PLA2R

Announced acceptance and Priority Review by the United States Food and Drug Administration (FDA) of the new drug application (NDA) for troriluzole in all-genotype spinocerebellar ataxia; expected Prescription Drug User Fee Act (PDUFA) date in 3Q 2025. Cash, cash equivalents, marketable securities and restricted cash as of December 31, 2024 totaled approximately $489 million. Reported positive degrader data with multiple doses of BHV-1300 achieving up to 84% reduction of total IgG, with a median reduction of 80%, after subcutaneous weekly 1000 mg dosing in the ongoing Phase 1 study. Optimized subcutaneous administration of BHV-1300 achieved rapid, deep and sustained lowering of total IgG, differentiating Biohaven's new small-molecule class of degraders from the monoclonal antibody FcRn-targeting competition Doses up to 2000 mg have been safe and well-tolerated. Dose escalation is ongoing with the optimized subcutaneous formulation of BHV-1300 to explore full range of IgG lowering and Phase 1 study completion expected in 1H 2025. Expect to initiate Phase 2 study in Graves' disease in mid-2025. Accelerating clinical development and operational execution across five innovative platforms including more than 10 assets in 6 therapeutic areas spanning immunology & inflammation, neuroscience, and oncology: Portfolio targeting large indications including obesity, epilepsy, depression, obsessive-compulsive disorder (OCD), migraine, pain, Alzheimer's disease, Parkinson's disease, Graves' disease, multiple sclerosis (MS), rheumatoid arthritis, and cancer. Also advancing treatments for rare diseases including myasthenia gravis, peripartum cardiomyopathy, spinal muscular atrophy, and IgA nephropathy. Pursuing targeted, patient-directed, immune-modulating treatment with next generation and selective TRAP™ degraders: IgA Nephropathy (IgAN) program: First-in-human dosing with BHV-1400, a next generation Targeted Removal of Aberrant Proteins (TRAP™) degrader, achieved rapid, deep, and selective lowering of only aberrant galactose-deficient IgA1 (Gd-IgA1), the antibody causing IgA nephropathy, while sparing normal IgA. The first and lowest dose tested (125 mg) of BHV-1400 in the ongoing Phase 1 trial achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration after a single dose. Maximal reduction exceeding 70% was observed within eight hours. Reductions were sustained for days even after a single dose. Additional SAD and MAD cohorts with BHV-1400 have been completed and will be presented at an upcoming conference. Peripartum cardiomyopathy (PPCM) program: First-in-human dosing with BHV-1600, a TRAP degrader of β1AR autoantibodies, was initiated and has been well-tolerated to date after the first two dosing cohorts without clinically significant changes in innate or adaptive immunity, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM. Additional SAD and MAD cohorts with BHV-1600 have been completed and will be presented at an upcoming conference. Both compounds have been safe and well tolerated and Phase 1 studies with BHV-1400 and BHV-1600 are expected to be completed in 1H 2025. Additional degraders advancing including IgG4 degrader, PLA2R autoantibody degrader, insulin autoantibody degrader, and TSH receptor autoantibody degrader. Pivotal clinical data and other developmental milestones expected across balance of portfolio: Troriluzole (novel glutamate modulator): Following FDA acceptance and Priority Review grant for troriluzole NDA, the Company is preparing for commercial launch in SCA in 2025, if approved. Topline data from Phase 3 OCD trial in 1H 2025. BHV-7000 (selective activator of Kv7.2/7.3 potassium channels): Registrational Phase 2/3 studies ongoing in major depressive disorder, focal epilepsy, and generalized epilepsy. Bipolar mania 3-week study did not statistically separate from the comparator on the Young Mania Rating Scale primary outcome measure and analyses are ongoing with results expected to be presented at an upcoming conference. Major depressive disorder topline results expected in 2H 2025. Focal epilepsy study topline results expected in 1H 2026. BHV-2100 (oral, selective TRPM3 antagonist offering novel, non-addictive treatment for migraine and neuropathic pain): Topline data from the laser-evoked potential study in 1H 2025; proof-of-concept in migraine ongoing. Taldefgrobep alfa (novel myostatin inhibitor): Expect FDA meeting to discuss SMA registrational path in 1H 2025; separately initiating taldefgrobep alfa Phase 2 study in obesity in 1H 2025. BHV-8000 (highly selective, oral, brain-penetrant, TYK2/JAK1 inhibitor, broad potential for neurodegenerative and neuroinflammatory disorders): Initiating BHV-8000 Phase 2/3 study in Parkinson's disease in 1H 2025 and advancing Alzheimer's disease, MS and ARIA programs in 2025. Advancing oncology next-generation antibody drug conjugate (ADC) portfolio: Milestones with novel ADC technology and strategic collaborations driving next-generation cancer therapies include: preliminary Phase 1 data with BHV-1510, and ongoing dose optimization as monotherapy and combination therapy with Libtayo® in epithelial tumors, with interim Phase 1 data anticipated in 2H 2025; Phase 1 trial initiation of the novel FGFR3-directed ADC, BHV-1530, planned in 1H 2025; and advancing additional ADC programs through collaborations with Merus and GeneQuantum. NEW HAVEN, Conn., March 3, 2025 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases, today provided a review of recent accomplishments and anticipated upcoming developments and reported financial results for the fourth quarter and full year ended December 31, 2024. Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "We have made considerable progress this past year in advancing our innovative and diversified portfolio. Most notably, we oversaw the advent of our groundbreaking degrader or MoDE™ technology continue to advance into the clinic, with today's added news that multiple doses of BHV-1300 lowered serum IgG by up to 84% from baseline. Modulation of IgG has proven to be an exciting and growing market in the treatment of autoimmune disease, and BHV-1300 has the potential to further advance the field. Our next generation TRAP™ degraders offer the additional advantage of selectively removing antigen-specific targets while sparing off-target effects to allow continued healthy immune functioning. The selectivity of MoDE and TRAP degraders demonstrated to date has the potential to redefine the immune-modulating treatment paradigm. The implications and applications of this selective targeting could be multi-organ, multi-disease and we are eager to continue unlocking the vast potential afforded by our innovative degrader technology." Dr. Coric continued, "Thanks to focused execution across the balance of our portfolio, we believe we are poised to deliver important milestones in 2025 and beyond, starting with the FDA accepting our troriluzole NDA filing resubmission and granting Priority Review. An approval in this indication could profoundly impact the outlook for nearly 40,000 patients living with spinocerebellar ataxia across the globe and we are making commercial plans in earnest as we await final regulatory outcomes; we separately await the results of critical Phase 3 data in each of our 2 identical ongoing studies in OCD. Our ion channel platform expects to report topline pivotal results with our Kv7.2/7.3 potassium channel activator, BHV-7000, in major depressive disorder in 2H 2025 and in focal epilepsy in 1H 2026. Furthering our expansion of knowledge for our ion channel platform, we expect to report data from the laser-evoked hyperalgesia and proof-of-concept migraine studies with TRPM3 antagonist, BHV-2100, in 1H 2025. With taldefgrobep alfa, our anti-myostatin agent, we likewise look forward to working with appropriate regulatory bodies to establish a potential path forward in spinal muscular atrophy as we work in tandem to initiate our Phase 2 study in obesity. Regarding our brain-penetrant TYK2/JAK1 Inhibitor, we are eager to initiate our Phase 2/3 study in Parkinson's disease in the first half of the year as we advance programs in Alzheimer's, MS, and ARIA in parallel. Finally, we are significantly advancing our ADC portfolio as new strategic collaborations and ongoing clinical and non-clinical work has invigorated our oncology franchise, with several milestones anticipated in 2025, including interim Phase 1 data with our lead clinical Trop-2 ADC program, BHV-1510 and a Phase 1 initiation with our novel FGFR3 ADC, BHV-1530, for patients with urothelial cancer & other tumors; we are also advancing multiple ADCs through our newly announced collaborations with Merus and GeneQuantum." "An exciting year awaits us to be sure, and as we move forward, I'm confident our strong momentum will continue thanks to the unwavering dedication of our talented team, underpinned by our relentless desire to innovate, serve patients, and generate value in lockstep." Full Year and Recent Business Highlights Glutamate Modulation Platform - Milestones and Next Steps: Troriluzole is a novel glutamate modulator currently in Phase 3 development for all-genotype spinocerebellar ataxia (SCA) and obsessive-compulsive disorder (OCD). The FDA has accepted for review the Company's NDA for troriluzole for the treatment of adult patients with SCA and has granted Priority Review; troriluzole previously received Orphan Drug and Fast-Track designations. EU marketing authorization application is also under review for troriluzole in all SCA genotypes. There are no FDA-approved treatments for SCA. Additionally, two Phase 3 trials with troriluzole in OCD are ongoing. Announced FDA acceptance and Priority Review of troriluzole NDA for the treatment of spinocerebellar ataxia: The FDA's decision regarding the NDA is expected within 6 months of filing (during 3Q 2025). Based on FDA Priority Review timelines and, if ultimately approved, Biohaven is prepared to commercialize troriluzole for SCA in the US in 2025. The Company had previously achieved positive topline results in a pivotal study of troriluzole in SCA. Troriluzole 200 mg dosed orally, once daily, in patients with SCA met the study's primary endpoint on the change from baseline in the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) at 3 years in all study population genotypes. Troriluzole also showed statistically significant superiority after both 1 and 2 years of treatment. Troriluzole achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. SCA patients treated with troriluzole showed a 50-70% slowing of disease progression, representing 1.5-2.2 years delay in disease progression over the 3-year study period. Upcoming milestones: Following FDA acceptance of the troriluzole all-genotype SCA NDA filing resubmission with Priority Review status and a 3Q 2025 PDUFA date, the Company is preparing for commercial launch in SCA in 2025, pending approval. Topline data from two Phase 3 OCD trials in 1H 2025 and 2H 2025, respectively. Inflammation and Immunology Platform - Milestones and Next Steps: Targeted Extracellular Protein Degradation Biohaven's novel immune-modulating extracellular degrader platform harnesses selectivity, rapidity, and patient-friendly self-administration to remove disease-causing proteins from the body to potentially treat a wide range of diseases; MoDEs™ (Molecular Degraders of Extracellular Proteins) uniquely harness the hepatic asialoglycoprotein receptor (ASGPR) for efficient and safe removal of circulating pathogenic targets. BHV-1300 and BHV-1310 are IgG degraders; Biohaven introduced next generation TRAPTM (Targeted Removal of Aberrant Protein) degraders, which are highly selective, each targeting a specific disease-causing protein for proteolysis; BHV-1400 is a TRAP degrader targeting Gd-IgA1. BHV-1600 is a TRAP degrader targeting β1-AR autoantibodies. Announced multiple advancements across MoDE and TRAP platforms: IgA Nephropathy (IgAN) program: First-in-human (FIH) dosing with BHV-1400 achieved rapid, deep, and selective lowering of only aberrant galactose-deficient IgA1 (Gd-IgA1).The first and lowest dose tested (125 mg) of BHV-1400 in the ongoing Phase 1 trial achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration after a single dose. Maximal reduction exceeding 70% was observed within eight hours. Reductions were sustained for days even after a single dose. BHV-1400 has been safe and well-tolerated in the Phase 1 study to date and demonstrated no clinically significant changes in innate or adaptive immunity. Peripartum cardiomyopathy (PPCM) program: FIH dosing with BHV-1600 was initiated and has been well-tolerated to date after the first two dosing cohorts without clinically significant changes in innate or adaptive immunity. Held INTERACT meeting with FDA in 4Q 2024. IgG degrader programs: BHV-1300: Advanced optimized subcutaneous formulation with deep reductions of total IgG exceeding 80% with 1,000 mg weekly dosed over four weeks in the ongoing Phase 1 study. Doses of up to 2,000 mg have been safe and well-tolerated. There were no clinically significant reductions in IgG3, IgA, IgE, IgM, or albumin, nor clinically significant increases in AST, ALT, bilirubin, or cholesterol. Upcoming milestones: IgG MoDE Degraders (1300/1310): BHV-1300 Phase 1 with the optimized subcutaneous formulation expected completion in 1H 2025. BHV-1310 completion of preclinical testing prior to anticipated first-in-human study initiating 1H 2025. Phase 2 study in Graves' disease expected to initiate mid-2025 and additional programs in rheumatoid arthritis and myasthenia gravis continue to be pursued. Phase 1 study with BHV-1400 and BHV-1600 expected to be completed in 1H 2025. Four additional degraders advancing including: IgG4 degrader, PLA2R autoantibody degrader, insulin autoantibody degrader, and TSH receptor autoantibody degrader. TYK2/JAK1 Inhibition BHV-8000 is an oral, brain-penetrant, selective TYK2/JAK1 inhibitor with broad potential for neuroinflammatory and neurodegenerative disorders. Completed Phase 1 study with BHV-8000: In the Phase 1 SAD/MAD study in healthy participants, BHV-8000 was generally safe and well-tolerated while producing significant reductions in inflammatory biomarkers relative to placebo. Biohaven completed interactions with FDA enabling registrational programs for Parkinson's disease and the prevention of ARIA. Upcoming milestones: Initiate BHV-8000 Phase 2/3 study in Parkinson's disease in 1H 2025. Advance Alzheimer's, MS and ARIA programs in 2025. Ion Channel Platform - Milestones and Next Steps: Kv7 Activation: Epilepsy & Neuropsychiatric Indications BHV-7000, the lead asset from the Kv7 platform, is a selective activator of Kv7.2/Kv7.3 potassium channels. Kv7 activation is a clinically validated target for treating mood disorders and epilepsy. Four registrational studies are ongoing in major depressive disorder, focal epilepsy, and generalized epilepsy. BHV-7000 once-daily extended-release formulation data presented: Reported expanded safety results from BHV-7000 Phase 1 MAD studies at the American Epilepsy Society (AES) 2024 Annual Meeting, including the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies, demonstrating excellent tolerability at all doses evaluated without central nervous system (CNS) adverse effects typically associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances. BHV-7000 was safe and well-tolerated at dose levels up to 120 mg daily for 15 days with no dose-limiting toxicities; 120 mg exceeds the doses being evaluated in ongoing Phase 2 and 3 clinical studies of up to 75 mg daily in focal epilepsy, idiopathic generalized epilepsy, and major depressive disorder. Completed a focused topline analysis of treatment with BHV-7000 in the acute treatment of manic episodes associated with bipolar disorder in a 3-week trial: BHV-7000 did not statistically differentiate from the comparator arm on the primary efficacy endpoint of improvement from Baseline to Day 21 on the Young Mania Rating Scale. Additional analyses are ongoing, and complete study results will be presented at an upcoming scientific meeting. BHV-7000 75 mg once daily, the highest dose of BHV-7000 being evaluated in Phase 2/3 trials, was safe and well-tolerated in this study. No adverse trends in vital signs, ECGs, or labs were noted. There were no treatment emergent serious adverse events. Most adverse events were mostly mild in intensity and resolved spontaneously. This offers a highly favorable and differentiated profile compared to other antiseizure medicines and is consistent with lack of GABA effects. Upcoming milestones: Pivotal major depressive disorder topline results expected in 2H 2025. Focal epilepsy study topline results expected in 1H 2026. TRPM3 Ion Channel Antagonism: Migraine & Neuropathic Pain BHV-2100 is an oral, selective TRPM3 antagonist potentially offering a novel, non-addictive treatment for migraine and neuropathic pain Phase 1 study data supports evaluation in migraine and pain: Based on favorable PK and safety data from Phase 1 studies in healthy subjects, a Phase 1b laser-evoked hyperalgesia trial completed and a proof-of-concept in the acute treatment of migraine is ongoing. Preliminary data from the laser-evoked hyperalgesia study demonstrated that BHV-2100 reduced laser heat-induced pain and brain evoked potentials in healthy volunteers, providing the first indication of potential clinical efficacy in pain with the novel TRPM3 mechanism recapitulating antinociceptive preclinical efficacy across a spectrum of pain models. Upcoming milestones: Data from the laser-evoked potential study and migraine proof-of-concept in 1H 2025. Myostatin Platform - Milestones and Next Steps: Taldefgrobep is a novel myostatin inhibitor that is optimized to block signaling of myostatin and other activin II receptor ligands, key regulators of muscle and fat metabolism. Biohaven is studying taldefgrobep in a global Phase 3 expansion study in Spinal Muscular Atrophy (SMA), as an adjunctive therapy to enhance muscle mass and function in patients treated with standard-of-care therapies. Provided update on Phase 3 taldefgrobep alfa program for spinal muscular atrophy: In November 2024, the Company presented analyses of prespecified subgroups by race and ethnicity demonstrating that the largest study population (87% Caucasian; n=180) showed clinically meaningful improvements on the MFM-32 at all timepoints, including Week 48, compared to the corresponding placebo+SOC group (p < 0.05), though the overall primary endpoint was not met. Additionally, robust target engagement (myostatin reduction) and beneficial impacts on body composition parameters (fat mass, lean muscle mass, and bone density) were noted, offering a potential paradigm shift in the treatment of obesity with opportunity to improve quality of weight loss; lower total body weight by specifically reducing fat mass while also preserving or increasing lean muscle mass. Upcoming milestones : Expect FDA meeting to discuss SMA registrational path in 1H 2025 Initiate taldefgrobep Phase 2 study in obesity in 1H 2025 Next-Generation ADC Platform - Milestones and Next Steps: Biohaven's antibody drug conjugate (ADC) technology is focused on novel, modular site-specific conjugation chemistry approaches, with the potential to drive superior clinical profiles compared to current industry standard maleimide and lipophilic click chemistries. BHV-1510, a clinical-stage TROP2 directed ADC with a highly differentiated preclinical efficacy and safety profile, has demonstrated early Phase 1 clinical activity and a tolerable safety profile of the novel topoisomerase 1 inhibitor (TopoIx) payload in early cohorts, with no payload associated interstitial lung disease, gastrointestinal toxicities or significant hematological toxicities. Dose escalation and optimization are ongoing as monotherapy and in combination with Libtayo (R) (cemiplimab), an anti-PD1 checkpoint inhibitor, through a clinical supply agreement with Regeneron. Based on the preclinical profile and encouraging early results with BHV-1510, Biohaven has entered into an expanded collaboration agreement with GeneQuantum, which provides broad target exclusivity for up to 18 ADC targets incorporating the TopoIx payload The next ADC program positioned to enter clinic, BHV-1530, is a novel FGFR3 ADC that incorporates the TopoIx payload. Similar to BHV-1510, this program has demonstrated a differentiated efficacy and safety profile in preclinical studies, including synergistic in vivo efficacy in combination with a checkpoint inhibitor. Potential indications include urothelial cancer and other FGFR3-driven solid tumors. In January 2025, Biohaven also announced a multi-target collaboration with Merus N.V. to co-develop three novel dual-targeted ADCs, leveraging Merus' Biclonics® technology platform, and Biohaven's next-generation ADC conjugation and payload technologies. Expected Upcoming Milestones: We believe Biohaven is well positioned to achieve significant milestones in 2025 and 2026 across numerous programs: MoDE™ Platform IgG MoDE Degraders (1300/1310): BHV-1300 Phase 1 with the optimized subcutaneous formulation completing in 1H 2025. BHV-1310 completion of preclinical testing prior to anticipated FIH study initiating 1H 2025. Expect to initiate Phase 2 study in Graves' disease in mid-2025, and additional programs in rheumatoid arthritis and myasthenia gravis continue to be pursued. Phase 1 with BHV-1400 and BHV-1600 expected to be completed in 1H 2025. Four additional degrader molecules advancing including: IgG4 degrader, PLA2R autoantibody degrader, insulin autoantibody degrader, and TSH receptor autoantibody degrader. Kv7 Activator (BHV-7000): Pivotal major depressive disorder topline results expected in 2H 2025. Focal epilepsy study topline results expected in 1H 2026. Glutamate Modulator (Troriluzole): Preparing for commercial launch in all-genotype SCA in 2025, following FDA filing acceptance and 3Q 2025 PDUFA date. Topline data from two Phase 3 OCD trials in 1H 2025 and 2H 2025, respectively. Myostatin (Taldefgrobep alfa): Expect FDA meeting to discuss SMA registrational path in 1H 2025. Initiate taldefgrobep Phase 2 study in obesity in 1H 2025. TRPM3 Antagonist (BHV-2100): Continue advancing enrollment in proof of concept trial with BHV-2100 in acute migraine; data from the laser-evoked potential study expected in 1H 2025. TYK2/JAK1 Inhibitor (BHV-8000): Initiate BHV-8000 Phase 2/3 study in Parkinson's disease in 1H 2025. Advance Alzheimer's, MS and ARIA programs. Next Generation ADC Platform: Interim Phase 1 data with BHV-1510 and dose optimization as monotherapy and combination therapy with Libtayo® in epithelial tumors in 2025. Initiate Phase 1 trial of BHV-1530 in 1H 2025. Advance Merus collaboration ADCs (undisclosed targets) and TopoIx ADCs in 2025. Capital Position: Cash, cash equivalents, marketable securities and restricted cash as of December 31, 2024 totaled approximately $489 million. Fourth Quarter 2024 Financial Highlights: Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $167.5 million for the three months ended December 31, 2024, compared to $134.8 million for the three months ended December 31, 2023. The increase of $32.7 million was due to additional and advancing clinical trials, including late Phase 3 and Phase 2/3 studies, and preclinical research programs in 2024, as compared to the same period in the prior year. Non-cash share-based compensation expense was $7.1 million for the three months ended December 31, 2024, a decrease of $2.0 million as compared to the same period in 2023. Non-cash share-based compensation expense was lower in the fourth quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 with no new annual equity incentive awards granted in the fourth quarter of 2024. General and Administrative (G&A) Expenses: G&A expenses were $22.5 million for the three months ended December 31, 2024, compared to $18.9 million for the three months ended December 31, 2023. The increase of $3.6 million was primarily due to increased personnel and legal costs for the three months ended December 31, 2024 as compared to the same period in 2023. Non-cash share-based compensation expense was $5.6 million for the three months ended December 31, 2024, a decrease of $1.1 million as compared to the same period in 2023. Non-cash share-based compensation expense was lower in the fourth quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 with no new annual equity incentive awards granted in the fourth quarter of 2024. Other Income, Net: Other income, net was $3.1 million for the three months ended December 31, 2024, compared to other income, net of $7.7 million for the three months ended December 31, 2023. The decrease of $4.6 million was primarily due to non-cash changes in the fair value of our forward contract and derivative liabilities recorded in connection with the amendment to our Membership Interest Purchase Agreement with Knopp Biosciences LLC in May 2024 (the Knopp Amendment) and decreased service revenue from the Transition Service Agreement we entered into with Biohaven Pharmaceutical Holding Company Ltd. (the "Former Parent"). Net Loss: Biohaven reported a net loss for the three months ended December 31, 2024 of $186.8 million, or $1.85 per share, compared to $144.8 million, or $1.81 per share, for the same period in 2023. Non-GAAP adjusted net loss for the three months ended December 31, 2024 was $173.3 million, or $1.71 per share, compared to $128.9 million, or $1.61 per share for the same period in 2023. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and losses from the change in fair value of derivatives. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below. Full Year 2024 Financial Highlights R&D Expenses: R&D expenses, including non-cash share-based compensation, were $795.9 million for the year ended December 31, 2024, compared to $373.3 million for the year ended December 31, 2023. The increase was largely due to non-cash expense of $171.9 million paid to Knopp for a milestone and royalty buyback related to BHV-7000 and the broader Kv7 platform that was recognized during the three months ended June 30, 2024. The buyback reduced our potential future milestone payments by $867.5 million, and replaced the scaled high single digit to low teens royalty payment obligations with a flat royalty payment in the mid-single digits for the Kv7 programs. The increase in R&D expenses was also related to advancing our clinical platforms including four Phase 3 study starts and one Phase 2 study start for BHV-7000, follow-on Kv7 assets, preclinical research programs, and increases in direct program spend for additional multiple clinical development programs in 2024, as compared to the same period in the prior year. The increase was also due to a $40.2 million increase in personnel costs, primarily due to increased non-cash share based compensation expense and increased headcount to support our expanding clinical and preclinical research programs. Non-cash share-based compensation expense was $42.6 million for the year ended December 31, 2024, an increase of $26.6 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the year ended December 31, 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and first quarter of 2024. G&A Expenses: G&A expenses, including non-cash share-based compensation costs, were $89.2 million for the year ended December 31, 2024, compared to $62.8 million for the year ended December 31, 2023. The increase of $26.5 million was primarily due to increased non-cash share-based compensation costs and increased legal costs. Non-cash share-based compensation expense was $29.4 million for the year ended December 31, 2024, an increase of $16.6 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in 2024 primarily due to our annual equity incentive awards being partially granted in the fourth quarter of 2023 with a greater portion granted in the first quarter of 2024, partially offset by the subsequent year annual equity incentive awards being granted in the first quarter of 2025 and no partial grants from such annual equity incentive awards in the fourth quarter of 2024. Other Income (Expense), Net: Other income (expense), net was income of $39.4 million for the year ended December 31, 2024, compared to income of $26.5 million for the year ended December 31, 2023. The increase of $12.9 million was primarily due to non-cash changes in the fair value of our forward contract and derivative liabilities recorded in connection with the Knopp Amendment as well as increased investment income. The increases were partially offset by a decrease in other income recognized during the year ended December 31, 2024 as compared to 2023 related to the Transition Services Agreement entered into with the Former Parent. Net Loss: The Company reported a net loss attributable to common shareholders for the year ended December 31, 2024 of $846.4 million, or $9.28 per share, compared to $408.2 million, or $5.73 per share for the same period in 2023. Non-GAAP adjusted net loss for the year ended December 31, 2024 was $790.6 million, or $8.67 per share, compared to $379.4 million, or $5.33 per share for the same period in 2023. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and losses from the change in fair value of derivatives. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below. Non-GAAP Financial Measures This press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and certain non-GAAP financial measures. In particular, Biohaven has provided non-GAAP adjusted net loss and adjusted net loss per share, which are adjusted to exclude non-cash share-based compensation, which is substantially dependent on changes in the market price of common shares, and changes in the fair value of derivative liabilities, which do not correlate to actual cash payment obligations in the relevant periods. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. However, Biohaven believes the presentation of non-GAAP adjusted net loss and adjusted net loss per share, when viewed in conjunction with GAAP results, provides investors with a more meaningful understanding of ongoing operating performance and can assist investors in comparing Biohaven's performance between periods. In addition, these non-GAAP financial measures are among those indicators Biohaven uses as a basis for evaluating performance, and planning and forecasting future periods. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between these non-GAAP measures and the most directly comparable GAAP measures is provided later in this news release. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and preclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA; myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules; and antibody drug conjugates for cancer. Forward-looking Statements This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates and the expected timing thereof; the potential for Biohaven's product candidates to be successful therapies; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. MoDEs and TRAP are trademarks of Biohaven Therapeutics Ltd. Libtayo is a registered trademark of Regeneron Pharmaceuticals, Inc. Investor Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] +1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] +1 (312) 961-2502 SOURCE Biohaven Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Presents progress and new anticipated milestones across portfolio of more than 10 assets and 6 therapeutic areas. Announces multiple advancements across the MoDETM (molecular degraders of extracellular proteins) platform and the next generation TRAPTM (targeted removal of aberrant protein) degraders, including: IgA Nephropathy (IgAN) program: First-in-human dosing with BHV-1400, a next generation TRAP degrader, achieved rapi­d, deep, and selective lowering of only aberrant galactose-deficient IgA1 (Gd-IgA1), the antibody causing IgA nephropathy, while sparing normal IgA. This selective and rapid approach to immunoglobulin lowering represents a second-generation therapeutic approach to IgAN, potentially allowing for strong disease control with less acute or long-term safety risks associated with complement inhibition or broad antibody suppression. The first and lowest dose tested (125mg) of BHV-1400 in the ongoing Phase 1 achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration after a single dose. Maximal reduction exceeding 70% was observed within eight hours. Reductions were sustained for days even after a single dose. This rapid reduction of Gd-IgA1 is unprecedented in drugs targeting Gd-IgA1 and could allow for potential indications in situations where rapid Gd-IgA1 lowering could be beneficial in addition to chronic active disease and long-term maintenance. BHV-1400 has been safe and well-tolerated in the Phase 1 study to date and demonstrated no clinically significant changes in innate or adaptive immunity, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM. There were no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. No dose limiting toxicities have been observed in the Phase 1 to date and further dose escalation is planned to explore the full range of Gd-IgA1 reductions possible with BHV-1400. A pivotal trial in IgA nephropathy is planned using an accelerated regulatory path forward upon completion of the Phase 1 trial. Peripartum cardiomyopathy (PPCM) program: First-in-human dosing with BHV-1600, a TRAP degrader of β1AR autoantibodies, was initiated and has been well-tolerated to date after the first two dose cohorts without clinically relevant changes in innate or adaptive immunity, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM. There were no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. β1AR autoantibodies are thought to cause peripartum cardiomyopathy, a rare form of heart failure that develops at the end of pregnancy or in the months following delivery and in severe cases, can be life-threatening. BHV-1600 has been shown to bind to β1AR autoantibodies in preclinical studies and biomarker levels will be measured in women with PPCM later in development. Completed INTERACT meeting with FDA regarding BHV-1600 in 4Q 2024; gained alignment for the study design to potentially pursue an accelerated approval pathway in PPCM. IgG degrader programs: BHV-1300: Advanced optimized subcutaneous formulation with deep reductions of targeted IgG >60% demonstrated in the lowest dose cohort of the MAD, in line with modeling projections and with differentiated safety profile. There were no clinically significant reductions in IgG3, IgA, IgE, IgM, or albumin, no liver function test abnormalities, nor increases in cholesterol compared to baseline. Phase 1 completing last remaining dose cohorts with the optimized subcutaneous formulation in 1H 2025. Lead indication for BHV-1300 announced in Graves' Disease, a common autoimmune disorder affecting approximately 80 million people globally. Graves' Disease is caused by IgG1 autoantibodies that hyperstimulate the TSH receptor, causing hyperthyroidism can result in the need for surgical removal, chemical ablation of the thyroid, or need for chronic anti-thyroid drugs. Additional programs in rheumatoid arthritis and myasthenia gravis also continue to be pursued with BHV-1300 and 1310. Study May Proceed letter received from FDA for BHV-1310 IND, a novel IgG degrader and Phase 1 initiating in 1H 2025. BHV-1300 and BHV-1310 are similar but will optimize therapeutic targeting and facilitate broader commercial development options. Next generation degrader targets advancing in 2025 include: IgG4 specific degrader, PLA2R autoantibody degrader for membranous nephropathy, pro-insulin autoantibody degrader for type 1 diabetes, and TSH receptor autoantibody degrader as a selective follow-on asset for Graves' Disease. IgA Nephropathy (IgAN) program: First-in-human dosing with BHV-1400, a next generation TRAP degrader, achieved rapi­d, deep, and selective lowering of only aberrant galactose-deficient IgA1 (Gd-IgA1), the antibody causing IgA nephropathy, while sparing normal IgA. This selective and rapid approach to immunoglobulin lowering represents a second-generation therapeutic approach to IgAN, potentially allowing for strong disease control with less acute or long-term safety risks associated with complement inhibition or broad antibody suppression. The first and lowest dose tested (125mg) of BHV-1400 in the ongoing Phase 1 achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration after a single dose. Maximal reduction exceeding 70% was observed within eight hours. Reductions were sustained for days even after a single dose. This rapid reduction of Gd-IgA1 is unprecedented in drugs targeting Gd-IgA1 and could allow for potential indications in situations where rapid Gd-IgA1 lowering could be beneficial in addition to chronic active disease and long-term maintenance. BHV-1400 has been safe and well-tolerated in the Phase 1 study to date and demonstrated no clinically significant changes in innate or adaptive immunity, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM. There were no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. No dose limiting toxicities have been observed in the Phase 1 to date and further dose escalation is planned to explore the full range of Gd-IgA1 reductions possible with BHV-1400. A pivotal trial in IgA nephropathy is planned using an accelerated regulatory path forward upon completion of the Phase 1 trial. Peripartum cardiomyopathy (PPCM) program: First-in-human dosing with BHV-1600, a TRAP degrader of β1AR autoantibodies, was initiated and has been well-tolerated to date after the first two dose cohorts without clinically relevant changes in innate or adaptive immunity, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM. There were no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. β1AR autoantibodies are thought to cause peripartum cardiomyopathy, a rare form of heart failure that develops at the end of pregnancy or in the months following delivery and in severe cases, can be life-threatening. BHV-1600 has been shown to bind to β1AR autoantibodies in preclinical studies and biomarker levels will be measured in women with PPCM later in development. Completed INTERACT meeting with FDA regarding BHV-1600 in 4Q 2024; gained alignment for the study design to potentially pursue an accelerated approval pathway in PPCM. IgG degrader programs: BHV-1300: Advanced optimized subcutaneous formulation with deep reductions of targeted IgG >60% demonstrated in the lowest dose cohort of the MAD, in line with modeling projections and with differentiated safety profile. There were no clinically significant reductions in IgG3, IgA, IgE, IgM, or albumin, no liver function test abnormalities, nor increases in cholesterol compared to baseline. Phase 1 completing last remaining dose cohorts with the optimized subcutaneous formulation in 1H 2025. Lead indication for BHV-1300 announced in Graves' Disease, a common autoimmune disorder affecting approximately 80 million people globally. Graves' Disease is caused by IgG1 autoantibodies that hyperstimulate the TSH receptor, causing hyperthyroidism can result in the need for surgical removal, chemical ablation of the thyroid, or need for chronic anti-thyroid drugs. Additional programs in rheumatoid arthritis and myasthenia gravis also continue to be pursued with BHV-1300 and 1310. Study May Proceed letter received from FDA for BHV-1310 IND, a novel IgG degrader and Phase 1 initiating in 1H 2025. BHV-1300 and BHV-1310 are similar but will optimize therapeutic targeting and facilitate broader commercial development options. Next generation degrader targets advancing in 2025 include: IgG4 specific degrader, PLA2R autoantibody degrader for membranous nephropathy, pro-insulin autoantibody degrader for type 1 diabetes, and TSH receptor autoantibody degrader as a selective follow-on asset for Graves' Disease. This selective and rapid approach to immunoglobulin lowering represents a second-generation therapeutic approach to IgAN, potentially allowing for strong disease control with less acute or long-term safety risks associated with complement inhibition or broad antibody suppression. The first and lowest dose tested (125mg) of BHV-1400 in the ongoing Phase 1 achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration after a single dose. Maximal reduction exceeding 70% was observed within eight hours. Reductions were sustained for days even after a single dose. This rapid reduction of Gd-IgA1 is unprecedented in drugs targeting Gd-IgA1 and could allow for potential indications in situations where rapid Gd-IgA1 lowering could be beneficial in addition to chronic active disease and long-term maintenance. BHV-1400 has been safe and well-tolerated in the Phase 1 study to date and demonstrated no clinically significant changes in innate or adaptive immunity, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM. There were no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. No dose limiting toxicities have been observed in the Phase 1 to date and further dose escalation is planned to explore the full range of Gd-IgA1 reductions possible with BHV-1400. A pivotal trial in IgA nephropathy is planned using an accelerated regulatory path forward upon completion of the Phase 1 trial. Completed INTERACT meeting with FDA regarding BHV-1600 in 4Q 2024; gained alignment for the study design to potentially pursue an accelerated approval pathway in PPCM. BHV-1300: Advanced optimized subcutaneous formulation with deep reductions of targeted IgG >60% demonstrated in the lowest dose cohort of the MAD, in line with modeling projections and with differentiated safety profile. There were no clinically significant reductions in IgG3, IgA, IgE, IgM, or albumin, no liver function test abnormalities, nor increases in cholesterol compared to baseline. Phase 1 completing last remaining dose cohorts with the optimized subcutaneous formulation in 1H 2025. Lead indication for BHV-1300 announced in Graves' Disease, a common autoimmune disorder affecting approximately 80 million people globally. Graves' Disease is caused by IgG1 autoantibodies that hyperstimulate the TSH receptor, causing hyperthyroidism can result in the need for surgical removal, chemical ablation of the thyroid, or need for chronic anti-thyroid drugs. Additional programs in rheumatoid arthritis and myasthenia gravis also continue to be pursued with BHV-1300 and 1310. Study May Proceed letter received from FDA for BHV-1310 IND, a novel IgG degrader and Phase 1 initiating in 1H 2025. BHV-1300 and BHV-1310 are similar but will optimize therapeutic targeting and facilitate broader commercial development options. Progresses ion channel programs for bipolar, depression, epilepsy and pain: BHV-7000, a selective activator of Kv7.2/7.3 potassium channels: Continues to advance in clinical trials for bipolar disorder, depression, and epilepsy with multiple readouts over the next year, including expected topline for bipolar in 1H 2025 and depression in 2H 2025. BHV-2100, a TRPM3 ion channel antagonist: Preliminary data from an innovative laser-evoked hyperalgesia study with BHV-2100 reduced laser heat-induced pain and brain evoked potentials in healthy volunteers. These exciting results with BHV-2100 represent the first clinical proof of concept for the novel TRPM3 inhibitor class in pain, recapitulating powerful preclinical evidence of efficacy for this approach across a spectrum of pain disorders. BHV-7000, a selective activator of Kv7.2/7.3 potassium channels: Continues to advance in clinical trials for bipolar disorder, depression, and epilepsy with multiple readouts over the next year, including expected topline for bipolar in 1H 2025 and depression in 2H 2025. BHV-2100, a TRPM3 ion channel antagonist: Preliminary data from an innovative laser-evoked hyperalgesia study with BHV-2100 reduced laser heat-induced pain and brain evoked potentials in healthy volunteers. These exciting results with BHV-2100 represent the first clinical proof of concept for the novel TRPM3 inhibitor class in pain, recapitulating powerful preclinical evidence of efficacy for this approach across a spectrum of pain disorders. Highlights expansion of Biohaven's antibody drug conjugate (ADC) portfolio in Oncology, including: BHV-1510, a Trop2-directed ADC using a novel topoisomerase 1 (TopoIx) payload: Demonstration of early Phase 1 clinical activity, including tumor shrinkage, and safety with BHV-1510 in advanced or metastatic epithelial tumors. Based upon these results, Biohaven has entered into an expanded collaboration agreement with GeneQuantum providing exclusivity to the TopoIx payload for up to 18 ADC targets. BHV-1530, a FGFR3-directed ADC using the TopoIx payload: US IND clearance received for BHV-1530, potential indications include urothelial cancers and other solid tumors driven by FGFR3 alterations and/or upregulated FGFR3 protein expression. The first-in-human study is planned to commence in 1H 2025. Announced a multi-target collaboration with Merus, an oncology-focused biotechnology company developing innovative, multi-specific (Biclonics® and Triclonics®) antibodies, to co-develop three programs encompassing highly differentiated next generation dual-targeted bispecific ADCs leveraging Biohaven's proprietary conjugation and payload technologies and Merus' leading Biclonics technology platform. BHV-1510, a Trop2-directed ADC using a novel topoisomerase 1 (TopoIx) payload: Demonstration of early Phase 1 clinical activity, including tumor shrinkage, and safety with BHV-1510 in advanced or metastatic epithelial tumors. Based upon these results, Biohaven has entered into an expanded collaboration agreement with GeneQuantum providing exclusivity to the TopoIx payload for up to 18 ADC targets. BHV-1530, a FGFR3-directed ADC using the TopoIx payload: US IND clearance received for BHV-1530, potential indications include urothelial cancers and other solid tumors driven by FGFR3 alterations and/or upregulated FGFR3 protein expression. The first-in-human study is planned to commence in 1H 2025. Announced a multi-target collaboration with Merus, an oncology-focused biotechnology company developing innovative, multi-specific (Biclonics® and Triclonics®) antibodies, to co-develop three programs encompassing highly differentiated next generation dual-targeted bispecific ADCs leveraging Biohaven's proprietary conjugation and payload technologies and Merus' leading Biclonics technology platform. Based upon these results, Biohaven has entered into an expanded collaboration agreement with GeneQuantum providing exclusivity to the TopoIx payload for up to 18 ADC targets. Key late-stage programs advancing across important indications in 2025 also include: BHV-8000, a highly selective, brain-penetrant TYK2/JAK1 inhibitor that avoids class risks associated with JAK2/3 inhibition, expected to initiate pivotal trials in Parkinson's and Alzheimer's disease in 2025. Taldefgrobep alfa, a novel myostatin inhibitor optimized to block two key regulators of muscle and fat metabolism, continues to be developed in spinal muscular atrophy and obesity. New Drug Application (NDA) for troriluzole in all SCA genotypes was submitted to the FDA, following completion of pre-NDA meeting in 4Q 2024. Troriluzole has Orphan Drug and Fast-Track designations and qualifies for potential Priority Review. Awaiting filing decision from FDA and preparing for potential commercial launch in 2025 if approved. BHV-8000, a highly selective, brain-penetrant TYK2/JAK1 inhibitor that avoids class risks associated with JAK2/3 inhibition, expected to initiate pivotal trials in Parkinson's and Alzheimer's disease in 2025. Taldefgrobep alfa, a novel myostatin inhibitor optimized to block two key regulators of muscle and fat metabolism, continues to be developed in spinal muscular atrophy and obesity. New Drug Application (NDA) for troriluzole in all SCA genotypes was submitted to the FDA, following completion of pre-NDA meeting in 4Q 2024. Troriluzole has Orphan Drug and Fast-Track designations and qualifies for potential Priority Review. Awaiting filing decision from FDA and preparing for potential commercial launch in 2025 if approved. NEW HAVEN, Conn. , Jan. 13, 2025 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) (" Biohaven "), a global clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of innovative and transformative therapies to treat individuals with rare and common diseases, today highlighted broad portfolio progress at the 43rd Annual J.P. Morgan Healthcare Conference , including positive Phase 1 data for BHV-1400, its highly differentiated investigational therapeutic for IgA nephropathy. BHV-1400 is a second generation TRAP™ degrader from its proprietary MoDE™ platform. A copy of the slide presentation is available on the Events and Presentations section of the Biohaven website. Vlad Coric , M.D., Chairman and Chief Executive Officer of Biohaven , commented, "While we are excited about the significant progress across our entire portfolio, the first-ever data of a TRAP degrader in humans is monumental and unparalleled. The ability to only remove aberrant proteins causing disease while leaving all other immune functioning intact will usher in a new era of precision immunology. As quickly as science can identify new disease-causing proteins, our technology can quickly advance treatments for patients. I am proud of our dedicated, passionate and gifted team's unrelenting drive to transform medical care for patients suffering from severe diseases." Biohaven 2025 Portfolio Review and Anticipated Milestones Biohaven is positioned to achieve significant milestones in 2025 across a broad spectrum of early- and late-stage programs targeting indications with high unmet need: Molecular Degrader of Extracellular Proteins (MoDE) Platform: Biohaven's novel immune-modulating extracellular degrader platform harnesses selectivity, rapidity, and patient-friendly self-administration to remove disease-causing proteins from the body to potentially treat a wide range of diseases. Biohaven introduced next generation TRAP degraders, which are highly selective, each targeting a specific disease-causing protein for proteolysis. Four INDs for MoDE and next generation TRAP degrader molecules (targeting IgG1, IgG2, IgG4, Gd-IgA1, and β1AR autoantibodies) have been accepted by the FDA in 2024 with several additional investigational agents in development. Three assets have been dosed in Phase 1 trials with the fourth anticipated to be dosed in the first half of 2025. The first-of-its-kind molecule, BHV-1300 is being developed for the treatment of common immune-mediated diseases, such as Graves' Disease and Rheumatoid Arthritis. With patient-centered design, Biohaven has advanced a proprietary subcutaneous formulation of BHV-1300 and has entered into an agreement with Ypsomed, to develop and manufacture BHV-1300 in an easy-to-use, autoinjector for self-administration. This BHV-1300 proprietary formulation has demonstrated deep and targeted reductions of IgG, with reductions > 60% within four hours and 70% reduction within eight hours in the lowest subcutaneous dose tested in the MAD. Reductions were sustained even after just a single dose administration. Targeted IgG reductions (IgG1, IgG2, and IgG4, over IgG3) have been consistent with projected modeling. Phase 1 dose escalation is completing in 1H 2025, with Graves' Disease Phase 2 trial to initiate mid-year. BHV-1300 was rationally designed to spare IgG3 to preserve host immune defense. The selectivity of BHV-1300 demonstrated in the Phase 1 trial establishes a differentiated safety profile for the treatment of autoimmune disease relative to other IgG-lowering agents and validates the precision of the platform. BHV-1400 and BHV-1600, currently in Phase 1 clinical trials, represent the next generation TRAP degraders focused on selectively clearing very specific pathogenic antibodies, while sparing healthy immunoglobulin to preserve immune function. TRAP molecules commence a new age of immune-modulating treatments, targeted removal of disease-causing proteins for removal while sparing the normal function of the healthy immune system. Data from the first, and lowest, dose cohort of BHV-1400 demonstrated clear differentiation from competitors in the IgA nephropathy space, with rapid lowering of Gd-IgA1 within four hours and preservation of host immunoglobulins including IgG, IgA, IgE, and IgM. IgA nephropathy is a rare chronic kidney disease affecting young and middle-aged adults that is caused by Gd-IgA1 and leads to kidney failure in up to 40% of patients within 10-20 years. Taken in total, the selectivity of MoDE and TRAP degraders demonstrated to date refine immune-modulating treatment representing a clear next generation of drug development technology in immunoglobulin and extracellular protein lowering. Existing mechanisms, both pharmaceutical and device (plasmapheresis), broadly reduce immunoglobulins subclasses and/or isotypes, leading to inefficient dosing, safety risks, necessity of procedures, delays in therapy, and potential efficacy impacts. MoDE and TRAP's new paradigm builds off the prior successes of immune modulation, while also providing a novel technology to fine tune therapies for immune-mediated diseases. As described below, the implications and applications of this selective targeting could be multi-organ, multi-disease. IgA Nephropathy (IgAN) Program: First-in-human dosing with BHV-1400 achieved rapid, deep, and selective lowering of only Gd-IgA1, the aberrant antibody that causes IgA nephropathy, while sparing normal IgA. The first and lowest dose tested (125 mg) of BHV-1400 in Phase 1 achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration. Maximal reduction exceeding 70% was observed within eight hours. Even after just a single dose administration of BHV-1400, reductions in Gd-IgA1 were sustained for days. The rapid reduction of Gd-IgA1 by BHV-1400 is unprecedented in drugs targeting Gd-IgA1 and could allow for potential indications in situations where rapid Gd-IgA1 lowering could be beneficial in addition to chronic active disease and long-term maintenance. The selective and rapid approach to Gd-IgA1 lowering of BHV-1400 represents a second-generation therapeutic approach to IgAN, potentially allowing for effective disease control with less acute- or long-term safety risks associated with B-cell directed therapy, complement inhibitors, or broad immunosuppression. BHV-1400 has been safe and well-tolerated in the Phase 1 study to date and demonstrated no clinically significant changes in innate or adaptive immune systems, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM, and no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. There have been no dose limiting toxicities observed in the Phase 1 study and dose escalation continues to explore the full range of Gd-IgA1 reductions possible with BHV-1400. A pivotal trial in IgA nephropathy is planned using an accelerated regulatory path upon completion of the Phase 1 trial. Additional opportunities in situations when rapid Gd-IgA1 reduction could be beneficial may also be feasible given the demonstrated dosing kinetics in the Phase 1 study. Biohaven further expands its renal franchise with the degrader platform, developing several investigational TRAPs for the treatment of immune-mediated renal disease, including a TRAP degrader to target PLA2R autoantibodies for the treatment of membranous nephropathy among others. The first and lowest dose tested (125 mg) of BHV-1400 in Phase 1 achieved rapid lowering of Gd-IgA1 with a median reduction of 60% within four hours of administration. Maximal reduction exceeding 70% was observed within eight hours. Even after just a single dose administration of BHV-1400, reductions in Gd-IgA1 were sustained for days. The rapid reduction of Gd-IgA1 by BHV-1400 is unprecedented in drugs targeting Gd-IgA1 and could allow for potential indications in situations where rapid Gd-IgA1 lowering could be beneficial in addition to chronic active disease and long-term maintenance. The selective and rapid approach to Gd-IgA1 lowering of BHV-1400 represents a second-generation therapeutic approach to IgAN, potentially allowing for effective disease control with less acute- or long-term safety risks associated with B-cell directed therapy, complement inhibitors, or broad immunosuppression. BHV-1400 has been safe and well-tolerated in the Phase 1 study to date and demonstrated no clinically significant changes in innate or adaptive immune systems, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM, and no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. There have been no dose limiting toxicities observed in the Phase 1 study and dose escalation continues to explore the full range of Gd-IgA1 reductions possible with BHV-1400. A pivotal trial in IgA nephropathy is planned using an accelerated regulatory path upon completion of the Phase 1 trial. Additional opportunities in situations when rapid Gd-IgA1 reduction could be beneficial may also be feasible given the demonstrated dosing kinetics in the Phase 1 study. Biohaven further expands its renal franchise with the degrader platform, developing several investigational TRAPs for the treatment of immune-mediated renal disease, including a TRAP degrader to target PLA2R autoantibodies for the treatment of membranous nephropathy among others. Peripartum cardiomyopathy (PPCM) program: First-in-human dosing with BHV-1600 has been safe and well-tolerated to date after two dose cohorts without clinically relevant changes in innate or adaptive immune systems, including white blood cells and immunoglobulins IgG, IgA, IgE, and IgM, and no clinically significant reductions in albumin, liver function test abnormalities, or increases in cholesterol compared to baseline. β1AR autoantibodies are thought to cause peripartum cardiomyopathy, a rare form of heart failure with no approved therapy that occurs at the end of pregnancy or following delivery and in severe cases, can be life-threatening. BHV-1600 has been shown to bind to β1AR autoantibodies in preclinical studies and biomarker levels will be measured in women with PPCM later in development. Completed INTERACT meeting with FDA regarding BHV-1600 in 4Q 2024 and gained alignment for the study design to potentially pursue an accelerated approval pathway in PPCM, a rare autoimmune life-threatening disease with no approved therapy. Completed INTERACT meeting with FDA regarding BHV-1600 in 4Q 2024 and gained alignment for the study design to potentially pursue an accelerated approval pathway in PPCM, a rare autoimmune life-threatening disease with no approved therapy. IgG MoDE degrader program: BHV-1300 Phase 1 is completing the last remaining dose cohorts with expected completion in 1H 2025. Study May Proceed letter received from the FDA for the BHV-1310 IND and Phase 1 initiating in 1H 2025. Lead indication for BHV-1300 announced in Graves' Disease, a common autoimmune disorder affecting approximately 3 million in the US and 80 million globally. Graves' Disease is caused by IgG1 autoantibodies that hyperstimulate the TSH receptor, causing hyperthyroidism and can result in the need for surgical removal, chemical ablation of the thyroid, or need for chronic anti-thyroid drug therapy. Additional programs in rheumatoid arthritis and myasthenia gravis also to be pursued with BHV-1300 and 1310. Study May Proceed letter received from FDA for BHV-1310 IND, a next generation IgG degrader and Phase 1 initiating in 1H 2025. BHV-1300 and BHV-1310 are similar but will optimize therapeutic targeting and facilitate broader commercial development options. Lead indication for BHV-1300 announced in Graves' Disease, a common autoimmune disorder affecting approximately 3 million in the US and 80 million globally. Graves' Disease is caused by IgG1 autoantibodies that hyperstimulate the TSH receptor, causing hyperthyroidism and can result in the need for surgical removal, chemical ablation of the thyroid, or need for chronic anti-thyroid drug therapy. Additional programs in rheumatoid arthritis and myasthenia gravis also to be pursued with BHV-1300 and 1310. Study May Proceed letter received from FDA for BHV-1310 IND, a next generation IgG degrader and Phase 1 initiating in 1H 2025. BHV-1300 and BHV-1310 are similar but will optimize therapeutic targeting and facilitate broader commercial development options. Next generation MoDE degrader targets advancing in 2025 include: IgG4 specific degrader PLA2R autoantibody degrader for membranous nephropathy Pro-insulin autoantibody degrader for type 1 diabetes TSH receptor autoantibody degrader as a selective follow-on asset for Graves' Disease IgG4 specific degrader PLA2R autoantibody degrader for membranous nephropathy Pro-insulin autoantibody degrader for type 1 diabetes TSH receptor autoantibody degrader as a selective follow-on asset for Graves' Disease Upcoming milestones in the degrader program include: IgG MoDE Degraders (1300/1310): BHV-1300 Phase 1 completing last remaining dose cohorts with the optimized subcutaneous formulation with expected completion in 1H 2025. BHV-1310 first-in-human study anticipated to initiate 1H 2025. Phase 2 study in Graves' Disease expected to initiate mid-2025 and additional programs in rheumatoid arthritis and myasthenia gravis continue to be pursued with BHV-1300/1310. Phase 1 with BHV-1400 and BHV-1600 expected to be completed in 1H 2025. Four molecules moving towards development candidate in 2025 including: IgG4 degrader, PLA2R autoantibody degrader, insulin autoantibody degrader, and TSH receptor autoantibody degrader. Tova Gardin , M.D., M.P.P, Biohaven Chief Translational Officer, reflected on the recent results from the MoDE degrader platform, "With the advancements across our degrader platform, including the highly selective TRAP molecules, Biohaven inaugurates a new age of immune-modulating treatment – one which opens the potential of treating the pathogenesis of disease with precision to restore healthy homeostasis. The results of BHV-1400 from the first and lowest SAD cohort highlight the speed, precision, and patient-centered innovation that drives development of each of our molecules. Lowering Gd-IgA1 by 60% within hours of dose administration, BHV-1400 realizes the precision possible with MoDE degraders: The possibility of selectively degrading the pathogenic driver of disease, leaving host immunity unperturbed. Innovation extends across the MoDE platform, with new programs launched for the treatment of Graves' Disease, peripartum cardiomyopathy, and other selective TRAP degraders advancing towards development candidate nominations to potentially treat membranous nephropathy, IgG4-mediated disease, and diabetes." BHV-2100: First-in-clinic, oral, selective TRPM3 antagonist that offers a novel, non-addictive treatment for migraine and neuropathic pain. Based on favorable pharmacokinetic and safety data from the Phase 1 studies in healthy subjects, a Phase 1b laser-evoked hyperalgesia trial was performed and a proof-of-concept in the acute treatment of migraine is ongoing. Preliminary data from the laser-evoked hyperalgesia study demonstrated that BHV-2100 reduced laser heat-induced pain and brain evoked potentials in healthy volunteers. This exciting result is a culmination of years of laboratory research and represents a powerful entree into the field. It provides the first indication of potential clinical efficacy in pain with the novel TRPM3 mechanism recapitulating antinociceptive preclinical efficacy across a spectrum of pain models. Data from the laser-evoked potential study and proof-of-concept migraine study expected in 1H 2025. BHV-7000: Selective activator of Kv7.2/7.3 potassium channels, a breakthrough target in neurology and neuropsychiatry with blockbuster potential. Kv7 activation is a clinically validated target for treating mood disorders and epilepsy. Registrational studies ongoing in bipolar disorder, major depressive disorder, focal epilepsy, and generalized epilepsy. Upcoming milestones in the BHV-7000 program include: Pivotal bipolar and major depressive disorder topline results expected in 1H 2025 and 2H 2025, respectively. Focal epilepsy study topline results expected in 1H 2026. Troriluzole: Troriluzole is a novel glutamate modulator currently in Phase 3 development for Spinocerebellar ataxia (SCA) and obsessive-compulsive disorder (OCD). A new drug application (NDA) was submitted to US FDA for troriluzole in all SCA genotypes, following completion of pre-NDA meeting in 4Q 2024. Troriluzole has Orphan Drug and Fast-Track designations and qualifies for potential Priority Review. EU marketing authorization application also under review for troriluzole in all SCA genotypes. There are no FDA-approved treatments for SCA. Additionally, two Phase 3 trials with troriluzole in OCD are ongoing. Upcoming milestones in the troriluzole program include: Preparing for commercial launch in SCA in 2025, while awaiting filing decision from FDA on the troriluzole all-genotype SCA NDA resubmission. Topline data from two Phase 3 OCD trials in 1H 2025 and 2H 2025, respectively. Taldefgrobep alfa: Taldefgrobep is a novel myostatin inhibitor that is optimized to block both myostatin and activin A signaling, two key regulators of muscle and fat metabolism. Biohaven is studying taldefgrobep in a global Phase 3 expansion study in Spinal Muscular Atrophy (SMA), as an adjunctive therapy to enhance muscle mass and function in patients treated with standard-of-care therapies. Analyses of prespecified subgroups by race and ethnicity demonstrated that the largest study population (87% Caucasian; n=180) showed clinically meaningful improvements on the MFM-32 at all timepoints, including Week 48, compared to the corresponding placebo+SOC group (p < 0.05), though the overall primary endpoint was not met. Robust target engagement (myostatin reduction) and beneficial impacts on body composition parameters (fat mass, lean muscle mass, and bone density) were noted, offering a potential paradigm shift in the treatment of obesity with opportunity to improve quality of weight loss; lower total body weight by specifically reducing fat mass while also preserving or increasing lean muscle mass. Upcoming milestones in the taldefgrobep program include: Expected FDA meeting to discuss SMA registrational path in 1H 2025. Initiate taldefgrobep Phase 2 study in obesity in 1H 2025. BHV-8000: BHV-8000 is a highly selective, oral, brain-penetrant, selective TYK2/JAK1 inhibitor with broad potential for neurodegenerative and neuroinflammatory disorders. In the Phase 1 SAD/MAD study in healthy participants, BHV-8000 was generally safe and well-tolerated while producing significant reductions in inflammatory biomarkers relative to placebo. Target indications for BHV-8000 include Parkinson's disease, Alzheimer's disease, prevention of amyloid-related imaging abnormalities (ARIA), and multiple sclerosis (MS). In 2024, Biohaven completed interactions with FDA enabling registrational programs for Parkinson's disease and the prevention of ARIA. Upcoming milestones in the BHV-8000 program include: Initiate BHV-8000 Phase 2/3 study in Parkinson's disease in 1H 2025 Advance Alzheimer's, MS and ARIA programs in 2025. Oncology antibody drug conjugate (ADC) portfolio: BHV-1510 (Trop2 ADC): Preliminary data from the initial Phase 1 study dosing cohorts of BHV-1510 have demonstrated promising clinical activity, including tumor shrinkage, with a tolerable safety profile of the novel topoisomerase 1 (TopoIx) payload. The Phase 1/2 study of BHV-1510 is progressing with robust enrollment in dose escalation and optimization, both as monotherapy and in combination with the anti-PD1 monoclonal antibody Libtayo® (cemiplimab-rwlc) through a clinical supply agreement with Regeneron. Preclinically, TopoIx has shown increased immunogenic cell death and synergistic activity when combined with anti-PD1/L1 checkpoint inhibitors, and a differentiated nonclinical toxicity profile; Clinical activity has been seen across dose cohorts tested to date, including the lowest dose tested of 2mg/kg Q3W; Early PK data demonstrates a stable ADC with very low serum concentrations of free payload; Preliminary safety data demonstrates a favorable profile, with no payload-associated interstitial lung disease, gastrointestinal toxicities, or significant hematological toxicities observed in early cohorts. The main toxicity observed thus far in Phase 1 study has been stomatitis, an expected on-target Trop2 class toxicity that has been manageable; Combination cohorts of BHV-1510 with Libtayo® have initiated. Based on these encouraging early results, Biohaven has entered into an expanded collaboration agreement with GeneQuantum, which provides broad target exclusivity for up to 18 ADC targets incorporating the novel topoisomerase 1 inhibitor (TopoIx) payload. Biohaven has incorporated the TopoIx payload into its next clinical-stage investigational agent, BHV-1530. BHV-1530 is an FGFR3-directed ADC with potential indications in cancers driven by FGFR3 alterations and/or upregulated FGFR3 protein expression, including urothelial cancers and other solid tumors. While FGFR3 has been clinically validated as a target in oncology, there are no other FGFR3 ADCs currently in clinical development. Biohaven retains global rights for BHV-1530 under the agreement via an exclusive license with GeneQuantum and Aimed Bio. The US IND has been opened, and a first-in-human study for solid tumors is planned for 1H 2025. In addition, Biohaven today announced a multi-target collaboration with Merus, an oncology-focused biotechnology company developing innovative, multi-specific (Biclonics® and Triclonics®) antibodies. This collaboration will co-develop three programs encompassing highly differentiated next generation dual-targeted bispecific ADCs leveraging Biohaven's proprietary conjugation and payload technologies along with Merus' leading Biclonics technology platform. Together, the announced milestones and collaborations represent a significant expansion of Biohaven's ADC portfolio, positioning the Company with potential to deliver highly differentiated therapeutics and address significant unmet needs in Oncology. Nushmia Khokhar , M.D., Biohaven Chief Medical Officer of Oncology, commented, "These are exciting times for Biohaven's oncology pipeline as we are well-positioned to introduce differentiated, next generation ADCs to the clinic. The early Phase 1 data with BHV-1510 is promising, showing not only signs of clinical activity but also minimal toxicities related to the free payload. This affirms the advantages of our conjugation technology, which provides high ADC stability. The distinct profile of the novel TopoIx payload, and its potential to synergize with checkpoint inhibitor therapy, could significantly benefit patients across various cancer types. Furthermore, our collaboration with Merus and the expanded partnership with GeneQuantum—utilizing the TopoIx payload for multiple targets—demonstrate the potential of Biohaven's upcoming innovative ADCs. This includes dual-targeting ADCs, which are exciting for their potential to address challenges like tumor heterogeneity and delivery of stable ADCs with an improved therapeutic index." Upcoming milestones in the oncology program include: Interim Phase 1 data with BHV-1510 and dose optimization as monotherapy and combination therapy with Libtayo® in epithelial tumors in 2025. Initiate Phase 1 trial of BHV-1530 in 1H 2025. Advance Merus collaboration ADCs (undisclosed targets) and TopoIx ADCs in 2025. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. Biohaven is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and nonclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA (spinocerebellar ataxia); myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules and antibody drug conjugates for cancer. For more information, visit www.biohaven.com. Forward-looking StatementsThis news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable US regulatory requirements; the potential commercialization of Biohaven's product candidates; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission , including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. MoDE is a trademark of Biohaven Therapeutics Ltd.TRAP is a trademark of Biohaven Therapeutics Ltd. Biclonics and Triclonics are registered trademarks of Merus NV.Libtayo® is a registered trademark of Regeneron. Investor Contact: Jennifer Porcelli Vice President, Investor Relationsjennifer.porcelli@biohavenpharma.com+1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. mikebeyer@sambrown.com+1 (312) 961-2502 View original content to download multimedia:https://www.prnewswire.com/news-releases/biohaven-highlights-portfolio-progress-innovation-and-anticipated-milestones-at-the-43rd-annual-jp-morgan-healthcare-conference-reports-positive-degrader-data-with-rapid-deep-and-selective-lowering-of-galactose-deficient-ig-302349336.html SOURCE Biohaven Ltd.

关注并星标CPHI制药在线 近段时间，国内药企云顶新耀传来好消息，其创新药EVER001胶囊在治疗原发性膜性肾病（pMN）的Ib/2a期临床试验中，取得阶段性积极结果。此次EVER001的积极进展具有重要意义，那么其背后有什么特殊背景？ 什么是膜性肾病？ 膜性肾病（MN）是成人肾病综合征常见的病理类型，可分为特发性原发性（约占80%病例）和继发性（约占20%病例）两大形式。研究证实，MN是一种针对正常肾小球上皮细胞膜上的抗原成分而产生的自身抗体介导的肾小球损害。其临床特征为水肿、低白蛋白血症和高脂血症等肾病综合征相关症状，同时会增加血栓、感染、心血管疾病等风险。长期未经治疗的患者将有近60%发生肾功能减退，且30-40%将在10年内最终进展为终末期肾病。 MN在我国的患病率正逐年上升，其占比从2001年~2006年的5.5%增长至2013年~2018年的22.5%，已成为仅次于免疫球蛋白A（IgA）肾病的原发性肾小球肾炎。目前，我国约有200万pMN患者，疾病负担远远高于其他国家（美国约有8万-10万患者，欧洲约有8万患者，日本约有4万患者）。 对于pMN的治疗，目前主要以缓解蛋白尿等症状的保守治疗为主。对于疾病进展风险高的患者，常采取免疫抑制剂以及联合治疗，包括传统的环磷酰胺、泼尼松及其他皮质激素，以及新型的免疫抑制剂如钙调磷酸酶抑制剂（环孢素和他克莫司）以及CD20单抗（利妥昔单抗等）。 但目前这些常用的免疫抑制剂，都处于超适应症应用状态，其安全性和疗效并不尽如人意。究其原因，这与膜性肾病全球暂无获批药物有关。也正因此，目前pMN已是导致透析的第一大原因，占比高达37%，甚至超过糖尿病肾病和高血压肾病透析的总和（约30%）。 因此，在膜性肾病赛道，亟需研发能提高治疗缓解率、降低高复发率的治疗药物。 EVER001是赛道黑马吗？ 云顶新耀的EVER001是一款新一代共价可逆布鲁顿酪氨酸激酶（BTK）抑制剂。BTK是B细胞受体信号通路的重要组成部分，可调节B淋巴细胞的存活、激活、增殖和分化。 I期临床研究证明，EVER001具有高选择性、强效靶点结合能力和良好的安全性特征。在针对以蛋白尿为特征的肾小球疾病患者的Ib/IIa期临床试验中，在已完成36周治疗的低剂量组患者中，81.8%（9/11）的患者实现临床缓解，高剂量组中已完成24周治疗的患者已有85.7%（6/7）实现临床缓解。低剂量组的24小时蛋白尿几何平均值在36周相较于基线下降78.3%，而高剂量组在24周即出现73.8%的下降。 在数据截止日，抗-PLA2R（磷脂酶A2受体）自身抗体水平达到接近100%的下降（抗-PLA2R抗体水平和临床疗效紧密相关，其降低预示着临床缓解，尤其是免疫学完全缓解）。 与目前指南推荐的利妥昔单抗联合疗法，以及在国内开展的一些研究中，12个月的缓解率在60%左右，部分甚至低至40%相比，EVER001疗效突出。而且EVER001未出现BTK抑制剂典型的不良反应。这对需要长期用药的肾病患者来说，着实难得。 而且与通过输液治疗pMN的利妥昔单抗相比，EVER001作为口服小分子化合物，使用更方便。 基于以上，EVER001或为pMN赛道黑马，将为全球pMN领域存在的巨大未被满足的临床需求提供解决方案。 MN药物研发现状 由于MN患者基数庞大，且现有治疗药物有限，因此，不少药企开始瞄准这一赛道，针对的靶点主要有CD38、BAFF（B 细胞激活因子）、补体CFB/D等。 CD38是一种跨膜糖蛋白，其在多发性骨髓瘤等非实体瘤中的高表达使其成为治疗这些疾病的有效靶点。同时，CD38单抗在自身免疫性疾病治疗中也显示出潜力。 Humanlmmunology Biosciences（以下简称HI-Bio）的Felzartamab是一种靶向CD38的全人源IgG1单克隆抗体，它通过抗体依赖性细胞毒性（ADCC）和抗体依赖性细胞吞噬作用（ADCP）消耗CD38+浆细胞，降低了致病性自身抗体的水平，进而对pMN、IgAN肾病、狼疮性肾炎(LN)等自身免疫性肾脏疾病的治疗产生积极影响。具体来说，Felzartamab可以抑制CD38+浆细胞分泌抗PLA2R自身抗体，减少免疫复合物在足细胞和肾小球基底膜之间的上皮下间隙的沉积，进而对pMN的治疗产生积极影响。 2024年6月6日，渤健和HI-Bio达成协议。根据协议条款，渤健将向HI-Bio支付11.5亿美元预付款(约83亿人民币)，以及6.5亿美元里程碑付款，Felzartamab被渤健收入囊中。 BAFF是一种B细胞稳态调节因子，贝利木单抗（Belimumab）通过靶向 BAFF，可能成为 MN 治疗中的一个新选择。贝利木单抗是一种靶向可溶性BAFF的 IgG-λ单克隆抗体，通过降低PLA2R抗体和诱导缓解在PLA2R阳性MN患者中显示出潜力。 值得注意的是，由于膜性肾病发病机制的复杂性，BTK抑制剂较少在该赛道涉足，国内众多在研BTK抑制剂中，仅有恒瑞医药的SHR-1459申报了膜性肾病适应症。截至目前，MN尚无获批的治疗药物，目前使用的治疗手段不仅副作用显著，而且仅有超过30%的患者无效。因此，此次云顶新耀的EVER001取得较为明显的优势，或许能成为MN赛道上一匹国产黑马。 主要参考资料： 1.  MEENA P, RAMACHANDRAN R, BOSE B, et al. Changing treatment paradigms for membranous nephropathies[J]. Nephrology Dialysis Transplantation, 2024: gfae141. 2.  Seifert L, et al. The classical pathway triggers pathogenic complement activation in membranous nephropathy. Nat Commun. 2023 Jan 28;14(1):473. doi: 10.1038/s41467-023-36068-0. PMID: 36709213; PMCID: PMC9884226. 3.  云顶新耀新闻稿 END 【智药研习社近期直播】 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~