Dosage forms comprising a VAV1 degrader

Abstract

Disclosed herein are dosage forms comprising a VAV1 degrader. More specifically, disclosed herein are dosage forms comprising 3-(2-chloro-4'-(2-oxopyridin-1(2H)-yl)-[1,1'- biphenyl]-3-yl)piperidine-2,6-dione or a pharmaceutically acceptable salt thereof. These dosage forms are useful, e.g., for treating a subject (e.g., a human subject) having a disorder or disease that can be treated by reducing the level of VAV1, for example an inflammatory or autoimmune disorder, a transplantation setting disorder, or a cancer.

Description

[0001] PAT059980-WO-PCT DOSAGE FORMS COMPRISING A VAV1 DEGRADER TECHNICAL FIELD Disclosed herein are dosage forms comprising a chemical entity (e.g. a compound or a pharmaceutically acceptable salt thereof) that degrades human proto-oncogene VAV1 protein (VAV1). More specifically, disclosed herein are dosage forms comprising a VAV1 degrader which is 3-(2-chloro-4'-(2-oxopyridin-1(2H)-yl)-[1,1'-biphenyl]-3-yl)piperidine-2,6-dione or a pharmaceutically acceptable salt thereof. These dosage forms are useful, e.g., for treating a subject (e.g., a human subject) having a disorder or disease that can be treated by reducing the level of VAV1, for example an inflammatory or autoimmune disorder, a transplantation setting disorder, or a cancer. BACKGROUND The ubiquitin proteasome system can be manipulated with different small molecules to trigger targeted degradation of specific proteins of interest. Promoting the targeted degradation of proteins using small molecule degraders is emerging as a new modality in the treatment of diseases. One such modality relies on redirecting the activity of E3 ligases such as cereblon (a phenomenon known as E3 reprogramming) using low molecular weight compounds, which have been termed molecular glues (also called molecular glue degraders; “MGDs”), to promote the poly-ubiquitination and ultimately proteasomal degradation of new protein substrates involved in the development of diseases. Molecular glues bind to both the E3 ligase and the target protein. It is believed that the interaction between the molecular glue and the E3 ligase creates a surface that promotes formation of a complex with the target protein, permitting subsequent degradation of the target protein. Examples of molecular glues for the E3 ligase cereblon include: Thalidomide, Lenalidomide and Pomalidomide, all of which are immunomodulatory imide drugs (IMiDs) approved by the FDA for use in hematological cancers. VAV family proteins, including VAV1, VAV2 and VAV3, are guanine nucleotide exchange factors (GEFs) for Rho family GTPases. VAV1 is a 95 kDa protein that is a positive regulator of T cell receptor and B cell receptor signaling. VAV1 expression is normally highly restricted to hematopoietic cells. VAV1 becomes rapidly phosphorylated on tyrosine in response to a variety of stimuli, including stimulation of T-cell receptor (TCR), B cell receptor (BCR), and various cytokine receptors. VAV1 regulates multiple cellular functions and signaling pathways in hematopoietic-derived cells (e.g., T- and B-cells, natural killer cells, and osteoclasts) through activation of certain GTPases. VAV1-mediated functions include gene transcription, development PAT059980-WO-PCT and activation of immune cells (e.g., T- and B-cells). VAV1 is a positive regulator of (TCR) signaling including nuclear factor of activated T cells (NFAT), interferon gamma (IFNɣ) and Interleukin-2 (IL-2) cytokine secretion. Knock-in mice having a mutated VAV1 with disrupted GEF activity, but intact GEF- independent function, show reduced T cells proliferation and activation in response to allogeneic stimulation and showed reduced expansion of T cells in a systemic graft-versus-host model (Haubert et al. 2012 Transplantation Immunology 26: 212, 2012). VAV1 deficient mice are resistant to MOG(5-55)-induced experimental autoimmune encephalomyelitis (EAE), a commonly used model of multiple sclerosis (Korn et al. 2003 Journal of Neuroimmunology 139:17). Finally, genome-wide CRISPR activation (CRISPRa) and interference (CRISPRi) screens in primary human T cells identified VAV1 as an important positive regulator of T cell function (Schmidt et al.2022 Science 375:6580). In summary, VAV1 is a dominant signal transduction protein in the adaptive immune system. It is a positive regulator of immune receptor signaling in both T cells and B cells. Thus, reduction in VAV1 can reduce immune cell activation, immune cell proliferation and the production of various cytokines. For at least these reasons, degradation of VAV1 can be therapeutically beneficial in a variety of disease conditions. PCT / US2024 / 010733 discloses chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that degrade and / or otherwise inhibit human Proto-oncogene VAV 1 protein (VAV1). These chemical entities are useful, e.g., for treating a subject (e.g., a human subject) having a disorder or disease that can be treated by reducing the level of VAV1, thereby reducing VAV activity in cells. By reducing the level of VAV1, the chemical entities can reduce signaling in certain immune cell activation pathways. For example, the chemical entities may be used to reduce inflammation or autoimmune activity, and thus the chemical entities are useful for treating a subject having an inflammatory or autoimmune disorder. They may be useful for treating, for example, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, chronic lymphocytic leukemia, ulcerative colitis, psoriasis, cutaneous lupus, axial spondyloarthritis, and graft versus host disease. The chemical entities are also useful, e.g., for treating a subject (e.g., a human subject) having a disorder or disease that is associated with VAV1 polymorphisms or dysregulated lymphocyte (e.g., T-cell). Amongst the chemical entities disclosed in PCT / US2024 / 010733 is 3-(2-chloro-4'-(2- oxopyridin-1(2H)-yl)-[1,1'-biphenyl]-3-yl)piperidine-2,6-dione. This compound is described herein as Compound A. Compound A has the following structure: PAT059980-WO-PCT . There is a need for dosage forms that can be used to administer Compound A to a subject. Ideally, such dosage forms will have advantageous characteristics such as long-term physical and chemical stability, uniformity, and suitability to facilitate delivery of the active ingredient to the target site in the subject to whom the dosage form is to be administered. Dosage form design can also contribute to improved bioavailability of the active ingredient. In addition, there is a desire for dosage forms that contain a precisely known amount of Compound A, as such dosage forms can facilitate accurate dosing. This is especially important because of the high potency of Compound A. SUMMARY Provided herein are dosage forms comprising Compound A, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, wherein the amount of Compound A is between 0.01 mg and 100 mg, and wherein Compound A is a compound of the following formula: . In some embodiments, Compound A is in an amorphous form. In some embodiments, the dosage form comprises less than 50% by weight of Compound A. In some embodiments, the total weight of the dosage form is between 5 and 1000 mg. In some embodiments, the dosage form comprises two or more pharmaceutically acceptable excipients. In some embodiments, the dosage form comprises three or more pharmaceutically acceptable excipients. In some embodiments, the dosage form comprises four or more pharmaceutically acceptable excipients. In some embodiments, the dosage form comprises five or more pharmaceutically acceptable excipients. In some embodiments, the dosage form is for oral administration. In some embodiments, the dosage form is a solid dosage form, for example a tablet or a capsule. In some embodiments, the dosage form is a tablet. In some embodiments, the tablet comprises a solid dispersion comprising Compound A and a polymer. In some embodiments, the polymer is HPMCAS HG. In some embodiments, the solid dispersion comprises Compound A and PAT059980-WO-PCT the polymer at a ratio of 1:3. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3 and the polymer is HPMCAS HG. In some embodiments, the tablet comprises (i) a solid dispersion comprising Compound A and a polymer, (ii) a filler, (iii) a glidant, (iv) a disintegrant, and (v) a lubricant. In some embodiments, the dosage form is a capsule. In some embodiments, the capsule is a softgel. In some embodiments, the softgel fill comprises a solubiliser. In some embodiments, the solubiliser comprises benzyl alcohol. In some embodiments, the softgel fill comprises an antioxidant. In some embodiments, the antioxidant comprises ascorbyl palmitate. DESCRIPTION OF DRAWINGS FIG. 1 is a schematic depiction of certain aspects of VAV1’s relationship to certain proteins involved in T cell receptor activation. VAV1 is a positive regular of T cell receptor signaling, including interferon gamma production and IL-2 secretion. FIG.2A shows dose-dependent decrease in VAV1 levels in primary human T-cells upon 24h treatment with Compound A relative to DMSO control as assessed by flow cytometry (y-axis represents normalized VAV1 levels relative to DMSO control; x-axis depicts doses of Compound A). FIG. 2B shows that VAV1 is significantly and selectively degraded by Compound A in Jurkat cells following 24h treatment as assessed by quantitative TMT proteomics (y-axis represents confidence p-value [-log10]; x-axis represents protein fold-change [log2] relative to DMSO control samples). FIGS. 3A-3C show that VAV1 degradation results in inhibition of various hallmarks of TCR-mediated activity following TCR stimulation of primary human T-cells. Cells were treated with Compound A for 24h followed by TCR stimulation (anti-CD3 / anti-CD28 antibodies). CD69 surface expression (24 hr), IL-2 secretion (48 hr), and proliferation (96 hr) were evaluated at various timepoints following TCR stimulation (y-axis depicts percent of CD69 activation, IL-2 secretion, or proliferation relative to TCR-stimulated DMSO control; x-axis depicts doses of Compound A). FIG. 4 shows the concentration of Compound A in plasma over time and associated decrease in normalized VAV1 to b-actin protein levels relative to pre-treatment after a single oral dose of Compound A at 10 mg / kg (y-axis represents hours post one single oral dose of Compound A [hour]; left y-axis represents the concentration of Compound A in ng / ml in plasma, filled PAT059980-WO-PCT rhombi; right y-axis represents percentage [%] VAV1 protein levels normalized to b-actin protein levels and relative to pre-dose in blood cells, filled triangles). FIG.5 shows that oral administration of Compound A in a MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) model led to inhibition of disease progression. Mice were immunized by subcutaneous injection at day 0 with an emulsified mixture consisting of the synthetic peptide derived from myelin oligodendrocyte glycoprotein (MOG35-55) and M. tuberculosis mixed with incomplete Freund’s adjuvant. Additionally, mice were injected intraperitoneally with pertussis toxin at 0 and 48 hours. Mice were followed for development of symptoms and scored for EAE clinical signs disease (0=no signs of disease; 1=limp tail or hind limb weakness; 2=limp tail and hind limb weakness; 3=partial hind limb paralysis; 4=complete hind limb paralysis; 5=moribund), once a day (QD) dosing started at day 12 and ended at day 18. Dexamethasone dosed QD orally from day 12 to day 18 was used as comparative treatment. 10 mg / kg Compound A prevented the progression of EAE disease as it was observed for the mice treated with Dexamethasone at 1 mg / kg (x-axis represents days post immunization initiation [days]; y-axis represents clinical EAE score, [mean ±SEM]; empty circle: vehicle, PO, QD; filled triangles inverted: Compound A 10 mg / kg, PO, QD; filled square: Dexamethasone 1 mg / kg, PO, QD). FIG. 6A shows that oral administration of Compound A in a MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) model led to inhibition of disease progression in a dose-dependent manner. Mice were immunized by subcutaneous injection at day -12 with an emulsified mixture consisting of the synthetic peptide derived from myelin oligodendrocyte glycoprotein (MOG35-55) and M. tuberculosis mixed with incomplete Freund’s adjuvant. Additionally, mice were injected intraperitoneally with pertussis toxin at day -12 and -10. Mice were followed for development of symptoms and scored for EAE clinical signs disease (0=no signs of disease; 1=limp tail or hind limb weakness; 2=limp tail and hind limb weakness; 3=partial hind limb paralysis; 4=complete hind limb paralysis; 5=moribund) every 3 days until day 0. Dosing started at day 0 and ended at day 13 with vehicle (PO, QD), dexamethasone (1 mg / kg, PO QD), and Compound A (1, 0.1, 0.01 mg / kg, PO, QD). 1 mg / kg Compound A prevented the progression of EAE disease as it was observed for the mice treated with Dexamethasone at 1 mg / kg (x-axis represents days post immunization initiation [days]; y- axis represents clinical EAE score, [mean ±SEM]; closed circle: vehicle; solid up triangle: Compound A 1 mg / kg; closed down triangle: Compound A 0.1 mg / kg; open up triangle: Compound A 0.01 mg / kg; open circle: Dexamethasone 1 mg / kg). PAT059980-WO-PCT FIG.6B shows that oral administration of Compound A degraded VAV1 in the spinal cord in a dose-dependent manner commensurate with reduction in clinical scores. On day 6, 4 mice per group were euthanized, spinal cords were excised and homogenized, and western blot was then used to assess VAV1 levels normalized to β-actin and shown relative to vehicle treated mice. Statistical analysis was performed using a one-way ANOVA with Dunnett’s multiple comparisons. ns = not significant, ***p<0.001, ****p<0.0001. FIG.7 shows that oral administration of Compound A in a T-cell transfer induced model of colitis led to inhibition of disease progression. CD17-SCID mice were injected intraperitoneally with 0.5 x 106non-pathogenic activated CD45RBlow(no disease control group) or pathogenic naïve CD45RBhigh (treatment groups) CD4+ T cells. From the day of cell transfer (day 0), the mice were monitored daily for disease activity index (DAI) comprising weight loss and stool consistency assessment. On day 0, two hours post-cell transfer, mice were treated orally (PO) daily (QD) with vehicle or Compound A 1 mg / kg for 42 days. 1 mg / kg Compound A prevented the progression of colitis (x-axis represents days post disease induction and treatment start [days]; y axis represents DAI score [mean ± SEM]; open circles, non-pathogenic control; closed black circles, vehicle; closed triangles, Compound A 1 mg / kg). FIG. 8A shows that oral administration of Compound A in a collagen-induced arthritis model led to inhibition of disease progression. To induce collagen-induced arthritis (CIA), fifteen DBA / 1 mice were injected intravenously with an emulsified mixture consisting of 100 μg of chicken collagen II emulsified in incomplete Freund’s adjuvant then 18 days later injected subcutaneously with chicken collagen II emulsified in complete Freund’s adjuvant. This immunization induces the activation and expansion of collagen specific T- and B-cells that migrate into the paw joints. Once in the paw joints, the activated T-cells induce destruction of the joint and bone tissue, leading to redness and swelling of the phalanges, and B-cells produce antibodies against collagen II. Following the second immunization, mice were monitored daily for clinical signs of disease as follows: 0=erythema and redness; 1=Erythema or mild redness near ear the tarsal, ankle, or metatarsal or one toe with erythema and redness; 2=Ankles and metatarsals are slightly erythematous and swollen with two or more toes with erythema and redness; 3=Moderate erythema and swelling of the ankle, wrists, and metatarsals; 4=Ankles, wrists, metatarsals, and toes are severely red and swollen. Upon disease onset, mice were randomly enrolled into treatment groups: vehicle (PO, QD), anti-TNF (10 mg / kg, IP, Q3D), or Compound A (1 mg / kg, PO, QD) and treated for 21 days. 1 mg / kg Compound A prevented the progression of arthritis (x-axis represents days post disease onset and treatment start [days]; y axis represents clinical score [mean ± SEM]; circles, vehicle; triangles, Compound A 1 mg / kg). PAT059980-WO-PCT FIG. 8B shows that oral administration of Compound A in a collagen-induced arthritis model led to decreased production of anti-collagen II IgG1 antibodies. At the end of the study, serum was collected and the amount of anti-collagen II IgG1 antibodies was measured by ELISA. Statistical analysis was performed using an unpaired two-tailed t-test. *p<0.05. FIG. 9 depicts VAV1 as a key mediator downstream of the B-cell receptor (BCR). Hallmarks of BCR pathway engagement include CD69 surface activation and secretion of IL-6 and IgG. FIGs. 10A-10C show that Compound A-mediated degradation of VAV1 reduces BCR- mediated CD69 expression and secretion of IL-6 and IgG of primary human B cells. Purified human primary B-cells were treated with Compound A 24 hrs followed by stimulation with anti- IgM and recombinant human IL-4 for 24 hours (for CD69 expression and IL-6 secretion) or with anti-IgM, BAFF, IL-21, and sCD40L for 5 days (for IgG secretion). FIG. 10A shows CD69 expression which was then assessed on CD19+ B cells by flow cytometry. CD69 expression is shown as a percentage (%) change relative to stimulated DMSO controls. Y-axis shows relative percentage of CD19+ B cells expressing CD69 and x-axis shows concentration of Compound A. FIG.10B shows IL-6 secretion which was assessed in the supernatant by alphalisa. IL-6 secretion is shown as a percentage (%) change relative to stimulated DMSO controls. Y-axis shows relative percentage of IL-6 level and x-axis shows concentration of Compound A. FIG.10C shows IgG secretion was assessed in the supernatant by alphalisa. IgG secretion is shown as a percentage (%) change relative to stimulated DMSO controls. Y-axis shows relative percentage of IgG level and x-axis shows concentration of Compound A. FIG.11 shows that Compound A treatment of selected B-cell lymphoma cell lines decrease growth with increasing concentration. REC-1, OCI-LY10, and SLVL cells were treated for 5 days with the indicated concentrations of Compound A. At 5 days of treatment, cell growth was measured by cell titer glow and normalized to T0 and DMSO. FIG. 12 shows that Compound A treatment of subcutaneously implanted REC-1 CDX decreases growth in vivo. CB17 SCID mice (10 per group) were inoculated subcutaneously on the right flank with 5x106REC-1 cells. After the average tumor volume of all mice reached 100-150 mm3, mice were treated with either vehicle or 10mg / kg Compound A PO QD. At indicated days post treatment initiation, tumor volume was measured. Mice were sacrificed when tumor volume reached 2000 mm3. PAT059980-WO-PCT FIG. 13 shows an X-ray powder diffraction (XRPD) pattern of crystalline form A of Compound A. FIG. 14 shows the results of an experiment to assess the amorphous solubility of Compound A in various polymers in FaSSIF medium. Amorphous solubilities were determined based on the onset of liquid-liquid phase separation using a solvent-shift UV assay. FIG.15 shows the results of an experiment to assess the kinetic solubility of spray-dried dispersions 1-4 in biorelevant media (FaSSGF and FaSSIF). Solubilities were determined based on the onset of liquid-liquid phase separation using a solvent-shift UV assay. FIG.16 is a tabletability plot showing tensile strength vs compression strength for tablet formulations 4-6. FIG. 17 is a compactability plot showing tensile strength vs solid fraction for tablet formulations 4-6. FIG.18 shows the results of a two-step dissolution test of softgel fill formulations S2, S3, S5, and S6. The test was carried out on a Pion instrument with a USP II apparatus, in which API concentration was determined by fiber optic probes. FIG. 19 gives average plasma concentration curves of Compound A administered at 0.5 mg / kg IV and 1 mg / kg PO to Cynomolgus monkeys (single male and female). Plasma samples were collected after IV at 0, 0.08, 0.25, 0.5, 1, 2, 4, 8, and 24 hr or PO administration at 0, 0.25, 0.5, 1, 2, 4, 8, and 24 hr. Data represents the average plasma concentrations (ng / mL) of Compound A on the primary y-axis. FIG. 20 shows relative Vav1 protein levels in PBMCs after a single administration of Compound A at 1.0 mg / kg PO to a male Cynomolgus monkey and a female Cynomolgus monkey. Data represents the percent change in the relative protein levels of Vav1 relative to pre-dose levels. PBMCs were collected at 0, 6 and 24 hrs post dose. Data are a single point for each sex. FIGS.21A-E show plasma concentration curves from an n=3 cynomolgus male monkey cross over PK study testing administration of Compound A within a 0.5 mg capsule, a 0.5 mg tablet, a 10 mg tablet, a 0.1 mg capsule or a 1 mg capsule. The separate curves in each plot represent data from the individual monkeys. PAT059980-WO-PCT FIG.22 shows AUC data resulting from oral administration of liquid formulations L21-24 to Cynomolgus monkeys at 20 mg / kg. FIG.23 shows a flow diagram of the softgel capsule API stock mix manufacturing process. FIG.24 shows a flow diagram of the softgel capsule main mix manufacturing process. DETAILED DESCRIPTION The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features and advantages of the invention will be apparent from the description and drawings, and from the claims. All documents referred to herein are incorporated by reference in their entirety. Definitions As used herein, the term “comprising” is in inclusive term which indicates that certain elements are included in an embodiment, but does not exclude the presence of other elements. The terms “comprising”, “including”, and “containing” are used interchangeably herein. Conversely, the term “consisting of” would exclude the presence of elements other than those recited. The term “consisting essentially of” indicates that further elements may be included in the embodiment to the extent that these further elements do not materially alter the fundamental characteristics of the embodiment. Thus, the term “consisting essentially of” allows for minor variations or additions that do not substantially alter the core functionality of the embodiment. Where values are specified herein in the form of ranges, the range is always inclusive, i.e. it includes the endpoint stated. For example, up to 10% includes 10%, less than 10% also includes 10%, and between 10 % and 30% includes both 10% and 30%. The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al., describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66:1–19. Pharmaceutically acceptable salts of the compounds of the present disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric PAT059980-WO-PCT acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2–hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2–naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p–toluenesulfonate, undecanoate, valerate salts, and the like. Pharmaceutically acceptable salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N+(C1–4alkyl)4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. Similarly, the term “pharmaceutically acceptable excipient” refers to an excipient which is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and is commensurate with a reasonable benefit / risk ratio. An “excipient” is an inactive substance included alongside the active substance in a pharmaceutical formulation. As used herein, “VAV1” refers to naturally occurring VAV1, also known as Vav or p95vav, (e.g. mammalian, preferably human (Homo sapiens) VAV1) and encompasses naturally occurring variants, such as allelic variants and splice variants, which retain VAV1 functional activity. A “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle–aged adult or senior adult)) and / or a non-human animal, e.g., a mammal such as primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In certain preferred embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The terms “human,” “patient,” and “subject” are used interchangeably herein. Disease, disorder, and condition are used interchangeably herein. As used herein, and unless otherwise specified, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a subject is suffering from the specified PAT059980-WO-PCT disease, disorder or condition, which reduces the severity of the disease, disorder or condition, or retards or slows the progression of the disease, disorder or condition (“therapeutic treatment”). In general, the “effective amount” of a compound refers to an amount sufficient to elicit the desired biological response. As will be appreciated by those of ordinary skill in this art, the effective amount of a compound of the present disclosure may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, health, and condition of the subject. As used herein, and unless otherwise specified, a “therapeutically effective amount” of a compound is an amount sufficient to provide a therapeutic benefit in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the disease, disorder or condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of disease or condition, or enhances the therapeutic efficacy of another therapeutic agent. An “amorphous” solid is a solid that has no long-range order in the position of its molecules. In other words, the solid is not crystalline. As used herein, a “filler” is an excipient that is added to a tablet formulation to add bulk or volume. Diluents may also aid processing, for example, by providing improved physical properties such as flow, compressibility, and tablet hardness. The terms “filler” and “diluent” are used interchangeably. As used herein, a “glidant” is an excipient that is added to a powder formulation to improve its flowability. A glidant can reduce interparticle friction and enhances the ability of the powder to flow more smoothly, which helps to ensure uniformity in the weight and content of tablets and capsules. By improving powder flow, glidants help to prevent issues such as sticking, clumping, and inconsistent dosing. As used herein, a “disintegrant” is an excipient that is added to a tablet formulation to promote the breakup or disintegration of the tablet after administration. The role of a disintegrant is to promote rapid dissolution of the drug by ensuring that the tablet or capsule disintegrates into smaller fragments in the gastrointestinal tract, allowing for faster release and absorption of the active pharmaceutical ingredient (API). Disintegrants work by swelling, wicking, or through deformation, which disrupts the physical integrity of the dosage form. This process helps to ensure that the medication is effective and provides the intended therapeutic effect. As used herein, a “lubricant” is an excipient that is added to a tablet formulation to reduce adhesion of the tablet formulation to surfaces (such as the tableting equipment) and / or to reduce PAT059980-WO-PCT interparticle friction within the tablet formulation, which can aid compression of tablets and ejection of tablets from the tableting equipment. As used herein in the context of excipients for formulations of an active ingredient, an “antioxidant” is a substance used to inhibit oxidative degradation of the active ingredient and / or other excipients included in the formulation. Antioxidants help maintain the stability and potency of the pharmaceutical product by neutralizing free radicals and preventing oxidative reactions. As used herein, a “solubiliser” is an excipient that is added to a formulation to increase the solubility of another ingredient, typically the active ingredient, in aqueous or other solvent systems. Solubilizers help increase the bioavailability of the API by ensuring it is adequately dissolved in the gastrointestinal fluids or other target environments, thereby improving its absorption and therapeutic efficacy. As used herein, a “non-ionic surfactant” is an amphiphilic molecule having a hydrophobic portion and a hydrophilic portion connected by one or more linkers, which allows it to be a surface active molecule, that is substantially non-ionised (i.e. uncharged) in water at neutral pH. As used herein, the term “particle size” or “median particle size” refers to the volume distributed median particle diameter (equivalent spherical diameter corresponding to 50% of the volume of all the particles, read on the cumulative distribution curve relating volume % to the diameter of the particles – often referred to as the “D(v,0.5)” value). Particle size distributions can be determined by routine laser diffraction techniques. Unless otherwise stated, particle size distribution measurements as specified or reported herein are as measured by Malvern Instruments’ conventional Malvern Mastersizer 3000 particle size analyzer. As used herein to characterize certain types of hydroxypropylmethylcellulose (HPMC, also known as hypromellose) and HPMC derivatives, viscosity is determined as a 2 weight % solution in water at 20 °C as described in the United States Pharmacopeia (USP 35, "Hypromellose", pages 423-424 and 3467-3469). As described in USP 35, viscosities of up to 600 mPa-s are determined by Ubbelohde viscosity measurement and viscosities above 600 mPa-s are determined using a Brookfield viscometer. USP 35 provides descriptions of preparing the 2 wt. % HPMC or HPMC derivative solution and both Ubbelohde and Brookfield viscosity measurement conditions. Active Ingredient The dosage forms provided herein comprise, as the active ingredient, Compound A or a pharmaceutically acceptable salt thereof. As explained above, Compound A is 3-(2- chloro-4'-(2-oxopyridin-1(2H)-yl)-[1,1'-biphenyl]-3-yl)piperidine-2,6-dione and has the following structure: PAT059980-WO-PCT . In some preferred embodiments, the dosage form comprises Compound A (i.e. in free form). In some embodiments, the dosage form comprises a pharmaceutically acceptable salt of Compound A. The term “Compound A” is intended to encompass isotopically labeled compounds which are identical to Compound A as described above, except that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated in such compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine, such as2H,3H,13C,14C,15N,18O,17O,31P,32P,35S,18F, and36Cl, respectively. For example, one or more H atoms may be replaced with deuterium. In addition, the term “Compound A” is intended to encompass all tautomeric forms, or “tautomers”, of Compound A as described above. To give a non-limiting example, Compound Amay be present as the following tautomer: Furthermore, the term “Compound A” is intended to encompass all stereoisomeric forms, specifically all enantiomeric forms, unless it is specifically stated or the context indicates otherwise. Compound A may be present within the embodiments disclosed herein as an isolated enantiomer (e.g. as the (R) enantiomer or (S) enantiomer) or a mixture of individual enantiomers, such as a racemate. In some embodiments, the dosage form comprises Compound A in the form of a single enantiomer, or a pharmaceutical acceptable salt thereof. In some embodiments, the dosage form comprises Compound A or a pharmaceutically acceptable salt thereof, wherein Compound A is the following enantiomer: . In some embodiments, the dosage form comprises Compound A or a pharmaceutically acceptable salt thereof, wherein Compound A is the following enantiomer: PAT059980-WO-PCT . In some embodiments, the dosage form comprises Compound A or a pharmaceutically acceptable salt thereof, wherein Compound A exists in a racemic mixture. Polymorphic form of Compound A Compound A in crystalline form may be obtained by the methods described herein, e.g., as described in Example 1.3, or as described in WO 2024 / 151547 A1. In some embodiments, Compound A exists as crystalline Form A (Compound A in free form: wherein the Form A exhibits an XRPD pattern comprising peaks at about 16.5±0.5, 17±0.5 and 17.8±0.5 degrees two-theta using copper K-alpha radiation. In some embodiments, the Form A exhibits an XRPD pattern comprising peaks at about 14±0.5, 16.5±0.5, 17±0.5, 17.8±0.5 and 19.5±0.5 degrees two-theta using copper K-alpha radiation. In some embodiments, the Form A exhibits an XRPD pattern comprising peaks at about 14±0.5, 16.5±0.5, 17±0.5, 17.8±0.5 and 19.5±0.5 degrees two-theta using copper K-alpha radiation, as well as peaks between 21.5-23, 25.5-27, 27-28 and 29.5-31 degrees two-theta using copper K-alpha radiation. In some embodiments, the margin of error is ±0.4; ±0.3; ±0.2; ±0.1; or ±0.05. In some embodiments, the crystalline Form A exhibits an XRPD pattern comprising the peaks shown in Table 1 below. Table 1: XRPD table of crystalline Form A of Compound A °2 Theta Appearance 14 Single 16.5 Single 17 Single 17.8 Single 19.5 Single 21.5-23 Multiple 25.5-27 Multiple 27-28 Multiple PAT059980-WO-PCT 29.5-31 Multiple In some embodiments, the crystalline Form A of Compound A exhibits an XRPD pattern which is substantially similar to FIG.13. In some embodiments, Compound A is provided in amorphous form. Dosage Forms Amount of Compound A The dosage forms provided herein comprise an amount of Compound A between 0.01 mg and 100 mg. As would be apparent to the skilled person, if using a pharmaceutically acceptable salt of Compound A, the amount will need to be adjusted in order to provide the requisite amount of Compound A, i.e. the free form equivalent. All amounts of Compound A herein are given as the amount of Compound A in free form, unless it is specified otherwise. In some embodiments, the amount of Compound A is between 0.01 mg and 20 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 10 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 5 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 2 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 0.5 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 0.2 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 0.1 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 0.05 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 20 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 10 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 5 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 2 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 0.5 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 0.2 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 0.1 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 20 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 10 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 5 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 2 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 0.5 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 0.2 mg. PAT059980-WO-PCT In some embodiments, the amount of Compound A is between 0.5 mg and 20 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 10 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 5 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 2 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 1 mg. In some embodiments, the amount of Compound A is between 1 mg and 10 mg. In some embodiments, the amount of Compound A is between 2 mg and 10 mg. In some embodiments, the amount of Compound A is between 3 mg and 10 mg. In some embodiments, the amount of Compound A is between 5 mg and 10 mg. In some embodiments, the amount of Compound A is between 1 mg and 5 mg. In some embodiments, the amount of Compound A is between 2 mg and 5 mg. In some embodiments, the amount of Compound A is between 3 mg and 5 mg. In some embodiments, the amount of Compound A is between 4 mg and 5 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 3 mg. In some embodiments, the amount of Compound A is between 1 mg and 3 mg. In some embodiments, the amount of Compound A is between 2 mg and 3 mg. In some embodiments, the amount of Compound A is between 0.25 mg and 2 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 2 mg. In some embodiments, the amount of Compound A is between 1 mg and 2 mg. In some embodiments, the amount of Compound A is between 1.5 mg and 2 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.2 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.3 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.4 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.6 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.7 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.8 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.9 mg and 1 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 20 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 10 mg. In some embodiments, the amount of Compound A is between 0.01 mg and 5 mg. In some embodiments, the amount of Compound is between 0.05 mg and 5 mg. In some embodiments, the amount of Compound is between 0.05 mg and 2 mg. In some embodiments, the amount of Compound is between 0.1 mg and 2 mg. In some embodiments, the amount of Compound is between 0.1 mg and 1 mg. In some embodiments, the amount of Compound is between 0.1 mg and 0.5 mg. PAT059980-WO-PCT In some embodiments, the amount of Compound A is between 0.01 mg and 20 mg. In some embodiments, the amount of Compound A is between 0.05 mg and 10 mg. In some embodiments, the amount of Compound A is between 0.1 mg and 5 mg. In some embodiments, the amount of Compound A is between 0.5 mg and 2 mg. In some embodiments, the dosage form comprises 0.1 mg of Compound A. In some embodiments, the dosage form comprises 0.5 mg of Compound A. In some embodiments, the dosage form comprises 1 mg of Compound A. In some embodiments, the dosage form comprises 2 mg of Compound A. In some embodiments, the dosage form comprises 10 mg of Compound A. In some embodiments, Compound A or a pharmaceutically acceptable salt thereof is present in a therapeutically effective amount. In some embodiments, the dosage form comprises less than 50% by weight of Compound A. In some embodiments, the dosage form comprises less than 40% by weight of Compound A. In some embodiments, the dosage form comprises less than 30% by weight of Compound A. In some embodiments, the dosage form comprises less than 20% by weight of Compound A. In some embodiments, the dosage form comprises less than 10% by weight of Compound A. In some embodiments, the dosage form comprises less than 5% by weight of Compound A. In some embodiments, the total weight of the dosage form is between 5 and 1000 mg. In some embodiments, the total weight of the dosage form is between 5 and 500 mg. In some embodiments, the total weight of the dosage form is between 5 and 400 mg. In some embodiments, the total weight of the dosage form is between 5 and 300 mg. In some embodiments, the total weight of the dosage form is between 5 and 200 mg. In some embodiments, the total weight of the dosage form is between 5 and 100 mg. In some embodiments, the total weight of the dosage form is between 5 and 50 mg. In some embodiments, the total weight of the dosage form is between 5 and 25 mg. In some embodiments, the amount of Compound A, its percentage by weight of the dosage form, and the total weight of the dosage form are as defined herein. For example: the amount of Compound A in the dosage form may be between 0.01 mg and 20 mg, between 0.01 mg and 10 mg, between 0.01 mg and 5 mg, between 0.01 mg and 2 mg, between 0.01 mg and 1 mg, between 0.01 mg and 0.5 mg, between 0.01 mg and 0.2 mg, between 0.01 mg and 0.1 mg, or between 0.01 mg and 0.05 mg; the dosage form may comprise less than 50%, less than 40%, less than 30%, less than 20%, less than 10% by weight of Compound A, or less than 5% by weight of Compound A; and / or the total weight of the dosage form may be between 5 and 1000 mg, between 5 and 500 mg, between 5 and 400 mg, between 5 and 300 mg, between 5 and 200 mg, between 5 and 100 mg, between 5 and 50 mg, or between 5 and 25 mg. The skilled person knows how to make dosage PAT059980-WO-PCT forms according to these embodiments, e.g. by selecting amounts of Compound A and various excipients which do not exceed the stated total weight of the dosage form. Preferably, the dosage form is a solid dosage form. As used herein, solid dosage forms are dosage forms that have a solid exterior. Thus, dosage forms that comprise a solid outer shell but have a liquid or semisolid interior (as is the case for softgel capsules), or that are hollow, are encompassed by the term “solid dosage form”. In some embodiments, the dosage form is a pill, tablet, capsule, or lozenge. In some embodiments, the dosage form is a pill, tablet, or capsule. In some embodiments, the dosage form is a tablet or a capsule. Solid dosage forms can be advantageous as, in general, solid dosage forms have a longer shelf life than liquid dosage forms, since drugs are generally more stable in the solid state and microbial growth is hindered. Solid dosage forms are also generally less bulky than liquid dosage forms, which is beneficial for transport and storage. In some embodiments, the dosage form is a liquid dosage form. In some embodiments, the dosage form is a unit dosage form. The term “unit dosage form” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect. Thus, unit dosage forms are useful for facilitating accurate dosing. Typical unit dosage forms include prefilled, premeasured ampules or syringes in the case of liquid compositions or pills, tablets, capsules or the like in the case of solid compositions. In addition to Compound A, the dosage forms provided herein comprise a pharmaceutically acceptable excipient. In some embodiments, the dosage form comprises two or more pharmaceutically acceptable excipients. In some embodiments, the dosage form comprises three or more pharmaceutically acceptable excipients. In some embodiments, the dosage form comprises four or more pharmaceutically acceptable excipients. In some embodiments, the dosage form comprises five or more pharmaceutically acceptable excipients. Tablets In some embodiments, the dosage form is a tablet. Preferably, the tablet comprises a solid dispersion as described below. Tablets typically contain one or more excipients selected from fillers / diluents, disintegrants, surfactants, binders, glidants, lubricants, colorants, and fragrances. Tablets may be prepared using conventional methods known to those skilled in the field of pharmaceutical formulation, for example as described in textbooks such as Remington: The PAT059980-WO-PCT Science and Practice of Pharmacy, 21st Ed., Lippincott Williams & Wilkins, Baltimore, Md. (2003); Ansel et al., Pharmaceutical Dosage Forms And Drug Delivery Systems, 7th Edition, Lippincott Williams & Wilkins, (1999); The Handbook of Pharmaceutical Excipients, 4th edition, Rowe et al., Eds., American Pharmaceuticals Association (2003); Gibson, Pharmaceutical Preformulation And Formulation, CRC Press (2001). For example, tablets can be prepared by compressing a powder or granular formulation, e.g. using a die punch. A granular formulation may be prepared by techniques that are well known to any person skilled in the art of pharmaceutical formulation, such as by wet granulation or dry granulation. Formulation of the API into granules can help to enhance the uniformity, flow, and compactability of the formulation. Solid dispersions comprising Compound A In some embodiments, the tablet comprises a solid dispersion comprising Compound A and a polymer. In some embodiments, the polymer is selected from the group consisting of: enteric polymers (such as methacrylate polymers, hydroxypropyl methyl cellulose phthalate (HPMCP), and cellulose acetyate phthalate (CAP)), hydrophilic polymers (such as starch, sodium carboxymethyl cellulose, sodium alginate, polyethylene glycol (PEG), polyvinyl pyrollidone (PVP), hydroxy propyl methyl cellulose (HPMC), polyvinyl alcohol (PVA), β-Cyclodextrin, mannitol, chitosan, and carrageenan), amphiphilic polymers (such as polyethylene oxides (PEO) / polypropylene glycol (PPG) copolymers, PEG-modified starches, vinyl acetate / vinylpyrrolidone random copolymers, polyacrylic acid, and polyacrylates), and combinations thereof. Examples of methacrylate polymers are Eudragit® E PO / 100, Eudragit® RLPO, Eudragit® L100, and Eudragit® S100. In some embodiments, the polymer is selected from the group consisting of: HPMCAS LG, HPMCAS MG, HPMCAS HG, HPMC E3, PVPVA 64, Eudragit L100, and combinations thereof. In preferred embodiments, the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, such as hydroxypropylmethylcellulose acetate succinate (HPMCAS), for example: HPMCAS LG, HPMCAS MG, HPMCAS HG, HPMC E3, or a combination thereof. In some embodiments, the polymer is HPMCAS MG and / or HPMCAS HG. In some embodiments, the polymer is HPMCAS HG. In some embodiments, the solid dispersion comprises Compound A and a polymer at a ratio of between 1:5 and 1:1. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of between 1:3 and 2:3. In some embodiments, the solid dispersion PAT059980-WO-PCT comprises Compound A and the polymer at a ratio of 1:3 or 1:2. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3 or 1:2, and the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, such as hydroxypropylmethylcellulose acetate succinate (HPMCAS), for example: HPMCAS LG, HPMCAS MG, HPMCAS HG, HPMC E3, or a combination thereof. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3 or 1:2, and the polymer is HPMCAS MG and / or HPMCAS HG. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3 or 1:2, and the polymer is HPMCAS HG. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3, and the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, for example: HPMCAS LG, HPMCAS MG, HPMCAS HG, HPMC E3, or a combination thereof. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3, and the polymer is HPMCAS MG and / or HPMCAS HG. In some embodiments, the solid dispersion comprises Compound A and the polymer at a ratio of 1:3, and the polymer is HPMCAS HG. In some embodiments, HPMCAS LG is characterized by one or more of the following properties: (i) an acetyl content of 5-9%; (ii) a succinoyl content of 14-18%; (iii) a methoxyl content of 20-24%; (iv) a hydroxypropoxy content of 5-9%; (v) solubility at a pH more than or equal to 5.5; (vi) a median particle size between about 300 µm and 1100 µm, for example between about 500 µm and 1000 µm; (vii) a viscosity in 2% w / w aqueous solution at 20 °C of 2.4-3.6 mPa•s. In some embodiments, HPMCAS LG is characterized by (i) and (ii). In some embodiments, HPMCAS LG is characterized by (i)-(iv). In some embodiments, HPMCAS LG is characterized by (i)-(v). In some embodiments, HPMCAS LG is characterized by (i)-(iv) and (vi). In some embodiments, HPMCAS LG is characterized by (i)-(iv) and (vii). In some embodiments, HPMCAS LG is characterized by (i)-(vi). In some embodiments, HPMCAS LG is characterized by all of (i)-(vii). In some embodiments, HPMCAS MG is characterized by one or more of the following properties: (i) an acetyl content of 7-11%; (ii) a succinoyl content of 10-14%; (iii) a methoxyl content of 21-25%; (iv) a hydroxypropoxy content of 5-9%; (v) solubility at a pH more than or equal to 6.0; (vi) a median particle size between about 300 µm and 1100 µm, for example between about 500 µm and 1000 µm; (vii) a viscosity in 2% w / w aqueous solution at 20 °C of 2.4-3.6 mPa•s. In some embodiments, HPMCAS MG is characterized by (i) and (ii). In some embodiments, HPMCAS MG is characterized by (i)-(iv). In some embodiments, HPMCAS MG is characterized by (i)-(v). In some embodiments, HPMCAS MG is characterized by (i)-(iv) and (vi). In some embodiments, HPMCAS MG is characterized by (i)-(iv) and (vii). In some embodiments, PAT059980-WO-PCT HPMCAS MG is characterized by (i)-(vi). In some embodiments, HPMCAS MG is characterized by all of (i)-(vii). In some embodiments, HPMCAS HG is characterized by one or more of the following properties: (i) an acetyl content of 10-14%; (ii) a succinoyl content of 4-8%; (iii) a methoxyl content of 22-26%; (iv) a hydroxypropoxy content of 6-10%; (v) solubility at a pH more than or equal to 6.5; (vi) a median particle size between about 300 µm and 1100 µm, for example between about 500 µm and 1000 µm; (vii) a viscosity in 2% w / w aqueous solution at 20 °C of 2.4-3.6 mPa•s. In some embodiments, HPMCAS HG is characterized by (i) and (ii). In some embodiments, HPMCAS HG is characterized by (i)-(iv). In some embodiments, HPMCAS HG is characterized by (i)-(v). In some embodiments, HPMCAS HG is characterized by (i)-(iv) and (vi). In some embodiments, HPMCAS HG is characterized by (i)-(iv) and (vii). In some embodiments, HPMCAS HG is characterized by (i)-(vi). In some embodiments, HPMCAS HG is characterized by all of (i)-(vii). In some embodiments, HPMCAS E3 is characterized by one or more of the following properties: (i) a methoxyl content of 28.0-30.0%, for example a methoxyl content of 29%; (ii) a hydroxypropyl content of 7.0-12.0%, for example a hydroxypropyl content of 10%; (iii) a viscosity in 2% w / w aqueous solution at 20 °C of 3 mPa•s. In some embodiments, HPMCAS E3 is characterized by (i) and (ii). In some embodiments, HPMCAS E3 is characterized by all of (i)- (iii). The solid dispersion may also comprise a surfactant. In some embodiments, the surfactant is selected from the group consisting of: polyethylene-polypropylene glycol, lecithin, bile salt, and lauroyl polyoxyl-32 glycerides. In some embodiments, the Compound A in the solid dispersion is substantially amorphous. In some embodiments, substantially amorphous means less than 15% of the Compound A is crystalline. In some embodiments, substantially amorphous means less than 10% of the Compound A is crystalline. In some embodiments, substantially amorphous means less than 5% of the Compound A is crystalline. In some embodiments, the Compound A in the solid dispersion is amorphous, i.e. the solid dispersion does not contain any crystalline Compound A. The particle size of Compound A in the solid dispersion may be reduced via co- micronisation. In some embodiments, Compound A is co-micronized with sodium lauryl sulfate or tocofersolan. In some embodiments, Compound A is co-micronized with sodium lauryl sulfate. In some embodiments, Compound A is co-micronized with tocofersolan. In some embodiments, Compound A is co-micronized with sodium lauryl sulfate or tocofersolan and the amount of Compound A in the dosage form is between 0.01 mg and 2 mg. In some embodiments, Compound A is co-micronized with sodium lauryl sulfate or tocofersolan and the amount of Compound A in PAT059980-WO-PCT the dosage form is between 0.01 mg and 1 mg. In some embodiments, Compound A is co- micronized with sodium lauryl sulfate or tocofersolan and the amount of Compound A in the dosage form is between 0.01 mg and 0.5 mg. In some embodiments, Compound A is co-micronized with sodium lauryl sulfate or tocofersolan and the amount of Compound A in the dosage form is between 0.01 mg and 0.2 mg. In some embodiments, Compound A is co-micronized with sodium lauryl sulfate or tocofersolan and the amount of Compound A in the dosage form is between 0.01 mg and 0.1 mg. In some embodiments, the solid dispersion makes up less than 50% by weight of the tablet. In some embodiments, the solid dispersion makes up less than 40% by weight of the tablet. In some embodiments, the solid dispersion makes up less than 30% by weight of the tablet. In some embodiments, the solid dispersion makes up less than 20% by weight of the tablet. In some embodiments, the solid dispersion makes up less than 10% by weight of the tablet. In some embodiments, the solid dispersion makes up less than 5% by weight of the tablet. In some embodiments, the solid dispersion makes up less than 3% by weight of the tablet. In some embodiments, the solid dispersion makes up less than 1% by weight of the tablet. In some embodiments, the solid dispersion is a spray dried dispersion. Spray drying is a process that is commonly used to prepare solid dispersions from a liquid suspension or solution, and the skilled person will be able to readily prepare solid dispersions as provided herein, for example using commercial spray drying equipment. Techniques and methods for spray drying may be found in Perry’s Chemical Engineering Handbook, 6th Ed., R. H. Perry, D. W. Green & J. O. Maloney, eds.), McGraw-Hill book co. (1984); and Marshall "Atomization and Spray Drying" 50, Chem. Eng. Prog. Monogr. Series 2 (1954). Some conventional spray drying process parameters are as follows. The load of solid material (i.e., drug and excipients) in the liquid starting material is generally from about 3% to about 30% by weight. The inlet temperature is generally from about 60 °C to about 200 °C. The outlet temperature is generally from about 30 °C to about 90 °C. The atomization flow rate is generally from about 4 kg / h to about 12 kg / h. The feed flow rate is generally from about 3 kg / h to about 10 kg / h. The atomization ratio is generally from about 0.3 to 1.7. The solvent in the liquid starting material may be acetone, cyclohexane, dichloromethane, N,N-dimethylacetamide (DMA), N,N-dimethylformamide (DMF), 1,3-dimethyl-2- imidazolidinone (DMI), dimethyl sulfoxide (DMSO), dioxane, ethyl acetate, ethyl ether, glacial acetic acid (HAc), methyl ethyl ketone (MEK), N-methyl-2-pyrrolidinone (NMP), methyl tert- butyl ether (MTBE), tetrahydrofuran (THF), pentane, acetonitrile, methanol, ethanol, isopropyl PAT059980-WO-PCT alcohol, isopropyl acetate, toluene, or a mixture thereof, for example acetone / DMSO, acetone / DMF, acetone / water, MEK / water, THF / water, or dioxane / water. Tablet In some embodiments, the tablet comprises one or more of the following excipients: (i) a filler; (ii) a glidant; (iii) a disintegrant; and (iv) a lubricant. In some embodiments, the tablet comprises (i) and (ii), (i) and (iii), (i) and (iv), (ii) and (iii), (ii) and (iv), or (iii) and (iv). In some embodiments, the tablet comprises (i), (ii), and (iii), (i), (ii), and (iv), (i), (iii), and (iv), or (ii), (iii), and (iv). In some embodiments, the tablet comprises (i), (ii), (iii), and (iv). In some embodiments, the tablet comprises a filler. The filler may be selected from the group consisting of: celluloses, modified celluloses (such as sodium carboxymethyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropylcellulose, cellulose acetate, microcrystalline cellulose, and silicified microcrystalline cellulose), calcium phosphates (such as dibasic calcium phosphate), starches (such as corn starch and potato starch), sugars (such as mannitol, sorbitol, lactose, and sucrose), and combinations thereof. In some embodiments, the filler is mannitol, microcrystalline cellulose, or silicified microcrystalline cellulose. In some embodiments, the filler is microcrystalline cellulose. If present, the filler makes up less than 98% by weight of the tablet. In some embodiments, the filler makes up between 10 and 98% by weight of the tablet. In some embodiments, the filler makes up between 20 and 98% by weight of the tablet. In some embodiments, the filler makes up between 30 and 98% by weight of the tablet. In some embodiments, the filler makes up between 40 and 98% by weight of the tablet. In some embodiments, the filler makes up between 50 and 98% by weight of the tablet. In some embodiments, the filler makes up less than 95% by weight of the tablet. In some embodiments, the filler makes up between 10 and 95% by weight of the tablet. In some embodiments, the filler makes up between 20 and 95% by weight of the tablet. In some embodiments, the filler makes up between 30 and 95% by weight of the tablet. In some embodiments, the filler makes up between 40 and 95% by weight of the tablet. In some embodiments, the filler makes up between 50 and 95% by weight of the tablet. PAT059980-WO-PCT In some embodiments, the tablet comprises a glidant. The glidant may be selected from the group consisting of: fumed silica, talc, and a combination thereof. In some embodiments, the glidant is fumed silica. If present, the glidant makes up less than 10% by weight of the tablet. In some embodiments, the glidant makes up less than 5% by weight of the tablet. In some embodiments, the glidant makes up less than 2% by weight of the tablet. In some embodiments, the glidant makes up 1% by weight of the tablet. In some embodiments, the tablet comprises a disintegrant. The disintegrant may be selected from the group consisting of: starches (such as corn starch and potato starch), modified starches (such as pregelatinized starch, sodium starch glycolate, and starch 1500), cellulose derivatives (such as microcrystalline cellulose, croscarmellose sodium, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose), natural gums (such as guar gum, xanthan gum, and locust bean gum), ion exchange resins (such as polacrilin potassium and Amberlite IRP69), calcium silicates (dicalcium phosphate and tricalcium phosphate), sodium alginate, cross-linked polyvinylpyrrolidone, chitosan, and combinations thereof. In some embodiments, the disintegrant is croscarmellose sodium. If present, the disintegrant makes up less than 10% by weight of the tablet. In some embodiments, the disintegrant makes up less than 5% by weight of the tablet. In some embodiments, the disintegrant makes up between 1 and 5% by weight of the tablet. In some embodiments, the disintegrant makes up between 2 and 4% by weight of the tablet. In some embodiments, the disintegrant makes up 3% by weight of the tablet. In some embodiments, the tablet comprises a lubricant. The lubricant may be selected from the group consisting of: magnesium stearate, stearic acid, calcium stearate, sodium stearyl fumarate, polyethylene glycols, beeswax, hydrogenated vegetable oil, and combinations thereof. In some embodiments, the lubricant is magnesium stearate. If present, the lubricant makes up less than 10% by weight of the tablet. In some embodiments, the lubricant makes up less than 5% by weight of the tablet. In some embodiments, the lubricant makes up less than 2% by weight of the tablet. In some embodiments, the lubricant makes up 1% by weight of the tablet. In these embodiments, each of (i)-(iv), if present, are preferably different materials. However, it may not be necessary to include all of (i)-(iv), for example if one material is capable of performing more than one excipient function. Where a material is capable of performing more than one excipient function, its weight may be counted only once, but may be assigned to any category of excipient of which it is a member. In some embodiments, the tablet comprises: PAT059980-WO-PCT (i) a filler up to 98% by weight of the tablet; (ii) a glidant that makes up less than 10% by weight of the tablet; (iii) a disintegrant that makes up less than 10% by weight of the tablet; and (iv) a lubricant that makes up less than 10% by weight of the tablet. In some embodiments, the tablet comprises: (i) a filler that makes up between 40 and 98% by weight of the tablet; (ii) a glidant that makes up less than 5% by weight of the tablet; (iii) a disintegrant that makes up between 1 and 5% by weight of the tablet; and (iv) a lubricant that makes up less than 5% by weight of the tablet. In some embodiments, the tablet comprises: (i) a filler that makes up between 50 and 98% by weight of the tablet; (ii) a glidant that makes up less than 2% by weight of the tablet; (iii) a disintegrant that makes up between 2 and 4% by weight of the tablet; and (iv) a lubricant that makes up less than 2% by weight of the tablet. In some embodiments, the tablet comprises: (i) a filler up to 95% by weight of the tablet; (ii) a glidant that makes up less than 10% by weight of the tablet; (iii) a disintegrant that makes up less than 10% by weight of the tablet; and (iv) a lubricant that makes up less than 10% by weight of the tablet. In some embodiments, the tablet comprises: (i) a filler that makes up between 40 and 95% by weight of the tablet; (ii) a glidant that makes up less than 5% by weight of the tablet; (iii) a disintegrant that makes up between 1 and 5% by weight of the tablet; and (iv) a lubricant that makes up less than 5% by weight of the tablet. In some embodiments, the tablet comprises: (i) a filler that makes up between 50 and 95% by weight of the tablet; (ii) a glidant that makes up less than 2% by weight of the tablet; (iii) a disintegrant that makes up between 2 and 4% by weight of the tablet; and (iv) a lubricant that makes up less than 2% by weight of the tablet. In some embodiments, the tablet comprises a granular formulation. In some embodiments, the tablet comprises an intragranular fraction and an extragranular fraction. In some embodiments, the Compound A is contained within the intragranular fraction. In some embodiments, the Compound A is contained within the intragranular fraction in a solid dispersion. PAT059980-WO-PCT In some embodiments, the intragranular fraction makes up over 95% by weight of the tablet. In some embodiments, the intragranular fraction makes up over 96% by weight of the tablet. In some embodiments, the intragranular fraction makes up over 97% by weight of the tablet. In some embodiments, the intragranular fraction makes up 98% by weight of the tablet. In some embodiments, the extragranular fraction makes up less than 5% by weight of the tablet. In some embodiments, the extragranular fraction makes up less than 4% by weight of the tablet. In some embodiments, the extragranular fraction makes up less than 3% by weight of the tablet. In some embodiments, the extragranular fraction makes up 2% by weight of the tablet. In some embodiments, the intragranular fraction comprises tablet excipients as described above. In some embodiments, the intragranular fraction comprises: (i) a filler that makes up between 30 and 80% by weight of the tablet; (ii) a glidant that makes up less than 5% by weight of the tablet; (iii) a disintegrant that makes up less than 10% by weight of the tablet; and (iv) a lubricant that makes up less than 5% by weight of the tablet. In some embodiments, the intragranular fraction comprises: (i) a filler that makes up between 40 and 70% by weight of the tablet; (ii) a glidant that makes up less than 2% by weight of the tablet; (iii) a disintegrant that makes up between 1 and 5% by weight of the tablet; and (iv) a lubricant that makes up less than 2% by weight of the tablet. In some embodiments, the intragranular fraction comprises: (i) a filler that makes up between 50 and 60% by weight of the tablet; (ii) a glidant that makes up less than 1% by weight of the tablet; (iii) a disintegrant that makes up between 2 and 4% by weight of the tablet; and (iv) a lubricant that makes up less than 1% by weight of the tablet. In some embodiments, the intragranular fraction comprises between 30 and 50% of a solid dispersion comprising Compound A. In some embodiments, the intragranular fraction comprises between 35 and 45% of a solid dispersion comprising Compound A. In some embodiments, the extragranular fraction comprises a disintegrant. In some embodiments, the disintegrant makes up less than 5% by weight of the tablet. In some embodiments, the disintegrant makes up less than 3% by weight of the tablet. In some embodiments, the disintegrant makes up between 1 and 2% by weight of the tablet. In some embodiments, the extragranular fraction comprises a lubricant. In some embodiments, the lubricant makes up less than 3% by weight of the tablet. In some embodiments, the lubricant makes up less than 2% by weight of the tablet. In some embodiments, the lubricant makes up less than 1% by weight of the tablet. PAT059980-WO-PCT In some embodiments, the extragranular fraction comprises a disintegrant and a lubricant. In some embodiments, the extragranular fraction comprises a disintegrant and a lubricant, wherein the disintegrant and lubricant are in any of the amounts recited in the previous two paragraphs. In some embodiments, the tablet comprises (a) a solid dispersion comprising Compound A and a polymer, (b) a filler, (c) a glidant, (d) a disintegrant, and (e) a lubricant, and the tablet has one or more of the following features: (i) the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, for example hydroxypropylmethylcellulose (HPMCAS), for example HPMCAS HG; (ii) the filler is microcrystalline cellulose; (iii) the glidant is fumed silica; (iv) the disintegrant is croscarmellose sodium; (v) the lubricant is magnesium stearate; (vi) the solid dispersion makes up less than 50% by weight of the tablet; (vii) the filler makes up between 50 and 98% by weight of the tablet; (viii) the glidant makes up less than 2% by weight of the tablet; (ix) the disintegrant makes up between 2 and 4% by weight of the tablet; (x) the lubricant makes up less than 2% by weight of the tablet; (xi) the tablet comprises between 0.05 mg and 20 mg of Compound A. In some embodiments, the tablet has features (i)-(v). In some embodiments, the tablet has features (vi)-(x). In some embodiments, the tablet has features (i)-(x). In some embodiments, the tablet has features (i)-(v) and (xi). In some embodiments, the tablet has features (vi)-(xi). In some embodiments, the tablet prepared has features (i)-(xi). In some embodiments, the tablet comprises (a) a solid dispersion comprising Compound A and a polymer, (b) a filler, (c) a glidant, (d) a disintegrant, and (e) a lubricant, and the tablet has one or more of the following features: (i) the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, for example hydroxypropylmethylcellulose (HPMCAS), for example HPMCAS HG; (ii) the filler is microcrystalline cellulose; (iii) the glidant is fumed silica; (iv) the disintegrant is croscarmellose sodium; (v) the lubricant is magnesium stearate; (vi) the solid dispersion makes up less than 1% by weight of the tablet; (vii) the filler makes up between 92 and 98% by weight of the tablet; (viii) the glidant makes up less than 2% by weight of the tablet; PAT059980-WO-PCT (ix) the disintegrant makes up between 2 and 4% by weight of the tablet; (x) the lubricant makes up less than 2% by weight of the tablet; (xi) the tablet comprises 0.1 mg of Compound A. In some embodiments, the tablet has features (i)-(v). In some embodiments, the tablet has features (vi)-(x). In some embodiments, the tablet has features (i)-(x). In some embodiments, the tablet has features (i)-(v) and (xi). In some embodiments, the tablet has features (vi)-(xi). In some embodiments, the tablet has features (i)-(xi). In some embodiments, the tablet comprises (a) a solid dispersion comprising Compound A and a polymer, (b) a filler, (c) a glidant, (d) a disintegrant, and (e) a lubricant, and the tablet has one or more of the following features: (i) the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, for example hydroxypropylmethylcellulose (HPMCAS), for example HPMCAS HG; (ii) the filler is microcrystalline cellulose; (iii) the glidant is fumed silica; (iv) the disintegrant is croscarmellose sodium; (v) the lubricant is magnesium stearate; (vi) the solid dispersion makes up between 1 and 3% by weight of the tablet; (vii) the filler makes up between 91 and 95% by weight of the tablet; (viii) the glidant makes up less than 2% by weight of the tablet; (ix) the disintegrant makes up between 2 and 4% by weight of the tablet; (x) the lubricant makes up less than 2% by weight of the tablet; (xi) the tablet comprises 0.5 mg of Compound A. In some embodiments, the tablet has features (i)-(v). In some embodiments, the tablet has features (vi)-(x). In some embodiments, the tablet has features (i)-(x). In some embodiments, the tablet has features (i)-(v) and (xi). In some embodiments, the tablet has features (vi)-(xi). In some embodiments, the tablet has features (i)-(xi). In some embodiments, the tablet comprises (a) a solid dispersion comprising Compound A and a polymer, (b) a filler, (c) a glidant, (d) a disintegrant, and (e) a lubricant, and the tablet has one or more of the following features: (i) the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, for example hydroxypropylmethylcellulose (HPMCAS), for example HPMCAS HG; (ii) the filler is microcrystalline cellulose; (iii) the glidant is fumed silica; (iv) the disintegrant is croscarmellose sodium; (v) the lubricant is magnesium stearate; PAT059980-WO-PCT (vi) the solid dispersion makes up between 6 and 10% by weight of the tablet; (vii) the filler makes up between 85 and 89% by weight of the tablet; (viii) the glidant makes up less than 2% by weight of the tablet; (ix) the disintegrant makes up between 2 and 4% by weight of the tablet; (x) the lubricant makes up less than 2% by weight of the tablet; (xi) the tablet comprises 2 mg of Compound A. In some embodiments, the tablet has features (i)-(v). In some embodiments, the tablet has features (vi)-(x). In some embodiments, the tablet has features (i)-(x). In some embodiments, the tablet has features (i)-(v) and (xi). In some embodiments, the tablet has features (vi)-(xi). In some embodiments, the tablet has features (i)-(xi). In some embodiments, the tablet comprises (a) a solid dispersion comprising Compound A and a polymer, (b) a filler, (c) a glidant, (d) a disintegrant, and (e) a lubricant, and the tablet has one or more of the following features: (i) the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, for example hydroxypropylmethylcellulose (HPMCAS), for example HPMCAS HG; (ii) the filler is microcrystalline cellulose; (iii) the glidant is fumed silica; (iv) the disintegrant is croscarmellose sodium; (v) the lubricant is magnesium stearate; (vi) the solid dispersion makes up between 35 and 45% by weight of the tablet; (vii) the filler makes up between 50 and 60% by weight of the tablet; (viii) the glidant makes up less than 2% by weight of the tablet; (ix) the disintegrant makes up between 2 and 4% by weight of the tablet; (x) the lubricant makes up less than 2% by weight of the tablet; (xi) the tablet comprises 10 mg of Compound A. In some embodiments, the tablet has features (i)-(v). In some embodiments, the tablet has features (vi)-(x). In some embodiments, the tablet has features (i)-(x). In some embodiments, the tablet has features (i)-(v) and (xi). In some embodiments, the tablet has features (vi)-(xi). In some embodiments, the tablet has features (i)-(xi). In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 0.4 ± 0.04 Microcrystalline cellulose 94.6 ± 9.46 PAT059980-WO-PCT Fumed silica 1 ± 0.1 Croscarmellose sodium 3 ± 0.3 Magnesium stearate 1 ± 0.1 Total 100 In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 0.4 Microcrystalline cellulose 94.6 Fumed silica 1 Croscarmellose sodium 3 Magnesium stearate 1 Total 100 In some embodiments, the tablet compositions in the two preceding paragraphs comprise of Compound A. In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 2 ± 0.2 Microcrystalline cellulose 93 ± 9.3 Fumed silica 1 ± 0.1 Croscarmellose sodium 3 ± 0.3 Magnesium stearate 1 ± 0.1 Total 100 In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 2 Microcrystalline cellulose 93 Fumed silica 1 Croscarmellose sodium 3 Magnesium stearate 1 Total 100 PAT059980-WO-PCT In some embodiments, the tablet compositions in the two preceding paragraphs comprise5 mg of Compound A. In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 8 ± 0.8 Microcrystalline cellulose 87 ± 8.7 Fumed silica 1 ± 0.1 Croscarmellose sodium 3 ± 0.3 Magnesium stearate 1 ± 0.1 Total 100 In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 8 Microcrystalline cellulose 87 Fumed silica 1 Croscarmellose sodium 3 Magnesium stearate 1 Total 100 In some embodiments, the tablet compositions in the two preceding paragraphs comprise mg of Compound A. In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A: HPMCAS HG 40 ± 4 Microcrystalline cellulose 55 ± 5.5 Intra-granular Fumed silica 1 ± 0.1 fraction (IG) Croscarmellose sodium 1.5 ± 0.15 Magnesium stearate 0.5 ± 0.05 IG Total 98 ± 9.8 Croscarmellose sodium 1.5 ± 0.15 Extra-granular fraction (EG) Magnesium stearate 0.5 ± 0.05 EG Total 100 PAT059980-WO-PCT In some embodiments, the tablet has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A: HPMCAS HG 40 Microcrystalline cellulose 55 Intra-granular Fumed silica 1 fraction (IG) Croscarmellose sodium 1.5 Magnesium stearate 0.5 IG Total 98 Croscarmellose sodium 1.5 Extra-granular fraction (EG) Magnesium stearate 0.5 EG Total 100 In some embodiments, the tablet compositions in the two preceding paragraphs comprise 10 mg of Compound A. Method of preparing tablets In one aspect, provided herein is a method of preparing a tablet described herein comprising (i) a solid dispersion comprising Compound A and a polymer, (ii) a filler, (iii) a glidant, (iv) a disintegrant, and (v) a lubricant. The method comprises one or more of the following steps: (1) Measuring out each of the ingredients onto a weight boat or the like (2) Pre-coating a container by adding about 10-15% (for example about 12.5%) of the filler to the container (3) Mixing the solid dispersion with about 20-30% (for example about 25%) by weight of the filler to form pre-mix 1 (4) Adding pre-mix 1, the glidant, and the disintegrant to the container (5) Adding about 10-15% (for example about 12.5%) of the filler to the container to form pre-mix 2, optionally wherein the about 10-15% (or 12.5%) of the filler is used to dry wash the weigh boat or the like used to measure out the solid dispersion before being added to the container (6) Mixing pre-mix 2, optionally wherein pre-mix 2 is mixed for about 5-15 minutes (for example about 10 minutes), and optionally wherein pre-mix 2 is mixed at about 30-35 RPM (for example about 32 RPM) (7) Sieving pre-mix 2 onto a weigh boat or the like, optionally wherein pre-mix 2 is sieved through a 500 µm screen PAT059980-WO-PCT (8) Adding about 40-60% (for example about 50%) of the remaining filler into the container (9) Adding pre-mix 2 from the weight boat or the like into the container (10) Adding the remaining filler into the container to form pre-mix 3, optionally wherein the remaining filler is used to dry wash the weight boat or the like used in step (7) before being added to the container (11) Mixing pre-mix 3, optionally wherein pre-mix 3 is mixed for about 3-7 minutes (for example about 5 minutes, and optionally wherein pre-mix 3 is mixed at about 30-35 RPM (for example about 32 RPM) (12) Sieving pre-mix 3, optionally wherein pre-mix 3 is sieved through a 500 µm screen (13) Mixing the sieved pre-mix 3, optionally wherein pre-mix 3 is mixed for about 5-15 minutes (for example about 10 minutes), and optionally wherein pre-mix 3 is mixed at about 30-35 RPM (for example about 32 RPM) (14) Sieving the magnesium stearate, optionally wherein the magnesium stearate is sieved through a 500 µm screen (15) Adding the sieved magnesium stearate to pre-mix 3 to form the final blend (16) Mixing the final blend, optionally wherein the final blend is mixed for about 1-3 minutes (for example about 2 minutes), optionally wherein the final blend is mixed at about 30-35 RPM (for example about 32 RPM) (17) Compressing the final blend In some embodiments, the method comprises steps (1)-(16). In some embodiments, the method comprises all of steps (1)-(17). In some embodiments, the tablet prepared has one or more of the following features: (i) the polymer is a hydroxypropylmethylcellulose (HPMC) derivative, for example hydroxypropylmethylcellulose (HPMCAS), for example HPMCAS HG; (ii) the filler is microcrystalline cellulose; (iii) the glidant is fumed silica; (iv) the disintegrant is croscarmellose sodium; (v) the lubricant is magnesium stearate; (vi) the solid dispersion makes up between 1 and 3% by weight of the tablet; (vii) the filler makes up over 90% by weight of the tablet; (viii) the glidant makes up less than 2% by weight of the tablet; (ix) the disintegrant makes up between 2 and 4% by weight of the tablet; (x) the lubricant makes up less than 2% by weight of the tablet; PAT059980-WO-PCT (xi) the tablet comprises 0.5 mg of Compound A. In some embodiments, the tablet prepared has features (i)-(v). In some embodiments, the tablet prepared has features (vi)-(x). In some embodiments, the tablet prepared has features (i)-(x). In some embodiments, the tablet prepared has features (i)-(v) and (xi). In some embodiments, the tablet prepared has features (vi)-(xi). In some embodiments, the tablet prepared has features (i)- (xi). In some embodiments, the tablet prepared has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 2 ± 0.2 Microcrystalline cellulose 93 ± 9.3 Fumed silica 1 ± 0.1 Croscarmellose sodium 3 ± 0.3 Magnesium stearate 1 ± 0.1 Total 100 In some embodiments, the tablet prepared has the following composition: Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 2 Microcrystalline cellulose 93 Fumed silica 1 Croscarmellose sodium 3 Magnesium stearate 1 Total 100 In some embodiments, the tablet compositions in the two preceding paragraphs comprise 0.5 mg of Compound A. Capsules In some embodiments, the dosage form is a capsule. The capsule may be a soft capsule, such as a softgel, or a hard capsule. The skilled practitioner will be familiar with conventional methods of preparing capsules. Hard capsules are typically produced from two halves that are sealed together after the active ingredient and any excipients are added. Hard capsules can be filled manually (e.g. with a pipette), or automatically (e.g. with an automated filling machine). Hard capsules may be made PAT059980-WO-PCT from gelatin, or HPMC (hydroxypropylmethyl cellulose), with the latter being preferred due to a reduction in capsule leakage compared to gelatin capsules. In some embodiments, the capsule is a softgel. Softgels have a gelatin-based shell surrounding a liquid or semi-solid fill. Many patients prefer softgel capsules to hard capsules as they can be easier to swallow.^In addition, it is straightforward to prepare a uniform lipid solution of Compound A for inclusion as the softgel fill, which facilitates highly accurate dosing. Softgels are produced using a softgel encapsulation machine, which uses a pump to deliver the softgel fill into the gelatin shell. Softgel shells are normally a combination of gelatin, water, and a plasticiser such as glycerin and / or sorbitol. In some embodiments, the softgel shell comprises gelatin, sorbitol glycerin blend, an opacifier such as titanium dioxide or iron oxide, and purified water. In some embodiments, the opacifier is titanium dioxide. In some embodiments, the softgel fill comprises a solubiliser. In some embodiments, the solubiliser is selected from the group consisting of emulsifiers, surfactants, and combinations thereof. In some embodiments, the solubiliser is selected from the group consisting of: monoglycerides (such as glyceryl monostearate), diglycerides, medium-chain triglycerides, poloxamers, polyoxyethylenesorbitan fatty acid esters, polyoxylglycerides, sucrose esters, cyclodextrins, PEGs, sodium lauryl sulfate, docusate sodium, polyoxyl 40 hydrogenated castor oil, propylene glycol alginate, and combinations thereof. In some embodiments, the solubiliser is selected from the group consisting of: benzyl alcohol, polyoxyl 35 castor oil, glyceryl monolinoleate, tocofersolan, propylene glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, glyceryl mono and dicaprylocaprate, lecithin, and combinations thereof. Preferably, the solubiliser comprises benzyl alcohol, as Compound A is particularly soluble in benzyl alcohol. In some embodiments, the solubiliser comprises benzyl alcohol, polyoxyl 35 castor oil, and glyceryl monolinoleate. In some embodiments, the solubiliser comprises benzyl alcohol, polyoxyl 35 castor oil, glyceryl monolinoleate, and lecithin. In some embodiments, the solubiliser is a non-ionic surfactant. In some embodiments, the non-ionic surfactant is selected from the group consisting of: vitamin E derivatives, fatty acid esters, fatty alcohol ethers, glycerol derivatives, sorbitan derivatives, co-polymers, and combinations thereof. In some embodiments, the non-ionic surfactant is selected from the group consisting of: d-α tocopherol polyethylene glycol 1000 succinate, Solutol HS15, Macrogol cetostearyl ether; Cremaphor EL, Cremaphor RH35, Cremaphor RH40, Labrasol ALF, Labrafac PC, Labrafil M 1944, Labrafil 2125, Gelucire 44 / 14, Gelucire 50 / 13, Tween 40, Tween 60, Tween 80, Softisan 378, Poloxamer P124, and mixtures thereof. PAT059980-WO-PCT In some embodiments, the solubiliser makes up greater than 50% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 60% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 70% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 80% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 90% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 95% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 98% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 99% by weight of the softgel fill. In some embodiments, the solubiliser makes up greater than 99.5% by weight of the softgel fill. In some embodiments, the softgel fill comprises an antioxidant. In some embodiments, the antioxidant is selected from the group consisting of: ascorbic acid and derivatives thereof, citric acid and derivatives thereof, sodium metabisulfate, sodium thiosulfate, cysteine, tryptophan, methionine, butylated hydroxytoluene, propyl, octyl, dodecyl esters of gallic acid, and combinations thereof. In some embodiments, the antioxidant is selected from the group consisting of: ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, and combinations thereof. In some embodiments, the antioxidant comprises ascorbyl palmitate, butylated hydroxyanisole, and butylated hydroxytoluene. In some embodiments, the antioxidant comprises butylated hydroxyanisole and butylated hydroxytoluene. It has been found that use of ascorbyl palmitate in particular as the antioxidant reduces degradation of Compound A (although this does not preclude the use of other antioxidants instead of or in addition to ascorbyl palmitate). Thus, the antioxidant preferably comprises ascorbyl palmitate. In some embodiments, the antioxidant makes up less than 5% by weight of the softgel fill. In some embodiments, the antioxidant makes up less than 3% by weight of the softgel fill. In some embodiments, the antioxidant makes up less than 2% by weight of the softgel fill. In some embodiments, the antioxidant makes up less than 1% by weight of the softgel fill. In some embodiments, the antioxidant makes up less than 0.5% by weight of the softgel fill. In some embodiments, the antioxidant makes up less than 0.3% by weight of the softgel fill. In some embodiments, the antioxidant makes up between 0.5 and 1.5% by weight of the softgel fill. In some embodiments, the antioxidant makes up between 1 and 2% by weight of the softgel fill. In some embodiments, the softgel fill comprises a solubiliser that makes up greater than 50% by weight of the softgel fill, and an antioxidant that makes up less than 5% by weight of the softgel fill. In some embodiments, the softgel fill comprises a solubiliser that makes up greater than 95% by weight of the softgel fill, and an antioxidant that makes up less than 3% by weight of the softgel fill. In some embodiments, the softgel fill comprises a solubiliser that makes up greater than 98% by weight of the softgel fill, and an antioxidant that makes up less than 2% by weight of PAT059980-WO-PCT the softgel fill. In some embodiments, the softgel fill comprises a solubiliser that makes up greater than 98% by weight of the softgel fill, and an antioxidant that makes up between 1 and 2% by weight of the softgel fill. In some embodiments, the softgel fill comprises a solubiliser that makes up greater than 98% by weight of the softgel fill, and an antioxidant that makes up between 0.5 and 1.5% by weight of the softgel fill. In some embodiments, the solubiliser comprises benzyl alcohol. In some embodiments, the benzyl alcohol makes up less than 20% by weight of the softgel fill. In some embodiments, the benzyl alcohol makes up between 5 and 15% by weight of the softgel fill. In some embodiments, the benzyl alcohol makes up between 8 and 12% by weight of the softgel fill. In some embodiments, the benzyl alcohol makes up 10% by weight of the softgel fill. In some embodiments, the solubiliser comprises polyoxyl 35 castor oil. In some embodiments, the polyoxyl 35 castor oil makes up between 30 and 60% by weight of the softgel fill. In some embodiments, the polyoxyl 35 castor oil makes up between 40 and 50% by weight of the softgel fill. In some embodiments, the polyoxyl 35 castor oil makes up between 43 and 47% by weight of the softgel fill. In some embodiments, the polyoxyl 35 castor oil makes up 45% by weight of the softgel fill. In some embodiments, the solubiliser comprises glyceryl monolinoleate. In some embodiments, the glyceryl monolinoleate makes up between 20 and 60% by weight of the softgel fill. In some embodiments, the glyceryl monolinoleate makes up between 30 and 50% by weight of the softgel fill. In some embodiments, the glyceryl monolinoleate makes up between 39 and 45% by weight of the softgel fill. In some embodiments, the glyceryl monolinoleate makes up 40% by weight of the softgel fill. In some embodiments, the solubiliser comprises lecithin. In some embodiments, the lecithin makes up less than 10% by weight of the softgel fill. In some embodiments, the lecithin makes up between 2.5 and 7.5% by weight of the softgel fill. In some embodiments, the lecithin makes up between 4.0 and 5.5% by weight of the softgel fill. In some embodiments, the lecithin makes up between 4.5 and 5% by weight of the softgel fill. In some embodiments, the antioxidant comprises ascorbyl palmitate. In some embodiments, the ascorbyl palmitate makes up less than 10% by weight of the softgel fill. In some embodiments, the ascorbyl palmitate makes up less than 5% by weight of the softgel fill. In some embodiments, the ascorbyl palmitate makes up less than 3% by weight of the softgel fill. In some embodiments, the ascorbyl palmitate makes up 1% by weight of the softgel fill. In some embodiments, the antioxidant comprises butylated hydroxyanisole. In some embodiments, the butylated hydroxyanisole makes up less than 1% by weight of the softgel fill. In some embodiments, the butylated hydroxyanisole makes up less than 0.5% by weight of the softgel PAT059980-WO-PCT fill. In some embodiments, the butylated hydroxyanisole makes up less than 0.1% by weight of the softgel fill. In some embodiments, the butylated hydroxyanisole makes up 0.05% by weight of the softgel fill. In some embodiments, the antioxidant comprises butylated hydroxytoluene. In some embodiments, the butylated hydroxytoluene makes up less than 1% by weight of the softgel fill. In some embodiments, the butylated hydroxytoluene makes up less than 0.5% by weight of the softgel fill. In some embodiments, the butylated hydroxytoluene makes up less than 0.1% by weight of the softgel fill. In some embodiments, the butylated hydroxytoluene makes up 0.05% by weight of the softgel fill. In some embodiments, the softgel fill comprises simethicone. In some embodiments, the simethicone makes up less than 1% by weight of the softgel fill. In some embodiments, the simethicone makes up less than 0.5% by weight of the softgel fill. In some embodiments, the simethicone makes up less than 0.1% by weight of the softgel fill. In some embodiments, the simethicone makes up less than 0.05% by weight of the softgel fill. In some embodiments, the simethicone makes up less than 0.03% by weight of the softgel fill. In some embodiments, the simethicone makes up 0.01% by weight of the softgel fill. In some embodiments, the softgel fill comprises povidone. In some embodiments, the povidone makes up between 1 and 9% by weight of the softgel fill. In some embodiments, the povidone makes up between 3 and 7% by weight of the softgel fill. In some embodiments, the povidone makes up between 4 and 5% by weight of the softgel fill. In some embodiments, the povidone makes up between 4.5 and 5% by weight of the softgel fill. In some embodiments, the capsule comprises (a) a solubiliser and (b) an antioxidant, and the capsule has one or more of the following features: (i) the solubiliser makes up greater than 90% by weight of the softgel fill; (ii) the antioxidant makes up less than 3% by weight of the softgel fill; (iii) the solubiliser comprises benzyl alcohol, polyoxyl 35 castor oil, and glyceryl monolinoleate; (iv) the benzyl alcohol makes up between 5 and 15% by weight of the softgel fill; (v) the polyoxyl 35 castor oil makes up between 40 and 50% by weight of the softgel fill; (vi) the glyceryl monolinoleate makes up between 30 and 50% by weight of the softgel fill; (vii) the antioxidant comprises butylated hydroxyanisole and butylated hydroxytoluene; (viii) the butylated hydroxyanisole makes up less than 1% by weight of the softgel fill; (ix) the butylated hydroxytoluene makes up less than 1% by weight of the softgel fill. PAT059980-WO-PCT In some embodiments, the capsule has features (i) and (ii). In some embodiments, the capsule has features (iii)-(vi). In some embodiments, the capsule has features (vii)-(ix). In some embodiments, the capsule has features (i) and (iii). In some embodiments, the capsule has features (i) and (iii)-(vi). In some embodiments, the capsule has features (ii) and (vii). In some embodiments, the capsule has features (ii) and (vii)-(ix). In some embodiments, the capsule has features (i), (ii), (iii) and (vii). In some embodiments, the capsule has features (i)-(ix). In some embodiments, the capsule comprises (a) a solubiliser and (b) an antioxidant, and the capsule has one or more of the following features: (i) the solubiliser makes up greater than 95% by weight of the softgel fill; (ii) the antioxidant makes up less than 2% by weight of the softgel fill; (iii) the solubiliser comprises benzyl alcohol, polyoxyl 35 castor oil, and glyceryl monolinoleate; (iv) the benzyl alcohol makes up between 8 and 12% by weight of the softgel fill; (v) the polyoxyl 35 castor oil makes up between 43 and 47% by weight of the softgel fill; (vi) the glyceryl monolinoleate makes up between 39 and 45% by weight of the softgel fill; (vii) the antioxidant comprises butylated hydroxyanisole and butylated hydroxytoluene; (viii) the butylated hydroxyanisole makes up less than 0.1% by weight of the softgel fill; (ix) the butylated hydroxytoluene makes up less than 0.1% by weight of the softgel fill. In some embodiments, the capsule has features (i) and (ii). In some embodiments, the capsule has features (iii)-(vi). In some embodiments, the capsule has features (vii)-(ix). In some embodiments, the capsule has features (i) and (iii). In some embodiments, the capsule has features (i) and (iii)-(vi). In some embodiments, the capsule has features (ii) and (vii). In some embodiments, the capsule has features (ii) and (vii)-(ix). In some embodiments, the capsule has features (i), (ii), (iii) and (vii). In some embodiments, the capsule has features (i)-(ix). In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.1 ± 0.01 Benzyl alcohol 10 ± 1 Polyoxyl 35 castor oil 45 ± 4.5 Glyceryl monolinoleate 44.3 ± 4.43 Butylated hydroxyanisole 0.05 ± 0.005 Butylated hydroxytoluene 0.05 ± 0.005 PAT059980-WO-PCT Ascorbyl palmitate 0.5 ± 0.05 In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.1 Benzyl alcohol 10 Polyoxyl 35 castor oil 45 Glyceryl monolinoleate 44.3 Butylated hydroxyanisole 0.05 Butylated hydroxytoluene 0.05 Ascorbyl palmitate 0.5 In some embodiments, the softgel fills in the two preceding paragraphs comprise 0.1mg Compound A. In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.01 ± 0.001 Glyceryl monolinoleate 40 ± 4 Polyoxyl 35 castor oil 45.19 ± 4.519 Benzyl alcohol 10 ± 1 Butylated hydroxytoluene 0.05 ± 0.005 Butylated hydroxyanisole 0.05 ± 0.005 Lecithin 4.69 ± 0.469 Simethicone 0.01 ± 0.001 In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.01 Glyceryl monolinoleate 40 Polyoxyl 35 castor oil 45.19 Benzyl alcohol 10 Butylated hydroxytoluene 0.05 Butylated hydroxyanisole 0.05 Lecithin 4.69 Simethicone 0.01 PAT059980-WO-PCT In some embodiments, the softgel fills in the two preceding paragraphs comprise 0.1mg Compound A. In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.1 ± 0.01 Glyceryl monolinoleate 43.8 ± 4.38 Polyoxyl 35 castor oil 45 ± 4.5 Benzyl alcohol 10 ± 1 Butylated hydroxytoluene 0.05 ± 0.005 Butylated hydroxyanisole 0.05 ± 0.005 Ascorbyl palmitate 1 ± 0.1 In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.1 Glyceryl monolinoleate 43.8 Polyoxyl 35 castor oil 45 Benzyl alcohol 10 Butylated hydroxytoluene 0.05 Butylated hydroxyanisole 0.05 Ascorbyl palmitate 1 In some embodiments, the softgel fills in the two preceding paragraphs comprise 0.1mg Compound A. In some embodiments, the softgel fills in the two preceding paragraphs comprise 0.5mg Compound A. In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.1 ± 0.01 Glyceryl monolinoleate 40 ± 4 Polyoxyl 35 castor oil 45 ± 4.5 Benzyl alcohol 10 ± 1 Lecithin 4.9 ± 0.49 In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.1 PAT059980-WO-PCT Glyceryl monolinoleate 40 Polyoxyl 35 castor oil 45 Benzyl alcohol 10 Lecithin 4.9 In some embodiments, the softgel fills in the two preceding paragraphs comprise 1mg Compound A. In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.2 ± 0.02 Glyceryl monolinoleate 40 ± 4 Polyoxyl 35 castor oil 45 ± 4.5 Benzyl alcohol 10 ± 1 Butylated hydroxytoluene 0.05 ± 0.005 Butylated hydroxyanisole 0.05 ± 0.005 Lecithin 4.69 ± 0.469 Simethicone 0.01 ± 0.001 In some embodiments, the softgel fill has the following composition: Component w / w% Compound A 0.2 Glyceryl monolinoleate 40 Polyoxyl 35 castor oil 45 Benzyl alcohol 10 Butylated hydroxytoluene 0.05 Butylated hydroxyanisole 0.05 Lecithin 4.69 Simethicone 0.01 In some embodiments, the softgel fills in the two preceding paragraphs comprise 2mg Compound A. Liquid Formulations In some embodiments, the dosage form is a liquid dosage form. The liquid dosage form may be a solution, suspension, emulsion, elixir, syrup, spirit, tincture, liniment, spray, aromatic water, or aerosol. Liquid dosage forms comprise a vehicle and the active ingredient, and may also PAT059980-WO-PCT include excipients such as co-solvents, preservatives, sweeteners, and flavours. The skilled practitioner will be able to prepare a variety of liquid dosage forms on the basis of methods of manufacture that are commonly known in the art. Advantages of liquid dosage forms include flexibility of dosing and ease of swallowing. In some embodiments, the vehicle is water. In some embodiments, the liquid dosage form comprises a polymer. In some embodiments, the polymer is selected from the group consisting of: a β-cyclodextrin, carboxymethyl cellulose, polyethylene glycol, and combinations thereof. In some embodiments, the β-cyclodextrin is a hydroxy propyl modified β-cyclodextrin. Inclusion of a polymer can help to solubilize Compound A. Techniques to improve solubility include complexation, use of co-solvents, chemical modifications, particle size reduction, and pH control. Methods of Use The dosage forms provided herein may be administered by a variety of routes including, but not limited to, oral (enteral) administration, parenteral (by injection) administration, rectal administration, transdermal administration, intradermal administration, intrathecal administration, subcutaneous (SC) administration, intravenous (IV) administration, intramuscular (IM) administration, and intranasal administration. Oral administration is the preferred method of administration. Thus, in preferred embodiments, the dosage form is for oral administration. In one aspect, this disclosure features methods of degrading VAV1 in a subject, which include administering to the subject an effective amount of Compound A, or a pharmaceutically acceptable salt thereof. Compound A causes degradation of VAV1 by binding to a specific amino acid sequence of a VAV1 protein as well as an E3 ligase, thereby mediating the interaction of the VAV1 protein with the E3 ligase. In some embodiments, VAV1 is a regulator of a lymphocyte. In some embodiments, the compound interacts with the E3 ligase prior to the interaction of VAV1 with the E3 ligase. In some embodiments, the E3 ligase comprises cereblon. Thus, in another aspect, this disclosure features methods of degrading VAV1, which include: (i) contacting Compound A or a pharmaceutically acceptable salt thereof with an E3 ligase; and (ii) interacting the contacted E3 ligase with VAV1, thereby degrading VAV1. In some embodiments, the E3 ligase comprises cereblon. In a further aspect, this disclosure features methods of treating a variety of disorders which include administering Compound A. Such disorders include, without limitation, autoimmune diseases (e.g., multiple sclerosis, rheumatoid arthritis, psoriatic arthritis, myasthenia gravis), PAT059980-WO-PCT transplantation setting disease (e.g., graft-versus-host disease), and cancers, tumours or other malignancies (e.g. a T cell or B cell malignancy). In an aspect, this disclosure features methods of treating a disorder caused by or associated with disregulation of lymphocyte development or activation in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the disorder is autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, psoriatic arthritis, myasthenia gravis). In some embodiments, the disorder is transplantation setting disease (e.g., graft-versus-host disease). In some embodiments, the disorder is a cancer or tumor. In some embodiments, the disorder is a malignancy (e.g., T cell or B cell malignancy). In some embodiment, the lymphocyte is T-cell. In some embodiments, the lymphocyte is B-cell. In an aspect, this disclosure features methods of treating a disorder caused by or associated with dysregulation of T-cell receptor signaling in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the T-cell receptor signaling are enhanced CD69 surface expression, IFNɣ or IL-2. In an aspect, this disclosure features methods of treating a disorder caused by or associated with VAV1 polymorphisms in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of Compound A or a pharmaceutically acceptable salt thereof. In an aspect, this disclosure features methods of treating a disorder caused by or associated with immunopathologies in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of Compound A or a pharmaceutically acceptable salt thereof. In some embodiments, the disorder is autoimmune disorder. In some embodiments, the autoimmune disorder is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, psoriatic arthritis, systemic lupus, erythematosus, Hashimoto’s thyroiditis, myasthenia gravis, diabetes type I or II, and the disorders associated therewith, vasculitis, pernicious anemia, Sjoegren syndrome, uveitis, psoriasis, Graves ophthalmopathy, alopecia areata and others, allergic diseases (e.g., allergic asthma, atopic dermatitis, allergic rhinitis / conjunctivitis, allergic contact dermatitis), inflammatory diseases optionally with underlying aberrant reactions (e.g., inflammatory bowel disease, Crohn’s disease or ulcerative colitis, intrinsic asthma, inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury), atherosclerosis, osteoarthritis, irritant contact dermatitis and further eczematous dermatitis, seborrheic dermatitis, cutaneous manifestations of immunologically-mediated disorders, inflammatory eye disease, keratoconjunctivitis, myocarditis or hepatitis. PAT059980-WO-PCT In some embodiments, the disorder is a cancer, tumour or other malignancy, optionally wherein the disorder is a T cell or B cell malignancy. In some embodiments, the disorder is selected from the group consisting of: leukemia, lymphoma, T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK cell leukemia, hairy-cell leukemia, nasal and nasal- type NK / T cell lymphoma, mycosis fungoides and Sezary syndrome, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma unspecified, adult T-cell leukemia / lymphoma (HTLV1+), anaplastic large cell lymphoma, primary cutaneous CD-30 positive T-cell lymphoproliferative disorders, cutaneous T-cell lymphoma, subcutaneous panniculitis like T-cell lymphoma, intestinal T-cell lymphoma (+enteropathy), hepatosplenic gamma / delta T-cell lymphoma, and non-Hodgkin lymphomas (e.g., B-cell non-Hodgkin lymphomas; e.g., Burkitt lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma). In some embodiments, the disorder is a transplantation setting disease. In some embodiments, the disorder is selected from graft-versus-host disease, chronic graft rejection, acute graft rejection, transplant vasculopathy, graft vessel disease, graft atherosclerosis, and transplant coronary disease. In some embodiments, the disorder is T-cell mediated. In some embodiments, the disorder is selected from the group consisting of Diabetes Type I or II, pernicious anemia, uveitis, psoriasis, alopecia areata, ulcerative colitis, Crohn’s disease, atherosclerosis, myocarditis, pericarditis, pulmonary fibrosis, systemic sclerosis, morphea, Alzheimer’s disease, Acute Graft-vs. Host Disease or T-cell mediated kidney disease. In some embodiments, the disorder is T / B-cell mediated. In some embodiments, the disorder is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, psoriatic arthritis, myasthenia gravis, Sjogren’s syndrome, Grave’s disease, an allergic disorder (e.g., asthma, allergic contact dermatitis, rhinitis or contact dermatitis), an autoimmune liver disease (e.g., biliary sclerosis or sclerosing cholangitis), chronic inflammatory demyelinating polyradiculoneuropathy, macular degeneration, systemic lupus erythematosus, Hashimoto’s thyroiditis, amyloidosis, inflammatory eye diseases, pemphigus, systemic lupus erythematosus, Chronic Graft vs. Host Disease, lupus nephritis, pulmonary arterial hypertension or vasculitis. In some embodiments, the disorder is selected from the group consisting of ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, psoriasis, multiple sclerosis, myasthenia gravis, cutaneous lupus or axial spondylarthritis. In some embodiments, the disorder is selected from the group consisting of B-cell lymphoma, B-cell leukemia, T-cell lymphoma, T-cell leukemia or acute myeloid leukemia. PAT059980-WO-PCT In some embodiments, the disclosure relates to a method of treating patients exhibiting CD226 overexpression. In some embodiments, the disclosure relates to a method of treating patients having a CD226 risk variant. In some embodiments, the disclosure relates to a method of treating patients having a CD226 polymorphism. In some embodiments, the disclosure relates to a method of treating patients having a Gly307Ser (G307S) amino acid substitution in CD226 (rs763361T allele). In an aspect, the disclosure provides a dosage form for use in any of the above-recited methods of treatment. In some embodiments, the dosage form is a dosage form as described herein. In a further aspect, the disclosure provides the use of a dosage form for the manufacture of a medicament for any of the above-recited methods of treatment. In some embodiments, the dosage form is a dosage form as described herein. EXAMPLES EXAMPLE 1: API SYNTHESIS Abbreviations: BPO: benzyl peroxide; DCE: dichloroethane; DMSO: dimethyl sulfoxide; ESI: electrospray ionization; h / hr: hours; HPLC: high-performance liquid chromatography; MS: mass spectrometry; NBS: N-bromosuccinimide; NMR: nuclear magnetic resonance; TBAF: tetrabutylammonium fluoride; TEA: triethylamine; THF: tetrahydrofuran; TMSCN: trimethylsilcyane Example 1.1: Synthesis of Compound A Synthesis of Intermediate A To a solution of 1-bromo-2-chloro-3-methylbenzene (30.0 g, 146 mmol, 1.00 eq) in tetrachloromethane (240 mL) was added N-bromosuccinimide (28.7 g, 161 mmol, 1.11 eq) and benzoyl peroxide (1.77 g, 7.30 mmol, 0.05 eq). The mixture was stirred at 90 °C for 16 hr. The reaction mixture was filtered and the filtered cake was washed with ethyl acetate (2 × 75 mL). PAT059980-WO-PCT The filtration was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; 200 g SepaFlash® Silica Flash Column, Eluent of 0~3% Ethyl acetate / Petroleum ether gradient @ 150 mL / min) to give 1-bromo-3-(bromomethyl)-2- chlorobenzene (20.8 g, 73.1 mmol, 50% yield) was obtained as colorless liquid.1H NMR (400 MHz, CDCl3) δ = 7.61 (dd, J = 8.0, 1.6 Hz, 1H), 7.41 (dd, J = 8.0, 1.6 Hz, 1H), 7.15 - 7.11 (m, 1H), 4.62 (s, 2H) To a solution of 1-bromo-3-(bromomethyl)-2-chlorobenzene (20.0 g, 70.3 mmol, 1.00 eq) and trimethylsilcyane (10.5 g, 105 mmol, 1.76 mL, 1.50 eq) in dichloromethane (200 mL) was added tetrabutylammonium fluoride (1.0 M in THF, 105 mL, 1.50 eq) dropwise at 0 °C. The mixture was stirred at 20 °C for 1.5 h. The reaction mixture was washed with water (3 × 150 mL), the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0~60% Ethyl acetate / Petroleum ether gradient @ 60mL / min) to give 2-(3-bromo-2-chlorophenyl)acetonitrile (13.2 g, 57.3 mmol, 81% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ = 7.65 (d, J = 8.0 Hz, 1H), 7.50 (dd, J = 8.0, 0.8 Hz, 1H), 7.20 (t, J = 8.0 Hz, 1H), 3.89 (s, 2H) To a solution of 2-(3-bromo-2-chlorophenyl)acetonitrile (13.2 g, 57.3 mmol, 1.00 eq) in tetrahydrofuran (130 mL) was added sodium methylate (620 mg, 11.5 mmol, 0.200 eq) and tert- butyl acrylate (7.34 g, 57.3 mmol, 8.31 mL, 1.00 eq) dropwise at 0 °C. Then, the mixture was stirred at 20 °C for 2 hr.. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 × 50 mL). The combined organic layers were washed with brine (3 × 80 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by reversed phase column (C18, 330 g, flow: 100 mL / min; gradient: from PAT059980-WO-PCT 10-65% water (0.1% formic acid ) in acetonitrile over 40min) to give tert-butyl 4-(3-bromo-2- chlorophenyl)-4-cyanobutanoate (7.50 g, 19.0 mmol, 33% yield) was obtained as colorless liquid.1H NMR (400 MHz, CDCl3) δ = 7.65 (dd, J = 8.0, 1.6 Hz, 1H), 7.53 (dd, J = 8.0, 1.6 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 4.49 (dd, J = 8.8, 5.6 Hz, 1H), 2.54 - 2.38 (m, 2H), 2.29 - 2.09 (m, 2H), 1.46 (s, 9H) To a solution of tert-butyl 4-(3-bromo-2-chlorophenyl)-4-cyanobutanoate (4.70 g, 11.9 mmol, 1.00 eq) in acetic acid (30 mL) was added sulfuric acid (5.52 g, 56.3mmol, 3.00 ml, 4.72 eq). The mixture was stirred at 90 °C for 3 hr. Cooled to room temperature, the reaction mixture was poured into ice water (120 mL) and filtered cake was washed with water (2 × 50 mL). The filter cake was dried under reduced pressure to afford 3-(3-bromo-2-chlorophenyl)piperidine- 2,6-dione (2.89 g, 9.46 mmol, 79% yield, 99% purity) as a white solid.1H NMR (400 MHz, DMSO-d6) δ = 10.93 (s, 1H), 7.72 (dd, J = 8.0, 0.8 Hz, 1H), 7.38 (dd, J = 8.0, 1.2 Hz, 1H), 7.30 - 7.26 (m, 1H), 4.32 (dd, J = 12.0, 4.8 Hz, 1H), 2.83 - 2.73 (m, 1H), 2.53 - 2.53 (m, 1H), 2.30 - 2.34 (m, 1H), 2.03-1.97 (m, 1H) MS (ESI) m / z 303.9[M+H]+ To a solution of 3-(3-bromo-2-chloro-phenyl)piperidine-2,6-dione (5.00 g, 16.5 mmol, 1.00 eq) in dioxane (80 mL) was added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3,2-dioxaborolane (5.04 g, 19.8 mmol, 1.20 eq), [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.21 g, 1.65 mmol, 0.10 eq) and potassium acetate (4.87 g, 49.6 mmol, 3.00 eq) in one portion at 20 °C under nitrogen PAT059980-WO-PCT atmosphere. The mixture was stirred at 85 °C for 3 h. The mixture was filtered and the filter cake was washed with ethyl acetate (2 × 30 mL). The combined filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, eluent of 0~50% ethyl acetate / petroleum ether gradient @ 60 mL / min) to give 3-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-piperidine- 2,6-dione (3.80 g, 8.70 mmol, 52% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ = 10.90 (s, 1H), 7.52 (dd, J = 2.0, 7.2 Hz, 1H), 7.41 (dd, J = 2.0, 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 4.26 (dd, J = 5.2, 12.4 Hz, 1H), 2.81 - 2.70 (m, 1H), 2.59 - 2.53 (m, 1H), 2.33 - 2.23 (m, 1H), 1.99 - 1.93 (m, 1H), 1.31 (s, 12H). MS (ESI) m / z 350.2 / 352.2 [M+H]+Synthesis of Compound A To a solution of 1,4-diiodobenzene (1.00 g, 3.03 mmol, 1.00 eq) and pyridin-2(1H)-one (28.26 mg, 3.03 mmol, 1.00 eq) in dimethyl sulfoxide (20 mL) was added copper(I) iodide (578 mg, 3.03 mmol, 1.00 eq) and potassium carbonate (2.01 g, 14.6 mmol, 4.80 eq) under nitrogen. The mixture was stirred at 120 °C for 3 h under nitrogen. The reaction mixture was partitioned between ethyl acetate (30 mL) and water (30 mL). The organic phase was separated, washed with water 60 mL (2 × 30 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 4 g SepaFlash® Silica Flash Column, Eluent of 0~10% Ethyl acetate / Petroleum ether gradient @ 20 mL / min) to give 1-(4-iodophenyl)pyridin-2(1H)-one (800 mg, 2.42 mmol, 79.9% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ = 7.91 - 7.80 (m, 2H), 7.69 - 7.60 (m, 1H), 7.51 (ddd, J = 2.0, 6.8, 9.2 Hz, 1H), 7.27 - 7.17 (m, 2H), 6.48 (d, J = 9.2 Hz, 1H), 6.32 (dt, J = 1.2, 6.8 Hz, 1H) MS (ESI) m / z 298.0 [M+H]+ PAT059980-WO-PCT To a solution of 3-(2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl)piperidine-2,6-dione (142 mg, 404 µmol, 1.20 eq) and 1-(4-iodophenyl)pyridin-2(1H)- one (100 mg, 337 µmol, 1.00 eq) in dioxane (5 mL) was added potassium phosphate (215 mg, 1.01 mmol, 3.00 eq) and [1,1-Bis (diphenylphosphino) ferrocene]dichloropalladium(II) (25.0 mg, 34.0 µmol, 0.100 eq). The mixture was stirred at 80 °C for 12 h. The reaction mixture was filtered through a pad of Celite and washed with ethyl acetate (30 mL). The filtrate was concentrated in vacuo. The residue was purified by Prep-HPLC (column: Phenomenex luna C18150 * 25mm * 10 µm; mobile phase: [water (formic acid)-acetonitrile]; B%: 36%-56%, 2min). And then the residue was purified by Prep-HPLC (column: YMC Triart C18150 * 25mm * 5µm; mobile phase: [water (hydrochloric acid) - acetonitrile] ; B%: 30%-60%,10min) to give 3-(2-chloro-4'-(2- oxopyridin-1(2H)-yl)-[1,1'-biphenyl]-3-yl)piperidine-2,6-dione (18.6 mg, 46.40 µmol, 13.79% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ = 10.94 (s, 1H), 7.76 - 7.71 (m, 1H), 7.58 - 7.49 (m, 5H), 7.46 - 7.35 (m, 3H), 6.51 (d, J = 9.2 Hz, 1H), 6.34 (t, J = 6.8 Hz, 1H), 4.37 (dd, J = 4.8, 12.0 Hz, 1H), 2.88 - 2.72 (m, 2H), 2.35 (dd, J = 4.0, 12.8 Hz, 1H), 2.12 - 2.01 (m, 1H) MS (ESI) m / z 393.0 [M+H]+. Example 1.2: Alternative synthesis of Compound A PAT059980-WO-PCT A mixture of (4-bromophenyl)boronic acid (3.00 g, 14.9 mmol, 1.00 eq), pyridin-2(1H)- one (1.70 g, 17.9 mmol, 1.20 eq), copper acetate (2.71 g, 14.9 mmol, 1.00 eq) and triethylamine (4.53 g, 44.8 mmol, 6.24 mL, 3.00 eq) in dichloroethane (5 mL) was degassed and purged with oxygen for 3 times, and then stirred at 25 °C for 3 hr. The reaction mixture was concentrated under reduced pressure to give a residue that was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0~80% Ethyl acetate / Petroleum ether gradient @ 40 mL / min) to afford 1-(4-bromophenyl)pyridin-2(1H)-one (1.6 g, 6.33 mmol, 42% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ = 7.75 - 7.67 (m, 2H), 7.67 - 7.60 (m, 1H) 7.51 (ddd, J = 9.2, 6.8, 2.0 Hz, 1H), 7.44 - 7.34 (m, 2H), 6.48 (d, J = 9.2 Hz, 1H), 6.32 (dt, J = 6.8, 1.2 Hz, 1H). MS (ESI) m / z 251.6 [M+H]+A mixture of 1-(4-bromophenyl)pyridin-2(1H)-one (500 mg, 2.00 mmol, 1.00 eq), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (558 mg, 2.20 mmol, 1.10 eq), [1,1-Bis(diphenylphosphino) ferrocene]dichloro-palladium(II) (146 mg, 199 umol, 0.100 eq) and potassium acetate (588 mg, 6.00 mmol, 3.00 eq) in dioxane (5 mL) was degassed and purged with nitrogen for 3 times, and then the mixture was stirred at 80 °C for 3 hr under nitrogen atmosphere. The reaction mixture was cooled to 25 °C and concentrated under reduced pressure to give a residue that was purified by flash silica gel chromatography (ISCO®; 25 g SepaFlash® Silica Flash Column, Eluent of 0~100% Ethyl acetate / Petroleum ether gradient @ 60 mL / min) to afford 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl)pyridin-2(1H)-one (500 mg, 1.53 mmol, 76% yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ = 7.79 (d, J = 7.6 Hz, 2H), 7.64 - 7.60 (m, 1H), 7.54 - 7.47 (m, 1H), 7.42 (d, J = 7.6 Hz, 2H), 6.48 (d, J = 9.2 Hz, 1H), 6.32 (t, J = 6.8 Hz, 1H), 1.31 (s, 12H). MS (ESI) m / z 298.0 [M+H]+ A mixture of 3-(3-bromo-2-chlorophenyl)piperidine-2,6-dione (2.78 g, 9.20 mmol, 1.00 eq), 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridin-2(1H)-one (3.00 g, 10.1 PAT059980-WO-PCT mmol, 1.10 eq) and [1,1-bis(diphen-ylphosphino)ferrocene]dichloropalladium(II) (672 mg, 918 μmol, 0.10 eq) and potassium phosphate (5.84 g, 27.5 mmol, 3.00 eq) in dimethylformamide (60 mL) was degassed and purged with nitrogen 3 times, then the mixture was stirred at 100 °C for 16 h under nitrogen atmosphere. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; 330 g SepaFlash® Silica Flash Column, Eluent of 100~100% Ethyl acetate and dichloromethane / Petroleum ether gradient @ 80 mL / min) followed by Prep-HPLC (column: Phenomenex luna C18 (250 × 70 mm, 10 μm); mobile phase: [water (formic acid) - acetonitrile]; B%: 20% - 50%, 20 min) and lyophilized to afford 3-(2-chloro-4'-(2-oxopyridin-1(2H)-yl)-[1,1'- biphenyl]-3-yl)piperidine-2,6-dione (926 mg, 2.33 mmol, 25% yield) as white solid.1H NMR (400 MHz, DMSO-d6) δ = 10.94 (s, 1H), 7.73 (dd, J = 1.6, 6.8 Hz, 1H), 7.58 - 7.49 (m, 5H), 7.47 - 7.35 (m, 3H), 6.51 (d, J = 8.8 Hz, 1H), 6.34 (dt, J = 1.6, 6.8 Hz, 1H), 4.43 - 4.33 (m , 1H), 2.87 - 2.74 (m, 1H), 2.60 - 2.54 (m, 1H), 2.42 - 2.29 (m, 1H), 2.12 - 2.02 (m, 1H); MS (ESI) m / z 392.9 [M+H]+Example 1.3: Further alternative synthesis of Compound A A mixture of 3-(3-bromo-2-chlorophenyl)piperidine-2,6-dione (26.5 g, 88.2 mmol, 1.0 eq.), 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridin-2(1H)-one (75% wt / wt, 35 g, 88.2 mmol, 1.0 eq.) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.39 g, 0.5 mmol, 0.006 eq.) was dissolved in THF (10 vol.). Aqueous Na2CO3 (5.5 vol., 290.7 mmol, 2.5 eq.) was added, and the reaction was stirred for 17 hours at an internal temperature of 30°C. The reaction was quenched with aq. sat. NH4Cl (13 vol.) until pH 7-8. The resulting suspension was filtered and washed with THF:H2O 8:2, EtOH, then heptane, to afford 3-(2-chloro-4'-(2- oxopyridin-1(2H)-yl)-[1,1'-biphenyl]-3-yl)piperidine-2,6-dione (30.1 g, 76.8 mmol, 86% yield, >99% purity) as a white solid. EXAMPLE 2: BIOLOGICAL ACTIVITY DATA FOR COMPOUND A PAT059980-WO-PCT Example 2.1: VAV1 Degradation Assay A heterozygous VAV1 C-terminal HiBiT knock-in pool was generated at Monte Rosa Therapeutics from a clonal Jurkat cell stably expressing LgBiT and possessing a homozygous GSPT1-G575N mutation. Cells were plated at 10,000 cells per well using Multiflo (BioTek) or Multi Drop Combi (Thermo Fisher) in 384-well white solid bottom plates (Corning, 3570BC) in 25 ul volume in RPMI 1640 media (Thermo Fischer, 22400105) containing 10% FBS (Corning, 35-075-CV), 1% Peniciliin / Streptomycin (ThermoFisher Scientific, 15140-122), and 1% Endurazine (Nano-Glo Endurazine Live Cell Substrate (Promega, N2571)). Cells were incubated for ~16 hours at 37°C, 5% CO2.25nL of test compounds at 10 µM were dosed into the plate using an Echo® 650 liquid handler (Labcyte). Cells were incubated at 37 °C, 5% CO2 and signal was read at 6 and 24 hours after Compound Addition on a Pherastar FSX using “LUM plus” optic module. Analysis was performed in Scinamic (Scinamic, Cambridge, MA). Luminescence response (R) was calculated by the formula: response = 100 * (S - N) / (P-N) where S is the signal of the well, N and P the mean negative and positive control values respectively of the same plate. The luminescence response was then fitted in Scinamic using a 3-parameter agonist logistic fit (hillslope = 1, EC50 > 0, top / bottom unconstrained). Compound A was found to have a DC50 value of 7 nM, and a Dmax of 97%. Example 2.2: VAV1 Degradation in T cells Frozen human Pan T cells purchased from STEMCELL technologies were thawed, washed with 1X PBS & resuspended in complete cell culture medium (RPMI + 10% FBS). Cells were plated at optimized cell density in U-bottom 96 well plate (Costar , catalog number Z707899) and treated with Compound A using a serial dilution ranging from 0.1 nM to 1000 nM and including a DMSO control. Plates were incubated for 24 hrs at 5% CO2, 37°C. Cells were fixed and permeabilized and then washed 2x with BD stain buffer and stained with anti-VAV1 antibody (CST #2502) for 30 minutes at 4 C. Following staining with VAV1 antibody cells were washed with PBS and incubated with PE conjugated Anti-rabbit IgG (H+L), F(ab')2 Fragment (CST # 79408) secondary antibody for 20 minutes at 4°C. Following 2x PBS washes, the PE fluorophore signal intensity (VAV1) was evaluated by flow cytometry and data reported as Geometric Mean and normalized to DMSO control levels. The result of this study are shown in FIG.2A. Example 2.3: Selectivity of VAV1 Degradation in a Human T-lymphocyte Cell Line PAT059980-WO-PCT Jurkat cells (ATCC # TIB-152) were treated with either DMSO or Compound A at 10 µM for 24hr (2 replicates per condition). Proteins were extracted with the PreOmics iST-NHS lysis buffer (PreOmics #P.O.00030). The samples were then processed using the PreOmics kit following their recommended protocol with minor modifications. In brief, the proteins were reduced, alkylated and digested for 2h at 37°C. The peptides were then labelled with TMT reagent (1:4; peptide:TMT label) (Thermo Fisher Scientific). After quenching, the peptides were purified, and the 16 samples were combined to a 1:1 ratio. Mixed and labeled peptides were subjected to high-pH reversed-phase HPLC fractionation on an Agilent X-bridge C18 column (2.1 mm ID, 3.5 µm particles and 15 cm in length). Using an Agilent 1260 Infinity II LC system, a 60 min linear gradient from 0 % to 45 % 10 mM ammonium formate in 90% acetonitrile separated the peptide mixture into a total of 60 fractions, which were then consolidated into 24 fractions. The dried 24 fractions were reconstituted in 0.1 % formic acid for LC-MS3 analysis. Labelled peptides were loaded onto an Aurora column from Ionopticks (75 µm ID, 1.6 µm particles, 25 cm in length) in an EASY-nLC 1200 system. The peptides were separated using a 168 min gradient from 4 % to 30 % buffer B (80 % acetonitrile in 0.1% formic acid) equilibrated with buffer A (0.1 % formic acid) at a flow rate of 400 nl / min. Eluted TMT peptides were analyzed on an Orbitrap Eclipse mass spectrometer (Thermo Fisher Scientific). MS1 scans were acquired at resolution 120,000 with 400-1400 m / z scan range, AGC target 4x105, maximum injection time 50 ms. Then, MS2 precursors were isolated using the quadrupole (0.7 m / z window) with AGC 1x104 and maximum injection time 50 ms. Precursors were fragmented by CID at a normalized collision energy (NCE) of 35 % and analyzed in the ion trap. Following MS2, synchronous precursor selection (SPS) MS3 scans were collected by using high energy collision-induced dissociation (HCD) and fragments were analyzed using the Orbitrap (NCE 55 %, AGC target 1x105, maximum injection time 120 ms, resolution 60,000). The real- time search algorithm was used to trigger MS3 quantification scans. Protein identification and quantification were performed using Proteome Discoverer 2.4.0.305 with the SEQUEST algorithm and Uniprot human database (2021-01-29, 20614 protein sequences). Mass tolerance was set at 10 ppm for precursors and at 0.6 Da for fragment. Maximum of 3 missed cleavages were allowed. Methionine oxidation was set as dynamic modification, while TMT tags on peptide N termini / lysine residues and cysteine alkylation (+113.084) were set as static modifications. The list of identified peptide spectrum matches (PSMs) was filtered to respect a 1% False Discovery Rate (FDR) after excluding PSMs with TMT reporter ion signal-to-noise value lower than 5 and a precursor interference level value higher than 100%. Subsequently, protein identifications were inferred from protein specific peptides, i.e. peptides matching multiple protein entries were excluded. Protein relative quantification was PAT059980-WO-PCT performed using an in-house developed java script. This analysis included multiple steps; adjustment of reporter ion intensities for isotopic impurities according to the manufacturer’s instructions, global data normalization by equalizing the total reporter ion intensity across all channels, summation of reporter ion intensities per protein and channel, calculation of protein abundance log2 fold changes (L2FC) and testing for differential abundance using moderated t- statistics where the resulting p-values reflect the probability of detecting a given L2FC across sample conditions by chance alone. The results of this study are shown in FIG.2B. Example 2.4: Degradation of VAV1 results in inhibition of TCR-mediated CD69 activation, IL-2 secretion, and proliferation of Primary T-cells Frozen human Pan T cells purchased from STEMCELL technologies were thawed, washed with 1X PBS & resuspended in complete cell culture medium (RPMI+10% FBS). Cells were plated at optimized cell density in U-bottom 96 well plate (Costar, Z707899) and treated with Compound A using a serial dilution ranging from 0.1 nM to 1000 nM and including a DMSO control and incubated for 24 hrs at 5% CO2, 37°C. Cells were transferred from treatment plate to anti-CD3 coated plate (5 ug / mL anti-CD3 antibody, clone OKT3) and co-stimulated with anti- CD28 (1 ug / mL, clone CD28.2). Cells were incubated at 5% CO2, 37°C and cells and / or supernatants harvested at various timepoints following anti-CD3 / anti-CD28 co-stimulation for various readouts (24h, CD69; 48h, IL-2; 96h, proliferation). For CD69 surface evaluation, cells were washed with PBS and stained for 20 minutes at 4 C with anti-CD69 allophycocyanin (APC) antibody. Cells washed with PBS and evaluated by flow cytometry. APC fluorophore signal intensity (CD69) reported as Geometric Mean. IL-2 was evaluated within cellular supernatants using an IL-2 ELISA kit (Abcam, ab270883) according to manufacturer protocol. Optical density (O.D.) values (IL-2) were obtained at 450 nM. For proliferation assays, cells were labeled with cell trace violet (final dye concentration 12.5 uM). Cells were analyzed as a percentage of cell trace violet dye dilution (relative to unstimulated cells) by flow cytometry. For all assays, data were normalized to anti-CD3 / anti-CD28 co-stimulated DMSO control levels. The results of this study are shown in FIGS.3A-3C. Example 2.5: VAV1 degradation by a MGD in PBMCs after a single oral dose in mice Mice were treated orally with a single dose of Compound A at 10 mg / kg and blood samples were collected pre-dose and at 2, 6 and 24 hours post-dose. Compound formulation was prepared fresh the day of administration in 50% PEG400+50% (20% Captisol in water) by first dissolving PAT059980-WO-PCT Compound A in PEG400 followed by vortex and sonification, then adding 50% of 20% captisol in water with vortex until a clear solution or a uniform suspension was obtained. Plasma samples collected pre and post dosed were analyzed by Mass spectrometry to evaluate the compound concentration in ng / ml and blood samples were used to assess VAV1 protein levels and b-actin as loading control by western blotting (WB). Briefly, cells were rinsed with PBS and lysed using 30 µL RIPA lysis buffer (Pierce 89901), supplemented with EDTA and PhosStop (Roche 04906845001). Samples were run on 4- 15% precast gels (Bio-Rad 161-0732) at 10-15 µg / lane and transferred to pre-activated PVDF membranes (Millipore IPVH00010). Primary antibodies (mouse VAV1, CST 2502S and b-actin, CST 3700S) was diluted in blocking buffer (dil. 1 / 1000) and incubated with the membranes overnight at 4°C. After three washes with 1x TBST (5 minutes each), secondary antibodies (anti- rabbit IgG, CST 7074, dil.1 / 1000 and IRDyeⓇ 680RD Goat anti-Mouse IgG (H+L), Licor 926- 68070, dil.1 / 5000) were diluted in blocking buffer, added to membranes and incubated for 1 hour at room temperature. Signals were detected using an WB image systems. First the VAV1 protein levels were normalized to b-actin levels within the same samples than the ratio between the normalized VAV1 protein levels and the pre-dose levels were calculated and used for representation. The results of this study are shown in FIG.4. Example 2.6: Inhibition of disease progression in a MOG35-55-induced multiple sclerosis experimental autoimmune encephalomyelitis (EAE) mouse model To induce experimental autoimmune encephalomyelitis (EAE), C57BL / 6J mice were injected subcutaneously with an emulsified mixture consisting of 100 μg of the synthetic peptide derived from myelin oligodendrocyte glycoprotein (MOG35-55) and 200 µg M. tuberculosis mixed with incomplete Freund’s adjuvant. Mice were additionally injected intraperitoneally with 200 ng pertussis toxin at 0 and 48 hours post immunization. This immunization induces the activation and expansion of peripheral myelin-specific encephalitogenic T cells and their migration into the CNS. Once in the CNS, the activated T-cells initiate an inflammatory cascade, which ultimately leads to myelin destruction and symptoms of paralysis. From the day before disease induction (day -1), the mice were monitored daily and scored for clinical signs of EAE disease as follows: 0=no signs of disease; 1=limp tail or hind limb weakness; 2=limp tail and hind limb weakness; 3=partial hind limb paralysis; 4=complete hind limb paralysis; 5=moribund. Mice were then treated with vehicle (50 / 50 (v / v) PEG400 and 20% captisol in water) or once daily (QD) orally (PO) at 10 mg / kg with Compound A (resuspended in 50 / 50 (v / v) PEG400 and 20% captisol in water) or QD PO at 1 mg / kg with Dexamethasone from day 12 to day 18. A Compound A formulation was prepared PAT059980-WO-PCT fresh the day of administration by first dissolving Compound A in PEG400 followed by vortex and sonification, then adding 50% of 20% captisol in water with vortex until a clear solution or a uniform suspension was obtained. The results of this study are shown in FIG.5. Example 2.7: Oral dosing of Compound A inhibits EAE disease progression in a dose- dependent manner To induce experimental autoimmune encephalomyelitis (EAE), twelve C57BL / 6 (Beijing Vital River Laboratoriy Animal Co; #213) mice were injected subcutaneously with an emulsified mixture consisting of 100 μg of the synthetic peptide derived from myelin oligodendrocyte glycoprotein (MOG35-55; GL Biochem Ltd; #51716)) and 200 µg M. tuberculosis (Fifco; #231141)mixed with incomplete Freund’s adjuvant (Sigma-Alrich; #F5506). Mice were additionally injected intraperitoneally with 200 ng pertussis toxin (List Biological Laboratories; #180235AIA) at 0 and 48 hours post immunization. This immunization induces the activation and expansion of peripheral myelin-specific encephalitogenic T cells and their migration into the CNS. Once in the CNS, the activated T-cells initiate an inflammatory cascade, which ultimately leads to myelin destruction and symptoms of paralysis. From the day of disease induction (day -12), the mice were monitored every 3 days for clinical signs of EAE disease as follows: 0=no signs of disease; 1=limp tail or hind limb weakness; 2=limp tail and hind limb weakness; 3=partial hind limb paralysis; 4=complete hind limb paralysis; 5=moribund. On day 0, at disease onset, mice were treated with vehicle (10% captisol in water) Compound A at 1, 0.1, or 0.01 mg / kg with Compound A (resuspended in 10% captisol in water), or QD PO at 1 mg / kg with Dexamethasone (dissolved in saline; Shanghai SPH Sine Pharmaceutical Co; #H31020793) from day 12 to day 24 and monitored every 3 days for clinical signs of EAE disease as described above. A Compound A formulation was prepared fresh the day of administration by dissolving the Compound A in 10% captisol in water then vortexed until a clear solution or a uniform suspension was obtained. At peak of disease (day 6 post-treatment start), spinal cords of four mice per group were excised and VAV1 levels (normalized to β-actin and relative to vehicle-treated mice) were measured by western blot. To determine the levels of Vav1 in the spinal cord, tissues were excised after euthanasia and snap frozen. For sample preparation, frozen samples were defrosted, 30-100 mg of tissue was placed in a 2 mL microcentrifuge tube, and 400 μL RIPA buffer (Sigma; #R0278) containing 1% protease inhibitor cocktail (Roche; #04693124001) and 1% phosphatase inhibitor cocktail 2 (Sigma; #P5726) was added to each tube. Tissues were ground using a Tissuelyser (Shanghai Jingzin; #JXSTPRP-CL) at 50 hZ for 5 mins. Samples were then incubated on ice for 30 mins. PAT059980-WO-PCT After incubation, samples were centrifuged at 13, 523 x g for 10 mins at 4ºC, then transferred into new, pre-chilled microcentrifuge tubes. Protein concentrations was determined using a BCA assay kit (Thermo Fisher; #23225)) and samples were diluted to a final concentration of 2 μg / μL in RIPA buffer containing 4X LDS sample buffer (Invitrogen; #NP0007) and 10X sample reducing agent (Invitrogen; #NP0009). Once diluted, samples were boiled at 100ºC for 10 mins. Denatured samples were then stored at -80ºC. For western blotting, protein samples were defrosted and 15 μL of each sample was loaded in 4-12% Bis-Tris gels (Invitrogen; #WG1402BOX). Electrophoresis was then run in MES running buffer (Invitrogen; #NP0002) at 80 V for 30 mins then 120 V for 90 mins. Proteins were transferred to a nitrocellulose membrane with an iBlot 2 Gel Transfer Device (Invitrogen) using P3 for 7 mins. After transfer, membranes were washed (10 mL 1X TBST, 5 mins, 3 times), blocked (TBS Blocking Buffer (LI-COR;#927-60001), 1 h with agitation, room temperature), and washed again (1X TBST (Bio-Serve; #BS-P-15), 10 mins, 3 times). Vav1 and β-actin were detected by incubation with anti-Vav1 (CST; 2502) and β-actin (CST; #4967) antibodies (1:1000 or 1:2000 respectively in TBS Blocking Buffer containing 0.1% Tween-20 (Sigma; #P2287) at 4ºC overnight with gentle agitation). Membranes were then washed (10 mL 1X TBST, 10 mins, 3 times) and then incubated with secondary detection goat anti-mouse IgG-IRDye 860RD (LI-COR; #926-68070) and goat anti-rabbit IgG-IRDye 800CW (LI-COR; #926-32211) antibodies (both 1:10000 in TBD Blocking Buffer containing 0.1% Tween-20 for 1h at room temperature with gentle agitation, protected from light). Membranes were then washed (10 mL 1X TBST, 5 mins, 5 times) and protein levels were detected by fluorescence signal using an Odessey CLx Imaging System (LI-COR). Vav1 protein levels were quantified by fluorescence intensity relative to β-actin and normalized to the vehicle treatment group. The results of this study are shown in FIGS.6A and 6B. Example 2.8: Oral dosing of Compound A inhibits disease progression in a T cell transfer-induced model of colitis and reduces expression of calprotectin subunits (S100a8 / S100a9) within colon tissue in a T cell transfer-induced model of colitis To induce colitis, eight CD17-SCID mice were injected intraperitoneally with 0.5 x 106non-pathogenic activated CD45RBlow(no disease control group) or pathogenic naïve CD45RBhigh(treatment groups) CD4+ T cells isolated from Balb / c mice. To isolate T cells, spleens were collected, homogenized, and CD4+ T cells were enriched using negative magnetic selection (Stemcell; #19852) as per the manufacturer’s instructions. After enrichment, cells were stained with viability stain 780 (BD; #BD-565388), blocked with rat anti-CD16 / 32 (BD; #BD-553141), stained with rat anti-mouse CD4-APC (BD; #BD-553051) and rat anti-mouse CD45RB-PE (BD; PAT059980-WO-PCT #BD-553101), and then sorted based on CD45RB expression using fluorescence activated cell sorting (FACS). Transfer of naïve CD4+ T cells induced microbe peptide-specific immune responses in the colon leading to colitis-like inflammation. From the day of cell transfer (day 0), the mice were monitored daily for disease activity index (DAI) comprising weight loss and stool consistency assessment. On day 0, two hours post-cell transfer, mice were treated orally (PO) daily with vehicle (10% captisol in water) or Compound A at 10 or 1 mg / kg (resuspended in 10% captisol in water) for 42 days. A Compound A formulation was prepared fresh the day of administration by dissolving the Compound A in 10% captisol in water then vortexed until a clear solution or a uniform suspension was obtained. The results of this study are shown in FIG.7. To determine gene expression changes, at the end of the study colons from each group were excised and stored in RNAlater (Sigma; #R0901) at -80ºC. Samples were then defrosted, and RNA was extracted using an Rneasy Mini Kit (Qiagen; 74104) as per the manufacturer’s instructions. RNA samples were then assessed by NanoDrop (Thermo; #AZY1705823) and Qubit (Inviitrogen; #2322618036279). After RNA quality assessment, samples were assessed using the Nanostring Autoimmune Panel as per the manufacturer’s instruction. Breifly, ~100 ng RNA was processed in a hybridization reaction (65ºC for 20 hours) and loaded onto an nCounter Prep Station (NanoString Technologies; #1609D0496) for automated purification and RNA immobilization on an nCounter Master Kit cartridge (NanoString; #NAA-AKIT-012). Cartridges were then transferred to an nCounter Digital Analyzer (NanoString; #1804C0565) and assessed using the nCounter Mouse Autoimmune Profiling Panel (NanoString; #XT-CSO-MAIPI1-12). Quality control (QC) included image QC, binding density, positive control linearity, and positive control limit of detection. Background signal was calculated as twice the standard deviation above the mean of the negative control. The limit of detection was determined by detection of a 0.5 fM positive control probe. For normalization of gene counts, 8 of 20 standard housekeeping genes were assessed using common normalization methods including the mean, geomean, median of ratio. Counts in each sample were then normalized using these parameters. Differential expression of genes (DEG) was then determined on normalized gene counts to provide significant variance between Compound A and vehicle treated groups. The results of this study are shown in Table 2 below. Table 2: Differential gene expression after oral dosing of Compound A Gene Log2 fold change Adjusted p value S100a9 -3.403.67x10-9 S100a8 -3.248.56x10-7 PAT059980-WO-PCT Table 2 shows that expression of the calprotectin subunit genes (S100a9 / S100a8) were significantly decreased in Compound A treated mice compared to vehicle. At the end of the study, colons were excised, homogenized, and assessed for gene expression using the Nanostring Autoimmune Panel. Gene expression was normalized to house keeping genes and differential expression of genes was compared between Compound A and vehicle treated mice (table shows log2 fold change and adjusted p value of gene expression in Compound A compared to vehicle treated mice). Example 2.9: Oral dosing of Compound A Attenuates Disease Progression in a CIA mouse model To induce collagen-induced arthritis (CIA), fifteen DBA / 1 mice (Shanghai Vital River Laboratory Animal Technology Co; #218) were injected intravenously on days 0 and 21 with a mixture consisting of 100 μg of bovine collagen II (Sichuan University) dissolved in 100 mM acetic acid (Sigma; #A8976) emulsified in complete Freund’s adjuvant (CFA; Sigma; #F5881) 2- 3 cm from the base of the tail. This immunization induces the activation and expansion of collagen specific T- and B-cells that migrate into the paw joints. Once in the paw joints, the activated T- cells induce destruction of the joint and bone tissue, leading to redness and swelling of the phalanges, and B-cells produce antibodies against collagen II. Following the second immunization, mice were monitored daily for clinical signs of disease as follows: 0=erythema and redness; 1=Erythema or mild redness near ear the tarsal, ankle, or metatarsal or one toe with erythema and redness; 2=Ankles and metatarsals are slightly erythematous and swollen with two or more toes with erythema and redness; 3=Moderate erythema and swelling of the ankle, wrists, and metatarsals; 4=Ankles, wrists, metatarsals, and toes are severely red and swollen. Upon disease onset, mice were randomly enrolled into treatment groups: vehicle (10% captisol in water; PO, QD) or Compound A (1 mg / kg, PO, QD) and treated for 21 days. Compound A formulation was prepared fresh the day of administration by dissolving the Compound A in 10% captisol in water then vortexed until a clear solution or a uniform suspension was obtained. At the end of the study, serum was collected from each mouse and assessed by ELISA for levels of anti-collagen II IgG1 antibodies. ELISA plates containing 100 μL / well of 40 μg / mL bovine collagen II in acetic acid were incubated overnight at 4ºC. The solution was then aspirated and washed 3 times with 400 μL Wash Buffer (0.001% Tween-20 in PBS) with 1 min soaking between each wash step. Wells were then blocked using 1% BSA in 1X PBS for 2 hours at room temperature. Wells were then washed as previously. A 2-fold serial dilution of IgG1 standard (starting at 2000 units / m) or prediluted serum (1:5000) were then added to individual wells and incubated for 2 hours at room temperature. PAT059980-WO-PCT Wells were then washed 4 times as described above. To detect antibody binding, 100 μL of secondary antibody (goat anti-mouse IgG1-HRP; Invitrogen; #PA1-74424) was added to wash well and incubated at room temperature for 1 hour. After incubation, 100 μL of TMB substrate (Abcam; #ab171523) was added to each well, incubated for 5-30 mins, then quenched by addition of 100 μL Stop Solution (Abcam; #ab171529). Plates were then read at 450 nm with 570 nm values substracted from those of 450 nm and analyzed. Using standards, concentrations of each group were calculated at units / mL. The results of this study are shown in FIGS.8A-8B. Example 2.10: Compound A Attenuates BCR-Mediated Activity in Primary Human B-cells Peripheral blood mononuclear cells (PBMC) were first isolated from human blood leukopaks. Each leukopak was diluted by adding 40 mL of the leukopak contents into 60mL of 1x PBS into a disposable Nalgene 150 mL bottle. The diluted blood mixture was transferred evenly among three Accupsin tubes (~30mL / tube). The mixture in Accuspin tubes was centrifuged at 720 x g for 20 minutes without brake at room temperature. Peripheral blood mononuclear cells) (PBMC) were collected from the interphase with a sterile transfer pipette and transferred into new 50 mL tubes. PBMCs were washed with 1X PBS and counted using Nexcelom cell counter. From the isolated PBMCs, B cells were isolated using EasySep B cell isolation kit (Stemcell; #17954) following the manufacturer’s manual magnetic isolation technique. Cells were treated with Compound A at the indicated final concentrations or DMSO control and incubated at 37°C in a humidified incubator with 5% CO2. After treatment, B cells were cultured in RPMI 1640 (Gibco; #22400089) supplemented with 10% fetal bovine serum (Gibco; #A31605-01; Lot#2408990P), 2mM L-glutamine (Gibco; #35050061), 100 IU / mL penicillin / streptomycin (Gibco; #15140122), 1 mM sodium pyruvate (Gibco, #11360070), 0.01 M HEPES (Gibco, #15630080), 1% non- essential amino acids (Gibco; #11140050), and 55 μM β-mercaptoethanol (Gibco; #21985023), and stimulated with assay-dependent stimuli. For CD69 expression and IL-6 secretion, B cells were stimulated with anti-IgM (1 μg / mL; Southern Biotech; #2022-14) and recombinant human IL-4 (10 ng / mL; R&D Systems; #305-IL-010) for 24 hrs. For IgG secretion, B cells were stimulated with anti-IgM (1 μg / mL), BAFF (30 ng / mL; R&D Systems; #7537-BF-025), IL-21 (100 ng / mL; PeproTech; #200-2), and soluble CD40L (50 ng / mL; R&D Systems; #6245-C) for 5 days. For CD69 expression, cells were blocked with TruStain FcX (BioLegend; #422302), stained with mouse anti-human CD19-BV421 (BD; #562440; Clone HIB19) and anti-human CD69-APC (BioLegend; 310910; Clone FN50) then, then assessed by flow cytometry. For IL-6 and IgG, supernatants were assessed by Alphalisa as per the manufacturer’s instructions. Mean fluorescence PAT059980-WO-PCT intensity (MFI) of CD69-APC was calculated on the CD19+ population using FlowJo (BD). MFI of CD69 for Compound A treated samples was normalized to DMSO stimulated and unstimulated control. Normalized data were transferred to Prism 9.3.1 (GraphPad) and fitted with a four- parameter model ([Inhibitor] vs. response -- Variable slope). The results of this study are shown in FIGS.10A-10C. EXAMPLE 3: TABLETS Example 3.1: Identification of polymers for solid dispersions of Compound A To evaluate which polymers would be most suitable for a solid dispersion of Compound A, the amorphous solubility of Compound A in different polymers in a biorelevant medium was assessed. The biorelevant medium used was Fasted State Simulated Intestinal Fluid (FaSSIF), which had a composition as shown in Table 3. If a substance is soluble in this medium, this suggests that the substance will also be soluble in the upper intestine of a subject when the subject is in the fasted state. Table 3: Composition of FaSSIF medium Component Concentration Sodium Taurocholate 3.0 mM Lecithin 0.75 mM Sodium Chloride 106 mM Monobasic Sodium Phosphate 28.4 mM Sodium Hydroxide 8.7 mM The following polymers were tested: • HPMCAS LG • HPMCAS MG • HPMCAS HG • HPMC E3 • PVPVA 64 • Eudragit L100 Amorphous solubilities (based on the onset of liquid-liquid phase separation (LLPS)) were determined at 37 °C and pH ~6.5 in FaSSIF medium with 300 µg / mL pre-dissolved polymer using the solvent-shift UV assay described in“Assessment of the Solubility of a Group of Diverse Drugs PAT059980-WO-PCT Using New Experimental and Theoretical Approaches”, Luis Almeida e Sousa, Susan M. Reutzel- Edens, Gregory A. Stephenson, and Lynne S. Taylor, Mol. Pharmaceutics. A concentrated stock solution of Compound A in DMSO was delivered into the FaSSIF medium to reach a concentration of ~120µg / mL and the solution was monitored for precipitation for five hours. Results are shown in FIG. 14. There was visual precipitation in the control and Eudragit L100 samples within 5 minutes of addition of the Compound A stock solution. There was visual precipitation in the PVPVA 64 sample within 25 minutes of addition of the Compound A stock solution. All samples except the HPMCAS HG sample had visible precipitation the following day. Based on these results, HPMCAS HG and HPMCAS MG are preferred polymers for a solid dispersion of Compound A due to their ability to sustain supersaturation of Compound A for up to 5 hours. Example 3.2: Solid dispersions comprising Compound A Four spray dried dispersions (SDDs) comprising Compound A were prepared. Their compositions are indicated in Table 4 below. Table 4: Compositions of SDDs comprising Compound A SDD Composition SDD 1 [1:3] Compound A: HPMCAS HG SDD 2 [2:3] Compound A: HPMCAS HG SDD 3 [1:3] Compound A: HPMCAS MG SDD 4 [2:3] Compound A: HPMCAS MG Preparation of spray dried dispersions 1-4 SDD spray solutions were prepared at a 5.0 wt% solids loading in 80:20 DCM:MeOH. The polymer was dissolved in the solvent system followed by addition of Compound A. The solutions were sprayed using a ProCepT 4M8-Trix pharmaceutical spray dryer with the parameters as shown in Table 5 below. The wet SDDs were oven dried in a vacuum oven at ~10 inHg and 40⁰C for ~24 hours. Table 5: Parameters used for preparation of SDDs 1-4 Parameter SDD 1 SDD 2 SDD 3 SDD 4 Nozzle type / size 2-fluid / 0.6mm Pump Speed (%) 62 Flow Rate (g / min) 10.96 11.68 11.06 11.14 PAT059980-WO-PCT Chamber Outlet Temperature (⁰C) 35.24 35.69 35.30 35.57 Pressure Drop over Cyclone (mBar) 50.11 49.50 49.81 49.03 Atom. Gas Flow (L / min) 5.90 5.59 5.68 5.78 Nozzle Pressure (Bar) 0.25 0.25 0.25 0.25 Solution Sprayed (g) 480.2 300.2 480.1 300.3 Spray time (m:s) 43:48 25:43 43:25 26:58 Dry Weight Powder (g) 19.9 12.1 20.8 12.9 Yield (%) Dried SDD 82.8 80.5 86.6 85.5 Chemical and physical characterisation The chemical and physical properties of SDDs 1-4 are summarised in Table 6 below. All SDDs had acceptable chemical and physical characteristics of an amorphous material. Table 6: Chemical and physical properties of SDDs 1-4 Test Material D m TGA Appearance PLM PXR DSC (°C) (% wt loss up to 150 °C) Compound A (standard; stored at Off-white powder Birefringent Crystalline 265.12 0.051 2-8 °C) SDD 1 Off-white Very slightly powder birefringent Amorphous 99.36 2.698 SDD 2 Off-white Slightly powder birefringent Amorphous 99.12 2.440 SDD 3 Off-white Slightly powder birefringent Amorphous 101.84 2.423 SDD 4 Off-white Slightly powder birefringent Amorphous 99.61 2.508 Test Material Karl Fischer As Main Peak Total Water say Purity Impu t (%) (% w rities Conten / w) (% area) (% area) Compound A (standard; stored at 0.0 98.6% 99.39% 0.61% 2-8 °C) SDD 1 1.6 101.3% 99.33% 0.67% SDD 2 1.4 98.0% 99.19% 0.81% SDD 3 1.7 97.9% 99.23% 0.77% SDD 4 1.9 100.1% 99.25% 0.75% PAT059980-WO-PCT Kinetic solubility testing The solubility of SDDs 1-4 when added to FaSSGF and then subsequently FaSSIF was tested using the method described in example 3.1 for the polymer identification. FaSSGF (Fasted State Simulated Gastric Fluid) is another biorelevant media. The FaSSGF media was at pH ~ 1.3 and had the composition shown in Table 7. If a substance is soluble in FaSSGF, this suggests that the substance will also be soluble in the stomach of a subject when the subject is in the fasted state. Table 7: Composition of FaSSIF medium Component Concentration Sodium Taurocholate 0.08 mM Lecithin 0.02 mM Sodium Chloride 34.2 mM Hydrochloric Acid 25.1 mM The target concentration of Compound A was ~200µg / mL for the FaSSGF medium, and ~100µg / mL for the FaSSIF medium. The results are shown in FIG.15. All SDDs sustained supersaturated concentrations over the 5.5 hour dissolution period and were ~7-9 times more soluble than crystalline Compound A. The SDDs with Compound A:polymer at a ratio of [1:3] achieved higher overall concentrations compared SDDS with Compound A:polymer at a ratio of [2:3]. SDDs with HPMCAS HG were able to sustain slightly higher concentrations compared to SDDs with HPMCAS MG. Thus, SDDs with Compound A and polymer at a ratio of [1:3], and SDDs with HPMCAS HG, are preferred. Stability testing SDDs 1-4 were stored for 2 weeks at 40°C and 75% relative humidity (RH) in a closed dish with no desiccant. SDDs 1-4 were chemically stable after this time, and the amorphous nature of the SDDs was maintained. SDDs 1, 2, and 4 were also physically stable. DSC data for SDD3 indicates that there is a secondary Tg at ~116°C, which is likely due to phase separation. This may have been caused by water uptake – Karl Fischer titration showed that SDD3 had the highest level of water content of SDDs 1-4, which is likely due to higher hygroscopicity of HPMCAS M compared to HPMCAS H. SDD3 therefore requires storage in a closed dish with a desiccant. Example 3.3: SDD1 Scale-Up Batch 1 PAT059980-WO-PCT ~500g of [1:3] Compound A:HPMCAS HG was produced on a ProCepT 4M8-Trix pharmaceutical spray dryer. Due to the large batch size, the batch was split into three sublots and produced over 3 days. The spray solution preparation and spray drying parameters matched those described above for SDD1, and are also described below. HPMCAS HG was obtained from Shin- Etsu, and dichloromethane (World / GMP grade) and methanol (World / GMP grade) was obtained from EMD Millipore. Spray solution preparation All spray solutions were prepared one day before the spray. Compound A was added to the solvent solution first and the solution was mixed for at least 1 hour. Then, the polymer was added and the solution was mixed overnight. Table 8 summarizes the spray solution composition. Table 8: Spray solution composition for scale-up batch of SDD1 Solids loading Spray Solvent AP Total amount (wt%) I amount (g) SDD (g) 7% [80:20] DCM:MeOH 142.2 568.8 Spray drying All spray solutions were sprayed using a Procept 4M8-Trix pharmaceutical spray dryer. The wet SDD for each sublot was collected into a 1L amber bottle. Table 9 summarizes the process parameters. Table 9: Spray drying parameters for scale-up batch of SDD1 Nozzle type / size 2-fluid / 0.6mm Pump speed (%) 65-70 Target 10.00 Flow Rate (g / min) Actual 10 - 11 Target - Atomization Gas Flow (L / min) Actual 6.34 Target 0.25 Nozzle Pressure (bar) Actual 0.25 Target 0.35 Drying Gas Flow (m3 / min) Actual 0.35 Target 60 Inlet Temperature (⁰C) Actual 60.36 PAT059980-WO-PCT Target 35 Outlet Temperature (⁰C) Actual 35.18 Target 35-50 Cyclone ΔP (mbar) Actual 36.86 Secondary drying Secondary drying was performed by placing uncapped bottles inside a vacuum oven with nitrogen purge. Secondary drying parameters are summarized in Table 10. Table 10: Secondary drying parameters for scale-up batch of SDD1 Parameter Value Temperature (°C) 40 Vacuum Setting (inHg) -5 N2Purge (CFH) 15 All sublots were removed from the oven after 45 hours of secondary drying. A small aliquot was collected from each bottle for PXRD analysis. Once the amorphous nature of each Sublot was confirmed, the material was combined by transferring all sublots into an LDPE bag and mixing by hand. The overall yield of the dry SDD was 74.9%. Characterization Results from physical and chemical characterization of the scale-up batch of SDD1 are summarized in Table 11. These properties were found to be acceptable. Table 11: Physical and chemical characterization results TGA Main Total Appearanc PLM PXRD mDSC (%wt loss Assay Peak Impuritie e (°C) up to 150 (% Purity w / w) (% s °C) area) (% area) Off-white Slightly powder birefringen Amorphous 100.12 1.842 24.6 99.82 0.20 t Example 3.4: SDD1 Scale-Up Batch 2 A further batch of SDD1 was prepared on a larger scale spray dryer, the Mobile Minor (MM). Due to differences in the atomization mechanism between the Procept and Mobile Minor, PAT059980-WO-PCT the materials produced generally have different particle size differences. The Procept utilizes a two fluid nozzle to atomize the spray solution whereas the Mobile Minor utilises a pressure nozzle. A two fluid nozzle generally produces finer droplets during spray drying, which results in smaller particles being produced for Procept sprays than for Mobile Minor sprays. SEM images showed that the Procept SDD had overall smaller particles compared to MM SDD, with largest particles sizes being ~60µm for the Procept material and 110µm for the MM SDD. Example 3.5: 0.5 mg tablet formulations Four tablet formulations were prepared with various fillers, including plastic fillers (ProSolv HD90 or Avicel PH 101) and a brittle filler (Pearlitol 100). The powder formulations were designed for a direct compression process, a 0.5mg dose strength, and a 100mg final tablet weight. Materials Table 12: Materials used for tablet formulations 1-5 Material Nonproprietary name Manufacturer ProSolv HD 90 Silicified microcrystalline cellulose JRS Pharma ProSolv SMCC 50 Silicified microcrystalline cellulose JRS Pharma Pearlitol 100 SD Mannitol Roquette Avicel PH 100 Microcrystalline cellulose DuPont Cabosil M-5P Fumed silica Cabot Ac-Di-Sol SD 711 Croscarmellose sodium DuPont Hyqual Magnesium stearate Avantar / Macron Tablet formulation compositions Table 13: Compositions of tablet formulations 1-4 Unit Weight, mg 100 Dose Strength, mg 0.5 Form.1 Form.2 Form.3 Form.4 % Unit Function % Formulation Composition Formulation weight, Composition mg SDD1 API 2.00% 2.00% 2.0% 2.0 SDD2 API 1.25% PAT059980-WO-PCT Prosolv HD Filler 90 (Form.1 & 2) 93.00% 93.75% Pearlitol 100 Filler SD (Form.3) 93.0% ProSolv Filler SMCC 50 (Form.4) 93.0% 93.0 Cabosil M- 5P Glidant 1.00% 1.00% 1.00% 1.00% 1.0 Ac-Di-Sol Disintegrant 3.00% 3.00% 3.00% 3.00% 3.0 Magnesium stearate Lubricant 1.00% 1.00% 1.00% 1.00% 1.0 Total 100.00% 100.00% 100.00% 100.00% 100.0 Table 14: Composition of tablet formulation 5 Unit Weight, mg 100 Dose Strength, mg 0.5 Function% Formulation Unit weight, Composition mg SDD1 API 2.00% 2.0 Avicel PH 101 Filler 93.00% 93.0 Cabosil M-5P Glidant 1.00% 1.0 Ac-Di-Sol Disintegrant 3.00% 3.0 Magnesium stearate Lubricant 1.00% 1.0 Total 100.00% 100.0 Blend procedure (direct compression process) 1. Components were weighed and SDD was pre-mixed with ~1 / 4 of filler components (pre- mix 1). 2. Glass container was pre-coated by adding 1 / 8 of filler components in an appropriately sized jar, followed by the addition of pre-mix 1, glidant, and disintegrant. The SDD weigh boat was dry washed with 1 / 8 filler components and the material was added to the jar to form pre-mix 2. 3. Pre-mix 2 was blended in a Turbula mixer at 32 RPM for 10 min, then sieved through a US 30 (500 um) screen onto a weigh boat. PAT059980-WO-PCT 4. ~1 / 2 remaining filler components were added back into the jar followed by all of the pre- mix 2. The weigh boat was then dry washed with all remaining filler components and the material was transferred to the jar (Pre-mix 3). 5. The blend was then mixed in a Turbula mixer at 32 RPM for 5 minutes. 6. Blend was sieved through a US 30 (500um) screen onto a weigh boat. The blend was then mixed in a Turbula mixer at 32 RPM for 10 minutes. 7. Blend uniformity samples were taken by pouring the blend onto a flat surface and collecting ~100mg blend uniformity sample from top, middle, and bottom sections in duplicate and analyzing via HPLC. 8. After obtaining passing blend uniformity results, magnesium stearate was sieved through 500 µm sieve and added to the rest of the blend. The blend was then mixed on a Turbula mixer for 2 min at 32 RPM. Example 3.6: 2mg tablet formulations A sixth tablet formulation was prepared with plastic filler component Avicel PH 101 using the same blend procedure as described above in example 3.5. This powder formulation was designed for a direct compression process, a 2mg dose strength, and a 100mg final tablet weight. Materials were as described above in example 3.5. Table 15: Composition of tablet formulation 6 Unit Weight, mg 100 Dose Strength, mg 2 % Unit FunctionFormulation weight, Composition mg SDD1 API 8.00% 8.0 Avicel PH 101 Filler 87.00% 87.0 Cabosil M-5P Glidant 1.00% 1.0 Ac-Di-Sol Disintegrant 3.00% 3.0 Magnesium Stearate Lubricant 1.00% 1.0 Total 100.00% 100.0 Example 3.7: 10 mg tablet formulations PAT059980-WO-PCT A seventh tablet formulation was prepared using a dry granulation process. This formulation was for a 10mg dose strength and 100mg final tablet weight. Materials were as described above in example 3.5. Table 16: Composition of tablet formulation 7 Formulation 7 Unit Weight, mg 100 Dose Strength, mg 10 Component Function % Formulation Unit Composition weight, mg SDD1 API 40.00% 40.0 Avicel PH 101 Filler 55.00% 55.0 Intra- granular Cabosil M-5P Glidant 1.00% 1.0 component Ac-Di-Sol Disintegrant 1.50% 1.5 (IG) Magnesium stearate Lubricant 0.50% 0.5 IG Total 98.00% 98.0 Extra- Ac-Di-Sol Disintegrant 1.50% 1.5 granular component Magnesium stearate Lubricant 0.50% 0.5 (EG) EG Total 100.00% 100.0 Blend procedure (dry granulation process) IG blend 1. Components were weighed. 2. Glass container was pre-coated by adding 1 / 2 of filler components in an appropriately sized jar, followed by the addition of all SDD, glidant, and disintegrant. The SDD weigh boat was dry washed with remaining filler components and the material was transferred to the jar. 3. Blend was mixed in a Turbula mixer at 32 RPM for 10 min, then sieved through a US 30 (500 um) screen onto a weigh boat and transferred back into the jar. 4. The blend was then mixed in a Turbula mixer at 32 RPM for 10 minutes. 5. Blend uniformity samples were taken by pouring the blend onto a flat surface and collecting ~100mg blend uniformity sample from top, middle, and bottom sections in duplicate and analyzing via HPLC. PAT059980-WO-PCT 6. After obtaining passing blend uniformity results, magnesium stearate was sieved through 500 µm sieve and added to the rest of the blend. The blend was then mixed on a Turbula mixer for 2 min at 32 RPM. EG blend 1. IG blend was slugged using GlobalPharma Single Station Tablet Press with 0.7” RF tooling, targeting a tensile strength of 0.8-1 MPa. 2. Slugs were milled using benchtop manual mill from Gerteis with 1 mm screen. 3. Granules were weighed and the amount of extra-granular disintegrant and lubricant were calculated. 4. ~1 / 2 granules were added to an appropriately sized glass jar, followed by all EG disintegrant then remaining granules. 5. Blend was mixed in a Turbula mixer at 32 RPM for 5 minutes. 6. Lubricant was sieved through 500 um screen then added to the blend. 7. Blend was mixed in a Turbula mixer at 32 RPM for 2 minutes. Example 3.8: 0.1 mg tablet formulations An eighth tablet formulation was prepared with plastic filler component Avicel PH 101 using the same blend procedure as described above in example 3.5. This powder formulation was designed for a direct compression process, a 0.1mg dose strength, and a 100mg final tablet weight. Materials were as described above in example 3.5. Table 17: Composition of tablet formulation 8 Unit Weight, mg 100 Dose Strength, mg 0.1 % Unit FunctionFormulation weight, Composition mg SDD1 API 0.40% 0.4 Avicel PH 101 Filler 94.60% 94.6 Cabosil M-5P Glidant 1.00% 1.0 Ac-Di-Sol Disintegrant 3.00% 3.0 Magnesium Stearate Lubricant 1.00% 1.0 Total 100.00% 100.0 PAT059980-WO-PCT Example 3.9: Testing of tablet formulations 1-8 Blend uniformity of tablet formulations 1-8 As described above, samples were collected from each formulation during the preparation process and then tested for blend uniformity due to the risk posed by very diluted blends. Results are summarized in Table 19 and Table 20. Formulations for which each sample has a potency within 95%-105% have good blend uniformity. Procedure for 0.1mg tablet blends and 0.5mg tablet blends 1. Pipette 3.0 mL (for 0.1mg tablet blend) or 10.0 mL (for 0.5mg tablet blend) of diluent (100% methanol) directly into vial containing blend uniformity sample 2. Extract Compound A with 30 minutes of sonication (swirling every 5 minutes) followed by 30 minutes of shaking 3. Centrifuge sample and transfer ~1.5mL of supernatant to a vial for UPLC analysis according to the parameters in Table 18. Target sample concentration: ~50 µg / mL Procedure for 2mg and 10mg tablet blends 1. Transfer powder from vial containing blend uniformity sample into a 50mL volumetric flask 2. Rinse vial with diluent (100% methanol) at least 3 times and transfer to flask 3. Fill flask to ~80% with diluent 4. Extract Compound A with 30 minutes of sonication (swirling every 5 minutes) followed by 30 minutes of shaking 5. Dilute flask to volume with diluent 6. Centrifuge sample and transfer ~1.5mL of supernatant to a vial for UPLC analysis according to the parameters in Table 18. Target sample concentration for 2mg tablet blend: ~40 µg / mL. Target sample concentration for 10mg tablet blend: ~200 µg / mL Table 18: Parameters for UPLC analysis of blend uniformity samples Condition Parameter 0.1mg and 0.5mg tablet blends 2mg and 10mg tablet blends Instrument Waters H-Class UPLC with TUV Detector Waters HPLC with TUV Detector PAT059980-WO-PCT Waters Acquity UPLC BEH Phenyl Column 2.1x50mm, 1.7µm Part No. HALO AQ-C184.6x150mm, 2.7µm 186002884 Part No.92814-722 Mobile Phase 0.1% Phosphoric Acid in [90:10] A Water: Acetonitrile 0.1% TFA in Water Purge 0.1% Phosphoric Acid in [90:10] Water: Acetonitrile 100% ACN Mobile Phase B 0.1% Phosphoric Acid in Acetonitrile 0.1% TFA in ACN Wash Solvent 100% Methanol 50 / 50 Water:ACN Flow mL / min) Ti MP A MP B Flow MP A MP B ( me (%) (%) (mL / min) Time (%) (%) 0.00 100.0% 0.0% 0.00 0.00 100.0% 1.00 100.0% 0.0% 5.00 100.0% 0.0% Gradient 3.50 0.0% 100.0 % 28.00 0.0% 100.0% 0.500 10 1.00 4.00 0.0% 0.0 % 32.00 0.0% 100.0% 4.01 100.0% 0.0% 32.10 100.0% 0.0% 6.5 100.0% 0.0% 35.00 100.0% 0.0% Column Temperature 30°C ± 3°C 30°C ± 5°C Sample Ambient temperature (0.1mg) Temperature 5°C (0.5mg) 5°C ± 5°C Diluent 90:10 Methanol:Water (0.1mg) 100% Methanol (0.5mg) 100% Methanol Injection Volume 5.0 µL 5.0 µL Sampling Rate 20 point / sec 2 point / sec Run Time 6.5 minutes 35 minutes Wavelength 308 nm 220 nm

[0002] PAT059980-WO-PCT Table 19: Blend uniformity results for tablet formulations 1-5 Form.1 Form.2 Form.3 Form.4 Form.5 Sample Number % Potency 1 88.4 89.4 1120 101.11 101.1 2 96.7 88.6 116.4 99.98 99.4 3 81.6 92.6 107.9 102.25 99.7 4 86.5 88.2 110.0 101.59 98.1 5 94.4 91.9 113.5 98.65 98.9 6 90.4 81.7 125.7 101.59 93.7 Average 89.7 88.7 114.3 100.9 98.3 % Relative Standard Deviation 6.1 4.4 5.5 1.3 2.6 Table 20: Blend uniformity results for tablet formulations 5-8 Form. 5 Form. 6 Form. 7Form. 8Sample Number % Potency 1 100.05 102.04 103.75 96.8 2 100.34 Sample Prep Error 102.21 98.3 3 100.55 99.75 104.32 100.1 4 99.5 100.18 104.05 97.2 5 98.22 97.09 103.59 98.1 6 99.44 100.5 101.71 97.0 Average 99.7 99.9 103.3 97.9 % Relative Standard 0.8 1.8 1.0 1.3 Deviation Bulk and tapped density of tablet formulations 4-7 Procedure Approximately 20 g of blend was placed into a 100mL graduated cylinder. The sample mass and bulk density were recorded. The graduated cylinder was then placed on an Autotap and tapped for 500 and 1000 taps to measure the tapped density. The bulk and tapped densities were used to calculate the Carr Index and Hausner Ratio using the equations below, and these values were used to designate the blend’s flowability in accordance with Table 21. PAT059980-WO-PCTEquation 1: Carr Index = 100 × (v^^^^^^^^−v^^^^^^^^^^^^v^^^^^^^^ )Equation 2: Hausner Ratio = (v^^^^^^^^ v^^^^^^^^^^^^) Table 21: Flow property description based on bulk / tapped densities Compressibility Index (Carr) Flow Character Hausner Ratio ≤ 10 Excellent 1.00 – 1.11 11-15 Good 1.12 – 1.18 16-20 Fair 1.19 – 1.25 21-25 Passable 1.26 – 1.34 26-31 Poor 1.35 – 1.45 32-37 Very poor 1.46 – 1.59 ≥ 38 Very, very poor ≥ 1.60 Results The results are shown in Table 22. All formulations exhibited acceptable flow properties. The formulation 6 granules showed similar flow properties to the formulation 6 IG blend, likely due to formation of fines during the manual granulation process. This phenomenon is expected to improve when producing granules during roller compaction via Gerteis as ribbons are less prone to forming fines during the milling process compared to slugs. Table 22: Bulk and tapped densities of tablet formulations 4-7 Density Summary Form.4 Form.5 Form.6 Form.7 Form.7 Blend Blend Blend IG Blend Granules Sample Mass (g): 16.6788 19.2750 19.4604 20.1611 23.3057 Bulk Volume (mL): 50 50 50 55 47.5 Bulk Density (g / mL): 0.3336 0.3855 0.3892 0.3666 0.4906 Volume (500 taps) (mL): 36.2 39.5 39.5 43.0 36.5 Volume (1000 taps) (mL): 35.5 38.5 38.5 41.5 36.0 Tapped Density (g / mL): 0.4698 0.5006 0.5055 0.4858 0.6474 Carr Index: 29.00 23.00 23.00 24.55 24.21 Hausner Ratio 1.41 1.30 1.30 1.33 1.32 Flow Property Poor Passable Passable Passable Passable Compression profiles for tablet formulations 4-7 PAT059980-WO-PCT 100 mg tablets of formulations 4-7 were compressed using 0.25” flat faced tooling at a range of compression pressures using a GlobalPharma Single Station Tablet Press to determine the compression properties of the formulated blends. Compression profiles of tabletability (FIG. 16) and compactability (FIG.17) were generated. Tabletability is a measure of how strong a tablet can be made at various compression stresses. Compactibility describes whether a tablet is able to achieve the desired tensile strength at the target solid fraction. The tablets were also tested for weight, thickness, and hardness. Formulations 5 and 6 exceeded the 2-3 MPa tensile strength and 0.7-0.8 solid fraction targets even at low compression pressures, and therefore have acceptable tabletability and compactibility properties for a direct compression process. It is important that the formulation 7 IG blend has acceptable compression properties so that the granules produced by the dry granulation process can be compressed a second time in the final tablet production. For roller compacted blends, achieving a maximum tensile strength between 3.0-4.0 Mpa below a compression stress of 300 Mpa is an ideal target. This allows for the blend to undergo multiple rounds of compression and maintain acceptable tensile strengths. The formulation 6 IG blend was able to exceed the 3-4 MPa tensile strength and 0.7-0.8 solid fraction targets even at low compression pressures, and therefore has acceptable compressibility, tabletability, and compactibility properties. Additionally, the formulation 7 EG blend was able to exceed the 2-3 MPa tensile strength and 0.7-0.8 solid fraction targets even at low compression pressures, and therefore has acceptable compressibility, tabletability, and compactibility properties. The 0.5mg and 2mg blends achieved the highest tensile strengths likely due to the higher concentration of filler present in those blends. Disintegration of tablets of formulations 5-7 Disintegration testing was performed on high tensile strength tablets (3.0 MPa) of formulations 5-7. Procedure 1. Setup DisiTest50 Automated Disintegration Tester per standard operating procedure SOP- 0146 with purified water and allow it to heat up to 37.0ºC ± 0.5ºC. 2. Perform disintegration testing, recording the time when the tablets are fully disintegrated. Full disintegration time is when the tablet core has dispersed, leaving only free floating powder. PAT059980-WO-PCT Results Table 23: Disintegration times for tablets with formulations 5-7 Tablet Disintegration Time min:sec 00:06 Formulation 5 ~3MPa Tensile Strength 00:06 00:08 00:06 Formulation 6 ~3MPa Tensile Strength 00:06 00:08 00:10 Formulation 7 EG ~3MPa Tensile Strength 00:12 00:12 All tablets across all three formulations showed rapid disintegration in water. Summary Overall, all formulated blends showed good tabletability and achieved acceptable tensile strengths within 250-300 MPa compression stress. Formulations 5 and 6 provided acceptable blend uniformity, flowability, compression profiles, and disintegrations times, and are therefore suitable for manufacturing direct compression immediate release tablets. In particular, tabletability of formulations 5 and 6 is considered excellent, with tablets at the desired tensile strength of 1.7-2.0 MPa expected to be produced at low compression stress (<100MPa). The formulation 7 intra-granular blend had acceptable blend uniformity, flowability, and roller compaction properties, and therefore is suitable for granulation. In particular, the intra- granular blend has good compactibility properties and is expected to produce strong granules, which can withstand downstream processing. The formulation 7 extra-granular blend also exhibited acceptable flowability, compression profile, and disintegration time. Formulation 7 is therefore acceptable for dry granulation and immediate release tablet manufacturing. Formulation 8 gave acceptable blend uniformity results for the 0.1 mg strength and demonstrated good chemical stability at 40 °C for 2 weeks. Direct blending was successful thus offering the advantage of a streamlined process. Direct compression could also be applied in this case and coating process was uneventful. Overall, formulation 8 is considered acceptable for a dry granulation and immediate release tablet manufacturing. PAT059980-WO-PCT EXAMPLE 4: SOFTGELS Example 4.1: Softgel fill formulation compositions Generic names of ingredients of softgel fill formulations The generic names of certain excipient products used in the examples below are provided in Table 24. Other products providing the same chemical substances as the particular excipient products used in the examples below can also be used to prepare softgels as provided by the present disclosure. Table 24: Generic names of ingredients used in softgel fill formulations Proprietary name Generic name Maisine CCGlyceryl monolinoleatePropylene glycol Capryol 90 monocaprylate Caprylocaproyl polyoxyl-8 Labrasol ALF glycerides Glyceryl mono and Labrafac MC60 dicaprylocaprate Kolliphor ELPolyoxyl 35 Castor OilKollidon K30PovidonePolyoxyl 35 Castor Oil, USP- Kolliphor ELP NF grade Various softgel fill formulations having compositions as shown in Table 25 were prepared. Exemplary preparation methods are shown in Examples 4.2 and 4.6. Table 25: Softgel fill formulations Fill formulation Component % w / w mg / g Compound A 0.1 1.0 Maisine CC 39.90 399 S1 Capryol 90 40.00 400 Tocofersolan 20.00 200 S2 Compound A 0.05 0.5 PAT059980-WO-PCT Maisine CC 19.95 199.5 Capryol 90 40.00 400.0 Tocofersolan 40.00 400.0 Compound A 0.1 1.0 Labrasol ALF 44.90 449.0 Labrafac MC60 40.00 400.0 Kolliphor EL 15.00 150.0 Compound A 0.1 1.0 Maisine CC 49.9 499 Kolliphor EL 35.00 350 Benzyl Alcohol 10.00 100 Lecithin 5.00 50 Compound A 0.1 1.0 Maisine CC 40.00 400.0 Kolliphor EL 45.00 450.0 Benzyl Alcohol 10.00 100.0 Lecithin 4.90 49.0 Compound A 0.1 1.0 Labrasol ALF 49.90 499.0 PEG 400 35.00 350.0 Benzyl Alcohol 15.00 150.0 Compound A 0.2 2.0 Maisine CC 40.00 400.0 Kolliphor EL 45.00 450.0 Benzyl Alcohol 10.00 100.0 BHT 0.05 0.5 BHA 0.05 0.5 Lecithin 4.70 47.0 Compound A 0.2 0.01 Maisine CC 44.7 44.89 Kolliphor EL 45.0 45.0 Benzyl Alcohol 10.0 10.0 PAT059980-WO-PCT BHT 0.05 0.05 BHA 0.05 0.05 Compound A 0.15 1.50 Maisine CC 44.75 447.50 Kolliphor EL 45.00 450.00 Benzyl Alcohol 10.00 100.00 S9 Butylated 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Compound A 0.10 1.00 Maisine CC 44.80 448.00 Kolliphor EL 45.00 450.00 Benzyl Alcohol 10.00 100.00 S10 Butylated 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Compound A 0.10 1.00 Maisine CC 40.80 448.00 Kollidon K30 4.70 47.00 Kolliphor EL 45.00 450.00 S11 Benzyl Alcohol 10.00 100.00 Butylated 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Compound A 0.10 1.00 Maisine CC 40.80 408.00 S12 Kolliphor EL 45.00 450.00 Benzyl Alcohol 10.00 100.00 Kollidon K30 4.70 47.0 PAT059980-WO-PCT Butylated 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Compound A 0.15 1.50 Maisine CC 40.75 407.50 Kolliphor EL 45.00 450.00 Benzyl Alcohol 10.00 100.00 S13 Kollidon K30 4.70 47.0 Butylated 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Compound A 0.10 1.00 Maisine CC 43.80 438.00 Kolliphor EL 45.00 450.00 Benzyl Alcohol 10.00 100.00 Butylated S14 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Hydrolyzed 1.00 10.00 Gelatin Compound A 0.10 1.00 Maisine CC 44.30 443.00 Kolliphor EL 45.00 450.00 Benzyl Alcohol 10.00 100.00 S15 Butylated 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Ascorbyl Palmitate 0.5 5.00 S16 Compound A 0.10 1.00 PAT059980-WO-PCT Maisine CC 44.80 448.00 Kolliphor EL 45.00 450.00 Benzyl Alcohol 10.00 100.00 Butylated 0.05 0.50 Hydroxytoluene Butylated 0.05 0.50 Hydroxyanisole Compound A 0.1 1 Benzyl Alcohol 10.0 100 Kolliphor ELP 45.0 450 S17 Maisine CC 43.8 438 BHA 0.05 0.5 BHT 0.05 0.5 Ascorbyl Palmitate 1.0 10 Compound A 0.10 1.00 Maisine CC 43.89 438.90 Kolliphor ELP 45.00 450.00 S18 Benzyl Alcohol 10.00 100.00 DL-α-tocopherol 0.01 0.10 Ascorbyl Palmitate 1.0 10.00 Compound A 0.01 0.1 Maisine CC, NF 44.89 448.9 Kolliphor EL, NF 45.0 450 Benzyl Alcohol, 10.0 100 NF S19 Butylated Hydroxytoluene, 0.05 0.5 NF Butylated Hydroxyanisole, 0.05 0.5 NF Compound A 0.05 0.5 S20 Maisine CC, NF 19.95 199.5 PAT059980-WO-PCT Capryol 90 40.0 400 Vitamin E TPGS 40.0 400 Example 4.2: Preparation of softgel fill formulations A 100g batch of softgel fill formulation S7 was prepared according to the following procedure. The other softgel fills described above can be prepared analogously. The sample preparation bottle was kept covered with parafilm to avoid any air getting into the formulation. 1. Weigh Compound A into a 60mL amber glass bottle. Add benzyl alcohol and homogenize using homogenizer with large blade at low speed (2 to 3) for 30 minutes. Observe whether all of Compound A is in solution. If not, mix for additional 15 minute increments until Compound A is in solution or until 1.5 hours have elapsed. 2. If Compound A dissolves in the benzyl alcohol, then once there is a clear solution, add 25 g of Kolliphor EL before homogenizing and mixing at slow speed (2-3) for 20 minutes. If Compound A does not dissolve in the benzyl alcohol after 1.5 hours of mixing, add 35 g of Kolliphor EL, then homogenize and mix at slow speed (2-3) for 40 minutes. Check for solubility of Compound A every 10 minutes. 3. Record Tare weight of empty 250mL amber glass bottle with cap. 4. Carefully transfer all material into the 250 mL amber glass bottle. Rinse the 60mL bottle with the remaining Kolliphor EL and transfer to 250 mL glass bottle. 5. Add 30 g Maisine CC to the 60 mL bottle, rinse by mixing slowly and transfer to 250 mL glass bottle. Add the remaining Maisine CC to 60 mL bottle, rinse by mixing slowly and transfer to 250 mL glass bottle. Add the lecithin to the 250 mL bottle. Then add the BHT and BHA. Add one drop of Simethicone to facilitate deaeration. 6. Homogenize and mix using homogenizer with large blade at low speed (2 to 3) for 30 to 45 minutes to obtain a clear, light yellow, slightly translucent solution. 7. De-aerate using vacuum. Example 4.3: Solubility of softgel fill formulations S2, S3, S5, and S6 The kinetic solubility of formulations S2, S3, S5, and S6 in biorelevant media was evaluated in vitro using a two-step dissolution test. This test involves measuring dissolution of the API in simulated gastric fluid (FaSSGF) which is subsequently converted into simulated intestinal fluid (FaSSIF). See Examples 3.1 and 3.2 for details of these media. This simulates the in vivo PAT059980-WO-PCT process after oral administration. The test was carried out on a Pion instrument with a USP II apparatus, in which API concentration was determined by fiber optic probes. The following parameters were used: final volume = 500 mL; temperature: 37⁰C; paddle: 75 RPM. 2-piece hardshell capsules containing approximately 2g of formulation were utilized for the test. Results are shown in FIG. 18. Due to the low concentration of Compound A in the formulation, there was a lot of background noise from the excipients. This meant that the data for the formulations in FaSSGF and the data for S5 could not be analysed. Example 4.4: Physical stability of softgel fill formulations Softgel fill formulation S7 Samples of softgel fill formulation S7 were spiked with water, glycerin, gel, or plasticizer (Sorbitol Special) and stored for 8 weeks at ambient conditions or at 40°C and 75% relative humidity. After 2 weeks each solution remained a clear, light yellow, translucent solution. After 4 weeks phase separation was observed in each sample. Table 26: Composition of spiked samples of softgel fill formulation S7 Sample composition 4.0g S7 spiked with 5% water 3.0g S7 spiked with 1.0g glycerin, USP 3.0g S7 spiked with 1.0g Sorbitol Special, NF 3.0g S7 spiked with 1.5g gelatin strip 4.0g S7 Softgel fill formulations S9-S11 Samples of softgel fill formulations S9-S11 were stored at 5°C and 40°C. No precipitation was observed in any of the samples at after 3 weeks. Example 4.5: Chemical stability of softgel fill formulations Certain softgel fill formulations described in example 4.1 were stored under various conditions and then analysed by HPLC. Results are shown in Table 29. The major impurity detected (with a relative retention time 0.96) was present in the API itself at 1.2%. Another impurity (with a relative retention time of 1.32) is due to free radical based oxidative degradation of Compound A. However, use of ascorbyl palmitate in fill formulation S15 avoids this. PAT059980-WO-PCT HPLC method HPLC was carried out with the parameters and gradient shown in the following tables. Table 27: HPLC parameters Parameter Condition HPLC System Waters Acquity Arc HPLC with a W2489 UV Detector Halo 90 AQ-C18, 2.7 µm, 150 x 4.6 mm (advanced Column materials technology), Part No.92814-722 Mobile Phase A 0.1% TFA in Water Mobile Phase B 0.1% TFA in ACN Needle Wash [50:50] Water:ACN Purge 100% ACN Column Temperature 30°C ± 5°C Sample Temperature 5°C ± 5°C Detection Wavelength 220 nm Injection Volume 5 µL Run Time 35.0 min Sampling Rate 2 pts / sec1Diluent Methanol2Nominal Concentration 100 µg / mL3(Assay) Nominal Concentration 500 µg / mL3(Impurities)1Sampling rate altered from 10 pts / sec to 2 pts / sec. ARC HPLC have high baseline noise above 2 pts / sec sampling rate.2Diluent switched from 0.1% TFA in [50:50] Water:ACN to methanol to improve solubility.3Nominal concentration altered from 350 µg / mL to 100 µg / mL for potency samples and 500 µg / mL for purity samples due to detector oversaturation Table 28: HPLC gradient Time (min) Flow Rate (mL / min) % Mobile Phase A % Mobile Phase B 0.00 1.00 100.0 0.0 5.00 1.00 100.0 0.0 28.00 1.00 0.0 100.0 PAT059980-WO-PCT 32.00 1.00 0.0 100.0 32.10 1.00 100.0 0.0 35.00 1.00 100.0 0.0 Chemical stability data Table 29: Chemical stability data for various softgel fill formulations. W = week(s); RH = relative humidity Softgel fill Timepoint and Total Impurities Assay (% formulation Storage Conditions (% area) w / w) Initial 95.3 1.70 S2 T = 2W; 40 °C 88.0 2.03 Initial 100.3 2.37 S3 T = 2W; 40 °C 98.3 1.28 Initial 102.9 2.05 S5 T = 2W; 40 °C 99.9 1.08 Initial 99.7 1.26 S6 T = 2W; 40 °C 91.5 1.23 T=0 Initial 0.73 96.9 S10 T = 4W; 40°C / 75% 2.04 93.3 RH T = 10 W; 5°C 0.61 96.6 T = 10W; Ambient 0.93 93.8 S12 T = 10W; 40°C / 75% 3.87 89.4 RH Initial 0.27 T = 1W; 40°C / 75% 1.7 S14 RH T = 1W; 50°C 3.2 T=2W; Ambient 0.39 Initial 0.25 T = 1W; 40°C / 75% S15 0.43 RH T = 1W; 50°C 0.72 PAT059980-WO-PCT T=2W; Ambient 0.38 Initial 0.4 T = 1W; 40°C / 75% 1.9 RH T = 1W; 50°C 3.4 S16 T=2W; Ambient 0.56 T = 10 W; 5°C 0.41 94.3 T = 10W; Ambient 1.2 91.0 T =10W; 40°C / 75% 9.9 79.1 RH Initial 0.25 99.7 T = 12 hours; 50°C 0.26 98.5 T = 1W; 5°C 0.26 98.0 T = 1W; 25°C 0.36 98.2 T = 1W; 30°C 0.25 97.8 T = 1W; 40°C / 75% 0.36 98.0 RH T = 2W; 5°C 0.35 99.2 S17 T = 2W; 25°C 0.35 99.3 T = 2W; 30°C 0.28 98.7 T =2W; 40°C / 75% 0.37 99.1 RH T = 4W; 5°C 0.34 99.2 T = 4W; 25°C 0.37 98.7 T =4W; 30°C 0.25 99.1 T =4W; 40°C / 75% 0.36 99.2 RH Initial 0.27 95.3 T = 1W; 5°C 0.27 96.2 T = 1W; 25°C 0.27 96.1 S18 T = 1W; 30°C 0.29 95.9 T = 1W; 40°C / 75% 0.27 96.0 RH PAT059980-WO-PCT T = 3W; 5°C 0.38 97.1 T = 3W; 25°C 0.37 96.9 T = 3W; 30°C 0.37 96.7 T = 3W; 40°C / 75% 0.38 97.0 RH T = 4W; 5°C 0.37 96.3 T= 4W; 25°C 0.37 96.1 T = 4W; 30°C 0.38 96.0 T = 4W; 40°C / 75% 0.37 95.9 RH Example 4.6: 0.1 mg, 1.0 mg and 2.0 mg softgel capsules Compositions of fill material of 0.1 mg, 1.0 mg and 2.0 mg softgels Table 30: Composition of fill material of 0.1 mg, 1.0 mg and 2.0 mg softgels Ingredient Ingredient (non-proprietary name) (proprietary name) % w / w mg / softgel g / batch 0.1 mg softgel Compound A 0.01% 0.10 0.2246 Glyceryl Monolinoleate, NF / EP Maisine CC 40.00% 400.00 880.0 Polyoxyl 35 Castor Oil, NF, EP Kolliphor EL 45.19% 451.90 994.2 Benzyl Alcohol, NF EP 10.00% 100.00 220.0 Butylated Hydroxytoluene (BHT), NF, EP 0.05% 0.50 1.10 Butylated Hydroxyanisole (BHA), NF, EP 0.05% 0.50 1.10 Lecithin (meets NF test specifications) 4.69% 46.90 103.4 Simethicone, USP Liveo Q7-2243 0.01% 0.10 0.1501 1.0 mg softgel Compound A 0.1% 1.0 Glyceryl Monolinoleate, NF / EP Maisine CC 40.00% 400.0 Polyoxyl 35 Castor Oil, NF, EP Kolliphor EL 45.00% 450.0 Benzyl Alcohol, NF EP 10.00% 100.0 Lecithin (meets NF test specifications) 4.90% 49.0 PAT059980-WO-PCT 2.0 mg softgel Compound A 0.20% 2.0 4.4900 Glyceryl Monolinoleate, NF / EP Maisine CC 40.00% 400.00 880.0 Polyoxyl 35 Castor Oil, NF, EP Kolliphor EL 45.00% 450.00 989.9 Benzyl Alcohol, NF EP 10.00% 100.00 220.0 Butylated Hydroxytoluene (BHT), NF, EP 0.05% 0.50 1.10 Butylated Hydroxyanisole (BHA), NF, EP 0.05% 0.50 1.10 Lecithin (meets NF test specifications) 4.69% 46.90 103.4 Simethicone, USP Liveo Q7-2243 0.01% 0.10 0.1399 Preparation of fill material A portion of benzyl alcohol and Kolliphore EL was added to a Becomix 2.5L. The simethicone was added to the Becomix 2.5L. The Compound A wetted with small portion of benzyl alcohol was transferred to the Becomix 2.5L and mixed for 60 minutes at 35 °C with the homogenizer speed 7.5m / s and the agitator speed 1.0m / s. Compound A dissolved in the fill material. All the remaining excipients were added to Becomix 2.5L and mixed for additional 30 minutes under same conditions. It was visually confirmed that there were no particles present. The material was deaerated under vacuum. Preparation of softgels The fill material was encapsulated to produce the softgels using a 7th generation encapsulation machine with die (16 oblong) in pilot plan. The gel formula for the softgels consisted of gelatin, sorbitol glycerin blend, titanium dioxide, and purified water. A moisture ingress study was performed to evaluate water migration from wet shell to fill material during encapsulation and it was determined that water migration was not significant. Therefore, in-process fill weight adjustment was not necessary. The softgels were dried after encapsulation in a drying tunnel. After drying the softgels were manually washed and then packaged in aluminium bags and sealed. The softgels were perfect in shape, with a good seam and no physical deformity. Testing of softgels PAT059980-WO-PCT The softgels were stored for 1 month at 25 °C and 60% relative humidity, and at 40 °C and 75% relative humidity, and analysed for stability, hardness, water content, and rupture. Results are shown in the tables below. The softgels did not leak under either storage condition. Table 31: Stability testing of softgel formulations. RRT = relative retention time Related substances (%) Softgels Storage ConditionsRRT-RRT- RRT- RRT- TotalAssay0.84 0.96 1.32 1.69 Impurities T=0 (Initial) 104.3 0.1 mg T = 1M 25°C / 6 Not tested 104.3 softgels 0% RH T = 1M 40°C / 75% RH 103.0 T=0 (Initial) - 0.26 0.09 0.08 0.26 98.9 2.0 mg T = 1M 25°C / - 0.26 0.08 0.09 0.26 98.8 softgels 60% RH T = 1M 40°C / 75% RH 0.12 0.25 0.20 0.09 0.57 100.7 Table 32: Hardness of 0.1mg and 2.0mg softgels Hardness (N) Sample number Initial T=1M 25 / 60 T = 1M 40 / 75 1 7.7 7.6 5.1 2 7.7 7.2 3.4 0.1mg 3 7.8 8.7 5.4 softgels 4 8.3 7.6 5.3 5 7.4 7.3 4.6 Average (mean) 7.8 7.7 4.8 1 8.3 8.6 4.1 2 8.6 8 5.4 2.0 mg 3 7.6 8 4.8 softgels 4 8.4 8.3 4.4 5 7.2 7.8 4.4 Average (mean) 8.0 8.1 4.5 Table 33: Water content of 0.1mg and 2.0mg softgels Water content PAT059980-WO-PCT Initial T=1M 25 / 60 T = 1M 40 / 75 0.1mg softgels 2.5 % 2.5 % 2.6 % 2.0 mg softgels 2.7 % 2.7 % 4.1 % Table 34: Rupture of 0.1mg and 2.0mg softgels Rupture (minutes) Sample number Initial T=1M 25 / 60 T = 1M 40 / 75 1 1.0 2 7 2 1.0 2 5 3 1.0 2 6 0.1mg 4 1.0 2 6 softgels 5 1.0 2 6 6 1.0 2 6 Average (mean) 1.0 2 6 1 1.0 2 6 2 2.0 2 6 3 1.0 2 5 2.0 mg 4 1.0 2 5 softgels 5 1.0 2 5 6 2.0 2 6 Average (mean) 1.0 2 6 Example 4.7: Manufacturing process for Compound A 0.1 mg and 0.5 mg softgel capsules The softgel capsules of Compound A contain approximately 100.0 mg of fill solution for the 0.1 mg capsule and approximately 500.0 mg of fill solution for the 0.5 mg capsule. For the encapsulation of the soft gelatin capsules, an opaque white gel mass is used. The clear gel mass is prepared by using gelatin, Sorbitol Special – Glycerin Blend as plasticizer, and purified water. The gel mass is then color-converted to an opaque white color by adding TiO2 and purified water to the gel mass. After drying is completed, the capsules are visually inspected for any physical defects and washed. The washed softgel capsules are counted and bulk-packaged in carton with polybag. The 0.1 and 0.5 mg softgel capsules are bottled, closed with a capper, and induction sealed. PAT059980-WO-PCT Table 35: Batch Formula for Compound A Softgel Capsules, 0.1 mg Theoretical Lot Quantity = 2,500 g (25,000 capsules) Quantity per Unit Theoretical Weight Component Dose (mg / dose) per Batch (g) Compound A 0.10 2.500 Glyceryl Monolinoleate 43.80 1,095.00 Polyoxyl 35 Castor Oil 45.00 1,125.00 Benzyl Alcohol 10.00 250.00 Butylated Hydroxytoluene (BHT) 0.05 1.250 Butylated Hydroxyanisole (BHA) 0.05 1.250 Ascorbyl Palmitate 1.00 25.00 Total 100.00 mg 2,500.00 Table 36: Batch Formula for Compound A Softgel Capsules, 0.5 mg Theoretical Lot Quantity = 10,000 g (20,000 capsules) Quantity per Unit Theoretical Weight Component Dose (mg / dose) per Batch (g) Compound A 0.50 10.00 Glyceryl Monolinoleate 219.00 4,380.00 Polyoxyl 35 Castor Oil 225.00 4,500.00 Benzyl Alcohol 50.00 1000.00 Butylated Hydroxytoluene (BHT) 0.25 5.00 Butylated Hydroxyanisole (BHA) 0.25 5.00 Ascorbyl Palmitate 5.00 100.00 Total 500.00 mg 10,000.00 g Table 37: Softgel Shell Ingredients of Compound A 0.1 mg and 0.5 mg Softgel Capsules Calculated Amount per Softgel on Dry Basis (mg) Gel Mass Component 0.1 mg Softgels 0.5 mg Softgels Die: G2VF Die: G9.5BC Gelatin, NF 59.039 207.302 Sorbitol- Glycerin Blend, 33.737 118.459 USP / NF Titanium dioxide, USP 0.649 2.278 Manufacture of API Stock Mix PAT059980-WO-PCT A flow diagram depicting an overview of the API stock mix manufacturing process is shown in FIG 23. • Compound A and Benzyl Alcohol (divided in 3 portions, one large portion of e.g. around 80% and two smaller portions of e.g. around 10%) are weighed in separate containers. • Portion 1 of Benzyl Alcohol (the larger portion) is added into the mixer. • Compound A and is wetted with Benzyl Alcohol Portion 2 (small portion) and added to the mixer. • The container of Compound A is rinsed with Benzyl Alcohol Portion 3 (small portion) and this is added to the mixer. • The solution is mixed for ~ 180 minutes while maintaining a temperature of 25°C - 35°C and maintaining a vacuum of -0.8 to -1.0 bar. Manufacture of 0.1 mg and 0.5 mg Softgel Capsules A flow diagram depicting an overview of the main mix manufacturing process is shown in FIG 24. • The API stock mix, Polyoxyl 35 Castor Oil (divided in 2 portions of e.g. around 50% each), Glyceryl Monolinoleate (divided in 2 portions of e.g. around 50% each), Butylated Hydroxytoluene, Butylated Hydroxyanisole, and Ascorbyl Palmitate are weighed and placed into separate stainless-steel containers. • First, Polyoxyl 35 Castor oil (portion 1) is added to the mixer, then the API stock mix. The API stock mix container is rinsed with Polyoxyl 35 Castor oil (portion 2, e.g. in at least five stages) which is also added to the mixer. Then Glyceryl Monolinoleate portion 1 is added, followed by Glyceryl Monolinoleate portion 2, Butylated Hydroxytoluene, Butylated Hydroxyanisole, and Ascorbyl Palmitate. The solution is mixed for about 30 minutes while maintaining a temperature of 25°C - 35°C and maintaining a vacuum of - 0.8 to -1.0 bar. • After mixing, the solution is de-aerated for about 30 minutes under agitation and with the homogenizer off. • The solution is discharged into a stainless-steel container which is then blanketed with nitrogen and kept at ambient lab conditions until encapsulation. • The opaque white gel mass for encapsulation is prepared using gelatin, Sorbitol-Glyceryl Blend as plasticizer, and purified water. • The gel mass for encapsulation was color-converted to opaque white color by adding TiO2 and purified water to the gel mass. PAT059980-WO-PCT • For 0.1 mg capsules, one die set was evaluated during the encapsulation process, G2VF. Die set G2VF was able to meet the seal thickness criteria and provide a size 2 softgel. • For 0.5 mg capsules, one die set was evaluated during the encapsulation process, G9.5BC. Die set G9.5BC was able to meet the seal thickness criteria and provide a size 9.5 softgel. o During encapsulation in-process checks are performed for fill weight, shell weight, and seal / seam thickness. • The softgel capsules are tunnel dried and undergo in-process testing for hardness every 12 ± 2 hours. o At each time point until completion of drying, five stratified softgels capsule samples were collected from the drying shallow trays and tested for hardness using Bareiss Hardness Durometer. • After drying is completed, the capsules are visually inspected for any physical defects and washed. • The washed softgels are counted and bulk-packaged in carton with polybag, then bottled and manually induction sealed. EXAMPLE 5: LIQUID FORMULATIONS Materials Other products providing the same chemical substances as the particular excipient products used in the examples below can also be used to prepare liquid formulations as provided by the present disclosure. Table 38: Excipients used in liquid formulations Excipient Grade Supplier Polyethylene glycol 400 Ph Eur Merck Propylene glycol Ph Eur Merck Glycerol (85 %) Ph Eur Merck Corn oil Ph Eur / USP Croda Crodamol GTCC (medium chain triglycerides) Ph Eur / USP Croda Maisine CC (glyceryl monolinoleate) Ph Eur / USP Croda Labrafac PG (propylene glycol dicaprylocaprate) Ph Eur / USP Gattefossé Labrafac MC60 (glyceryl mono and Ph Eur / USP Gattefossé dicaprylocaprate) PAT059980-WO-PCT Transcutol HP (diethylene glycol monoethyl Ph Eur / USP Gattefossé ether) Cavasol W7 HP Pharma (2-hydroxypropyl-β- cyclodextrin with 0.59-0.73 molar substitution per anhydro glucose unit; maximum 1 % β- Ph Eur / USP Ashland cyclodextrin, maximum 10% loss on drying; IU / g bacterial endotoxin not tested) Cavitron W7 HP5 Pharma (2-hydroxypropyl-β- cyclodextrin with 0.59-0.73 molar substitution per anhydro glucose unit; maximum 1 % β- Ph Eur / USP Ashland cyclodextrin; maximum 10% loss on drying; maximum 10 IU / g bacterial endotoxin) Cavitron W7 HP7 Pharma (2-hydroxypropyl-β- cyclodextrin with 0.86-1.14 molar substitution per anhydro glucose unit; maximum 1 % β- Ph Eur / USP Ashland cyclodextrin; maximum 10% loss on drying; maximum 10 IU / g bacterial endotoxin) Hydroxypropyl Betadex (2-hydroxypropyl-β- N / A Sigma Aldrich cyclodextrin) Kolliphor EL (polyoxyl 35 castor oil), Ph Eur / USP BASF Tween 80 (polysorbate 80) Ph Eur / USP Merck Labrasol ALF (caprylocaproyl polyoxyl-8 Ph Eur / USP Gattefossé glycerides) Kolliphor P407 (poloxamer 407) Ph Eur / USP BASF Aqualon CMC 7LF PH (sodium carboxymethyl USP Ashland cellulose) Natrosol 250L PH (hydroxyethyl cellulose) Ph Eur / USP Ashland Benzyl alcoholPh Eur / USPSAFCdi-Sodium hydrogen phosphate dihydrate Ph Eur Merck Sodium dihydrogen phosphate monohydrate Ph Eur Merck NaOH (1 M) Ph Eur Merck Merck HCl (1 M) Ph Eur Emprove Milli-Q purified water (purified water) N / A Millipore PAT059980-WO-PCT Example 5.1: Liquid formulations L1-L30 (solutions and suspensions) Composition and solubility of formulations L1-L28 Compound A was combined with various excipients to produce liquid formulations L1- L28. Details of the excipient(s) used in each formulation can be found in Table 39 below. The formulations were prepared by mixing 5 mg of Compound A in a glass vial with aliquots of the excipient(s) of 5mL or more. Mixing was carried out using a small (10 mm) magnet stirrer bar at 200-300 rpm. Excipient(s) were added until the resulting solution was visually clear by naked eye. The final volume of the formulations was 5-50mL. Solubility data is presented in Table 39 below. Table 39: Composition and solubility of liquid formulations L1-L28 Liquid Solubility Excipient formulation (mg / mL) L1 Polyethylene glycol 400 ~ 0.3 L2 Propylene glycol << 0.1 L3 Glycerol << 0.1 L4 Corn oil << 0.1 L5 Crodamol GTCC << 0.1 L6 Maisine CC << 0.1 L7 Labrafac PG << 0.1 L8 Labrafac MC60 << 0.1 L9 Transcutol HP 0.5-1 Cavasol W7 HP Pharma (10% solution in ~ 0.1 (or slightly L10 water) less than) Cavitron W7 HP5 Pharma (10% solution in ~ 0.1 (or slightly L11 water) less than) Cavitron W7 HP7 Pharma (10% solution in L12 << 0.1 water) L13 Kolliphor EL (1% solution in water) << 0.1 L14 Tween 80 (1% solution in water) << 0.1 L15 Labrasol ALF (1% solution in water) << 0.1 L16 Kolliphor P407 (2% solution in water) << 0.1 L17 Aqualon CMC 7LF PH (2% solution in water) << 0.1 L18 Natrosol 250L PH (2% solution in water) << 0.1 PAT059980-WO-PCT L19 Benzyl alcohol (2% solution in water) << 0.1 L20 200 mg / mL Cavasol W7 HP Pharma in water ~ 0.6 L21 300 mg / mL Cavasol W7 HP Pharma in water ~ 0.9 200 mg / mL Cavitron W7 HP5 Pharma in L22 ≥ 0.5 water L24 200 mg / mL Hydroxypropyl Betadex in water ~ 0.6 90:10 (vol / vol) 200 mg / mL Cavasol W7 HP L25 ≤ 0.5 Pharma in water:Transcutol HP 90:10 (vol / vol) 200 mg / mL Cavasol W7 HP L26 ≤ 0.5 Pharma in water:PEG400 200 mg / mL Cavasol W7 HP Pharma in water, L27 diluted 9:1 (vol / vol) with glycerol 200 mg / mL Cavasol W7 HP Pharma in 20 L28 mM phosphate buffer and 1 M HCl / NaOH to adjust pH to 6 200 mg / mL Cavasol W7 HP Pharma in 20 L29 mM phosphate buffer and 1 M HCl / NaOH to adjust pH to 7 200 mg / mL Cavasol W7 HP Pharma in 20 L30 mM phosphate buffer and 1 M HCl / NaOH to adjust pH to 8 Stability Liquid formulations L20 and L25-L30 were stored at different temperatures (refrigerated, at room temperature, or at 40°C) and analysed via HPLC to assess stability. Compound A was assayed by quantitation against a 100% standard of Compound A. Results are shown in Table 40. It was found that storage at refrigerated temperatures resulted in the lowest formation of impurities. Table 40: Stability data for liquid formulations L20 and L25-L30 Assay Total impurities (% Sample Compound A area of main peak)1(mg / mL) L20, initial 0.53 0.51 L20, 6 days 4˚C 0.54 0.85 PAT059980-WO-PCT L20, 13 days 4˚C 0.55 1.16 L20, 6 days RT 0.53 0.98 L20, 13 days RT 0.56 1.31 L20, 6 days 40˚C 0.50 5.47 L20, 13 days 40˚C 0.51 10.06 L25, initial20.47 0.85 L25, 6 days RT 0.48 1.02 L26, initial 0.55 0.64 L26, 6 days RT 0.56 0.86 L27, initial 0.46 0.39 L27, 7 days 2-8˚C 0.44 0.48 L27, 14 days 2-8˚C 0.44 0.50 L27, 28 days 2-8˚C 0.44 0.58 L28, initial 0.59 0.48 L28, 7 days 2-8˚C 0.58 0.48 L28, 21 days 2-8˚C 0.59 0.55 L29, initial 0.59 0.49 L29, 7 days 2-8˚C 0.59 0.79 L29, 21 days 2-8˚C 0.59 1.29 L30, initial 0.58 1.02 L30, 7 days 2-8˚C 0.57 3.22 L30, 21 days 2-8˚C 0.55 7.511Impurities < 0.05 % disregarded; placebo peaks from excipients disregarded.2Sample was filtered prior to analysis due to cloudy appearance, i.e. indication of non-dissolved API. However, assay indicates that Compound A was almost completely dissolved since measured value agrees well with theoretical (0.55 mg / mL). Example 5.2: Larger scale batch of oral solution L20 The first batch of L20 was exposed to daylight for 4-5 hours during preparation and could have reached a temperature of 30-35° C due to heat from the magnetic stirrer device. A second, larger scale batch of L20 was prepared under a more controlled environment with limited heat and light exposure and shorter mixing times. This batch had a total volume of 100mL and consisted of a solution of 0.5 mg / mL Compound A in 200 mg / mL 2-hydroxypropyl-β-cyclodextrin in water. PAT059980-WO-PCT Ingredients Table 41: Ingredients in 100mL batch of liquid formulation L20 Component Function Amount Compound A API 50.0 mg Cavasol W7 HP Solubility enhancer 20.0 g Pharma Purified water Solvent / vehicle 86.0 g Preparation protocol 1. The water was added to a container and stirred at about 300 rpm using a 30 mm magnetic stir bar. 2. The cyclodextrin was added and allowed to dissolve (this is usually complete in less than 15 minutes). 3. Compound A was added and allowed to dissolve (this usually takes around 1.5 hours), resulting in a clear solution that was almost completely free from visible particles. Stability and pH data The new batch of L20 was then stored refrigerated and analysed. Results of the analysis are shown in Table 42. Assay data indicated complete dissolution of Compound A in the vehicle (99.8% recovery) and improved stability. The pH of the formulation was close to 7 (about 7.3), which is acceptable for an oral solution. Table 42: Stability and pH data for second batch of liquid formulation L20 Assay Total impurities Sample Compound A (% area of main pH (mg / mL) peak) L20, initial 0.50 0.40 7.3 L20, 7 days 2-8˚C 0.49 0.40 L20, 14 days 2-8˚C 0.49 0.46 6.7 L20, 28 days 2-8˚C 0.50 0.51 7.1 Example 5.3: Further liquid formulations for oral dosing The following dosing formulations were prepared and used in Examples 6.2 and 6.3 below. The formulations were prepared at appropriate concentrations to meet dose level requirements. PAT059980-WO-PCT The appropriate amount of Compound A was accurately weighed and mixed with the appropriate excipients to obtain a clear solution or a uniform suspension. Vortexing or sonication at room temperature was also used for some formulations. Table 43: Liquid formulations L31-L34 Liquid Formulation Composition 0.5% CMC and 0.1% Tween 80 in DI L31 water(w / v / v) 10% PEG400 / 90% (10% captisol in DI L32 water(w / v)) L33 50 / 50 PEG400 / 20% captisol in water L34 10% captisol in water EXAMPLE 6: IN VIVO TESTING OF DOSAGE FORMS List of abbreviations AUC Area under the curve AUC0-last Area under the concentration-time curve from time 0 to the last measurable concentration AUC0-24hr Area under the curve from t0 to 24-hour point plasma concentration AUC0-t Area under the curve from t0 to time of last quantifiable plasma concentration AUC0-t / D Area under the curve from t0 to time of last quantifiable plasma concentration divided by dose BLOQ Below limit of quantitation C Plasma concentration Clp Plasma clearance Cmax Maximum observed plasma concentration DI Deionized ESI+ Electrospray ionization (positive) F Female F% Absolute oral bioavailability hr Hour HPLC High performance liquid chromatography ISTD Internal standard PAT059980-WO-PCT IV Intravenous kg Kilogram LC Liquid chromatography LC-MS / MS Liquid chromatography / mass spectrometry / mass spectrometry L Liter LLOQ Lower limit of quantitation M Male µg Microgram mg Milligram mL Milliliter mm Millimeter MRM Multiple reaction monitoring MRT0-lastMean resonance time calculated from time 0 to last measured time point N / A Not Applicable NCA Non-compartmental analysis ng Nanogram PBMC Peripheral blood mononuclear cell PK Pharmacokinetics PO Oral (per os) SDD Spray dry dispersion T½ Plasma elimination half-life Tmax Apparent time to reach plasma Cmax Tlast The last collection time point µm Micrometer Vdss Apparent volume of distribution at steady state Example 6.1: Pharmacokinetics and pharmacodynamics of Compound A in male and female cynomolgus monkeys Several Compound A clinical formulations were investigated in a cynomolgus male monkey cross over PK study to understand their utility following oral dosing. One form was a 0.5 mg softgel capsule filled with fill formulation S20 as described in Example 4.1. Softgel capsules of 0.1 mg (filled with fill formulation S19 as described in Example 4.1) and 1.0 mg strengths (filled with fill formulation S5 as described in Example 4.1) were also investigated. Tablets of two different strengths (0.5 and 10 mg; approximate average of 0.2 and 3.2 mg / kg, respectively) were PAT059980-WO-PCT also used. The 0.5mg tablet was prepared from tablet formulation 5 as described in Example 3.5, and the 10mg tablet was prepared from tablet formulation 7 as described in Example 3.7. In addition, a study was run to evaluate the pharmacokinetic and pharmacodynamic properties of single IV and PO doses of Compound A in adult female and male cynomolgus monkeys. The exposure of Compound A up to 300 mg / kg in adult male and female cynomolgus monkeys was also evaluated. This study used Compound A formulated in liquid composition L33. Dosing Administration of Compound A to adult female and male Cynomolgus monkeys (n =2) or adult male (n =3) was performed at WuXi AppTec (Shanghai) Co., Ltd., or Pharmaron (Ningbo). The monkeys weighed 2.1-4.15 kg at dosing. The liquid formulation (L33) was also tested at 0.2 mg / kg, 5.0 mg / kg, 10 mg / kg, 30 mg / kg, and 100 mg / kg (data not shown). Table 4417: Dosing information Formulation L33 L33 L33 L33 Capsule Tablet 0.02 0.1 mg, 0.5 mg 0.5 mg or Dose 0.5 mg / kg 1.0 mg / kg 300 mg / kg mg / kg or 1.0 mg 10 mg Dose concentratio 0.02 0.5 0.2 30 N / A N / A n (mg / mL) N (M / F) 1 / 1 1 / 1 1 / 1 1 / 1 3M 3M Solution / Suspensio Solution Solution Solution N / A N / A Suspension n Route PO IV PO PO PO PO (IV / PO) Verapamil or Internal Verapami Verapami Verapami Verapami Verapamil Dexamethason Standard l l l l e LLOQ 0.05 1 2 1 0.05 or 0.2 0.05 (ng / mL) Calibration Curve, Instruments and LC-MS / MS Procedure Known amounts of Compound A were added to thawed Cynomolgus monkey plasma from non-dosed animals, to yield a concentration range of Compound A from 0.05, 0.2 or 1 to 150, 500 or 3,000 ng / mL. Plasma proteins were precipitated using acetonitrile containing the internal PAT059980-WO-PCT standard (ISTD) verapamil or dexamethasone. Twenty (20) μL or three (3) μL of the analyte mixture was injected for LC-MS / MS analysis. The calibration curves were constructed by plotting the peak-area of analyzed peaks against known concentrations. The lower limits of quantitation were 0.05, 0.2 or 1 ng / mL plasma. The data were subjected to linear regression analysis with 1 / x2weighting. Analysis was performed on an LC-MS / MS system comprised of a Sciex API4000, API5500 or API6500 tandem mass spectrometer (AB Sciex, Foster City, CA) interfaced to an ACQUITY UPLC system (Waters, Milford, MA) or Shimadzu. Analyses were performed using an ACQUITY UPLC BEH C18 (1.7 μm 2.1 × 50 mm) or Shim-pack Velox Biphenyl (1.8 μm 2.1*50mm) for chromatographic separations at a column temperature of 50°C. Mass spectrometric detection of the analyte was accomplished using the ESI+ ionization mode. The transitions of the protonated precursor ions to the selected product ions were as follows: Compound A (393.2 → 320.1 amu) or (393.05 → 320.20 amu), and the ISTD, verapamil (455.2 → 164.9 amu) or dexamethasone (393.14→373.10 amu). Data Analysis The pharmacokinetic parameters of Compound A were calculated by a non-compartmental analysis using WinNonlin Version 6.3 (Pharsight, Mountain View, CA). Maximum plasma concentrations (Cmax) and their time of occurrence (Tmax) were both obtained directly from the measured data. Microsoft Office Excel 2012 (Redmond, WA) was used for calculation of mean and standard deviation. Results Average PK parameters of Compound A are presented inTable 45 and Table 46 below and graphically in FIG 19. A pharmacodynamic (PD) measure is graphically shown in FIG 20. Plasma concentration curves for individual monkeys dosed with tablets and capsules are shown in FIGS. 21A-E. Compound A exposure data for the capsule and tablet formulations based on AUC(0- last) / Dose was compared with the oral dose solution and / or suspensions up to 5 mg / kg. Exposures using either the Compound A capsule or tablet form was similar to that using the oral solutions / suspensions. After a bolus push of an IV dose at 0.5 mg / kg in fasted monkeys, Compound A showed a plasma clearance of 1.2 mL / min / kg. The corresponding value for the estimated apparent volume of distribution at steady-state (Vdss) was approximately 0.7 L / kg, which is slightly larger than that PAT059980-WO-PCT of total body water. The average AUC0-last value was 6407 ng•hr / mL. The plasma clearance and apparent volume of distribution values resulted in a plasma elimination half-life of 8.2 hr (Table 45). Compound A, dosed PO at 1 mg / kg in a fasted state, was rapidly absorbed resulting in an average maximum plasma concentration (Cmax) of 799 ng / mL at an apparent Tmax of 3.0 hr. The average systemic exposure (AUC0-last) was 7386 ng•hr / mL which gave rise to an absolute oral bioavailability value of 58% (Table 46). When investigating the dose linearity of Compound A in free form dosed orally from 0.02 to 300 mg / kg, Compound A was found to be variable across the dose range and less than proportional. In addition, there does not appear to be any differences in exposure of Compound A between the two sexes (data not shown). VAV1 degradation was also measured after a 1 mg / kg Compound A PO dose (FIG.20). Compound A reduced VAV1 protein levels by 6 hrs post dose and those levels were maintained to 24 hrs. Table 45: Average IV pharmacokinetic parameters for Compound A in male and female cynomolgus monkeys N (M / F) 1 / 1 Dose (mg / kg) 0.5 AUC(0-last) (ng•hr / mL) 6407 AUC(0-last) / D 12813 Clp (mL / min / kg) 1.2 Vdss (L / kg) 0.7 T½ (hr), calculated 8.2 from 6 to 24 hrs Tlast (hr) 24 MRT0-last (hr) 7.3 Table 46: Average PO pharmacokinetic parameters for Compound A in male and female cynomolgus monkeys Formulatio Capsul Table Table L33 L33 L33 Capsule Capsule n e t t 0.02 1.0 300 0.5 10 Dose mg / k mg / k 0.1 mg 0.5 mg 1.0 mg mg / kg mg mg g g PAT059980-WO-PCT N (M / F) 1 / 1 1 / 1 1 / 1 3M 3M 3M 3M 3M Fasted / Non Faste Faste Faste Faste Fasted Fasted Fasted Fasted -fasted d d d d 52976 AUC(0-last)13380 2556 ± 1786 257 7386 439±58 5962±1864 ± (ng•hr / mL) 8 280 ± 244 7121 9896 14909 AUC(0- 14484±166 13799 21025±194 12850 7386 446 ± ± last) / Dose 5 ± 810 7 1374 3786 Cmax 23.4±7.5 132 ± 386±236 125 ± 3810 18.8 799 9070 (ng / mL) 35 37 ± 278 3.3±1.2 6.7 ± 4 Tmax(hr) 4.0 3.0 4 3 ± 2 3 ± 1 2.3 Tlast (hr) 72 24 24 48 48 48 48 48 F(%)* 100 58 3 100 100 100 77 100 *IV data from Table 45 used for calculation of absolute oral bioavailability Conclusion Both capsule and tablet forms of Compound A yield similar exposures as measured by AUC as the oral solution / suspension formulations. Compound A exhibited an average Clp value about 1 / 20th that of hepatic blood flow (1.2 mL / min / kg), an average AUC0-last value of 6407 ng•hr / mL and an average Vdss value of 0.7 L / kg, yielding an average plasma elimination t1 / 2 of 8.2 hr following a single IV dose of 0.5 mg / kg. Compound A, dosed PO, once, at 0.02 to 30 mg / kg, showed an increase in exposure and was saturating at doses above 100 mg / kg. The subsequently average absolute oral bioavailability across doses ranged from 3-100%. Example 5.4: In vivo comparison of liquid formulations L31-L34 Liquid formulations L31-L34 were administered orally to Cynomolgus monkeys and rats at 30 mg / kg. Pharmacokinetic data are shown in Table 47 and Table 48 and AUC data for Cynomolgus monkeys is graphically depicted in FIG.22. PAT059980-WO-PCT Table 47: Pharmacokinetic results of oral administration of Compound A to Cynomolgus monkeys Dose T1 / 2 Tmax Cmax AUC0-24 Formulation Sex (mg / kg) (hr) (hr) (ng / mL) (hr*ng / mL) 0.5% CMC and 0.1% Tween female 30 9.54 4 2600 30000 80 in DI water(w / v / v) male 30 10.1 4 1600 28000 Mean 9.821 4 2100 29000 10% PEG400 / 90% (10% female 30 8.76 2 11000 140000 captisol in DI water(w / v)) male 30 10.37 4 8300 130000 Mean 9.566 3 9400 140000 50 / 50 PEG400 / 20% captisol female 30 2 6000 90000 in water male 30 4 7000 95000 Mean 3 6500 93000 Table 48: Pharmacokinetic results of oral administration of Compound A to rats Dose Formulation Sex T1 / 2 (hr) Tmax (hr) Cmax (ng / mL) (mg / kg) 0.5% CMC and 0.1% Tween female 30 8 5784 85411 80 in DI water(w / v / v) male 30 1 7155 27723 female 30 1 14791 161818 10% captisol in water male 30 0.5 14053 27078 50 / 50 PEG400 / 20% captisol female 30 2 17456 134895 in water male 30 1 6965 31341 EQUIVALENTS Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments described herein. Such equivalents are intended to be encompassed in the scope of the following claims.

Claims

PAT059980-WO-PCT CLAIMS 1. A dosage form comprising Compound A, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, wherein the amount of Compound A is between 0.01 mg and 100 mg, and wherein Compound A is a compound of the following formula:.

2. The dosage form of claim 1, wherein the amount of Compound A is: (i) between 0.01 mg and 20 mg; (ii) between 0.01 mg and 10 mg; (iii) between 0.01 mg and 5 mg; (iv) between 0.01 mg and 2 mg; (v) between 0.01 mg and 1 mg; (vi) between 0.01 mg and 0.5 mg; (vii) between 0.01 mg and 0.2 mg; (viii) between 0.01 mg and 0.1 mg; or (ix) between 0.01 mg and 0.05 mg.

3. The dosage form of claim 1, wherein the amount of Compound A is: (i) between 0.05 mg and 20 mg; (ii) between 0.05 mg and 10 mg; (iii) between 0.05 mg and 5 mg; (iv) between 0.05 mg and 2 mg; (v) between 0.05 mg and 1 mg; (vi) between 0.05 mg and 0.5 mg; (vii) between 0.05 mg and 0.2 mg; or (viii) between 0.05 mg and 0.1 mg.

4. The dosage form of claim 1, wherein the amount of Compound A is: (i) between 0.1 mg and 20 mg; (ii) between 0.1 mg and 10 mg; (iii) between 0.1 mg and 5 mg; (iv) between 0.1 mg and 2 mg; (v) between 0.1 mg and 1 mg;PAT059980-WO-PCT (vi) between 0.1 mg and 0.5 mg; or (vii) between 0.1 mg and 0.2 mg.

5. The dosage form of claim 1, wherein the amount of Compound A is: (i) between 0.5 mg and 20 mg; (ii) between 0.5 mg and 10 mg; (iii) between 0.5 mg and 5 mg; (iv) between 0.5 mg and 2 mg; or (v) between 0.5 mg and 1 mg.

6. The dosage form of claim 1, wherein the amount of Compound A is: (i) 0.1 mg; (ii) 0.5 mg; (iii) 2 mg; or (iv) 10 mg.

7. The dosage form of any one of claims 1-6, wherein the dosage form comprises: (i) less than 50% by weight of Compound A; (ii) less than 40% by weight of Compound A; (iii) less than 30% by weight of Compound A; (iv) less than 20% by weight of Compound A; (v) less than 10% by weight of Compound A; or (vi) less than 5% by weight of Compound A.

8. The dosage form of any one of claims 1-6, wherein the dosage form comprises: (i) between 0.05 and 50% by weight of Compound A; (ii) between 0.05 and 40% by weight of Compound A; (iii) between 0.05 and 30% by weight of Compound A; (iv) between 0.05 and 20% by weight of Compound A; (v) between 0.05 and 10% by weight of Compound A; or (vi) between 0.05 and 5% by weight of Compound A.

9. The dosage form of any one of claims 1-6, wherein the dosage form comprises: (i) between 0.1 and 50% by weight of Compound A; (ii) between 0.1 and 40% by weight of Compound A; (iii) between 0.1 and 30% by weight of Compound A; (iv) between 0.1 and 20% by weight of Compound A;PAT059980-WO-PCT (v) between 0.1 and 10% by weight of Compound A; or (vi) between 0.1 and 5% by weight of Compound A.

10. The dosage form of any one of claims 1-6, wherein the dosage form comprises: (i) 0.1% by weight of Compound A; (ii) 0.5% by weight of Compound A; (iii) 2% by weight of Compound A; or (iv) 10% by weight of Compound A.

11. The dosage form of any one of claims 1-10, wherein the total weight of the dosage form is: (i) between 5 and 1000 mg; (ii) between 5 and 500 mg; (iii) between 5 and 400 mg; (iv) between 5 and 300 mg; (v) between 5 and 200 mg; (vi) between 5 and 100 mg; (vii) between 5 and 50 mg; or (viii) between 5 and 25 mg.

12. The dosage form of any one of claims 1-11, wherein the total weight of the dosage form is 100 mg.

13. The dosage form of any one of claims 1-12, wherein the dosage form comprises: (i) two or more pharmaceutically acceptable excipients; (ii) three or more pharmaceutically acceptable excipients; (iii) four or more pharmaceutically acceptable excipients; or (iv) five or more pharmaceutically acceptable excipients.

14. The dosage form of any one of claims 1-13, wherein the dosage form is for oral administration.

15. The dosage form of any one of claims 1-14, wherein the dosage form is a solid dosage form.

16. The dosage form of claim 15, wherein the solid dosage form is a tablet or a capsule.

17. The dosage form of claim 16, wherein the solid dosage form is a tablet.PAT059980-WO-PCT 18. The dosage form of claim 16 or claim 17, wherein the tablet comprises a solid dispersion comprising Compound A and a polymer.

19. The dosage form of claim 18, wherein the polymer is selected from the group consisting of: enteric polymers (such as methacrylate polymers, hydroxypropyl methyl cellulose phthalate (HPMCP), and cellulose acetyate phthalate (CAP)), hydrophilic polymers (such as starch, sodium carboxymethyl cellulose, sodium alginate, polyethylene glycol (PEG), polyvinyl pyrollidone (PVP), hydroxy propyl methyl cellulose (HPMC), HPMC derivatives, polyvinyl alcohol (PVA), β-cyclodextrin, mannitol, chitosan, and carrageenan), and amphiphilic polymers (such as polyethylene oxides (PEO) / polypropylene glycol (PPG) copolymers, PEG-modified starches, vinyl acetate / vinylpyrrolidone random copolymers, polyacrylic acid, and polyacrylates), and a combination thereof.

20. The dosage form of claim 19, wherein the polymer is a hydroxypropylmethylcellulose (HPMC) derivative.

21. The dosage form of claim 20, wherein the polymer is hydroxypropylmethylcellulose acetate succinate (HPMCAS), such as HPMCAS MG and / or HPMCAS HG.

22. The dosage form of claim 20, wherein the polymer is HPMCAS HG.

23. The dosage form of any one of claims 18-22, wherein the solid dispersion comprises Compound A and the polymer at a ratio of between 1:5 and 1:

1.

24. The dosage form of any one of claims 18-23, wherein the solid dispersion comprises Compound A and the polymer at a ratio of 1:3 or 1:

2.

25. The dosage form of any one of claims 18-24, wherein the solid dispersion comprises Compound A and the polymer at a ratio of 1:

3.

26. The dosage form of any one of claims 18-25, wherein the solid dispersion makes up less than 50% by weight of the tablet.

27. The dosage form of any one of claims 18-26, wherein the solid dispersion makes up between 0.1% to 50% by weight of the tablet.

28. The dosage form of any one of claims 18-27, wherein the solid dispersion makes up 0.4%, 2%, 8% or 40% by weight of the tablet.PAT059980-WO-PCT 29. The dosage form of any one of claims 17-28, wherein the tablet further comprises one or more of the following: (i) a filler; (ii) a glidant; (iii) a disintegrant; and (iv) a lubricant.

30. The dosage form of claim 29, wherein the tablet comprises each of the following: (i) a filler; (ii) a glidant; (iii) a disintegrant; and (iv) a lubricant.

31. The dosage form of claim 29 or claim 30, wherein the filler is selected from the group consisting of: celluloses, modified celluloses (such as sodium carboxymethyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropylcellulose, cellulose acetate, microcrystalline cellulose, and silicified microcrystalline cellulose), calcium phosphates (such as dibasic calcium phosphate), starches (such as corn starch, and potato starch), sugars (such as mannitol, sorbitol, lactose, and sucrose), and combinations thereof.

32. The dosage form of claim 31, wherein the filler is microcrystalline cellulose.

33. The dosage form of any one of claims 29-32, wherein the filler makes up: (i) less than 98% by weight of the tablet; (ii) less than 95% by weight of the tablet; (iii) between 10 and 98% by weight of the tablet; (iv) between 10 and 95% by weight of the tablet; (v) between 20 and 98% by weight of the tablet; (vi) between 20 and 95% by weight of the tablet; (vii) between 30 and 98% by weight of the tablet; (viii) between 30 and 95% by weight of the tablet; (ix) between 40 and 98% by weight of the tablet; (x) between 40 and 95% by weight of the tablet; (xi) between 50 and 98% by weight of the tablet; or (xii) between 50 and 95% by weight of the tablet.PAT059980-WO-PCT 34. The dosage form of any one of claims 29-33, wherein the glidant is selected from the group consisting of: fumed silica, talc, and a combination thereof.

35. The dosage form of any one of claims 29-34, wherein the glidant is fumed silica.

36. The dosage form of any one of claims 29-35, wherein the glidant makes up: (i) less than 10% by weight of the tablet; (ii) less than 5% by weight of the tablet; (iii) less than 2% by weight of the tablet; or (iv) 1% by weight of the tablet.

37. The dosage form of any one of claims 29-36, wherein the disintegrant is selected from the group consisting of: starches (such as corn starch or potato starch), modified starches (such as pregelatinized starch, sodium starch glycolate, and starch 1500), cellulose derivatives (such as microcrystalline cellulose, croscarmellose sodium, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose), natural gums (such as guar gum, xanthan gum, and locust bean gum), ion exchange resins (such as polacrilin potassium and Amberlite IRP69), calcium silicates (dicalcium phosphate and tricalcium phosphate), sodium alginate, cross- linked polyvinylpyrrolidone, chitosan, and combinations thereof.

38. The dosage form of any one of claims 29-37, wherein the disintegrant is croscarmellose sodium.

39. The dosage form of any one of claims 29-38, wherein the disintegrant makes up: (i) less than 10% by weight of the tablet; (ii) less than 5% by weight of the tablet; (iii) between 1 and 5% by weight of the tablet; (iv) between 2 and 4% by weight of the tablet; or (v) 3% by weight of the tablet.

40. The dosage form of any one of claims 29-39, wherein the lubricant is selected from the group consisting of: magnesium stearate, stearic acid, calcium stearate, sodium stearyl fumarate, polyethylene glycols, beeswax, hydrogenated vegetable oil, and combinations thereof.

41. The dosage form of any one of claims 29-40, wherein the lubricant is magnesium stearate.

42. The dosage form of any one of claims 29-41, wherein the lubricant makes up: (i) less than 10% by weight of the tablet;PAT059980-WO-PCT (ii) less than 5% by weight of the tablet; (iii) less than 2% by weight of the tablet; or (iv) 1% by weight of the tablet.

43. The dosage form of any one of claims 17-42, wherein the tablet has one of the following compositions: (a) Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 0.4 ± 0.04 Microcrystalline cellulose 94.6 ± 9.46 Fumed silica 1 ± 0.1 Croscarmellose sodium 3 ± 0.3 Magnesium stearate 1 ± 0.1 Total 100 Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 2 ± 0.2 Microcrystalline cellulose 93 ± 9.3 Fumed silica 1 ± 0.1 Croscarmellose sodium 3 ± 0.3 Magnesium stearate 1 ± 0.1 Total 100 Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 8 ± 0.8 Microcrystalline cellulose 87 ± 8.7 Fumed silica 1 ± 0.1 Croscarmellose sodium 3 ± 0.3 Magnesium stearate 1 ± 0.1 Total 100PAT059980-WO-PCT (d) Component % by weight of tablet Compound A solid dispersion: [1:3] Compound A:HPMCAS HG 40 ± 4 Microcrystalline cellulose 55 ± 5.5 Intra-granular Fumed silica 1 ± 0.1 fraction (IG) Croscarmellose sodium 1.5 ± 0.15 Magnesium stearate 0.5 ± 0.05 IG Total 98 ± 9.8 Croscarmellose sodium 1.5 ± 0.15 Extra-granular fraction (EG) Magnesium stearate 0.5 ± 0.05 EG Total 100 44. The dosage form of any one of claims 17-43(a), wherein the tablet comprises 0.1 mg of Compound A.

45. The dosage form of any one of claims 17-42 or 43(b), wherein the tablet comprises 0.5 mg of Compound A.

46. The dosage form of any one of claims 17-42 or 43(c), wherein the tablet comprises 2 mg of Compound A.

47. The dosage form of claim any one of claims 17-42 or 43(d), wherein the tablet comprises 10 mg of Compound A.

48. The dosage form of claim 16, wherein the solid dosage form is a capsule.

49. The dosage form of claim 16 or claim 48, wherein the capsule is a softgel.

50. The dosage form of claim 49, wherein the softgel fill comprises a solubiliser.

51. The dosage form of claim 50, wherein the solubiliser is selected from the group consisting of: docusate sodium, glyceryl monostearate, monoglycerides, diglycerides, medium-chain triglycerides, poloxamers, polyoxyethylenesorbitan fatty acid esters, polyoxyl 40 hydrogenated castor oil, polyoxylglycerides, sodium lauryl sulfate, sucrose esters, propylene glycol alginate, cyclodextrins, PEGs, and combinations thereof.

52. The dosage form of claim 50, wherein the solubiliser is selected from the group consisting of: benzyl alcohol, polyoxyl 35 castor oil, glyceryl monolinoleate, tocofersolan, propylenePAT059980-WO-PCT glycol monocaprylate, caprylocaproyl polyoxyl-8 glycerides, glyceryl mono and dicaprylocaprate, lecithin, and combinations thereof.

53. The dosage form of claim 50, wherein the solubiliser comprises benzyl alcohol.

54. The dosage form of claim 50, wherein the solubiliser comprises benzyl alcohol, polyoxyl 35 castor oil, and glyceryl monolinoleate.

55. The dosage form of claim 50, wherein the solubiliser comprises benzyl alcohol, polyoxyl 35 castor oil, glyceryl monolinoleate, and lecithin.

56. The dosage form of any one of claims 50-55, wherein the solubiliser makes up: (i) greater than 50% by weight of the softgel fill; (ii) greater than 60% by weight of the softgel fill; (iii) greater than 70% by weight of the softgel fill; (iv) greater than 80% by weight of the softgel fill; (v) greater than 90% by weight of the softgel fill; (vi) greater than 95% by weight of the softgel fill; (vii) greater than 98% by weight of the softgel fill; (viii) greater than 99% by weight of the softgel fill; or (ix) greater than 99.5% by weight of the softgel fill.

57. The dosage form of any one of claims 49-56, wherein the softgel fill comprises an antioxidant.

58. The dosage form of claim 57, wherein the antioxidant is selected from the group consisting of: ascorbic acid and derivatives thereof, citric acid and derivatives thereof, sodium metabisulfate, sodium thiosulfate, cysteine, tryptophan, methionine, butylated hydroxytoluene, propyl, octyl, dodecyl esters of gallic acid, and combinations thereof.

59. The dosage form of claim 57, wherein the antioxidant is selected from the group consisting of: ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, and combinations thereof.

60. The dosage form of claim 57, wherein the antioxidant comprises ascorbyl palmitate.

61. The dosage form of any one of claims 57-60, wherein the antioxidant makes up: (i) less than 5% by weight of the softgel fill;PAT059980-WO-PCT (ii) less than 3% by weight of the softgel fill; (iii) less than 2% by weight of the softgel fill; (iv) less than 1% by weight of the softgel fill; (v) less than 0.5% by weight of the softgel fill; (vi) less than 0.3% by weight of the softgel fill; (vii) between 0.5 and 1.5% by weight of the softgel fill; or (viii) between 1 and 2% by weight of the softgel fill.

62. The dosage form of any one of claims 49-61, wherein the softgel fill has one of the following compositions: (a) Component w / w% Compound A 0.1 ± 0.01 Benzyl alcohol 10 ± 1 Polyoxyl 35 castor oil 45 ± 4.5 Glyceryl monolinoleate 44.3 ± 4.43 Butylated hydroxyanisole 0.05 ± 0.005 Butylated hydroxytoluene 0.05 ± 0.005 Ascorbyl palmitate 0.5 ± 0.05 (b) Component w / w% Compound A 0.01 ± 0.001 Glyceryl monolinoleate 40 ± 4 Polyoxyl 35 castor oil 45.19 ± 4.519 Benzyl alcohol 10 ± 1 Butylated hydroxytoluene 0.05 ± 0.005 Butylated hydroxyanisole 0.05 ± 0.005 Lecithin 4.69 ± 0.469 Simethicone 0.01 ± 0.001 (c) Component w / w% Compound A 0.1 ± 0.01 Glyceryl monolinoleate 43.8 ± 4.38PAT059980-WO-PCT Polyoxyl 35 castor oil 45 ± 4.5 Benzyl alcohol 10 ± 1 Butylated hydroxytoluene 0.05 ± 0.005 Butylated hydroxyanisole 0.05 ± 0.005 Ascorbyl palmitate 1 ± 0.1 (d) Component w / w% Compound A 0.1 ± 0.01 Glyceryl monolinoleate 40 ± 4 Polyoxyl 35 castor oil 45 ± 4.5 Benzyl alcohol 10 ± 1 Lecithin 4.9 ± 0.49 (e) Component w / w% Compound A 0.2 ± 0.02 Glyceryl monolinoleate 40 ± 4 Polyoxyl 35 castor oil 45 ± 4.5 Benzyl alcohol 10 ± 1 Butylated hydroxytoluene 0.05 ± 0.005 Butylated hydroxyanisole 0.05 ± 0.005 Lecithin 4.69 ± 0.469 Simethicone 0.01 ± 0.001 63. The dosage form of any one of claims 49-62, wherein the softgel fill comprises 0.1mg Compound A.

64. The dosage form of any one of claims 49-62, wherein the softgel fill comprises 0.5mg Compound A.

65. The dosage form of any one of claims 49-62, wherein the softgel fill comprises 1mg Compound A.PAT059980-WO-PCT 66. The dosage form of any one of claims 49-62, wherein the softgel fill comprises 2mg Compound A.

67. The dosage form of any one of claims 1-14, wherein the dosage form is a liquid dosage form comprising a vehicle.

68. The dosage form of claim 67, wherein the liquid dosage form comprises a polymer.

69. The dosage form of claim 68, wherein the polymer is selected from the group consisting of: a β-cyclodextrin, carboxymethyl cellulose, polyethylene glycol, and combinations thereof.

70. The dosage form of claim 69, wherein the β-cyclodextrin is a hydroxy propyl modified β- cyclodextrin.

71. The dosage form of any one of claims 67-70, wherein the vehicle is water.

72. The dosage form of any one of claims 1-71, wherein Compound A is the following enantiomer:.

73. The dosage form of any one of claims 1-71, wherein Compound A is the following enantiomer:.

74. The dosage form of any one of claims 1-71, wherein Compound A exists in a mixture of the following enantiomers:, .

75. The dosage form of claim 74, wherein Compound A exists in a racemic mixture.PAT059980-WO-PCT 76. A method of treating a disorder in a patient in need thereof, comprising the step of administering to the patient the dosage form of any one of claims 1-75, wherein the disorder is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, psoriatic arthritis, systemic lupus, erythematosus, Hashimoto’s thyroiditis, myasthenia gravis, diabetes type I or II, and the disorders associated therewith, vasculitis, pernicious anemia, Sjoegren syndrome, uveitis, psoriasis, Graves ophthalmopathy, alopecia areata and others, allergic diseases (e.g., allergic asthma, atopic dermatitis, allergic rhinitis / conjunctivitis, allergic contact dermatitis), inflammatory diseases optionally with underlying aberrant reactions (e.g., inflammatory bowel disease, Crohn’s disease or ulcerative colitis, intrinsic asthma, inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury), atherosclerosis, osteoarthritis, irritant contact dermatitis and further eczematous dermatitis, seborrheic dermatitis, cutaneous manifestations of immunologically-mediated disorders, inflammatory eye disease, keratoconjunctivitis, myocarditis or hepatitis.

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