9 November 2018 - - US-based clinical-stage company Vedanta Biosciences has released preclinical data for VE800, the company's orally-administered, live biotherapeutic product candidate in immuno-oncology, the company said.

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.

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 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.

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.

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.

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.

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.

The company is 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' 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.