Microbiome-Derived Immune Modulators

(VE303, VE202, VE416, VE800)

Immune System

TRIAL PHASE
MECHANISMINDICATION(S)PRODUCT NAMEPreclinicalPhase 1Phase 2Phase 3
Microbiome-Derived Immune Modulators
C. Difficile, IBD, Food Allergy, Immuno-Oncology
Vedanta
(VE303, VE202, VE416, VE800)

Immune System

Microbiome-Derived Immune Modulators
INDICATION(S):C. Difficile, IBD, Food Allergy, Immuno-Oncology
NAME:Vedanta (VE303, VE202, VE416, VE800)
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
    • Inflammatory bowel disease is estimated to affect over one million people in the U.S. and four million worldwide. In addition to IBD, other autoimmune diseases affect over 20 million patients in the U.S. Many of the existing interventions are limited by toxicities and systemic immune suppression
    • The CDC considers C. difficile infections one of the most urgent bacterial threats. C. difficile infections account for nearly 30,000 deaths each year in the U.S. alone. Existing interventions for C. difficile infections include antibiotics, such as vancomycin or metronidazole, which have an undesirable side effect of damaging the gut microbiome and leaving patients vulnerable to re-infection. Fecal transplantation is an alternative experimental procedure which will, in our view, be exceedingly difficult to standardize and scale. It is also fraught with potential safety issues
    • Despite profound survival improvements in some patients, checkpoint inhibitors (PD-1/PDL-1, CTLA-4) are only effective in 20-30% of patients. Common tumor types where checkpoint inhibitors are utilized include lung, bladder and renal cancers. We are developing commensal bacterial cocktails designed to potentially to improve the efficacy of approved checkpoint inhibitors
    • Food allergies are a growing U.S. public health concern – they affect 8% of children and have an annual economic cost near $25 billion. For food allergies, current treatment options primarily center around allergen avoidance. Desensitization regimens are risky and require treatment for life. Our commensal bacterial cocktails are being developed to potentially safely induce permanent tolerance to food allergens
  • Our Approach to Solving the Problem
    • Recent discoveries, including seminal scientific papers from our collaborators, suggest that the gut microbiome influences important processes related to the proper functioning of the immune system and resistance to infection
    • Our approach is based on administration of defined bacterial products, designed to have specific effects on the immune system, in a capsule, 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 worldwide intellectual property coverage, including exclusive rights to over 46 issued patents and patent applications. This IP puts us in a unique leadership position in the microbiome field
    • Our IP portfolio includes fundamental patents covering compositions and therapeutic uses of products containing bacteria belonging to Clostridium clusters IV and XIVa, as well as spore-forming fractions obtained from stool samples. Bacteria within these clusters are among the most abundant colonizers of the human intestine and they play an important role in human health, including regulating immune responses
    • Our IP estate includes issued patents in the major pharmaceutical markets (US, Europe, and Japan), and these patents provide coverage through at least 2031, and their earliest priority dates are in 2010
  • Team
    • The team includes leading experts in immunology and microbiology
    • Key advisors are:

      Dr. Ruslan Medzhitov, best known for his work pioneering the current understanding of the innate immune system;

      Dr. Alexander Rudensky, Chairman of the Immunology Program and Director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center (MSKCC) and an Investigator with the Howard Hughes Medical Institute;

      Dr. Kenya Honda, Professor in the Department of Microbiology and Immunology, Keio University School of Medicine, and the Team leader of Laboratory for Gut Homeostasis, RIKEN Center for Integrative Medical Sciences (IMS);

      Dr. Brett Finlay, Professor in the Michael Smith Laboratories, the Departments of Biochemistry and Molecular Biology, and Microbiology and Immunology at the University of British Columbia;

      Dr. Jeremiah Faith, Assistant Professor of Clinical Immunology and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai Hospital; and

      Dr. Dan Littman, who has made numerous groundbreaking discoveries in the field of virology and immunology

    • Vedanta was developed and is being run by Dr. Bernat Olle, alongside Dr. Bruce Roberts and Dan Couto.
  • Milestones Achieved
    • Vedanta declared clinical candidates for two new programs in food allergy and immuno-oncology
    • We initiated a Phase 1a/1b clinical trial of VE303, its 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 (rCDI).
    • Key in-house manufacturing milestones have been achieved, which places a Phase 2 study of VE303 on track to start in 2018.
    • The collaboration with Janssen Biotech, Inc. on VE202 for inflammatory bowel disease continues and is anticipated to enter the clinic in the second half of 2018.
    • We are working in collaboration with leading oncology researchers around the world, to gather data from interventional human clinical studies of checkpoint inhibitors to inform its immuno-oncology platform.
    • In collaboration with cofounder, Dr. Kenya Honda, we are working on a candidate consisting of a rationally defined bacterial consortium that potentiates cytotoxic CD8+ T-cells, which are key modulators of checkpoint therapy responses. We intend to file an IND for that candidate in 2018. 

  • Grants
    • Vedanta was awarded a $5.4 million research grant from CARB-X (Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) to support clinical testing of our lead oral product candidate, VE303, to address serious bacterial infections.
  • Collaborations
    • We have a collaboration agreement with Janssen Biotech, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, for VE202, a bacterial consortia drug candidate for Inflammatory Bowel Diseases. This collaboration continues to flourish and is anticipated to enter the clinic in the first half of 2018

     

    Clinical and Translational Collaborations

    • We have entered into a translational collaboration with the NYU Langone Medical Center to focus on developing novel microbiome-derived immunotherapies for cancer patients being treated with checkpoint inhibitors
    • We have also entered into a clinical translational medicine collaboration with Stanford University School of Medicine, which focuses on food allergies in children. Through this collaboration, we are analyzing changes in the gut microbiome as they relate to responses to oral immunotherapies in children with food allergies
    • We have entered into a clinical translational medicine collaboration with Leiden University Medical Center that focuses on patients with C. difficile infection or graft-versus-host disease. We are generating clinical data from interventional studies of fecal transplantation in C. difficile patients, as well as clinical data from patients with graft-versus-host disease

     

    Additional Licenses

    • We have exclusively licensed key intellectual property from Keio University to develop and commercialize microbiome-derived cancer immunotherapies based on live biotherapeutics
    • 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 

     

    Publications

    • Data on our microbiome technologies has been featured in high impact academic journals such as Nature, Science, and Cell [See publications]
  • Expected Milestones and Timing
    • Results are anticipated from the VE303 (recurrent C. difficile infections program) Phase 1 clinical trial in healthy volunteers in the first half of 2018
    • Initiation of the VE202 (in collaboration with Janssen Biotech, Inc. for inflammatory bowel disease) Phase 1 clinical trial 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 investigational new drug (IND) application for VE800, our cancer immunotherapy candidate

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