# PureTech Health Vedanta Biosciences Publishes Phase 2 Results

- Link: https://www.directorstalkinterviews.com/puretech-health-vedanta-biosciences-publishes-phase-2-results/4121114991
- Published: 2023-04-17T08:10:24+01:00
- Author: Emily Johnson

**PureTech Health plc** (Nasdaq: PRTC, LON:PRTC), a clinical-stage biotherapeutics
company, has 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, has 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_

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](https://www.vedantabio.com/news-media/press-releases/detail/2881/vedanta-presents-data-from-multiple-studies-at-digestive)
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 ](https://www.vedantabio.com/)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](http://science.sciencemag.org/content/331/6015/337)_,_
[Nature](https://www.nature.com/articles/nature12331), and [Cell](https://www.ncbi.nlm.nih.gov/pubmed/26411289)__–
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.

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