RCS - PureTech Health PLC - PRTC's Vedanta Publishes Ph2 in Nature Medicine

Puretech HealthAnnouncement

27/01/2025 07:00

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RNS Number : 6935U  PureTech Health PLC  27 January 2025

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 (https://puretechhealth.com/) (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
(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.vedantabio.com%2F&esheet=54189611&newsitemid=20250123611854&lan=en-US&anchor=Vedanta+Biosciences&index=1&md5=4c7264b0d238c0293919d8f2ee83d6ac&_gl=1*1rott6d*_gcl_au*MjA1MzM2MjM5NC4xNzMzODc4NjQ3*_ga*MTg0Njc0NDM1NS4xNzEwMTkxODMy*_ga_ZQWF70T3FK*MTczNzczMzI0NS4xNDIuMC4xNzM3NzMzMjQ1LjYwLjAuMA..)
, 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
(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41591-024-03337-4&esheet=54189611&newsitemid=20250123611854&lan=en-US&anchor=can+be+viewed+online&index=2&md5=b7413945128ab3e65bcd127dc67c0042&_gl=1*1rott6d*_gcl_au*MjA1MzM2MjM5NC4xNzMzODc4NjQ3*_ga*MTg0Njc0NDM1NS4xNzEwMTkxODMy*_ga_ZQWF70T3FK*MTczNzczMzI0NS4xNDIuMC4xNzM3NzMzMjQ1LjYwLjAuMA..)
.

 

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)
(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fjamanetwork.com%2Fjournals%2Fjama%2Ffullarticle%2F2803996&esheet=54189611&newsitemid=20250123611854&lan=en-US&anchor=Journal+of+the+American+Medical+Association+%28JAMA%29&index=3&md5=9c0447f9e3088f90fd31250823dd41ff&_gl=1*4w7ivn*_gcl_au*MjA1MzM2MjM5NC4xNzMzODc4NjQ3*_ga*MTg0Njc0NDM1NS4xNzEwMTkxODMy*_ga_ZQWF70T3FK*MTczNzczMzI0NS4xNDIuMC4xNzM3NzMzMjQ1LjYwLjAuMA..)
, 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
(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.vedantabio.com%2F&esheet=54189611&newsitemid=20250123611854&lan=en-US&anchor=Vedanta+Biosciences&index=1&md5=4c7264b0d238c0293919d8f2ee83d6ac&_gl=1*1rott6d*_gcl_au*MjA1MzM2MjM5NC4xNzMzODc4NjQ3*_ga*MTg0Njc0NDM1NS4xNzEwMTkxODMy*_ga_ZQWF70T3FK*MTczNzczMzI0NS4xNDIuMC4xNzM3NzMzMjQ1LjYwLjAuMA..)
, 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
(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41591-024-03337-4&esheet=54189611&newsitemid=20250123611854&lan=en-US&anchor=can+be+viewed+online&index=2&md5=b7413945128ab3e65bcd127dc67c0042&_gl=1*1rott6d*_gcl_au*MjA1MzM2MjM5NC4xNzMzODc4NjQ3*_ga*MTg0Njc0NDM1NS4xNzEwMTkxODMy*_ga_ZQWF70T3FK*MTczNzczMzI0NS4xNDIuMC4xNzM3NzMzMjQ1LjYwLjAuMA..)
.

 

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)
(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fjamanetwork.com%2Fjournals%2Fjama%2Ffullarticle%2F2803996&esheet=54189611&newsitemid=20250123611854&lan=en-US&anchor=Journal+of+the+American+Medical+Association+%28JAMA%29&index=3&md5=9c0447f9e3088f90fd31250823dd41ff&_gl=1*4w7ivn*_gcl_au*MjA1MzM2MjM5NC4xNzMzODc4NjQ3*_ga*MTg0Njc0NDM1NS4xNzEwMTkxODMy*_ga_ZQWF70T3FK*MTczNzczMzI0NS4xNDIuMC4xNzM3NzMzMjQ1LjYwLjAuMA..)
, 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
(http://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 (mailto:publicrelations@puretechhealth.com)

Investor Relations

IR@puretechhealth.com (mailto:IR@puretechhealth.com)

 

UK/EU Media

Ben Atwell, Rob Winder

+44 (0) 20 3727 1000

puretech@fticonsulting.com (mailto:puretech@fticonsulting.com)

 

US Media

Justin Chen

+1 609 578 7230

justin@tenbridgecommunications.com (mailto:justin@tenbridgecommunications.com)

 

 

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