The Human Microbiome - A New Frontier in Drug Discovery

Our body is home to trillions of microbes (collectively, our human microbiome) that play important roles in metabolism, development of the immune system, and intestinal homeostasis. Research on the human microbiome is transforming our understanding of a broad range of human diseases. Microbiome imbalances are being associated with a growing number of autoimmune, infectious, and metabolic diseases, and in some cases have been shown to have an important role in driving pathology.

While food companies have commercialized probiotics for years, the typical organisms in yogurt do not survive long term in the human gut and we believe that their effects in human health are inconsequential. We believe that Vedanta Biosciences’ approach represents a radical departure from food probiotics: we focus on communities of organisms that are essential dwellers of the gut ecosystem.

We have co-evolved with our microbiome, communicating in a language that is critical to how autoimmune, infectious, and metabolic diseases develop. Vedanta will focus on decoding this language.
— Ruslan Medzhitov (HHMI, Yale Professor, Vedanta Co-Founder)

A New Class of Drugs

Vedanta Biosciences is developing a class of drugs that work by modulating the human microbiome, with an initial emphasis in autoimmune diseases and inflammatory diseases.

Vedanta Biosciences’ proprietary approach leverages foundational discoveries in the field of mucosal immunology to generate safe and potent treatments that induce tolerance and restore

intestinal homeostasis acting via mechanisms that are orthogonal to all existing drug classes.

By modulating the microbiome, we have the opportunity to potentially treat a range of autoimmune and inflammatory diseases in new ways and impact the lives of patients.

Telling "Good" from "Bad"

Video courtesy of the Nature Publishing Group, view the entire article here.

Why did we evolve an immune system? We believe the answer is not simply ‘to fight pathogens’. We believe our immune system evolved to control the composition of our microbiome in ways that guarantee our health. To tell “good” microbes from “bad” microbes, and decide which get a warm welcome in our bodies and which get kicked out. When our immune system loses the ability to welcome the “good” and kick out the “bad”, autoimmune and infectious disease can result.

Vedanta’s scientific co-founders have pioneered the current understanding of how the immune system recognizes and responds to microbes. We are developing tools to learn how a healthy immune system tells “good” from “bad” because we believe the answer holds the key to development of a new class of immunotherapies. Our first drug candidate epitomizes this: it uses good microbes to stop autoimmune reactions.

One Example of How the Immune System Induces Tolerance to "Good" Microbes

Regulatory T cells are a critical “self-check” built into our immune systems to prevent excessive immune reactions. Deficiencies in these cells can result in a range of autoimmune diseases

Work led by Dr. Kenya Honda, a researcher at the RIKEN Center for Integrative Medical Sciences in Japan and scientific co-founder of Vedanta, has uncovered that a community of microbes belonging to the genus Clostridium, which are among the most abundant microbes in the gut of healthy humans, are essential for the development of regulatory T cells in the colon and help preserve the intestinal barrier.

Independent research groups have established that damage to this same community of microbes is associated with Inflammatory Bowel Diseases (ulcerative colitis and Crohn’s Disease) as well as allergies.

Vedanta is developing a drug based on a proprietary consortia of the most potent regulatory T cell-inducing Clostridium bacteria in the human gut.

Reprinted with permission from AAAS

Reprinted with permission from AAAS