CAMBRIDGE, Mass.--(BUSINESS WIRE)--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 preclinical data for VE800, the Company’s orally-administered, live biotherapeutic product candidate in immuno-oncology. The study showed that VE800 elicited an anti-tumor immune response as a monotherapy and also enhanced effects of immune 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. The data will be presented at the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting by Dr. Bruce Roberts, Chief Scientific Officer of Vedanta Biosciences, on November 8. Vedanta Biosciences expects to initiate a clinical study of VE800 in mid-2019.
“Our work shows that VE800 induces robust tumor infiltration by cytotoxic T cells - one of the strongest predictors of response to checkpoint inhibitors - and promotes suppression of tumor growth and enhanced survival in a range of cancer models,” said Bruce Roberts, Ph.D., Chief Scientific Officer of Vedanta Biosciences. “To our knowledge, VE800 is the most advanced immuno-oncology product candidate based on a defined consortium of human microbiome-derived bacteria, a therapeutic modality that Vedanta is pioneering. With our cGMP manufacturing processes in place, we’re well-positioned to take VE800 into the clinic in the coming months.”
In the preclinical study, VE800 was assessed alone and in combination with various checkpoint inhibitors in colon carcinoma and melanoma tumor models. VE800 was assessed for its ability to induce CD8+ T cells, an important marker of anti-tumor response, as well for its ability to influence accumulation of tumor infiltrating lymphocytes. The study was conducted in collaboration with Dr. Kenya Honda of Keio University, a leader in the microbiome field and a scientific co-founder of Vedanta Biosciences.
Data highlights include:
1. VE800 robustly promoted induction of interferon-gamma producing CD8+
T cells via activation of intestinal dendritic cells and stimulation of
interferon-gamma producing CD8+ T cells in a manner dependent on the
transcription factor BATF3
2. VE800 enhanced the anti-tumor
activity of both anti-PD-1 and anti-CTLA4 antibodies by increasing the
level of tumor infiltrating CD8+ T cells
3. VE800 also promoted
systemic immune cell activation as evidenced by accumulation of CD8+ T
cells in the spleen.
Unlike fecal transplants or single strain approaches to microbiome modulation, Vedanta Biosciences uses pure, clonal cell banks to produce defined collections, or consortia, of bacterial strains designed to effect durable therapeutic changes in a patient’s microbiota. This bypasses the need to rely on direct sourcing of fecal donor material of inconsistent composition.
About VE800
VE800 is Vedanta Biosciences’ oral
immuno-oncology product candidate. It consists of a rationally-defined
bacterial consortium that activates cytotoxic CD8+ T cells, a type of
white blood cell that is the predominant effector in cancer
immunotherapy. In preclinical studies, VE800 has been shown to enhance
the ability of these T cells to infiltrate tumors, thereby promoting
suppression of tumor growth and improving survival. Data also suggest
that VE800 may enhance the effects of checkpoint inhibitors. Vedanta
Biosciences is evaluating VE800 alone and in combination with checkpoint
inhibitors as a potential treatment for patients with advanced or
metastatic cancers.
About Vedanta Biosciences
Vedanta
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 live bacteria drugs. 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).
