APRIL

Long-term improvements observed in the quartet of findings defining disease modification supports atacicept’s potential to prevent kidney failure in patients with IgAN;Long-term results from the ORIGIN Phase 2b study were simultaneously published in the Journal of the American Society of Nephrology;Company will host an investor call and webcast on Monday October 28 at 8:00 AM ET BRISBANE, Calif., Oct. 26, 2024 (GLOBE NEWSWIRE) -- Vera Therapeutics, Inc. (Nasdaq: VERA), a late clinical-stage biotechnology company focused on developing and commercializing transformative treatments for patients with serious immunological diseases, today announced data from its ORIGIN Phase 2b trial of atacicept in immunoglobulin A nephropathy (IgAN) that show stabilized kidney function through 96 weeks of long-term follow-up. These data were presented in a late-breaking oral presentation at the American Society of Nephrology Kidney Week 2024 in San Diego, California, and simultaneously published in a manuscript in the Journal of the American Society of Nephrology. “The 96-week results from the ORIGIN Phase 2b study demonstrated sustained and substantial reductions in Gd-IgA1, hematuria and proteinuria as measured by UPCR with long-term stabilization of eGFR,” said Jonathan Barratt, MD, PhD, FRCP, Mayer Professor of Renal Medicine at the University of Leicester. “Converting patients with IgAN from an eGFR profile of unrelenting decline to a profile consistent with the general population without kidney disease is a differentiated and compelling finding. Collectively, the data support the potential of atacicept to modify the natural history of the disease and prevent kidney failure during the lifetime of patients with IgAN.” “We are excited to present these long-term efficacy and safety data from the ORIGIN Phase 2b study, which further demonstrate atacicept’s potential to address the underlying pathogenesis of IgAN. The stabilization of kidney function through two years—the longest duration of data among B cell modulators to date—positions atacicept as a potential best- and first-in-class treatment option for patients with IgAN,” said Marshall Fordyce, M.D., Founder and CEO of Vera Therapeutics. “We look forward to announcing expected topline results from the Phase 3 ORIGIN 3 trial in Q2 2025, with planned BLA submission to the U.S. FDA later in the year.” Over 96 weeks, participants treated with atacicept demonstrated a -66% reduction in galactose-deficient IgA1 (Gd-IgA1), resolution of hematuria in 75% of participants, a -52% reduction in proteinuria, and a mean annualized estimated glomerular filtration rate (eGFR) slope of -0.6 mL/min/1.73m2/year. The cumulative generally favorable safety profile of atacicept remained consistent with that observed during the randomized period, with a 90% completion rate of atacicept treatment. Figure 1. ORIGIN Phase 2b long-term 96-week results with atacicept was consistent with disease-modifying IgAN profile The Company believes these data support the potential for atacicept to offer long-term, comprehensive IgAN disease modification and provide further confidence in the ongoing pivotal Phase 3 ORIGIN 3 trial of atacicept in IgAN. The Company will host an investor call and webcast to discuss the data update on Monday, October 28, at 8:00 AM ET. The live webcast will be available on the Company’s Investor Calendar at https://ir.veratx.com/news-events/investor-calendar, with the recording and presentation available immediately following the event. The Kidney Week 2024 presentation and posters are available on the Company’s website at https://ir.veratx.com/news-events/presentations. Upcoming milestones: ORIGIN Extend – plan to initiate a study in Q4 2024 that will provide ORIGIN participants with extended access to atacicept prior to commercial availability in their region, as well as an opportunity to capture longer-term data.Pivotal ORIGIN 3 trial on track to announce topline results in Q2 2025, with planned BLA submission to the U.S. FDA later in the yearPIONEER Study – plan to initiate a study in 2025 that will evaluate the efficacy and safety of atacicept in: Expanded IgAN populations – The first set of cohorts will include adults with low kidney function (eGFR 20 to <30 mL/min/1.73 m2), low (UPCR <1.0 g/g) or high proteinuria (UPCR ≥5.0 g/g) or IgAN recurrence after kidney transplant; adolescents at high risk of progression (UPCR ≥0.3 g/g); as well as adolescents and adults with IgA vasculitis nephritis.Anti-PLA2R and anti-nephrin podocytopathies – The PIONEER study will expand to additional autoimmune glomerular diseases characterized by the presence of antibodies to glomerular antigens, including primary membranous nephropathy, focal segmental glomerulosclerosis, and minimal change disease. About the Phase 2b ORIGIN clinical trialThe Phase 2b ORIGIN clinical trial (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of atacicept in 116 patients with IgAN who continue to have persistent proteinuria and remain at high risk of disease progression despite being on a stable prescribed regimen of a renin-angiotensin-aldosterone system inhibitor for at least 12 weeks that is the maximum labeled or tolerated dose. The Phase 2b ORIGIN clinical trial evaluated three dose strengths of atacicept versus placebo, administered weekly by prefilled syringe. Patients were randomized 2:2:1:2 to atacicept 150 mg, atacicept 75 mg, atacicept 25 mg or matching placebo. Upon completion of the 36-week blinded treatment period, all patients were offered open-label atacicept 150 mg for an additional 60 weeks. The primary endpoint was the change in proteinuria as evaluated by urine protein to creatinine ratio (UPCR) at week 24, and the key secondary endpoint was the change in proteinuria as evaluated by UPCR at week 36. Additional exploratory endpoints include change in proteinuria as evaluated by UPCR at weeks 12, 48, and 96; change in eGFR; change in serum immunoglobulin levels, and change in serum Gd-IgA1 levels; safety and tolerability; and serum pharmacokinetics. The trial met its primary and key secondary endpoints, with statistically significant and clinically meaningful proteinuria reductions and stabilization of eGFR versus placebo through week 36. The safety profile was comparable between atacicept and placebo. For more information about the Phase 2b ORIGIN clinical trial, please visit www.clinicaltrials.gov. About the Phase 3 ORIGIN 3 clinical trialThe ORIGIN 3 clinical trial (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the safety and efficacy of atacicept in patients with IgAN who continue to have persistent proteinuria and remain at high risk of disease progression despite being on a stable prescribed regimen of renin-angiotensin system inhibitors for at least 12 weeks that is the maximum labeled or tolerated dose. The objectives of the trial are to determine the effect of atacicept on proteinuria and preservation of kidney function compared to placebo. For more information about the ORIGIN 3 clinical trial, please visit http://www.clinicaltrials.gov. About AtaciceptAtacicept is an investigational recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor that binds to the cytokines B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL). These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases, including IgAN and lupus nephritis. The Phase 2b ORIGIN clinical trial of atacicept in IgAN met its primary and key secondary endpoints, with statistically significant and clinically meaningful proteinuria reductions and stabilization of eGFR versus placebo through 36 weeks. The safety profile during the randomized period was comparable between atacicept and placebo. Through 72 weeks, atacicept demonstrated further reductions in Gd-IgA1, hematuria and proteinuria, as well as stabilization of eGFR reflecting a profile consistent with that of the general population without IgAN. Atacicept has received FDA Breakthrough Therapy Designation for the treatment of IgAN, which reflects the FDA’s determination that, based on an assessment of data from the Phase 2b ORIGIN clinical trial, atacicept may demonstrate substantial improvement on a clinically significant endpoint over available therapies for patients with IgAN. Vera believes atacicept is positioned for best-in-class potential, targeting B cells and plasma cells to reduce autoantibodies and having been administered to more than 1,500 patients in clinical studies across different indications. About VeraVera Therapeutics is a late clinical-stage biotechnology company focused on developing treatments for serious immunological diseases. Vera’s mission is to advance treatments that target the source of immunological diseases in order to change the standard of care for patients. Vera’s lead product candidate is atacicept, a fusion protein self-administered as a subcutaneous injection once weekly that blocks both BAFF and APRIL, which stimulate B cells and plasma cells to produce autoantibodies contributing to certain autoimmune diseases, including IgAN, also known as Berger’s disease, and lupus nephritis. In addition, Vera is evaluating additional diseases where the reduction of autoantibodies by atacicept may prove medically useful. Vera is also developing MAU868, a monoclonal antibody designed to neutralize infection with BKV, a polyomavirus that can have devastating consequences in certain settings such as kidney transplant. Vera retains all global developmental and commercial rights to atacicept and MAU868. For more information, please visit www.veratx.com. Forward-looking StatementsStatements contained in this press release regarding matters, events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, Vera’s expectations regarding the expansion of its development pipeline for atacicept, atacicept’s potential to be a best-in-class treatment for patients with IgAN, Vera’s expectations regarding the potential for B cell modulation through BAFF/APRIL dual inhibition to transform the treatment landscape for certain autoimmune diseases, Vera’s plans to initiate the ORIGIN Extend study in the fourth quarter of 2024 providing extended access to atacicept to ORIGIN participants, Vera’s plans to initiate the PIONEER study in 2025, Vera’s anticipated presentations of clinical trial data, including the announcement of topline results from the Phase 3 ORIGIN 3 trial in the second quarter of 2025, Vera’s plans for a BLA filing for atacicept in 2025 and Vera’s product candidates, strategy, and regulatory matters. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believes,” “expects,” “plan,” “potential,” “will,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Vera’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks related to the regulatory approval process, results of earlier clinical trials may not be obtained in later clinical trials, preliminary results may not be predictive of topline results, risks and uncertainties associated with Vera’s business in general, the impact of macroeconomic and geopolitical events, and the other risks described in Vera’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Vera undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. For more information, please contact: Investor Contact:Joyce AllaireLifeSci Advisors212-915-2569jallaire@lifesciadvisors.com Media Contact:Madelin HawtinLifeSci CommunicationsMHawtin@lifescicomms.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/e8cbc495-7104-43c9-a2ed-6d0e38ad21ae

- New data on povetacicept 80 mg SC Q4 weeks in IgA nephropathy shows mean UPCR reduction from baseline of 66% observed at 48 weeks, associated with stable renal function (eGFR) and 63% achieving clinical remission -- - First proteinuria data on povetacicept in primary membranous nephropathy shows mean UPCR reduction from baseline of 62% at 24 weeks – - Global Phase 3 RAINIER trial of povetacicept in IgA nephropathy now underway – – Enrollment and dosing ongoing in Phase 3 portion of the global Phase 2/3 pivotal clinical trial of inaxaplin for the treatment of APOL1-mediated kidney disease – BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today provided updates on multiple kidney diseases in its pipeline including IgA nephropathy (IgAN), primary membranous nephropathy (pMN), and APOL1-mediated kidney disease (AMKD). These updates demonstrate the transformative potential of Vertex’s investigational therapies in multiple serious kidney diseases, and include positive new data on povetacicept, a dual inhibitor of the BAFF and APRIL pathways, in IgAN and pMN, presented at the American Society of Nephrology’s (ASN) Kidney Week Congress on October 23-27 in San Diego, California. “We are very pleased with the broadening of our innovative pipeline in renal medicine which now spans programs in AMKD, IgAN, pMN and polycystic kidney disease,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “The new data in IgAN and pMN we shared at this year’s ASN congress continue to reinforce povetacicept as a potential best-in-class therapy and demonstrate its potential as a pipeline-in-a-product. We also continue to make progress in AMKD and autosomal dominant polycystic kidney disease (ADPKD) where we are advancing the first potential treatments to address the underlying cause of these diseases.” Povetacicept in IgAN Vertex presented data on 54 patients with IgAN who received povetacicept 80 mg or 240 mg subcutaneously every 4 weeks (SC Q4W). Treatment with povetacicept 80 mg SC Q4W demonstrated a clinically meaningful decrease in proteinuria, with a mean 66% reduction from baseline in urine protein to creatinine ratio at 48 weeks (UPCR; n=8) associated with stable renal function over 48 weeks as assessed by estimated glomerular filtration rate (eGFR). By 48 weeks, 63% (5 out of 8) of study participants achieved clinical remission, defined as UPCR 50% reduction in UPCR from baseline. Anti-PLA2R1 autoantibodies, which are a marker of disease activity and associated with clinical outcomes, decreased from baseline by a mean of 87% at week 20. Povetacicept was well tolerated in patients with pMN, with AEs that were mild or moderate in severity. There were no SAEs related to povetacicept. A poster presentation #TH-PO589 entitled “Updated Results with Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Primary Membranous Nephropathy (RUBY-3 Study)” was presented during the poster session on October 24 from 10:00 a.m. to 12:00 p.m. PDT. AMKD Vertex is developing inaxaplin, a potential first-in-class, investigational, oral small molecule inhibitor of APOL1, with the goal of targeting the underlying cause of AMKD. Enrollment and dosing are ongoing in the Phase 3 portion of the global Phase 2/3 pivotal AMPLITUDE clinical trial of inaxaplin. Vertex has the following AMKD poster presentations at ASN: Poster presentation #TH-P01203 entitled “AMPLITUDE: A Phase 2/3 Adaptive Trial of Inaxaplin in APOL1-mediated Kidney Disease” was presented during the poster session on October 24 from 10:00 a.m. to 12:00 p.m. PDT. Poster presentation #SA-PO701 entitled “Small Molecule APOL1 Channel Inhibitor Reduces Proteinuria, Rescues Podocyte Injury, and Reverses eGFR Decline in an APOL1-Mediated Kidney Disease Mouse Model” will be presented during the poster session on October 26 from 10:00 a.m. to 12:00 p.m. PDT. Poster presentation #SA-PO700 entitled “Small Molecule Inhibition of APOL1 Channel Activity Protects Podocytes from Mitochondrial Dysfunction, Cell Death and Barrier Disruption Induced by APOL1 Risk Variants” will be presented during the poster session on October 26 from 10:00 a.m. to 12:00 p.m. PDT. All accepted abstracts are available online on the ASN website . About IgA Nephropathy (IgAN) IgAN is a serious, progressive, life-threatening, B cell-mediated chronic kidney disease that is the most common cause of primary (idiopathic) glomerulonephritis, affecting people worldwide including approximately 130,000 people in the U.S. IgAN results from deposition of circulating immune complexes consisting of immunoglobulins and galactose-deficient immunoglobulin A (Gd-IgA1) in the renal glomerular mesangium, triggering kidney injury and fibrosis. A high percentage of people with IgAN progress to end-stage renal disease. There are no approved therapies that specifically target the underlying cause of IgAN. About RAINIER RAINIER is a global Phase 3 pivotal trial of povetacicept 80 mg vs. placebo on top of standard of care in approximately 480 people with IgAN. The study is designed to have a pre-planned interim analysis evaluating UPCR for the povetacicept arm versus placebo after a certain number of patients reach 36 weeks of treatment. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval in the U.S. Final analysis will occur at two years of treatment, with a primary endpoint of total eGFR slope through Week 104. About Primary Membranous Nephropathy (pMN) Primary membranous nephropathy is a serious, progressive, life-threatening B cell-mediated chronic kidney disease affecting people worldwide, with approximately 60,000 people diagnosed in the U.S. pMN causes a patient’s immune system to damage the glomeruli and may cause progressive loss of kidney function. There are no approved therapies that specifically target the underlying cause of pMN. About RUBY-3 RUBY-3 is an ongoing, multiple ascending dose, multi-cohort, open label, Phase 1/2 basket study of povetacicept in autoimmune glomerulonephritis, including IgAN, pMN, lupus nephritis and ANCA-associated vasculitis with glomerulonephritis where povetacicept is being administered subcutaneously for up to 104 weeks. About Povetacicept Povetacicept is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, T cells and innate immune cells. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept has higher binding affinity and greater potency in preclinical studies versus other inhibitors of BAFF and/or APRIL alone and has demonstrated potential best-in-class efficacy in a clinical trial in patients with IgA nephropathy and primary membranous nephropathy. Povetacicept is also in development for multiple serious diseases including other autoimmune kidney diseases and autoimmune cytopenias. About APOL1-Mediated Kidney Disease (AMKD) AMKD is a genetic kidney disease affecting approximately 100,000 people in the U.S. and Europe. AMKD is caused by two variants of the APOL1 gene, which exert a toxic effect on kidney cells, leading to cell injury, cell death and damage to glomeruli (which filter blood to the kidney). Even after treatment with currently available therapies, people with AMKD often progress to kidney failure. Kidney failure is treated with frequent, long-term dialysis or a kidney transplant. Both require lifelong treatment and follow-up and carry a high mortality risk . There are currently no approved treatments that address the underlying cause of AMKD. About Inaxaplin Inaxaplin is a potential first-in-class, investigational small molecule inhibitor of APOL1, and the first investigational therapy aimed at treating the underlying cause of AMKD. About AMPLITUDE AMPLITUDE is a global Phase 2/3 pivotal trial of inaxaplin for the treatment of AMKD, in which a 45 mg once daily oral dose is compared to placebo, on top of standard of care. The study is designed to have a pre-planned interim analysis at Week 48 evaluating estimated glomerular filtration rate (eGFR) slope, a measure of kidney function, supported by a percent change from baseline in proteinuria, in the inaxaplin arm versus placebo. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval in the U.S. Enrollment and dosing are ongoing in the Phase 3 portion of the study. About Autosomal Dominant Polycystic Kidney Disease (ADPKD) ADPKD is the most common inherited kidney disease and one of the most common severe Mendelian genetic diseases, affecting approximately 250,000 diagnosed people in the U.S. and Europe. As an autosomal dominant disease, one affected parent can pass on the disease to their children. In most cases, ADPKD is caused by variants in the PKD1 and PKD2 genes, which express proteins known as polycystins. The majority of ADPKD patients (~80%) have a variant in the PKD1 gene, resulting in a loss of function of polycystin 1 (PC1). This leads to the proliferation of kidney epithelial cells, increased fluid secretion and the formation and expansion of numerous fluid-filled cysts. The progressive cyst formation causes an increase in kidney size and decline in kidney function. Around half of patients with ADPKD experience kidney failure by the age of 60. Kidney cysts can also lead to severe abdominal pain, cyst infection, blood in the urine and kidney stones, all of which significantly impair quality of life. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry’s top places to work, including 15 consecutive years on Science magazine’s Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex’s history of innovation, visit or follow us on LinkedIn , Facebook , Instagram , YouTube and X . Vertex Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the statements by Carmen Bozic, M.D., in this press release, and statements regarding Vertex’s expectations and plans for the global Phase 3 RAINIER study of povetacicept, including the potential for an interim analysis to serve as the basis to seek accelerated approval in the U.S., and expectations and plans for the Phase 3 portion of the clinical trial of inaxaplin, including the potential for an interim analysis to serve as the basis to seek accelerated approval in the U.S. While we believe the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company’s beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company’s development programs may not support registration or further development of its compounds due to safety, efficacy, and other reasons, and other risks listed under the heading “Risk Factors” in Vertex’s most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at and available through the company’s website at . You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN) Contacts Vertex Pharmaceuticals Incorporated Investors: InvestorInfo@vrtx.com Media: mediainfo@vrtx.com or International: +44 20 3204 5275 or U.S.: 617-341-6992 or Heather Nichols: +1 617-839-3607

PRINCETON, NJ, USA & TOKYO, Japan I October 22, 2024 I Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical, Co. Ltd. (Otsuka), today announce positive topline interim data from the ongoing Phase 3 clinical trial of sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgA nephropathy) in adults. Sibeprenlimab is an investigational, anti-APRIL monoclonal antibody ( A PR oliferation- I nducing L igand) that blocks a key initiating step in the immune pathogenic cascade of IgA nephropathy by limiting Gd-IgA1 production and immune complex formation. IgA nephropathy is a progressive, autoimmune, chronic kidney disease that can lead to end-stage kidney disease (ESKD) over the lifetime of most patients. 1,2,3,4 Otsuka was previously granted Breakthrough Therapy designation for sibeprenlimab following favorable results of the Phase 2 ENVISION clinical trial. 3 The pre-specified interim analysis review, conducted by an independent data monitoring committee, found that the Phase 3 VISIONARY study (NCT05248646) met its primary endpoint by demonstrating that sibeprenlimab produced a statistically significant and clinically meaningful reduction in 24-hour uPCR (urine protein-to-creatine ratio) compared to placebo after nine months of treatment. 5 The study, a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 530 adult patients (largest of its kind) with IgA nephropathy who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor), was designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo. The primary efficacy endpoint was to evaluate the change in 24-hour uPCR at 9 months compared with baseline. 5 “The positive interim data from this trial suggest that by targeting APRIL, we could provide a new therapeutic strategy for people living with this progressive kidney disease,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “We look forward to the completion of this study and reviewing the full results at a future timepoint. We are deeply appreciative to the patients with IgA nephropathy who participated in this trial, their caregivers, and investigators, all of whom continue to contribute greatly to this research.” Brian Pereira, M.D., CEO of Visterra, Inc., an Otsuka U.S. affiliate, which designed and engineered sibeprenlimab, said, “We are encouraged by sibeprenlimab’s continuing progress and its potential to provide a needed and possibly disease-modifying treatment option to IgA nephropathy patients.” The ongoing Phase 3 study continues in a blinded manner to evaluate the change in kidney function over 24 months as measured by estimated glomerular filtration rate (eGFR) and is expected to be completed in early 2026. Further prespecified and exploratory analyses of the data will be conducted to determine the full potential of sibeprenlimab for the treatment of IgA nephropathy. Otsuka plans to review interim analysis results with the FDA to enable a potential regulatory submission for accelerated approval. About Sibeprenlimab Sibeprenlimab (formerly VIS649) was designed and engineered by Visterra, Inc., a wholly owned subsidiary of Otsuka. Pre-clinical and early-stage trials of sibeprenlimab were also conducted by Visterra. Sibeprenlimab is an investigational monoclonal antibody that blocks the action of APRIL ( A PR oliferation- I nducing L igand), that plays a key role in IgA nephropathy’s four-hit pathogenic cascade. APRIL is an important sustaining factor in IgA nephropathy progression by promoting the production of pathogenic Gd-IgA1 and immune complex formation.​ By binding and neutralizing APRIL, sibeprenlimab may help reduce the amount of immunoglobulin A (IgA) and Gd-IgA1. Lower levels of Gd-IgA1 may then result in reduced auto-antibody production, which in turn may result in fewer immune complexes, decreased immune complex deposits in the kidney, and reduced proteinuria and kidney inflammation. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward ESKD. 1,2,3,5 By blocking APRIL, sibeprenlimab may help address one of the IgA nephropathy-specific drivers for nephron loss. About Immunoglobulin A Nephropathy and APRIL IgA nephropathy, also known as Berger’s disease, is a progressive, autoimmune, chronic kidney disease that typically manifests in adults aged 20-40 years and leads to ESKD over the lifetime of most patients. 4, 6, 7 It is characterized by the accumulation of IgA in the kidneys – a type of antibody that plays a critical role in the immune system.IgA nephropathy can lead to progressive kidney dysfunction and, eventually, ESKD, imposing a significant burden on patients. 6 Despite supportive care, including therapies that focus on treating the symptoms of IgA nephropathy, continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients. 6 APRIL ( A PR oliferation- I nducing L igand), a cytokine in the tumor necrosis factor (TNF) family, is integral to the development and progression of IgA nephropathy. It promotes the survival and class switching of B cells to produce IgA, particularly the pathogenic galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes in the kidneys. 8 About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide . Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does. Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,250 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Co., Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 34,400 people worldwide and had consolidated sales of approximately USD 14.2 billion in 2023. All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS . Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/. About Visterra Visterra is a biologics research and early-stage clinical development biotechnology company committed to developing innovative antibody-based therapies for the treatment of patients with immune-mediated kidney diseases and other hard-to-treat diseases. Its proprietary Hierotope® platform enables the design and engineering of precision biologics-based product candidates that specifically bind to, and modulate, key disease targets that are not adequately addressed by traditional therapeutic approaches. The platform also includes Fc engineering capabilities for half-life extension, bispecific antibodies and antibody-drug conjugates (ADCs). Visterra’s pipeline includes programs targeting kidney diseases, immunologically-driven diseases and infectious diseases. Visterra is an indirect subsidiary of Otsuka Pharmaceutical Co., Ltd. For more information, visit www.visterrainc.com . References 1. Mathur M, Barratt J, Chacko B, et al. A Phase 2 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy Patients. NEJM. 2023 https://www.nejm.org/doi/full/10.1056/NEJMoa2305635 2. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy (nih.gov) 3. Mathur M, Barratt J, Suzuki Y, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG2 Monoclonal Antibody, in Healthy Volunteers. Kidney Int Rep. 2022;7(5):993-1003. 4. Pitcher, D. Braddon, et. al Long-term outcomes in IGA nephropathy. Clinical journal of the American Society of Nephrology : CJASN. https://pubmed.ncbi.nlm.nih.gov/37055195/ . 5. Otsuka Pharmaceutical Development & Commercialization, Inc.Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN). Clinicaltrials.gov. 6. Cheung CK, Barratt J, Liew A, Zhang H, Tesar V, Lafayette R. The role of BAFF and April in IGA nephropathy: Pathogenic mechanisms and targeted therapies. Frontiers in nephrology. February 1, 2024. 7. Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016. https://pubmed.ncbi.nlm.nih.gov/27189177/ . 8. Yeo SC et al. Is immunoglobulin A nephropathy different in different ethnic populations? April 2019. https://onlinelibrary.wiley.com/doi/full/10.1111/nep.13592 . SOURCE: Otsuka Pharmaceuticals