Vedanta Biosciences Announces Successful Phase 1a/1b Data Demonstrating Safety, Tolerability, & Proof of Mechanism for Lead, ...
October 04 2018 - 1:00AM
Business Wire
All doses were safe and well-tolerated
VE303 treatment resulted in rapid, durable,
dose-dependent colonization and accelerated gut microbiota
restoration after antibiotics
A Phase 2 study in recurrent C. difficile
infection is expected to begin in the fourth quarter of 2018
Three other programs in immuno-oncology,
allergy, and inflammatory bowel disease are expected to enter the
clinic within the next nine months
Vedanta Biosciences, a clinical-stage company developing a new
category of therapies for immune-mediated diseases based on
rationally defined consortia of human microbiome-derived bacteria,
today announced preliminary results from the Phase 1a/1b clinical
study in healthy volunteers for its lead, orally-administered live
biotherapeutic product (LBP) candidate for recurrent Clostridium
difficile infection (rCDI), VE303. With these Phase 1 data to
support dosage selection, Vedanta Biosciences expects to begin a
Phase 2 study before the end of the year to evaluate the safety and
efficacy of VE303 in patients with rCDI. Additional exploration of
VE303 in healthy volunteers to inform dose selection in other
indications is ongoing.
This study was designed to evaluate safety and tolerability of a
range of doses of VE303 in healthy adult volunteers. The study also
evaluated pharmacokinetics of intestinal colonization by the VE303
strains and pharmacodynamics of recovery of the gut microbiota
after administration of antibiotics followed by a course of
VE303.
Summary of Key Findings:
1.
Single and multiple doses of VE303, after vancomycin
administration, ranging up to 1.1 x 1011 total colony forming units
(CFU), were safe and well-tolerated. Adverse events related to
VE303 administration occurred in less than one third of study
volunteers and all were Grade 1. 2. Abundant colonization of VE303
strains that lasted for at least 12 weeks was detected at all
doses. 3. Repeated dosing led to increased robustness of strain
colonization (i.e., a majority of VE303 strains colonized in a
majority of volunteers). 4. VE303 accelerated microbiota recovery
after vancomycin administration in a dose-dependent manner compared
to recovery without VE303, demonstrating proof of mechanism.
“We believe these Phase 1a/1b results represent a significant
milestone for the microbiome field. VE303’s favorable safety
profile, and - most notably - its ability to rapidly, abundantly,
and durably colonize a heterogenous population of healthy adults
provides a scientific rationale for use of defined bacterial
consortium drugs and moves the field beyond the use of undefined
fecal transplants,” said Bernat Olle, Ph.D., Co-founder and Chief
Executive Officer of Vedanta Biosciences. “The robust relationship
between dose exposure and response we have observed informs a
rational dose selection for VE303 Phase 2 studies and supports its
potential as a first-in-class therapy for prevention of recurrent
Clostridium difficile infection.”
Unlike single strain approaches to microbiome modulation,
Vedanta Biosciences is developing consortia of bacterial strains
designed to effect robust and durable therapeutic changes in a
patient’s gut microbiota. Unlike fecal transplants or
administration of fecal fractions, Vedanta Biosciences’ consortia
are defined compositions of bacteria manufactured from pure, clonal
cell banks, bypassing the need to rely on direct sourcing of fecal
donor material of inconsistent composition. VE303 is the first
product candidate, to the Company’s knowledge, consisting of a
rationally-defined bacterial consortium in lyophilized powder form
to be clinically investigated.
About the StudyThe Phase 1a/1b study was an open-label,
single-center, single- and multiple- dose-escalation study
assessing the safety and tolerability of VE303 in healthy adult
volunteers. Twenty-three volunteers were enrolled to receive VE303
after vancomycin administration, three cohorts received single
ascending doses of VE303 that ranged from 1.6x109 to
8x109 CFU, and two cohorts received total cumulative doses of
VE303 ranging from 4x1010 to 1.1x1011 CFU over five or 14
days. The study also included a control cohort of five volunteers
who received only vancomycin. Metagenomic sequencing of fecal
samples collected longitudinally over 12 weeks was used to assess
VE303’s pharmacokinetics (speed, durability, abundance, and
robustness of bacterial strain colonization) and the
pharmacodynamics of VE303’s impact on post-antibiotic gut
microbiota restoration.
About VE303VE303 is an orally-administered
investigational live biotherapeutic product (LBP). It is produced
from pure, clonal bacterial cell banks, which yield a standardized
drug product in powdered form and bypasses the need to rely on
direct sourcing of fecal donor material of inconsistent
composition. VE303 consists of a defined consortium of live
bacteria designed to restore colonization resistance against gut
pathogens, including C. difficile. In 2017, Vedanta Biosciences
received a $5.4 million research grant from CARB-X (Combating
Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) to
support clinical studies of VE303. VE303 was granted Orphan Drug
Designation in 2017 by the United States Food and Drug
Administration (FDA) for the prevention of recurrent C. difficile
infection (rCDI).
About Vedanta BiosciencesVedanta Biosciences is
a clinical-stage company developing a new category of therapies for
immune-mediated diseases based on rationally defined consortia of
human microbiome-derived bacteria. Vedanta Biosciences is a leader
in the microbiome field with capabilities and deep expertise to
discover, develop, and manufacture LBPs. These include what is
believed to be the largest collection of human
microbiome-associated bacterial strains, a suite of proprietary
assays to select pharmacologically potent strains, vast proprietary
datasets from human interventional studies, and facilities for
cGMP-compliant manufacturing of rationally-defined bacterial
consortia in powder form. Vedanta Biosciences’ pioneering work, in
collaboration with its scientific co-founders, has led to the
identification of human commensal bacteria that induce a range of
immune responses – including induction of regulatory T cells, CD8+
T cells, and Th17 cells, among others. These advances have been
published in leading peer-reviewed journals, including Science
(multiple), Nature (multiple), Cell,
and Nature Immunology. Vedanta Biosciences has harnessed these
biological insights and its capabilities to generate a pipeline of
programs in infectious disease, autoimmune disease, allergy, and
immuno-oncology.
Vedanta Biosciences was founded by PureTech Health (PRTC.L). Its
scientific co-founders are world-renowned experts in immunology and
microbiology who have pioneered the fields of innate immunity, Th17
and regulatory T cell biology, and include Dr. Ruslan Medzhitov
(Yale and Howard Hughes Medical Institute (HHMI)), Dr. Brett Finlay
(University of British Columbia and HHMI), Dr. Kenya Honda
(inventor of Vedanta Biosciences’ lead product candidate; Keio
University and RIKEN), Dr. Dan Littman (New York University and
HHMI), Dr. Alexander Rudensky (Sloan Kettering and HHMI), and Dr.
Jeremiah Faith (Mount Sinai School of Medicine).
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For Vedanta BiosciencesInvestorsAllison Mead Talbot, +1
617-651-3156amt@puretechhealth.comorUS mediaTom Donovan, +1
857-559-3397tom@tenbridgecommunications.com
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