Vedanta Biosciences, Inc.

VE303 high dose associated with reduction in antibiotic resistance genes (ARGs) High VE303 strain colonization also associated with reduced ARGs Presence of ARGs increases the risk of drug-resistant infections Pivotal Phase 3 trial, RESTORATiVE303, underway CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vedanta Biosciences , a late clinical-stage company developing defined bacterial consortia as oral therapies with an initial focus on gastrointestinal diseases, today announced the oral presentation of additional analyses from its completed Phase 2 CONSORTIUM study of VE303, an orally administered defined bacterial consortium candidate that is being developed for the prevention of recurrent Clostridioides difficile infection (rCDI). These analyses document the positive impact of VE303 treatment on the levels of antibiotic resistance genes (ARG) in the gut microbiomes of patients enrolled in the CONSORTIUM study, revealing associations between higher dosage and colonization of VE303 strains with lower levels of ARGs. The late-breaking oral presentation will be given this Friday October 18, in Los Angeles, CA, as part of Infectious Diseases Week (IDWeek) 2024. “The intestinal tract is ordinarily an important line of defense against antibiotic-resistant organisms. A gut microbiome that is disrupted by multiple courses of antibiotics can become a reservoir for these potentially dangerous organisms, which could lead to development of a hard-to-treat infection elsewhere in the body,” said Jeffrey L. Silber, M.D., Chief Medical Officer of Vedanta Biosciences. “By helping to restore a healthier, more diverse gut microbiome, administration of VE303 appears to reduce the prevalence of organisms carrying these resistance genes. The analyses we are presenting at IDWeek document an additional dimension to VE303’s therapeutic profile, in addition to its ability to prevent further recurrence of CDI.” In the Phase 2 CONSORTIUM Study, VE303 was well tolerated, reduced the odds of CDI recurrence by >80% compared with placebo, colonized the gut well, and led to early restoration of healthy, diverse, native gut bacteria. The results of the study were published in the Journal of the American Medical Association in 2023. During the study, serial stool samples were analyzed for the presence of ARGs over time, beginning at the completion of antibiotic treatment for the most recent CDI episode. Compared with pre-treatment baseline samples, when study participants across the treatment groups were carrying an average of almost 60 ARGs, receipt of the VE303 high dose resulted in significantly fewer ARGs overall (p<0.005) and fewer ARGs carried by Proteobacteria (p<0.005), including Klebsiella , which can cause potentially serious infections. These significant reductions were seen by the end of treatment on Day 14 and were observed through Day 28 (the final timepoint in this analysis). In contrast, recipients of the VE303 low dose or placebo did not have a reduction in ARGs. Vedanta’s late-breaking oral presentation is titled “Impact of VE303, a Defined Bacterial Consortium, on Antimicrobial Resistant Gene Prevalence in Patients with Clostridioides difficile Infection (CDI)” and will be presented at 1:45pm PDT on Friday October 18 by Dr. Rajita Menon, Vedanta’s Director of Modeling & Statistics. About the RESTORATiVE303 Study RESTORATiVE303 is a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the safety and efficacy of VE303 in patients at high risk for recurrence of CDI after completing a course of antibiotics for a prior CDI episode. The trial is being conducted at approximately 200 sites in 23 countries, across five continents. The primary endpoint is the comparison of CDI recurrence rates at eight weeks in the VE303 and placebo groups. The Phase 3 study design and VE303 dosing regimen are based on the completed Phase 2 trial, in which VE303 met its primary endpoint for preventing CDI recurrence at eight weeks and was observed to be generally well-tolerated. For more information on RESTORATiVE303 ( NCT06237452 ), please visit clinicaltrials.gov. About VE303 VE303 is a potential first-in-class Live Biotherapeutic Product candidate for the prevention of recurrent Clostridioides difficile infection (rCDI). It consists of an orally administered defined bacterial consortium composed of eight strains that were selected using Vedanta’s product discovery engine. VE303 is produced from pure, clonal bacterial cell banks, which yield a standardized drug product in powdered form and bypass the need to rely on direct sourcing of donor fecal material of inconsistent composition. Vedanta published positive results in JAMA in April 2023 from the Phase 2 CONSORTIUM trial, in which VE303 met its primary endpoint of preventing C. difficile infection recurrence at eight weeks. Vedanta is currently enrolling patients into a registrational Phase 3 study, RESTORATiVE303, for the prevention of recurrent C. difficile infection. Vedanta Biosciences received a $5.4 million research grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) in 2017 and a contract for up to $114 million from Biomedical Advanced Research and Development Authority (BARDA) to support clinical studies of VE303. The U.S. Food and Drug Administration (FDA) granted VE303 Orphan Drug Designation in 2017 and Fast Track designation in 2023 for the prevention of recurrent CDI. About IDWeek 2024 IDWeek 2024 TM is an annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). With the theme “Advancing Science, Improving Care,” IDWeek features the latest science and bench-to-bedside approaches in prevention, diagnosis, treatment and epidemiology of infectious diseases, including HIV, across the lifespan. IDWeek 2024™ takes place Oct. 16-19 at the Los Angeles Convention Center (1201 S Figueroa St) in Los Angeles, CA. For more information, visit . About Vedanta Biosciences Vedanta Biosciences is a late clinical-stage company developing defined bacterial consortia as oral therapies with an initial focus on gastrointestinal diseases. The company’s lead assets are potential first-in-class oral therapies: VE303, in a Phase 3 registrational trial for prevention of recurrent C. difficile infection, and VE202, in a Phase 2 trial for treatment of ulcerative colitis. Vedanta’s pipeline has been built using the company’s industry-leading product engine for the development of therapies based on defined consortia of bacteria. The product engine, supported by broad foundational intellectual property, includes one of the largest libraries of bacteria isolated from the human microbiome, vast clinical datasets, proprietary capabilities in consortium design, and end-to-end CGMP manufacturing capabilities at commercial launch scale. Contacts Media Tom Donovan TBCVedanta@tenbridgecommunications.com Investors Chris Brinzey +1 617-835-9304 Chris.Brinzey@westwicke.com

The European Commission has granted conditional approval for Ipsen's IQIRVO (elafibranor) for the treatment of primary biliary cholangitis in adults, marking the first new therapy for this condition to be approved in the EU in almost ten years. With this approval, other companies such as CymaBay Therapeutics, Zydus Therapeutics, GlaxoSmithKline, and others also geared up to bring their candidates into the primary biliary cholangitis market. LAS VEGAS, Oct. 2, 2024 /PRNewswire/ -- Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is a long-term liver condition characterized by the gradual destruction of the small bile ducts within the liver, known as intrahepatic bile ducts. Over time, prolonged bile flow obstruction can result in cirrhosis and the development of portal hypertension. As per DelveInsight analysis, in 2023, the total diagnosed prevalent cases of primary biliary cholangitis in the 7MM were approximately 298K. These cases are projected to increase further during the forecast period (2024–2034). In 2023, the United States had the highest proportion of diagnosed prevalent cases of primary biliary cholangitis among the 7MM, comprising approximately 48% of the total cases. DelveInsight's epidemiology model for primary biliary cholangitis estimates a higher prevalence among females across the 7MM. Specifically, in the US in 2023, it suggests approximately 25K cases among males and 117K cases among females, indicating a female predominance. The primary treatment objectives are to reduce the progression rate of the disease and manage symptoms such as itching, osteoporosis, and dry eye/mouth (sicca syndrome). Liver transplantation remains the only life-saving option. Ursodeoxycholic acid (UDCA) is the main medication used to slow disease progression. Patients in the early stages often experience clinical, biochemical, and histological improvements. Studies suggest UDCA postpones the need for liver transplantation and extends survival, though its effectiveness in advanced stages like cirrhosis is uncertain. While initially approved by the US FDA for treating primary biliary cholangitis, UDCA now has generic versions available. The use of corticosteroids in patients without signs of autoimmune hepatitis remains a subject of ongoing research. Studies have shown that combining UDCA with dexamethasone can enhance the activity of the anion exchanger from two alternate promoters in liver cells in vitro. Budesonide is being considered due to its extensive first-pass hepatic metabolism, which may help minimize side effects. Corticosteroids may help relieve symptoms and improve biochemical and histological outcomes, though corticosteroid-induced osteoporosis is a major concern. The criteria for liver transplantation in patients with primary biliary cholangitis are generally the same as those for other chronic liver diseases. However, severe and unmanageable itching is a unique reason for considering a transplant. Fatigue, which may continue after transplantation, is not regarded as an indication for the procedure. Liver transplantation for PBC patients typically offers a better prognosis than for most other chronic liver diseases, with a 5-year survival rate of 84–87% and a 10-year survival rate of 79–84%. In May 2016, the US FDA granted accelerated approval for OCALIVA (obeticholic acid) as a treatment for primary biliary cholangitis. It is approved for use alongside UDCA in adults who do not respond adequately to UDCA, or as a standalone treatment for those who cannot tolerate UDCA. OCALIVA is a semi-synthetic bile acid analog with the chemical structure 6α-ethyl-chenodeoxycholic acid. OCALIVA remains the only approved second-line therapy for this condition. Later, in December 2016, the European Commission gave conditional approval for OCALIVA for the same uses—either in combination with UDCA or as monotherapy for adults unable to tolerate UDCA. Learn more about the FDA-approved primary biliary cholangitis drugs @ Drugs for Primary Biliary Cholangitis Treatment Recently, the European Commission has granted conditional approval for IQIRVO (elafibranor) 80mg tablets for treating primary biliary cholangitis. It can be used alongside ursodeoxycholic acid in adults who have an inadequate response to UDCA or as a standalone therapy for those who cannot tolerate UDCA. This decision follows a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on July 26, 2024, and the US FDA's Accelerated Approval granted on June 10, 2024. Elafibranor, a pioneering molecule, has been marketed and commercialized in the US by Ipsen under the brand name IQIRVO since June 2024. It was originally developed by GENFIT, from its discovery through the completion of a 52-week Phase III clinical trial. In 2021, Ipsen obtained exclusive global rights to elafibranor, except for China, Hong Kong, Taiwan, and Macau, through a licensing agreement with GENFIT. The EU approval was based on favorable outcomes from the Phase III ELATIVE trial, which demonstrated a 47% clinical benefit of IQIRVO combined with UDCA compared to placebo plus UDCA on the composite primary endpoint. The main objective for cholestasis response was defined as alkaline phosphatase (ALP) being less than 1.67 times the upper limit of normal (ULN), with a ≥15% reduction in ALP and total bilirubin levels within the normal range after one year. Additionally, the treatment showed a reduction in pruritus when compared to placebo. Additionally, in August 2024, Gilead Sciences, Inc. announced that the FDA has granted accelerated approval for LIVDELZI (seladelpar) to treat primary biliary cholangitis. This treatment can be used alongside ursodeoxycholic acid in adults who have not responded adequately to UDCA or as a standalone therapy for those unable to tolerate UDCA. Livdelzi is not advised for patients with or who develop decompensated cirrhosis. Seladelpar (MBX-8025) is a potent and selective PPARδ agonist, administered orally, and is currently being developed for patients with PBC who either do not respond to or cannot tolerate UDCA. In March 2024, Gilead Sciences completed its acquisition of CymaBay and announced the validation of a Marketing Authorization Application (MAA) for Seladelpar by the European Medicines Agency (EMA). Seladelpar has been granted Breakthrough Therapy Designation (BTD) by the US FDA, PRIME status by the EMA, and Orphan Drug Designation (ODD) from both agencies, which may accelerate the approval process. To know more about primary biliary cholangitis treatment options, visit @ New Treatment for Primary Biliary Cholangitis With this approval, several companies have also geared up to bring their lead assets into the market. The expected launch of emerging therapies, such as Saroglitazar Magnesium (Zydus Therapeutics), Linerixibat (GlaxoSmithKline), Setanaxib (Calliditas Therapeutics AB), Bezafibrate + obeticholic acid (Intercept Pharmaceuticals/Alfasigma), Volixibat (Mirum Pharmaceuticals), EP547 (Escient Pharmaceuticals), and others are expected to create a positive impact on the market. Other therapies in the early stages of the trial are also being developed. Discover which therapies are expected to grab major primary biliary cholangitis market share @ Primary Biliary Cholangitis Market Report Saroglitazar (LIPAGLYN) comprises two primary types of PPAR agonists: PPARα (alpha) and PPARγ (gamma). This medication simultaneously reduces lipid and glucose levels, effectively decreasing elevated triglycerides and blood sugar while enhancing insulin sensitivity. The US FDA has awarded Saroglitazar orphan drug designation (ODD) and fast track designation (FTD) for primary biliary cholangitis (PBC). It is presently undergoing Phase II/III trials for this condition. Linerixibat (GSK2330672) is a medication under development for patients with primary biliary cholangitis who suffer from itching. It is a small molecule inhibitor of the ileal bile acid transporter (IBAT) that is minimally absorbed and taken as an oral tablet. By preventing the reabsorption of bile acids in the small intestine, linerixibat lowers the levels of pruritic bile acids in the bloodstream. In 2019, the FDA designated it as an orphan drug (ODD). It is currently being evaluated in a Phase III trial for treating cholestatic pruritus in individuals with PBC. Discover more about drugs for primary biliary cholangitis in development @ Primary Biliary Cholangitis Clinical Trials The anticipated launch of these emerging therapies for primary biliary cholangitis are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the primary biliary cholangitis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the primary biliary cholangitis market saw a significant emergence of a dominant treatment modality, valued at USD 1.1 billion in the 7MM. This modality likely reflects advancements in therapeutic approaches such as first-line agents like UDCA, second-line treatments like obeticholic acid, and potentially emerging biologics or combination therapies aiming to address the complex pathophysiology of PBC, thus enhancing patient outcomes and market share. DelveInsight's latest published market report titled as Primary Biliary Cholangitis Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the primary biliary cholangitis country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The primary biliary cholangitis market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent cases of Primary Biliary Cholangitis Gender-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis Age-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM primary biliary cholangitis market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis up to 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this primary biliary cholangitis market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the primary biliary cholangitis market. Also, stay abreast of the mitigating factors to improve your market position in the primary biliary cholangitis therapeutic space. Related Reports Primary Biliary Cholangitis Pipeline Primary Biliary Cholangitis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key PBC companies, including Genfit, Zydus Discovery, Ohara Pharmaceutical, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Novartis, CymaBay Therapeutics, among others. Primary Biliary Cholangitis Epidemiology Forecast Primary Biliary Cholangitis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and PBC epidemiology trends. Liver Cirrhosis Market Liver Cirrhosis Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key liver cirrhosis companies, including Madrigal Pharmaceuticals, Inc., Galectin Therapeutics Inc., Grifols Therapeutics LLC, CymaBay Therapeutics, Akero Therapeutics, Inc., NGM Biopharmaceuticals, Inc., Gilead Sciences, Novo Nordisk A/S, Cellaion, Promethera Therapeutics, Lipocine Inc., Bristol Myers Squibb, Prism Pharma, Ohara Pharmaceutical, Shionogi, among others. Liver Cirrhosis Pipeline Liver Cirrhosis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key liver cirrhosis companies, including Versantis AG, Mirum Pharmaceuticals, Sagimet Biosciences, TenNor Therapeutics, Prism Pharma, Vedanta Biosciences, Intercept Pharmaceuticals, Boehringer Ingelheim, Ohara Pharmaceutical, Ocelot Bio, Calliditas Therapeutics, Galecto Biotech, Pharmicell, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . 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European Microbiome Innovation for Health and Microbiome Therapeutics Innovation Group Announce New Collaboration Agreement Paris, France, September 23, 2024, 2:00 pm CET - The European Microbiome Innovation for Health (EMIH) association today announced an agreement between the Microbiome Therapeutics Innovation Group (MTIG) and EMIH for a collaboration to advance microbiome drug development, explore synergies between international regulators, and convene cross-continental meetings to incorporate the perspectives of a wide-range of drug developers. This new collaboration will incorporate diverse perspectives with the goal of further accelerating microbiome therapeutic product development to expand availability of life-changing and life-saving regulatory approved microbiome therapies to patients. A main priority of the agreement is to harmonize regulatory frameworks from multiple regions to create a more cohesive approach in seeking the necessary policy and regulatory solutions for the issues faced by MT drug developers. “MTIG’s founding principal is to accelerate patients’ access to innovative microbiome therapeutics through our communal efforts,” said Dr. Nikole Kimes, Chairman of MTIG and CEO of Siolta Therapeutics. “The EMIH represents innovative microbiome companies aligned with this core mission, and we look forward to sharing insights with one another to amplify our collective voice and transform the lives of patients on both sides of the Atlantic.” Hervé Affagard, President of EMIH and CEO and co-founder of MaaT Pharma, stated "As leading associations in the microbiome field, we understand that our strength lies in collaboration. By joining forces with MTIG, we will accelerate the development and delivery of microbiome therapies, ensuring that groundbreaking treatments reach those who need them most, swiftly and safely. This partnership embodies our shared commitment to harmonizing regulatory frameworks, and we look forward to working closely with MTIG." EMIH and its members are dedicated to advancing knowledge and fostering the development of bioproductions, diagnostics, and medical devices based on the microbiome for human health. The organization is committed to ensuring equitable access to these innovations by adhering to regulatory frameworks that uphold the highest quality standards, while maintaining an economic balance to support ongoing therapeutic innovation. All pharmaceutical and biotechnology companies seeking regulatory approvals in Europe for microbiome bioproductions, diagnostics, and medical devices are eligible for membership consideration in EMIH. If you are interested in learning more, please contact EMIH here. About The Microbiome Therapeutics Innovation Group The Microbiome Therapeutics Innovation Group (MTIG) is a coalition of companies leading the research and development of FDA-approved microbiome therapeutics and microbiome-based products to address unmet medical needs, improve clinical outcomes, and reduce health care costs. The human microbiome is one of the new frontiers of medical innovation that has the potential to benefit patients suffering from numerous diseases afflicting millions of patients and consuming billions of dollars of healthcare resources. MTIG is committed to working with stakeholders who share in our mission and seek tangible policy and regulatory solutions in the emerging microbiome arena. Through a collective voice, the MTIG membership works together to enhance the regulatory, investment, and commercial environment to accelerate microbiome therapeutic product development and enable the field to reach its potential to benefit patients. Today, MTIG is comprised of eleven microbiome therapeutics companies: BiomeSense, Biose Industrie, Freya Biosciences, MaaT Pharma, Microba Life Sciences, Rebiotix Inc., a Ferring Company, Seres Therapeutics, Siolta Therapeutics, and Vedanta Biosciences. For more information, visit www.microbiometig.org About European Microbiome Innovation for Health The European Microbiome Innovation for Health (EMIH) is an independent coalition within the European Union, the United Kingdom, and Switzerland, currently comprising 20+ major players from the public and private sectors. From the laboratory to the patient’s bedside, EMIH covers the entire value chain of the microbiome industry. Its goal is to position Europe as a global leader in the development, production, and commercialization of microbiome-based therapeutic innovations. EMIH members include Bioaster, Biocodex, BioGaia, Biofortis, Biose Industrie, Eligo Bioscience, GMT Science, INRAe, Lallemand Health Solutions, Life Avocats, Enosis Santé, EnteroBiotix, Pelican Health, MaaT Pharma, mbiomics, Microbiotica, Microbiome Foundation, MRM Health, Nexbiome, Novobiome, Seventure Partners and SwipeBiome. For more information, please visit www.europeanmicrobiome.org Contact for European Microbiome Innovation for Health Email: p.richaud@europeanmicrobiome.org Attachment EMIH MTIG PR Final_240923