27
January 2025
PureTech
Health plc
PureTech Founded 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
PureTech Health plc
(Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated to
changing the lives of patients with devastating diseases, noted
that its Founded Entity,
Vedanta Biosciences, a late
clinical-stage company developing defined bacterial consortia as
oral therapies for gastrointestinal diseases, today announced the
publication of additional results from the Phase 2 CONSORTIUM study
for its lead candidate, VE303, which is being evaluated for
prevention of recurrent Clostridioides difficile infection
(rCDI). The new analyses were published this month in Nature
Medicine and
can be viewed online.
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 80% compared with placebo.
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
CAMBRIDGE, Mass., January 23, 2025
--
Vedanta Biosciences, a late
clinical-stage company developing defined bacterial consortia as
oral therapies for gastrointestinal diseases, today announced the
publication of additional results from the Phase 2 CONSORTIUM study
for its lead candidate, VE303, which is being evaluated for
prevention of recurrent Clostridioides difficile infection
(rCDI). The new analyses were published this month in Nature
Medicine and
can be viewed online.
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 80% compared with placebo. VE303
organisms rapidly and robustly colonize the gut in a dose-dependent
manner. Colonization predicted greater recurrence-free probability,
establishing a direct connection between exposure and clinical
response.
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 $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 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 U.S. Food and Drug Administration. A number of
these programs are being advanced by PureTech or its Founded
Entities in various indications and stages of clinical development,
including registration enabling studies. 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.
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.
Contact:
PureTech
Public Relations
publicrelations@puretechhealth.com
Investor Relations
IR@puretechhealth.com
UK/EU Media
Ben Atwell, Rob Winder
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Justin Chen
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