PureTech Founded Vedanta Biosciences Publishes Additional Phase 2 VE303 Results in Nature Medicine
PureTech's Founded Entity, Vedanta Biosciences, published additional Phase 2 results for VE303, their lead candidate for preventing recurrent Clostridioides difficile infection (rCDI), in Nature Medicine. The study showed VE303, a first-in-class Live Biotherapeutic Product consisting of eight bacterial strains, was well-tolerated and reduced CDI recurrence odds by over 80% compared to placebo.
The new analyses revealed that VE303 works through multiple mechanisms, including restoring healthy gut microbial community, decreasing inflammation, and increasing protective metabolites. The research identified predictors of VE303 colonization and clinical response, showing that strain abundance was predictive of remaining recurrence-free.
These findings informed the design of the ongoing global Phase 3 RESTORATiVE303 study, with topline data expected in 2026.
PureTech's Entità Fondata, Vedanta Biosciences, ha pubblicato ulteriori risultati della Fase 2 per VE303, il loro candidato principale per prevenire l'infezione ricorrente da Clostridioides difficile (rCDI), su Nature Medicine. Lo studio ha dimostrato che VE303, un prodotto bioterapeutico vivo di prima classe composto da otto ceppi batterici, è stato ben tollerato e ha ridotto le probabilità di recidiva di CDI di oltre l'80% rispetto al placebo.
Le nuove analisi hanno rivelato che VE303 agisce attraverso molteplici meccanismi, tra cui il ripristino della sana comunità microbica intestinale, la diminuzione dell'infiammazione e l'aumento dei metaboliti protettivi. La ricerca ha identificato i predittori della colonizzazione da VE303 e della risposta clinica, dimostrando che l'abbondanza dei ceppi era predittiva del mantenimento dello stato di assenza di recidive.
Questi risultati hanno informato la progettazione dello studio globale in corso di Fase 3 RESTORATiVE303, con i dati preliminari attesi nel 2026.
PureTech's Entidad Fundada, Vedanta Biosciences, publicó resultados adicionales de la Fase 2 para VE303, su candidato principal para prevenir la infección recurrente por Clostridioides difficile (rCDI), en Nature Medicine. El estudio mostró que VE303, un producto bioterapéutico vivo de primera clase compuesto por ocho cepas bacterianas, fue bien tolerado y redujo las probabilidades de recurrencia de CDI en más del 80% en comparación con el placebo.
Los nuevos análisis revelaron que VE303 actúa a través de múltiples mecanismos, incluidos el restablecimiento de la comunidad microbiana intestinal saludable, la disminución de la inflamación y el aumento de metabolitos protectores. La investigación identificó predictores de la colonización de VE303 y de la respuesta clínica, mostrando que la abundancia de cepas era predictiva de permanecer libre de recurrencias.
Estos hallazgos informaron el diseño del estudio global en curso de Fase 3 RESTORATiVE303, con datos preliminares esperados para 2026.
PureTech's 설립된 회사인 Vedanta Biosciences는 Clostridioides difficile 재발 감염(rCDI) 예방을 위한 주요 후보 물질 VE303의 추가 임상 2상 결과를 Nature Medicine에 발표했습니다. 연구 결과, VE303은 8종의 박테리아 균주로 구성된 최초의 생물치료제 제품으로, 잘 견딜 수 있으며, 위약 대비 CDI 재발 확률을 80% 이상 줄인 것으로 나타났습니다.
새로운 분석 결과 VE303이 건강한 장내 미생물 군집을 복원하고 염증을 감소시키며 보호 대사물을 증가시키는 등의 여러 메커니즘을 통해 작용한다는 것이 밝혀졌습니다. 연구는 VE303의 군집 형성과 임상 반응의 예측 인자를 확인하였으며, 균주 풍부성이 재발 없음의 예측 인자라는 것을 보여주었습니다.
이러한 발견은 진행 중인 글로벌 3상 RESTORATiVE303 연구의 설계에 기여했으며, 주요 데이터는 2026년에 예상됩니다.
PureTech's Entité Fondée, Vedanta Biosciences, a publié des résultats supplémentaires de la Phase 2 pour VE303, leur principal candidat pour prévenir les infections récurrentes à Clostridioides difficile (rCDI), dans Nature Medicine. L'étude a montré que VE303, un produit biothérapeutique vivant de première classe composé de huit souches bactériennes, était bien toléré et réduisait les chances de récurrence de CDI de plus de 80 % par rapport au placebo.
Les nouvelles analyses ont révélé que VE303 fonctionne par plusieurs mécanismes, y compris la restauration d'une communauté microbienne intestinale saine, la diminution de l'inflammation et l'augmentation des métabolites protecteurs. La recherche a identifié des prédicteurs de la colonisation par VE303 et de la réponse clinique, montrant que l'abondance des souches était prédictive d'un état sans récurrence.
Ces résultats ont informé la conception de l'étude mondiale en cours de Phase 3 RESTORATiVE303, avec des résultats préliminaires attendus en 2026.
PureTech's gegründete Einheit, Vedanta Biosciences, veröffentlichte weitere Ergebnisse der Phase 2 für VE303, ihren Hauptkandidaten zur Verhinderung wiederkehrender Clostridioides difficile-Infektionen (rCDI), in Nature Medicine. Die Studie zeigte, dass VE303, ein einzigartiges biotherapeutisches Produkt bestehend aus acht bakteriellen Stämmen, gut vertragen wurde und die Wahrscheinlichkeit eines CDI-Rückfalls um über 80% im Vergleich zu Placebo verringerte.
Die neuen Analysen ergaben, dass VE303 durch mehrere Mechanismen wirkt, einschließlich der Wiederherstellung einer gesunden Mikrobiota im Darm, der Verringerung von Entzündungen und der Erhöhung von schützenden Metaboliten. Die Forschung identifizierte Prädiktoren für die Kolonisierung von VE303 und die klinische Reaktion, wobei die Stämmenhäufigkeit als prädiktiv für die Rückfallfreiheit auftrat.
Diese Ergebnisse flossen in das Design der laufenden globalen Phase 3-Studie RESTORATiVE303 ein, mit ersten Ergebnissen, die für 2026 erwartet werden.
- Phase 2 results showed 80% reduction in CDI recurrence odds vs placebo
- VE303 demonstrated multiple beneficial mechanisms of action
- Strong correlation between VE303 colonization and clinical benefits
- Study findings directly informed Phase 3 trial design
- Phase 3 results not expected until 2026
Insights
The publication of additional Phase 2 results for VE303 in Nature Medicine represents a significant milestone in the microbiome therapeutics field. The data reveals multiple compelling aspects that strengthen VE303's clinical profile:
The 80% reduction in CDI recurrence is particularly notable as rCDI affects approximately 170,000 patients annually in the US alone, with current treatments showing efficacy. VE303's defined consortium of eight bacterial strains offers several advantages over first-generation fecal microbiota transplants:
- Predictable composition and manufacturing scalability
- Clear mechanism of action through multiple pathways
- Ability to study pharmacokinetic-pharmacodynamic relationships
- Identification of response predictors
The mechanistic insights showing increased short-chain fatty acids and secondary bile acids, along with reduced inflammatory markers, provide a strong scientific rationale for VE303's efficacy. The 14-day treatment duration, designed to account for variable antibiotic clearance, demonstrates sophisticated clinical trial design.
While the Phase 3 data expected in 2026 seems distant, this timeline is reasonable given the complexity of microbiome studies. The BARDA support indicates government recognition of VE303's potential public health impact, particularly in addressing antimicrobial resistance concerns.
VE303 was well tolerated and decreased the odds of rCDI through multiple mechanisms
Analyses identified predictors of VE303 colonization and protection from CDI recurrence
Topline data for the ongoing Phase 3 pivotal RESTORATiVE303 study are expected in 2026
VE303 is a potential first-in-class Live Biotherapeutic Product for the prevention of rCDI, which consists of a defined consortium of eight bacterial strains. Clinical results from Vedanta’s successful Phase 2 CONSORTIUM study, published in the Journal of the American Medical Association (JAMA), demonstrated that the higher dose of VE303 studied was well tolerated and reduced the odds of CDI recurrence by more than
The new publication which is entitled “Multi-omic Profiling a Defined Bacterial Consortium for Treatment of Recurrent Clostridioides difficile Infection,” reports additional results from CONSORTIUM. Profiling of microbiome composition, fecal metabolites, and host immune function indicated that VE303 works through multiple mechanisms to prevent rCDI by restoring a healthy gut microbial community, decreasing inflammation, and increasing levels of protective metabolites. In addition, the work identified predictors of high or low VE303 colonization and clinical response.
Taken together, these results demonstrate that VE303 works through multiple mechanisms to reduce CDI recurrence. Results from the CONSORTIUM study informed the design and dose selection for the global, pivotal Phase 3 study, RESTORATiVE303, that is currently underway to confirm the efficacy and safety profile of VE303 in the prevention of rCDI. Topline data for this study are expected in 2026.
The full text of the announcement from Vedanta is as follows:
Vedanta Biosciences Publishes Additional Phase 2 VE303 Results in Nature Medicine
VE303 was well tolerated and decreased the odds of rCDI through multiple mechanisms
Analyses identified predictors of VE303 colonization and protection from CDI recurrence
Topline data for the ongoing Phase 3 pivotal RESTORATiVE303 study are expected in 2026
VE303 is a potential first-in-class Live Biotherapeutic Product for the prevention of rCDI, which consists of a defined consortium of eight bacterial strains. Clinical results from Vedanta’s successful Phase 2 CONSORTIUM study, published in the Journal of the American Medical Association (JAMA), demonstrated that the higher dose of VE303 studied was well tolerated and reduced the odds of CDI recurrence by more than
The publication which is entitled “Multi-omic Profiling a Defined Bacterial Consortium for Treatment of Recurrent Clostridioides difficile Infection,” reports additional results from CONSORTIUM. Profiling of microbiome composition, fecal metabolites, and host immune function indicated that VE303 works through multiple mechanisms to prevent rCDI by restoring a healthy gut microbial community, decreasing inflammation, and increasing levels of protective metabolites. In addition, the work identified predictors of high or low VE303 colonization and clinical response.
“This clinical research offers new insights into the mechanisms of action of VE303, providing a rationale for the drug’s protective effects in rCDI,” said Bernat Olle, Ph.D., Chief Executive Officer of Vedanta Biosciences. “Due to VE303’s precisely known, defined composition, we can study its mechanisms of action and PK-PD relationships in a rigorous way, taking a step towards understanding why some patients respond better than others to a microbiome restoration intervention. We believe this line of work helps fill a knowledge gap in the field, since characterization of the mechanisms of action of first-generation fecal microbiota products has been very limited.”
Highlights of the publication include:
- Abundance of specific VE303 strains, and of VE303 strains overall, was predictive of remaining recurrence-free.
- The strains that colonized well differed across individuals, suggesting that efficacy is derived from strains working together as a consortium.
- VE303 colonization and clinical benefit correlated with increased levels of short-chain fatty acids and key secondary bile acids, both of which have beneficial effects in conferring resistance to CDI.
- Faster recovery of a more diverse microbiome, which was seen in the high dose recipients of VE303, was associated with non-recurrence.
- The elimination rate of the antibiotic used for the CDI episode was a predictor of VE303 colonization. Given that clearance of residual antibiotic from stool varies significantly among individuals and can take a week or longer, treating with VE303 for 14 consecutive days following completion of standard-of-care antibiotics enabled VE303 strains to be inoculated when the intestinal environment was most permissive to colonization.
- VE303 use led to lower levels of pro-inflammatory and potentially pathogenic Gram-negative species, including Klebsiella and Citrobacter, that are linked to CDI recurrence and AMR bacterial infections.
Taken together, these results demonstrate that VE303 works through multiple mechanisms to reduce CDI recurrence. Results from the CONSORTIUM study informed the design and dose selection for the global, pivotal Phase 3 study, RESTORATiVE303, that is currently underway to confirm the efficacy and safety profile of VE303 in the prevention of rCDI. Topline data for this study are expected in 2026.
This project has been supported in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50120C00177.
About VE303
VE303 is a potential first-in-class Live Biotherapeutic Product for the prevention of recurrent Clostridioides difficile infection (rCDI). VE303 is an orally administered, defined bacterial consortium therapeutic candidate which consists of eight strains that were rationally selected using Vedanta’s product 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 Phase 3 RESTORATiVE303 registrational study of VE303 for the prevention of recurrent C. difficile infection. Vedanta Biosciences received a
About Vedanta Biosciences
Vedanta Biosciences is a clinical-stage biopharmaceutical company developing medicines for the treatment of 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 grown from pure clonal cell banks. 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.
About PureTech Health
PureTech is a clinical-stage biotherapeutics company dedicated to giving life to new classes of medicine to change the lives of patients with devastating diseases. The Company has created a broad and deep pipeline through its experienced research and development team and its extensive network of scientists, clinicians and industry leaders that is being advanced both internally and through its Founded Entities. PureTech's R&D engine has resulted in the development of 29 therapeutics and therapeutic candidates, including three that have been approved by the
For more information, visit www.puretechhealth.com or connect with us on X (formerly Twitter) @puretechh.
Cautionary Note Regarding Forward-Looking Statements
This press release contains statements that are or may be 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 should be considered forward-looking statements, including without limitation those related to Vedanta’s development plans for its pipeline of therapeutics of defined bacterial consortia as oral therapies for gastrointestinal diseases, including VE303, the timing of topline results for ongoing clinical trials, potential benefits to patients, and Vedanta’s and our future prospects, developments 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, 2023, 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.
View source version on businesswire.com: https://www.businesswire.com/news/home/20250126745982/en/
PureTech
Public Relations
publicrelations@puretechhealth.com
Investor Relations
IR@puretechhealth.com
Ben Atwell, Rob Winder
+44 (0) 20 3727 1000
puretech@fticonsulting.com
US Media
Justin Chen
+1 609 578 7230
justin@tenbridgecommunications.com
Source: PureTech Health plc
FAQ
What were the key findings of VE303's Phase 2 CONSORTIUM study for PRTC?
When will PureTech's VE303 Phase 3 trial results be available?
How does VE303 work to prevent recurrent CDI?
What are the predictors of VE303 treatment success?
