VEDANTA (Microbiome-Derived Immune Modulators)

(VE303, VE202, VE416, VE800)

Immune System

Microbiome-Derived Modulators for Immune and Infectious Disease

Immune System

Microbiome-Derived Modulators for Immune and Infectious Disease
Modulating the immune system via the gut microbiome

Founded by PureTech Health as part of its microbiome initiative, PureTech’s Vedanta Biosciences is developing a new category of therapies for immune-mediated diseases based on a 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 live bacteria drugs. These include what is believed to be a leading IP position with 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 clinical pipeline of programs in infectious disease, autoimmune disease, allergy, and immuno-oncology.

In 2017, we initiated a Phase 1a/1b clinical trial of VE303, our lead product candidate for the treatment of recurrent C. difficile infection. We also continued to expand our internal, state-of-the-art cGMP-compliant manufacturing capabilities, giving us a distinct competitive advantage in the microbiome field. A Phase 2 study of VE303 is on track to begin in the second half of 2018. Three additional product candidates are also expected to enter clinical development in 2018, with Phase 1 trial initiations planned in inflammatory bowel disease (IBD) and food allergy, and the submission of an investigational new drug application (IND) for an immuno-oncology product candidate.

  • Patient Need & Market Potential
    • Despite profound survival improvements in some patients, checkpoint inhibitors (PD-1/ PDL-1, CTLA-4) are only effective in 20-30 percent of patients. Common tumor types where checkpoint inhibitors are utilized include lung, bladder, skin, and renal cancers. Vedanta Biosciences’ immuno-oncology product candidate, VE800, is designed to act in combination with approved checkpoint inhibitors and potentially other immunotherapies to safely improve their efficacy.
    • Food allergies are a growing U.S. public health concern – they affect eight percent of children and have an annual economic cost near $25 billion. Current treatment options primarily center around allergen avoidance. Desensitization regimens in development have limited efficacy, are risky, and require treatment for life. Vedanta Biosciences’ product candidate, VE416, is being developed to safely induce permanent tolerance to food allergens including peanut allergy.
    • Inflammatory bowel disease (IBD) is estimated to affect over one million people in the U.S. and four million worldwide, and other autoimmune diseases affect over 20 million people in the U.S. Many of the existing interventions are limited by toxicities and systemic immune suppression. Vedanta Biosciences’ collaborator, Janssen Biotech Inc., is advancing a product candidate, VE202, designed to modulate the activity of regulatory T cells and thereby potentially treat IBD.
    • The Center for Disease Control and Prevention (CDC) considers C. difficile infections one of the most urgent bacterial threats. C. difficile infections account for nearly 15,000 deaths each year in the U.S. alone. Existing interventions include antibiotics such as vancomycin or metronidazole, which have the undesirable side effect of damaging the gut microbiome and leaving patients vulnerable to re-infection. A related intervention, fecal transplantation, is an experimental procedure which is exceedingly difficult to standardize and scale and is fraught with potential safety issues. Vedanta Biosciences’ lead, orally-administered live biotherapeutic product candidate, VE303, is designed to restore colonization resistance against gut pathogens, including C. difficile, following recurrence.
  • Our Approach to Solving the Problem
    • Unlike fecal transplants, which require use of donors and are untargeted, inherently variable procedures, Vedanta Biosciences’ approach is based on bacterial consortia therapeutics, which are defined drug compositions produced from clonally isolated bacteria that can trigger targeted immune responses. Unlike reductionistic approaches such as single strain probiotics, defined consortia can robustly shift the composition of the gut microbiota and provide colonization resistance against a range of intestinal infectious pathogens. These therapeutics can also stimulate a range of immune responses ranging from immunoregulatory responses, which hold potential in the treatment of autoimmune and allergic diseases, to immunopotentiating responses, which hold potential in cancer and vaccination.
    • Vedanta Biosciences’ collaborators have pioneered the fields of innate immunity, Th17, and regulatory T cell biology. These discoveries, which have formed the leading scientific foundation for Vedanta Biosciences, have been reported in seminal scientific papers and published in leading journals such as Science, Nature and Cell, demonstrating that the gut microbiome influences important processes related to the proper functioning of the immune system and resistance to infection.
    • Vedanta Biosciences’ novel product candidates are administered in a lyophilized powder in a capsule dosage form, designed to have specific effects on the immune system, with the aim of restoring the balance of the microbiome in the gut to treat immune and infectious diseases safely and effectively.
  • Intellectual Property
    • Vedanta Biosciences has broad intellectual property coverage worldwide, currently owning or having exclusive rights to one hundred and eight (108) patent applications and issued patents in sixteen (16) families of patent filings, including seven (7) patents that issued in 2018.
    • Vedanta Biosciences’ IP estate positions the company as a leader in the microbiome field.
    • Vedanta Biosciences’ IP portfolio includes foundational patents covering compositions and therapeutic uses of products containing microbiome bacteria belonging to Clostridium clusters IV and XIVa, which are among the most abundant colonizers of the human intestine and play an important role in human health, including regulating inflammatory responses and other immune responses.
    • The IP estate includes issued patents in the major pharmaceutical markets (U.S., Europe, and Japan). These patents provide coverage through at least 2031, with priority filing dates as early as 2010.
  • Team
    • Dr. Bernat Olle (previously PureTech Health) serves as Chief Executive Officer, Dr. Bruce Roberts (previously Sanofi-Genzyme) serves as Chief Scientific Officer, and Mr. Dan Couto (previously ContraFect Corp) serves as Chief Technical Officer and head of manufacturing.
    • Scientific co-founders and advisory board members include some of the world’s leading immunologists, including Dr. Ruslan Medzhitov (Yale and Howard Hughes Medical Institute (HHMI)), Dr. B Brett Finlay (University of British Columbia and HHMI), Dr. Kenya Honda (inventor of Vedanta Biosciences’ IBD product candidate; Keio University and RIKEN), Dr. Dan Littman (NYU School of Medicine, Howard Hughes Medical Institute; member of the Board of Pfizer), Dr. Alexander Rudensky (Sloan Kettering and HHMI), and Dr. Jeremiah Faith (Mount Sinai School of Medicine).
  • Milestones Achieved
    • Vedanta Biosciences initiated the Phase 2 study for its lead, orally-administered, live biotherapeutic product (LBP) candidate for recurrent Clostridium difficile infection (rCDI), VE303, in December 2018. Dose selection for this study was based on the results from the Phase 1a/1b study in healthy volunteers, which demonstrated safety, tolerability, and proof of mechanism for VE303. Specifically, the Phase 1a/1b showed that VE303 treatment resulted in rapid, durable, dose-dependent colonization and accelerated gut microbiota restoration after antibiotics.
    • Preclinical data announced at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting showed that VE800 elicited an anti-tumor immune response as a monotherapy and also enhanced the effects of checkpoint inhibitors. Additionally, the results describe a mechanism of action for VE800 as the robust interferon-gamma producing CD8+ (cytotoxic) T cell response was elicited via activation of dendritic cells.
    • Vedanta Biosciences announced the initiation of a Phase 1 clinical study in healthy volunteers of VE202, its orally-administered LBP candidate for inflammatory bowel disease (IBD). The study is being conducted by Janssen Research & Development, LLC. In conjunction with the initiation of this study, Vedanta Biosciences will receive $12 million from Janssen in milestone payments as part of its ongoing collaboration.
    • In December 2018, Vedanta Biosciences completed a $27 million financing round with participation from the Bill & Melinda Gates Foundation, Bristol-Myers Squibb, Rock Springs Capital, Invesco Asset Management, Seventure Partners, and PureTech Health.

  • Collaborations
    • In January 2019, important research that underlies Vedanta’s proprietary oral immuno-oncology product candidate, VE800, was published in one of the top scientific journals, Nature. The research revealed a new mechanism by which human microbiota induce an important immune cell that is key to the body’s ability to generate anti-tumor immunity.
    • Additional data on Vedanta Biosciences’ microbiome technologies has been featured in high impact academic journals such as Nature, Science, and Cell.
    • Vedanta Biosciences announced a clinical collaboration with Bristol-Myers Squibb to evaluate VE800 in combination with Bristol-Myers Squibb’s programmed death-1 (PD-1) immune checkpoint inhibitor Opdivo (nivolumab) in patients with advanced or metastatic cancers. Bristol-Myers Squibb is a strategic equity investor in Vedanta Biosciences. Under the terms of the agreement, Vedanta Biosciences will maintain control of its VE800 program, including global R&D and commercial rights.
    • As part of the collaboration with Janssen Biotech, Vedanta Biosciences has received $24 million in payments and is entitled to milestone payments up to $339 million, plus royalties.
    • Vedanta Biosciences received funding from the Crohn’s & Colitis Foundation to advance its new microbiome-derived therapeutic program for the treatment and potential interception of IBD.
    • Vedanta Biosciences has exclusively licensed key intellectual property from Keio University to develop and commercialize microbiome-derived cancer immunotherapies based on live biotherapeutics.
  • Expected Milestones and Timing
    • PK/PD results are anticipated in the second half of 2019 from the Phase 1 healthy subject study of VE202.
    • Initiation of a Phase 1b/2 clinical study of VE416 for peanut allergy is expected in 2019.
    • Initiation of a Phase 1b/2 clinical study of VE800 in combination with Bristol-Myer-Squibb’s Opdivo in patients with metastatic or advanced cancers is anticipated in 2019.
    • Clinical efficacy results for VE303, VE800, and VE416 are anticipated in 2020.

Unlike fecal transplants or single strain approaches to microbiome modulation, Vedanta Biosciences uses pure, clonal cell banks to produced defined collections, or consortia, of bacterial strains designed to effect durable therapeutic changes in a patient’s gut microbiota. This bypasses the need to rely on direct sourcing of fecal donor material of inconsistent composition.

Our In-House, State-of-the-Art GMP Manufacturing Plant