1,4-dihydroquinazolinone compositions for the treatment of cardiac conditions

Abstract

Treatments of cardiovascular diseases, such as hypertrophic cardiomyopathy with compositions comprising (R)-N-(1-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-1,4-dihydroquinazolin-3(2H)-yl)acetamide or N-((R)-1-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-4-hydroxy-2-oxo-1,4-dihydroquinazolin-3(2H)-yl)acetamide, as well as solid forms of Compound 1 and pharmaceutical compositions of Compound 1 and Compound 2, are described herein.

Description

1,4-DIHYDROQUINAZOLINONE COMPOSITIONS FOR THE TREATMENT OFCARDIAC CONDITIONSCROSS-REFERENCE

[0001] This application claims the benefit of US Provisional Application Serial Number 63 / 633,654 filed on April 12, 2024, the entirety of which is hereby incorporated by reference herein; and US Provisional Application Serial Number 63 / 681,729 filed on August 9, 2024, the entirety of which is hereby incorporated by reference herein.BACKGROUND OF THE INVENTION

[0002] Hypertrophic cardiomyopathy HCM is a chronic, progressive disease of the cardiac sarcomere. The etiology of HCM is multifactorial; a significant portion of affected people have at least one mutation in the genes that encode cardiac sarcomere proteins. Regardless of the cause of HCM, in many cases, excess myosin-ac will tin crossbridge formation in systole and diastole leads to hyperdynamic contraction and impaired relaxation. Over time this excess stress leads to tissue remodeling characterized histologically by myocyte hypertrophy, myofilament disarray, microvascular remodeling, and fibrosis. HCM may be genetic (e.g., heritable) or not genetic. HCM includes a group of highly penetrant, monogenic, autosomal dominant myocardial diseases. Such HCM may be caused by one or more of over 1,000 known point mutations in any one of the proteins contributing to the functional unit of myocardium, the sarcomere. About 1 in 500 individuals in the general population are found to have left ventricular hypertrophy unexplained by other known causes (e.g., hypertension or valvular disease), and many of these can be shown to have HCM, e.g., once other heritable (e.g., lysosomal storage diseases), metabolic, or infiltrative causes have been excluded.

[0003] Medical therapy for HCM is limited and many patients’ symptoms are empirically managed with beta-blockers, non-dihydropyridine calcium channel blockers, and / or disopyramide. None of these agents carry labeled indications for treating HCM, and essentially no rigorous clinical trial evidence is available to guide their use. In approximately 60% of patients with HCM, the left ventricular outflow tract becomes obstructed, impeding the flow of blood and creating a pressure gradient between the LV cavity and the aorta. For patients with hemodynamically significant outflow tract obstruction (gradient >50 mmHg), surgical myectomy or alcohol septal ablation can be utilized to alleviate the hemodynamic obstruction albeit with significant clinical morbidity and mortality. Provided herein are new therapeutic agents and methods that remedy the long-felt need for improved treatment of HCM and related cardiac disorders.SUMMARY OF THE INVENTION

[0004] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject in need thereof a dose of about 5 mg to about 2000 mg per day of Compound 1 :

[0005] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject in need thereof a dose of about 5 mg to about 2000 mg per day of Compound 2:

[0006] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to reduce Left Ventricular Ejection Fraction (LVEF) by about 1% or more.

[0007] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 2 in an amount sufficient to reduce Left Ventricular Ejection Fraction (LVEF) by about 1% or more relevant to pretreatment levels.

[0008] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to maintain or modulate Left Ventricular Ejection Fraction (LVEF) to a range between about 0.40 and about 0.60.

[0009] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 2 in an amount sufficient to maintain or modulate Left Ventricular Ejection Fraction (LVEF) to a range between about 0.40 and about 0.60.

[0010] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to increase contractility of the left ventricle during isovolumic contraction.

[0011] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 2 in an amount sufficient to increase contractility of the left ventricle during isovolumic contraction.

[0012] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient to modulating left ventricular outflow tract (LVOT) gradient in the subject relative to pre-treatment by about 1% or more.

[0013] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient to modulating left ventricular outflow tract (LVOT) gradient in the subject relative to pre-treatment by about 1% or more.

[0014] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient to modulating protein concentration of one or more biomarkers in the subject relative to a pre-treatment protein concentration of the one or more biomarkers by about 5 % or more.

[0015] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient to modulating protein concentration of one or more biomarkers in the subject relative to a pre-treatment protein concentration of the one or more biomarkers by about 5 % or more.

[0016] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient achieve a plasma concentration Cmax level of between about 10 and about 2000 ng / mL.

[0017] Disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient achieve a plasma concentration Cmax level of between about 10 and about 2000 ng / mL.

[0018] Disclosed herein is a unit dose for oral administration, comprising Compound 1 in an amount from 5 mg to about 200 mg, and one or more pharmaceutically acceptable excipient(s). Disclosed herein is a unit dose for oral administration, comprising Compound 1 in an amount from 5 mg to about 200 mg, and pharmaceutically acceptable excipients.

[0019] Disclosed herein is a unit dose for oral administration, comprising Compound 2 in an amount from about 5 mg to about 200 mg, and one or more pharmaceutically acceptable excipient(s).Disclosed herein is a unit dose for oral administration, comprising Compound 2 in an amount from 5 mg to about 200 mg, and pharmaceutically acceptable excipients.

[0020] Disclosed herein is a kit, comprising an oral pharmaceutical composition and instructions for administration to a subject in need thereof, wherein the oral pharmaceutical composition comprises a compound of Compound 1 and one or more pharmaceutically acceptable excipient(s). Disclosed herein is a kit, comprising an oral pharmaceutical composition and instructions for administration toa subject in need thereof, wherein the oral pharmaceutical composition comprises a compound of Compound 1 and pharmaceutically acceptable excipients.

[0021] Disclosed herein is a kit, comprising an oral pharmaceutical composition and instructions for administration to a subject in need thereof, wherein the oral pharmaceutical composition comprises a compound of Compound 2 and one or more pharmaceutically acceptable excipient(s). Disclosed herein is a kit, comprising an oral pharmaceutical composition and instructions for administration to a subject in need thereof, wherein the oral pharmaceutical composition comprises a compound of Compound 2 and pharmaceutically acceptable excipients. Disclosed herein are solid forms of (R)-N- (l-(5-cy ano-3-fluoropyri din-2 -yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)- yljacetamide. In some embodiments, the solid forms are crystalline. In some embodiments, the solid form exhibits an X-ray powder diffraction pattern reflection at a 20 value of 13.0° ± 0.3°. Disclosed herein is a crystalline solid form of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2- oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits at least one X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. Disclosed herein is a crystalline solid form of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2- oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits at least one or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.3°,13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9°± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. Disclosed herein is a crystalline solid form of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits at least one or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°

[0022] Disclosed herein is a pharmaceutical composition comprising Compound 1 or Compound 2 and one or more pharmaceutically acceptable excipients.INCORPORATION BY REFERENCE

[0023] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patentapplication was specifically and individually indicated to be incorporated by reference. Patent publication WO2024073426 is herein incorporated by reference.BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages 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 (also “Figure” and “FIG.” herein), of which:

[0025] 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.

[0026] FIG. 1 Shows the X-ray diffraction pattern of crystalline Form 1.

[0027] FIG. 2 Shows the X-ray diffraction pattern of crystalline Form 2.

[0028] FIG. 3 Shows the X-ray diffraction pattern of crystalline Form 3.

[0029] FIG. 4 Shows the X-ray diffraction pattern of crystalline Form 4.

[0030] FIG. 5 Shows the X-ray diffraction pattern of crystalline Form 5.

[0031] FIG. 6 Shows the X-ray diffraction pattern of crystalline Form 6.

[0032] FIG. 7 Shows the X-ray diffraction pattern of crystalline Form 7.

[0033] FIG. 8 Shows the X-ray diffraction pattern of crystalline Form 8.

[0034] FIG. 9 Shows the X-ray diffraction pattern of crystalline Form 9.

[0035] FIG. 10 Shows the X-ray diffraction pattern of crystalline Form 10.

[0036] FIG. 11 Shows the X-ray diffraction pattern of crystalline Form 11.

[0037] FIG. 12 Shows the X-ray diffraction pattern of crystalline Form 12.

[0038] FIG. 13 Shows the X-ray diffraction pattern of crystalline Form 13.

[0039] FIG. 14 Shows the X-ray diffraction pattern of crystalline Form 14.

[0040] FIG. 15 Shows the X-ray diffraction pattern of crystalline Form 15.

[0041] FIG. 16 Shows the X-ray diffraction pattern of crystalline Form 16.

[0042] FIG. 17 Shows the X-ray diffraction pattern of crystalline Form 17.

[0043] FIG. 18 Shows the differential scanning calorimetry and thermogravimetric analysis of Form 1.

[0044] FIG. 19 Shows the differential scanning calorimetry and thermogravimetric analysis of Form 2.

[0045] FIG. 20 Shows the differential scanning calorimetry and thermogravimetric analysis of Form3.

[0046] FIG. 21 Shows the differential scanning calorimetry and thermogravimetric analysis of Form4.

[0047] FIG. 22 Shows the differential scanning calorimetry and thermogravimetric analysis of Form5.

[0048] FIG. 23 Shows the differential scanning calorimetry and thermogravimetric analysis of Form6.

[0049] FIG. 24 Shows the differential scanning calorimetry and thermogravimetric analysis of Form7.

[0050] FIG. 25 Shows the differential scanning calorimetry and thermogravimetric analysis of Form8.

[0051] FIG. 26 Shows the differential scanning calorimetry and thermogravimetric analysis of Form9.

[0052] FIG. 27 Shows the differential scanning calorimetry and thermogravimetric analysis of Form10.

[0053] FIG. 28 Shows the differential scanning calorimetry and thermogravimetric analysis of Form11.

[0054] FIG. 29 Shows the differential scanning calorimetry and thermogravimetric analysis of Form12.

[0055] FIG. 30 Shows the differential scanning calorimetry and thermogravimetric analysis of Form13.

[0056] FIG. 31 Shows the differential scanning calorimetry and thermogravimetric analysis of Form14.

[0057] FIG. 32 Shows the differential scanning calorimetry and thermogravimetric analysis of Form15.

[0058] FIG. 33 Shows the differential scanning calorimetry and thermogravimetric analysis of Form16.

[0059] FIG. 34 Shows the differential scanning calorimetry and thermogravimetric analysis of Form17.

[0060] FIG. 35 Shows the thermal treatment profile of crystalline Form 9.

[0061] FIG. 36 Shows the dynamic vapor sorption plot and dynamic vapor sorption mass plot of Form 9.

[0062] FIG. 37 Shows the X-ray diffraction pattern of Form 9 after dynamic vapor sorption testing.

[0063] FIG. 38 Shows the dynamic vapor sorption plot and dynamic vapor sorption mass plot of Form 12.

[0064] FIG. 39 Shows the X-ray diffraction pattern of Form 12 after dynamic vapor sorption testing.

[0065] FIG. 40 Shows the interconversion studies of Form 1 into Form 12.

[0066] FIG. 41 Shows the overlaid X-ray diffraction pattern of Form 12 water activity studies

[0067] FIG. 42 Shows the overlaid X-ray diffraction patterns and high performance liquid chromatography (HPLC) chromatograms of Form 12 stability samples

[0068] FIG. 43 Shows the photomicrograph of Compound 1 single crystals

[0069] FIG. 44 Shows the asymmetric unit of Compound 1 crystal structure

[0070] FIG. 45 Shows the mean plasma concentrations at various doses of Compounds 1 and 2

[0071] FIG. 46 Shows LVOT-G Responses in the Absence of Intra-Patient Dose-Optimization for the efficacy evaluable population

[0072] FIG. 47 Shows LVOT-G Response in the Absence of Intra-Patient Dose-Optimization for the safety population

[0073] FIG. 48 Shows NT-proBNP levels in participants with oHCM for the safety population

[0074] FIG. 49 Shows a plot of e’ vs. time for the safety population

[0075] FIG. 50 Shows a depiction of changes in left ventrictular disastolic for the safety population

[0076] FIG. 51 Shows a Plot of KCQQ-OSS for the safety population

[0077] FIG. 52 Shows NT-proBNP levels in participants with nHCM

[0078] FIG. 53 Shows Diastolic improvements vs. time in nHCM patients

[0079] FIG. 54 Shows LVEF in patients with oHCM

[0080] FIG. 55 Shows LVEF in patientsiwth nHCMDETAILED DESCRIPTION OF THE INVENTION

[0081] 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.

[0082] In certain aspects, the disclosure provides methods for treating a cardiac disease in an individual in need thereof, the method comprising administering a therapeutically effective amountof Compound 1. Compound 1 is shown below as (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2- (5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide.(J?)-A-(l-(5-cyano-3-fhjoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2Z / )- yl)acetamideIn certain aspects, the disclosure provides methods for treating a cardiac disease in an individual in need thereof, the method comprising administering a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof.

[0083] In certain aspects, the disclosure provides methods for treating a cardiac disease in an individual in need thereof, the method comprising administering a therapeutically effective amount of Compound 2. Compound 2 is shown below as N-((R)-l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2- (5,6-difluoro-4-hydroxy-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide.7V-((A)-l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-4-hydroxy-2-oxo-l,4-dihydroquinazolin- 3 (2J7)-yl )acetami de. In certain aspects, the disclosure provides methods for treating a cardiac disease in an individual in need thereof, the method comprising administering a therapeutically effective amount of Compound 2 or a pharmaceutically acceptable salt thereof.

[0084] Diseases treated by the methods described herein include, but are not limited to, cardiac diseases. Cardiac diseases treated by the method described herein include, but are not limited to, heart muscle disease (cardiomyopathy), hypertrophic cardiomyopathy (HCM), abnormal heart rhythms, aorta disease, Marfan syndrome, coronary artery disease, heart attack, heart failure, rhematic heart disease, peripheral vascular disease, stroke, deep vein thrombosis and pulmonary embolism.

[0085] Cardiomyopathy is a heart disease wherein the heart may be abnormally enlarged, thicked, and / or stiffened and may have few or no symptoms early on. As the disease gets worse, symptoms include, but are not limited to, shortness of breath, feeling tired, irregular heartbeat, fainting, and onset of heart failure. Types of cardiomyopathy include, but are not limited to arrhythmogenic rightventricular dysplasia, dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and Takotsubo cardiomyopathy.

[0086] Hypertrophic cardiomyopathy (HCM) may be genetic (e.g., heritable) or not genetic. HCM may be obstructive or nonobstructive. Genetic hypertrophic cardiomyopathy (HCM) comprises a group of highly penetrant, monogenic, autosomal dominant myocardial diseases. HCM may be caused by one or more of over 1,000 known point mutations in any one of the proteins contributing to the functional unit of myocardium, the sarcomere.

[0087] In approximately two-thirds of HCM subjects, the path followed by blood exiting the heart, known as the left ventricular outflow tract (LVOT), becomes obstructed by the enlarged and diseased muscle, restricting the flow of blood from the heart to the rest of the body (obstructive HCM). In other subjects, the thickened heart muscle does not block the LVOT, and their disease is driven by diastolic impairment due to the enlarged and stiffened heart muscle (non-obstructive HCM). In either obstructive or non-obstructive HCM subjects, exertion can result in fatigue or shortness of breath, interfering with a subject’s ability to participate in activities of daily living. HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and sudden cardiac death.

[0088] Currently available therapies for HCM are variably effective in alleviating symptoms but may show decreased efficacy with increasing disease duration. Patients may be thus empirically managed with beta-blockers, non-dihydropyridine calcium channel blockers, and / or disopyramide.Mavacamten may also be used. In approximately 60% of patients with HCM, the left ventricular outflow tract becomes obstructed, impeding the flow of blood and creating a pressure gradient between the LV cavity and the aorta. For patients with hemodynamically significant outflow tract obstruction (gradient >50 mmHg), surgical myectomy or alcohol septal ablation can be utilized to alleviate the hemodynamic obstruction albeit with significant clinical morbidity and mortality. Provided are new therapeutic agents and methods that remedy the long-felt need for improved treatment of HCM and related cardiac disorders.

[0089] The compounds of the invention or their pharmaceutically acceptable salts can alter the natural history of HCM and other diseases rather than merely palliating symptoms. The mechanisms conferring clinical benefit to HCM patients can extend to patients with other forms of heart disease sharing similar pathophysiology, with or without demonstrable genetic influence. For example, an effective treatment for HCM, by improving ventricular relaxation during diastole, can also be effective in a broader population characterized by diastolic dysfunction. The compounds of the invention or their pharmaceutically acceptable salts can specifically target the root causes of the conditions or act upon other downstream pathways. Accordingly, the compounds of the invention or their pharmaceutically acceptable salts can also confer benefit to patients suffering from diastolicheart failure with preserved ejection fraction, ischemic heart disease, angina pectoris, or restrictive cardiomyopathy. Compounds of the invention or their pharmaceutically acceptable salts can also promote salutary ventricular remodeling of left ventricular hypertrophy due to volume or pressure overload; e.g., chronic mitral regurgitation, chronic aortic stenosis, or chronic systemic hypertension; in conjunction with therapies aimed at correcting or alleviating the primary cause of volume or pressure overload (valve repair / replacement, effective antihypertensive therapy). By reducing left ventricular filling pressures the compounds could reduce the risk of pulmonary edema and respiratory failure. Reducing or eliminating functional mitral regurgitation and / or lowering left atrial pressures may reduce the risk of paroxysmal or permanent atrial fibrillation, and with it reduce the attendant risk of arterial thromboembolic complications including but not limited to cerebral arterial embolic stroke. Reducing or eliminating either dynamic and / or static left ventricular outflow obstruction may reduce the likelihood of requiring septal reduction therapy, either surgical or percutaneous, with their attendant risks of short- and long term complications. The compounds or their pharmaceutically acceptable salts may reduce the severity of the chronic ischemic state associated with HCM and may thereby reduce the risk of Sudden Cardiac Death (SCD) or its equivalent in patients with implantable cardioverter-defibrillators (frequent and / or repeated ICD discharges) and / or the need for potentially toxic anti arrhythmic medications. The compounds or their pharmaceutically acceptable salts could be valuable in reducing or eliminating the need for concomitant medications with their attendant potential toxicities, drug-drug interactions, and / or side effects. The compounds or their pharmaceutically acceptable salts may reduce interstitial myocardial fibrosis and / or slow the progression, arrest, or reverse left ventricular hypertrophy.Definitions

[0090] 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.

[0091] The phrase “compounds of the invention” refers to Compound 1 and Compound 2.

[0092] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.

[0093] The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrastemal injection and infusion.

[0094] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0095] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” as used herein includes a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution;(19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic compatible substances employed in pharmaceutical formulations.

[0096] As used herein, “treatment” or “treating” refers to an approach for obtaining beneficial or desired results with respect to a disease, disorder, or medical condition including but not limited to a therapeutic benefit and / or a prophylactic benefit. A therapeutic benefit can include, for example, the eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit can include, for example, the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. In certain embodiments, for prophylactic benefit, the compositions are administered to a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made. Treatment via administration of a compound described herein does not require the involvement of a medical professional.

[0097] The terms “hydrate” and “solvate” are meant to describe crystalline forms, e.g., of Compound 1, that include an amount of water or solvent, e.g., as supported by data derived from differentialscanning calorimetry (DSC) experiments, thermogravimetric analysis (TGA) experiments, X-ray diffraction experiments, 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 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 of 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.

[0098] 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.

[0099] The terms “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 1 of Compound 1,” “crystalline hydrate Form 1 of Compound 1,” and “XRPD Pattern 1 of Compound 1” refer to the same crystalline matter (e.g., the same crystalline phase of Compound 1).

[0100] 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.

[0101] 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.Therapeutic Applications

[0102] Methods of administration of Compound 1 (and e.g., solid forms thereof), or Compound 2, or a pharmaceutically acceptable salt thereof, discussed herein may be used for the treatment of diseases and disorders resulting from the dysfunction of muscle myosin. Methods of administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof, discussed herein may be used for the treatment of diseases and disorders through the modulation of muscle myosin. In some embodiments, the muscle myosin is cardiac muscle myosin (e.g., of ventircular or atrial tissue). In some embodiments, the muscle myosin is cardiac muscle myosin. One embodiment provides use of Compound 1 (or a solid form thereof, or a pharmaceutical composition thereof, or apharmaceutical composition comprising a solid form thereof) or Compound 2 (or a pharmaceutical composition thereof) provided herein in the manufacture of a medicament for the treatment of human disease (e.g., cardiovascular disease or a related condition, e.g., HCM, e.g., HFpEF).

[0103] Methods of administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof, discussed herein may be used for the treatment of diseases and disorders through the modulation of myosin cross-bridge cycling.

[0104] Methods of administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof, may be used for the modulation of cardiac muscle myosin. Methods of administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof, may be used for the treatment of cardiovascular disease or a related condition. In some embodiments, the cardiovascular disease or a related condition is selected from: hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HFpEF); heart failure with reduced ejection fraction (HFrEF); dilated cardiomyopathy (DCM); ischemic cardiomyopathy; cardiac transplant allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease; left ventricular (LV) hypertrophy; ischemia; angina; chronic heart failure; toxic cardiomyopathy; myocarditis; and acute and chronic decompensated heart failure optionally resulting from any of the the he cardiovascular disease or a related conditions disclosed herein. In some embodiments, said heart failure with preserved ejection fraction (HFpEF) comprises one or more disorders selected from disorders of relaxation and disorders of chamber stiffness (diabetic HFpEF). In some embodiments, said left ventricular (LV) hypertrophy comprises malignant left ventricular (LV) hypertrophy. In some embodiments, said restrictive cardiomyopathy comprises one or more subgroups selected from inflammatory subgroups, infiltrative subgroups, storage subgroups, idiopathic / inherited subgroups, congenital heart disease subgroups. In some embodiments, said inflammatory subgroups comprise one or more subgroups selected from Loefflers, EMF, amyloid, sarcoid, and XRT. In some embodiments, said storage subgroups comprise one or more subgroups selected from hemochromatosis, Fabry, and glycogen storage disease. In some embodiments, said idiopathic / inherited subgroups comprise one or more subgroups selected from Trop I (beta myosin HC), Trop T (alpha cardiac actin), and desmin related subgroups. In some embodiments, said congenital heart disease subgroups comprise one or more subgroups selected from pressure-overloaded RV, Tetralogy of Fallot, and pulmonic stenosis. In some embodiments, the cardiovascular disease or a related condition is hypertrophy cardiomyopathy. In some embodiments, hypertrophic cardiomyopathy is obstructive hypertrophic cardiomyopathy or non-obstructive hypertrophic cardiomyopathy. In some embodiments, hypertrophic cardiomyopathy is obstructive hypertrophic cardiomyopathy. In some embodiments, hypertrophic cardiomyopathy is non-obstructive hypertrophic cardiomyopathy. In someembodiments, cardiovascular disease or a related condition comprises heart failure with preserved ejection fraction. In some embodiments, cardiovascular disease or a related condition comprises left ventricle stiffness.

[0105] Methods of administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof, may be used for the modulation of cardiac muscle myosin. Methods of administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof, may be used for the treatment of cardiovascular disease or a related condition. Examples of cardiovascular disease or a related condition include but are not limited to heart attack, heart failure, heart infection, endocarditis, myocarditis, pericarditis, arrhythmia, abnormal heart rhythms, aorta disease, Marfan syndrome, vascular disease, stroke, congenital heart disease, coronary artery disease, rhematic heart disease, peripheral vascular disease, heart valve disease, pericardial disease, heart muscle disease, cardiomyopathy, deep vein thrombosis, and embolism (e.g., pulmonary embolism). Examples of heart infections include but are not limited to endocarditis, myocarditis, and pericarditis.

[0106] In some embodiments, the present disclosure provides a method of treating a condition selected from hypertrophic cardiomyopathy (HCM). In some embodiments, the present disclosure provides a method of treating a condition selected from hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HFpEF); disorders of relaxation; disorders of chamber stiffness (diabetic HFpEF); dilated cardiomyopathy (DCM); ischemic cardiomyopathy; cardiac transplant allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease (e.g., aortic stenosis - including elderly post AVR / TAVR and congenital forms); left ventricular (LV) hypertrophy; ischemia; and angina. In some embodiments, the present disclosure provides a compound for use in treating one or more condition(s) selected from: hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HFpEF); disorders of relaxation; disorders of chamber stiffness (diabetic HFpEF); dilated cardiomyopathy (DCM); ischemic cardiomyopathy; cardiac transplant allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease (e.g., aortic stenosis - including elderly post AVR / TAVR and congenital forms); left ventricular (LV) hypertrophy; ischemia; and angina. In some embodiments, said heart failure with preserved ejection fraction (HFpEF) comprises one or more disorders selected from disorders of relaxation and disorders of chamber stiffness (diabetic HFpEF). In some embodiments, said heart failure with preserved ejection fraction (HFpEF) comprises HFpEF related to hypertension. In some embodiments, said heart failure with preserved ejection fraction (HFpEF) comprises HFpEF related to aortic valvular disease. In some embodiments, said left ventricular (LV) hypertrophy is malignant left ventricular (LV) hypertrophy. In some embodiments, said restrictive cardiomyopathy comprises one or more subgroups selected from inflammatory subgroups, infiltrative subgroups, storagesubgroups, idiopathic / inherited subgroups, congenital heart disease subgroups. In some embodiments, said inflammatory subgroups comprise one or more subgroups selected from Loefflers and EMF. In some embodiments, said inflammatory subgroups comprise one or more subgroups selected from amyloid, sarcoid, and XRT. In some embodiments, said storage subgroups comprise one or more subgroups selected from hemochromatosis, Fabry, and glycogen storage disease. In some embodiments, said idiopathic / inherited subgroups comprise one or more subgroups selected from Trop I (beta myosin HC), Trop T (alpha cardiac actin), and desmin related subgroups. In some embodiments, said congenital heart disease subgroups comprise one or more subgroups selected from pressure-overloaded RV, Tetralogy of Fallot, and pulmonic stenosis. In an aspect, the present disclosure provides a method of treating hypertrophic cardiomyopathy or a related condition comprising administering to a subject in need thereof a compound or salt disclosed herein (e.g., Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof). In an aspect, the present disclosure provides a method of treating obstructive hypertrophic cardiomyopathy comprising administering to a subject in need thereof a compound or salt disclosed herein. In an aspect, the present disclosure provides a method of treating non-obstructive hypertrophic cardiomyopathy comprising administering to a subject in need thereof a compound or salt of disclosed herein. In an aspect, the present disclosure provides a method of treating heart failure with preserved ejection fraction comprising administering to a subject in need thereof a compound or disclosed herein. In an aspect, the present disclosure provides a method of treating left ventricle stiffness comprising administering to a subject in need thereof a compound or salt disclosed herein. In an aspect, the present disclosure provides a method of treating a condition selected from hypertrophic cardiomyopathy (HCM); disorders of relaxation; ischemic cardiomyopathy; cardiac transplant allograft vasculopathy; restrictive cardiomyopathy; left ventricular (LV) hypertrophy; ischemia; and andangin, the method comprising administering a ventricular-selective agent.

[0107] In an aspect, the present disclosure provides methods of treating atrial cardiopathy, Heart failure with ejection fraction (e.g., Heart failure with preserved ejection fraction (HFpEF), Heart failure with reduced ejection fraction (HFrEF)), arrhythmia (e.g., Atrial fibrillation), stroke (e.g., Cardioembolic stroke, Cryptogenic stroke), valve disease (e.g., Mitral valve disease, or Tricuspid valve disease), comprises administering an atrial-selective agent. In an aspect, the present disclosure provides methods of treating atrial cardiopathy, Heart failure with preserved ejection fraction (HFpEF), Heart failure with reduced ejection fraction (HFrEF), Atrial fibrillation, Cardioembolic stroke, Cryptogenic stroke, Mitral valve disease, or Tricuspid valve disease. In some embodiments, the method comprises administering an atrial-selective agent. In an aspect, the present disclosure provides methods of treating atrial cardiopathy. In some embodiments, the present disclosureprovides a method of treating HFpEF. In some embodiments, the present disclosure provides a method of treating HFrEF. In some embodiments, the present disclosure provides a method of treating Atrial fibrillation. In some embodiments, the present disclosure provides a method of treating Cardioembolic stroke. In some embodiments, the present disclosure provides a method of treating Cryptogenic stroke. In some embodiments, the present disclosure provides a method of treating Mitral valve disease. In some embodiments, the present disclosure provides a method of treating Tricuspid valve disease. In some embodiments, the present disclosure provides a method of treating one or more diseases selected from atrial cardiopathy, HFpEF, HFrEF, Atrial fibrillation, Cardioembolic stroke, Cryptogenic stroke, Mitral valve disease, and Tricuspid valve disease. In some embodiments, the method comprises administering Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof. In some embodiments, Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof is for use in treating one or more diseases selected from atrial cardiopathy, HFpEF, HFrEF, Atrial fibrillation, Cardioembolic stroke, Cryptogenic stroke, Mitral valve disease, and Tricuspid valve disease, comprises an atrial-selective agent. In some embodiments, the atrial-selective agent selectively inhibits atrial myosin relative to ventricular myosin or relative to skeletal myosin.

[0108] In an aspect, disclosed herein are methods to treat cardiovascular disease or a related condition by the administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the cardiovascular disease or related condition is selected from hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HFpEF); disorders of relaxation; disorders of chamber stiffness (diabetic HFpEF); dilated cardiomyopathy (DCM); ischemic cardiomyopathy; cardiac transplant allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease (e.g., aortic stenosis - including elderly post AVR / TAVR and congenital forms); left ventricular (LV) hypertrophy; ischemia; angina; and myocarditis. In some embodiments, the condition is cardiac dysfunction related to acute or chronic myocarditis. In some embodiments, the myocarditis is parasitic, bacterial, viral, or non-infectious. In some embodiments, the myocarditis is auto-immune myocarditis. In some embodiments, the myocarditis is eosinophilic myocarditis. In some embodiments, said heart failure with preserved ejection fraction (HFpEF) comprises one or more disorders selected from disorders of relaxation and disorders of chamber stiffness (diabetic HFpEF). In some embodiments, said left ventricular (LV) hypertrophy is malignant left ventricular (LV) hypertrophy. In some embodiments, said restrictive cardiomyopathy comprises one or more subgroups selected from inflammatory subgroups, infiltrative subgroups, storage subgroups, idiopathic subgroups, inherited subgroups, congenital heart disease subgroups. In some embodiments, said inflammatory subgroups comprise one or more subgroups selected fromLoefllers and EMF. In some embodiments, said inflammatory subgroups comprise one or more subgroups selected from amyloid, sarcoid, and radiation (e.g., XRT, radiation therapy, or radiation injury). In some embodiments, said storage subgroups comprise one or more subgroups selected from hemochromatosis, Fabry, and glycogen storage disease. In some embodiments, said inherited subgroups is related to conditions associated with Troponin I (beta myosin Heavy Chain), Troponin T (e.g. alpha cardiac actin), or desmin. In some embodiments, said congenital heart disease subgroups comprises one or more subgroups selected from pressure-overloaded right ventricle (RV), Tetralogy of Fallot, and pulmonic stenosis. In an aspect, the present disclosure provides a method of treating hypertrophic cardiomyopathy or a related condition comprising administering to a subject in need thereof a compound or salt disclosed herein. In some embodiments, the cardiomyopathy is a toxic cardiomyopathy. In some embodiments, disclosed herein are methods to treat toxic cardiomyopathy by the administration of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the toxic cardiomyopathy is related to exposure to chemotherapeutic agents, ethanol, cocaine, other toxic substances, or any combination thereof.

[0109] In an aspect, the present disclosure provides a method of treating obstructive hypertrophic cardiomyopathy comprising administering to a subject in need thereof a compound or salt disclosed herein. In an aspect, the present disclosure provides a method of treating non-obstructive hypertrophic cardiomyopathy comprising administering to a subject in need thereof a compound or salt of disclosed herein. In an aspect, the present disclosure provides a method of treating heart failure with preserved ejection fraction comprising administering to a subject in need thereof a compound or disclosed herein. In an aspect, the present disclosure provides a method of treating left ventricle stiffness comprising administering to a subject in need thereof a compound or salt disclosed herein.

[0110] In some embodiments, the present disclosure provides a method of treating dilated (DCM) cardiomyopathy. In some embodiments, the present disclosure provides a method of treating sudden cardiac death.[OHl] In an aspect, the present disclosure provides a method of treating a cardiovascular disease or a related condition, the method comprising administering Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof to a subject in need thereof. In some embodiments, administering Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof modulates the subject’s heart rate (HR), end diastolic volume (EDV), or fractional shortening (FS). In some embodiments, the administering the compound or salt increases the subject’s HR. In some embodiments, the administering the compound or salt increases the subject’s FS. In some embodiments, the administering the compound or salt increases the subject’s EDV. In someembodiments, the administering the compound or salt decreases the subject’s HR. In some embodiments, the administering the compound or salt decreases the subject’s FS. In some embodiments, the administering the compound or salt decreases the subject’s EDV. In some embodiments the administering the compound or salt does not change (e.g., does not significantly change) the subject’s HR. In some embodiments the administering the compound or salt does not change (e.g., does not significantly change) the subject’s FS. In some embodiments the administering the compound or salt does not change (e.g., does not significantly change) the subject’s EDV. In some embodiments, the administering the compound or salt modulates an index of left- ventricular fractional shortening (FS) and systolic wall-thickening index (SWT). In some embodiments, the administering the compound or salt modulates an index of left- ventricular fractional shortening (FS). In some embodiments, the administering the compound or salt modulates an index of systolic wall-thickening index (SWT). In some embodiments, administering the compound or salt of any one of Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof modulates the subject’s isovolumic contraction time (IVCT), or Pre-ejection period, or isovolumic relaxation time (IVRT), or ejection fraction (EF). In some embodiments, the administering the compound or salt increases the subject’s IVCT. In some embodiments, the administering the compound or salt increases the subject’s Pre-ejection period. In some embodiments, the administering the compound or salt increases the subject’s IVRT. In some embodiments, the administering the compound or salt increases the subject’s EF. In some embodiments, the administering the compound or salt decreases the subject’s IVCT. In some embodiments, the administering the compound or salt decreases the subject’s Pre-ejection period. In some embodiments, the administering the compound or salt decreases the subject’s IVRT. In some embodiments, the administering the compound or salt decreases the subject’s EF. In some embodiments, the administering the compound or salt does not change (e.g., does not significantly change) the subject’s IVCT. In some embodiments, the administering the compound or salt does not change (e.g., does not significantly change) the subject’s Pre-ejection period. In some embodiments, the administering the compound or salt does not change (e.g., does not significantly change) the subject’s IVRT. In some embodiments, the administering the compound or salt does not change (e.g., does not significantly change) the subject’s EF. In some embodiments, the administering the compound or salt modulates actomyosin cycling rates. In some embodiments, the administering the compound or salt modulates peak E-wave velocity (E). In some embodiments, the administering the compound or salt modulates peak A-wave velocity (A). In some embodiments, the administering the compound or salt modulates peak early diastolic mitral annular velocity (e’). In some embodiments, E-wave and A-wave may refer two distinct periods of filling of the ventricle (e.g., left ventricle) withblood from the atrium (e.g., left atrium), e.g., wherein the E-wave may occur early in diastole, and e.g., wherein the A-wave may occur late in diastole, e.g., when the atrium contracts. In some embodiments, the change in HR, FS, SWT, IVCT, IVRT, EF, or pre-ejection period is from about 1% from baseline to about 30% from baseline.

[0112] In some embodiments, the method comprising administering Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof and further comprises further comprising administering an additional active agent.

[0113] In an aspect, the present disclosure provides a pharmaceutical composition comprising a steer and one or more excipient(s) (e.g., one or more pharmaceutically acceptable excipient(s)).

[0114] In an aspect, the present disclosure provides a method of modulating a light chain (e.g., a myosin light chain). Alternatively, or in addition, in some embodiments, the present disclosure provides a method of modulating a heavy chain (e.g., a myosin heavy chain). In some embodiments, a compound or salt of the present disclosure (e.g., Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof) modulates a light chain. In some embodiments, a compound or salt of the present disclosure modulates a regulatory light chain (RLC) (e.g., a myosin regulatory light chain). In some embodiments, a compound or salt of the present disclosure modulates an essential light chain (ELC) (e.g., a myosin essential light chain). In some embodiments, the regulatory light chain is a cardiac myosin regulatory light chain. In some embodiments, the modulating the regulatory light chain is inhibiting the regulatory light chain (e.g., inhibiting the function of the RLC). Alternatively, or in addition, in some embodiments, the modulating the rlc is activating the RLC (e.g., activating the function of the RLC). In some embodiments, the method changes the ability of a myosin lever arm to develop force. In some embodiments, the method modulates cross bridge cycling. In some embodiments, administering the compound or salt overcomes a disturbance in an interaction between myosin regulatory light chain and myosin heavy chain. In some embodiments, the disturbance is caused by a genetic mutation. In some embodiments, the method of modulating an RLC is for use in treating hypertrophic cardiomyopathy. In some embodiments, a compound or salt of the present disclosure directly binds myosin RLC. Alternatively, on in addition, in some embodiments, a compound or salt of the present disclosure indirectly modulates one or more other protein(s) (e.g., other sarcomeric protein(s), or e.g., protein(s) other than myosin RLC). In some embodiments, a compound or salt of the present disclosure indirectly modulates myosin or myosin binding protein C, or one or more thin-filament protein(s).

[0115] In some embodiments, the compound or salt is an inhibitor of myosin ATP-ase. In some embodiments, administering a compound of the present disclosure modulates ATP cycling rates of one or more sarcomeric protein(s) (e.g., actomyosin cycling). In some embodiments, administering acompound of the present disclosure activates ATP cycling rates of sarcomeric proteins. Alternatively, in some embodiments, administering a compound of the present disclosure inhibits ATP cycling rates of sarcomeric proteins. In some embodiments, the modulating ATP cycling rates of sarcomeric proteiens is through interactions (e.g., binding) with one or more sarcomere protein(s) (e.g., myosin, myosin regulatory light chain, myosin essential light chain, or myosin binding protein- c).

[0116] In some embodiments, administering a compound or salt of the present disclosure modulates actin floating on myosin. In some embodiments, administering a compound or salt of the present disclosure modulates actin floating on myosin in a different way than a direct myosin inhibitor modulates actin floating on myosin (e.g., as shown in a Motility assay).

[0117] In an aspect, administering a compound or salt of the disclosure (e.g., Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof) modulates one or more sarcomeric protein(s). In an aspect, administering a compound or salt of the disclosure (e.g., Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof) modulates a myosin (e.g., myosin in cardiac muscle, myosin in skeletal muscle). In an aspect, administering a compound or salt of the disclosure (e.g., Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof) modulates a myosin light chain (e.g., essential myosin light chain, regulatory myosin light chain). In some embodiments, administering a compound or salt of the disclosure modulates a regulatory light chain (e.g., myosin regulatory light chain). In some embodiments, the compound or salt of the disclosure inhibits a regulatory light chain. Alternatively, in some embodiments, the compound or salt of the disclosure activates a myosin regulatory light chain.

[0118] In an aspect, administering a compound of the present disclosure treats a patient (e.g., with HCM) through modulation of a myosin regulatory light chain (e.g., cardiac myosin regulatory light chain).

[0119] In some embodiments, the patient to which a compound of the present disclosure is administered exhibits a myosin heavy chain mutation (e.g., on chromosome 14 ql 1.2-3, e.g., MYH7). In some embodiments, the patient exhibits a P-myosin heavy chain mutation (e.g., on chromosome 14 ql 1.2-3, e.g., MYH7). In some embodiments, the patient exhibits an insertion / deletion polymorphism in the gene encoding for angiotensin converting enzyme (e.g., ACE). In some embodiments, the patient with the insertion / deletion polymorphism in the gene encoding for ACE exhibits more marked hypertrophy of the left ventricle. In some embodiments, the patient exhibits a troponin mutation (e.g., troponin T or troponin C). In some embodiments, the patient exhibits a myosin binding protein C (MYBPC) mutation. In some embodiments, the patient exhibits a myosin 7 mutation. In some embodiments, the patient exhibits multiple mutations selectedfrom troponin, RLC, MYBPC, myosin 7, myosin heavy chain, and ACE. In some embodiments, the patient exhibits multiple mutations selected from troponin, RLC, MYBPC, and myosin 7.

[0120] In some embodiments, the patient to which a compound of the present disclosure is administered exhibits a myosin regulatory light chain mutation (e.g., E22K mutation). In some embodiments, the myosin regulatory light chain mutation disturbs the interaction of myosin regulatory light chain with myosin heavy chain. In some embodiments, the disturbance in the interaction between myosin regulatory light chain and myosin heavy chain leads to structural abnormalities in the myosin cross bridge (e.g., in the myosin cross bridge, e.g., in the lever arm of the myosin cross bridge). In some embodiments, the mutation in the myosin regulatory light chain leads to reduced contractility. In some embodiments, the mutation in the myosin regulatory light chain leads to decreased cardiac output.

[0121] In some embodiments, modulation of the myosin regulatory light chain overcomes a disturbance in an interaction between myosin regulatory light chain and myosin heavy chain (e.g., which leads to structural abnormalities in the myosin cross bridge, e.g., in the lever arm of the myosin cross bridge). In some embodiments, administering a compound of the present disclosure (e.g., to a patient with an RLC mutation) changes a myosin lever arm’s ability to develop force. In some embodiments, the myosin lever arm’s changed ability to develop force results in slowed contraction. In some embodiments, the myosin lever arm’s changed ability to develop force results in accelerated relaxation. In some embodiments, the myosin lever arm’s changed ability to develop force results in slowed contraction and accelerated relaxation. In some embodiments, this helps overcome mutations (e.g., that enhance the proportion of force-developing myosin heads, e.g., HCM mutations). In some embodiments, this action (e.g., slowed contraction or accelerated relaxation) is greater at low calcium (e.g., diastolic) compared to high calcium (e.g., systolic) (e.g., which may modulate its inhibitory action as the heart contracts and relaxes). In some embodiments, modulation of the myosin regulatory light chain leads to reduced contractility. In some embodiments, modulation of the myosin regulatory light chain leads to decreased cardiac output. In some embodiments, modulation of the myosin regulatory light chain leads to slowing of early contraction (e.g., resulting from slower walking of myosin heads along actin). In some embodiments, the slowing of early contraction is used to treat HCM (e.g., obstructive HCM, oHCM). In some embodiments, treatment through this mechanism is administered for genetic HCM or non-genetic HCM.

[0122] In some embodiments, one or more cardiac mutation(s) (e.g., a mutation in the myosin regulatory light chain) in a patient (e.g., a patient with HCM) modulate(s) a spatial gradient of myosin regulatory light chain phosphorylation (e.g., modulate relative to that in the heart of a patient without HCM). In some embodiments, a mutation in the myosin regulatory light chain modulates thespatial gradient of myosin regulatory light chain phosphorylation. In some embodiments, a mutation in the myosin regulatory light chain decreases cardiac torsion (e.g., so that blood is less efficiently wrung out of the heart). In some embodiments, a mutation in the myosin regulatory light chain decreases cardiac torsion by altering the mechanism by which the spatial gradient of myosin light chain phosphorylation across the heart inversely alters tension production. In some embodiments, a mutation in the myosin regulatory light chain decreases cardiac torsion by altering the mechanism by which the spatial gradient of myosin light chain phosphorylation across the heart inversely alters the stretch activation response. In some embodiments, a mutation in the myosin regulatory light chain decreases cardiac torsion by modulating a mechanism by which the spatial gradient of myosin light chain phosphorylation across the heart inversely alters tension production and the stretch activation response. In some embodiments, treatment through this mechanism is administered for genetic HCM or non-genetic HCM.

[0123] In some embodiments, modulation of the myosin regulatory light chain increases cardiac torsion in a patient (e.g., with HCM) relative to a patient without HCM. In some embodiments, modulation of myosin regulatory light chain increases torsion by modulating the spatial gradient of myosin light chain phosphorylation across the heart.

[0124] In some embodiments, the myosin regulatory light chain mutation decreases calcium- activated tension. In some embodiments, the myosin regulatory light chain mutation decreases calcium-activated stiffness. In some embodiments, the myosin regulatory light chain mutation reduces myofilament Ca2+ sensitivity. In some embodiments, modulation of the myosin regulatory light chain increases calcium-activated tension. In some embodiments, modulation of the myosin regulatory light chain increases calcium-activated stiffness. In some embodiments, modulation of the myosin regulatory light chain increases myofilament Ca2+ sensitivity. In some embodiments, upon administration of a compound or salt of the present disclosure, changes in calcium sensitivity are length dependent. In some embodiments, upon administration of a compound or salt of the present disclosure, changes in calcium sensitivity are length dependent (e.g., except with decreases in calcium sensitivity at long sarcomere lengths). In some embodiments, administering a compound of the present disclosure changes calcium sensitivity. In some embodiments, administering a compound of the present disclosure changes calcium sensitivity when the sarcomere is stretched. In some embodiments, treatment through this mechanism is administered for genetic HCM or non-genetic HCM.

[0125] In an aspect, a compound of the present disclosure selectively inhibits function of ventricular myosin. In some embodiments, a compound of the present disclosure selectively inhibits function of ventricular myosin relative to atrial myosin. In some embodiments, a compound of the presentdisclosure selectively inhibits function of ventricular myosin relative to skeletal myosin. In some embodiments, a compound of the present disclosure selectively inhibits function of ventricular myosin relative to atrial myosin and skeletal myosin.

[0126] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject in need thereof a dose of about 5 mg to about 2000aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject in need thereof a dose of about 5 mg to about 2000 mg per day of Compound 2:. In some embodiments, the dose is about 5 mg to about 300 mg per day of the compound of Compound 1 or Compound 2. In some embodiments, the dose is about 10 mg to about 200 mg per day of the compound of Compound 1 or Compound 2. In some embodiments, the dose is about 15 mg to about 200 mg per day of the compound of Compound 1 or Compound 2. In some embodiments, the dose is about 25 mg to about 200 mg per day of the compound of Compound 1 or Compound 2. In some embodiments, the dose is about 50 mg to about 200 mg per day of the compound of Compound 1 or Compound 2. In some embodiments, the dose is about 75 mg to about 150 mg per day of the compound of Compound 1 or Compound 2. In some embodiments, the dose is about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, these tier 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, pacer 120 mg, about 125 mg, about 130 mg, about 135 mg, please dear 140 mg, about 145 mg, about 150 mg, about 175 mg, about 200 mg, exterior 250 mg, or a steer 300 mg per day of the compound of Compound 1 or Compound 2. In some embodiments, the dose per day is about 5 mg to about 2,000 mg. In some embodiments, the dose per day is about 5 mg to about 25 mg, about 5 mg to about 50 mg, about 5 mg to about 75 mg, about 5 mg to about 100 mg, about 5 mg to about 125 mg, about 5 mg to about 150 mg, about 5 mg to about 200 mg, about 5 mg to about 300 mg, about 5 mg to about 500 mg, about 5 mg to about 1,000 mg, about 5 mg to about 2,000 mg, about 25 mg to about 50 mg, about 25 mg to about 75 mg, about 25 mg to about 100 mg, about 25 mg to about 125 mg, about 25 mg to about 150 mg, about 25 mg toabout 200 mg, about 25 mg to about 300 mg, about 25 mg to about 500 mg, about 25 mg to about 1,000 mg, about 25 mg to about 2,000 mg, about 50 mg to about 75 mg, about 50 mg to about 100 mg, about 50 mg to about 125 mg, about 50 mg to about 150 mg, about 50 mg to about 200 mg, about 50 mg to about 300 mg, about 50 mg to about 500 mg, about 50 mg to about 1,000 mg, about 50 mg to about 2,000 mg, about 75 mg to about 100 mg, about 75 mg to about 125 mg, about 75 mg to about 150 mg, about 75 mg to about 200 mg, about 75 mg to about 300 mg, about 75 mg to about 500 mg, about 75 mg to about 1,000 mg, about 75 mg to about 2,000 mg, about 100 mg to about 125 mg, about 100 mg to about 150 mg, about 100 mg to about 200 mg, about 100 mg to about 300 mg, about 100 mg to about 500 mg, about 100 mg to about 1,000 mg, about 100 mg to about 2,000 mg, about 125 mg to about 150 mg, about 125 mg to about 200 mg, about 125 mg to about 300 mg, about 125 mg to about 500 mg, about 125 mg to about 1,000 mg, about 125 mg to about 2,000 mg, about 150 mg to about 200 mg, about 150 mg to about 300 mg, about 150 mg to about 500 mg, about 150 mg to about 1,000 mg, about 150 mg to about 2,000 mg, about 200 mg to about 300 mg, about 200 mg to about 500 mg, about 200 mg to about 1,000 mg, about 200 mg to about 2,000 mg, about 300 mg to about 500 mg, about 300 mg to about 1,000 mg, about 300 mg to about 2,000 mg, about 500 mg to about 1,000 mg, about 500 mg to about 2,000 mg, or about 1,000 mg to about 2,000 mg. In some embodiments, the dose per day is about 5 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 300 mg, about 500 mg, about 1,000 mg, or about 2,000 mg. In some embodiments, the dose per day is at least about 5 mg, about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 300 mg, about 500 mg, or about 1,000 mg. In some embodiments, the dose per day is at most about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 200 mg, about 300 mg, about 500 mg, about 1,000 mg, or about 2,000 mg. In some embodiments, the dose is about 25 mg, about 50 mg, about 100 mg, or about 200 mg.

[0127] In some embodiments, the dose of compound 1 is administered once per day. In some embodiments, the dose of compound 1 is administered twice per day (e.g., one dose in the morning, one dose at night). In some embodiments, the dose of compound 1 is administered three times per day. In some embodiments, the dose of compound 1 is administered four times per day.

[0128] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to reduce Left Ventricular Ejection Fraction (LVEF) by about 1% or more. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 2 in an amount sufficient to reduce Left Ventricular Ejection Fraction (LVEF) by about 1% or more relevant to pretreatment levels. In some embodiments, the LVEF is reducedabout by 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, about 20 %, or more. In some embodiments, the LVEF is reduced by about 1 % to about 20 %. In some embodiments, the LVEF is reduced by about 1% to about 10 %. In some embodiments, the LVEF is reduced by about 1% to about 5 %. In some embodiments, the LVEF is reduced by about 1 % to about 20 %. In some embodiments, the LVEF is reduced by about 1 % to about 2 %, about 1 % to about 3 %, about 1 % to about 4 %, about 1 % to about 5 %, about 1 % to about 6 %, about 1 % to about 7 %, about 1 % to about 8 %, about 1 % to about 9 %, about 1 % to about 10 %, about 1 % to about 15 %, about 1 % to about 20 %, about 2 % to about 3 %, about 2 % to about 4 %, about 2 % to about 5 %, about 2 % to about 6 %, about 2 % to about 7 %, about 2 % to about 8 %, about 2 % to about 9 %, about 2 % to about 10 %, about 2 % to about 15 %, about 2 % to about 20 %, about 3 % to about 4 %, about 3 % to about 5 %, about 3 % to about 6 %, about 3 % to about 7 %, about 3 % to about 8 %, about 3 % to about 9 %, about 3 % to about 10 %, about 3 % to about 15 %, about 3 % to about 20 %, about 4 % to about 5 %, about 4 % to about 6 %, about 4 % to about 7 %, about 4 % to about 8 %, about 4 % to about 9 %, about 4 % to about 10 %, about 4 % to about 15 %, about 4 % to about 20 %, about 5 % to about 6 %, about 5 % to about 7 %, about 5 % to about 8 %, about 5 % to about 9 %, about 5 % to about 10 %, about 5 % to about 15 %, about 5 % to about 20 %, about 6 % to about 7 %, about 6 % to about 8 %, about 6 % to about 9 %, about 6 % to about 10 %, about 6 % to about 15 %, about 6 % to about 20 %, about 7 % to about 8 %, about 7 % to about 9 %, about 7 % to about 10 %, about 7 % to about 15 %, about 7 % to about 20 %, about 8 % to about 9 %, about 8 % to about 10 %, about 8 % to about 15 %, about 8 % to about 20 %, about 9 % to about 10 %, about 9 % to about 15 %, about 9 % to about 20 %, about 10 % to about 15 %, about 10 % to about 20 %, or about 15 % to about 20 %. In some embodiments, the LVEF is reduced by about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %. In some embodiments, the LVEF is reduced by at least about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, or about 15 %. In some embodiments, the LVEF is reduced by at most about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %.

[0129] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient that does not modulate Left Ventricular Ejection Fraction (LVEF). In some embodiments, LVEF is modulated only very little. In some embodiments, LVEF is modulated by at most about 0%. In some embodiments, LVEF is modulated by at most about 0.5%. In some embodiments, LVEF is modulated by at most about 1%. In some embodiments, LVEF is modulated by at most about 1.5%.In some embodiments, LVEF is modulated by at most about 2.0%. In some embodiments, LVEF is modulated by at most about 2.5%. In some embodiments, LVEF is modulated by at most about 3.5%. In some embodiments, LVEF is modulated by at most about 4%. In some embodiments, LVEF is modulated by at most about 4.5%. In some embodiments, LVEF is modulated by at most about 5%. In some embodiments, LVEF is modulated by at most about 6%. In some embodiments, LVEF is modulated by at most about 7%. In some embodiments, LVEF is modulated by at most about 8%. In some embodiments, LVEF is modulated by at most about 9%. In some embodiments, LVEF is modulated by at most about 10%. In some embodiments, LVEF is modulated by at most about 15%. In some embodiments, LVEF is modulated by at most about 20%. In some embodiments, LVEF is modulated by about 0 % to about 10 %. In some embodiments, LVEF is modulated by at least about 0 %. In some embodiments, LVEF is modulated by at most about 10 %. In some embodiments, LVEF is modulated by about 0 % to about 0.1 %, about 0 % to about 0.25 %, about 0 % to about 0.5 %, about 0 % to about 0.75 %, about 0 % to about 1 %, about 0 % to about 2 %, about 0 % to about 3 %, about 0 % to about 4 %, about 0 % to about 5 %, about 0 % to about 7.5 %, about 0 % to about 10 %, about 0.1 % to about 0.25 %, about 0.1 % to about 0.5 %, about 0.1 % to about 0.75 %, about 0.1 % to about 1 %, about 0.1 % to about 2 %, about 0.1 % to about 3 %, about 0.1 % to about 4 %, about 0.1 % to about 5 %, about 0.1 % to about 7.5 %, about 0.1 % to about 10 %, about 0.25 % to about 0.5 %, about 0.25 % to about 0.75 %, about 0.25 % to about 1 %, about 0.25 % to about 2 %, about 0.25 % to about 3 %, about 0.25 % to about 4 %, about 0.25 % to about 5 %, about 0.25 % to about 7.5 %, about 0.25 % to about 10 %, about 0.5 % to about 0.75 %, about 0.5 % to about 1 %, about 0.5 % to about 2 %, about 0.5 % to about 3 %, about 0.5 % to about 4 %, about 0.5 % to about 5 %, about 0.5 % to about 7.5 %, about 0.5 % to about 10 %, about 0.75 % to about 1 %, about 0.75 % to about 2 %, about 0.75 % to about 3 %, about 0.75 % to about 4 %, about 0.75 % to about 5 %, about 0.75 % to about 7.5 %, about 0.75 % to about 10 %, about 1 % to about 2 %, about 1 % to about 3 %, about 1 % to about 4 %, about 1 % to about 5 %, about 1 % to about 7.5 %, about 1 % to about 10 %, about 2 % to about 3 %, about 2 % to about 4 %, about 2 % to about 5 %, about 2 % to about 7.5 %, about 2 % to about 10 %, about 3 % to about 4 %, about 3 % to about 5 %, about 3 % to about 7.5 %, about 3 % to about 10 %, about 4 % to about 5 %, about 4 % to about 7.5 %, about 4 % to about 10 %, about 5 % to about 7.5 %, about 5 % to about 10 %, or about 7.5 % to about 10 %. In some embodiments, LVEF is modulated by about 0 %, about 0.1 %, about 0.25 %, about 0.5 %, about 0.75 %, about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 7.5 %, or about 10 %. In some embodiments, LVEF is modulated by about 0 % to about 5 %. In some embodiments, LVEF is modulated by at least about 0 %. In some embodiments, LVEF is modulated by at most about 5 %. In some embodiments, LVEF is modulated by about 0 % to about 0.01 %, about 0 % to about 0.05%, about 0 % to about 0.1 %, about 0 % to about 0.2 %, about 0 % to about 0.3 %, about 0 % to about 0.4 %, about 0 % to about 0.5 %, about 0 % to about 0.75 %, about 0 % to about 1 %, about 0 % to about 2.5 %, about 0 % to about 5 %, about 0.01 % to about 0.05 %, about 0.01 % to about 0.1 %, about 0.01 % to about 0.2 %, about 0.01 % to about 0.3 %, about 0.01 % to about 0.4 %, about 0.01 % to about 0.5 %, about 0.01 % to about 0.75 %, about 0.01 % to about 1 %, about 0.01 % to about 2.5 %, about 0.01 % to about 5 %, about 0.05 % to about 0.1 %, about 0.05 % to about 0.2 %, about 0.05 % to about 0.3 %, about 0.05 % to about 0.4 %, about 0.05 % to about 0.5 %, about 0.05 % to about 0.75 %, about 0.05 % to about 1 %, about 0.05 % to about 2.5 %, about 0.05 % to about 5 %, about 0.1 % to about 0.2 %, about 0.1 % to about 0.3 %, about 0.1 % to about 0.4 %, about 0.1 % to about 0.5 %, about 0.1 % to about 0.75 %, about 0.1 % to about 1 %, about 0.1 % to about 2.5 %, about 0.1 % to about 5 %, about 0.2 % to about 0.3 %, about 0.2 % to about 0.4 %, about 0.2 % to about 0.5 %, about 0.2 % to about 0.75 %, about 0.2 % to about 1 %, about 0.2 % to about 2.5 %, about 0.2 % to about 5 %, about 0.3 % to about 0.4 %, about 0.3 % to about 0.5 %, about 0.3 % to about 0.75 %, about 0.3 % to about 1 %, about 0.3 % to about 2.5 %, about 0.3 % to about 5 %, about 0.4 % to about 0.5 %, about 0.4 % to about 0.75 %, about 0.4 % to about 1 %, about 0.4 % to about 2.5 %, about 0.4 % to about 5 %, about 0.5 % to about 0.75 %, about 0.5 % to about 1 %, about 0.5 % to about 2.5 %, about 0.5 % to about 5 %, about 0.75 % to about 1 %, about 0.75 % to about 2.5 %, about 0.75 % to about 5 %, about 1 % to about 2.5 %, about 1 % to about 5 %, or about 2.5 % to about 5 %. In some embodiments, LVEF is modulated by about 0 %, about 0.01 %, about 0.05 %, about 0.1 %, about 0.2 %, about 0.3 %, about 0.4 %, about 0.5 %, about 0.75 %, about 1 %, about 2.5 %, or about 5 %.

[0130] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to increase the subject’s Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS). In some embodiments, the KCCQ-OSS is increased by at least 1 point, at least 2 points, at least 3 points, at least 4 points, at least 5 points, at least 7 points, at least 10 points, at least 13 points, at least 17 points, at least 20 points, at least 23 points, at least 25 points, at least 30 points, at least 35 points, at least 40 points, or more. In some embodiments, the KCCQ-OSS is increased by about 1 point to about 40 points. In some embodiments, the KCCQ-OSS is increased by at least about 1 point. In some embodiments, the KCCQ-OSS is increased by at most about 40 points. In some embodiments, the KCCQ-OSS is increased by about 1 point to about 3 points, about 1 point to about 4 points, about 1 point to about 5 points, about 1 point to about 7 points, about 1 point to about 10 points, about 1 point to about 15 points, about 1 point to about 20 points, about 1 point to about 23 points, about 1 point to about 25 points, about 1 point to about 30 points, about 1 point to about 40 points,about 3 points to about 4 points, about 3 points to about 5 points, about 3 points to about 7 points, about 3 points to about 10 points, about 3 points to about 15 points, about 3 points to about 20 points, about 3 points to about 23 points, about 3 points to about 25 points, about 3 points to about 30 points, about 3 points to about 40 points, about 4 points to about 5 points, about 4 points to about 7 points, about 4 points to about 10 points, about 4 points to about 15 points, about 4 points to about 20 points, about 4 points to about 23 points, about 4 points to about 25 points, about 4 points to about 30 points, about 4 points to about 40 points, about 5 points to about 7 points, about 5 points to about 10 points, about 5 points to about 15 points, about 5 points to about 20 points, about 5 points to about 23 points, about 5 points to about 25 points, about 5 points to about 30 points, about 5 points to about 40 points, about 7 points to about 10 points, about 7 points to about 15 points, about 7 points to about 20 points, about 7 points to about 23 points, about 7 points to about 25 points, about 7 points to about 30 points, about 7 points to about 40 points, about 10 points to about 15 points, about 10 points to about 20 points, about 10 points to about 23 points, about 10 points to about 25 points, about 10 points to about 30 points, about 10 points to about 40 points, about 15 points to about 20 points, about 15 points to about 23 points, about 15 points to about 25 points, about 15 points to about 30 points, about 15 points to about 40 points, about 20 points to about 23 points, about 20 points to about 25 points, about 20 points to about 30 points, about 20 points to about 40 points, about 23 points to about 25 points, about 23 points to about 30 points, about 23 points to about 40 points, about 25 points to about 30 points, about 25 points to about 40 points, or about 30 points to about 40 points. In some embodiments, the KCCQ-OSS is increased by about 1 point, about 3 points, about 4 points, about 5 points, about 7 points, about 10 points, about 15 points, about 20 points, about 23 points, about 25 points, about 30 points, or about 40 points.

[0131] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to increase the subject’s Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-CSS). In some embodiments, the KCCQ-CSS is increased by at least 1 point, at least 2 points, at least 3 points, at least 4 points, at least 5 points, at least 7 points, at least 10 points, at least 13 points, at least 17 points, at least 20 points, at least 23 points, at least 25 points, at least 30 points, at least 35 points, at least 40 points, or more. In some embodiments, the KCCQ-CSS is increased by about 1 point to about 40 points. In some embodiments, the KCCQ-CSS is increased by at least about 1 point. In some embodiments, the KCCQ-CSS is increased by at most about 40 points. In some embodiments, the KCCQ-CSS is increased by about 1 point to about 3 points, about 1 point to about 4 points, about 1 point to about 5 points, about 1 point to about 7 points, about 1 point to about 10 points, about 1 point to about 15 points, about 1 point to about 20 points, about 1 point to about 23 points,about 1 point to about 25 points, about 1 point to about 30 points, about 1 point to about 40 points, about 3 points to about 4 points, about 3 points to about 5 points, about 3 points to about 7 points, about 3 points to about 10 points, about 3 points to about 15 points, about 3 points to about 20 points, about 3 points to about 23 points, about 3 points to about 25 points, about 3 points to about 30 points, about 3 points to about 40 points, about 4 points to about 5 points, about 4 points to about 7 points, about 4 points to about 10 points, about 4 points to about 15 points, about 4 points to about 20 points, about 4 points to about 23 points, about 4 points to about 25 points, about 4 points to about 30 points, about 4 points to about 40 points, about 5 points to about 7 points, about 5 points to about 10 points, about 5 points to about 15 points, about 5 points to about 20 points, about 5 points to about 23 points, about 5 points to about 25 points, about 5 points to about 30 points, about 5 points to about 40 points, about 7 points to about 10 points, about 7 points to about 15 points, about 7 points to about 20 points, about 7 points to about 23 points, about 7 points to about 25 points, about 7 points to about 30 points, about 7 points to about 40 points, about 10 points to about 15 points, about 10 points to about 20 points, about 10 points to about 23 points, about 10 points to about 25 points, about 10 points to about 30 points, about 10 points to about 40 points, about 15 points to about 20 points, about 15 points to about 23 points, about 15 points to about 25 points, about 15 points to about 30 points, about 15 points to about 40 points, about 20 points to about 23 points, about 20 points to about 25 points, about 20 points to about 30 points, about 20 points to about 40 points, about 23 points to about 25 points, about 23 points to about 30 points, about 23 points to about 40 points, about 25 points to about 30 points, about 25 points to about 40 points, or about 30 points to about 40 points. In some embodiments, the KCCQ-CSS is increased by about 1 point, about 3 points, about 4 points, about 5 points, about 7 points, about 10 points, about 15 points, about 20 points, about 23 points, about 25 points, about 30 points, or about 40 points.

[0132] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to increase Mitral Annulus Velocity (e’). In some embodiments, e’ is increased by at least about 1%, at least about 2%, at least about 3%, at least about 5%, at least about 10%, at least about 12.5%, at least about 15%, at least about 17.5%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 25%, at least about 27.5, at least about 30%, at least about 35%, at least about 40%, or more. In some embodiments, e’ is increased by at most about 1%, at most about 2%, at most about 3%, at most about 5%, at most about 10%, at most about 12.5%, at most about 15%, at most about 17.5%, at most about 20%, at most about 21%, at most about 22%, at most about 23%, at most about 25%, at most about 27.5, at most about 30%, at most about 35%, at most about 40%, or less. In some embodiments, e’ is increased by about 1 % to about 50 %. In some embodiments, e’ isincreased by at least about 1 %. In some embodiments, e’ is increased by at most about 50 %. In some embodiments, e’ is increased by about 1 % to about 5 %, about 1 % to about 10 %, about 1 % to about 15 %, about 1 % to about 17.5 %, about 1 % to about 20 %, about 1 % to about 21 %, about 1 % to about 22.5 %, about 1 % to about 25 %, about 1 % to about 30 %, about 1 % to about 40 %, about 1 % to about 50 %, about 5 % to about 10 %, about 5 % to about 15 %, about 5 % to about 17.5 %, about 5 % to about 20 %, about 5 % to about 21 %, about 5 % to about 22.5 %, about 5 % to about 25 %, about 5 % to about 30 %, about 5 % to about 40 %, about 5 % to about 50 %, about 10 % to about 15 %, about 10 % to about 17.5 %, about 10 % to about 20 %, about 10 % to about 21 %, about 10 % to about 22.5 %, about 10 % to about 25 %, about 10 % to about 30 %, about 10 % to about 40 %, about 10 % to about 50 %, about 15 % to about 17.5 %, about 15 % to about 20 %, about 15 % to about 21 %, about 15 % to about 22.5 %, about 15 % to about 25 %, about 15 % to about 30 %, about 15 % to about 40 %, about 15 % to about 50 %, about 17.5 % to about 20 %, about 17.5 % to about 21 %, about 17.5 % to about 22.5 %, about 17.5 % to about 25 %, about 17.5 % to about 30 %, about 17.5 % to about 40 %, about 17.5 % to about 50 %, about 20 % to about 21 %, about 20 % to about 22.5 %, about 20 % to about 25 %, about 20 % to about 30 %, about 20 % to about 40 %, about 20 % to about 50 %, about 21 % to about 22.5 %, about 21 % to about 25 %, about 21 % to about 30 %, about 21 % to about 40 %, about 21 % to about 50 %, about 22.5 % to about 25 %, about 22.5 % to about 30 %, about 22.5 % to about 40 %, about 22.5 % to about 50 %, about 25 % to about 30 %, about 25 % to about 40 %, about 25 % to about 50 %, about 30 % to about 40 %, about 30 % to about 50 %, or about 40 % to about 50 %. In some embodiments, e’ is increased by about 1 %, about 5 %, about 10 %, about 15 %, about 17.5 %, about 20 %, about 21 %, about 22.5 %, about 25 %, about 30 %, about 40 %, or about 50 %.

[0133] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to maintain or modulate Left Ventricular Ejection Fraction (LVEF) to a range between about 0.40 and about 0.60. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 2 in an amount sufficient to maintain or modulate Left Ventricular Ejection Fraction (LVEF) to a range between about 0.40 and about 0.60. In some embodiments, the range of LVEF is about 0.45 to about 0.55. In some embodiments, the range of LVEF is about 0.5 to about 0.6. In some embodiments, the LVEF is about 0.45 to about 0.6. In some embodiments, the LVEF is about 0.45 to about 0.5, about 0.45 to about 0.51, about 0.45 to about 0.52, about 0.45 to about 0.53, about 0.45 to about 0.54, about 0.45 to about 0.55, about 0.45 to about 0.56, about 0.45 to about 0.57, about 0.45 to about 0.58, about 0.45 to about 0.59, about 0.45 to about 0.6, about 0.5 to about 0.51, about 0.5 to about 0.52, about 0.5 to about 0.53,about 0.5 to about 0.54, about 0.5 to about 0.55, about 0.5 to about 0.56, about 0.5 to about 0.57, about 0.5 to about 0.58, about 0.5 to about 0.59, about 0.5 to about 0.6, about 0.51 to about 0.52, about 0.51 to about 0.53, about 0.51 to about 0.54, about 0.51 to about 0.55, about 0.51 to about 0.56, about 0.51 to about 0.57, about 0.51 to about 0.58, about 0.51 to about 0.59, about 0.51 to about 0.6, about 0.52 to about 0.53, about 0.52 to about 0.54, about 0.52 to about 0.55, about 0.52 to about 0.56, about 0.52 to about 0.57, about 0.52 to about 0.58, about 0.52 to about 0.59, about 0.52 to about 0.6, about 0.53 to about 0.54, about 0.53 to about 0.55, about 0.53 to about 0.56, about 0.53 to about 0.57, about 0.53 to about 0.58, about 0.53 to about 0.59, about 0.53 to about 0.6, about 0.54 to about 0.55, about 0.54 to about 0.56, about 0.54 to about 0.57, about 0.54 to about 0.58, about 0.54 to about 0.59, about 0.54 to about 0.6, about 0.55 to about 0.56, about 0.55 to about 0.57, about 0.55 to about 0.58, about 0.55 to about 0.59, about 0.55 to about 0.6, about 0.56 to about 0.57, about 0.56 to about 0.58, about 0.56 to about 0.59, about 0.56 to about 0.6, about 0.57 to about 0.58, about 0.57 to about 0.59, about 0.57 to about 0.6, about 0.58 to about 0.59, about 0.58 to about 0.6, or about 0.59 to about 0.6. In some embodiments, the LVEF is about 0.45, about 0.5, about 0.51, about 0.52, about 0.53, about 0.54, about 0.55, about 0.56, about 0.57, about 0.58, about 0.59, or about 0.6. In some embodiments, the LVEF is at least about 0.45, about 0.5, about 0.51, about 0.52, about 0.53, about 0.54, about 0.55, about 0.56, about 0.57, about 0.58, or about 0.59. In some embodiments, the LVEF is at most about 0.5, about 0.51, about 0.52, about 0.53, about 0.54, about 0.55, about 0.56, about 0.57, about 0.58, about 0.59, or about 0.6.

[0134] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to increase contractility of the left ventricle during isovolumic contraction. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 2 in an amount sufficient to increase contractility of the left ventricle during isovolumic contraction. In some embodiments, the contractility of the left ventricle is increased by about 1% or more. In some embodiments, the contractility of the left ventricle is increased by about by 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, about 20 %, or more. In some embodiments, the contractility of the left ventricle is increased by about 1 % to about 20 %. In some embodiments, the contractility of the left ventricle is increased by about 1% to about 10 %. In some embodiments, the contractility of the left ventricle is increased by about 1% to about 5 %. In some embodiments, contractility is measured by PEP / ET. In some embodiments, contractility is measured by IVCTZET. In some embodiments, the contractility of the left ventricle is increased by about 1 % to about 20 %. In some embodiments, the contractility of the left ventricle is increased by about 1 % to about 2 %, about 1 % to about 3 %, about 1 % toabout 4 %, about 1 % to about 5 %, about 1 % to about 6 %, about 1 % to about 7 %, about 1 % to about 8 %, about 1 % to about 9 %, about 1 % to about 10 %, about 1 % to about 15 %, about 1 % to about 20 %, about 2 % to about 3 %, about 2 % to about 4 %, about 2 % to about 5 %, about 2 % to about 6 %, about 2 % to about 7 %, about 2 % to about 8 %, about 2 % to about 9 %, about 2 % to about 10 %, about 2 % to about 15 %, about 2 % to about 20 %, about 3 % to about 4 %, about 3 % to about 5 %, about 3 % to about 6 %, about 3 % to about 7 %, about 3 % to about 8 %, about 3 % to about 9 %, about 3 % to about 10 %, about 3 % to about 15 %, about 3 % to about 20 %, about 4 % to about 5 %, about 4 % to about 6 %, about 4 % to about 7 %, about 4 % to about 8 %, about 4 % to about 9 %, about 4 % to about 10 %, about 4 % to about 15 %, about 4 % to about 20 %, about 5 % to about 6 %, about 5 % to about 7 %, about 5 % to about 8 %, about 5 % to about 9 %, about 5 % to about 10 %, about 5 % to about 15 %, about 5 % to about 20 %, about 6 % to about 7 %, about 6 % to about 8 %, about 6 % to about 9 %, about 6 % to about 10 %, about 6 % to about 15 %, about 6 % to about 20 %, about 7 % to about 8 %, about 7 % to about 9 %, about 7 % to about 10 %, about 7 % to about 15 %, about 7 % to about 20 %, about 8 % to about 9 %, about 8 % to about 10 %, about 8 % to about 15 %, about 8 % to about 20 %, about 9 % to about 10 %, about 9 % to about 15 %, about 9 % to about 20 %, about 10 % to about 15 %, about 10 % to about 20 %, or about 15 % to about 20 %. In some embodiments, the contractility of the left ventricle is increased by about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %. In some embodiments, the contractility of the left ventricle is increased by at least about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, or about 15 %. In some embodiments, the contractility of the left ventricle is increased by at most about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %.

[0135] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient to modulating left ventricular outflow tract (LVOT) gradient in the subject relative to pre-treatment by about 1% or more. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient to modulating left ventricular outflow tract (LVOT) gradient in the subject relative to pre-treatment by about 1% or more. In some embodiments, the LVOT gradient is increased by about 1% or more. In some embodiments, the LVOT gradient is increased by a about by 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, about 20 %, or more. In some embodiments, the LVOT gradient is increased by about 1 % to about 20 %. In some embodiments, the LVOT gradient is increased by about 1% to about 10 %. In some embodiments, the LVOTgradient is increased by about 1% to about 5 %. In some embodiments, the (LVOT) gradient is increased by about 1 % to about 20 %. In some embodiments, the (LVOT) gradient is increased by about 1 % to about 2 %, about 1 % to about 3 %, about 1 % to about 4 %, about 1 % to about 5 %, about 1 % to about 6 %, about 1 % to about 7 %, about 1 % to about 8 %, about 1 % to about 9 %, about 1 % to about 10 %, about 1 % to about 15 %, about 1 % to about 20 %, about 2 % to about 3 %, about 2 % to about 4 %, about 2 % to about 5 %, about 2 % to about 6 %, about 2 % to about 7 %, about 2 % to about 8 %, about 2 % to about 9 %, about 2 % to about 10 %, about 2 % to about 15 %, about 2 % to about 20 %, about 3 % to about 4 %, about 3 % to about 5 %, about 3 % to about 6 %, about 3 % to about 7 %, about 3 % to about 8 %, about 3 % to about 9 %, about 3 % to about 10 %, about 3 % to about 15 %, about 3 % to about 20 %, about 4 % to about 5 %, about 4 % to about 6 %, about 4 % to about 7 %, about 4 % to about 8 %, about 4 % to about 9 %, about 4 % to about 10 %, about 4 % to about 15 %, about 4 % to about 20 %, about 5 % to about 6 %, about 5 % to about 7 %, about 5 % to about 8 %, about 5 % to about 9 %, about 5 % to about 10 %, about 5 % to about 15 %, about 5 % to about 20 %, about 6 % to about 7 %, about 6 % to about 8 %, about 6 % to about 9 %, about 6 % to about 10 %, about 6 % to about 15 %, about 6 % to about 20 %, about 7 % to about 8 %, about 7 % to about 9 %, about 7 % to about 10 %, about 7 % to about 15 %, about 7 % to about 20 %, about 8 % to about 9 %, about 8 % to about 10 %, about 8 % to about 15 %, about 8 % to about 20 %, about 9 % to about 10 %, about 9 % to about 15 %, about 9 % to about 20 %, about 10 % to about 15 %, about 10 % to about 20 %, or about 15 % to about 20 %. In some embodiments, the (LVOT) gradient is increased by about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %. In some embodiments, the (LVOT) gradient is increased by at least about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, or about 15 %. In some embodiments, the (LVOT) gradient is increased by at most about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %. In some embodiments, the LVOT pressure gradient is decreased by about 1 % to about 80 %. In some embodiments, the LVOT pressure gradient is decreased by about 1 % to about 5 %, about 1 % to about 10 %, about 1 % to about 20 %, about 1 % to about 30 %, about 1 % to about 40 %, about 1 % to about 50 %, about 1 % to about 55 %, about 1 % to about 60 %, about 1 % to about 65 %, about 1 % to about 70 %, about 1 % to about 80 %, about 5 % to about 10 %, about 5 % to about 20 %, about 5 % to about 30 %, about 5 % to about 40 %, about 5 % to about 50 %, about 5 % to about 55 %, about 5 % to about 60 %, about 5 % to about 65 %, about 5 % to about 70 %, about 5 % to about 80 %, about 10 % to about 20 %, about 10 % to about 30 %, about 10 % to about 40 %, about 10 % to about 50 %, about 10 % to about 55 %, about 10 % to about 60 %, about 10 % to about 65 %, about 10 % to about 70 %, about10 % to about 80 %, about 20 % to about 30 %, about 20 % to about 40 %, about 20 % to about 50 %, about 20 % to about 55 %, about 20 % to about 60 %, about 20 % to about 65 %, about 20 % to about 70 %, about 20 % to about 80 %, about 30 % to about 40 %, about 30 % to about 50 %, about 30 % to about 55 %, about 30 % to about 60 %, about 30 % to about 65 %, about 30 % to about 70 %, about 30 % to about 80 %, about 40 % to about 50 %, about 40 % to about 55 %, about 40 % to about 60 %, about 40 % to about 65 %, about 40 % to about 70 %, about 40 % to about 80 %, about 50 % to about 55 %, about 50 % to about 60 %, about 50 % to about 65 %, about 50 % to about 70 %, about 50 % to about 80 %, about 55 % to about 60 %, about 55 % to about 65 %, about 55 % to about 70 %, about 55 % to about 80 %, about 60 % to about 65 %, about 60 % to about 70 %, about 60 % to about 80 %, about 65 % to about 70 %, about 65 % to about 80 %, or about 70 % to about 80 %. In some embodiments, the LVOT pressure gradient is decreased by about 1 %, about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, about 70 %, or about 80 %. In some embodiments, the LVOT pressure gradient is decreased by at least about 1 %, about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, or about 70 %. In some embodiments, the LVOT pressure gradient is decreased by at most about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, about 70 %, or about 80 %. In some embodiments, the provokable LVOT-G is decreased by about 1 % to about 80 %. In some embodiments, the provokable LVOT-G is decreased by about 1 % to about 5 %, about 1 % to about 10 %, about 1 % to about 20 %, about 1 % to about 30 %, about 1 % to about 40 %, about 1 % to about 50 %, about 1 % to about 55 %, about 1 % to about 60 %, about 1 % to about 65 %, about 1 % to about 70 %, about 1 % to about 80 %, about 5 % to about 10 %, about 5 % to about 20 %, about 5 % to about 30 %, about 5 % to about 40 %, about 5 % to about 50 %, about 5 % to about 55 %, about 5 % to about 60 %, about 5 % to about 65 %, about 5 % to about 70 %, about 5 % to about 80 %, about 10 % to about 20 %, about 10 % to about 30 %, about 10 % to about 40 %, about 10 % to about 50 %, about 10 % to about 55 %, about 10 % to about 60 %, about 10 % to about 65 %, about 10 % to about 70 %, about 10 % to about 80 %, about 20 % to about 30 %, about 20 % to about 40 %, about 20 % to about 50 %, about 20 % to about 55 %, about 20 % to about 60 %, about 20 % to about 65 %, about 20 % to about 70 %, about 20 % to about 80 %, about 30 % to about 40 %, about 30 % to about 50 %, about 30 % to about 55 %, about 30 % to about 60 %, about 30 % to about 65 %, about 30 % to about 70 %, about 30 % to about 80 %, about 40 % to about 50 %, about 40 % to about 55 %, about 40 % to about 60 %, about 40 % to about 65 %, about 40 % to about 70 %, about 40 % to about 80 %, about 50 % to about 55 %, about 50 % to about 60 %, about 50 % to about 65 %, about 50 % to about 70 %, about 50 % to about 80 %, about 55 % to about 60 %, about 55 % to about 65 %, about 55 % toabout 70 %, about 55 % to about 80 %, about 60 % to about 65 %, about 60 % to about 70 %, about 60 % to about 80 %, about 65 % to about 70 %, about 65 % to about 80 %, or about 70 % to about 80 %. In some embodiments, the provokable LVOT-G is decreased by about 1 %, about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, about 70 %, or about 80 %. In some embodiments, the provokable LVOT-G is decreased by at least about 1 %, about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, or about 70 %. In some embodiments, the provokable LVOT-G is decreased by at most about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, about 70 %, or about 80 %.

[0136] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient to modulating protein concentration of one or more biomarkers in the subject relative to a pre-treatment protein concentration of the one or more biomarkers by about 1 % or more. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient to modulating protein concentration of one or more biomarkers in the subject relative to a pre-treatment protein concentration of the one or more biomarkers by about 1 % or more. In some embodiments, the biomarker is high sensitivity troponin I (hsTnl) or NT-proBNP. In some embodiments, the biomarker increase is about 1 % to about 20 %. In some embodiments, the biomarker increase is about 1 % to about 2 %, about 1 % to about 3 %, about 1 % to about 4 %, about 1 % to about 5 %, about 1 % to about 6 %, about 1 % to about 7 %, about 1 % to about 8 %, about 1 % to about 9 %, about 1 % to about 10 %, about 1 % to about 15 %, about 1 % to about 20 %, about 2 % to about 3 %, about 2 % to about 4 %, about 2 % to about 5 %, about 2 % to about 6 %, about 2 % to about 7 %, about 2 % to about 8 %, about 2 % to about 9 %, about 2 % to about 10 %, about 2 % to about 15 %, about 2 % to about 20 %, about 3 % to about 4 %, about 3 % to about 5 %, about 3 % to about 6 %, about 3 % to about 7 %, about 3 % to about 8 %, about 3 % to about 9 %, about 3 % to about 10 %, about 3 % to about 15 %, about 3 % to about 20 %, about 4 % to about 5 %, about 4 % to about 6 %, about 4 % to about 7 %, about 4 % to about 8 %, about 4 % to about 9 %, about 4 % to about 10 %, about 4 % to about 15 %, about 4 % to about 20 %, about 5 % to about 6 %, about 5 % to about 7 %, about 5 % to about 8 %, about 5 % to about 9 %, about 5 % to about 10 %, about 5 % to about 15 %, about 5 % to about 20 %, about 6 % to about 7 %, about 6 % to about 8 %, about 6 % to about 9 %, about 6 % to about 10 %, about 6 % to about 15 %, about 6 % to about 20 %, about 7 % to about 8 %, about 7 % to about 9 %, about 7 % to about 10 %, about 7 % to about 15 %, about 7 % to about 20 %, about 8 % to about 9 %, about 8 % to about 10 %, about 8 % to about 15 %, about 8 % to about 20 %, about 9 % to about 10 %, about 9 % to about 15 %,about 9 % to about 20 %, about 10 % to about 15 %, about 10 % to about 20 %, or about 15 % to about 20 %. In some embodiments, the biomarker increase is about 1 %, about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %. In some embodiments, the biomarker increase is at least about 1 %, about 2 %, about 3 %, about4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, or about 15 %. In some embodiments, the biomarker increase is at most about 2 %, about 3 %, about 4 %, about 5 %, about 6 %, about 7 %, about 8 %, about 9 %, about 10 %, about 15 %, or about 20 %. In some embodiments, NT -proBNP is decreased by about 1 % to about 80 %. In some embodiments, NT-proBNP is decreased by about 1 % to about 5 %, about 1 % to about 10 %, about 1 % to about 20 %, about 1 % to about 30 %, about 1 % to about 40 %, about 1 % to about 50 %, about 1 % to about 55 %, about 1 % to about 60 %, about 1 % to about 65 %, about 1 % to about 70 %, about 1 % to about 80 %, about5 % to about 10 %, about 5 % to about 20 %, about 5 % to about 30 %, about 5 % to about 40 %, about 5 % to about 50 %, about 5 % to about 55 %, about 5 % to about 60 %, about 5 % to about 65 %, about 5 % to about 70 %, about 5 % to about 80 %, about 10 % to about 20 %, about 10 % to about 30 %, about 10 % to about 40 %, about 10 % to about 50 %, about 10 % to about 55 %, about 10 % to about 60 %, about 10 % to about 65 %, about 10 % to about 70 %, about 10 % to about 80 %, about 20 % to about 30 %, about 20 % to about 40 %, about 20 % to about 50 %, about 20 % to about 55 %, about 20 % to about 60 %, about 20 % to about 65 %, about 20 % to about 70 %, about 20 % to about 80 %, about 30 % to about 40 %, about 30 % to about 50 %, about 30 % to about 55 %, about 30 % to about 60 %, about 30 % to about 65 %, about 30 % to about 70 %, about 30 % to about 80 %, about 40 % to about 50 %, about 40 % to about 55 %, about 40 % to about 60 %, about 40 % to about 65 %, about 40 % to about 70 %, about 40 % to about 80 %, about 50 % to about 55 %, about 50 % to about 60 %, about 50 % to about 65 %, about 50 % to about 70 %, about 50 % to about 80 %, about 55 % to about 60 %, about 55 % to about 65 %, about 55 % to about 70 %, about 55 % to about 80 %, about 60 % to about 65 %, about 60 % to about 70 %, about 60 % to about 80 %, about 65 % to about 70 %, about 65 % to about 80 %, or about 70 % to about 80 %. In some embodiments, NT-proBNP is decreased by about 1 %, about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, about 70 %, or about 80 %. In some embodiments, NT-proBNP is decreased by at least about 1 %, about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, or about 70 %. In some embodiments, NT-proBNP is decreased by at most about 5 %, about 10 %, about 20 %, about 30 %, about 40 %, about 50 %, about 55 %, about 60 %, about 65 %, about 70 %, or about 80 %. In some embodiments, NT-proBNP is decreased by about 60% to aboug 70%. In some embodiments, NT-proBNP is decreased by about 60% to aboug 65%. In some embodiments, NT-proBNP isdecreased by about 60% to aboug 62%. In some embodiments, NT-proBNP is decreased by about 40% to aboug 60%. In some embodiments, NT-proBNP is decreased by about 40% to aboug 50%. In some embodiments, NT-proBNP is decreased by about 40% to aboug 45%. In some embodiments, NT-proBNP is decreased by about 42%. In some embodiments, NT-proBNP is decreased by about 50%.

[0137] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient achieve a plasma concentration Cmax level of between about 10 and about 2000 ng / mL. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient achieve a plasma concentration Cmax level of between about 10 and about 2000 ng / mL. In some embodiments, the plasma concentration Cmax level is between about 10 and about 700 ng / mL. In some embodiments, the plasma concentration Cmax level is between about 10 and about 500 ng / mL. In some embodiments, the plasma concentration Cmax level is between about 10 and about 300 ng / mL. In some embodiments, the plasma concentration Cmax level is between about 100 and about 300 ng / mL. In some embodiments, the plasma concentration Cmax level is about 100 ng / mL to about 3,000 ng / mL. In some embodiments, the plasma concentration Cmax level is about 100 ng / mL to about 200 ng / mL, about 100 ng / mL to about 300 ng / mL, about 100 ng / mL to about 400 ng / mL, about 100 ng / mL to about 500 ng / mL, about 100 ng / mL to about 600 ng / mL, about 100 ng / mL to about 750 ng / mL, about 100 ng / mL to about 900 ng / mL, about 100 ng / mL to about 1,000 ng / mL, about 100 ng / mL to about 1,500 ng / mL, about 100 ng / mL to about 2,000 ng / mL, about 100 ng / mL to about 3,000 ng / mL, about 200 ng / mL to about 300 ng / mL, about 200 ng / mL to about 400 ng / mL, about 200 ng / mL to about 500 ng / mL, about 200 ng / mL to about 600 ng / mL, about 200 ng / mL to about 750 ng / mL, about 200 ng / mL to about 900 ng / mL, about 200 ng / mL to about 1,000 ng / mL, about 200 ng / mL to about 1,500 ng / mL, about 200 ng / mL to about 2,000 ng / mL, about 200 ng / mL to about 3,000 ng / mL, about 300 ng / mL to about 400 ng / mL, about 300 ng / mL to about 500 ng / mL, about 300 ng / mL to about 600 ng / mL, about 300 ng / mL to about 750 ng / mL, about 300 ng / mL to about 900 ng / mL, about 300 ng / mL to about 1,000 ng / mL, about 300 ng / mL to about 1,500 ng / mL, about 300 ng / mL to about 2,000 ng / mL, about 300 ng / mL to about 3,000 ng / mL, about 400 ng / mL to about 500 ng / mL, about 400 ng / mL to about 600 ng / mL, about 400 ng / mL to about 750 ng / mL, about 400 ng / mL to about 900 ng / mL, about 400 ng / mL to about 1,000 ng / mL, about 400 ng / mL to about 1,500 ng / mL, about 400 ng / mL to about 2,000 ng / mL, about 400 ng / mL to about 3,000 ng / mL, about 500 ng / mL to about 600 ng / mL, about 500 ng / mL to about 750 ng / mL, about 500 ng / mL to about 900 ng / mL, about 500 ng / mL to about 1,000 ng / mL, about 500 ng / mL to about 1,500 ng / mL, about 500 ng / mL to about 2,000 ng / mL,about 500 ng / mL to about 3,000 ng / mL, about 600 ng / mL to about 750 ng / mL, about 600 ng / mL to about 900 ng / mL, about 600 ng / mL to about 1,000 ng / mL, about 600 ng / mL to about 1,500 ng / mL, about 600 ng / mL to about 2,000 ng / mL, about 600 ng / mL to about 3,000 ng / mL, about 750 ng / mL to about 900 ng / mL, about 750 ng / mL to about 1,000 ng / mL, about 750 ng / mL to about 1,500 ng / mL, about 750 ng / mL to about 2,000 ng / mL, about 750 ng / mL to about 3,000 ng / mL, about 900 ng / mL to about 1,000 ng / mL, about 900 ng / mL to about 1,500 ng / mL, about 900 ng / mL to about 2,000 ng / mL, about 900 ng / mL to about 3,000 ng / mL, about 1,000 ng / mL to about 1,500 ng / mL, about 1,000 ng / mL to about 2,000 ng / mL, about 1,000 ng / mL to about 3,000 ng / mL, about 1,500 ng / mL to about 2,000 ng / mL, about 1,500 ng / mL to about 3,000 ng / mL, or about 2,000 ng / mL to about 3,000 ng / mL. In some embodiments, the plasma concentration Cmax level is about 100 ng / mL, about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 600 ng / mL, about 750 ng / mL, about 900 ng / mL, about 1,000 ng / mL, about 1,500 ng / mL, about 2,000 ng / mL, or about 3,000 ng / mL. In some embodiments, the plasma concentration Cmax level is at least about 100 ng / mL, about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 600 ng / mL, about 750 ng / mL, about 900 ng / mL, about 1,000 ng / mL, about 1,500 ng / mL, or about 2,000 ng / mL. In some embodiments, the plasma concentration Cmax level is at most about 200 ng / mL, about 300 ng / mL, about 400 ng / mL, about 500 ng / mL, about 600 ng / mL, about 750 ng / mL, about 900 ng / mL, about 1,000 ng / mL, about 1,500 ng / mL, about 2,000 ng / mL, or about 3,000 ng / mL.

[0138] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient achieve a plasma concentration Tmax of between about 0.5 h and about 6 h. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient achieve a plasma concentration Tmax of between about 0.5 h and about 6 h. In some embodiments, the plasma concentration Tmaxis about 0.5 h to about 6 h. In some embodiments, the plasma concentration Tmaxis about 0.5 h to about 0.75 h, about 0.5 h to about 1 h, about 0.5 h to about 1.25 h, about 0.5 h to about 1.5 h, about 0.5 h to about 1.75 h, about 0.5 h to about 2 h, about 0.5 h to about 2.5 h, about 0.5 h to about 3 h, about 0.5 h to about 4 h, about 0.5 h to about 5 h, about 0.5 h to about 6 h, about 0.75 h to about 1 h, about 0.75 h to about 1.25 h, about 0.75 h to about 1.5 h, about 0.75 h to about 1.75 h, about 0.75 h to about 2 h, about 0.75 h to about 2.5 h, about 0.75 h to about 3 h, about 0.75 h to about 4 h, about 0.75 h to about 5 h, about 0.75 h to about 6 h, about 1 h to about 1.25 h, about 1 h to about 1.5 h, about 1 h to about 1.75 h, about 1 h to about 2 h, about 1 h to about 2.5 h, about 1 h to about 3 h, about 1 h to about 4 h, about 1 h to about 5 h, about 1 h to about 6 h, about 1.25 h to about 1.5 h, about 1.25 h to about 1.75 h, about 1.25 h to about 2 h, about 1.25 h to about 2.5 h, about 1.25 h to about 3 h, about 1.25 h to about 4 h, about1.25 h to about 5 h, about 1.25 h to about 6 h, about 1.5 h to about 1.75 h, about 1.5 h to about 2 h, about 1.5 h to about 2.5 h, about 1.5 h to about 3 h, about 1.5 h to about 4 h, about 1.5 h to about 5 h, about 1.5 h to about 6 h, about 1.75 h to about 2 h, about 1.75 h to about 2.5 h, about 1.75 h to about 3 h, about 1.75 h to about 4 h, about 1.75 h to about 5 h, about 1.75 h to about 6 h, about 2 h to about 2.5 h, about 2 h to about 3 h, about 2 h to about 4 h, about 2 h to about 5 h, about 2 h to about 6 h, about 2.5 h to about 3 h, about 2.5 h to about 4 h, about 2.5 h to about 5 h, about 2.5 h to about 6 h, about 3 h to about 4 h, about 3 h to about 5 h, about 3 h to about 6 h, about 4 h to about 5 h, about 4 h to about 6 h, or about 5 h to about 6 h. In some embodiments, the plasma concentration Tmax is about 0.5 h, about 0.75 h, about 1 h, about 1.25 h, about 1.5 h, about 1.75 h, about 2 h, about 2.5 h, about 3 h, about 4 h, about 5 h, or about 6 h. In some embodiments, the plasma concentration Tmax is at least about 0.5 h, about 0.75 h, about 1 h, about 1.25 h, about 1.5 h, about 1.75 h, about 2 h, about 2.5 h, about 3 h, about 4 h, or about 5 h. In some embodiments, the plasma concentration Tmaxis at most about 0.75 h, about 1 h, about 1.25 h, about 1.5 h, about 1.75 h, about 2 h, about 2.5 h, about 3 h, about 4 h, about 5 h, or about 6 h.

[0139] In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient achieve a plasma concentration AUCo-24h level of between about 100 and about 150,000 h*ng / mL. In an aspect, disclosed herein is a method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 2 in an amount sufficient achieve a plasma concentration AUCo-24h level of between about 100 and about 150,000 h*ng / mL. In some embodiments, the plasma concentration AUCo-24h level is about 100 h*ng / mL to about 150,000 h*ng / mL. In some embodiments, the plasma concentration AUCo-24h level is about 100 h*ng / mL to about 3,000 h*ng / mL, about 100 h*ng / mL to about 5,000 h*ng / mL, about 100 h*ng / mL to about 10,000 h*ng / mL, about 100 h*ng / mL to about 20,000 h*ng / mL, about 100 h*ng / mL to about 30,000 h*ng / mL, about 100 h*ng / mL to about 40,000 h*ng / mL, about 100 h*ng / mL to about 50,000 h*ng / mL, about 100 h*ng / mL to about 60,000 h*ng / mL, about 100 h*ng / mL to about 80,000 h*ng / mL, about 100 h*ng / mL to about 100,000 h*ng / mL, about 100 h*ng / mL to about 150,000 h*ng / mL, about 3,000 h*ng / mL to about 5,000 h*ng / mL, about 3,000 h*ng / mL to about 10,000 h*ng / mL, about 3,000 h*ng / mL to about 20,000 h*ng / mL, about 3,000 h*ng / mL to about 30,000 h*ng / mL, about 3,000 h*ng / mL to about 40,000 h*ng / mL, about 3,000 h*ng / mL to about 50,000 h*ng / mL, about 3,000 h*ng / mL to about 60,000 h*ng / mL, about 3,000 h*ng / mL to about 80,000 h*ng / mL, about 3,000 h*ng / mL to about 100,000 h*ng / mL, about 3,000 h*ng / mL to about 150,000 h*ng / mL, about 5,000 h*ng / mL to about 10,000 h*ng / mL, about 5,000 h*ng / mL to about 20,000 h*ng / mL, about 5,000 h*ng / mL to about 30,000 h*ng / mL, about 5,000 h*ng / mL to about 40,000h*ng / mL, about 5,000 h*ng / mL to about 50,000 h*ng / mL, about 5,000 h*ng / mL to about 60,000 h*ng / mL, about 5,000 h*ng / mL to about 80,000 h*ng / mL, about 5,000 h*ng / mL to about 100,000 h*ng / mL, about 5,000 h*ng / mL to about 150,000 h*ng / mL, about 10,000 h*ng / mL to about 20,000 h*ng / mL, about 10,000 h*ng / mL to about 30,000 h*ng / mL, about 10,000 h*ng / mL to about 40,000 h*ng / mL, about 10,000 h*ng / mL to about 50,000 h*ng / mL, about 10,000 h*ng / mL to about 60,000 h*ng / mL, about 10,000 h*ng / mL to about 80,000 h*ng / mL, about 10,000 h*ng / mL to about 100,000 h*ng / mL, about 10,000 h*ng / mL to about 150,000 h*ng / mL, about 20,000 h*ng / mL to about 30,000 h*ng / mL, about 20,000 h*ng / mL to about 40,000 h*ng / mL, about 20,000 h*ng / mL to about 50,000 h*ng / mL, about 20,000 h*ng / mL to about 60,000 h*ng / mL, about 20,000 h*ng / mL to about 80,000 h*ng / mL, about 20,000 h*ng / mL to about 100,000 h*ng / mL, about 20,000 h*ng / mL to about 150,000 h*ng / mL, about 30,000 h*ng / mL to about 40,000 h*ng / mL, about 30,000 h*ng / mL to about 50,000 h*ng / mL, about 30,000 h*ng / mL to about 60,000 h*ng / mL, about 30,000 h*ng / mL to about 80,000 h*ng / mL, about 30,000 h*ng / mL to about 100,000 h*ng / mL, about 30,000 h*ng / mL to about 150,000 h*ng / mL, about 40,000 h*ng / mL to about 50,000 h*ng / mL, about 40,000 h*ng / mL to about 60,000 h*ng / mL, about 40,000 h*ng / mL to about 80,000 h*ng / mL, about 40,000 h*ng / mL to about 100,000 h*ng / mL, about 40,000 h*ng / mL to about 150,000 h*ng / mL, about 50,000 h*ng / mL to about 60,000 h*ng / mL, about 50,000 h*ng / mL to about 80,000 h*ng / mL, about 50,000 h*ng / mL to about 100,000 h*ng / mL, about 50,000 h*ng / mL to about 150,000 h*ng / mL, about 60,000 h*ng / mL to about 80,000 h*ng / mL, about 60,000 h*ng / mL to about 100,000 h*ng / mL, about 60,000 h*ng / mL to about 150,000 h*ng / mL, about 80,000 h*ng / mL to about 100,000 h*ng / mL, about 80,000 h*ng / mL to about 150,000 h*ng / mL, or about 100,000 h*ng / mL to about 150,000 h*ng / mL. In some embodiments, the plasma concentration AUCo-24h level is about 100 h*ng / mL, about 3,000 h*ng / mL, about 5,000 h*ng / mL, about 10,000 h*ng / mL, about 20,000 h*ng / mL, about 30,000 h*ng / mL, about 40,000 h*ng / mL, about 50,000 h*ng / mL, about 60,000 h*ng / mL, about 80,000 h*ng / mL, about 100,000 h*ng / mL, or about 150,000 h*ng / mL. In some embodiments, the plasma concentration AUCo-24h level is at least about 100 h*ng / mL, about 3,000 h*ng / mL, about 5,000 h*ng / mL, about 10,000 h*ng / mL, about 20,000 h*ng / mL, about 30,000 h*ng / mL, about 40,000 h*ng / mL, about 50,000 h*ng / mL, about 60,000 h*ng / mL, about 80,000 h*ng / mL, or about 100,000 h*ng / mL. In some embodiments, the plasma concentration AUCo-24h level is at most about 3,000 h*ng / mL, about 5,000 h*ng / mL, about 10,000 h*ng / mL, about 20,000 h*ng / mL, about 30,000 h*ng / mL, about 40,000 h*ng / mL, about 50,000 h*ng / mL, about 60,000 h*ng / mL, about 80,000 h*ng / mL, about 100,000 h*ng / mL, or about 150,000 h*ng / mL.

[0140] in some embodiments, Compound 1, or Compound 2, or a pharmaceutically acceptable salt thereof, is administered. To In some embodiments, the compound is administered once a day, twice aday, three times a day, once every two days, once every three days, once every four days, once every five days, once every six days or once a week. In some embodiments, the compound is administered once a day. In some embodiments administering is once every 2 days.

[0141] In some embodiments, the compound is administered for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months. In some embodiments, the compound is administered for more than 1 month, more than 2 months, more than 3 months, more than 4 months, more than 5 months, more than 6 months, more than 7 months, more than 8 months, more than 9 months, more than 10 months, more than 11 months, or more than 12 months.Solid FormsCrystalline Forms

[0142] In an aspect, the present invention provides crystalline Compound 1 of Form 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17. In an aspect, the present invention provides crystalline Compound 1 of Form 1, 9, and 12. In an aspect, the present invention provides crystalline Compound 1 of Form 1. In an aspect, the present invention provides crystalline Compound 1 of Form 2. In an aspect, the present invention provides crystalline Compound 1 of Form 3. In an aspect, the present invention provides crystalline Compound 1 of Form 4. In an aspect, the present invention provides crystalline Compound 1 of Form 5. In an aspect, the present invention provides crystalline Compound 1 of Form 6. In an aspect, the present invention provides crystalline Compound 1 of Form 7. In an aspect, the present invention provides crystalline Compound 1 of Form 8. In an aspect, the present invention provides crystalline Compound 1 of Form 9. In an aspect, the present invention provides crystalline Compound 1 of Form 10. In an aspect, the present invention provides crystalline Compound 1 of Form 11. In an aspect, the present invention provides crystalline Compound 1 of Form 12. In an aspect, the present invention provides crystalline Compound 1 of Form 13. In an aspect, the present invention provides crystalline Compound 1 of Form 14. In an aspect, the present invention provides crystalline Compound 1 of Form 15. In an aspect, the present invention provides crystalline Compound 1 of Form 16. In an aspect, the present invention provides crystalline Compound 1 of Form 17. In one embodiment, the crystalline Forms are characterized by the interlattice plane intervals determined by a X-ray powder diffraction (e.g., XRPD) pattern. The spectrum of XRPD can be 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 XRPD can be selected according to the peak locations and their relative intensity to conveniently distinguish this crystalline structure from others.

[0143] Measurements of XRPD peak locations (e.g., angles) and / or intensity for a given crystalline form of the same compound can vary within a margin of error. The values of degree 20 may allow error margins. Typically, the error margins can be represented by "±". For example, the degree 20 = "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). In some embodiments, the margin of error for a 20 peak in an XRPD can be ± 0.5°; ± 0.4°; ± 0.3°; ± 0.2°; ± 0.1°; ± 0.05°; or less; or more. In some embodiments, calibration techniques applied to the instruments, human operational variation, and etc. influence the margin of error.

[0144] Additional details of the methods and equipment used for the XRPD analysis are described in the Examples section.

[0145] Unless otherwise specified, all 20 values reported correspond to 20 values as measured by x- ray powder diffraction using an X-ray wavelength of 1.5418 A.

[0146] In some embodiments, the crystalline forms are characterized by Differential Scanning Calorimetry (DSC) and Therm ogravimetric Analysis (TGA). The DSC thermogram can be expressed by a diagram plotting the normalized heat flow (e.g., in units of Watts / gram ("W / g")) versus the measured sample temperature in degree C. The DSC thermogram can be evaluated for extrapolated onset and end (e.g., outset) temperatures, peak temperature, and heat of fusion. The single maximum value of a DSV thermogram can be used as the characteristic peak to distinguish one crystalline form from another crystalline form. The TGA thermogram can be expressed by a diagram plotting the weight loss percentage (%) versus the measured sample temperature in degree C.

[0147] Measurements of the DSC and TGA thermograms for a given crystalline form of the same compound can 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 °C" denotes a range from 53.09 °C + 10.0 °C, (i.e., 63.1 °C) to about 53.1 °C - 10.0 °C (i.e., 43.1 °C). In some embodiments, the margin of error for any of the DSC or TGA measurements (e.g., onset temperature, endotherm, or temperature of TGA weight loss) described herein can depend on sample preparation techniques, crystallization conditions, calibration techniques applied to the instruments, human operational variations, and etc. In some embodiments, the margin of error for a single maximum value can be ± 20 °C, ± 15 °C, ± 10.0 °C; ± 7.5 °C; ± 5.0 °C; ± 2.5 °C; ± 2 °C; ± 1.5 °C; ± 1 °C; ± 0.5 °C; or less; or more for any of the DSC or TGA measurements (e.g., onset temperature, endotherm, or temperature of TGA weight loss) described herein. In some embodiments, the margin of error for the extent of weight loss can depend on sample preparation techniques, crystallization conditions, calibration techniques applied to the instruments, human operational variations, and etc. In some embodiments, the margin of error for the extent of weight loss can be ± 1.0%, ± 0.9%, ± 0.8%, ± 0.7%, ± 0.6%, ± 0.5%, ± 0.4%, ±0.3%, ± 0.2%, ± 0.1%, ± 0.05%, or less or more. In some embodiments, the percentage of weight loss expressed is a weight percentage (e.g., prepresenting the percentage of weight lost relative to the weight of the initial sample).

[0148] In some embodiments, the present disclosure provides a solid form of Compound 1.Form 1 of Compound 1(Form 1 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0149] In some embodiments, the present disclosure provides crystalline anhydrate Form 1 of Compound 1. In some embodiments, Form 1 exhibits an XRPD of that in Fig. 1. In some embodiments, Form 1 exhibits an DSC and TGA of that in Fig. 18.

[0150] In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.4° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3° and 13.0° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, and 14.6° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, and 15.3° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, and 8.9° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, and 17.9° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, and 27.6° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, and 20.5° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, and 10.9° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, and28.6° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, and 25.8° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, and 24.2° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, 23.6° ± 0.3°, 9.5° ± 0.3°, 21.8° ± 0.3°, 31.0° ± 0.3°, 22.5° ± 0.3°, 29.6° ± 0.3°, 37.9° ± 0.3°, 7.2° ± 0.3°, 18.6° ± 0.3°, 26.7° ± 0.3°, 30.1° ± 0.3°, and 39.0° ± 0.3°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.3°, 13.0° ± 0.3°, 14.6° ± 0.3°, 15.3° ± 0.3°, 8.9° ± 0.3°, 17.9° ± 0.3°, 27.6° ± 0.3°, 20.5° ± 0.3°, 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, and 37.9° ± 0.3°. In some embodiments, thesolid form exhibits an XRPD pattern reflection at a 20 value of 5.4° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.6° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.9° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 17.9° ± 0.3°, 27.6° ± 0.3°, and 20.5° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 10.9° ± 0.3°, 28.6° ± 0.3°, 25.8° ± 0.3°, 24.2° ± 0.3°, 23.6° ± 0.3°, and 9.5° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 21.8° ± 0.3°, 31.0° ± 0.3°, 22.5° ± 0.3°, 29.6° ± 0.3°, 37.9° ± 0.3°, and 7.2° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 18.6° ± 0.3°, 26.7° ± 0.3°, 30.1° ± 0.3°, and 39.0° ± 0.3°.

[0151] In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.4° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2° and 13.0° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, and 14.6° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, and 15.3° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, and 8.9° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, and 17.9° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, and 27.6° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, and 20.5° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, and 10.9° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, and 28.6° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, and 25.8° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, and 24.2° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, and 37.9° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, 23.6° ± 0.2°, 9.5° ± 0.2°, 21.8° ± 0.2°, 31.0° ± 0.2°, 22.5° ± 0.2°, 29.6° ± 0.2°, 37.9° ± 0.2°, 7.2° ± 0.2°, 18.6° ± 0.2°, 26.7° ± 0.2°, 30.1° ± 0.2°, and 39.0° ± 0.2°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, and 37.9° ± 0.2°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, and 37.9° ± 0.2°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, and 37.9° ± 0.2°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, and 37.9° ± 0.2°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.2°, 13.0° ± 0.2°,14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ±0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, and 37.9° ± 0.2°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.2°, 13.0° ± 0.2°, 14.6° ± 0.2°, 15.3° ± 0.2°, 8.9° ± 0.2°, 17.9° ± 0.2°, 27.6° ± 0.2°, 20.5° ± 0.2°, 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, and 37.9° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.4° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.6° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.9° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 17.9° ± 0.2°, 27.6° ± 0.2°, and 20.5° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 10.9° ± 0.2°, 28.6° ± 0.2°, 25.8° ± 0.2°, 24.2° ± 0.2°, 23.6° ± 0.2°, and 9.5° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 21.8° ± 0.2°, 31.0° ± 0.2°, 22.5° ± 0.2°, 29.6° ± 0.2°, 37.9° ± 0.2°, and 7.2° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 18.6° ± 0.2°, 26.7° ± 0.2°, 30.1° ± 0.2°, and 39.0° ± 0.2°.

[0152] In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.4° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.1° and 13.0° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.1°, 13.0° ± 0.1°, and 14.6° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, and 15.3° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, and 8.9° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, and 17.9° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, and 27.6° ± 0.1°. In some embodiments, the presentdisclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, and 20.5° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, and 10.9° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, and 28.6° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, and 25.8° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, and 24.2° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, and 37.9° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, 23.6° ± 0.1°, 9.5° ± 0.1°, 21.8° ± 0.1°, 31.0° ± 0.1°, 22.5° ± 0.1°, 29.6° ± 0.1°, 37.9° ± 0.1°, 7.2° ± 0.1°, 18.6° ± 0.1°, 26.7° ± 0.1°, 30.1° ± 0.1°, and 39.0° ± 0.1°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 26 value(s) independently selected from 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, and 37.9° ± 0.1°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 26 value(s) independently selected from 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, and 37.9° ± 0.1°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 26 value(s) independently selected from 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, and 37.9° ± 0.1°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 26 value(s) independently selected from 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3°± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, and 37.9° ± 0.1°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, and 37.9° ± 0.1°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4° ± 0.1°, 13.0° ± 0.1°, 14.6° ± 0.1°, 15.3° ± 0.1°, 8.9° ± 0.1°, 17.9° ± 0.1°, 27.6° ± 0.1°, 20.5° ± 0.1°, 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, and 37.9° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.4° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.6° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.3° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.9° ± 0.1°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 17.9° ± 0.1°, 27.6° ± 0.1°, and 20.5° ± 0.1°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 10.9° ± 0.1°, 28.6° ± 0.1°, 25.8° ± 0.1°, 24.2° ± 0.1°, 23.6° ± 0.1°, and 9.5° ± 0.1°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 21.8° ± 0.1°, 31.0° ± 0.1°, 22.5° ± 0.1°, 29.6° ± 0.1°, 37.9° ± 0.1°, and 7.2° ± 0.1°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 18.6° ± 0.1°, 26.7° ± 0.1°, 30.1° ± 0.1°, and 39.0° ± 0.1°.

[0153] In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4° and 13.0°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, and 14.6°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, and 15.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, and 8.9°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, and 17.9°. In some embodiments, thepresent disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, and 27.6°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, and 20.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, and 10.9°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, and 28.6°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, and 25.8°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, and 24.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, and 37.9°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, 23.6°, 9.5°, 21.8°, 31.0°, 22.5°, 29.6°, 37.9°, 7.2°, 18.6°, 26.7°, 30.1°, and 39.0°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, and 37.9°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, and 37.9°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, and 37.9°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, and 37.9°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, and 37.9°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 5.4°, 13.0°, 14.6°, 15.3°, 8.9°, 17.9°, 27.6°, 20.5°, 10.9°, 28.6°, 25.8°, 24.2°, and 37.9°. In some embodiments, the solid form exhibits anXRPD pattern reflection at a 20 value of 5.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.6°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.9°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 17.9°, 27.6°, and 20.5°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 10.9°, 28.6°, 25.8°, 24.2°, 23.6°, and 9.5°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 21.8°, 31.0°, 22.5°, 29.6°, 37.9°, and 7.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 18.6°, 26.7°, 30.1°, and 39.0°.

[0154] In some embodiments, crystalline anhydrate Form 1 exhibits at least one of the X-ray powder diffraction pattern reflections in Table 1. In some embodiments, Form 1 is an anhydrate.Table 1. Peaks from the X-ray powder diffractogram of crystalline anhydrate Form 1 of Compound 1 above 2% relative intensity

[0155] In some embodiments, the solid form exhibits the XRPD pattern as shown in Figure 1. In some embodiments, the solid form exhibits an XRPD pattern substantially similar to that shown in Figure 1.

[0156] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 197.2 °C ± 25.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 197.2 °C ± 20.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 197.2 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at197.2 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 197.2 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at197.2 °C ± 2.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 197.2 °C ± 1.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at197.2 °C ± 0.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 197.2 °C.

[0157] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 195.8 °C ± 25.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 195.8 °C ± 20.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 195.8 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at195.8 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 195.8 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at195.8 °C ± 2.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 195.8 °C ± 1 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at195.8 °C ± 0.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 195.8 °C.

[0158] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 182.7 °C ± 25.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 182.7 °C ± 20.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 182.7 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at182.7 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 182.7 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at182.7 °C ± 2.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 182.7 °C ± 1 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at182.7 °C ± 0.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 182.7 °C.

[0159] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 178.5 °C ± 25.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 178.5 °C ± 20.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 178.5 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at178.5 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 178.5 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at178.5 °C ± 2.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 178.5 °C ± 1.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at178.5 °C ± 0.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 178.5 °C.

[0160] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram as shown in Figure 18. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram substantially similar to that shown in Figure 18.

[0161] In some embodiments, the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 18. In some embodiments, the solid form exhibits a thermogravimetric analysis thermogram substantially similar to that shown in Figure 18. In some embodiments, the solid form exhibits 0% weight loss upon thermogravimetric analysis.

[0162] In some embodiments, the solid form is crystalline. In some embodiments, the solid form is an anhydrate. In some embodiments, the solid form is solid Form 1 of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide. In some embodiments, the solid form is crystalline and obtained from methanol, ethanol, isopropanol, toluene, water, acetonitrile, heptane, acetone, tert-butyl methyl ether, 2-butanone, ethyl acetate,isopropyl acetate, tetrahydrofuran, or any combination thereof. In some embodiments, the present disclosure provides a pharmaceutical composition comprising any solid form described herein (e.g., Form 1 of Compound 1) and one or more pharmaceutically acceptable excipient(s).Form 2 of Compound 1(Form 2 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0163] In some embodiments, the present disclosure provides crystalline Form 2 of Compound 1. In some embodiments, Form 2 exhibits an XRPD of that in Fig. 2. In some embodiments, Form 2 exhibits an DSC and TGA of that in Fig. 19.

[0164] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 55.0 °C ± 5.0 °C. In some embodiments, the endothermic peak comprises an onset temperature at 33.6 ° C ± 5.0 °C.

[0165] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 162.9 °C ± 5.0 °C. In some embodiments, the endothermic peak comprises an onset temperature at 157.6° C ± 5.0 °C.

[0166] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an exothermic peak at 165.7 °C ± 5.0 °C. In some embodiments, the exothermic peak comprises an onset temperature at 164.5° C ± 5.0 °C.

[0167] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 203.6 °C ± 5.0 °C. In some embodiments, the endothermic peak comprises an onset temperature at 199.7° C ± 5.0 °C.

[0168] In some embodiments, the solid form exhibits a sample weight loss of 0.2% ± 0.1% at 90 °C ± 10.0 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 1.0% ± 0.5% at 160 °C ± 10.0 °C as determined by thermogravimetric analysis.

[0169] In some embodiments, crystalline Form 2 exhibits at least one of the X-ray powder diffraction pattern reflections below. In some embodiments, Form 2 is a solvate.

[0170] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 2 of Compound 1 are shown below: in Table 2. In some embodiments, Form 2 is a solvate (e.g., of EtOH).Table 2. Peaks from the X-ray powder diffractogram of crystalline Form 2 of Compound 1 above 2% relative intensityForm 3 of Compound 1(Form 3 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0171] In some embodiments, the present disclosure provides crystalline Form 3 of Compound 1. In some embodiments, Form 3 exhibits an XRPD of that in Fig. 3. In some embodiments, Form 3 exhibits an DSC and TGA of that in Fig. 20. In some embodiments, crystalline Form 3 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0172] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 137.2 °C ± 5.0 °C. In some embodiments, the endothermic peak comprises an onset temperature at 127.9° C ± 5.0 °C.

[0173] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 152.7 °C ± 5.0 °C. In some embodiments, the endothermic peak comprises an onset temperature at 149.3° C ± 5.0 °C.

[0174] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an exothermic peak at 154.9 °C ± 5.0 °C. In some embodiments, the exothermic peak comprises an onset temperature at 154.1° C ± 5.0 °C.

[0175] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 201.7 °C ± 5.0 °C. In some embodiments, the endothermic peak comprises an onset temperature at 200.5° C ± 5.0 °C.

[0176] In some embodiments, the solid form exhibits a sample weight loss of 1.4% ± 0.5% at 150 °C ± 10.0 °C as determined by thermogravimetric analysis.

[0177] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 3 of Compound 1 are shown in Table 3. In some embodiments, Form 3 is a solvate (e.g., of IP A). In some embodiments, Form 3 is a hydrate. In some embodiments, Form 3 is a solvate and a hydate.Table 3. Peaks from the X-ray powder diffractogram of crystalline Form 3 of Compound 1Form 4 of Compound 1(Form 4 of (A)-A-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0178] In some embodiments, the present disclosure provides crystalline Form 4 of Compound 1. In some embodiments, Form 4 exhibits an XRPD of that in Fig. 4. In some embodiments, Form 4 exhibits an DSC and TGA of that in Fig. 21. In some embodiments, crystalline Form 4 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0179] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 4 of Compound 1 are shown in Table 4. In some embodiments, Form 4 is a solvate (e.g., of ACN). In some embodiments, Form 4 is a hydrate. In some embodiments, Form 4 is a hydrate and solvate. Table 4. Peaks from the X-ray powder diffractogram of crystalline Form 4 of Compound 1Form 5 of Compound 1(Form 5 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0180] In some embodiments, the present disclosure provides crystalline Form 5 of Compound 1. In some embodiments, Form 5 exhibits an XRPD of that in Fig. 5. In some embodiments, Form 5 exhibits an DSC and TGA of that in Fig. 22. In some embodiments, crystalline Form 5 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0181] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 5 of Compound 1 are shown in Table 5. In some embodiments, Form 5 is a solvate (e.g., of 2-methyl- THF).Table 5. Peaks from the X-ray powder diffractogram of crystalline Form 5 of Compound 1Form 6 of Compound 1(Form 6 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0182] In some embodiments, the present disclosure provides crystalline Form 6 of Compound 1. In some embodiments, Form 6 exhibits an XRPD of that in Fig. 6. In some embodiments, Form 6 exhibits an DSC and TGA of that in Fig. 23. In some embodiments, crystalline Form 6 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0183] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 6 of Compound 1 are shown in Table 6. In some embodiments, Form 6 is a solvate (e.g., of DCM). In some embodiments, Form 6 is a hydrate. In some embodiments, Form 6 is a hydrate and solvate. Table 6. Peaks from the X-ray powder diffractogram of crystalline Form 6 of Compound 1Form 7 of Compound 1(Form 7 of (A)-A-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0184] In some embodiments, the present disclosure provides crystalline Form 7 of Compound 1. In some embodiments, Form 7 exhibits an XRPD of that in Fig. 7. In some embodiments, Form 7 exhibits an DSC and TGA of that in Fig. 24. In some embodiments, crystalline Form 7 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0185] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 7 of Compound 1 are shown in Table 7. In some embodiments, Form 7 is an anhydrate.Table 7. Peaks from the X-ray powder diffractogram of crystalline Form 7 of Compound 1Form 8 of Compound 1(Form 8 of (A)-A-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0186] In some embodiments, the present disclosure provides crystalline Form 8 of Compound 1. In some embodiments, Form 8 exhibits an XRPD of that in Fig. 8. In some embodiments, Form 8 exhibits an DSC and TGA of that in Fig. 25. In some embodiments, crystalline Form 8 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0187] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 8 of Compound 1 are shown in Table 8. In some embodiments, Form 8 is a solvate (e.g., of ethyl acetate). Table 8. Peaks from the X-ray powder diffractogram of crystalline Form 8 of Compound 1Form 9 of Compound 1(Form 9 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0188] In some embodiments, the present disclosure provides crystalline Form 9 of Compound 1. In some embodiments, Form 9 exhibits an XRPD of that in Fig. 9. In some embodiments, Form 9 exhibits an DSC and TGA of that in Fig. 26.

[0189] In some embodiments, the present disclosure provides crystalline hydrate Form 9 of Compound 1. In some embodiments, the crystalline hydrate Form 9 of Compound 1 can be at least partially dehydrated to form a dehydrate. In some embodiments, the crystalline hydrate Form 9 of Compound 1 can be dehydrated to form a dehydrate. In some embodiments, the peaks in the X-ray powder diffraction of the hydrate and dehydrate vary by less than 20 values of less than 0.3°. In some embodiments, the peaks in the X-ray powder diffraction of the hydrate and dehydrate vary byless than 20 values of less than 0.2°. In some embodiments, the peaks in the X-ray powder diffraction of the hydrate and dehydrate vary by less than 20 values of less than 0.1°.

[0190] In some embodiments, Form 9 is a hydrate wherein hydration may be in the lattice. In some embodiments, Form 9 is a hydrate wherein hydration is in the lattice. In some embodiments, Form 9 is a hydrate wherein hydration might not be in the surface. In some embodiments, Form 9 is a hydrate wherein hydration is not in the surface.

[0191] In some embodiments, dehydration of Form 9 (e.g., to form a dehydrated sample) occurs when humidity is lower than about 20% RH. In some embodiments, the dehydrated sample can reabsorb water when humidity is higher than about 10% RH. In some embodiments, after this dehydration and rehydration process, XRPD pattern of the solid remains substantially unchanged. In some embodiments, Form 9 exhibits reversible water updatke of about 2% w / w to about 3% w / w (e.g., under DVS conditions)

[0192] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction (e.g., XRPD) pattern reflection at a 20 value of 13.0° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5° and 15.7° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, and 14.5° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, and 10.6° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, and 24.2° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, and 20.8° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, and 19.8° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, and 27.8° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ±0.5°, and 8.6° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, and 5.2° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, and 4.3° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, and 8.1° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, and 15.9° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, and 16.3° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.5°, 15.7° ± 0.5°, 19.8° ± 0.5°, 20.8° ± 0.5°, 15.9° ± 0.5°, 8.6° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 14.5° ± 0.5°, 27.8° ± 0.5°, 5.2° ± 0.5°, 16.3° ± 0.5°, 4.3° ± 0.5°, 20.1° ± 0.5°, 17.4° ± 0.5°, 25.7° ± 0.5°, 8.1° ± 0.5°, 28.8° ± 0.5°, 19.0° ± 0.5°, 19.3° ± 0.5°, 23.5° ± 0.5°, 25.1° ± 0.5°, 17.9° ± 0.5°, 30.7° ± 0.5°, 26.3° ± 0.5°, 28.2° ± 0.5°, 36.4° ± 0.5°, 33.2° ± 0.5°, 21.9° ± 0.5°, 27.0° ± 0.5°, 27.3° ± 0.5°, 34.5° ± 0.5°, 32.3° ± 0.5°, 26.7° ± 0.5°, 33.9° ± 0.5°, 30.5° ± 0.5°, 18.8° ± 0.5°, 30.1° ± 0.5°, 21.2° ± 0.5°, 22.4° ± 0.5°, 36.8° ± 0.5°, 23.7° ± 0.5°, 35.7° ± 0.5°, 29.5° ± 0.5°, 23.1° ± 0.5°, 31.5° ± 0.5°, 11.9° ± 0.5°, and 18.2° ± 0.5°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°,5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.5°, 15.7° ± 0.5°, 14.5° ± 0.5°, 10.6° ± 0.5°, 24.2° ± 0.5°, 20.8° ± 0.5°, 19.8° ± 0.5°, 27.8° ± 0.5°, 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, 8.1° ± 0.5°, 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.5°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 20.8° ± 0.5°, 19.8° ± 0.5°, and 27.8° ± 0.5°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 8.6° ± 0.5°, 5.2° ± 0.5°, 4.3° ± 0.5°, and 8.1° ± 0.5°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 15.9° ± 0.5°, 16.3° ± 0.5°, and 17.4° ± 0.5°.

[0193] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction (e.g., XRPD) pattern reflection at a 20 value of 13.0° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4° and 15.7° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, and 14.5°± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, and 10.6° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, and 24.2° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, and 20.8° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, and 19.8° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, and 27.8° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, and 8.6° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, and 5.2° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, and 4.3° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, and 8.1° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, and 15.9° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, and 16.3° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.4°, 15.7° ± 0.4°, 19.8° ± 0.4°, 20.8° ± 0.4°, 15.9° ± 0.4°, 8.6° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 14.5° ± 0.4°, 27.8° ± 0.4°, 5.2° ± 0.4°, 16.3° ± 0.4°, 4.3° ± 0.4°, 20.1° ± 0.4°, 17.4° ± 0.4°, 25.7° ± 0.4°, 8.1° ± 0.4°, 28.8° ± 0.4°, 19.0° ± 0.4°, 19.3° ± 0.4°, 23.5° ± 0.4°, 25.1° ± 0.4°, 17.9° ± 0.4°, 30.7° ± 0.4°, 26.3° ± 0.4°, 28.2° ± 0.4°,36.4° ± 0.4°, 33.2° ± 0.4°, 21.9° ± 0.4°, 27.0° ± 0.4°, 27.3° ± 0.4°, 34.5° ± 0.4°, 32.3° ± 0.4°, 26.7° ±0.4°, 33.9° ± 0.4°, 30.5° ± 0.4°, 18.8° ± 0.4°, 30.1° ± 0.4°, 21.2° ± 0.4°, 22.4° ± 0.4°, 36.8° ± 0.4°,23.7° ± 0.4°, 35.7° ± 0.4°, 29.5° ± 0.4°, 23.1° ± 0.4°, 31.5° ± 0.4°, 11.9° ± 0.4°, and 18.2° ± 0.4°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.4°, 15.7° ± 0.4°, 14.5° ± 0.4°, 10.6° ± 0.4°, 24.2° ± 0.4°, 20.8° ± 0.4°, 19.8° ± 0.4°, 27.8° ± 0.4°, 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, 8.1° ± 0.4°, 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.4°. In some embodiments, the solid form exhibits anXRPD pattern reflection at a 20 value of 14.5° ± 0.4°. In some embodiments, the solid form exhibitsan XRPD pattern reflection at a 20 value of 10.6° ± 0.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.4°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 20.8° ± 0.4°, 19.8° ± 0.4°, and 27.8° ± 0.4°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 8.6° ± 0.4°, 5.2° ± 0.4°, 4.3° ± 0.4°, and 8.1° ± 0.4°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 15.9° ± 0.4°, 16.3° ± 0.4°, and 17.4° ± 0.4°.

[0194] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction (e.g., XRPD) pattern reflection at a 20 value of 13.0° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3° and 15.7° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, and 14.5° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, and 10.6° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, and 24.2° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, and 20.8° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, and 19.8° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, and 27.8° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, and 8.6° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ±0.3°, and 5.2° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, and 4.3° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, and 8.1° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, and 15.9° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, and 16.3° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.3°, 15.7° ± 0.3°, 19.8° ± 0.3°, 20.8° ± 0.3°, 15.9° ± 0.3°, 8.6° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 14.5° ± 0.3°, 27.8° ± 0.3°, 5.2° ± 0.3°, 16.3° ± 0.3°, 4.3° ± 0.3°, 20.1° ± 0.3°, 17.4° ± 0.3°, 25.7° ± 0.3°, 8.1° ± 0.3°, 28.8° ± 0.3°, 19.0° ± 0.3°, 19.3° ± 0.3°, 23.5° ± 0.3°, 25.1° ± 0.3°, 17.9° ± 0.3°, 30.7° ± 0.3°, 26.3° ± 0.3°, 28.2° ± 0.3°, 36.4° ± 0.3°, 33.2° ± 0.3°, 21.9° ± 0.3°, 27.0° ± 0.3°, 27.3° ± 0.3°, 34.5° ± 0.3°, 32.3° ± 0.3°, 26.7° ± 0.3°, 33.9° ± 0.3°, 30.5° ± 0.3°, 18.8° ± 0.3°, 30.1° ± 0.3°, 21.2° ± 0.3°, 22.4° ± 0.3°, 36.8° ± 0.3°, 23.7° ± 0.3°, 35.7° ± 0.3°, 29.5° ± 0.3°, 23.1° ± 0.3°, 31.5° ± 0.3°, 11.9° ± 0.3°, and 18.2° ± 0.3°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8'± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.3°, 15.7° ± 0.3°, 14.5° ± 0.3°, 10.6° ± 0.3°, 24.2° ± 0.3°, 20.8° ± 0.3°, 19.8° ± 0.3°, 27.8° ± 0.3°, 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, 8.1° ± 0.3°, 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 20.8° ± 0.3°, 19.8° ± 0.3°, and 27.8° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 8.6° ± 0.3°, 5.2° ± 0.3°, 4.3° ± 0.3°, and 8.1° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 15.9° ± 0.3°, 16.3° ± 0.3°, and 17.4° ± 0.3°.

[0195] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction (e.g., XRPD) pattern reflection at a 20 value of 13.0° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2° and 15.7° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, and 14.5° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, and 10.6° ± 0.2°. In some embodiments, the present disclosure provides a solid form ofCompound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, and 24.2° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, and 20.8° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, and 19.8° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, and 27.8° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, and 8.6° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, and 5.2° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, and 4.3° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, and 8.1° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, and 15.9° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, and 16.3° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 19.8° ± 0.2°, 20.8° ±0.2°, 15.9° ± 0.2°, 8.6° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 14.5° ± 0.2°, 27.8° ± 0.2°, 5.2° ± 0.2°, 16.3° ± 0.2°, 4.3° ± 0.2°, 20.1° ± 0.2°, 17.4° ± 0.2°, 25.7° ± 0.2°, 8.1° ± 0.2°, 28.8° ± 0.2°, 19.0° ± 0.2°, 19.3° ± 0.2°, 23.5° ± 0.2°, 25.1° ± 0.2°, 17.9° ± 0.2°, 30.7° ± 0.2°, 26.3° ± 0.2°, 28.2° ± 0.2°, 36.4° ± 0.2°, 33.2° ± 0.2°, 21.9° ± 0.2°, 27.0° ± 0.2°, 27.3° ± 0.2°, 34.5° ± 0.2°, 32.3° ± 0.2°, 26.7° ± 0.2°, 33.9° ± 0.2°, 30.5° ± 0.2°, 18.8° ± 0.2°, 30.1° ± 0.2°, 21.2° ± 0.2°, 22.4° ± 0.2°, 36.8° ± 0.2°, 23.7° ± 0.2°, 35.7° ± 0.2°, 29.5° ± 0.2°, 23.1° ± 0.2°, 31.5° ± 0.2°, 11.9° ± 0.2°, and 18.2° ± 0.2°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least eight or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least nine or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least ten or more XRPDpattem reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least eleven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least twelve or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least fourteen or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits at least fifteen or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits two XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits three XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits four XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits five XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits six XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits seven XRPD pattern reflection(s) at 20 value(s) independentlyselected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits eight XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits nine XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits ten XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits eleven XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits twelve XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits thirteen XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°. In some embodiments, the solid form exhibits fourteen XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

[0196] In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 20.8° ± 0.2°, 19.8° ± 0.2°, and 27.8° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20value(s) independently selected from 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, and 8.1° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

[0197] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction (e.g., XRPD) pattern reflection at a 20 value of 13.0° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1° and 15.7° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, and 14.5° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, and 10.6° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, and 24.2° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, and 20.8° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, and 19.8° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, and 27.8° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, and 8.6° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, and 5.2° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, and 4.3° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ±0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, and 8.1° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, and 15.9° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, and 16.3° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 26 values of 13.0° ± 0.1°, 15.7° ± 0.1°, 19.8° ± 0.1°, 20.8° ± 0.1°, 15.9° ± 0.1°, 8.6° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 14.5° ± 0.1°, 27.8° ± 0.1°, 5.2° ± 0.1°, 16.3° ± 0.1°, 4.3° ± 0.1°, 20.1° ± 0.1°, 17.4° ± 0.1°, 25.7° ± 0.1°, 8.1° ± 0.1°, 28.8° ± 0.1°, 19.0° ± 0.1°, 19.3° ± 0.1°, 23.5° ± 0.1°, 25.1° ± 0.1°, 17.9° ± 0.1°, 30.7° ± 0.1°, 26.3° ± 0.1°, 28.2° ± 0.1°, 36.4° ± 0.1°, 33.2° ± 0.1°, 21.9° ± 0.1°, 27.0° ± 0.1°, 27.3° ± 0.1°, 34.5° ± 0.1°, 32.3° ± 0.1°, 26.7° ± 0.1°, 33.9° ± 0.1°, 30.5° ± 0.1°, 18.8° ± 0.1°, 30.1° ± 0.1°, 21.2° ± 0.1°, 22.4° ± 0.1°, 36.8° ± 0.1°, 23.7° ± 0.1°, 35.7° ± 0.1°, 29.5° ± 0.1°, 23.1° ± 0.1°, 31.5° ± 0.1°, 11.9° ± 0.1°, and 18.2° ± 0.1°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 26 value(s) independently selected from 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 26 value(s) independently selected from 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 26 value(s) independently selected from 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 26 value(s) independently selected from 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°. In some embodiments, the solid formexhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.1°, 15.7° ± 0.1°, 14.5° ± 0.1°, 10.6° ± 0.1°, 24.2° ± 0.1°, 20.8° ± 0.1°, 19.8° ± 0.1°, 27.8° ± 0.1°, 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, 8.1° ± 0.1°, 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.1°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 20.8° ± 0.1°, 19.8° ± 0.1°, and 27.8° ± 0.1°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 8.6° ± 0.1°, 5.2° ± 0.1°, 4.3° ± 0.1°, and 8.1° ± 0.1°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 15.9° ± 0.1°, 16.3° ± 0.1°, and 17.4° ± 0.1°.

[0198] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction (e.g., XRPD) pattern reflection at a 20 value of 13.0° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05° and 15.7° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, and 14.5° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, and 10.6° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, and 24.2° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, and 20.8° ± 0.05°. In some embodiments, the present disclosure provides a solid formof Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, and 19.8° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, and 27.8° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, and 8.6° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, and 5.2° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, and 4.3° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, and 8.1° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, and 15.9° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, and 16.3° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° ± 0.05°, 15.7° ± 0.05°, 19.8° ± 0.05°, 20.8° ± 0.05°, 15.9° ± 0.05°, 8.6° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 14.5° ± 0.05°, 27.8° ± 0.05°, 5.2° ± 0.05°, 16.3° ± 0.05°, 4.3° ± 0.05°, 20.1° ± 0.05°, 17.4° ± 0.05°, 25.7° ± 0.05°, 8.1° ± 0.05°, 28.8° ± 0.05°, 19.0° ± 0.05°, 19.3° ± 0.05°, 23.5° ± 0.05°, 25.1° ± 0.05°, 17.9° ± 0.05°, 30.7° ± 0.05°, 26.3° ± 0.05°, 28.2° ± 0.05°, 36.4° ± 0.05°, 33.2° ± 0.05°, 21.9°± 0.05°, 27.0° ± 0.05°, 27.3° ± 0.05°, 34.5° ± 0.05°, 32.3° ± 0.05°, 26.7° ± 0.05°, 33.9° ± 0.05°, 30.5° ± 0.05°, 18.8° ± 0.05°, 30.1° ± 0.05°, 21.2° ± 0.05°, 22.4° ± 0.05°, 36.8° ± 0.05°, 23.7° ± 0.05°, 35.7° ± 0.05°, 29.5° ± 0.05°, 23.1° ± 0.05°, 31.5° ± 0.05°, 11.9° ± 0.05°, and 18.2° ± 0.05°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.05°, 15.7° ± 0.05°, 14.5° ± 0.05°, 10.6° ± 0.05°, 24.2° ± 0.05°, 20.8° ± 0.05°, 19.8° ± 0.05°, 27.8° ± 0.05°, 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, 8.1° ± 0.05°, 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.05°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 20.8° ± 0.05°, 19.8° ± 0.05°, and 27.8° ± 0.05°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selectedfrom 8.6° ± 0.05°, 5.2° ± 0.05°, 4.3° ± 0.05°, and 8.1° ± 0.05°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 15.9° ± 0.05°, 16.3° ± 0.05°, and 17.4° ± 0.05°.

[0199] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction (e.g., XRPD) pattern reflection at a 20 value of 13.0° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0° and 15.7°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, and 14.5°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, and 10.6°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, and 24.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, and 20.8°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, and 19.8°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, and 27.8°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, and 8.6°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, and 5.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, and 4.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, and 8.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, and 15.9°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid formexhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, and 16.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, 16.3°, and 17.4°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 13.0°, 15.7°, 19.8°, 20.8°, 15.9°, 8.6°, 10.6°, 24.2°, 14.5°, 27.8°, 5.2°, 16.3°, 4.3°, 20.1°, 17.4°, 25.7°, 8.1°, 28.8°, 19.0°, 19.3°, 23.5°, 25.1°, 17.9°, 30.7°, 26.3°, 28.2°, 36.4°, 33.2°, 21.9°, 27.0°, 27.3°, 34.5°, 32.3°, 26.7°, 33.9°, 30.5°, 18.8°, 30.1°, 21.2°, 22.4°, 36.8°, 23.7°, 35.7°, 29.5°, 23.1°, 31.5°, 11.9°, and 18.2°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, 16.3°, and 17.4°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, 16.3°, and 17.4°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, 16.3°, and 17.4°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, 16.3°, and 17.4°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, 16.3°, and 17.4°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 13.0°, 15.7°, 14.5°, 10.6°, 24.2°, 20.8°, 19.8°, 27.8°, 8.6°, 5.2°, 4.3°, 8.1°, 15.9°, 16.3°, and 17.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 20.8°, 19.8°, and 27.8°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 8.6°, 5.2°, 4.3°, and 8.1°. In some embodiments, the solid form exhibitsone or more XRPD pattern reflection(s) at 20 value(s) independently selected from 15.9°, 16.3°, and 17.4°.

[0200] In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.5°. In some embodiments, the solid form of Compound 1 is solid Form 9 of Compound 1. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.8° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.8° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.9° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.6° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.8° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.2° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 16.3° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.3° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.1° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.4° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.7° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.1° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.8° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.0° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.3° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.5° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.1° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.9° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.7° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.3° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.2° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a20 value of 36.4° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.2° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.9° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.0° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.3° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 34.5° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 32.3° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.7° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.9° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.5° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.8° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.1° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.2° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 22.4° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.8° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.7° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 35.7° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 29.5° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.1° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 31.5° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 11.9° ± 0.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.2° ± 0.5°.

[0201] In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.3°. In some embodiments, the solid form of Compound 1 is solid Form 9 of Compound 1. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.8° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.8° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.9° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.6° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of10.6° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.8° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.2° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 16.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.1° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.4° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.7° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.1° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.8° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.0° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.1° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.9° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.7° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.2° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.4° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.2° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.9° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.0° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 34.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 32.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.7° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.9° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.8° ± 0.3°. Insome embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.1° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.2° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 22.4° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.8° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.7° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 35.7° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 29.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.1° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 31.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 11.9° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.2° ± 0.3°.

[0202] In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.2°. In some embodiments, the solid form of Compound 1 is solid Form 9 of Compound 1. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.8° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.8° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.9° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.6° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.8° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.2° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 16.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.1° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.4° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.7° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.1° ± 0.2°. In some embodiments, thesolid form exhibits an XRPD pattern reflection at a 20 value of 28.8° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.0° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.1° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.9° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.7° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.2° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.4° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.2° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.9° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.0° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 34.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 32.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.7° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.9° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.8° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.1° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.2° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 22.4° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.8° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.7° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 35.7° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 29.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.1° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 31.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPDpattem reflection at a 20 value of 11.9° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.2° ± 0.2°.

[0203] In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.1°. In some embodiments, the solid form of Compound 1 is solid Form 9 of Compound 1. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.8° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.8° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.9° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.6° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.8° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.2° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 16.3° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.3° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.1° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.4° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.7° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.1° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.8° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.0° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.3° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.5° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.1° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.9° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.7° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.3° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.2° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a20 value of 36.4° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.2° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.9° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.0° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.3° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 34.5° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 32.3° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.7° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.9° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.5° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.8° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.1° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.2° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 22.4° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.8° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.7° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 35.7° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 29.5° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.1° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 31.5° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 11.9° ± 0.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.2° ± 0.1°.

[0204] In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0° ± 0.05°. In some embodiments, the solid form of Compound 1 is solid Form 9 of Compound 1. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.8° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.8° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.9° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.6° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a20 value of 10.6° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.8° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.2° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 16.3° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.3° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.1° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.4° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.7° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.1° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.8° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.0° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.3° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.5° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.1° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.9° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.7° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.3° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.2° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.4° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.2° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.9° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.0° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.3° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 34.5° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 32.3° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.7° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.9° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.5° ± 0.05°. In some embodiments, the solid form exhibits an XRPDpattem reflection at a 20 value of 18.8° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.1° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.2° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 22.4° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.8° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.7° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 35.7° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 29.5° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.1° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 31.5° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 11.9° ± 0.05°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.2° ± 0.05°.

[0205] In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 13.0°. In some embodiments, the solid form of Compound 1 is solid Form 9 of Compound 1. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.7°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.8°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.8°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 15.9°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.6°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 10.6°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 24.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.8°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 5.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 16.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 20.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.7°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 8.1°. In some embodiments, the solid formexhibits an XRPD pattern reflection at a 20 value of 28.8°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.0°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 25.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 17.9°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.7°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 28.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.9°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.0°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 27.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 34.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 32.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 26.7°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 33.9°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.8°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 30.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 21.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 22.4°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 36.8°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.7°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 35.7°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 29.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 23.1°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 31.5°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 11.9°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 18.2°.

[0206] In some embodiments, Form 9 (e.g., crystalline hydrate Form 9) exhibits at least one of the X-ray powder diffraction pattern reflections in Table 9. In some embodiments, Form 9 is a hydrate.Table 9. Peaks from the X-ray powder diffractogram of crystalline hydrate Form 9 of Compound 1 above 2% relative intensity

[0207] In some embodiments, the solid form exhibits the XRPD pattern as shown in Figure 9. In some embodiments, the solid form exhibits an XRPD pattern substantially similar to that shown in Figure 9.

[0208] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 25.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 20.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at202.2 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at202.2 °C ± 4.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 3.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at202.2 °C ± 2.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 1.0 °C. In some embodiments, the solidform exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 0.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at about 202.2 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature (e.g., the onset temperature of the 202.2 °C peak may be) at 201.3 °C ± 25.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 20.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 4.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 3.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 2.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 1.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C ± 0.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at about 201.3 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 201.3 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an enthalpy of (e.g., the endothermic peak at about 202.2 may have an enthalpy of) about 90.3 J / g ± 5.0 J / g.

[0209] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 2.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 1.0 °C. In some embodiments, the solid form exhibits adifferential scanning calorimetry thermogram comprising an endothermic peak at about 63.8 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 45.9 °C ± 15.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature (e.g., the onset temperature of the 63.8 °C peak may be) at 45.9 °C ± 10.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 45.9 °C ± 5.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 45.9 °C ± 2.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 45.9 °C ± 1.0 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 45.9 °C ± 0.5 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at about 45.9 °C. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an onset temperature at 45.9 °C.

[0210] In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram as shown in Figure 26. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram substantially similar to that shown in Figure 26. In some embodiments, the solid form exhibits a differential scanning calorimetry thermogram comprising an enthalpy of (e.g., the endothermic peak at about 63.8 may have an enthalpy of) about 35.4 J / g ± 5.0 J / g.

[0211] In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 1.0% at 90 °C ± 20.0 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.5% at 90 °C ± 10.0 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.4% at 90 °C ± 5.0 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.3% at 90 °C ± 3.0 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.2% at 90 °C ± 2.0 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.1% at 90 °C ± 1.0 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.05% at 90 °C ± 0.05 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.5% at 90 °C ± 0.1 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% ± 0.1% at 90 °C ± 5 °C as determined by thermogravimetric analysis. In someembodiments, the solid form exhibits a sample weight loss of about 2.1% at about 90 °C as determined by thermogravimetric analysis. In some embodiments, the solid form exhibits a sample weight loss of 2.1% at 90 °C as determined by thermogravimetric analysis.

[0212] In some embodiments, the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 26. In some embodiments, the solid form exhibits a thermogravimetric analysis (e.g., TGA) thermogram substantially similar to that shown in Figure 26.

[0213] In some embodiments, the solid form is a monoclinic crystal system. In some embodiments, the solid form comprises a unit cell of space group P2i. In some embodiments, the solid form comprises a unit cell of volume 1781 A3± 100 A3. In some embodiments, the solid form comprises a unit cell with unit cell distances of 18.3 A ± 3.0 A, 4.8 A ± 3.0 A, and 22.0 A ± 3.0 A. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90° ± 3°, 113.4° ± 3.0°, and 90° ± 3°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90° ± 3°, 113.4° ± 3.0°, and 90°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90°, 113.4° ± 3.0°, and 90°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90°, 113.4° ± 2.0°, and 90°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90°, 113.4° ± 1.0°, and 90°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90°, 113.4° ± 0.5°, and 90°. In some embodiments, the solid form comprises a unit cell with unit cell angles of about 90°, 113.4°, and 90°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90°, 113.4°, and 90°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90° ± 3.0°, 113.4° ± 3.0°, and 90° ± 3.0°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90° ± 2°, 113.4° ± 2.0°, and 90° ± 2°. In some embodiments, the solid form comprises a unit cell with unit cell angles of 90° ± 2.0°, 113.4° ± 2.0°, and 90° ± 2.0°. In some embodiments, the solid form comprises a unit cell with two unit cell angles of about 90°. In some embodiments, the solid form comprises a unit cell with two unit cell angles of 90°. In some embodiments, the solid form comprises a unit cell with one unit cell angle of 113.4° ± 3.0°, 113.4° ± 2.0°, 113.4° ± 1.0°, or 113.4° ± 0.5°, or about 113.4°, or 113.4°. In some embodiments, the solid form is crystalline. In some embodiments, the solid form is a hydrate. In some embodiments, the solid form is a dehydrate. In some embodiments, the solid form is solid Form 9 of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)- 2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide. In some embodiments, the solid form is crystalline and obtained from methanol, ethanol, isopropanol, toluene, water, acetonitrile, heptane, acetone, tert-butyl methyl ether, 2-butanone, ethyl acetate, isopropyl acetate, tetrahydrofuran, or any combination thereof. In some embodiments, the solid form is crystalline and obtained from methanol, water, acetonitrile, acetone, or any combination thereof. In someembodiments, the solid form is crystalline and obtained by slurry or anti-solvent precipitation. In some embodiments, the solid form is crystalline and obtained from methanol and water. In some embodiments, the solid form is obtained by anti-solvent precipitation. In some embodiments, the solid form is crystalline and obtained from acetone and water. In some embodiments, the solid form is obtained by slurry.

[0214] In some embodiments, the present disclosure provides a composition comprising Form 9 of Compound 1. In some embodiments, the present disclosure provides a composition comprising Form 9 and optionally one or more other Forms of Compound 1. In some embodiments, the amount of other crystalline or amorphous forms in the composition comprising Form 9 is 10% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms in the composition comprising Form 9 is 5% (w / w) or less. In some embodiments, the amount of other crystalline or amorphous forms in the composition comprising Form 9 is 1% (w / w) or less. In some embodiments, provided is a composition comprising solid Form 9 of Compound 1 in 97% chemical purity or more. In some embodiments, provided is a composition comprising solid Form 9 of Compound 1 in 98% chemical purity or more. In some embodiments, provided is a composition comprising solid Form 9 of Compound 1 in 99% chemical purity or more. In some embodiments, provided is a composition comprising solid Form 9 of Compound 1 in 99.5% chemical purity or more.

[0215] In some embodiments, provided herein is a crystalline Form of Compound 1, wherein the Crystalline Form has at least one of the following properties: (i) an XRPD pattern substantially the same as that shown in Figure 9; (ii) at least two XRPD pattern reflection(s) at 20 values independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°,20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ±0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°; (iii) a TGA similar to the one set forth in Figure 26; (iv) DSC substantially similar to the one set forth in Figure 26; (v) a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 15.0 °C; a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 15.0 °C; weight loss of 2.1% ± 0.5% at 90 °C ± 10.0 °C as determined by thermogravimetric analysis; a monoclinic crystal system; a 2i unit cell; a unit cell volume of 1781 A3± 100 A3; a unit cell with unit cell distances of 18.3 A ± 3.0 A, 4.8 A ± 3.0 A, and 22.0 A ± 3.0 A; a unit cell with unit cell angles of 90° ± 3.0, 113.4° ± 3.0°, and 90° ± 3.0; or an XRPD with peaks that vary by 20 values of less than 0.3° in the X-ray powder diffraction between hydrated dehydrated states.

[0216] In some embodiments, provided herein is a crystalline Form of Compound 1, wherein the Crystalline Form has at least one of the following properties: (i) an XRPD pattern substantially thesame as that shown in Figure 9; (ii) at least two XRPD pattern reflection(s) at 20 values independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°,20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ±0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°; (iii) a TGA similar to the one set forth in Figure 26; (iv) DSC substantially similar to the one set forth in Figure 26; (v) a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 5.0 °C with onset at 45.9 °C ± 5.0 °C; a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 15.0 °C with onset at 201.3 °C ± 15.0 °C; weight loss of 2.1% ± 0.5% at 90 °C ± 10.0 °C as determined by thermogravimetric analysis; a monoclinic crystal system; a 2i unit cell; a unit cell volume of 1781 A3± 100 A3; a unit cell with unit cell distances of 18.3 A ± 3.0 A, 4.8 A ± 3.0 A, and 22.0 A ± 3.0 A; or a unit cell with unit cell angles of 90°, 113.4° ± 3.0°, and 90°.

[0217] In some embodiments, the present disclosure provides a pharmaceutical composition comprising any of the solid forms disclosed herein (e.g., Form 9 of Compound 1) and one or more pharmaceutically acceptable excipient(s).Form 10 of Compound 1(Form 10 of (A)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0218] In some embodiments, the present disclosure provides crystalline Form 10 of Compound 1.In some embodiments, Form 10 exhibits an XRPD of that in Fig. 10. In some embodiments, Form 10 exhibits an DSC and TGA of that in Fig. 27. In some embodiments, crystalline Form 10 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0219] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 10 of Compound 1 are shown in Table 10. In some embodiments, Form 10 is a solvate (e.g., of methyl ethyl ketone).Table 10. Peaks from the X-ray powder diffractogram of crystalline Form 10 of Compound 1 aForm 11 of Compound 1(Form 11 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0220] In some embodiments, the present disclosure provides crystalline Form 11 of Compound 1.In some embodiments, Form 11 exhibits an XRPD of that in Fig. 11. In some embodiments, Form 11 exhibits an DSC and TGA of that in Fig. 28. In some embodiments, crystalline Form 11 exhibits at least one of the X-ray powder diffraction pattern reflections below.

[0221] In some embodiments, peaks from the X-ray powder diffractogram of crystalline Form 11 of Compound 1 are shown in Table 11. In some embodiments, Form 11 is a solvate (e.g., of diethylether). In some embodiments, Form 11 is a hydrate. In some embodiments, Form 11 is a hydrate and solvate.

[0222] Table 11. Peaks from the X-ray powder diffractogram of crystalline Form 11 of Compound 1Form 12 of Compound 1(Form 12 of (7?)-7V-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide)

[0223] In some embodiments, the present disclosure provides crystalline anhydrate Form 12 of Compound 1.

[0224] In some embodiments, the present disclosure provides crystalline anhydrate Form 12 of Compound 1. In some embodiments, Form 12 exhibits an XRPD of that in Fig. 12. In some embodiments, Form 12 exhibits an DSC and TGA of that in Fig. 29.

[0225] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3° and 4.1° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid formexhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, and 3.8° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, and 3.8° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, and 19.4° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, and 12.9° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, and 19.1° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, and 21.5° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, and 25.1° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, and 12.5° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, and 24.6° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, and 18.0° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, and 10.7° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, and 28.4. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ±0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, 19.9° ± 0.3°, 27.3° ± 0.3°, 17.6° ± 0.3°, 23.2° ± 0.3°, 20.9° ± 0.3°, 6.9° ± 0.3°, 13.2° ± 0.3°, 22.5° ± 0.3°, 16.7° ± 0.3°, 28.1° ± 0.3°, 17.0° ± 0.3°, 15.5° ± 0.3°, 26.1° ± 0.3°, 22.1° ± 0.3°, 15.9° ± 0.3°, 29.3° ± 0.3°, 30.1° ± 0.3°, 5.2° ± 0.3°, and 8.9° ± 0.3°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°. In some embodiments, the solid form exhibits at least seven or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.3°, 4.1° ± 0.3°, 3.8° ± 0.3°, 19.4° ± 0.3°, 12.9° ± 0.3°, 19.1° ± 0.3°, 21.5° ± 0.3°, 25.1° ± 0.3°, 12.5° ± 0.3°, 24.6° ± 0.3°, 18.0° ± 0.3°, 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.1° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 3.8° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.4° ± 0.3°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 12.9° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selectedfrom 19.1° ± 0.3°, 21.5° ± 0.3°, and 25.1° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 12.5° ± 0.3°, 24.6° ± 0.3°, and 18.0° ± 0.3°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 10.7° ± 0.3°, 28.4° ± 0.3°, and 27.3° ± 0.3°.

[0226] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2° and 4.1° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, and 3.8° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, and 3.8° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, and 19.4° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, and 12.9° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, and 19.1° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, and 21.5° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, and 25.1° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, and 12.5° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, and 24.6° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°,19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, and 18.0° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, and 10.7° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, and 28.4. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, 19.9° ± 0.2°, 27.3° ± 0.2°, 17.6° ± 0.2°, 23.2° ± 0.2°, 20.9° ± 0.2°, 6.9° ± 0.2°, 13.2° ± 0.2°, 22.5° ± 0.2°, 16.7° ± 0.2°, 28.1° ± 0.2°, 17.0° ± 0.2°, 15.5° ± 0.2°, 26.1° ± 0.2°, 22.1° ± 0.2°, 15.9° ± 0.2°, 29.3° ± 0.2°, 30.1° ± 0.2°, 5.2° ± 0.2°, and 8.9° ± 0.2°. In some embodiments, the solid form exhibits at least two or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°. In some embodiments, the solid form exhibits at least three or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°. In some embodiments, the solid form exhibits at least four or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°. In some embodiments, the solid form exhibits at least five or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°. In some embodiments, the solid form exhibits at least six or more XRPD pattern reflection(s) at 20 value(s) independently selected from 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°. In some embodiments, the solid form exhibits at least seven or more XRPD patternreflection(s) at 20 value(s) independently selected from 14.5° ± 0.2°, 4.1° ± 0.2°, 3.8° ± 0.2°, 19.4° ± 0.2°, 12.9° ± 0.2°, 19.1° ± 0.2°, 21.5° ± 0.2°, 25.1° ± 0.2°, 12.5° ± 0.2°, 24.6° ± 0.2°, 18.0° ± 0.2°, 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 4.1° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 3.8° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 19.4° ± 0.2°. In some embodiments, the solid form exhibits an XRPD pattern reflection at a 20 value of 12.9° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 19.1° ± 0.2°, 21.5° ± 0.2°, and 25.1° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 12.5° ± 0.2°, 24.6° ± 0.2°, and 18.0° ± 0.2°. In some embodiments, the solid form exhibits one or more XRPD pattern reflection(s) at 20 value(s) independently selected from 10.7° ± 0.2°, 28.4° ± 0.2°, and 27.3° ± 0.2°.

[0227] In some embodiments, the present disclosure provides a solid form of (R)-N-(l-(5-cyano-3- fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an XRPD pattern reflection at a 20 value of 14.5° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1° and 4.1° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, and 3.8° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, and 3.8° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, and 19.4° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits an XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, and 12.9° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, and 19.1° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, and 21.5° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°,4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, and 25.1° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, 25.1° ± 0.1°, and 12.5° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, 25.1° ± 0.1°, 12.5° ± 0.1°, and 24.6° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, 25.1° ± 0.1°, 12.5° ± 0.1°, 24.6° ± 0.1°, and 18.0° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, 25.1° ± 0.1°, 12.5° ± 0.1°, 24.6° ± 0.1°, 18.0° ± 0.1°, and 10.7° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, 25.1° ± 0.1°, 12.5° ± 0.1°, 24.6° ± 0.1°, 18.0° ± 0.1°, 10.7° ± 0.1°, and 28.4. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, 25.1° ± 0.1°, 12.5° ± 0.1°, 24.6° ± 0.1°, 18.0° ± 0.1°, 10.7° ± 0.1°, 28.4° ± 0.1°, and 27.3° ± 0.1°. In some embodiments, the present disclosure provides a solid form of Compound 1, wherein the solid form exhibits XRPD pattern reflections at 20 values of 14.5° ± 0.1°, 4.1° ± 0.1°, 3.8° ± 0.1°, 19.4° ± 0.1°, 12.9° ± 0.1°, 19.1° ± 0.1°, 21.5° ± 0.1°, 25.1° ± 0.1°, 12.5° ± 0.1°, 24.6° ± 0.1°, 18.0° ± 0.1°, 10.7° ± 0.1°, 28.4° ± 0.1°, 19.9° ± 0.1°, 27.3° ± 0.1°, 17.6° ± 0.1°, 23.2° ± 0.1°, 20.9° ± 0.1°, 6.9° ± 0.1°, 13.2° ± 0.1°, 22.5° ± 0.1...

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A crystalline solid form of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2- oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction pattern reflection at a 20 value of 13.0° ± 0.2°.

2. A crystalline solid form of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2- oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits X-ray powder diffraction pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, and 14.5° ± 0.2°.

3. A crystalline solid form of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2- oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits an X-ray powder diffraction pattern reflections at 20 values of 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, and 20.8° ± 0.2°.

4. A crystalline solid form of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2- oxo-l,4-dihydroquinazolin-3(2H)-yl)acetamide, wherein the solid form exhibits at least two or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

5. The crystalline solid form of claim 4, wherein the solid form exhibits at least three or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

6. The crystalline solid form of claim 4 or claim 5, wherein the solid form exhibits at least four or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

7. The crystalline solid form of any one of claims 4 to 6, wherein the solid form exhibits at least five or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

8. The crystalline solid form of any one of claims 4 to 7, wherein the solid form exhibits at least six or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

9. The crystalline solid form of any one of claims 4 to 8, wherein the solid form exhibits at least seven or more X-ray powder diffraction pattern reflection(s) at 20 value(s) independently selected from 13.0° ± 0.2°, 15.7° ± 0.2°, 14.5° ± 0.2°, 10.6° ± 0.2°, 24.2° ± 0.2°, 20.8° ± 0.2°, 19.8° ± 0.2°, 27.8° ± 0.2°, 8.6° ± 0.2°, 5.2° ± 0.2°, 4.3° ± 0.2°, 8.1° ± 0.2°, 15.9° ± 0.2°, 16.3° ± 0.2°, and 17.4° ± 0.2°.

10. The crystalline solid form of any one of claims 1 to 9, wherein the solid form exhibits the X- ray powder diffraction pattern as shown in Figure 9.

11. The crystalline solid form of any one of claims 1 to 10, wherein the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 202.2 °C ± 15.0 °C.

12. The crystalline solid form of claim 11, wherein the onset temperature of the endothermic peak is at 201.3 °C ± 15.0 °C.

13. The crystalline solid form of any one of claims 1 to 12, wherein the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 63.8 °C ± 15.0 °C.

14. The crystalline solid form of claim 13, wherein the onset temperature of the endothermic peak is at 45.9 °C ± 15.0 °C.

15. The crystalline solid form of any one of claims 1 to 14, wherein the solid form exhibits a differential scanning calorimetry thermogram as shown in Figure 26.

16. The crystalline solid form of any one of claims 1 to 15, wherein the solid form exhibits a sample weight loss of 2.1% ± 0.5% at 90 °C ± 10.0 °C as determined by thermogravimetric analysis.

17. The crystalline solid form of any one of claims 1 to 16, wherein the solid form exhibits the thermogravimetric analysis thermogram as shown in Figure 26.

18. The crystalline solid form of any one of claims 1 to 17, wherein the volume of the unit cell is 1781 A3± 100 A3.

19. The crystalline solid form of claim 18, wherein the solid form comprises a unit cell with unit cell distances of 18.3 A ± 3.0 A, 4.8 A ± 3.0 A, and 22.0 A ± 3.0 A.

20. The crystalline solid form of claim 18 or 19, wherein the solid form comprises a unit cell withunit cell angles of 90°, 113.4° ± 2.0°, and 90°.

21. The crystalline solid form of any one of claims 1 to 20, wherein the solid form is a hydrate.

22. The crystalline solid form of any one of claims 1 to 21, wherein the solid form is a dehydrate.

23. The crystalline solid form of any one of claims 1 to 22, wherein the solid form is solid Form9 of (R)-N-(l-(5-cyano-3-fluoropyridin-2-yl)ethyl)-2-(5,6-difluoro-2-oxo-l,4- dihydroquinazolin-3(2H)-yl)acetamide.

24. A pharmaceutical composition comprising the solid form of any one of claims 1 to 23 and one or more pharmaceutically acceptable excipient(s).

25. A pharmaceutical composition comprising Compound 1 or Compound 2, and one or more pharmaceutically acceptable excipient(s).

26. A pharmaceutical composition in the form of a solid oral dosage form comprising: (i)Compound(Compound 1) or a pharmaceutically acceptable salt or solvate thereof and (ii) one or more pharmaceutically acceptable excipient(s).

27. A pharmaceutical composition in the form of a solid oral dosage form comprising: (i)Compound(Compound 2) or a pharmaceutically acceptable salt or solvate thereof and (ii) one or more pharmaceutically acceptable excipient(s).

28. The pharmaceutical composition of any one of claims 24 to 27, wherein the pharmaceutical composition comprises between about 5 mg and about 300 mg of Compound 1 or Compound 2, or of a pharmaceutically acceptable salt or solvate of either Compound 1 or Compound 2.

29. The pharmaceutical composition of any one of claims 24 to 28, wherein the pharmaceutical composition comprises about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1.

30. The pharmaceutical composition of any one of claims 24 to 29, wherein Compound 1, or a pharmaceutically acceptable salt or solvate thereof, is in the form of microparticles.

31. The pharmaceutical composition of claim 30, wherein the microparticles are obtained from jet milling Compound 1.

32. The pharmaceutical composition of any one of claims 24 to 31, wherein the pharmaceutical composition comprises one or more surfactactant(s), one or more filler(s), one or more binder(s), one or more disintegrant(s), one or more coloring agent(s), one or more flavoring agent(s), one or more preservative(s), one or more adjustor(s), one or more anti adherents, one or more coating agent(s), one or more moisturizing agent(s), or one or more solvent(s).

33. The pharmaceutical composition of any one of claims 24 to 32, wherein the pharmaceutical composition comprises one or more filler(s), binder(s), disintegrant(s), wetting agent(s), lubricant(s), or glidant(s).

34. The pharmaceutical composition of any one of claims 24 to 33, wherein the pharmaceutical composition comprises one or more polymer(s).

35. The pharmaceutical composition of any one of claims 24 to 34, wherein the pharmaceutical composition comprises one or more filler(s).

36. The pharmaceutical composition of any one of claims 24 to 35, wherein the pharmaceutical composition comprises one or more binder(s).

37. The pharmaceutical composition of any one of claims 24 to 36, wherein the pharmaceutical composition comprises one or more disinegrant(s).

38. The pharmaceutical composition of any one of claims 24 to 37, wherein the pharmaceutical composition comprises one or more wetting agent(s).

39. The pharmaceutical composition of any one of claims 24 to 38, wherein the pharmaceutical composition comprises one or more lubricant(s).

40. The pharmaceutical composition of any one of claims 24 to 39, wherein the pharmaceutical composition comprises one or more glidant(s).

41. The pharmaceutical composition of any one of claims 24 to 40, wherein the pharmaceutical composition comprises microcrystalline cellulose.

42. The pharmaceutical composition of any one of claims 24 to 41, wherein the pharmaceutical composition comprises one or more surfactant(s).

43. The pharmaceutical composition of any one of claims 24 to 42, wherein the pharmaceutical composition comprises one or more wetting agent(s) independently selected from sodium lauryl sulfate (SLS).

44. The pharmaceutical composition of any one of claims 24 to 43, wherein the pharmaceutical composition comprises one or more antioxidant(s).

45. The pharmaceutical composition of any one of claims 24 to 44, wherein the pharmaceutical composition comprises one or more antioxidant(s) independently selected from an alkylated hydroxyarene, acetone, sodium formaldehyde, sulfoxylate, thiourea, EDTA, tertbutylhydroquinone, gallic acid, a gallate, pyrogallol, ascorbic acid, a derivative of ascorbic acid, fumaric acid, a derivative of fumaric acid, citric acid, a derivative of citric acid, a sulfite, a bisulfite, a metasulfite, a thiosulfate, a sulfinate, hypophosphorous acid, a derivative of hypophosphorous acid, monothioglycerol, vitamin E, cyanidins, lutein, lycopene, antioxidant 1135, tris(4-tert-butyl-3-hydroxy-2,6-dimethyl-benzyl), malic acid, methionine, capsorubin, tartaric acid, erythorbic acid, thymol, and clove extract.

46. The pharmaceutical composition of any one of claims 24 to 45, wherein the pharmaceutical composition comprises one or more antioxidant(s) selected from butylated hydroxytoluene.

47. The pharmaceutical composition of any one of claims 24 to 46, wherein the pharmaceutical composition one or more disintegrant(s) independently selected from silicified MCC and croscarmellose sodium.

48. The pharmaceutical composition of any one of claims 24 to 47, wherein the pharmaceutical composition comprises a disintegrant independently selected from Croscarmellose Sodium.

49. The pharmaceutical composition of any one of claims 24 to 48, wherein the pharmaceutical composition comprises one or more filler(s) independently selected from lactose, silicified MCC, and mannitol SD 100.

50. The pharmaceutical composition of any one of claims 24 to 49, wherein the pharmaceutical composition comprises a filler independently selected from lactose.

51. The pharmaceutical composition of any one of claims 24 to 50, wherein the pharmaceutical composition comprises a glidant independently selected from colloidal silicon dioxide.

52. The pharmaceutical composition of any one of claims 24 to 51, wherein the pharmaceutical composition comprises a lubricant independently selected from sodium stearyl fumarate (SSF).

53. The pharmaceutical composition of any one of claims 24 to 52, wherein the pharmaceutical composition comprises about 5% w / w to about 25% w / w Compound 1.

54. The pharmaceutical composition of any one of claims 24 to 53, wherein the pharmaceutical composition comprises about 0.3% w / w to about 2.5% w / w sodium laurel sulfate.

55. The pharmaceutical composition of any one of claims 24 to 54, wherein the pharmaceutical composition comprises about 1% w / w to about 5% w / w hydroxypropyl cellulose.

56. The pharmaceutical composition of any one of claims 24 to 55, wherein the pharmaceutical composition comprises about 2% w / w to about 15% w / w colloidal silicon dioxide.

57. The pharmaceutical composition of any one of claims 24 to 56, wherein the pharmaceutical composition comprises about 2.5% w / w to about 45% w / w croscarmellose sodium.

58. The pharmaceutical composition of any one of claims 24 to 57, wherein the pharmaceutical composition comprises about 0.5% w / w to about 5% w / w sodium stearyl fumarate.

59. The pharmaceutical composition of any one of claims 24 to 58, wherein the pharmaceutical composition comprises about 5% w / w to about 40% w / w microcrystalline cellulose.

60. The pharmaceutical composition of any one of claims 24 to 59, wherein the pharmaceutical composition comprises about 10% w / w to 60% w / w lactose monohydrate.

61. The pharmaceutical composition of any one of claims 24 to 60, wherein the pharmaceutical composition comprises about 15% w / w to about 20% w / w Compound 1, about 55% w / w to about 70% w / w one or more filler(s), about 2% w / w to about 5% w / w one or more binder(s), about 5% w / w to about 15% w / w one or more disintegrant(s), about 1% w / w to about 3% w / w one or more wetting agent(s), about 0.5% w / w to about 2% w / w one or more lubricant(s), and about 1% w / w to about 5% w / w one or more glidant(s).

62. The pharmaceutical composition of any one of claims 24 to 61, wherein the pharmaceutical composition comprises about 15% w / w to about 20% w / w Compound 1, about 55% w / w to about 70% w / w one or more filler(s), about 2% w / w to about 5% w / w one or more binder(s), about 5% w / w to about 15% w / w one or more disintegrant(s), about 1% w / w to about 3% w / w one or more wetting agent(s), about 0.5% w / w to about 2% w / w one or more lubricant(s), about 1% w / w to about 5% w / w one or more glidant(s), and about 1% w / w to about 5% w / w of a film coting.

63. The pharmaceutical composition of any one of claims 24 to 62, wherein the pharmaceutical composition comprises microcrystalline cellulose, lactose monohydrate, hydroxypropyl cellulose, croscarmellose sodium, sodium lauryl sulfate, sodium stearyl fumarate, and colloidal silicon dioxide.

64. The pharmaceutical composition of any one of claims 24 to 63, wherein the pharmaceutical composition comprises microcrystalline cellulose, lactose monohydrate, hydroxypropyl cellulose, croscarmellose sodium, sodium lauryl sulfate, sodium stearyl fumarate, colloidal silicon dioxide, and a film coating.

65. The pharmaceutical composition of any one of claims 24 to 64, wherein the pharmaceutical composition comprises Compound 1, microcrystalline cellulose, lactose monohydrate, hydroxypropyl cellulose, croscarmellose sodium, sodium lauryl sulfate, sodium stearyl fumarate, colloidal silicon dioxide, and a film coating.

66. The pharmaceutical composition of any one of claims 24 to 65, wherein the pharmaceutical composition comprises about 15% w / w to about 20% w / w microcrystalline cellulose, about 40% w / w to about 50% w / w lactose monohydrate, about 2% w / w to about 5% w / w hydroxypropyl cellulose, about 5% w / w to about 15% w / w croscarmellose sodium, about 1% w / w to about 3% w / w sodium lauryl sulfate, about 0.5% w / w to about 2% w / w sodium stearyl fumarate, and about 1% w / w to about 5% w / w colloidal silicon dioxide.

67. The pharmaceutical composition of any one of claims 24 to 66, wherein the pharmaceutical composition comprises about 15% w / w to about 20% w / w Compound 1, about 15% w / w to about 20% w / w microcrystalline cellulose, about 40% w / w to about 50% w / w lactose monohydrate, about 2% w / w to about 5% w / w hydroxypropyl cellulose, about 5% w / w to about 15% w / w croscarmellose sodium, about 1% w / w to about 3% w / w sodium lauryl sulfate, about 0.5% w / w to about 2% w / w sodium stearyl fumarate, about 1% w / w to about 5% w / w colloidal silicon dioxide, and about 1% w / w to about 5% w / w of a film coting.

68. The pharmaceutical composition of any one of claims 24 to 67 wherein the Compound 1 is the solid form of any one of claims 1 to 23.

69. A method of treating a cardiovascular disease or related condition, comprising administering to a subject in need thereof a dose of about 5 mg to about 2000 mg per day of Compound 1 :

70. The method of claim 69, comprising administering to the subject a dose of about 5 mg to about 300 mg per day of Compound 1.

71. The method of claim 69, comprising administering to the subject a dose of about 25 mg to about 200 mg per day of Compound 1.

72. The method of claim 69, comprising administering to the subject a dose of about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, per day.

73. The method of claim 69, comprising administering to the subject a dose of about 25 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, once per day.

74. The method of claim 69, comprising administering to the subject a dose of about 50 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, once per day.

75. The method of claim 69, comprising administering to the subject a dose of about 100 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, once per day.

76. The method of claim 69, comprising administering to the subject a dose of about 150 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, once per day.

77. The method of claim 69, comprising administering to the subject a dose of about 200 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, once per day.

78. The method of claim 69, comprising administering to the subject a dose of about 25 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, twice per day.

79. The method of claim 69, comprising administering to the subject a dose of about 50 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, twice per day.

80. The method of claim 69, comprising administering to the subject a dose of about 100 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, twice per day.

81. The method of claim 69, comprising administering to the subject a dose of about 150 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, twice per day.

82. The method of claim 69, comprising administering to the subject a dose of about 200 mg of Compound 1, or of a pharmaceutically acceptable salt or solvate of Compound 1, twice per day.

83. A method of treating a cardiovascular disease or related condition, the method comprising administering to a subject Compound 1, wherein Left Ventricular Ejection Fraction (LVEF) of the patient by is modulated by no more than about 5%.

84. A method of treating a cardiovascular disease or related condition, the method comprising administering to a subject Compound 1, wherein Left Ventricular Ejection Fraction (LVEF) of the patient by is modulated by about 0% to about 10%.

85. A method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to maintain or modulate Left Ventricular Ejection Fraction (LVEF) to a range between about 0.40 and about 0.60.

86. A method of treating a cardiovascular disease or related condition, comprising administering to a subject a Compound 1 in an amount sufficient to increase contractility of the left ventricle during isovolumic contraction.

87. The method of claim 86, wherein the contractility of the left ventricle is increased by about 1% to about 10 %.

88. A method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient to modulating left ventricular outflow tract (LVOT) gradient in the subject relative to pre-treatment by about 1% or more.

89. The method of claim 88, wherein the patient undergoes a reduction in LVOT of about 40% to about 80 %.

90. The method of claim 88, wherein the patient undergoes a reduction in LVOT of about 50% to about 70 %.

91. The method of claim 88, wherein the patient undergoes a reduction in resting LVOT pressure gradient (LVOT-G) of about 40% to about 80 %.

92. The method of claim 88, wherein the patient undergoes a reduction in resting LVOT pressure gradient (LVOT-G) of about 60% to about 70 %.

93. The method of claim 88, wherein the patient undergoes a reduction in resting LVOT pressure gradient (LVOT-G) of about 67%.

94. The method of claim 88, wherein the patient undergoes a reduction in provokable (Valsalva) LVOT-G of about 40% to about 80%.

95. The method of claim 88, wherein the patient undergoes a reduction in provokable (Valsalva) LVOT-G of about 45% to about 60%.

96. The method of claim 88, wherein the patient undergoes a reduction in provokable (Valsalva) LVOT-G of about 55%.

97. A method of treating a cardiovascular disease or related condition, the method comprising administering to a subject Compound 1 in an amount sufficient to modulating protein concentration of one or more biomarkers in the subject relative to a pre-treatment protein concentration of the one or more biomarkers by about 5 % or more.

98. The method of claim 97, wherein the one or more biomarker(s) are modulated by 10% or more.

99. A method of treating a cardiovascular disease or related condition, comprising administering to a subject Compound 1 in an amount sufficient achieve a plasma concentration Cmax level of between about 10 and about 2000 ng / mL.

100. The method of claim 99, wherein the plasma concentration Cmax level is between about 10 and about 700 ng / mL.

101. The method of claim 100, wherein the plasma concentration Cmax level is between about 100 and about 300 ng / mL.

102. The method of any one of claims 69 to 101, wherein administering comprises administering Compound 1 or Compound 2 once a day, twice a day, three times a day, once every two days, once every three days, once every four days, once every five days, once every six days or once a week.

103. The method of claim 102, wherein administering is once a day.

104. The method of claim 103, wherein administering is once every 2 days.

105. The method of any one of claims 69 to 104, wherein the administering comprises administering Compound 1 or Compound 2 to the subject for 2 months or more, 3 months or more, 4 months or more, 5 months or more, 6 months or more, or 7 months or more.

106. The method of any one of claims 69 to 105, wherein the cardiovascular disease or a related condition is selected from: hypertrophic cardiomyopathy (HCM); heart failure with preserved ejection fraction (HfpEF); heart failure with reduced ejection fraction (HfrEF); dilated cardiomyopathy (DCM); ischemic cardiomyopathy; cardiac transplant allograft vasculopathy; restrictive cardiomyopathy; valvular heart disease; left ventricular (LV) hypertrophy; ischemia; angina; chronic heart failure; toxic cardiomyopathy; myocarditis; and acute and chronic decompensated heart failure optionally resulting from any of the the he cardiovascular disease or a related conditions disclosed herein.

107. IThe method of claim 106, wherein the cardiovascular disease or a related condition is hypertrophic cardiomyopathy.

108. The method of claim 107, wherein hypertrophic cardiomyopathy is obstructive hypertrophic cardiomyopathy.

109. The method of claim 107, wherein hypertrophic cardiomyopathy is non-obstructive hypertrophic cardiomyopathy.

110. The method of claim 106, wherein cardiovascular disease or a related condition comprises heart failure with preserved ejection fraction.

111. The method of claim 106, wherein cardiovascular disease or a related condition comprises left ventricle stiffness.

112. The method of any one of claims 69 to 111, wherein the solid form of any one of claims 1 to 23 is administered to a subject in need thereof.

113. The method of any one of claims 69 to 112, wherein the pharmaceutical composition of any one of claims 24 to 68 is administered to a subject in need thereof.

114. The method of any one of claims 69 to 113, wherein the solid form or the pharmaceutical composition is co-administered with an additional active agent.

115. The method of claim 114, wherein the additional active agent comprises a betablocker, a calcium channel blocker, a sodium channel blocker, a cardiac myosin inhibitor, a partial fatty acid oxidation inhibitor, an anti-arrhythmic cibenzoline succinate, or a selective copper II chelator, an SGLT1 / SGLT2 inhibitor, a myosin binding protein C3-targeting gene therapy, a cardiac troponin 13 modulator, or any combination thereof.

116. The method of any one of claims 6 to 114, wherein Left Ventricular Ejection Fraction (LVEF) is modulated only between 0% and 3%.

117. The method of any one of claims 6 to 114, whereby Left Ventricular Ejection Fraction (LVEF) is not affected or is affected very little.

118. The method of any one of claims 6 to 114, wherein Left Ventricular Ejection Fraction (LVEF) is not affected.

119. A kit, comprising an oral pharmaceutical composition and instructions for administration to a subject in need thereof, wherein the oral pharmaceutical composition comprises a compound of Compound 1 and one or more pharmaceutically acceptable excipient(s).

120. The kit of claim 119, wherein the Compound 1 is the solid form of any one of claims 1 to 23, and the pharmaceutical composition is the pharmaceutical composition of any one of claims 24 to 68.

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