° ± 0.3, 17.0° ± 0.3, 18.8° ± 0.3, 20.0° ± 0.3, 24.1° ± 0.3, and 25.8° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form II is selected from ±0.5°; ±0.4°; ±0.3°; ±0.2°; ±0.1°; and ±0.05°. In some embodiments, Compound 1WSGR Ref. No. 53699-722.601Form II exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 4. In some embodiments, Compound 1 Form II exhibits at least one of the X-ray powder diffraction pattern reflections in Table 2.Table 2. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form II.WSGR Ref. No. 53699-722.601

[0083] In some embodiments, the crystalline solid state of Compound 1 Form II exhibits a DSC thermogram substantially similar to that shown in Figure 5. In some embodiments, the crystalline solid state of Compound 1 Form II exhibits a DSC endotherm at 50.2 °C ± 5.0. In some embodiments, the crystalline solid state of Compound 1 Form II exhibits a DSC endotherm at 188.6°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 1 Form II are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C. In certain embodiments, the margin of error for the exotherms of the crystalline solid state of Compound 1 Form II are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0084] In some embodiments, the crystalline solid state of Compound 1 Form II exhibits a TGA thermogram substantially similar to that shown in Figure 5. In some embodiments, the crystalline solid state of Compound 1 Form II exhibits TGA weight loss of 3.5 % ± 0.5 (w / w) from 35 to 85 °C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 1 Form II is selected from ±5.0 °C; ±2.0 °C; ±1.0 °C; ±0.5 °C; and ±0.1 °C.

[0085] In some embodiments, the crystalline solid state of Compound 1 Form II exhibits a Dynamic Vapor Sorption Isotherm Plot substantially similar to that shown in Figure 6.

[0086] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 1 Form II is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0087] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form II has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form II has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form II has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form II has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form II has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form II has a chemical purity of 99.5% or more. Compound 1 Form III

[0088] In some embodiments, the present invention provides crystalline solid state form of Compound 1 Form III. In some embodiments, the solid form of Compound 1 Form III exhibitsWSGR Ref. No. 53699-722.601 an X-ray powder diffraction reflection at a 2-theta value of l l. l° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits an X-ray powder diffraction reflection at a 2- theta value of 20.5° ± 0.3 and 21.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.5° ± 0.3, 10.4° ± 0.3, and 19.2° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 21.4° ± 0.3, 21.9° ± 0.3, and 22.5° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 11.7° ± 0.3, 16.8° ± 0.3, 18.6° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 8.5° ± 0.3, 16.0° ± 0.3, 17.6° ± 0.3, and 19.9° ± 0.3.

[0089] In some embodiments, the solid form Compound 1 Form III exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.33. In some embodiments, the solid form of Compound 1 Form III exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ±WSGR Ref. No. 53699-722.6010.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits at least seven X-ray powder diffraction reflections selected from the group consisting 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits at least eight X-ray powder diffraction reflections selected from the group consisting 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form III exhibits at least nine X-ray powder diffraction reflections selected from the group consisting 7.5° ± 0.3, 8.5° ± 0.3, 10.4° ± 0.3, 11.1° ± 0.3, 11.7° ± 0.3, 16.0° ± 0.3, 16.8° ± 0.3, 17.6° ± 0.3, 18.6° ± 0.3, 19.2° ± 0.3, 19.9° ± 0.3, 20.5° ± 0.3, 21.0° ± 0.3, 21.4° ± 0.3, 21.9° ± 0.3, 22.5° ± 0.3, and 26.6° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form III is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form III exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 7. In some embodiments, Compound 1 Form III exhibits at least one of the X-ray powder diffraction pattern reflections in Table 3.Table 3. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form III.WSGR Ref. No. 53699-722.601

[0090] In some embodiments, the crystalline solid state of Compound 1 Form III exhibits a DSC thermogram substantially similar to that shown in Figure 8. In some embodiments, the crystalline solid state of Compound 1 Form III exhibits a DSC endotherm at 70.5°C ± 5.0. In some embodiments, the crystalline solid state of Compound 1 Form III exhibits a DSC endotherm at 160.7°C ± 5.0. In certain embodiments, the margin of error for the endotherms ofWSGR Ref. No. 53699-722.601 the crystalline solid state of Compound 1 Form III are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C. In certain embodiments, the margin of error for the exotherms of the crystalline solid state of Compound 1 Form III are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0091] In some embodiments, the crystalline solid state of Compound 1 Form III exhibits a TGA thermogram substantially similar to that shown in Figure 8. In some embodiments, the crystalline solid state of Compound 1 Form III exhibits TGA weight loss of 1.3 % ± 0.5 (w / w) from 40.0 to 105.0 °C ± 10.0. In some embodiments, the crystalline solid state of Compound 1 Form III exhibits TGA weight loss of 6.8 % ± 0.5 (w / w) from 125.0 to 195.0 °C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 1 Form III is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0092] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 1 Form III is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0093] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form III has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form III has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form III has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form III has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form III has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form III has a chemical purity of 99.5% or more.Compound 1 Form IV

[0094] In some embodiments, the present invention provides crystalline solid state form of Compound 1 Form IV. In some embodiments, the solid form of Compound 1 Form IV exhibits an X-ray powder diffraction reflection at a 2-theta value of 11.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits an X-ray powder diffraction reflection at a 2- theta value of 10.6° ± 0.3 and 19.5° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits an X-ray powder diffraction reflection at a 2-theta value of 20.9° ± 0.3, 21.4° ± 0.3, and 22.9° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.7° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, andWSGR Ref. No. 53699-722.60121.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits an X-ray powder diffraction reflection at a 2-theta value of 17.9° ± 0.3, 20.3° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits an X-ray powder diffraction reflection at a 2-theta value of 8.7° ± 0.3, 16.3° ± 0.3, 22.3° ± 0.3, and 23.4° ± 0.3.

[0095] In some embodiments, the solid form of Compound 1 Form IV exhibits at least one X- ray powder diffraction reflection selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits at least seven X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits atWSGR Ref. No. 53699-722.601 least eight X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form IV exhibits at least nine X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 16.3° ± 0.3, 17.9° ± 0.3, 19.0° ± 0.3, 19.5° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.8° ± 0.3, 22.3° ± 0.3, 22.9° ± 0.3, 23.4° ± 0.3, 27.1° ± 0.3, and 27.6° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form IV is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form IV exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 9. In some embodiments, Compound 1 Form IV exhibits at least one of the X-ray powder diffraction pattern reflections in Table 4.Table 4. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form IV.WSGR Ref. No. 53699-722.601

[0096] In some embodiments, the crystalline solid state of Compound 1 Form IV exhibits a DSC thermogram substantially similar to that shown in Figure 10. In some embodiments, the crystalline solid state of Compound 1 Form IV exhibits a DSC endotherm at 67 ,0°C ± 5.0. In some embodiments, the crystalline solid state of Compound 1 Form IV exhibits a DSC endotherm at 163.3°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 1 Form IV are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C. In certain embodiments, the margin of error for the exotherms of the crystalline solid state of Compound 1 Form IV are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.WSGR Ref. No. 53699-722.601

[0097] In some embodiments, the crystalline solid form Compound 1 Form IV exhibits a TGA thermogram substantially similar to that shown in Figure 10. In some embodiments, the crystalline solid state of Compound 1 Form IV exhibits TGA weight loss of 4.4% ± 0.5 (w / w) from 35.0 to 170.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 1 Form IV is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0098] In some embodiments, the crystalline solid state of Compound 1 Form IV exhibits a Dynamic Vapor Sorption Isotherm Plot substantially similar to that shown in Figure 11.

[0099] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form IV is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0100] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form IV has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form IV has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form IV has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form IV has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form IV has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form IV has a chemical purity of 99.5% or more. Compound 1 Form V

[0101] In some embodiments, the present invention provides crystalline solid state form of Compound 1 Form V. In some embodiments, the solid form of Compound 1 Form V exhibits an X-ray powder diffraction reflection at a 2-theta value of 6.9° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.0° ± 0.3 and 18.5° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.2° ± 0.3, 16.1° ± 0.3, and 17.8° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits an X-ray powder diffraction reflection at a 2-theta value of 4.6° ± 0.3, 12.1° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3.WSGR Ref. No. 53699-722.601

[0102] In some embodiments, the solid form Compound 1 Form V exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 4.6 ° ± 0.3, 6.9° ± 0.3, 9.2° ± 0.3, 12.1° ± 0.3, 14.0° ± 0.3, 16.1° ± 0.3, 17.8° ± 0.3, 18.5° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 4.6 ° ± 0.3, 6.9° ± 0.3, 9.2° ± 0.3, 12.1° ± 0.3, 14.0° ± 0.3, 16.1° ± 0.3, 17.8° ± 0.3, 18.5° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 4.6 ° ± 0.3, 6.9° ± 0.3, 9.2° ± 0.3, 12.1° ± 0.3, 14.0° ± 0.3, 16.1° ± 0.3, 17.8° ± 0.3, 18.5° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 4.6 ° ± 0.3, 6.9° ± 0.3, 9.2° ± 0.3, 12.1° ± 0.3, 14.0° ± 0.3, 16.1° ± 0.3, 17.8° ± 0.3, 18.5° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 4.6 ° ± 0.3, 6.9° ± 0.3, 9.2° ± 0.3, 12.1° ± 0.3, 14.0° ± 0.3, 16.1° ± 0.3, 17.8° ± 0.3, 18.5° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 4.6 ° ± 0.3, 6.9° ± 0.3, 9.2° ± 0.3, 12.1° ± 0.3, 14.0° ± 0.3, 16.1° ± 0.3, 17.8° ± 0.3, 18.5° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form V exhibits at least seven X-ray powder diffraction reflections selected from the group consisting of 4.6 ° ± 0.3, 6.9° ± 0.3, 9.2° ± 0.3, 12.1° ± 0.3, 14.0° ± 0.3, 16.1° ± 0.3, 17.8° ± 0.3, 18.5° ± 0.3, 19.6° ± 0.3, and 21.4° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form V is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form V exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 12. In some embodiments, Compound 1 Form V exhibits at least one of the X-ray powder diffraction pattern reflections in Table 5.Table 5. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form V.WSGR Ref. No. 53699-722.601

[0103] In some embodiments, the crystalline solid state of Compound 1 Form V exhibits a DSC thermogram substantially similar to that shown in Figure 13. In some embodiments, theWSGR Ref. No. 53699-722.601 crystalline solid state of Compound 1 Form V exhibits a DSC endotherm at 78.8°C ± 5.0. In some embodiments, the crystalline solid state of Compound 1 Form V exhibits a DSC endotherm at 142.1°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 1 Form V are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C. In certain embodiments, the margin of error for the exotherms of the crystalline solid state of Compound 1 Form V are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0104] In some embodiments, the crystalline solid state Compound 1 Form V exhibits a TGA thermogram substantially similar to that shown in Figure 13. In some embodiments, the crystalline solid state Compound 1 Form V exhibits TGA weight loss of 3.7 % ± 0.5 (w / w) from 30.0 to 130.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 1 Form V is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0105] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form V is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0106] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form V has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form V has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form V has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form V has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form V has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form V has a chemical purity of 99.5% or more. Compound 1 Form VI

[0107] In some embodiments, the present invention provides a crystalline solid state form of Compound 1 Form VI. In some embodiments, the solid form of Compound 1 Form VI exhibits an X-ray powder diffraction reflection at a 2-theta value of 11.4° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits an X-ray powder diffraction reflection at a 2- theta value of 10.6° ± 0.3 and 11.9° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.7° ± 0.3, 8.7° ±WSGR Ref. No. 53699-722.6010.3, 20.3° ± 0.3, and 20.9° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.0° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3.

[0108] In some embodiments, the solid form of Compound 1 Form VI exhibits at least one X- ray powder diffraction reflection selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3. In some embodiments, the solid form exhibits of Compound 1 Form VI at least two X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VI exhibits at least seven X-ray powder diffraction reflections selected from the group consisting of 7.7° ± 0.3, 8.7° ± 0.3, 10.6° ± 0.3, 11.4° ± 0.3, 11.9° ± 0.3, 19.0° ± 0.3, 20.3° ± 0.3, 20.9° ± 0.3, 21.4° ± 0.3, 21.7° ± 0.3, and 23.0° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form VI is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form VI exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 14. In some embodiments, Compound 1 Form VI exhibits at least one of the X- ray powder diffraction pattern reflections in Table 6.Table 6. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form VI.WSGR Ref. No. 53699-722.601

[0109] In some embodiments, the crystalline solid state Compound 1 Form VI exhibits a DSC thermogram substantially similar to that shown in Figure 15. In some embodiments, the crystalline solid state of Compound 1 Form VI exhibits a DSC endotherm at 86.2°C ± 5.0. In some embodiments, the crystalline solid state of Compound 1 Form VI exhibits a DSC endotherm at 163.8°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 1 Form VI are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C. In certain embodiments, the margin of error for the exotherms of the crystalline solid state of Compound 1 Form VI are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0110] In some embodiments, the crystalline solid state Compound 1 Form VI exhibits a TGA thermogram substantially similar to that shown in Figure 15. In some embodiments, theWSGR Ref. No. 53699-722.601 crystalline solid state of Compound 1 Form VI exhibits TGA weight loss of 5.9% ± 0.5 (w / w) from 35.0 to 155.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 1 Form VI is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0111] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 1 Form VI is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0112] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form VI has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form VI has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form VI has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form VI has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form VI has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form VI has a chemical purity of 99.5% or more. Compound 1 Form VII

[0113] In some embodiments, the present invention provides a crystalline solid state form of Compound 1 Form VII. In some embodiments, the solid form of Compound 1 Form VII exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VII exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.2° ± 0.3 and 19.7° ± 0.3. In some embodiments, the solid form of Compound 1 Form VII exhibits an X-ray powder diffraction reflection at a 2-theta value of 10.2° ± 0.3 and 15.2° ± 0.3.

[0114] In some embodiments, the solid form Compound 1 Form VII exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.0° ± 0.3, 10.2° ± 0.3, 15.2° ± 0.3, and 19.7° ± 0.3. In some embodiments, the solid form Compound 1 Form VII exhibits at least two X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.0° ± 0.3, 10.2° ± 0.3, 15.2° ± 0.3, and 19.7° ± 0.3. In some embodiments, the solid form Compound 1 Form VII exhibits at least three X-ray powder diffraction reflection selectedWSGR Ref. No. 53699-722.601 from the group consisting of 7.2° ± 0.3, 9.0° ± 0.3, 10.2° ± 0.3, 15.2° ± 0.3, and 19.7° ± 0.3. In some embodiments, the solid form Compound 1 Form VII exhibits at least four X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.0° ± 0.3, 10.2° ± 0.3, 15.2° ± 0.3, and 19.7° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form VII is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form VII exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 16. In some embodiments, Compound 1 Form VII exhibits at least one of the X-ray powder diffraction pattern reflections in Table 7.Table 7. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form VII.

[0115] In some embodiments, the crystalline solid state Compound 1 Form VII exhibits a DSC thermogram substantially similar to that shown in Figure 17. In some embodiments, the crystalline solid state Compound 1 Form VII exhibits a DSC endotherm at 191.2°C ± 5.0. InWSGR Ref. No. 53699-722.601 certain embodiments, the margin of error for the endotherms of the crystalline solid state Compound 1 Form VII are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C. In certain embodiments, the margin of error for the exotherms of the crystalline solid state Compound 1 Form VII are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0116] In some embodiments, the crystalline solid state Compound 1 Form VII exhibits a TGA thermogram substantially similar to that shown in Figure 17. In some embodiments, the crystalline solid state of Compound 1 Form VII exhibits TGA weight loss of 0.8% ± 0.5 (w / w) from 180.0 to 265.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 1 Form VII is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0117] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form VII is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0118] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form VII has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form VII has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form VII has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form VII has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form VII has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form VII has a chemical purity of 99.5% or more. Compound 1 Form VIII

[0119] In some embodiments, the present invention provides a crystalline solid state form of Compound 1 Form VIII. In some embodiments, the solid form of Compound 1 Form VIII exhibits an X-ray powder diffraction reflection at a 2-theta value 6.3° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits an X-ray powder diffraction reflection at a 2-theta value of 8.5° ± 0.3 and 17.6° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits an X-ray powder diffraction reflection at a 2-theta value of 12.7° ± 0.3, 20.1° ± 0.3, and 27.0° ± 0.3. In some embodiments, the solid form of Compound 1WSGR Ref. No. 53699-722.601Form VIII exhibits an X-ray powder diffraction reflection at a 2-theta value of 11.3° ± 0.3, 13.6° ± 0.3, 20.9° ± 0.3, and 24.2° ± 0.3.

[0120] In some embodiments, the solid form of Compound 1 Form VIII exhibits at least one X- ray powder diffraction reflection selected from the group consisting of 6.3° ± 0.3, 8.5° ± 0.3, 11.3° ± 0.3, 12.7° ± 0.3, 13.6° ± 0.3, 17.6° ± 0.3, 20.1° ± 0.3, 20.9° ± 0.3, 24.2° ± 0.3, and 27.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits at least two X- ray powder diffraction reflection selected from the group consisting of 6.3° ± 0.3, 8.5° ± 0.3, 11.3° ± 0.3, 12.7° ± 0.3, 13.6° ± 0.3, 17.6° ± 0.3, 20.1° ± 0.3, 20.9° ± 0.3, 24.2° ± 0.3, and 27.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits at least three X- ray powder diffraction reflection selected from the group consisting of 6.3° ± 0.3, 8.5° ± 0.3, 11.3° ± 0.3, 12.7° ± 0.3, 13.6° ± 0.3, 17.6° ± 0.3, 20.1° ± 0.3, 20.9° ± 0.3, 24.2° ± 0.3, and 27.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits at least four X- ray powder diffraction reflection selected from the group consisting of 6.3° ± 0.3, 8.5° ± 0.3, 11.3° ± 0.3, 12.7° ± 0.3, 13.6° ± 0.3, 17.6° ± 0.3, 20.1° ± 0.3, 20.9° ± 0.3, 24.2° ± 0.3, and 27.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits at least five X- ray powder diffraction reflection selected from the group consisting of 6.3° ± 0.3, 8.5° ± 0.3, 11.3° ± 0.3, 12.7° ± 0.3, 13.6° ± 0.3, 17.6° ± 0.3, 20.1° ± 0.3, 20.9° ± 0.3, 24.2° ± 0.3, and 27.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits at least six X- ray powder diffraction reflection selected from the group consisting of 6.3° ± 0.3, 8.5° ± 0.3, 11.3° ± 0.3, 12.7° ± 0.3, 13.6° ± 0.3, 17.6° ± 0.3, 20.1° ± 0.3, 20.9° ± 0.3, 24.2° ± 0.3, and 27.0° ± 0.3. In some embodiments, the solid form of Compound 1 Form VIII exhibits at least seven X- ray powder diffraction reflection selected from the group consisting of 6.3° ± 0.3, 8.5° ± 0.3, 11.3° ± 0.3, 12.7° ± 0.3, 13.6° ± 0.3, 17.6° ± 0.3, 20.1° ± 0.3, 20.9° ± 0.3, 24.2° ± 0.3, and 27.0° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form VIII is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form VIII exhibits an X-ray powder diffraction pattern substantially similar to that shown in Figure 18. In some embodiments, Compound 1 Form VIII exhibits at least one of the X-ray powder diffraction pattern reflections in Table 8.Table 8. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form VIII.WSGR Ref. No. 53699-722.601

[0121] In some embodiments, the crystalline solid state Compound 1 Form VIII exhibits a DSC thermogram substantially similar to that shown in Figure 19. In some embodiments, the crystalline solid state of Compound 1 Form VIII exhibits a DSC endotherm at 103.6°C ± 5.0. InWSGR Ref. No. 53699-722.601 some embodiments, the crystalline solid state of Compound 1 Form VIII exhibits a DSC endotherm at 170.3°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state Compound 1 Form VIII are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C. In certain embodiments, the margin of error for the exotherms of the crystalline solid state Compound 1 Form VIII are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0122] In some embodiments, the crystalline solid state Compound 1 Form VIII exhibits a TGA thermogram substantially similar to that shown in Figure 19. In some embodiments, the crystalline solid state Compound 1 Form VIII exhibits TGA weight loss of 12.3% ± 0.5 (w / w) from 50.0 to 140.0°C ± 10.0. In some embodiments, the crystalline solid state Compound 1 Form VIII exhibits TGA weight loss of 12.7% ± 0.5 (w / w) from 140.0 to 180.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state Compound 1 Form VIII is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0123] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 1 Form VIII is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0124] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form VIII has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 1 Form VIII has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form VIII has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form VIII has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form VIII has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form VIII has a chemical purity of 99.5% or more. Compound 1 Form IX

[0125] In some embodiments, the present invention provides a crystalline solid state form of Compound 1 Form IX. In some embodiments, the solid form of Compound 1 Form IX exhibits an X-ray powder diffraction reflection at a 2-theta value 6.7° ± 0.3. In some embodiments, the solid form of Compound 1 Form IX exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.4° ± 0.3 and 13.5° ± 0.3. In some embodiments, the solid form of Compound 1 FormWSGR Ref. No. 53699-722.601IX exhibits an X-ray powder diffraction reflection at a 2-theta value of 8.6° ± 0.3, 14.4° ± 0.3, and 20.1° ± 0.3.

[0126] In some embodiments, the solid form of Compound 1 Form IX exhibits at least one X- ray powder diffraction reflection selected from the group consisting of 6.7° ± 0.3, 8.6° ± 0.3, 9.4° ± 0.3, 13.5° ± 0.3, 14.4° ± 0.3, and 20.1° ± 0.3. In some embodiments, the solid form of Compound 1 Form IX exhibits at least two X-ray powder diffraction reflection selected from the group consisting of 6.7° ± 0.3, 8.6° ± 0.3, 9.4° ± 0.3, 13.5° ± 0.3, 14.4° ± 0.3, and 20.1° ± 0.3. In some embodiments, the solid form of Compound 1 Form IX exhibits at least three X-ray powder diffraction reflection selected from the group consisting of 6.7° ± 0.3, 8.6° ± 0.3, 9.4° ± 0.3, 13.5° ± 0.3, 14.4° ± 0.3, and 20.1° ± 0.3. In some embodiments, the solid form of Compound 1 Form IX exhibits at least four X-ray powder diffraction reflection selected from the group consisting of 6.7° ± 0.3, 8.6° ± 0.3, 9.4° ± 0.3, 13.5° ± 0.3, 14.4° ± 0.3, and 20.1° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 1 Form IX is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 1 Form IX exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 20. In some embodiments, Compound 1 Form IX exhibits at least one of the X-ray powder diffraction pattern reflections in Table 9.Table 9. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 1 Form IX.WSGR Ref. No. 53699-722.601

[0127] In some embodiments, the crystalline solid state Compound 1 Form IX exhibits a DSC thermogram substantially similar to that shown in Figure 21. In some embodiments, the crystalline solid state Compound 1 Form IX exhibits a DSC endotherm at 139.5°C ± 5.0. In some embodiments, the crystalline solid state Compound 1 Form IX exhibits a DSC endotherm at 260.7°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state Compound 1 Form IX are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0128] In some embodiments, the crystalline solid state Compound 1 Form IX exhibits a TGA thermogram substantially similar to that shown in Figure 21. In some embodiments, the crystalline solid state Compound 1 Form IX exhibits TGA weight loss of 15.3% ± 0.5 (w / w) from 70.0 to 160.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state Compound 1 Form IX is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0129] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form IX is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0130] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 1 Form IX has a chemical purity of 95% or more. In some embodiments,WSGR Ref. No. 53699-722.601 the crystalline solid state form Compound 1 Form IX has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 1 Form IX has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 1 Form IX has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 1 Form IX has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 1 Form IX has a chemical purity of 99.5% or more. Compound 2

[0131] In some embodiments, the present invention provides a crystalline solid state of (7R, 14R)- 1 -(difluoromethoxy)- 11 -(4-(dimethylphosphoryl)-3 -fluorophenyl)- 10-fluoro-6- (methyl-d3)-6,7-dihydro-7,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)- one besylate, also known as Compound 2. In some embodiments, provided herein is crystalline Compound 2 Form I.Compound 2 Form I

[0132] In some embodiments, the present invention provides crystalline solid state form of Compound 2 Form I. In some embodiments, the solid form of Compound 2 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.9° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 22.1° ± 0.3 and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 16.9° ± 0.3, 17.6° ± 0.3, and 18.5° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.7° ± 0.3, 16.4° ± 0.3, and 19.4° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 8.4° ± 0.3, 9.4° ± 0.3, and 26.1° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 12.8° ± 0.3, 13.5° ± 0.3, 20.9° ± 0.3, and 24.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.7° ± 0.3, 18.9° ± 0.3, 23.5° ± 0.3, and 27.5° ± 0.3.

[0133] In some embodiments, the solid form of Compound 2 Form I exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least two X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3,WSGR Ref. No. 53699-722.60117.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least three X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least four X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least five X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least six X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least seven X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least eight X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In some embodiments, the solid form of Compound 2 Form I exhibits at least nine X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ± 0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ± 0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 2 Form I isWSGR Ref. No. 53699-722.601 selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 2 Form I exhibits an X-ray powder diffraction pattern substantially similar to that shown in Figure 22. In some embodiments, Compound 2 Form I exhibits at least one of the X-ray powder diffraction pattern reflections in Table 10.Table 10. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 2 Form I.WSGR Ref. No. 53699-722.601

[0134] In some embodiments, the crystalline solid state of Compound 2 Form I exhibits a DSC thermogram substantially similar to that shown in Figure 23. In some embodiments, the crystalline solid state of Compound 2 Form I exhibits a DSC endotherm at 236.2°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 2 Form I are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0135] In some embodiments, the crystalline solid state of Compound 2 Form I exhibits a TGA thermogram substantially similar to that shown in Figure 23. In some embodiments, the crystalline solid state of Compound 2 Form I exhibits TGA weight loss of 0% ± 2.0 (w / w) between 30 and 230 °C ± 10.0 as determined by thermogravimetric analysis. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 2 Form I is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0136] In some embodiments, the crystalline solid state of Compound 2 Form I exhibits a Dynamic Vapor Sorption Isotherm Plot substantially similar to that shown in Figure 24.

[0137] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 2 Form I is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 %WSGR Ref. No. 53699-722.601(w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0138] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 2 Form I has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 2 Form I has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 2 Form I has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 2 Form I has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 2 Form I has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 2 Form I has a chemical purity of 99.5% or more. Compound 3

[0139] In some embodiments, the present invention provides a crystalline solid state of (7R, 14R)- 1 -(difluoromethoxy)- 11 -(4-(dimethylphosphoryl)-3 -fluorophenyl)- 10-fluoro-6- (methyl-d3)-6,7-dihydro-7,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)- one phosphate, also known as Compound 3. In some embodiments, provided herein is crystalline Compound 3 Form I. In some embodiments, provided herein is crystalline Compound 3 Form II. In some embodiments, provided herein is crystalline Compound 3 Form III.Compound 3 Form I

[0140] In some embodiments, the present invention provides crystalline solid state form of Compound 3 Form I. In some embodiments, the solid form of Compound 3 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 16.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 6.5° ± 0.3 and 14.8° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.3° ± 0.3 and 23.1° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 20.5° ± 0.3, 21.2° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits an X-ray powder diffraction reflection at a 2-theta value of 17.0° ± 0.3, 17.9° ± 0.3, and 23.9° ± 0.3.

[0141] In some embodiments, the solid form of Compound 3 Form I exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least two X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3,WSGR Ref. No. 53699-722.60116.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least three X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least four X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least five X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least six X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least seven X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least eight X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In some embodiments, the solid form of Compound 3 Form I exhibits at least nine X-ray powder diffraction reflection selected from the group consisting of 6.5° ± 0.3, 14.8° ± 0.3, 16.7° ± 0.3, 17.0° ± 0.3, 17.9° ± 0.3, 19.3° ± 0.3, 20.5° ± 0.3, 21.2° ± 0.3, 23.1° ± 0.3, 23.9° ± 0.3, and 24.7° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 3 Form I is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 3 Form I exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 25. In some embodiments, Compound 3 Form I exhibits at least one of the X-ray powder diffraction pattern reflections in Table 11.Table 11. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 3 Form I.WSGR Ref. No. 53699-722.601

[0142] In some embodiments, the crystalline solid state of Compound 3 Form I exhibits a DSC thermogram substantially similar to that shown in Figure 26. In some embodiments, the crystalline solid state of Compound 3 Form I exhibits a DSC endotherm at 67.5 °C ± 5.0. InWSGR Ref. No. 53699-722.601 some embodiments, the crystalline solid state of Compound 3 Form I exhibits a DSC endotherm at 250.6 °C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 3 Form I are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0143] In some embodiments, the crystalline solid state of Compound 3 Form I exhibits a TGA thermogram substantially similar to that shown in Figure 26. . In some embodiments, the crystalline solid state of Compound 3 Form I exhibits TGA weight loss of 3.3 % ± 0.5 (w / w) from 30.0 to 150.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 3 Form I is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0144] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 3 Form I is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0145] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 3 Form I has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 3 Form I has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 3 Form I has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 3 Form I has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 3 Form I has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 3 Form I has a chemical purity of 99.5% or more.Compound 3 Form II

[0146] In some embodiments, the present invention provides a crystalline solid state form of Compound 3 Form II. In some embodiments, the solid form of Compound 3 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 21.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 18.3° ± 0.3 and 21.2° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.4° ± 0.3 and 22.4° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 16.4° ± 0.3, 21.7° ± 0.3, and 23.8° ± 0.3. In someWSGR Ref. No. 53699-722.601 embodiments, the solid form of Compound 3 Form II exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.2° ± 0.3, 9.1° ± 0.3, 17.3° ± 0.3, and 27.5° ± 0.3.

[0147] In some embodiments, the solid form of Compound 3 Form II exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least two X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least three X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least four X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least five X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least six X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least seven X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least eight X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form II exhibits at least nine X-ray powder diffraction reflection selected from the group consisting of 7.2° ± 0.3, 9.1° ± 0.3, 14.4° ± 0.3, 16.4° ± 0.3, 17.3° ± 0.3, 18.3° ± 0.3, 21.2° ± 0.3, 21.5° ± 0.3, 21.7° ± 0.3, 22.4° ± 0.3, 23.8° ± 0.3, and 27.5° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 3 Form II is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1;WSGR Ref. No. 53699-722.601 and ±0.05. In some embodiments, Compound 3 Form II exhibits the X-ray powder diffraction pattern substantially similar to that shown in Figure 27. In some embodiments, Compound 3 Form II exhibits at least one of the X-ray powder diffraction pattern reflections in Table 12. Table 12. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 3 Form II.WSGR Ref. No. 53699-722.601

[0148] In some embodiments, the crystalline solid state of Compound 3 Form II exhibits a DSC thermogram substantially similar to that shown in Figure 28. In some embodiments, the crystalline solid state of Compound 3 Form II exhibits a DSC endotherm at 128.8°C ± 5.0. In some embodiments, the crystalline solid state of Compound 3 Form II exhibits a DSC endotherm at 162.9°C ± 5.0. In some embodiments, the crystalline solid state of Compound 3 Form II exhibits a DSC endotherm at 245.4°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 3 Form II are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0149] In some embodiments, the crystalline solid state of Compound 3 Form II exhibits a TGA thermogram substantially similar to that shown in Figure 28. In some embodiments, the crystalline solid state of Compound 3 Form II exhibits TGA weight loss of 3.8 % ± 0.5 (w / w) from 40.0 to 160.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 3 Form II is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.

[0150] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 3 Form II is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0151] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 3 Form II has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 3 Form II has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 3 Form II has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 3 Form II has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 3 Form II has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 3 Form II has a chemical purity of 99.5% or more.WSGR Ref. No. 53699-722.601Compound 3 Form III

[0152] In some embodiments, the present invention provides a crystalline solid state form of Compound 3 Form III. In some embodiments, the solid form of Compound 3 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.4° ± 0.3. In some embodiments, the solid form of Compound 3 Form III exhibits an X-ray powder diffraction reflection at a 2- theta value of 10.5° ± 0.3 and 20.1° ± 0.3. In some embodiments, the solid form of Compound 3 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.0° ± 0.3, 20.4° ± 0.3, and 23.5° ± 0.3. In some embodiments, the solid form of Compound 3 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form of Compound 3 Form III exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.6° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, and 24.7° ± 0.3.

[0153] In some embodiments, the solid form Compound 3 Form III exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least two X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least three X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least four X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least five X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least six X- ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least seven X-ray powder diffraction reflection selected from the groupWSGR Ref. No. 53699-722.601 consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least eight X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In some embodiments, the solid form Compound 3 Form III exhibits at least nine X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3. In certain embodiments, the margin of error for any one of the reflections of Compound 3 Form III is selected from ±0.5; ±0.4; ±0.3; ±0.2; ±0.1; and ±0.05. In some embodiments, Compound 3 Form III exhibits the X- ray powder diffraction pattern substantially similar to that shown in Figure 29. In some embodiments, Compound 3 Form III exhibits at least one of the X-ray powder diffraction pattern reflections in Table 13.Table 13. Peak listing for the X-ray powder diffractogram of the crystalline solid state form of Compound 3 Form III.WSGR Ref. No. 53699-722.601

[0154] In some embodiments, the crystalline solid state of Compound 3 Form III exhibits a DSC thermogram substantially similar to that shown in Figure 30. In some embodiments, the crystalline solid state of Compound 3 Form III exhibits a DSC endotherm at 245.5°C ± 5.0. In certain embodiments, the margin of error for the endotherms of the crystalline solid state of Compound 3 Form III are selected from ±15.0 °C; ±10.0 °C; ±5.0 °C; and ±2.0 °C.

[0155] In some embodiments, the crystalline solid state of Compound 3 Form III exhibits a TGA thermogram substantially similar to that shown in Figure 30. In some embodiments, the crystalline solid state of Compound 3 Form III exhibits TGA weight loss of 0 % ± 2.0 (w / w) between 50.0 and 230.0°C ± 10.0. In certain embodiments, the margin of error for the TGA weight loss for the crystalline solid state of Compound 3 Form III is selected from ±5.0; ±2.0; ±1.0; ±0.5; and ±0.1.WSGR Ref. No. 53699-722.601

[0156] In some embodiments, the crystalline solid state of Compound 3 Form III exhibits a Dynamic Vapor Sorption Isotherm Plot substantially similar to that shown in Figure 31.

[0157] In some embodiments, provided herein is a composition wherein the crystalline solid state form of Compound 3 Form III is substantially free of other crystalline or amorphous forms. In some embodiments, the amount of other crystalline or amorphous forms is 20 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 15 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 10 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 5 % (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms is 1 % (w / w) or less.

[0158] In some embodiments, provided herein is a composition wherein the crystalline solid state form Compound 3 Form III has a chemical purity of 95% or more. In some embodiments, the crystalline solid state form Compound 3 Form III has a chemical purity of 96% or more. In some embodiments, the crystalline solid state form Compound 3 Form III has a chemical purity of 97% or more. In some embodiments, the crystalline solid state form Compound 3 Form III has a chemical purity of 98% or more. In some embodiments, the crystalline solid state form Compound 3 Form III has a chemical purity of 99% or more. In some embodiments, the crystalline solid state form Compound 3 Form III has a chemical purity of 99.5% or more.Pharmaceutical Compositions

[0159] In certain embodiments, Compound 1, Compound 2, or Compound 3 is administered as a pure chemical. In other embodiments, Compound 1, Compound 2, or Compound 3 is combined with a pharmaceutically suitable or acceptable carrier (also referred to herein as a pharmaceutically suitable (or acceptable) excipient, physiologically suitable (or acceptable) excipient, or physiologically suitable (or acceptable) carrier) selected on the basis of a chosen route of administration and standard pharmaceutical practice as described, for example, in Remington: The Science and Practice of Pharmacy (Gennaro, 21stEd. Mack Pub. Co., Easton, PA (2005)).

[0160] One embodiment provides a pharmaceutical composition comprising a solid form of any one of the compounds provided herein and a pharmaceutically acceptable excipient.

[0161] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing a solid form of a compound provided herein, and a pharmaceutically acceptable carrier.

[0162] Provided herein is a pharmaceutical composition comprising at least one of Compound 1, Compound 2, or Compound 3 together with one or more pharmaceutically acceptable carriers. The carrier(s) (or excipient(s)) is acceptable or suitable if the carrier is compatible with the otherWSGR Ref. No. 53699-722.601 ingredients of the composition and not deleterious to the recipient (i.e., the subject or the patient) of the composition.

[0163] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and Compound 1, Compound 2, or Compound 3.

[0164] One embodiment provides a method of preparing a pharmaceutical composition comprising mixing Compound 1, Compound 2, or Compound 3 and a pharmaceutically acceptable carrier.

[0165] In certain embodiments, Compound 1, Compound 2, or Compound 3 is substantially pure, in that it contains less than about 5%, or less than about 1%, or less than about 0.1%, of other organic small molecules, such as unreacted intermediates or synthesis by-products that are created, for example, in one or more of the steps of a synthesis method.

[0166] The dose of the composition comprising Compound 1, Compound 2, or Compound 3, differs depending upon the subject or patient's (e.g., human) condition. In some embodiments, such factors include general health status, age, and other factors.

[0167] Pharmaceutical compositions are administered in a manner appropriate to the disease to be treated (or prevented). An appropriate dose and a suitable duration and frequency of administration will be determined by such factors as the condition of the patient, the type and severity of the patient's disease, the particular form of the active ingredient, and the method of administration. In general, an appropriate dose and treatment regimen provides the composition(s) in an amount sufficient to provide therapeutic and / or prophylactic benefit (e.g., an improved clinical outcome, such as more frequent complete or partial remissions, or longer disease-free and / or overall survival, or a lessening of symptom severity. Optimal doses are generally determined using experimental models and / or clinical trials. The optimal dose depends upon the body mass, weight, or blood volume of the patient.

[0168] Oral doses typically range from about 1.0 mg to about 1000 mg, one to four times, or more, per day.Methods of Treatment

[0169] One embodiment provides Compound 1, Compound 2, or Compound 3, for use in a method of treatment of the human or animal body.

[0170] One embodiment provides Compound 1, Compound 2, or Compound 3, for use in a method of treating an inflammatory or autoimmune disease or disorder. In some embodiments, the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease,WSGR Ref. No. 53699-722.601 sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

[0171] One embodiment provides a use of Compound 1, Compound 2, or Compound 3, in the manufacture of a medicament for the treatment of an inflammatory or autoimmune disease or disorder. In some embodiments, the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

[0172] In some embodiments, described herein is a method of treating an inflammatory or autoimmune disease or disorder in a patient in need thereof comprising administering to the patient Compound 1, Compound 2, or Compound 3. In some embodiments, described herein is a method of treating an inflammatory or autoimmune disease or disorder in a patient in need thereof comprising administering to the patient a pharmaceutical composition comprising Compound 1, Compound 2, or Compound 3, and a pharmaceutically acceptable excipient. In some embodiments, the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO)

[0173] Provided herein is the method wherein the pharmaceutical composition is administered orally.

[0174] One embodiment provides a solid form of a compound provided herein for use in a method of treatment of the human or animal body.

[0175] One embodiment provides a solid form of a compound provided herein for use in a method of treatment of an inflammatory or autoimmune disease or disorder. In some embodiments, the inflammatory or autoimmune disease or disorder is selected from the groupWSGR Ref. No. 53699-722.601 consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behget's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO)

[0176] One embodiment provides use of a solid form of a compound provided herein in the manufacture of a medicament for the treatment of an inflammatory or autoimmune disease or disorder. In some embodiments, the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

[0177] One embodiment provides a method of treating a disease or disorder in a patient in need thereof, comprising administering to the patient a solid form of a compound provided herein. In some embodiments, the disease or disorder is an inflammatory or autoimmune disease or disorder. In some embodiments, the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

[0178] One embodiment provides a method of treating a disease or disorder in a patient in need thereof, comprising administering to the patient a solid form of a compound provided herein and a pharmaceutically acceptable excipient. In some embodiments, the disease or disorder is an inflammatory or autoimmune disease or disorder. In some embodiments, the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis,WSGR Ref. No. 53699-722.601 systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behget's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

[0179] Other embodiments and uses will be apparent to one skilled in the art in light of the present disclosures. The following examples are provided merely as illustrative of various embodiments and shall not be construed to limit the invention in any way.EXAMPLES

[0180] The present disclosure is further illustrated by the following examples, which should not be construed as limiting in any way. The experimental procedures to generate the data shown are discussed in more detail below. The disclosure has been described in an illustrative manner, and it is to be understood that the terminology used is intended to be in the nature of description rather than of limitation.General Experimental, Instrument, and Methodology Details

[0181] A general synthesis for (7R, 14R)-1 -(difluorometh oxy)- 11 -(4-(dimethylphosphoryl)-3 - fluorophenyl)- 10-fluoro-6-(methyl-d3 )-6, 7-dihy dro-7, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one is described in PCT / US2023 / 080758.X-Ray Powder Diffraction (XRPD)

[0182] XRPD diffractograms were collected with an X-ray diffractometer. The sample was prepared on a zero background silicon wafer by gently pressing onto the flat surface. The paramaters of XRPD diffraction are provided in Table 14.Table 14. Parameters for XRPD TestingWSGR Ref. No. 53699-722.601Differential Scanning Calorimetry (DSC)

[0183] DSC analysis was performed with a TA Instrument. About 1-3 mg of the sample was placed into an aluminum pan with pin-hole and heated with the parameters in Table 15. The data was analyzed using TRIOS.Table 15. Parameters for DSC AnalysisThermo-Gravimetric Analysis (TGA)

[0184] TGA analysis was performed using a TA Instrument. About 1-5 mg of the sample was loaded onto a pre-tared aluminum pan and heated with the parameters in Table 16. The data was analyzed using TRIOS.Table 16. Parameters for TGA AnalysisDynamic Vapor Sorption (DVS)

[0185] Moisture sorption / desorption data were collected on a DVS Intrinsic PLUS (SMS, UK). The sample was placed into a tared sample chamber and automatically weighed. Samples (e.g., anhydrate, hydrate) were analyzed with the setting parameters listed in Table 17.Table 17. Parameters for DVS experimentsWSGR Ref. No. 53699-722.601Proton Nuclear Magnetic Resonance (1H-NMR)

[0186] ^-NMR was performed using Bruker 400 MHz instrument. Samples were measured with the parameters in Table 18.Table 18. Parameters for 'H-NMR AnalysisHigh Performance Liquid Chromatography (HPLC) Method

[0187] HPLC analysis was performed with an Agilent HPLC 1260 series instrument. HPLC method for solubility and stability testing is listed in Table 19 for the polymorph screen of Compound 2 and the salt screen of Example 1, and in Table 20 for the polymorph screen of Compound 1.Table 19: Parameters for HPLC experimentsTable 20. Parameters for HPLC experimentsWSGR Ref. No. 53699-722.601Example 1: Summary of Salt Screen

[0188] A total of seven acids were used for the salt screen and are presented in Table 21 below.Table 21. Acids Used for Salt Screen

[0189] The solvents used for solubility estimation and salt screening listed in Table 22 below were used for the screen.Table 22. Solvents used for Salt Screen

[0190] Based on the results of p / C and estimated solubility of Compound 1 Form I, salt screen was conducted with seven pharmaceutically acceptable acids in four solvent systems - THF, IP A, acetone / water (49 / 1, v / v) and EtOAc.

[0191] Salts were prepared on 25 mg scale. An appropriate amount of Compound 1 Form I was dispersed into 0.5 - 0.6 mL selected solvents. Then 1.1 eq. acid was added into the system at RT for salt formation, as well as additional 0.55 eq. for H2SO4. The acids (HC1, H2SO4, MsOH and H3PO4) were pre-diluted in corresponding solvent systems before addition, and the mixture was stirred at RT or 50 °C for 1 d (50 °C for EtOAc only). If clear solutions were obtained, anti-solvents were added. If oils were observed, these oily samples were transferred to stirring at 50 °C for maturation. The suspensions were filtered, and the solids were vacuum dried at 40 °C for 3-4 h. Salt screening results are summarized in Table 23 below.WSGR Ref. No. 53699-722.601

[0192] Of the seven acids screened, six formed crystalline salts, and a total of 10 crystalline salts were discovered.Table 23. Salt Screen ResultsHCl Salt

[0193] HC1 salt was prepared with 1.1 eq. of HC1 at RT or 50 °C for 1 d. Two crystalline HC1 salt were obtained in selected solvents, assigned as HC1 salt Forms I and II.

[0194] HC1 salt Form I, obtained by slurry reaction in THF with 1.1 eq. HC1 at RT for 1 d, was characterized. Thermal analysis showed two-step weight loss of 6.2% at 30-125 °C and 4.5% at 125-185 °C in TGA, and two endothermic peaks with onset temperature of 52 and 147 °C were observed in DSC, due to dehydration and melting. Negligible THF residue was detected by1H- NMR. Hence, HC1 salt Form I is postulated to be a hydrate.WSGR Ref. No. 53699-722.601

[0195] HC1 salt Form II, obtained by slurry reaction in acetone / water (49 / 1, v / v) with 1.1 eq. HC1 at RT for 1 d, was characterized. Thermal analysis showed two-step weight loss of 8.0% at 35-130 °C and 3.4% at 130-190 °C in TGA, and three endothermic peaks with onset temperature of 52, 126 and 143 °C were observed in DSC, due to dehydration and melting. Negligible acetone residue was detected by 'H-NMR. Hence, HC1 salt Form II is postulated to be a hydrate.Sulfate Salt

[0196] Sulfate salt was prepared with 1.1 / 0.55 eq. of H2SO4 at RT or 50 °C. Two crystalline sulfate forms were obtained in selected solvents, assigned as Sulfate Forms I and II. The XRPD patterns of Sulfate Forms I and II were similar.

[0197] Sulfate Form I, obtained by slurry reaction in IPA with 1.1 eq. H2SO4 at RT for 1 d, was characterized. Thermal analysis showed 4.3% weight loss at 35 - 130 °C in TGA, and two endothermic peaks at 56 and 179 °C (onset) in DSC. Negligible IPA residue was detected by1H- NMR. Hence, Sulfate Form I is a hydrate.

[0198] Sulfate Form II, obtained by slurry reaction in 2-MeTHF with 1.1 eq. H2SO4 at RT for 3 d, was characterized. Thermal analysis showed 1.1% weight loss at 35 - 150 °C in TGA, and two endothermic peaks at 64 and 193 (onset) in DSC. 1.0% 2-MeTHF was detected by 'H- NMR. Hence, Sulfate Form II might be an anhydrate with solvent occlusion.Tosylate Salt

[0199] Tosylate salt was prepared with 1.1 eq. / >-TsOH at RT or 50 °C. One crystalline tosylate was obtained, assigned as Tosylate Form I. Tosylate Form I, obtained by slurry reaction in EtOAc at 50 °C for 1 d, was characterized. Thermal analysis showed 4.4% weight loss at 35 - 160 °C in TGA, and two endothermic peaks at 36 and 213 °C (onset) in DSC. Negligible EtOAc residue was detected by ' H-NMR, and the salt ratio was 1 : 1. Hence, Tosylate Form I is postulated to be an anhydrate with hygroscopicity.Mesylate Salt

[0200] Mesylate salt was prepared with 1.1 eq. MsOH at RT or 50 °C for 1 d. No crystalline mesylate was observed.Maleate Salt

[0201] Maleate salt was prepared with 1.1 / 3.0 eq. maleic acid at RT or 50 °C. One crystalline maleate was obtained, assigned as Maleate Form I. Maleate Form I, obtained by slurry reaction in EtOAc at 50 °C for 1 d, was characterized. Thermal analysis showed two-step weight loss of 1.3% at 35 - 80 °C and 15.1% at 100 - 250 °C in TGA, and multiple endothermic peaks in DSC.WSGR Ref. No. 53699-722.601Negligible EtOAc residue was detected by1H-NMR, and the salt ratio was 1 : 1. Hence, Maleate Form I is likely a hydrate.Phosphate Salt

[0202] Phosphate salt was prepared with 1.1~ 5.0 eq. H3PO4 at RT or 50 °C for 1 - 3 d. Three crystal forms of phosphate were obtained, assigned as Compound 3 Form I, Compound 3 Form II, and Compound 3 Form III. Compound 3 Form I, obtained by slurry reaction with 1.1 eq. HsPChin THF at RT for 1 d, was characterized. Thermal analysis showed 3.3% weight loss at 30 - 150 °C in TGA, and two endothermic peaks at 35.6 and 245.2 °C (onset) in DSC (See Fig. 26). Negligible THF residue was detected by 'H-NMR. Hence, Compound 3 Form I might be an anhydrate with hygroscopicity.

[0203] Compound 3 Form II, obtained by slurry reaction in acetone / water (49 / 1) with 1.1 eq.H3PO4 at RT for 1 d, was characterized. Thermal analysis showed 3.8% weight loss from 40 - 150 °C in TGA, and three endothermic peaks at 99.1, 153.4 and 232.7 °C (onset) in DSC (See Fig. 28). 2.9% acetone (~ 0.34 eq.) was detected by 'H-NMR. Hence, Compound 3 Form II might be an acetone solvate.

[0204] Compound 3 Form III, obtained by slurry reaction in EtOH with 2.1 eq. H3PO4 at 50 °C for 1 d, was characterized. Thermal analysis showed negligible weight loss before 220 °C in TGA, and one endothermic peak in DSC (See Fig. 30). Hence, Compound 3 Form III is postulated to be an anhydrate.Besylate Salt

[0205] Besylate was prepared with 1.1 eq. BsOH at RT or 50 °C. One crystalline besylate was obtained, assigned as Compound 2 Form I. Compound 2 Form I, obtained by slurry reaction in EtOAc at 50 °C for 1 d, was characterized. Thermal analysis showed negligible weight loss before melting in TGA, and one endothermic peak in DSC, due to melting (See Fig. 23). 1.2% EtOAc was detected by ' H-NMR, and the salt ratio was 1 : 1. Hence, Compound 2 Form I is postulated to be an anhydrate.Example 2: Polymorph Screen of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6.,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one (Compound 1)

[0206] A polymorph screen of Compound Iwas performed to identify crystalline forms for further development. The solvents used for the polymorph screen of Compound 1 are provided in Table 24 below. In Table 24 below: dimethyl sulfoxide (DMSO), dichloromethane (DCM), methanol (MeOH), ethanol (EtOH), 2-Propanol (IP A), / / -Butanol, ethyl acetate (EA), isopropyl acetate (IP Ac), methyl acetate, tert-Butyl methyl ether (MTBE), anisole, 2-methyltetrahydrofuranWSGR Ref. No. 53699-722.601(2-Me-THF), tetrahydrofuran (THF), acetonitrile (ACN), acetone, butanone (MEK), Methyl isobutyl ketone (MIBK), toluene, cyclohexane (CYH), / / -Heptane, acetic acid.Table 24. List of Solvents used in Polymorph Screen of Compound 1Example 3: Synthesis of Crystalline Form of (7R,14R)-l-(difluoromethoxy)-ll-(4-(dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6,7-dihvdro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one (Compound 1 Form I)

[0207] Compound 1 Form I was used as the starting material for the polymorph screen. Compound Form I could be obtained in most non-aqueous solvents. Compound 1 Form I showed irregular crystals with aggregation under microscope. XRPD showed with high crystallinity (See Fig. 1). Thermal analysis of Compound 1 Form I showed negligible weight loss before melting in TGA and one endothermic peak at 258.3 °C (onset) in DSC, due to melting (See Fig. 2). 'H-NMR showed negligible EA residue. Compound 1 Form I was determined to be an anhydrate.

[0208] DVS result showed moisture adsorption was 1.3 / 2.1% at 80 / 90% RH (Fig. 3), indicating that Form I was slightly hygroscopic. After DVS testing, the crystal form remained unchanged.Example 4: Synthesis of Crystalline Form of (7R,14R)-l-(difluoromethoxy)-ll-(4-(dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6,7-dihvdro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one (Compound 1 Form II)

[0209] Compound 1 Form II was prepared by slurry of Compound 1 Form I in acetone / water (1 / 9, v / v) at 50 °C for 7 days and then vacuum dried at 40 °C for ~ 4 h. Compound 1 Form II was fine crystals with aggregation and showed high crystallinity (See Fig. 4). TGA showed 3.5% weight loss at 35 - 85 °C (See Fig. 5). DSC showed three endothermic peaks at 26.4, 183.9 and 254.4 °C (onset) and one exothermic peak at 191.2 °C (onset) due to dehydration, phase transition and melting (See Fig. 5). 'H-NMR showed no residual acetone. Therefore, Compound 1 Form II is determined to be a hydrate.WSGR Ref. No. 53699-722.601

[0210] Thermal treatment of Compound 1 Form II was performed by DSC. Compound 1 FormII remained unchanged after heating to 100 °C and converted into Compound 1 Form I after heating to 235 °C. DVS result of Compound 1 Form II showed two plateaus, suggesting different hydration states (See Fig. 6). After DVS test, Compound 1 Form II was observed.Example 5: Synthesis of Crystalline Form III of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one (Compound 1 Form III)

[0211] Compound 1 Form III was obtained by slow evaporation and cyclic heating-cooling in EtOH with Compound 1 Form I as starting material. The characterized Compound 1 Form III was recrystallized in EtOH / heptane. The sample was irregular crystals and showed high crystallinity (See Fig. 7). Thermal analysis showed a two-step weight loss of 1.3% at 40-105 °C and 6.8% at 125-195 °C in TGA, and three endothermic peaks at 40.3, 151.8 and 258.7 °C (onset) and one exothermic peak at 179.8 °C (onset) in DSC (See Fig. 8). 'H-NMR showed 7.4% EtOH. Therefore, Form III is determined to be an EtOH solvate.

[0212] Thermal treatment of Compound 1 Form III was conducted by DSC. Compound 1 FormIII remained unchanged after heating to 110 °C and converted into Compound 1 Form I between 170 and 230 °C.Example 6: Synthesis of Crystalline Form IV of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one (Compound 1 Form IV)

[0213] Compound 1 Form IV could be obtained in aqueous solvents with Compound 1 Form I as starting material. In addition, Compound 1 Form IV was also formed in MeOH, so it is speculated that there exists a MeOH solvate that has similar crystal lattice. The characterized Compound 1 Form IV was prepared by slurry of Compound 1 Form III in water at RT for 1 day. Its XRPD pattern was similar with that of the EtOH solvate Compound 1 Form III with minor differences (See Fig. 7 and Fig. 9).

[0214] The sample was irregular crystals with aggregation and showed high crystallinity (See Fig. 9). TGA showed 4.4% weight loss at 35-170 °C (See Fig. 10). DSC showed three endothermic peaks at 29.4, 154.7 and 259.4 °C (onset) and one exothermic peak at 191.0 °C (onset) (See Fig. 10). ’H-NMR showed 0.9% residual EtOH. Therefore, Compound 1 Form IV was determined to be a hydrate.WSGR Ref. No. 53699-722.601

[0215] Thermal treatment of Compound 1 Form IV was conducted by DSC. Compound 1 FormIV remained unchanged after heating to 125 °C, converted into amorphous after heating to 170 °C, and recrystallized into Compound 1 Form I after heating to 225 °C.

[0216] DVS result showed the moisture adsorption was 7.8 / 7.9% at 80 / 90% RH, and there was no hysteresis during sorption and desorption cycles, indicating that Compound 1 Form IV is potentially a channel hydrate. The crystal form remained unchanged after DVS test.Example 7: Synthesis of Crystalline Form V of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one (Compound 1 Form V)

[0217] Compound 1 Form V was prepared by lyophilization in ACN / water. The sample was needle-like crystals with aggregation and showed high crystallinity (See Fig. 12). Thermal analysis showed 3.7% weight loss at 30-130 °C in TGA, and three endothermic peaks at 58.4, 137.0 and 258.9 °C (onset) and one exothermic peak 201.0°C (onset) in DSC (See Fig. 13).1H- NMR showed no residual ACN. Therefore, Form V is a hydrate.

[0218] Thermal treatment of Compound 1 Form V was conducted by DSC. Compound 1 FormV lost most of its crystallinity after heating to 120 °C, converted into amorphous after heating to 155 °C, and recrystallized into Compound 1 Form I after heating to 215 °C (See Fig. 13).Example 8: Synthesis of Crystalline Form VI of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one (Compound 1 Form VI)

[0219] Compound 1 Form VI was prepared by anti-solvent precipitation in DCM / heptane with Compound 1 Form I as starting material and then vacuum dried at 40 °C for ~ 3 h. XRPD showed that there were minor changes in XRPD pattern after aging in DCM / heptane for 24 h or vacuum drying. The sample was fine crystals with aggregation (See Fig. 14). TGA showed 5.9% weight loss at 35-155 °C (See Fig. 15). DSC showed three endothermic peaks at 51.6, 155.9 and 259.5 °C (onset) and one exothermic peak at 176.5 °C (onset) (See Fig. 15). 'H-NMR showed 3.4% DCM. Therefore, Compound 1 Form VI is likely a DCM solvate.

[0220] Thermal treatment of Compound 1 Form VI was conducted by DSC. Compound 1 FormVI remained unchanged after heating to 150 °C, converted into low-crystallinity Compound 1 Form I after heating to 160 °C, and converted into Compound 1 Form I after heating to 200 °C.WSGR Ref. No. 53699-722.601Example 9: Synthesis of Crystalline Form VII of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one (Compound 1 FormVII)

[0221] Compound 1 Form VII was prepared by slow evaporation in MeOH / EA with Compound 1 Form I as starting material and vacuum dried at 40 °C for ~ 3 h. Compound 1 Form VII is the dehydrated form of Compound 1 Form II.

[0222] The sample was plate-like crystals and showed high crystallinity (See Fig. 16). TGA (See Fig. 17) showed 0.8% weight loss at 180-265 °C. DSC (Fig. 17) showed two endothermic peaks at 187.8 and 259.0 °C (onset) and one exothermic peak at 192.2 °C (onset). 'H-NMR showed 0.2% EA. Therefore, Compound 1 Form VII is likely an anhydrate.

[0223] Thermal treatment of Compound 1 Form VII was performed by DSC. After heating to 190 and 200 °C, Compound 1 Form VII converted into Compound 1 Form I.Example 10: Synthesis of Crystalline Form VIII of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one (Compound 1 FormVIII)

[0224] Compound 1 Form VIII was prepared by slow evaporation in MeOH / 2-MeTHF with Compound 1 Form I as starting material and vacuum dried at 40 °C for ~ 6 h. Compound 1 Form VII was plate-like crystals with high crystallinity (See Fig. 18). TGA (See Fig. 19) showed a two-step weight loss of 12.3% at 50-140 °C and 12.7% at 140-180 °C. DSC (See Fig. 19) showed three endothermic peaks at 84.9, 152.7 and 255.1 °C (onset) and one exothermic peak at 173.4 °C (onset). 'H-NMR showed no residual MeOH and 2-MeTHF, but significant nonvolatile matter from 2-MeTHF. Compound 1 Form VIII is postulated to be a solvate.

[0225] Thermal treatment of Compound 1 Form VIII was conducted by DSC. Compound 1 Form VIII remained unchanged after heating to 140 °C, and converted into Compound 1 Form I after heating to 180 °CExample 11: Synthesis of Crystalline Form IX of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-flnorophenyl)-10-flnoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one maleate (Compound 1)

[0226] 25 mg of Compound 1 Form I was dissolved in 0.45 mL of 1,2-Propanediol (PG), then 0.45 mL of pH 3 buffer (10 mM citrate) was added. The mixture was sonicated for 1.5 h. The solids were collected by filtration and vacuum dried at 40 °C for 3 h. Form IX was plate-like crystals andWSGR Ref. No. 53699-722.601 showed high crystallinity (See Fig. 20). TGA showed 15.3% weight loss at 70-160 °C (See Fig. 21). DSC showed two endothermic peaks at 123.5 and 259.9 °C (onset) (See Fig. 21). 'H-NMR showed 19.7% PG. Therefore, Compound 1 Form IX is likely a PG solvate.

[0227] Thermal treatment of Compound 1 Form IX was conducted by DSC. After heating to 160 °C, Compound 1 Form IX converted into Compound 1 Form I.Example 13: Characterization and Comparison of the Crystalline Forms of (7R,14R)-1- (difluoromethoxy)-ll-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)- 6,7-dihydro-7,14-methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one (Compound 1)

[0228] A summary of the characterization data for the solid forms of Compound 1 identified is shown below in Table 25. Results from the polymorph screening can be found summarized below in Table 26. Compound 1 Form IX was discovered during a formulation study in PG / pH 3 buffer (10 mM citrate).Table 25. Summary of characterization data.WSGR Ref. No. 53699-722.601Table 26. Summary of polymorph screening of Compound 1.Example 14: Competitive Slurry between Form and Form VIII of (7R,14R)-1-(difluoromethoxy)-ll-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)- 6,7-dihydro-7,14-methanobenzo[f|benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one (Compound 1)

[0229] Competitive slurry was conducted between the two anhydrates of Compound 1 Form I and Compound 1 Form VII. An appropriate amount of Compound 1 Form I was suspended in EA and acetone at RT for 2 h for pre-saturation. After filtration, 3 mg each of Compound 1 Form I and Compound 1 Form VII was added into the filtrate. The suspension was stirred at RT for 1 day. The remaining solid was sampled for XRPD test. The results showed that Form I is more stable than Form VH at RT, as presented in Table 27. Combined with that Form VII converted to Form I upon heating to 190 °C, Form I is more stable than Form VII above RT.Table 27: Results of Competitive Slurry between Compound 1 Forms I and VII at RTExample 15: Critical Water Activity Study of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihvdro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one (Compound 1)Example 15 A: Competitive Slurry of Compound 1 Forms I and II

[0230] About 10 mg of Compound 1 Form I was suspended in DMSO / water mixtures at RT for 1 h for pre-saturation. After filtration, 5 mg each of Compound 1 Forms I and II was added into the filtrate. The suspension was stirred at RT for 3 days. The remaining solid was sampled for XRPDWSGR Ref. No. 53699-722.601 test. The results are presented in Table 28. Form I is more stable than Form II at RT with aw< 0.5, and Form II is more stable with aw> 0.75.Table 28Example 15B: Competitive Slurry of Compound 1 Forms I and IV

[0231] An appropriate amount of Compound 1 Form I was suspended in DMSO / water mixtures at RT for 1 h for pre-saturation. After filtration, 5 mg each of Compound 1 Form I and 5 mg of Compound 1 Form IV was added into the filtrate. The suspension was stirred at RT for up to 9 days. The remaining solid was sampled for XRPD test. The results are presented in Table 29. Compound 1 Form I is more stable than Compound 1 Form II at RT with aw< 0.5, and Form IV is more stable with aw> 0.75.Table 29Example 15C: Competitive Slurry of Compound 1 Form V

[0232] An appropriate amount of Compound 1 Form V was suspended in DMSO / water mixtures at RT for 5 d. The remaining solid was sampled for XRPD test. The results are presented in Table 30. Form I is more stable than Form V at RT with aw< 0.5, and Form IV is more stable with aw> 0.75. In pure water, Form V gelled.Table 30Example 16: Solubility of Compound 1 Form

[0233] The solubility of Compound 1 Form I was determined in bio-relevant media (SGF, FaSSIF and FeSSIF) and water at 37 °C with 800 rpm for up to 24 h. About 10 mg of Compound 1 Form I was suspended in 2 mL of bio-relevant media and water. At 0.5, 2 and 24 h, about 0.6 mL of eachWSGR Ref. No. 53699-722.601 suspension was filtered, the filtrate was analyzed by HPLC and pH meter, and the filter cake was analyzed by XRPD. Due to high viscosity in FaSSIF and SGF, supernatants were collected by centrifugation and then filtered. Duplicated samples were prepared for each medium. The results are presented in Table 31.

[0234] Form I showed better solubility in FeSSIF (174 pg / mL @ 0.5 h) and SGF (78 pg / mL @ 0.5 h) than FaSSIF and water, likely due to solubilization effect of bile salt and pH. Gelation was observed after Form I was suspended in all the aqueous media. LOQ is 0.125 pg / mL.Table 31Example 17: Solid-state Stability of Compound 1 Form

[0235] Solid-state stability of two samples of Compound 1 Form I was evaluated at 60 °C (capped) and 40 °C / 75% RH (open) conditions for 7 days. Duplicated samples were prepared at each condition. The stability sample was dissolved in ACN to prepare solution at ~ 0.25 mg / mL for HPLC purity analysis. Solids were characterized by XRPD to check the crystal form. The results are summarized in Table 32. Compound 1 Form I was physically and chemically at 40 °C / 75% RH (open) and 60 °C (capped) for 7 days.Table 32Example 18: Mechanical Stability Study of Compound 1 Form

[0236] An appropriate amount of Compound 1 Form I was manually ground by pestle and mortar for about 2 and 5 min, and the ground samples were analyzed by XRPD. The crystal form of Compound 1 Form I remained unchanged with little crystallinity decrease after grinding, indicating acceptable mechanical stability.WSGR Ref. No. 53699-722.601Example 19: Additional Solubility Studies of Compound 1 Form IExample 19 A: Preliminary Solubility Estimation

[0237] The solubility of Compound 1 Form I was estimated at RT by visual observation. Approximately 5 mg of starting material was weighed into 8 mL glass vial, and then solvent was added stepwise until the solid dissolved completely or a total of solvent volume reached 5 mL. The results are summarized in Table 33. Starting material had high solubility (> 50 mg / mL) in DCM and DMSO. Values are reported as “<” if dissolution not observed and as “>” if dissolution observed at first aliquot.Table 33: Estimated Solubility of Compound 1 Form I at RTExample 19B: Slurry Conversion

[0238] About 25 mg of Compound 1 Form I was added into different solvents to make suspensions which were kept stirring at RT and 50 °C for 7 days and at 80 °C for 3 days. Solid samples were collected by filtration and analyzed by XRPD. Results can be found summarized in Tables 34-36 below. Compound 1 Form I remained unchanged in most non-aqueous solvents. Compound 1 Form IV was obtained by suspension of Compound 1 Form I in aqueous solvents. Table 34: Results of Slurry at RT for Compound 1 Form IWSGR Ref. No. 53699-722.601Table 35: Results of Slurry at 50 °C for Compound 1 Form I#: Clear solution was obtained, and 1 mL of heptane was added as anti-solvent at Day 3.Table 36: Results of Slurry at 80 °C for Compound 1 Form IExample 19B: Anti-solvent Precipitation

[0239] According to the solubility data, DCM, DMSO, acetone / water (1 / 1, v / v), MeOH, EtOH and ft-butanol / anisole (1 / 1, v / v) were used as the good solvents for anti-solvent precipitation.The experiments were performed at 50 °C in MeOH and EtOH, due to the low solubility at RT.As presented in Table 37, Form IV was observed in aqueous solvents and MeOH / MTBE, FormWSGR Ref. No. 53699-722.601VI was observed in DCM-related solvent systems, and Form VIII was discovered in MeOH / 2- MeTHF by follow-up evaporation.Table 37: Results of Anti-solvent Crystallization for Compound 1 Form IExample 19C: Slow Evaporation

[0240] About 15 mg of Compound 1 Form I was weighted into a vial and then dissolved in the select solvent. The vial was covered with pin-hole film and placed at ambient condition for slowWSGR Ref. No. 53699-722.601 evaporation until solid precipitation. The wet cakes were collected by filtration and then analyzed by XRPD. The results are summarized in Table 38. Form III and Form IV were obtained.Table 38: Results of Slow Evaporation for Compound 1 Form IExample 19D: Cyclic Heating-cooling

[0241] Cyclic heating-cooling experiments were carried out in Crystal 16 Parallel Crystallizer.About 15 mg of Compound 1 Form I was added into 0.75 mL solvent, and a heating-cooling program was performed:1. Equilibrate first at 20 °C, and heat to 60-90 °C at 0.5 °C / min (the elevated temperature is set according to boiling point of solvent).2. Hold at 60-90 °C for 1 h.3. Cool to 20 °C at 0.5 °C / min, and hold for 6 h.4. Repeat the above procedures once.

[0242] Turbidimeter from Crystal 16 recorded if the solids were completely dissolved during heating. The results are summarized in Table 39. Forms I, III and Form IV were obtained. Table 39: Results of Cyclic Heating-cooling for Compound 1 Form IWSGR Ref. No. 53699-722.601Example 20: Polymorph Screen of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6.,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate (Compound 2)

[0243] A polymorph screen of Compound 2 was performed to identify additional crystalline forms and to identify stable forms with favorable properties. The solvents used for the polymorph screen of Compound 2 are provided in Table 40 below. In Table 40 below: methanol (MeOH), ethanol (EtOH), 2-Propanol (IP A), / / -Butanol, acetone, 2-butanone (MEK), methyl isobutyl ketone (MIBK), ethyl acetate (EA), isopropyl acetate (IP Ac), methyl acetate, tetrahydrofuran (THF), 2-methyl tetrahydrofuran (2-MeTHF), anisole, tert-Butyl methyl ether (MTBE), acetonitrile (ACN), dichloromethane (DCM), / / -Heptane, toluene, dimethyl sulfoxide (DMSO), water.Table 40. List of Solvents used in Polymorph Screen of Compound 2

[0244] Polymorph screening was carried out using commonly used solvents and various crystallization methods, including slurry conversion, cooling, evaporation, anti-solvent precipitation and cyclic heating-cooling. No new crystal form of Compound 2 was found. However, one additional low intensity peak at 5.8° (20) appeared in many crystallization conditions. It was observed that the intensity did not increase substantially with longer aging time. The standard XRPD pattern of Compound 2 Form I calculated from single crystal structure confirmed the peak is extraneous and possibly from another physical phase. Competitive slurry results showed Compound 2 Form I + 5.8° (20) could convert to pure Compound 2 Form I in ACN, anisole and THF at either RT or 50 °C.

[0245] Compound 2 Form I was physically and chemically stable at 40 °C / 75% RH (open) and 60 °C (capped) for 6 weeks and showed acceptable mechanical stability. Physicochemical properties of Compound 2 Form I are presented in Table 41 below.WSGR Ref. No. 53699-722.601Table 41: Summary of Compound 2 Form I Properties

[0246] Compound 2 Form I is a stable anhydrate with acceptable solid-state properties and is recommended for use in development. In salt formation, any residual sulfuric acid present in benzenesulfonic acid should be controlled carefully to avoid the precipitation of sulfate salt. Process solvents should be screened further to assess formation of the extraneous peak at 5.8° (20) when applying mechanical stirring. A PK study of Compound 2 Form I will be helpful to determine if the salt offers advantages for in vivo performance.Example 21: Synthesis of Crystalline Form of (7R,14R)-l-(difluoromethoxy)-ll-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihvdro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate (Compound 2 Form I)

[0247] About 2.4 g of Compound 1 was suspended in 30 mL ACN at 50 °C. Then 1.1 eq. of BsOH (Vendor: Sigma; Lot#: BCCJ4267; Purity: 98%) was added (pre-diluted in 4 mL ACN) and stirred at 50 °C overnight and then at RT for 6 h. The solid was collected by filtration and vacuum dried atWSGR Ref. No. 53699-722.60140 °C for 3 h. Compound 2 Form I was obtained with a yield of 71% and was characterized by PLM, XRPD, TGA, DSC, DVS and1H-NMR.

[0248] The sample was rod crystals under microscope. XRPD showed it was consistent with calculated Compound 2 Form I. Thermal analysis showed negligible weight loss before melting in TGA and one endothermic peak at 233.9 °C (onset) in DSC, due to melting (See Fig. 23). About 0.1% ACN was detected by ' H-NMR, and the salt ratio was determined to be 1 / 1 (B / A). IC result showed the content of sulfate anion was < LOQ (1000 ppm).

[0249] DVS result showed Compound 2 Form I was non-hygroscopic with water uptake of 0.18 / 0.19% at 80 / 90% RH (See Fig. 24). The crystal form was unchanged after DVS testing. Example 22: Solid-state Study of Form of (7R,14R)-l-(difluoromethoxy)-ll-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one besylate (Compound 2 Form I)

[0250] Solid-state stability trials of Compound 2 Form I was conducted at 60 °C (capped) and 40 °C / 75% RH (open) for 1, 2 and 6 weeks. The stability sample was dissolved in ACN / water (9 / 1, v / v) to prepare a solution at ~ 0.25 mg / mL for HPLC purity analysis. Solid sample was characterized by XRPD to check the crystal form. The results are summarized in Table 42 below. Compound 2 Form I was physically and chemically stable under tested conditions for 6 weeks.Table 42: Solid-state Stability Results for Compound 2 Form IExample 23: Mechanical Stability Study of Form of (7R,14R)-l-(difluoromethoxy)-ll-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6.,7-dihvdro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one besylate (Compound 2 Form I)

[0251] An appropriate amount of Compound 2 Form I was manually ground by pestle and mortar for 2 and 5 minutes. The ground samples were analyzed by XRPD. The crystal form ofWSGR Ref. No. 53699-722.601Form I remained unchanged with little crystallinity decrease after grinding for 5 min, indicating acceptable mechanical stability.Example 24: Competitive Slurry Study of Form of (7R,14R)-l-(difluoromethoxy)-ll-(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6.,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate (Compound 2 Form I)

[0252] The peak at 5.8° (20) appeared randomly in many different solvents and could not be separated. Competitive slurry experiments were performed. About 15 mg of Compound 2 Form 1 + 5.8° were suspended in 1 mL solvent (pre-saturated by Form I) at RT or 50 °C. Then samples were collected by filtration at certain time and characterized by XRPD

[0253] The results are presented in Table 43 below. Compound 2 Form I + 5.8° converted to pure Compound 2 Form I in ACN at RT and 50 °C, in THF at 50 °C and in anisole at RT for 3 daysTable 43. Competitive Slurry of Compound 2 Form IExample 25: Additional Polymorph Screening Tests of Compound 2 FormExample 25A: Preliminary Solubility Test

[0254] The solubility of Compound 2 Form I was estimated by visual observation.Approximately 5 mg solids were weighed into 8 mL glass vial, and then solvent was added stepwise until solids were dissolved completely or a total of solvent volume reached 5 mL. The results are summarized in Table 44 below. Compound 2 Form I showed distributed solubility in tested solvents. Values are reported as”>” if clear solution was observed and as “<” if dissolution was not observed.WSGR Ref. No. 53699-722.601Table 44. Estimated Solubility Results of Compound 2 Form IExample 25B: Slurry Conversion

[0255] About 20 mg of Compound 2 Form I was added into different solvents to make suspensions which were kept stirring at RT and 50 °C for up to 7 days and at 75 °C for 3 days. Solid samples were collected by filtration and analyzed by XRPD. The results are presented in Tables 45-47 below. Oil was obtained in water. Form I or Form 1 + 5.8° was obtained in other tested solvents.Table 45. Results of Slurry at RTTable 46. Results of Slurry at 50 °CWSGR Ref. No. 53699-722.601Table 47. Results of Slurry at 75 °CExample 25C: Evaporation Crystallization

[0256] Evaporation crystallization was performed in eight selected solvents according to the solubility data. Clear solutions or suspensions of Compound 2 Form I were prepared in selected solvents at RT. After filtration, the filtrate was covered with pin-hole film and placed at ambient condition for slow evaporation. The results are summarized in Table 48 below. Form I was obtained by evaporation in DCM, MeOH / MEK and MeOHZEA, and amorphous solid was obtained in the other tested solvents.Table 48. Evaporation ResultsWSGR Ref. No. 53699-722.601Example 25D: Cooling Crystallization

[0257] Cooling crystallization was performed in ten selected solvents. About 15 mg of Compound 2 Form I was weighed into a glass vial, and then selected solvent was added to make a suspension with stirring at 60 °C for ~30 min. If clear solution was observed, more solids would be added. After hot filtration, the filtrate was placed at RT for cooling crystallization. If no precipitation occurred, the filtrate was further cooled to 4 °C and -20 °C. Solid samples were collected by filtration and analyzed by XRPD. The results are summarized below in Table 49. Compound 2 Form I was obtained by cooling crystallization in IP A, ACN and ACN / water (99 / 1, v / v).Table 49. Cooling Crystallization ResultsExample 25E: Cyclic Heating-cooling

[0258] Cyclic heating-cooling experiments were carried out in Crystal 16 Parallel Crystallizer.About 15 mg of Compound 2 Form I was added into 1 mL solvents, and a heating-cooling program was performed:1. Equilibrate first at 20 °C, and heat to 75 or 100 °C at 10 °C / min2. Hold at 75 or 100 °C for 0.5 h3. Cool to 20 °C at 0.2 °C / min, and hold for 0.5 h.4. Repeat the above procedures once

[0259] Turbidimeter from Crystal 16 recorded if the solids were completely dissolved during heating. The results are presented in Table 50 below. Compound 2 Form I or Compound 2 Form 1 + 5.8° was obtained in tested solvents.Table 50. Cyclic Heating-cooling ResultsWSGR Ref. No. 53699-722.601Example 25F: Anti-solvent Precipitation

[0260] Anti-solvent precipitation was performed according to solubility data. An appropriate amount of Compound 2 Form I was weighed into 8-mL glass vials and then selected solvent was added to make a clear solution at RT. After filtration, anti-solvent was added in steps into the filtrate until solids precipitated out or 5 mL of anti-solvent was reached. If precipitation occurred, solids were isolated by filtration and characterized accordingly.

[0261] The results are summarized in Table 51 below. Compound 2 Form I + 5.8° was obtained in MeOH / toluene and MeOH / MTBE, and pure Compound 2 Form I was obtained in other tested solvents.WSGR Ref. No. 53699-722.601Table 51. Anti-solvent Precipitation ResultsExample 25G: Investigation of Extra Diffraction Peaks

[0262] In the salt screen, Compound 2 Form I was obtained by reaction with 1.1 eq. BsOH in IP Ac. Then Compound 2 Form I was scaled up for ~2.7 g at the same condition using BsOH and the collected Compound 2 Form I was used for polymorph screening. During polymorph screening, three extra diffraction peaks were found at 6.9°, 6.5° and 5.8° (20) in many conditions, named as pkl, pk2 and pk3 for convenience, respectively.

[0263] In polymorph screening, pure pkl could be isolated in DCM, and it converted to pure pk2 after slurry in 2-MeTHF. XRPD patterns of pkl and pk2 were consistent with Sulfate Forms I and II (See Example 1), which was caused by residual sulfuric acid in BsOH. Sulfate wasWSGR Ref. No. 53699-722.601 supposed to have much lower solubility than besylate. Therefore, high-grade BsOH is needed to prepare Compound 2 Form I.

[0264] The diffraction peaks of pkl and pk2 disappeared when using high-grade BsOH, while pk3 was still existed during polymorph screening. Two samples of Compound 2 Form 1 + 5.8° were prepared by anti-solvent precipitation in MeOH / toluene. Compound 2 Form I + 5.8° was analyzed by TGA and DSC, and the results showed negligible weight loss before melting and one endothermic peak at 216.7 °C (onset) (See Fig. 32), lower than the melting point of 233.9 °C for Compound 2 Form I (See Fig. 23). The crystal form remained unchanged after heating to 190 °C. Another sample of Compound 2 Form I + 5.8° was analyzed by 'H-NMR, IC and HPLC. The salt ratio was 1 : 1, sulfate anion was < LOQ (1000 ppm) and the purity was 98.21%, slightly lower than 99.62% purity of starting material.

[0265] In an effort to obtain pure form containing pk3, different methods were tried, including reaction with 2 eq. of BsOH, slurry at 70 °C with extended time (MIBK; 2-Me THF), reverse anti-solvent precipitation and exposing amorphous solid to high humidity. But no pure phase of pk3 was obtained. Process solvents should be screened to assess the formation of the additional peak at 5.8° (20) when applying mechanical stirring.Example 26: Scale up Synthesis of Crystalline Form III of (7R,14R)-l-(difluoromethoxy)- ll-(4-(dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6.,7-dihydro-7,14- methanobenzo[f]benzo[4.,5]imidazo[l.,2-a][l.,4]diazocin-5(14H)-one phosphate (Compound 3)

[0266] Compound 3 Form III was scaled up and fully characterized by PLM, XPRD, DSC, TGA and 'H-NMR. The hygroscopicity was tested by DVS, and only salt with acceptable hygroscopicity would be selected for solubility and stability study.

[0267] About 325 mg of Compound 1 Form I was stirred in 1.5 mL of EtOH at 50 °C. Then 2.1 eq. of H3PO4 was pre-diluted in EtOH and the acid solution was added into the suspension. A small amount of seed was added and the resulting mixture was stirred at 50 °C for 1 d. The suspension was filtered under nitrogen protection, and the filter cake was vacuum dried at 40 °C for ~ 3 h. Compound 3 Form III was obtained with a yield of 60% and characterized by PLM, XPRD, DSC, TGA, DVS and 'H-NMR. The sample showed irregular crystals under microscope and the crystal form was consistent with Compound 3 Form III. Thermal analysis showed negligible weight loss before melting in TGA and two adjacent endothermic peaks at 240 °C (onset) in DSC. Negligible EtOH was detected by 'H-NMR and the salt ratio was determined to 1 : 1 by IC. DVS result (See Fig. 31) showed Compound 3 Form III was slightly hygroscopic withWSGR Ref. No. 53699-722.601 water uptake of 0.24 / 0.63% at 80 / 90% RH, and the crystal form remained unchanged after DVS testing.Example 27: Stability and Solubility of Compound 1 Form I, Compound 2 Form I, and Compound 3 Form III

[0268] Based on the salt screen results, Compound 2 Form I and Compound 3 Form III were selected for solubility and stability evaluation, and were compared with Compound 1 Form I. Example 27 A: Solid-state Stability

[0269] Solid-state stability trials of Compound 2 Form I and Compound 3 Form III were conducted at 60 °C (capped) and 40 °C / 75% RH (open) for 7 days. The stability sample was dissolved in ACN / water (9 / 1, v / v) to prepare solution at ~ 0.25 mg / mL for purity analysis. Solid samples were analyzed by XRPD to check the crystal form.

[0270] The results are summarized in Table 52 below. No form change or obvious purity decrease was observed for the stability samples. The three solid forms were all physically and chemically stable at 60 °C (capped) and 40 °C / 75% RH (open) for 7 days.Table 52. Solid-state Stability Study ResultsExample 27B: Solubility in Bio-relevant Media

[0271] The solubility trials of Compound 1 Form I, Compound 2 Form I and Compound 3 Form III were measured in bio-relevant media (SGF, FaSSIF and FeSSIF) and water at 37 °C with 800 rpm for up to 24 h. About 9-12 mg of target forms were weighed into sample vials, and then 1.8 mL of three bio-relevant media and water were added to make suspensions with freebase equivalent of 5 mg / mL. At 0.5, 2 and 24 h, about 0.6 mL of each suspension was filtered, the filtrate was analyzed by HPLC and pH meter, and the filter cake was analyzed by XRPD.Results are summarized below in Table 53. LOQ is 0.125 pg / mL, AM = amorphous solid, and means difficult to isolate because of high viscosity.

[0272] Compared to Compound 1 Form I, Compound 2 Form I and Compound 3 Form III showed higher solubility (~2 folds) in FaSSIF at 0.5 h, indicating that the salts might provideWSGR Ref. No. 53699-722.601 rapid dissolution. In SGF and FeSSIF, the two salts showed similar solubility with free base.Compound 2 and Compound 3 showed similar solubility profile in each medium, but Compound 2 showed some slower gelling trend.Table 53. Results of Solubility Test in Bio-relevant Media

[0273] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

WSGR Ref. No. 53699-722.601CLAIMS1. A solid form of (7R, 14R)-l-(difluorom ethoxy)- 11 -(4-(dimethylphosphoryl)-3 - fluorophenyl)- 10-fluoro-6-(methyl-d3 )-6, 7-dihy dro-7, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one, depicted below as Compound 1,Compound 1 wherein the solid form is crystalline.

2. The solid form of claim 1, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.1° ± 0.3.

3. The solid form of claim 2, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 10.3° ± 0.3 and 17.7° ± 0.3.

4. The solid form of claim 2 or 3, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 12.6° ± 0.3, 17.3° ± 0.3, and 24.0° ± 0.3.

5. The solid form of any one of claims 2 to 4, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.5° ± 0.3, 21.0° ± 0.3, and 25.3° ± 0.3.

6. The solid form of any one of claims 2 to 5, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.5° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, and 24.3° ± 0.3.

7. The solid form of claim 1, wherein the solid form exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3.

8. The solid form of claim 1, wherein the solid form exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3.WSGR Ref. No. 53699-722.6019. The solid form of claim 1, wherein the solid form exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3.

10. The solid form of claim 1, wherein the solid form exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3.

11. The solid form of claim 1, wherein the solid form exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3.

12. The solid form of claim 1, wherein the solid form exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 10.3° ± 0.3, 12.6° ± 0.3, 14.5° ± 0.3, 17.3° ± 0.3, 17.7° ± 0.3, 19.1° ± 0.3, 19.5° ± 0.3, 21.0° ± 0.3, 22.8° ± 0.3, 23.7° ± 0.3, 24.0° ± 0.3, 24.3° ± 0.3, and 25.3° ± 0.3.

13. The solid form of claim 1, wherein the solid form exhibits the X-ray powder diffraction pattern as shown in Figure 1.

14. The solid form of any one of claims 1 to 13, wherein the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 259.3 °C ± 5.0.

15. The solid form of any one of claims 1 to 13, wherein the solid form exhibits the differential scanning calorimetry thermogram as shown in Figure 2.

16. The solid form of any one of claims 1 to 13, wherein the solid form exhibits a weight loss of 0% ± 2.0 between 50 and 300 °C ± 10.0 as determined by thermogravimetric analysis.

17. The solid form of any one of claims 1 to 13, wherein the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 2.

18. The solid form of any one of claims 1 to 13, wherein the amount of other crystalline or amorphous forms is 10% (w / w) or less.

19. The solid form of any one of claims 1 to 13, wherein the amount of other crystalline or amorphous forms is 5% (w / w) or less.

20. The solid form of any one of claims 1 to 13, wherein the amount of other crystalline or amorphous forms is 1% (w / w) or less.WSGR Ref. No. 53699-722.60121. The solid form of any one of claims 1 to 13, wherein the solid form has a chemical purity of 97% or more.

22. The solid form of any one of claims 1 to 13, wherein the solid form has a chemical purity of 98% or more.

23. The solid form of any one of claims 1 to 13, wherein the solid form has a chemical purity of 99% or more.

24. The solid form of any one of claims 1 to 13, wherein the solid form has a chemical purity of 99.5% or more.

25. A solid form of (7R, 14R)-l-(difluorom ethoxy)- 11 -(4-(dimethylphosphoryl)-3 - fluorophenyl)- 10-fluoro-6-(methyl-d3 )-6, 7-dihy dro-7, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate, depicted below as Compound 2,Compound 2 wherein the solid form is crystalline.

26. The solid form of claim 25, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.9° ± 0.3.

27. The solid form of claim 26, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 22.1° ± 0.3 and 27.8° ± 0.3.

28. The solid form of claim 26 or 27, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 16.9° ± 0.3, 17.6° ± 0.3, and 18.5° ± 0.3.

29. The solid form of any one of claims 26 to 28, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.7° ± 0.3, 16.4° ± 0.3, and 19.4° ± 0.3.

30. The solid form of any one of claims 26 to 29, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 8.4° ± 0.3, 9.4° ± 0.3, and 26.1° ± 0.3.WSGR Ref. No. 53699-722.60131. The solid form of any one of claims 26 to 30, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 12.8° ± 0.3, 13.5° ± 0.3, 20.9° ± 0.3, and 24.8° ± 0.3.

32. The solid form of any one of claims 26 to 31, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.7° ± 0.3, 18.9° ± 0.3, 23.5° ± 0.3, and 27.5° ± 0.3.

33. The solid form of claim 25, wherein the solid form exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ±0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ±0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ±0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3.

34. The solid form of claim 25, wherein the solid form exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ±0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ±0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3.

35. The solid form of claim 25, wherein the solid form exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ±0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ±0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ±0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3.

36. The solid form of claim 25, wherein the solid form exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ±0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ±0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3.

37. The solid form of claim 25, wherein the solid form exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ±0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ±0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ±0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3.

38. The solid form of claim 25, wherein the solid form exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ±WSGR Ref. No. 53699-722.6010.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ±0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ±0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3.

39. The solid form of claim 25, wherein the solid form exhibits at least seven X-ray powder diffraction reflections selected from the group consisting of 8.4° ± 0.3, 9.4° ± 0.3, 9.7° ± 0.3, 12.8° ± 0.3, 13.5° ± 0.3, 14.7° ± 0.3, 16.4° ± 0.3, 16.9° ± 0.3, 17.6° ± 0.3, 18.5° ±0.3, 18.9° ± 0.3, 19.4° ± 0.3, 19.9° ± 0.3, 20.9° ± 0.3, 22.1° ± 0.3, 23.5° ± 0.3, 24.8° ±0.3, 26.1° ± 0.3, 27.5° ± 0.3, and 27.8° ± 0.3.

40. The solid form of claim 25, wherein the solid form exhibits the X-ray powder diffraction pattern as shown in Figure 22.

41. The solid form of any one of claims 25 to 40, wherein the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 236.2 °C ± 5.0.

42. The solid form of any one of claims 25 to 40, wherein the solid form exhibits the differential scanning calorimetry thermogram as shown in Figure 23.

43. The solid form of any one of claims 25 to 40, wherein the solid form exhibits a weight loss of 0% ± 2.0 between 30 and 230 °C ± 10.0 as determined by thermogravimetric analysis.

44. The solid form of any one of claims 25 to 40, wherein the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 23.

45. The solid form of any one of claims 25 to 40, wherein the amount of other crystalline or amorphous forms is 10% (w / w) or less.

46. The solid form of any one of claims 25 to 40, wherein the amount of other crystalline or amorphous forms is 5% (w / w) or less.

47. The solid form of any one of claims 25 to 40, wherein the amount of other crystalline or amorphous forms is 1% (w / w) or less.

48. The solid form of any one of claims 25 to 40, wherein the solid form has a chemical purity of 97% or more.

49. The solid form of any one of claims 25 to 40, wherein the solid form has a chemical purity of 98% or more.

50. The solid form of any one of claims 25 to 40, wherein the solid form has a chemical purity of 99% or more.

51. The solid form of any one of claims 25 to 40, wherein the solid form has a chemical purity of 99.5% or more.WSGR Ref. No. 53699-722.60152. A solid form of (7R, 14R)-l-(difluorom ethoxy)- 11 -(4-(dimethylphosphoryl)-3 - fluorophenyl)- 10-fluoro-6-(methyl-d3 )-6, 7-dihy dro-7, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one phosphate, depicted below as Compound 3,Compound 3 wherein the solid form is crystalline.

53. The solid form of claim 52, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.4 ° ± 0.3.

54. The solid form of claim 53, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 10.5° ± 0.3 and 20.1° ± 0.3.

55. The solid form of claim 53 or 54, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 14.0° ± 0.3, 20.4° ± 0.3, and 23.5° ± 0.3.

56. The solid form of any one of claims 53 to 55, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3.

57. The solid form of any one of claims 53 to 56, wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 7.6 ° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, and 24.7° ± 0.3.

58. The solid form of claim 52, wherein the solid form exhibits at least one X-ray powder diffraction reflection selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3.

59. The solid form of claim 52, wherein the solid form exhibits at least two X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3.WSGR Ref. No. 53699-722.60160. The solid form of claim 52, wherein the solid form exhibits at least three X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3.

61. The solid form of claim 52, wherein the solid form exhibits at least four X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3.

62. The solid form of claim 52, wherein the solid form exhibits at least five X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3.

63. The solid form of claim 52, wherein the solid form exhibits at least six X-ray powder diffraction reflections selected from the group consisting of 7.6° ± 0.3, 10.5° ± 0.3, 14.0° ± 0.3, 14.3° ± 0.3, 16.1° ± 0.3, 19.4° ± 0.3, 20.1° ± 0.3, 20.4° ± 0.3, 23.5° ± 0.3, 24.7° ± 0.3, 25.4° ± 0.3, 25.9° ± 0.3, and 28.0° ± 0.3.

64. The solid form of claim 52, wherein the solid form exhibits the X-ray powder diffraction pattern as shown in Figure 29.

65. The solid form of any one of claims 52 to 64, wherein the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 245.5 °C ± 5.0.

66. The solid form of any one of claims 52 to 64, wherein the solid form exhibits the differential scanning calorimetry thermogram as shown in Figure 30.

67. The solid form of any one of claims 52 to 64, wherein the solid form exhibits a weight loss of 0% ± 2.0 between 50 and 230 °C ± 10.0 as determined by thermogravimetric analysis.

68. The solid form of any one of claims 52 to 64, wherein the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 30.

69. The solid form of any one of claims 52 to 64, wherein the amount of other crystalline or amorphous forms is 10% (w / w) or less.

70. The solid form of any one of claims 52 to 64, wherein the amount of other crystalline or amorphous forms is 5% (w / w) or less.

71. The solid form of any one of claims 52 to 64, wherein the amount of other crystalline or amorphous forms is 1% (w / w) or less.WSGR Ref. No. 53699-722.60172. The solid form of any one of claims 52 to 64, wherein the solid form has a chemical purity of 97% or more.

73. The solid form of any one of claims 52 to 64, wherein the solid form has a chemical purity of 98% or more.

74. The solid form of any one of claims 52 to 64, wherein the solid form has a chemical purity of 99% or more.

75. The solid form of any one of claims 52 to 64, wherein the solid form has a chemical purity of 99.5% or more.

76. A pharmaceutically acceptable salt of (7R, 14R)-l-(difhiorom ethoxy)- 11 -(4- (dimethylphosphoryl)-3-fluorophenyl)-10-fluoro-6-(methyl-d3)-6,7-dihydro-7,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one wherein the salt is selected from the group consisting of chloride, sulfate, tosylate, mesylate, maleate, phosphate, and besylate.

77. A compound (7R, 14R)-l-(difluorom ethoxy)- 11 -(4-(dimethylphosphoryl)-3 - fluorophenyl)- 10-fluoro-6-(methyl-d3 )-6, 7-dihy dro-7, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one besylate.

78. A compound (7R, 14R)-l-(difluorom ethoxy)- 11 -(4-(dimethylphosphoryl)-3 - fluorophenyl)- 10-fluoro-6-(methyl-d3 )-6, 7-dihy dro-7, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-5(14H)-one phosphate.

79. A pharmaceutical composition comprising the solid form of any one of claims 1-78, and a pharmaceutically acceptable excipient.

80. A method of preparing a pharmaceutical composition comprising mixing a solid form of any one of claims 1-78, and a pharmaceutically acceptable carrier.

81. A solid form of any one of claims 1-78 for use in a method of treatment of the human or animal body.

82. A solid form of any one of claims 1-78 for use in a method of treatment of inflammatory or autoimmune disease or disorder.

83. The use of claim 82, wherein the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasisjuvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-WSGR Ref. No. 53699-722.601 associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

84. Use of a solid form of any one of claims 1-78, in the manufacture of a medicament for the treatment of inflammatory or autoimmune disease or disorder.

85. The use of claim 84, wherein the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasisjuvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor- associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

86. A method of treating inflammatory or autoimmune disease or disorder in a patient in need thereof, the method comprising administering to the patient a solid form as described in any one of claims 1-78.

87. The method of claim 86, wherein the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis uvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor- associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

88. A method of treating inflammatory or autoimmune disease or disorder in a patient in need thereof, the method comprising administering to the patient a solid form as described in any one of claims 1-79 and a pharmaceutically acceptable excipient.

89. The method of claim 88, wherein the inflammatory or autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasisjuvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), inflammatory bowel diseases (IBD), Crohn’s disease, ulcerative colitis, systemic lupus erythematosus (SLE), spondyloarthritis (SpA), Behcet's disease, sarcoidosis, multiple sclerosis (MS), palmoplantar pustulosis (PPP), atopic dermatitis, graft versus host disease, sepsis, neuropathic pain, fibromyalgia, Schnitzler syndrome, Blau syndrome, TNF receptor-WSGR Ref. No. 53699-722.601 associated periodic syndrome (TRAPS), pyogenic arthritis, pyoderma Gangrenosum, and chronic recurrent multifocal osteomyelitis (CRMO).

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