JAMA publication includes in-depth safety and efficacy results from Vedanta’s successful Phase 2 study of VE303

PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) (“PureTech” or the “Company”), a clinical-stage biotherapeutics company, noted today that its Founded Entity, Vedanta Biosciences, a clinical-stage company that is developing a potential new category of oral therapies based on defined bacterial consortia, announced the publication of Phase 2 study results from its lead program, VE303, in the Journal of the American Medical Association (JAMA), as well as a late-breaker oral presentation at the European Congress of Clinical Microbiology in Infectious Diseases (ECCMID) annual event.

The JAMA paper, “VE303, a Defined Bacterial Consortium, vs. Placebo for the Prevention of Recurrent Clostridioides difficile Infection: A Randomized Trial,” expands on the results of the Phase 2 study of VE303, which was designed to identify the recommended dose for a Phase 3 study of VE303. The study data confirmed that VE303 prevented recurrent Clostridioides difficile infection (CDI) compared with placebo in the study population. The publication announced today includes new analyses of secondary efficacy endpoints, such as CDI recurrence rates at week 24, and stool microbiome endpoints, which included both VE303 strain colonization and gut microbiome diversity.

The ECCMID presentation offers more in-depth scrutiny of VE303 strain colonization dynamics and its relationship to the observed clinical effect.

The full text of the announcement from Vedanta is as follows:

Vedanta Biosciences Publishes Phase 2 Results in the Journal of the American Medical Association and Presents at ECCMID

JAMA publication includes in-depth safety and efficacy results from successful Phase 2 study of VE303

Additional analyses support a relationship between VE303 exposure and clinical response via enhanced bacterial colonization, in addition to new evidence of inflammation modulation in treated patients

CAMBRIDGE, MA, April 17, 2023 – Vedanta Biosciences, a clinical-stage company that is developing a potential new category of oral therapies based on defined bacterial consortia, today announced the publication of Phase 2 study results from its lead program, VE303, in the Journal of the American Medical Association (JAMA), as well as a late-breaker oral presentation at the European Congress of Clinical Microbiology in Infectious Diseases (ECCMID) annual event. The publication includes analyses of safety, efficacy, in preventing recurrence of Clostridioides difficile infection (rCDI), and VE303 strain colonization data from the successfully completed Phase 2 study of VE303. The ECCMID presentation offers more in-depth scrutiny of VE303 strain colonization dynamics and its relationship to the observed clinical effect. Colonization dynamics is analogous to traditional drug pharmacokinetics and refers to the growth and persistence over time of bacterial strain populations in the human gut.

“First-generation microbiome approaches use fecal donor material of variable composition, resulting in inconsistent efficacy outcomes across different clinical studies. In contrast, the results of our VE303 Phase 2 study demonstrate the potential utility of reproducible product candidates that are based on defined bacterial strains grown from clonal cell banks, in a manner analogous to monoclonal antibody production,” said Jeffrey L. Silber, M.D., Chief Medical Officer of Vedanta. “Our targeted approach offers consistent composition and quality attributes, which we believe could provide more consistent clinical benefit. Defined bacterial consortia also avoid the risk of pathogen transfer from donor stool—since there is no donor—and enable greater scalability compared with fecal-derived approaches.”

“Vedanta’s VE303 candidate is based on compelling science that illustrates the role of gut dysbiosis in persistent inflammatory states and the potential for a rationally designed bacterial consortium to restore that balance and support healthy homeostasis of bacterial populations,” said Darrell Pardi, M.D., Chair of the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota, and senior author of the JAMA paper. “The notorious difficulty of preventing recurrent CDI creates a large population of patients struggling with the condition, with few therapeutic options. VE303 provides an approach that is designed to address the underlying biology in a novel way. The clinical data to-date have been extremely promising, and we are eager to see future updates on this program as it progresses through the clinic.”

The Journal of the American Medical Association Publication

The JAMA paper, “VE303, a Defined Bacterial Consortium, vs. Placebo for the Prevention of Recurrent Clostridioides difficile Infection: A Randomized Trial,” expands on the results of the Phase 2 study of VE303, which was designed to identify the recommended dose for a Phase 3 study of VE303. The study data confirmed that VE303 prevented recurrent CDI compared with placebo in the study population. The publication announced today includes new analyses of secondary efficacy endpoints, such as CDI recurrence rates at week 24, and stool microbiome endpoints, which included both VE303 strain colonization and gut microbiome diversity.

ECCMID Presentation

This presentation, titled, “An 8-strain defined bacterial consortium promotes microbiota restoration and limits inflammation in patients with recurrent Clostridioides difficile infection (rCDI)” details how VE303 dosing was associated with reduced inflammation within subjects at high risk of rCDI, determined by biomarkers that included a reduction in fecal calprotectin levels and changes in circulating serum cytokines. This analysis demonstrates the possibility that VE303 may provide benefit beyond microbiome restoration in patients with CDI, by limiting pathological inflammation.

About VE303

VE303 is a defined bacterial consortium therapeutic candidate designed for the prevention of recurrent Clostridioides difficile infection (rCDI). It consists of eight strains that were rationally selected using Vedanta’s 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 reported positive topline results in October 2021 from the Phase 2 CONSORTIUM trial, in which VE303 was associated with a 31.7% absolute risk reduction in the rate of recurrence when compared with placebo, representing a greater than 80% reduction in the odds of a CDI recurrence. Vedanta believes VE303 has the potential to become a first-in-class therapeutic based on a defined bacterial consortium. Vedanta Biosciences received a $5.4 million research grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) in 2017 and a contract of up to $81.9 million from Biomedical Advanced Research and Development Authority (BARDA) in 2020 to support clinical studies of VE303. VE303 was granted Orphan Drug Designation in 2017 by the U.S. Food and Drug Administration (FDA) for the prevention of recurrent CDI.

About Vedanta Biosciences

Vedanta Biosciences is leading the development of a potential new category of oral therapies based on defined consortia of bacteria isolated from the human microbiome and grown from pure clonal cell banks. The company’s clinical-stage pipeline includes product candidates being evaluated for the prevention of recurrent C. difficile infection, inflammatory bowel diseases, food allergy, and liver disease. These investigational therapies are grounded in pioneering research by our scientific cofounders – published in leading journals including Science, Nature, and Cell – to identify beneficial bacteria that live symbiotically within the healthy human gut, fight pathogens, and induce a range of potent immune responses. Vedanta Biosciences controls a foundational portfolio of more than 70 patents and has built what it believes is the industry-leading platform for development of defined bacterial consortia drugs. This platform includes one of the largest libraries of bacteria derived from the human microbiome, vast datasets from human interventional studies, proprietary capabilities in consortium design, and end-to-end capabilities for CGMP-compliant manufacturing of oral drug candidates spanning cell banking, fermentation, lyophilization, and fill finish.

About Defined Bacterial Consortia

Defined Bacterial Consortia are assemblies of bacteria of standardized composition that act cooperatively to exert a therapeutic effect. The constituent strains in each consortium are rationally selected from Vedanta’s extensive in-house strain library, and grown from pure, clonal cell banks using scalable fermentation processes. Each capsule contains precisely controlled compositions and doses of the same live bacterial strains and is formulated for stable oral delivery to the lower gastrointestinal tract. We believe that our targeted approach offers consistent composition and quality attributes, may provide more consistent clinical benefit, limits safety risk, and enables greater scalability compared with fecal-derived approaches.

About PureTech Health

PureTech is a biotherapeutics company dedicated to changing the treatment paradigm for devastating diseases. The Company has created a broad and deep pipeline through the expertise of its experienced research and development team and its extensive network of scientists, clinicians and industry leaders. This pipeline, which is being advanced both internally and through PureTech's Founded Entities, is comprised of 26 therapeutics and therapeutic candidates, including two (Plenity® and EndeavorRx®) that have received both U.S. FDA clearance and European marketing authorization and a third (KarXT) that will soon be filed for FDA approval, as of the most recent update by the Company. All of the underlying programs and platforms that resulted in this pipeline of therapeutic candidates were initially identified or discovered and then advanced by the PureTech team through key validation points based on unique insights in immunology and drug development.

For more information, visit www.puretechhealth.com or connect with us on Twitter @puretechh.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact, including without limitation those related to the Phase 2 study results of Vedanta’s VE303, the potential therapeutic benefits of VE303, and Vedanta’s and PureTech's future prospects, development plans and strategies. The forward-looking statements are based on current expectations and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results, performance and achievements to differ materially from current expectations, including, but not limited to, those risks, uncertainties and other important factors described under the caption "Risk Factors" in our Annual Report on Form 20-F for the year ended December 31, 2021 filed with the SEC and in our other regulatory filings. These forward-looking statements are based on assumptions regarding the present and future business strategies of the Company and the environment in which it will operate in the future. Each forward-looking statement speaks only as at the date of this press release. Except as required by law and regulatory requirements, we disclaim any obligation to update or revise these forward-looking statements, whether as a result of new information, future events or otherwise.

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