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

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 www.idweek.org.

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.

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