Microbiome-Derived Immune Modulators

(VE303, VE202, VE416, VE800)

Immune System

Microbiome-Derived Immune Modulators
C. Difficile, IBD, Food Allergy, Immuno-Oncology

Immune System

Microbiome-Derived Immune Modulators
INDICATION(S):C. Difficile, IBD, Food Allergy, Immuno-Oncology
NAME:Vedanta (71.5%*)
STAGE:Phase 1
Microbiome-Derived Immune Modulators

Our Vedanta Biosciences affiliate is developing a new category of therapies for immune-mediated and infectious diseases based on a rationally-defined consortium of human microbiome-derived bacteria. Our product candidates are designed to modulate pathways of interaction between the human microbiome and the host immune system to treat serious diseases. As a leader in the field of defined microbial consortia for autoimmune disorders, infections, and immuno-oncology, we are advancing a pipeline of product candidates that seek to address these serious diseases. 

  • Patient Need & Market Potential
    • 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. We are collaborating with Janssen Biotech, Inc. to advance a microbiome-derived candidate in IBD.
    • The Centers 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. Our lead, administered product candidate, VE303, was designed to restore colonization resistance against gut pathogens, including C. difficile, following recurrence. VE303 was granted Orphan Drug Designation in 2017 by the United States Food and Drug Administration (FDA).
    • 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. Our product candidates are designed to act in combination with approved checkpoint inhibitors and potentially other immunotherapies to 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 are risky and require treatment for life. Our product candidates are being developed to safely induce permanent tolerance to food allergens.
  • Our Approach to Solving the Problem
    • Unlike fecal transplants, which require use of donors and are an untargeted, inherently variable procedure, our 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.
    • Our 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.
    • Our 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
    • We have broad intellectual property coverage worldwide, currently owning or having exclusive rights to 69 patent applications and issued patents in 13 families of patent filings, including 10 patents that issued in the U.S. and Japan in 2017.
    • Our IP estate positions Vedanta Biosciences as a leader in the microbiome field.
    • Our 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
    • Scientific co-founders and advisory board members include some of the world’s leading immunologists. 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 (New York University and HHMI and member of the Pfizer Board), Dr Alexander Rudensky (Sloan Kettering and HHMI), and Dr Jeremiah Faith (Mount Sinai School of Medicine).
    • Dr. Bernat Olle serves as Chief Executive Officer, Dr. Bruce Roberts serves as Chief Scientific Officer, and Mr. Dan Couto serves as Chief Technical Officer and head of manufacturing.
  • Milestones Achieved
    • We initiated a Phase 1a/1b clinical trial of VE303, our lead, orally-administered, human microbiome-derived product candidate. VE303 is the first known investigational drug consisting of rationally-defined bacterial consortium in powder form to enter the clinic and is being evaluated for the treatment of recurrent C. difficile infection.
    • VE303 was also granted Orphan Drug Designation in 2017 by the United States Food and Drug Administration (FDA). Key in-house manufacturing milestones have also been achieved, which places a Phase 2 study of VE303 on track to start in the second half of 2018.
    • We have partnered with Janssen Biotech, Inc. for the development and commercialization of VE202, which has demonstrated preclinical efficacy for IBD and food allergy and is expected to enter the clinic in the second half of 2018.
    • In collaboration with co-founder Dr. Kenya Honda, we are working on an additional product candidate, VE800, consisting of a rationally defined bacterial consortium that potentiates cytotoxic CD8+ T-cells, which are key modulators of immuno-oncology checkpoint therapy responses. We intend to file an IND for VE800 in 2018.

  • Collaborations
    • Data on our microbiome technologies has been featured in high impact academic journals such as Nature, Science, and Cell.
    • In June 2016, we raised $50 million in equity investments, with new investors Rock Springs Capital, Invesco Asset Management, and Health for Life Capital (Seventure) joining PureTech Health in the financing.
    • In November 2017, we were awarded a $5.4 million research grant from CARB-X (Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) to support clinical testing of VE303.
    • In December 2017, we were awarded $248,000 from the Crohn’s & Colitis Foundation to support efforts to develop a live bacterial consortium for decolonization of pathobiont species in individuals newly diagnosed with IBD.
    • We have exclusively licensed key intellectual property from Keio University to develop and commercialize microbiome-derived cancer immunotherapies based on live biotherapeutics.
    • We also entered into clinical translational medicine collaborations with top academic institutions including Stanford University School of Medicine, Leiden University Medical Center, and NYU Langone Medical Center.
    • In March 2016, we entered into a licensing agreement with RIKEN, the University of Tokyo and Azabu University for a new immune-boosting microbiome technology with potential applications in infectious disease and immuno-oncology.
  • Expected Milestones and Timing
    • Results are anticipated from the VE303 (recurrent C. difficile infections program) Phase 1a/1b clinical trial in healthy volunteers in the second quarter of 2018. Initiation of a Phase 2 study with VE303 in patients with recurrent C. difficile infections in the second half of 2018.
    • Initiation of the VE202 (collaboration with Janssen Biotech, Inc.) Phase 1 clinical trial in IBD is anticipated in the second half of 2018.
    • Initiation of the VE416 Phase 1 clinical trial in food allergy is anticipated in the second half of 2018.
    • Filing of an IND application for VE800, our cancer immunotherapy candidate, is anticipated in 2018.

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.

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