WO2024148269A2 - Oral dosage forms and oral dosing regimens for treatment of complement mediated diseases - Google Patents

Abstract

Disclosed is Compound A and pharmaceutically acceptable salts and prodrugs thereof, which are inhibitors of the complement system. Also provided are oral dosage forms comprising such a compound, salt, or prodrug. Also disclosed are methods of using the compounds, salts, and prodrugs, and oral dosage forms thereof, in the treatment or prevention of a disease or condition characterized by aberrant complement system activity (e.g., IgA nephropathy, complement 3 glomerulopathy, and paroxysmal nocturnal hemoglobinuria).

Description

BPX-05425 ORAL DOSAGE FORMS AND ORAL DOSING REGIMENS FOR TREATMENT OF COMPLEMENT MEDIATED DISEASES RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63/437,469, filed January 6, 2023; U.S. Provisional Patent Application No. 63/525,265, filed July 6, 2023; and U.S. Provisional Patent Application No.63/546,957, filed November 2, 2023. FIELD OF THE INVENTION The invention relates to oral dosage forms and oral dosing regimens for Compound A [2-(2-((7-(2-(aminomethyl)pyridin-4-yl)-2-methylbenzofuran-5-yl)methoxy)phenyl)acetic acid]. Such oral dosing regimens may be used to treat a disease or condition related to aberrant complement system activity. BACKGROUND OF THE INVENTION Complement activation is an innate defense mechanism that, when uncontrolled, leads to inflammation and local tissue damage. The complement system consists of 3 linked pathways: the classical pathway (CP), lectin pathway (LP), and alternative pathway (AP). Dysregulation of AP activity by germ line or somatic genetic mutations of complement regulatory proteins or enzymes, neutralizing antibodies to complement regulatory proteins, or stabilizing antibodies to complement enzyme complexes predisposes individuals to diverse disorders, including, but not limited to, IgA nephropathy, complement 3 glomerulopathy (C3G), paroxysmal nocturnal hemoglobinuria (PNH), dry age-related macular degeneration, and atypical hemolytic uremic syndrome (aHUS). The complement system can be activated by each of the three complement pathways (i.e., the CP, the LP, or the AP) and subsequently amplified by the AP amplification loop. Activation of the AP amplification loop by any of the 3 pathways leads to opsonization with C3b, release of the anaphylatoxins C3a and C5a, and assembly of the terminal membrane attack complex (MAC) (also known as C5b-9) on the target surface, resulting in cell lysis. Factor D is the rate-limiting enzyme of the AP and the AP amplification loop. In addition, Factor D is required for the AP amplification loop following generation of C3b by the AP, LP, or CP As an example, C3G is a group of rare kidney diseases in which dysregulation of the complement system results in prominent C3 fragment deposition within the glomerulus, with BPX-05425 an estimated incidence between 0.2 to 3 cases per 1 million people in the United States (US) and Europe. The resultant glomerular damage often leads to end-stage renal disease that recurs after renal transplantation. C3G is typically categorized into two subsets: 1) dense deposit disease (DDD), which is diagnosed based on linear, hyperosmiophilic electron-dense deposits occupying the middle layer of the glomerular basement membrane; and 2) C3 glomerulonephritis (C3GN) which refers to those cases of C3G in which dense deposits do not have the characteristics indicative of DDD. Abnormal glomerular accumulation of C3 fragments occurs due to uncontrolled C3b production via the alternative pathway (AP) of complement. In some patients with C3G, acquired or genetic defects in AP regulation can be demonstrated. In others, autoantibodies to complement proteins and complexes that stabilize C3 convertase lead to C3 consumption and deposition of C3 fragments in the kidney. There are no approved therapies specific for C3G. Current standard of care focuses on supportive care that includes blood pressure control and inhibition of the renin-angiotensin system to minimize proteinuria. PNH is a chronic, non-malignant, disorder of the hematopoietic stem cells and is associated with significant morbidity and mortality. The overall survival at 10 years after diagnosis with PNH has been estimated to be 65% to 77.6%. PNH is characterized by episodes of intravascular hemolysis, chronic hemolytic anemia, bone marrow failure, and thrombosis. Thrombosis is the leading cause of death in PNH and, while it is relatively rare as a presenting symptom, it occurs in up to 40% of patients during the course of the disease. PNH is caused by a somatic mutation in the phosphatidylinositol glycan anchor biosynthesis class A (PIG-A) gene in hematopoietic stem cells, resulting in the deficiency of glycosylphosphatidylinositol-anchored proteins including the complement regulators CD55 and CD59. CD55 regulates the formation and stability of the C3 and C5 convertases, whereas CD59 blocks formation of the MAC. Due to the absence of both regulators (CD55 and CD59) from PNH red blood cell (RBC) membranes, physiologic AP "tickover" results in membrane- bound active C3b, unregulated AP amplification, formation of functional MAC, and C3 fragment opsonization. AP activation on PNH RBC membranes manifests clinically with chronic hemolytic anemia, with recurrent exacerbations, anemia, smooth muscle cell dystonia, and a high risk of thrombosis. Eculizumab and ravulizumab, each monoclonal antibodies against C5, are the only therapeutic agents approved in the United States and the European Union for the treatment of patients with PNH. The blockade of the terminal complement pathway by these antibodies BPX-05425 abrogates intravascular hemolysis in almost all patients suffering from PNH. However, anemia, hyperbilirubinemia, and reticulocytosis persist in essentially all treated patients, with only approximately half achieving transfusion independence after treatment due to continued opsonization by C3b, rendering the RBCs susceptible to extravascular hemolysis. Given the chronic, progressive nature of complement mediated diseases and the shortcomings of currently existing therapies, there is a need for new effective therapies that target the underlying pathophysiology of complement mediated diseases, particularly those in which factor D plays a role. SUMMARY OF THE INVENTION In certain aspects, the invention provides an oral dosage form comprising Compound A [2-(2-((7-(2-(aminomethyl)pyridin-4-yl)-2-methylbenzofuran-5-yl)methoxy)phenyl)acetic acid] or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier. In certain embodiments, the oral dosage form is a capsule.

Compound A In further aspects, the invention provides methods of treating or preventing a disease or condition characterized by aberrant complement system activity, comprising orally administering to a patient in need thereof a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1 shows plasma concentration of Compound A (ng/mL) vs time profiles following oral administration of single ascending doses of Compound A (1 mg to 200 mg) in healthy subjects. For ease of visualization, error bars are drawn to show only the positive value. FIG.2 shows plasma concentration of Compound A (ng/mL) vs time profiles following oral administration of a single dose of Compound A (80 mg) in healthy subjects in the fasted and fed state. FIG.3 shows plasma concentration of Compound A (ng/mL) vs time profiles following oral administration of multiple ascending doses of Compound A (20 mg QD for 7 days and 40, 80 and 160 mg QD for 14 days) in healthy subjects. BPX-05425 FIG.4 shows AP Wieslab activity vs median interquartile (IQR) time profiles following oral administration of single ascending doses of Compound A (1 mg to 200 mg) in healthy subjects. FIG. 5 shows AP Wieslab dose response following oral administration of single ascending doses of Compound A (1 mg to 110 mg) in healthy subjects at 12 and 24 hours post- dose. FIG. 6 shows AP Wieslab activity vs time profiles following oral administration of multiple ascending doses of Compound A (20 mg QD for 7 days and 40 mg and 80 mg QD for 14 days) in healthy subjects on day 1 (first dose) and day 7 or 14 (last dose). FIG.7 shows plasma concentration of Compound A (ng/mL) vs time profiles following oral administration of a single dose of Compound A (40 mg) in the dihydrochloride form of the free base form in healthy subjects. FIG.8 shows the geometric least squares mean ratios and 90% confidence interval for PK parameters between Compound A in the dihydrochloride form and the free base form following single oral administration of Compound A (40 mg) in healthy subjects. FIG. 9 shows shows AP Wieslab dose response following oral administration of 160 mg QD doses of Compound A in healthy subjects a up to 24 hours post-dose on Day 1 and day of last dose, Day 14. FIG. 10 shows shows AP Wieslab dose response following oral administration of placebo, 20, 40, 80 and 160 mg QD doses of Compound A in healthy subjects 24 hours post- last dose on Day 14, with n=10 active and N=2 placebo per cohort. FIG.11 is a schematic illustrating a Phase 1b study of Compound A for the treatment of PNH. DETAILED DESCRIPTION Inhibitors of the complement system are useful in therapeutic methods and compositions suitable for use in treating disorders of the immune, renal, cardiovascular, and neurological systems. Compound A is a potent, selective, and orally bioavailable small- molecule inhibitor of human factor D. In preclinical in vitro studies, Compound A suppressed the AP-mediated hemolysis of erythrocytes from patients with PNH and blocked AP-mediated C3 fragment deposition on PNH erythrocytes at low nanomolar drug concentrations. Oral dosing of Compound A achieved >95% suppression of AP mediated hemolysis in preclinical in vivo studies of complement activity in monkeys. Therefore, targeting proximal complement BPX-05425 inhibition by Factor D inhibition through administration of Compound A has the potential to prevent AP-mediated complement function in subjects. Definitions The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Generally, nomenclature used in connection with, and techniques of, chemistry, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, pharmacology, genetics and protein and nucleic acid chemistry, described herein, are those well-known and commonly used in the art. The methods and techniques of the present disclosure are generally performed, unless otherwise indicated, according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout this specification. See, e.g. “Principles of Neural Science”, McGraw-Hill Medical, New York, N.Y. (2000); Motulsky, “Intuitive Biostatistics”, Oxford University Press, Inc. (1995); Lodish et al., “Molecular Cell Biology, 4th ed.”, W. H. Freeman & Co., New York (2000); Griffiths et al., “Introduction to Genetic Analysis, 7th ed.”, W. H. Freeman & Co., N.Y. (1999); and Gilbert et al., “Developmental Biology, 6th ed.”, Sinauer Associates, Inc., Sunderland, MA (2000). Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. Chemistry terms used herein, unless otherwise defined herein, are used according to conventional usage in the art, as exemplified by “The McGraw-Hill Dictionary of Chemical Terms”, Parker S., Ed., McGraw-Hill, San Francisco, C.A. (1985). The term “pharmaceutically acceptable salt” as used herein includes salts derived from inorganic or organic acids including, for example, hydrochloric acid, hydrobromic, sulfuric, nitric, perchloric, phosphoric, formic, acetic, lactic, maleic, fumaric, succinic, tartaric, glycolic, salicylic, citric, methanesulfonic, benzenesulfonic, benzoic, malonic, trifluoroacetic, trichloroacetic, naphthalene-2-sulfonic, and other acids. Pharmaceutically acceptable salt forms can include forms wherein the ratio of molecules comprising the salt is not 1:1. For example, the salt may comprise more than one inorganic or organic acid molecule per molecule of base, such as two hydrochloric acid molecules per molecule of a Compound A. As another BPX-05425 example, the salt may comprise less than one inorganic or organic acid molecule per molecule of base, such as two molecules of a Compound A per molecule of tartaric acid. The terms “carrier” and “pharmaceutically acceptable carrier” as used herein refer to a diluent, adjuvant, excipient, or vehicle with which a Compound is administered or formulated for administration. Non-limiting examples of such pharmaceutically acceptable carriers include liquids, such as water, saline, and oils; and solids, such as gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like. In addition, auxiliary, stabilizing, thickening, lubricating, flavoring, and coloring agents may be used. Other examples of suitable pharmaceutical carriers are described in Remington’s Pharmaceutical Sciences by E.W. Martin. Any publications, patents, published patent applications, or other references referred to in this application are specifically incorporated by reference herein. In case of conflict, the present specification, including its specific definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. A “patient,” “subject,” or “individual” are used interchangeably and refer to a human. In certain embodiments, Compound A may be administered alone or conjointly administered with another therapeutic agent. The phrases “conjoint administration” and “administered conjointly” refer to any form of administration of two or more different therapeutic agents such that the second agent is administered while the previously administered therapeutic agent is still effective in the body (e.g., the two agents are simultaneously effective in the subject, which may include synergistic effects of the two agents). For example, the different therapeutic agents can be administered either in the same formulation or in a separate formulation, either concomitantly or sequentially. In certain embodiments, the different therapeutic agents can be administered within one hour, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, or a week of one another. Thus, a subject who receives such treatment can benefit from a combined effect of different therapeutic agents. In certain embodiments, conjoint administration of Compound A with one or more additional therapeutic agent(s) provides improved efficacy relative to each individual administration of Compound A and/or the one or more additional therapeutic agent(s). In certain such embodiments, the conjoint administration provides an additive effect, wherein an additive effect refers to the sum of each of the effects of individual administration of Compound A and the one or more additional therapeutic agent(s). The term “treating” includes prophylactic and/or therapeutic treatments. The term “prophylactic or therapeutic” treatment is art-recognized and includes administration to the BPX-05425 subject of one or more of the disclosed compositions. If it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the subject) then the treatment is prophylactic (i.e., it protects the subject against developing the unwanted condition), whereas if it is administered after manifestation of the unwanted condition, the treatment is therapeutic (i.e., it is intended to diminish, ameliorate, or stabilize the existing unwanted condition or side effects thereof). The term “prodrug” is intended to encompass Compounds which, under physiologic conditions, are converted into therapeutically active agents. A common method for making a prodrug is to include one or more selected moieties which are hydrolyzed under physiologic conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the host animal. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids) and esters or amides of phosphates and phosphonic acids are preferred prodrugs of the present invention. “Administering” or “administration of” Compound A, or a pharmaceutically acceptable salt or prodrug thereof, to a subject can be carried out using one of a variety of methods known to those skilled in the art. For example, Compound A are preferably administered orally. Administering can also be performed, for example, once, a plurality of times, and/or over one or more extended periods. Appropriate methods of administering a substance, a Compound or an agent to a subject will also depend, for example, on the age and/or the physical condition of the subject and the chemical and biological properties of the Compound or agent (e.g., solubility, digestibility, bioavailability, stability and toxicity). In some embodiments, a Compound or an agent is administered orally. In some embodiments, the orally administered Compound or agent is in an extended release or slow release formulation. An “effective amount” is an amount sufficient to effect beneficial or desired results. A “therapeutically effective amount” is one that achieves the desired therapeutic effect. This amount can be the same or different from a prophylactically effective amount, which is an amount necessary to protect against onset of disease or disease symptoms. A therapeutically effective amount can be administered in one or more administrations, applications or dosages. A therapeutically effective amount of a compound or composition depends on the compound or composition selected. The compound or compositions can be administered from one or more times per day to one or more times per week; including once every other day. The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous BPX-05425 treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of the compositions described herein can include a single treatment or a series of treatments. Oral Dosage Forms of Compound A The present invention provides oral dosage forms comprising Compound A [2-(2-((7- (2-(aminomethyl)pyridin-4-yl)-2-methylbenzofuran-5-yl)methoxy)phenyl)acetic acid], or pharmaceutically acceptable salts or prodrugs thereof, and a pharmaceutically acceptable carrier. In certain embodiments, the oral dosage form is a capsule.

Compound A The disclosed oral dosage forms may be used in methods of treating a disease or condition related to aberrant complement system activity. Synthetic methods, characterization data, and assay data for Compound A are disclosed in U.S. Provisional Patent Application No.62/654,108, filed April 6, 2018; International Patent Application No. PCT/US19/26054, filed April 5, 2019; and U.S. Patent Application No. 16/511,642, filed July 15, 2019. In certain embodiments, Compound A is administered as a pharmaceutically acceptable salt. In certain embodiments, Compound A is administered as a hydrochloride salt. In certain embodiments, Compound A is administered as a dihydrochloride salt. In certain embodiments, Compound A is administered as a free base. Pharmaceutical Compositions The invention provides a pharmaceutical composition comprising Compound A, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical composition further comprises an additional therapeutic agent useful in the treatment of a disease or condition characterized by aberrant complement system activity in addition to Compound A. Pharmaceutical compositions of the invention can be prepared by combining Compound A, or a pharmaceutically acceptable salt or prodrug thereof, with a BPX-05425 pharmaceutically acceptable carrier and, optionally, one or more additional pharmaceutically active agents. Methods of Use Compound A, or a pharmaceutically acceptable salt or prodrug thereof, are useful for treating or preventing a disease or condition characterized by aberrant complement system activity. The present invention provides Compound A, or a pharmaceutically acceptable salt or prodrug thereof, for use in treating or preventing a disease or condition characterized by aberrant complement system activity. In certain aspects, the invention provides Compound A, or a pharmaceutically acceptable salt or prodrug thereof, for use as a medicament. In certain aspects, the invention provides for the use of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, in treating or preventing a disease or condition characterized by aberrant complement system activity. In certain aspects, the invention provides methods of treating or preventing a disease or condition characterized by aberrant complement system activity. The method includes the step of orally administering to a subject in need thereof a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, thereby treating or preventing the disease or condition characterized by aberrant complement system activity. By reducing complement system activity in the subject, the disease or condition characterized by aberrant complement system activity is treated. Alternatively, in certain aspects, the invention provides the use of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, for the manufacture of a medicament for use in treatment of a disease or condition characterized by aberrant complement system activity, wherein the medicament is formulated for oral administration. As used herein, a “disease or condition characterized by aberrant complement system activity” refers to any disease or condition in which it is desirable to reduce complement system activity. For example, it may be desirable to reduce complement system activity in the setting of inappropriate activation or hyperactivation of the complement system. In certain embodiments, the disease or condition characterized by aberrant complement system activity is complement 3 glomerulopathy (C3G), dense-deposit disease, C3 glomerulonephritis (C3GN), paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, myasthenia gravis, neuromyelitis optica, membranoproliferative glomerulonephritis, cold agglutinin disease, or catastrophic antiphospholipid syndrome. BPX-05425 In other embodiments, the disease or condition characterized by aberrant complement system activity is anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), warm autoimmune hemolytic anemia, IgA nephropathy, IgA vasculitis, primary membranous neuropathy, focal segmental glomerulosclerosis, rhabdomylosis-induced acute kidney injury, lupus nephritis, IgA nephritis, myasthenia gravis, hematopoietic stem cell transplantation (HSCT) transplant associated thrombotic microangiopathy (TA-TMA) or thrombotic thrombocytopenic purpura. In certain embodiments, the disease or condition characterized by aberrant complement system activity is macular degeneration, age-related macular degeneration (AMD), wet AMD, dry AMD, macular edema, diabetic macular edema, choroidal neovascularization (CNV), uveitis, Behcet’s uveitis, proliferative diabetic retinopathy, non-proliferative diabetic retinopathy, glaucoma, hypertensive retinopathy, a corneal neovascularization disease, post- corneal transplant rejection, a corneal dystrophic disease, an autoimmune dry eye disease, Stevens-Johnson syndrome, Sjogren’s syndrome, an environmental dry eye disease, Fuchs’ endothelial dystrophy, retinal vein occlusion, or post-operative inflammation. In certain embodiments, the disease or condition characterized by aberrant complement system activity is Guillain–Barré syndrome variants, chronic inflammatory demyelinating polyneuropathy, genetic demyelinating neuropathy, IgM neuropathy, neuropathic pain, Lambert– Eaton myasthenic syndrome, dermatomyositis, or necrotizing autoimmune myositis. In certain embodiments, the disease or condition characterized by aberrant complement system activity is multiple sclerosis, neuromyelitis optica spectrum disorders, autoimmune encephalopathies, traumatic brain injury, amyotrophic lateral sclerosis, Huntington disease, and schizophrenia. In certain embodiments, the disease or condition characterized by aberrant complement system activity is IgA nephropathy. In certain embodiments, the disease or condition characterized by aberrant complement system activity is C3G. In certain embodiments, the disease or condition characterized by aberrant complement system activity is dense-deposit disease. In certain embodiments, the disease or condition characterized by aberrant complement system activity is C3GN. In certain embodiments, the disease or condition characterized by aberrant complement system activity is anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). BPX-05425 In certain embodiments, the disease or condition characterized by aberrant complement system activity is thrombotic thrombocytopenic purpura. In certain embodiments, the disease or condition characterized by aberrant complement system activity is atypical hemolytic uremic syndrome. In certain embodiments, the disease or condition characterized by aberrant complement system activity is PNH. In certain embodiments, the disease or condition characterized by aberrant complement system activity is dry AMD. In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, results in a change from baseline in 24-hour urinary protein excretion normalized to urine creatinine as measured by percentage change in urinary protein- to-creatinine ration (uPCR). In an aspect of this embodiment, the administration of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, results in a 50% or greater reduction in uPCR over 24 hours. In another aspect of this embodiment, the administration of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, results in a uPCR value of less than or equal to 500 mg/g. In another aspect of this embodiment, the administration of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, results in a uPCR value of less than or equal to 200 mg/g. In some embodiments, the administration of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, results in a change from baseline in 24-hour urinary protein excretion, estimated glomerular filtration rate, and/or serum albumin. In certain embodiments, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is about 20 mg to about 1,000 mg, such as about 60 mg to about 900 mg, about 60 mg to about 800 mg, about 60 mg to about 700 mg, about 60 mg to about 600 mg, about 60 mg to about 500 mg, about 60 mg to about 400 mg, about 60 mg to about 300 mg, about 60 mg to about 200 mg, or about 60 mg to about 100 mg. In a preferred embodiment, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally once per day. In a further preferred embodiment, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally once per day in a single oral dosage form. In certain embodiments, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is about 80 mg to about 600 mg, such as about 80 mg to about 550 mg, about 80 mg to about 500 mg, about 80 mg to about 450 mg, about 80 mg to about 400 mg, about 80 mg to about 350 mg, about 80 mg to about 300 mg, BPX-05425 about 80 mg to about 250 mg, about 80 mg to about 200 mg, about 80 mg to about 160 mg, or about 80 mg to about 100 mg. In a preferred embodiment, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally once per day. In a further preferred embodiment, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally once per day in a single oral dosage form. In certain embodiments, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, 150 mg, 160 mg, 200 mg, 240 mg, 250 mg, 280 mg, 300 mg, 320 mg, 350 mg 360 mg, 400 mg, 440 mg, 450 mg, 480 mg, 500 mg, 520 mg, 560 mg, 600 mg, 640 mg, 680 mg, 700 mg, 740 mg, 780 mg, 800 mg, 820 mg, 860 mg, 900 mg, 940 mg, 980 mg, or 1,000 mg. In a preferred embodiment, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally once per day. In a further preferred embodiment, the therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally once per day in a single oral dosage form. In certain embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered once daily. In other embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered twice daily. Formulations, Routes of Administration, and Dosing Compound A, or a pharmaceutically acceptable salt or prodrug thereof, can be formulated as pharmaceutical compositions for oral administration to a subject, preferably a human subject. In preferred embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally in combination with a pharmaceutically acceptable carrier. Compound A, or a pharmaceutically acceptable salt or prodrug thereof, may be enclosed in hard- or soft-shell gelatin capsules or may be compressed into tablets. Such compositions should contain at least 0.1% of an active agent (i.e., Compound A, or a pharmaceutically acceptable salt or prodrug thereof). The percentage of active agent in such pharmaceutical compositions may, of course, be varied and may conveniently be between about 2% to about 60% of the weight of a given unit dose form. In certain embodiments, the amount of active agent in such therapeutically useful pharmaceutical compositions is such that an effective amount or a therapeutically effective amount will be administered to the subject. BPX-05425 The oral dosage forms may also contain one or more of the following pharmaceutically acceptable carriers: binders (such as, but not limited to, gum tragacanth, acacia, corn starch or gelatin), fillers (such as, but not limited to, starch, lactose, inorganic salts, magnesium carbonate, calcium carbonate, calcium phosphate, and microcrystalline cellulose), glidants (such as, but not limited to, colloidal silicas, cornstarch, talc, and magnesium stearate), lubricants (such as, but not limited to, hydrophobic substances, magnesium stearate, calcium stearate and stearic acid), disintegrants (such as, but not limited to, corn starch, potato starch, alginic acid, croscarmellose sodium, sodium starch glycolate, and crospovidone), surfactants (such as, but not limited to, sodium lauryl sulfate and sodium docusate) plasticizer (such as, but not limited to, polyalcohols, glycerol, polypropylene glycol, low molecular weight polyethylene glycol), colourants, opacifying agents, preservatives, and sweetening agents (such as, but not limited to, sucrose, fructose, lactose or aspartame or a flavoring agent). When the unit dosage form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier, such as a vegetable oil or a polyethylene glycol. Various other materials may be present as coatings or to otherwise modify the physical form of the solid unit dosage form. For instance, tablets, pills, or capsules may be coated with gelatin, wax, shellac or sugar and the like. Of course, any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non-toxic in the amounts employed. In addition, the active compound may be incorporated into sustained-release preparations and devices. Compound A, or a pharmaceutically acceptable salt or prodrug thereof, can be conveniently formulated in an oral dosage form. In certain embodiments, a single oral unit dose form contains a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt or prodrug thereof. For example, an oral unit dose form may contain 40 to 1000 mg, such as for example, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg, 140 mg, 150 mg, 160 mg, 200 mg, 240 mg, 250 mg, 280 mg, 300 mg, 320 mg, 350 mg 360 mg, 400 mg, 440 mg, 450 mg, 480 mg, 500 mg, 520 mg, 560 mg, 600 mg, 640 mg, 680 mg, 700 mg, 740 mg, 780 mg, 800 mg, 820 mg, 860 mg, 900 mg, 940 mg, 980 mg, or 1,000 mg of Compound A, or a pharmaceutically acceptable salt or prodrug thereof. In one embodiment, the invention provides a composition comprising Compound A, or pharmaceutically acceptable salts or prodrugs thereof, formulated in such a unit dosage form. In certain embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is present in the oral dosage form as the dihydrochloride salt. In certain embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is present in the oral dosage form as the free base. BPX-05425 In certain embodiments, the oral dosage form is a capsule. In some such embodiments, the capsule is a hard gelatin capsule or a soft gelatin capsule. In other embodiments, the oral dosage form is a tablet. In some such embodiments, the tablet is a coated tablet. The desired dose may conveniently be presented in a single unit dose form for oral administration. Alternatively, the desired dose may be presented in two or more unit dose forms to be administered together or at appropriate intervals, for example, as two, three, four or more sub-doses per day. In certain embodiments, the desired dose is administered as a single dose per day via a single unit dose form. In certain embodiments, the desired dose is administered as sub-doses, such as two sub-doses per day or three sub-doses per day. Compound A, or a pharmaceutically acceptable salt or prodrug thereof, can be administered to subjects for treatment for any period of time. Suitable duration of treatment may be based on several factors, such as the disease or condition being treated or other conditions the patient may have, and can be determined by those of ordinary skill in the art. In certain embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is be administered for years to weeks, such as 5 years, 4 years, 4 years, 2 years, 1 year, 48 weeks, such as 24 weeks, 12 weeks, 6 weeks, 3 weeks, 2 weeks, or 1 week. In certain embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, can be administered to a subject chronically. Compound A, or a pharmaceutically acceptable salt or prodrug thereof, can be administered to patients in either the fasted or the fed state (e.g., with or after a high-fat meal). Compound A, or a pharmaceutically acceptable salt or prodrug thereof, can also be administered in combination with other therapeutic agents, for example, other agents that are useful for treating a disease or condition related to aberrant complement system activity. In certain embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, can also be administered in via time-release, delayed release, or sustained release delivery systems such as are well-known in the art. In certain embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered once daily. In other embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered twice daily. In still other embodiments, Compound A, or a pharmaceutically acceptable salt or prodrug thereof, is administered three times daily. EXAMPLES Example 1- In vitro Studies BPX-05425 A standard battery of safety pharmacology studies, as outlined in the International Council for Harmonisation (ICH) guidance S7A (ICH 2001), was conducted to evaluate Compound A, using in vitro studies and in vivo studies in rats and dogs. In in vitro studies, Compound A was highly selective towards Factor D, with minimal or no activity towards other serine proteases. Compound A also showed no interaction with the majority of studied G-protein coupled receptors (GPCRs). Inhibition of AP activity by Compound A was assessed in normal human serum (AP Wieslab assay). Compound A potently inhibited AP activity with a mean IC₅₀ (± standard error) of 30.5 ± 3.2 nM. Inhibition of AP activity by Compound A was further assessed using RBCs from patients with PNH as overactivity of the AP and/or AP amplification loop is the common pathogenesis underlying C3G, PNH, and other complement-mediated disorders. In the Ham test using 20% acidified normal human serum, Compound A inhibited hemolysis of erythrocytes from 3 patients with PNH with mean IC₅₀ and IC₉₀ values of 51 and 212 nM, respectively, demonstrating that inhibition of Factor D by Compound A can suppress complement-mediated destruction of a host cell. Compound A also potently inhibited C3 opsonization of erythrocytes from patients with PNH with mean IC₅₀ and IC₉₀ values of 32.3 and 87.8 nM, respectively. Thus, the data shows that Compound A treatment has the potential to prevent EVH in patients with PNH who are receiving anti-C5 therapy and have residual anemia and has the potential to prevent complement-mediated cell injury in C3G by inhibiting Factor D and the subsequent deposition of C3 fragments in the kidney. Compound A inhibition of the human ether-a-go-go related gene (hERG) ion channel current indicated a low risk of clinically significant effect on the QT interval. Compound A was not mutagenic or clastogenic in in vitro genotoxicity studies. Further, based on in vitro studies in mouse 3T3 fibroblast, Compound A is considered of low concern for phototoxicity. Compound A had no effects on cardiovascular, respiratory, or central nervous systems in a standard battery of safety pharmacology studies. Example 2- Animal Studies Single-dose oral administration of Compound A at doses up to 1000 mg/kg in rats, dogs, and non-human primates (NHPs) produced no adverse findings. A summary of the no- observed-adverse-effect levels (NOAELs) and associated toxicokinetic parameters in completed repeat-dose toxicity studies is provided in Table 1. BPX-05425 Table 1: Summary of NOAELs and Toxicokinetic Parameters at the NOAEL in Repeat-dose Toxicity Studies of Compound A

Abbreviations: AUC_0-24 = area under the concentration vs. time curve from time 0 to 24 hours post dose; C_max = maximum observed concentration; NHP = non-human primate; NOAEL = no-observed-adverse-effect level. Example 3- Part 1: Single Ascending Dose and Pilot Food Effect Compound A was evaluated in a Phase 1 first-in-human study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of Compound A in healthy subjects. The study is currently ongoing. Part 1 of the study is designed to evaluate the safety, tolerability, PK, and PD of single ascending oral doses of Compound A or placebo in healthy subjects. Approximately 72 subjects are planned to be enrolled in 9 cohorts, with 8 subjects in each cohort (6 subjects per cohort will receive Compound A and 2 subjects per cohort will receive matching placebo). Escalation to the next higher dose level in Part 1 occurred/will occur only after satisfactory review of clinical safety and pharmacokinetic data. Based on the emerging data, the dose escalation scheme may be adjusted, including modifying, adding, omitting, or repeating dose cohorts. In addition, the number of subjects per Cohort may also be adjusted if the inter-subject variability in PK and/or PD data is higher than expected. The planned dose cohorts in Part 1 are: ^ Part 1, Cohort 1: 1 mg Compound A or placebo orally, × 1 dose ^ Part 1, Cohort 2: 3 mg Compound A or placebo orally, × 1 dose ^ Part 1, Cohort 3: 10 mg Compound A or placebo orally, × 1 dose ^ Part 1, Cohort 4: 40 mg Compound A or placebo orally, × 1 dose ^ Part 1, Cohort 5: 80 mg Compound A or placebo orally, × 1 dose ^ Part 1, Cohort 6: 110 mg Compound A or placebo orally, × 1 dose ^ Part 1, Cohort 7: BPX-05425 ⁃ Period 1: 80 mg Compound A or placebo orally, × 1 dose, administered under fasted conditions ⁃ Period 2: 80 mg Compound A or placebo orally, × 1 dose, administered under fed conditions ^ Part 1, Cohort 8: 160 mg Compound A or placebo orally, × 1 dose ^ Part 1, Cohort 9: 200 mg Compound A or placebo orally, × 1 dose For Cohorts 1-6 and 8-9, subjects will be screened from 28 to 2 days prior to Day 1. Eligible subjects will be admitted to the Phase 1 clinical research unit (CRU) on Day -1. A single oral dose of Compound A or placebo will be administered on Day 1. Subjects will remain at the CRU for approximately 72 hours after dose administration and will be discharged from the CRU on Day 4. Subjects will return for a follow-up visit on Day 16 (± 2 days). If a subject has clinically significant safety findings that are ongoing at a scheduled visit, the subject will be followed at additional visits until the findings are resolved or stabilized at a new baseline. For Cohort 7 (pilot food effect) subjects will be screened from 28 to 2 days prior to Day 1 of Period 1. Eligible subjects will be admitted to the CRU on Day -1 of Period 1. A single oral dose of 80 mg Compound A or placebo will be administered on Day 1 of Period 1 under fasted conditions. Subjects will remain at the CRU for approximately 72 hours after dose administration and will be discharged from the CRU on Day 4 of Period 1. Subjects will return to the CRU at least 7 days or 5 half-lives (t_1/2) of Compound A (whichever is longer) after dose administration, for Period 2. The same assessments as in Period 1 will be performed in Period 2, with admission to the clinic occurring on Day -1 of Period 2. Compound A or placebo will be administered on Day 1 of Period 2 following a high-fat meal. Subjects will be discharged from the CRU on Day 4 of Period 2 and will return for a follow-up visit on Day 16 (± 2 days) of Period 2. Subjects will receive the same study drug (Compound A or placebo) and dose in both Period 1 and Period 2 of Cohort 7. If a subject has clinically significant safety findings that are ongoing at a scheduled visit, the subject will be followed at additional visits until the findings are resolved or stabilized at a new baseline. The Compound A dose tested in Cohort 7 may be adjusted based on emerging data. Key Assessments Part 1: Plasma and urine samples to determine concentrations of Compound A will be collected at regular intervals up to 72 hours or longer post dose. Urine samples may not be collected in Cohort 7. Concentrations of metabolites may also be determined in the plasma and urine samples. Samples for PD analyses (alternative pathway [AP] activity, Factor Bb, and Factor D in blood; and Factor Ba in urine) will be collected at regular intervals up to 72 hours or longer BPX-05425 post dose. For all samples, collection timepoints may be adjusted based on available data. Additionally, concentrations of metabolites may also be determined in the plasma and urine samples. Example 4- Part 2: Multiple-dose Cohorts Part 2 of the study will evaluate the safety, tolerability, PK, and PD of multiple ascending oral doses of Compound A or placebo in healthy subjects. Approximately 48 subjects are planned to be enrolled in 4 sequential ascending dose cohorts, with 12 subjects in each cohort (10 subjects per cohort will receive Compound A and 2 subjects per cohort will receive matching placebo). Subjects in Cohort 1 will receive Compound A or placebo for 7 days. However, based on the half-life of Compound A, cumulative findings from Part 1, and any emerging data from Part 2, the duration of dosing in the remaining Part 2 cohorts may be adjusted (for example, from 3 to 28 days of dosing). The daily dose may be administered once daily (QD) or split equally into 2 daily doses (BID). In addition, the number of subjects per Cohort may also be adjusted if the inter-subject variability in PK and/or PD data is higher than expected. Escalation to the next higher dose level in Part 2 will occur only after satisfactory review of clinical safety and pharmacokinetic data. Based on the emerging data, the dose escalation scheme may be adjusted, including modifying, adding, omitting, or repeating dose cohorts. In addition, the number of subjects per Cohort may also be adjusted if the inter-subject variability in PK and/or PD data is higher than expected. The planned dose cohorts in Part 2 are: ^ Part 2, Cohort 1: 20 mg Compound A or placebo/day orally, 7 days ^ Part 2, Cohort 2: 40 mg Compound A or placebo/day orally, 14 days ^ Part 2, Cohort 3: 80 mg Compound A or placebo/day orally, 14 days ^ Part 2, Cohort 4: 160 mg Compound A or placebo/day orally, up to 28 days Subjects will be screened from 28 to 2 days prior to Day 1. Eligible subjects will be admitted to the CRU on Day -1 and will remain at the clinic until completion of all assessments at 72 hours after the final dose. Compound CRU for an additional approximately 72 hours after administration of the last dose and will then be discharged from the clinic. Subjects will return for a follow-up visit 12 (± 2) days after discharge. If a subject has clinically significant safety findings that are ongoing at a scheduled visit, the subject will be followed at additional visits until the findings are resolved or stabilized at a new baseline. If the duration of study drug administration is adjusted based on the available data, the visit days will be adjusted accordingly. BPX-05425 Key Assessments Part 2: Plasma and urine samples to determine concentrations of Compound A will be collected pre-dose and at regular intervals up to 24 hours or longer post dose on Day 1 and up to 72 hours after or longer after the final dose. Samples for PD analyses (AP activity, Factor Bb, and Factor D in blood; and Factor Ba in urine) will be collected pre-dose and at regular intervals up to 24 hours or longer post dose on Day 1 and up to 72 hours or longer after the final dose. For all samples, collection timepoints may be adjusted based on available data. Concentrations of metabolites may also be determined in the plasma and urine samples. Example 5- Part 3: Japanese Ethnobridging Part 3 of the study will evaluate the safety, tolerability, PK, and PD of single and multiple oral doses of Compound A or placebo in healthy Japanese subjects. Eligible Japanese subjects must be first generation, born in Japan, not having lived outside Japan for more than 5 years, able to trace maternal and paternal Japanese ancestry, and have no significant change in lifestyle, including diet, since leaving Japan. Approximately 22 Japanese subjects are planned to be enrolled in 1 single-dose and 1 multiple-dose cohort. Part 3 Cohort 1 (Single Dose): The planned single-dose for Cohort 1 of Part 3 is: 80 mg Compound A or placebo orally, × 1 dose. Based on emerging data, the dose levels in Part 3 Cohort 1 may be adjusted. The dosing, visit, and assessment schedule will be the same as described for Cohorts 1 through 6 in Part 1. Part 3 Cohort 2 (Multiple Dose): The planned multiple-dose for Cohort 2 of Part 3 is: 80 mg Compound A, or placebo/day orally, up to 28 days Based on emerging data, the dose level, dosing regimen, duration of treatment, and other factors may be adjusted to match the design in Part 2. The dosing, visit, and assessment schedule will be the same as described for Part 2. For Cohorts 1 and 2 of Part 3, additional dose levels may be evaluated to assist in bridging the PK data to that obtained in Part 1 and Part 2, respectively, and the number of subjects per cohort may also be adjusted to account for inter-subject variability in PK and/or PD data if required. Example 6- Part 4 Part 4 of the study will evaluate the safety, tolerability, and PK (and optionally PD) of single oral doses of Compound A administered as dihydrochloride salt (reference formulation BPX-05425 used in Parts 1 through 3) and free base formulation (new test formulation only used in Part 4) in healthy subjects. Approximately 12 healthy subjects are planned to be enrolled in 1 open-label, randomized, two-period crossover cohort. Each subject in Part 4 will receive 2 single doses of 40 mg Compound A administered on 2 separate occasions as: ^ Regimen A: 40 mg Compound A as dihydrochloride salt ^ Regimen B: 40 mg Compound A as free base Based on the emerging PK data, the number of subjects and the dose may be adjusted. Subjects will be randomized in a 1:1 ratio to receive the regimens in one of the two sequences: AB (i.e., Regimen A in Period 1 and Regimen B in Period 2) or BA (i.e., Regimen B in Period 1 and Regimen A in Period 2). Based on the emerging data, the dose of Compound A and the number of subjects may be adjusted. Subjects will be screened from 28 to 2 days prior to Day 1 of Period 1. Eligible subjects will be admitted to the CRU on Day -1 of Period 1. A single oral dose of assigned regimen will be administered on Day 1 of Period 1. Subjects will remain at the CRU for an additional approximately 72 hours after dose administration and will be discharged from the CRU on Day 4 of Period 1. Subjects will return to the CRU at least 7 days or 5 half-lives of COMPOUND A (whichever is longer) after dose administration, for Period 2. The same procedure described in Period 1 will be performed in Period 2. Subjects will be discharged from the CRU on Day 4 of Period 2 and will return for a follow-up visit on Day 16 (± 2 days) of Period 2. Key Assessments Part 4: Plasma samples to determine concentrations of Compound A will be collected at regular intervals up to 72 hours post-dose or longer in both periods. Urine samples for PK analysis may also be collected, if needed. Based on emerging data, PK sampling may be extended beyond 72 hours. Concentrations of additional metabolites may also be determined in plasma and urine samples if needed. Plasma and urine samples for PD analyses may also be collected, if needed. Example 7- Safety Results In the ongoing clinical studies, preliminary safety and PK data were available from Part 1 Cohorts 1 to 9, Part 2 Cohorts 1 to 3, and Part 4. There have been no clinically significant findings from laboratory assessments, vital signs, physical exams, or electrocardiograms (ECGs), and all reported treatment-emergent adverse events (TEAEs) are derived from subject- reported symptoms and signs, as assessed by the investigator. BPX-05425 One hundred twenty-four subjects have been dosed with Compound A or placebo across all cohorts in the study to date. Forty-eight (39%) subjects experienced any TEAE. All TEAEs were non-serious, with no serious AEs (SAEs) reported. Six (5%) subjects experienced a TEAE severity greater than Grade 1, with no Grade 3 or Grade 4 TEAEs reported. Six (5%) subjects experienced a TEAE assessed by the investigator as related to blinded study drug. Across all cohorts, 7 TEAEs were experienced by more than 2 subjects: headache (13 subjects), back pain (5 subjects), dysmenorrhoea (4 subjects), viral upper respiratory tract infection (4 subjects), COVID-19 (3 subjects), medical device site reaction (3 subjects), and nausea (3 subjects). There were no trends in the number or types of TEAEs with increasing dose or increasing dosing duration of Compound A vs. placebo. No safety concerns for Compound A have been identified from the review of blinded safety data from Parts 1, 2, and 4 of the study, and Compound A was generally well tolerated. Per study protocol, the sponsor is unblinded and may conduct unblinded reviews of data during the study for the purpose of safety assessment. The sponsor’s internal review of the unblinded safety data also identified no safety or tolerability concerns for Compound A. Example 8- Pharmacokinetics Results Parts 1 and 2 Following single oral administration of Compound A (Part 1; Cohorts 1 to 6 and 8 to 9; 1 to 200 mg) in healthy subjects, Compound A was rapidly absorbed into the systemic circulation with a median time of maximum concentration (T_max) ranging from 0.75 to 1.0 hours post dose for fasted dosing. The mean terminal half-life (t_1/2) of Compound A ranged from 11.6 to 18.9 hours at doses ≥ 10 mg. Plasma Compound A C_max and AUC_0-24 increased in an approximately dose-proportional manner across the evaluated dose range. Concentration-time profiles of Compound A after oral administration of single doses of Compound A ranging from 1 to 110200 mg are shown in FIG.1. Compound A PK parameters from Part 1 are summarized in Table 2. Compared to the fasted state, dosing of Compound A with a high-fat meal resulted i_n ^{delayed/prolonged absorption (median T} _max ^{3.0 vs. 1.0 hours) and reduced C} _max ^{, but a similar} _{extent of absorption as evidenced by the AUC (FIG. 2 and Table 2). The} geometric least squares mean (GLSM) ratio and 90% confidence intervals (CI) for the c_{omparison between fed vs. fasted dosing was} ^{0.536 (0.434, 0.663) for C} _max ^{and 1.05} (1.00, 1.11) for AUC from time 0 extrapolated to infinite time (AUC_0-inf). BPX-05425 Concentration-time profiles of Compound A after oral administration for 7 (20 mg dose cohort) or 14 days (40, 80 and 160 mg dose cohorts) are shown in FIG.3. Preliminary plasma PK parameters for Compound A are presented in Tables 3 and 6. Following administration of Compound A, 20 to 160 mg QD for 7 or 14 days, the median Compound A was rapidly absorbed into the systemic circulation with a median time of maximum observed concentration [T_max] ranging from 0.5 to 1.0 hours post dose and T_max ranged from 0.75 to 1.0 hour post dose on the last day of dosing. Compound A accumulated in plasma with median values for C_max, AUC_0-24, and C_tau that increased by up to, 40%, and 93%, respectively, on the last day of dosing compared to Day 1. Plasma Compound A C_max and AUC_0-24 increased in an approximately dose-proportional manner across the studied dose range. Steady state for Compound A was not reached in all participants by Day 7 but was likely reached by Day 14. Example 9- Pharmacodynamic Results Parts 1 and 2 Suppression of the AP activity by Compound A was assessed using AP Wieslab assay, which measures functional activity of the complement system. In this assay, the AP was activated ex vivo in 5.6% serum using an AP-specific activator. The end-product of complement activation, C5b9 (membrane attack complex [MAC]), was detected with a specific antibody by an enzyme-linked immunosorbent assay (ELISA) method. Preliminary pharmacodynamic data from the AP Wieslab assay in healthy subjects receiving single (1 to 200 mg) doses of Compound A in Cohorts 1-6 and 8-9 of Part 1 are shown in FIG.4 (showing time course of suppression of AP Activity). FIG.5 (showing dose response of AP activity suppression 12- and 24-hours post dose of 1 to 110 mg of compound A) . The onset of AP inhibition was rapid, occurring within 1 hour following dosing. The extent of suppression increased in a dose-dependent manner and was clearly differentiated from placebo at doses > 3 mg. At the highest single dose level tested to date, 200 mg, AP activity was suppressed by ≥ 99% at 24 hours post dose in all subjects. AP Wieslab activity returned approximately to baseline levels within 72 hours of dosing in accordance with declining plasma Compound A concentrations Preliminary pharmacodynamic data from the AP Wieslab assay in healthy subjects receiving multiple doses of Compound A in Cohorts 1-3 of Part 2 are shown in FIG. 6. The onset of AP inhibition was rapid, occurring within 1 hour following dosing. The extent of mean suppression increased from the 20 to 40 mg dose level and was comparable for the 40 and 80 mg dose levels. At the 80 mg dose level, the highest percentage of subjects (40%) achieved complete inhibition of AP Wieslab (≥ 98% suppression), while only 10% of subjects at 40 mg BPX-05425 and none of the subjects at 20 mg achieved complete inhibition of AP Wieslab. At 80 mg Compound A, the mean suppression of AP Wieslab at 24 hours post dose was 85.4%. AP Wieslab activity returned approximately to baseline levels within 72 hours of administration of the last dose in accordance with declining Compound A plasma concentrations. The pharmacodynamic profile of Compound A is characterized by rapid (within 1 hour), robust, and sustained inhibition of the AP as measured via the AP Wieslab assay. Following a single dose of 200 mg Compound A, ≥ 99% AP Wieslab suppression was maintained through 24 hours in all participants. Recovery of AP activity appears to directly follow declining plasma concentrations of Compound A, and typically returns to approximately baseline levels within 72 hours of cessation of dosing. Example 10- Part 3 Results Part 3 is currently ongoing. Eight Japanese subjects received a single dose of 80 mg Compound A and 2 subjects received placebo in the fasted state. Preliminary plasma PK parameters for Compound A are summarized in Table 4 for subjects in Part 3 Cohort 1. The effects of Japanese ethnicity on the Compound A exposures (geometric least-squares means [GLSMs] and 90% confidence intervals [CIs]) are summarized in Table 5. Following administration of a single Compound A 80 mg dose in healthy Japanese subjects, absorption of Compound A was rapid with plasma concentrations that peaked at a median T_max of 1.0 hour post dose. The exposure to Compound A was higher in Japanese subjects (test) compared to non-Japanese subjects (reference) who received a single dose of 80 mg of Compound A under fasting conditions. The Compound A C_max was increased by 15%, while the AUC_0-inf and AUC_0-24 were increased by 37% and 48%, respectively, in Japanese subjects compared to non-Japanese subjects. The exposures in Japanese subjects at 80 mg of Compound A were similar to the exposures in non-Japanese subjects administered a single dose of 110 mg Compound A. There was no impact of Japanese ethnicity on the T_max of Compound A. The onset of AP inhibition was rapid, occurring within 1 hour following dosing. Following a single administration of 80 mg Compound A in Japanese subjects, AP activity was suppressed by a mean of 96.6% at 24 hours post dose, similar to the response observed in non-Japanese subjects at 110 mg Compound A (mean of 97.8% suppression). AP Wieslab activity returned approximately to baseline levels within 72 hours of dosing in accordance with declining plasma Compound A concentrations. BPX-05425 Example 11- Part 4 Results Results from Part 4 are shown in FIG.7. The plasma concentration profiles of Compound A were similar for each formulation (dihydrochloride salt, reference formulation, and free base, test formulation) across the 72-hour sampling interval. The GLSM ratios and 90% Cis (FIG.8) showed the Compound A C_max and AUC were similar between the dihydrochloride salt (reference) and free base (test) formulations following administration of 40 mg Compound A to healthy subjects. There were no clinically meaningful differences in the exposures to Compound A following administration of either formulation. Example 12- Therapeutic Evaluation of Compound A for Treatment of C3G Compound A will be used in a Phase 1b study to evaluate the safety, tolerability, PK, PD, and therapeutic potential in subjects with C3G. The study is an open label study and will enroll approximately 6 to 12 adult subjects with confirmed C3G. Subjects will initially be treated with study drug for 12 weeks. If, at the Week 12 visit, the investigator confirms that continuation in the study is in the subject’s best interest with sponsor agreement, the subject will be allowed to continue for a further 12 weeks for a total of 24 weeks of study drug dosing. Initiation of Compound A therapy will occur in the clinic on Day 1. Subjects will be evaluated either in the clinic or at home for weekly visits for the first 2 weeks after initiation of therapy with Compound A and for 2 weeks after dose escalation. Subjects will otherwise be evaluated in the clinic approximately every 4 weeks until they complete the study drug dosing period or until the subject’s participation in the study is discontinued. Subjects will be administered 80 mg QD Compound A for Weeks 1 to 12. For subjects who continue therapy past Week 12, the dose level for Weeks 13 to 24 will be determined by the subject’s proteinuria remission status as determined by the uPCR result from the planned Week 1224-hour urine collection: subjects with a complete remission (uPCR ≤ 500 mg/g) will maintain the 80 mg QD dose of Compound A for Weeks 13 to 24 and subjects with a partial or no remission (uPCR > 500 mg/g) will escalate to a dose of 160 mg QD of Compound A for Weeks 13 to 24. Compound A will be administered orally QD via capsules without regard to food intake. Higher dose level(s) of Compound A may be explored in future efforts if data from this study indicate that a higher dose is needed to achieve satisfactory therapeutic response. Twenty-four-hour urine samples for urinary protein analyses will be collected at the following timepoints: i) screening, ii) Day 1 prior to the first dose of Compound A, iii) at weeks 4, 8, 12, 16, 20, and 24 (as applicable), and iv) on the final clinic visit. Blood samples BPX-05425 for PK and PD biomarker analyses will be collected at the following timepoints: i) Day 1, Week 8, and Week 20: pre-dose and 0.5, 1, 2, 4, and 6 hours post dose, ii) Weeks 16 and 24: pre-dose, 1 hour post dose, and 1 sample, PK only, between 4 to 12 hours post dose, and iii) Weeks 4 and 12: pre-dose. Proteinuria will be assessed by 24-hour urine collection for total daily proteinuria, albuminuria, uPCR ratio, and uACR (urinary albumin-to-creatinine) ratio; serum albumin and serum creatinine will also be assessed. Blood and urine samples for measurement of the concentrations of Compound A will be collected. The extent of plasma protein binding may be assessed for selected timepoints. Blood PD and complement biomarker assessments may include but are not limited to: ex vivo AP activity (as assessed by AP Wieslab); ex vivo AP- activated complement biomarker levels (Factor Bb, C3a, C5a, and sC5b9); serum complement biomarker levels (Factor D, Factor Bb, C3, and sC5b-9). Urine PD and complement biomarkers may include, but are not limited to: Factor Ba, C3a, C5a, sC5b-9, and inflammatory cytokines/chemokines. Example 13- Therapeutic Evaluation of Compound A for Treatment of PNH Compound A will be used in a Phase 1b study to evaluate the safety, tolerability, PK, PD, and therapeutic potential in subjects with PNH. The study is an open label study and will enroll approximately 6 to 15 adult subjects in 2 cohorts. Cohort 1 will enroll approximately 3 to 6 subjects, and Cohort 2 will enroll approximately 3 to 9 subjects. Subjects in Cohorts 1 and 2 will initially be treated with Compound A for at least 4 weeks at Dose Level 1. Following the initial 4 weeks of dosing (and approximately every 4 weeks thereafter) dose escalation will occur in compliance with the dose escalation rules until a subject’s LDH at a given Dose Level is < 1.5 x upper limit of normal (ULN). Once LDH is ≤ 1.5 × ULN, additional dose escalation is permissible following at least 12 weeks of treatment at a given Dose Level if a subject’s total PNH RBC clone size to PNH WBC clone size ratio is < 0.90. After 12 weeks of Compound A treatment, a given subject may continue dosing for up to 12 additional weeks (i.e., up to 24 weeks total treatment duration) only if continued treatment is assessed by the investigator to be in the subject’s best interest, with agreement by the sponsor. The study design is illustrated in FIG.11. Compound A will be administered in the clinic on scheduled study visits when PK and/or PD/biomarker samples are to be collected, and the time of dosing will be recorded in the electronic case report form. On these days, subjects must refrain from eating or drinking (other than water) beginning 2 hours prior to study drug administration and continuing through 2 hours post dose. The time of dosing on the day prior to each study visit (scheduled BPX-05425 and unscheduled) that includes PK and/or PD sampling must also be reported by the subject and recorded. Compound A will be administered orally QD via capsules without regard to food intake, preferably in the morning. The planned dose escalation rules are as follows: i) each Dose Level must be administered to a subject for at least 4 weeks before dose escalation may occur for that given subject; ii) the escalated Dose Level must be ≤ 2.0-fold the total daily dose of the preceding Dose Level; iii) the escalated Dose Level must be ≤ a total daily dose of 240 mg Compound A; and iv) the Dose Level may be reduced and/or the total daily dose may be administered once daily (QD) or twice daily (BID). The planned Dose Levels for Cohort 1 are: i) Dose Level 1- 80 mg QD, ii) Dose Level 2- 160 mg QD, and iii) Dose Level 3- 240 mg QD. The planned Dose Levels for Cohort 2 are: i) Dose Level 1- 160 mg QD and ii) Dose Level 2- 240 mg QD. For both Cohorts 1 and 2, the planned Dose Levels may be adjusted based on the emerging data from this study and/or other studies involving Compound A. Urine samples for PK and PD/biomarker analysis will be collected at the following timepoints: i) Day 1, Week 2, and Week 4 (pre-dose and all urine from 0 to 6 hours post- dose); and ii) at In-Clinic visits occurring 2 and 4 weeks after each dose escalation. Blood samples for PK and PD/biomarker analyses will be collected at the following timepoints: i) Day 1, Week 2, and Week 4: pre-dose and 0.5, 1, 2, 4, and 6 hours post dose, ii) at In-Clinic visits occurring 2 and 4 weeks after each dose escalation; and iii) pre-dose samples will be collected every 4 weeks once a Dose Level has been maintained for at least 4 weeks. Clinical and laboratory measurements of PNH to be analyzed may include, but are not limited to, LDH, ratio of total PNH red blood cell (RBC) to PNH white blood cell (WBC) clone size, hemoglobin (Hb), number of packed RBC (pRBC) transfusions and number of pRBC units administered, absolute reticulocyte count (ARC), total PNH RBC clone size, haptoglobin, bilirubin, aspartate aminotransferase (AST), and assessment of PNH-associated clinical symptoms (e.g., hemoglobinuria, abdominal pain, esophageal pain, erectile dysfunction, incidence of ASH, and incidence of thrombotic events). Patient recorded outcomes may also be collected using the FACIT Fatigue Scale. Blood and urine samples for measurement of the concentrations of Compound A will be collected. The extent of plasma protein binding may be assessed for selected timepoints. Blood PD and complement biomarker assessments may include but are not limited to: ex vivo AP activity (as assessed by AP Wieslab); ex vivo AP-activated complement levels of Factor Bb BPX-05425 (additional biomarkers may also be assessed). Urine PD and complement biomarkers may include, but are not limited to: Factor Ba; D-dimer will be assessed as a marker of fibrinolysis.

BPX-05425 , ² _{0 0 0} ⁰ ₀ 0 ² _{0 0 0 7} ⁰ _{8 d} ^c ₀ ^{. b} ₅ ^{0 0 4 4} _{0 0} ^{6 o} _d ⁰ _{4 9 ,} ^{0 0} ₃ ^{0 0} _{4 g} ⁱ _r ^e F ^. ₃ ^, ₀ ^{3 5 0} ₈ ⁸ ₄ ^{8 ,} _{0 4} ⁶ ₉ ^{4 ,} ₀ m ^e P ^0. _{3 3 8} ¹ _{2 2} ⁰ _{8 3 3} ⁰ ₁ 0 _{1 2} ¹ ₂ ⁹ _{2 1} ^t _r ^a _P ⁿ i ^A _d ⁿ _u ^o _p ^m _o ^Cf _o ⁿ _o ^it _a ^rt _s ⁱ _{n i} ^m _d ^{A g} _ni ^w _o ^ll _o ^F _s ^r _et ^e _m ^a _r ^a

_{P 2 3} ^ci _t ^e _ni ^k _{2 o} ^{t c} _r ^a ₀ ^0. ₁ ^{0 6} ₆ ⁰ _{7 a} ^o g ⁴ h ^m _{= 5} ^7. ₁ ^, ₃ ⁰ ₆ ⁸ ₂ ^, _{7 1} ⁰ _{1 6 8} ² ₁ o _{N 0 0 2 1 9} ⁷ ₈ ¹ ₉ ^, ₆ ⁸ ₉ ⁹ ₉ ^, ₁ ^m _{3 r C} ^5. ₀ ⁷ ₁ ² ₆ ⁸ ₆ ^a _h ^P _y ^e _{1 0} ⁰ _{2 0 8 K} t_r ^{a o} g ⁵ ₀ ^. _{1 3. 5.} ⁰ ₁ ^{3 7} h ^m ₌ ^{0. o} _{1 N 1} ^, ₀ ⁵ ₇ ^{9 ,} _{5 8 5 3 9 6 6} ⁸ ₃ ⁰ ₄ ^, ₃ ⁶ ₄ ⁴ ₄ ^, _{5 C} ^5. _{7 . 0} ⁸ ₄ ⁷ ₂ ⁵ ₃ ^: ₂ ^el _b ^re ^{x x x a} _{t a a a} ^x _T ^{e K n} _{a P m} ^{m n} _a a _{i i} ^{m n} _ai ^{m n} _{a a} ^m r ^{d ,} _n ⁿa ^{d ,} _n ⁿa ^{d ,} _n ⁿa _i ^{d ,} _n a _{e i e e i e e i e e i P} ^{M M M M M M M M M M M} BPX-05425 , ² _{5 d} ^c _{5 9 3} ² _{. 4 4 4} ^{0 b o} _{d g} ⁱ _r ^e F ³ ₃ ⁰ ₃ ^, _{. 1} ⁵ _{. 1} ⁵ _{2 1} ^, _4. m ^e P ⁷ ₂ ^{1 0} _{1 8} ^, ₇ t_r ^o _{, h} ^{1 o} C _d ^oi _r ^e P ₆ t_r ^o _h ^o C

5 t _{0 r} ^bg ⁶ _{4 6} ⁹ _{. 9 9} ^{5 o m} ₌ ⁷ ₄ ⁵ ₄ ^, _{. . 2 h} ^o _{2 2} ^{8 8 , 0} _{7 1 1 5. C 8 N} ¹ ₁ ² ₁ ) L ₄ t_r ^{b m} ₎ g ⁶ _{/ 6} ^{8 h o} _{( 1.} ⁵ h ^m ₌ ^g _n o ^{0 (} ₇ ³ _{9 1} ² _{1 1} ^, ₃ ² . t^/ ₅ 1 _. ² _{8. 1} ¹ _{1 1} ^, _{3. C 4 N 4} C ^{2 7} ₉ ¹ _{1 3} t _{4 r} ^bg ⁶ _. ⁶ _3. ^{9 o} _{= 1. 0. 7 9. 2. 1 h} ^{m 3 o 0} _{N 4} ⁶ ₃ ^, _8. ¹ ₁ ⁰ ₁ ^, _{7 C 1} ³ ₂ ^9. _{8 2} t_r ^a ₉ 4 _. ^{4 d} ₇ ^{8. o} g ₇ ² ₆ ¹ ₁ 5 ₃ ³ _{9 h} ^m ₌ ^{. . , o} _{3 N 9 8 6} ^7. ₇ ^. ₇ ^, _{9 C} ^8. ₅ ^4. _{6 1} t_r ^a ₀ ^{9. d} _2. ^{4 o} g ⁵ ₈ ⁷ ₀ ⁰ ₈ 0 _{9 1 h} ^m ₌ ^{. . ,} ₀ ^{6. 0. , o} _{1 N 1 0 C} ^0. _{9 9 5 0} ^9. ₅ r_et ^x _a ^{x e n} _a K P _m ^{a n} _ai ^{m n} r _a ^{, n} _ai ^{m a} _e ^d _{e ni ae} ^d _e ^, _{ni P} ^{M M M M M M} BPX-05425

Abbreviations: AUC = area under the concentration vs. time curve; AUC_0-24 = AUC from time 0 to 24 hours; AUC_0-inf = AUC from time 0 extrapolated to infinite time; C₂₄ = concentration at 24 hours post dose; C_max = maximum concentration; max = maximum; min = minimum; PK = pharmacokinetic; t_1/2 = terminal half-life; T_max = time to C_max. Notes: All doses refer to the Compound A dose. All doses were administered fasted unless otherwise specified. Data cutoff 20 September 2022. ^a Administered as a solution dosage form. ^b Administered as a capsule dosage form. ^c Number of subjects not presented for Period 2 to preserve the blind for the subject who discontinued the study. ^d Compound A concentrations were not quantifiable beyond 16 hours (majority of subjects) for the 1 mg dose and beyond 24 hours (all subjects) for the 3 mg dose, so the t_1/2 estimation may not be representative of that at higher doses. BPX-05425 ₂ ^t _r ^a _P ⁿ _i ^A _d ⁿ _u ^o _p ^m _o ^Cf _o ⁿ _o ^it _a ^rt _s ⁱ _{n i} ^m _d ^{A g} _n ⁱ _w ^ol _l ^o _F s_r ^et _e ^m _a ^r _a ^P _c ⁱ

^t _{g ,} ^, _e ^{m a} ₌ ^. ₁ ⁰ ₀ ⁹ ₂ ⁹ _{, 2} ⁰ _, ⁵ _, ^{4 ,} ₀ ⁷ ₁ ⁴ _{1 2. N N N N} ^{ni 0} _{D n (} ^5. ₅ ⁸ _{1 1} ⁰ ₇ ⁸ _{9 k 4 0 1 ,} ^{0 o} _{1 c} ^{s a} _y ^{a 0} _m ^r _{d a} ^{7 7} ₎ ^{0 h} _{× y} ⁹ _{0 0 0 .} ⁰ ₀ 1 ^{0 0} ₂ ^{0 0 1,} ₂ ⁹ _{9. 6 9 1} ^{6 a} ₌ ^0. _, ⁰ ₁ ⁸ ₅ ^{2 7} _{, 5} ³ ₂ ^{8 1} ₃ ² ₇ ^{1 1} _{1 , 9 .} ³ _. ^{4 ,} _{P D n 1 0 1 1} ⁰ _{9 8 , 1 1 1 1 7.} ^A ₁ ^Q _{D (} ^5. ₅ ^{3 0} ₅ ^{1 6} ₈ ⁰ ₁ t ₎ ⁰ _{0 1 7 d r} ^{A n o} _{d 1 u h} ⁿ ₌ ^{o o} _{u p C} ^o _p ^N ₍ ^{) 0} ₀ ⁰ _{0 6} ^{m m 1} _{0 o o y} ^{1 0} _0. ^{9 a} _{= 0} ^{2 0 5.} _, ⁰ ₁ ⁰ ₈ ^{3, 2 5} ₈ ^{1 0 4} _, ⁰ ₀ ^{0 1} _{8 1 6} 4 ¹ _{. 2. 1 ,} ^{8 C C} ₆ ⁴ ₆ ^, ₄ ^{A A A A} . _{N N N N g D n ( 0 0} ⁵ _{1 1 1 7 6} ⁰ ₈ ¹ _y ^{. e m} ₀ ² ₁ ⁴ _{4 5 K} ⁰ ₂ ) ^K _{L P} ^{m A )} _/ h^: _{d x L x} ^. _g ⁾ ₃ ^{n r} _e ^{a m/ a n} _x ^a _{L x} ^a _x ^{a el} _{u b} ^o _t ^a _p ^e _{) n} ^a m ^h ( ⁱ _{m g n d} ^{, a ma} _n ⁿ ₍ ⁿ _a ⁱ _{m (} ⁴ d ^, 2 _n ^a n _- ^{0 n} _a ⁱ _m ^m _{/ n d} ^{, g n} _a ^ai _{m n d} ^, a₎ ⁿ _a ^ai _{m d} ^, r ^x _a ^{e i x} _a ^{e e i} C ^{e e} _n ⁱ _n ⁽ ₄ ^{e e} _n ^{i h} ( ^{e e} _n ⁱ _{T o M M M M M M M M M M M} ² _{n M M M} C ^a P T ^{m m U 2} C _A C t^{/ 1} BPX-05425 Table 4: Compound A PK Parameters Following Administration of a Single 80 mg Oral Dose of Compound A in Healthy Japanese Subjects

Abbreviations: AUC = area under the concentration vs. time curve; AUC_0-24 = AUC from time 0 to 24 hours; AUC_0-inf = AUC from time 0 extrapolated to infinite time; C₂₄ = concentration at 24 hours post dose; Cmax = maximum concentration; CV = coefficient of variance; max = maximum; min = minimum; PK = pharmacokinetic. All doses were administered fasted.

BPX-05425 Table 5: Effect of Japanese Ethnicity on Compound A Exposures

Abbreviations: AUC = area under the concentration vs. time curve; AUC_0-24 = AUC from time 0 to 24 hours; AUC_0-inf = AUC from time 0 extrapolated to infinite time; CI = confidence interval; C_max = maximum concentration; GLSM = geometric least-squares means. Test population: Japanese subjects administered 80 mg Compound A under fasting conditions (Part 3 Cohort 1). Reference population: non-Japanese subjects administered 80 mg Compound A under fasting conditions (Part 1 Cohort 5 and Cohort 7 Period 1).

BPX-05425 _f ^{o n} _o ^it _a ^rt _s ⁱ _{n i} ^m _d ^{A g} _n ⁱ _w ^ol _l ^o _F

^s

_r ^et _e ^m _a ^r _a ^{P ci} _t ^e _ni ^k _o ^c _a ^m _r ^a _{h 1} ^{P t} _r ^{a A} _P ^{d n} i _n ^u _o ^{A p} _{d m} ^{n o} _u ^o _{C p y} ^{m e} _{o K} ^C _f ^o s^{es :} _{o 6} ^{D el e} _b ^{l a} _{g T} ⁿⁱ _S - 35 - FH11781014.1

Claims

BPX-05425 We claim: 1. An oral dosage form comprising 2-(2-((7-(2-(aminomethyl)pyridin-4-yl)-2- methylbenzofuran-5-yl)methoxy)phenyl)acetic acid, or a pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier. 2. The oral dosage form of claim 1 comprising about 80 mg to about 600 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 3. The oral dosage form of claim 1 comprising about 80 mg to about 550 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 4. The oral dosage form of claim 1 comprising about 80 mg to about 500 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 5. The oral dosage form of claim 1 comprising about 80 mg to about 450 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 6. The oral dosage form of claim 1 comprising about 80 mg to about 400 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 7. The oral dosage form of claim 1 comprising about 80 mg to about 350 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 8. The oral dosage form of claim 1 comprising about 80 mg to about 300 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 9. The oral dosage form of claim 1 comprising about 80 mg to about 250 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 10. The oral dosage form of claim 1 comprising about 80 mg to about 200 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 11. The oral dosage form of claim 1 comprising about 80 mg to about 160 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 12. The oral dosage form of claim 1 comprising about 80 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 13. The oral dosage form of claim 1 comprising about 160 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 14. The oral dosage form of claim 1 comprising about 320 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 15. The oral dosage form of claim 1 comprising about 480 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. - 36 - FH11781014.1 BPX-05425 16. The oral dosage form of claim 1 comprising about 100 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 17. The oral dosage form of claim 1 comprising about 200 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 18. The oral dosage form of claim 1 comprising about 300 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 19. The oral dosage form of claim 1 comprising about 400 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 20. The oral dosage form of claim 1 comprising about 500 mg of the compound or a pharmaceutically acceptable salt or prodrug thereof. 21. The oral dosage form of any one of claims 1-20, wherein the oral dosage form is a tablet or capsule. 22. A method of treating or preventing a disease or condition characterized by aberrant complement system activity, comprising orally administering to a patient in need thereof a therapeutically effective amount of 2-(2-((7-(2-(aminomethyl)pyridin-4-yl)-2- methylbenzofuran-5-yl)methoxy)phenyl)acetic acid, or a pharmaceutically acceptable salt or prodrug thereof. 23. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is IgA nephropathy. 24. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is complement 3 glomerulopathy. 25. The method of claim 23, wherein complement 3 glomerulopathy is dense-deposit disease or C3 glomerulonephritis. 26. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is paroxysmal nocturnal hemoglobinuria. 27. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is atypical hemolytic uremic syndrome, myasthenia gravis, neuromyelitis optica, membranoproliferative glomerulonephritis, cold agglutinin disease, or catastrophic antiphospholipid syndrome. 28. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is anti-neutrophil cytoplasmic antibody-associated vasculitis, warm autoimmune hemolytic anemia, IgA nephropathy, IgA vasculitis, primary membranous neuropathy, focal segmental glomerulosclerosis, rhabdomylosis-induced acute kidney injury, - 37 - FH11781014.1 BPX-05425 lupus nephritis, IgA nephritis, myasthenia gravis, hematopoietic stem cell transplantation transplant associated thrombotic microangiopathy or thrombotic thrombocytopenic purpura. 29. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is macular degeneration, age-related macular degeneration (AMD), wet AMD, dry AMD, macular edema, diabetic macular edema, choroidal neovascularization, uveitis, Behcet’s uveitis, proliferative diabetic retinopathy, non- proliferative diabetic retinopathy, glaucoma, hypertensive retinopathy, a corneal neovascularization disease, post-corneal transplant rejection, a corneal dystrophic disease, an autoimmune dry eye disease, Stevens-Johnson syndrome, Sjogren’s syndrome, an environmental dry eye disease, Fuchs’ endothelial dystrophy, retinal vein occlusion, or post- operative inflammation 30. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is Guillain–Barré syndrome variants, chronic inflammatory demyelinating polyneuropathy, genetic demyelinating neuropathy, IgM neuropathy, neuropathic pain, Lambert–Eaton myasthenic syndrome, dermatomyositis, or necrotizing autoimmune myositis. 31. The method of claim 22, wherein the disease or condition characterized by aberrant complement system activity is multiple sclerosis, neuromyelitis optica spectrum disorders, autoimmune encephalopathies, traumatic brain injury, amyotrophic lateral sclerosis, Huntington disease, and schizophrenia. 32. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 600 mg. 33. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 550 mg. 34. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 500 mg. 35. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 450 mg. 36. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 400 mg. 37. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 350 mg. 38. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 300 mg. - 38 - FH11781014.1 BPX-05425 39. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 250 mg. 40. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 200 mg. 41. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg to about 160 mg. 42. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 80 mg. 43. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 160 mg. 44. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 320 mg. 45. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 480 mg. 46. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 100 mg. 47. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 200 mg. 48. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 300 mg. 49. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 400 mg. 50. The method of any one of claims 22-31, wherein the therapeutically effective amount is about 500 mg. 51. The method of any one of claims 22-50, wherein the compound or a pharmaceutically acceptable salt or prodrug thereof is administered once daily. 52. The method of any one of claims 22-51, wherein the compound or a pharmaceutically acceptable salt or prodrug thereof is administered as an oral dosage form. 53. The method of any one of claims 52 wherein the oral dosage form is a tablet or capsule. 54. 2-(2-((7-(2-(aminomethyl)pyridin-4-yl)-2-methylbenzofuran-5- yl)methoxy)phenyl)acetic acid, or a pharmaceutically acceptable salt or prodrug thereof, for use in the treatment of a disease of condition characterized by aberrant complement system activity, wherein 2-(2-((7-(2-(aminomethyl)pyridin-4-yl)-2-methylbenzofuran-5- - 39 - FH11781014.1 BPX-05425 yl)methoxy)phenyl)acetic acid, or a pharmaceutically acceptable salt or prodrug thereof, is administered orally. - 40 - FH11781014.1