Vedanta Biosciences 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:
- 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.
- Abundant colonization of VE303 strains that lasted for at least 12 weeks was detected at all doses.
- Repeated dosing led to increased robustness of strain colonization (i.e., a majority of VE303 strains colonized in a majority of volunteers).
- 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 Study
The 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 1.6×109 to 8×109 CFU, and two cohorts received total cumulative doses of VE303 ranging from 4×1010 to 1.1×1011 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.
VE303 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).