Summarizing everything there is to know about Vedanta Biosciences is a huge task as it is one of the original companies dedicated to microbiome-based therapeutics. For this reason I will focus mainly on their science and clinical trials. Founded in 2010, Vedanta focuses their microbiome therapeutics on autoimmune and inflammatory bowel diseases of the gut. In particular they are focusing on the imbalances of the intestinal mucosa, which is the seat of the human body’s largest population of immune cells.
One major cause of human exposure to pathogens or foreign particles/toxins over the course of human evolutionary history has been the food we ingest, thus the intestinal mucosa is one of our first and strongest lines of defense. Any bacteria or foreign materials entering the stomach and then intestine are exposed to the intestinal mucosa, where specialized patches, called Peyer’s patches, allow all particles brief contact with T- and B-cells which then form antibodies against them. This is a tightly controlled immune response to familiarize the body with mostly harmless bacteria or particles entering the system, and, if necessary, to trigger an immune response if something truly toxic is present. In a normally functioning intestinal immune response only toxic or harmful substances initiate the body’s immune system to become reactive and inflamed, for the most part the regulatory T-cells keep the immune system calm. However, in people with inflammatory bowel disease, the regulatory T-cells malfunction, which leads to an overactive immune response at the intestinal lining, which may cause a breach in the mucosal protective layer allowing bacteria and pathogens to seep in. This can turn into a vicious cycle causing even more damage to the intestinal lining, more inflammation, and even more bacteria.
Vedanta’s drugs attempt to restore the intestinal homeostasis by tweaking the pathways where human immune cells and the human microbiome interact. Specifically, the genus of bacteria known as Clostridium is important in the gut. Certain strains of Clostridia are essential for the healthy development of regulatory T-cells in the colon, which in turn are responsible for quieting the immune inflammatory response. When certain species of Clostridia are absent or there is an imbalance in the population or number of the necessary Clostridia, regulatory T-cells will not develop normally and leads to inflammatory bowel diseases. These beneficial Clostridia species are not to be confused with Clostridium difficile, which is also in the Clostridium genus but causes acute infection in the gut if it gets out of control. Vedanta’s first two drug candidates are both combinations of beneficial Clostridia species, initially cultured by the company from human stool, delivered in pill form in hopes to re-balance the intestinal T-cell response. This is what they call “rationally defined drugs”, basically specific bacterial strains that induce a specific metabolic effect in humans.
Vedanta’s first drug VE-202 is a consortia of 17 different Clostridial strains meant to treat IBD. It completed pre-clinical trials in 2016 and begins clinical trials this year in 2017. While manufacturing and clinical trials are very expensive, Vedanta nabbed $50 million in 2016 from various investors, and expanded to a larger facility in Cambridge with more staff. Results from this clinical trial should be expected in early 2018. The company is also seeking to expand is development of microbiome therapies to treat hospital-acquired infections, allergies, and is moving into the booming immuno-oncology space. Vedanta has financial backing from Janssen, which is also a Johnson and Johnson company. They also have an ongoing collaboration with NYU Langone Medical Center for developing cancer therapies. Definitely a strong microbiome company to follow in coming years!
References:
http://www.vedantabio.com
http://www.vedantabio.com/07-10-2013
http://www.the-scientist.com/?articles.view/articleNo/36433/title/Gut-Microbes-Treat-Illness/
https://www.wired.com/2016/11/microbiome-therapy-making-fecal-transplants-better/
https://www.forbes.com/sites/luketimmerman/2016/06/06/microbiome-startup-vedanta-gets-50m-to-make-rationally-defined-bugs-into-drugs/#47af0e32528a
One major cause of human exposure to pathogens or foreign particles/toxins over the course of human evolutionary history has been the food we ingest, thus the intestinal mucosa is one of our first and strongest lines of defense. Any bacteria or foreign materials entering the stomach and then intestine are exposed to the intestinal mucosa, where specialized patches, called Peyer’s patches, allow all particles brief contact with T- and B-cells which then form antibodies against them. This is a tightly controlled immune response to familiarize the body with mostly harmless bacteria or particles entering the system, and, if necessary, to trigger an immune response if something truly toxic is present. In a normally functioning intestinal immune response only toxic or harmful substances initiate the body’s immune system to become reactive and inflamed, for the most part the regulatory T-cells keep the immune system calm. However, in people with inflammatory bowel disease, the regulatory T-cells malfunction, which leads to an overactive immune response at the intestinal lining, which may cause a breach in the mucosal protective layer allowing bacteria and pathogens to seep in. This can turn into a vicious cycle causing even more damage to the intestinal lining, more inflammation, and even more bacteria.
Vedanta’s drugs attempt to restore the intestinal homeostasis by tweaking the pathways where human immune cells and the human microbiome interact. Specifically, the genus of bacteria known as Clostridium is important in the gut. Certain strains of Clostridia are essential for the healthy development of regulatory T-cells in the colon, which in turn are responsible for quieting the immune inflammatory response. When certain species of Clostridia are absent or there is an imbalance in the population or number of the necessary Clostridia, regulatory T-cells will not develop normally and leads to inflammatory bowel diseases. These beneficial Clostridia species are not to be confused with Clostridium difficile, which is also in the Clostridium genus but causes acute infection in the gut if it gets out of control. Vedanta’s first two drug candidates are both combinations of beneficial Clostridia species, initially cultured by the company from human stool, delivered in pill form in hopes to re-balance the intestinal T-cell response. This is what they call “rationally defined drugs”, basically specific bacterial strains that induce a specific metabolic effect in humans.
Vedanta’s first drug VE-202 is a consortia of 17 different Clostridial strains meant to treat IBD. It completed pre-clinical trials in 2016 and begins clinical trials this year in 2017. While manufacturing and clinical trials are very expensive, Vedanta nabbed $50 million in 2016 from various investors, and expanded to a larger facility in Cambridge with more staff. Results from this clinical trial should be expected in early 2018. The company is also seeking to expand is development of microbiome therapies to treat hospital-acquired infections, allergies, and is moving into the booming immuno-oncology space. Vedanta has financial backing from Janssen, which is also a Johnson and Johnson company. They also have an ongoing collaboration with NYU Langone Medical Center for developing cancer therapies. Definitely a strong microbiome company to follow in coming years!
References:
http://www.vedantabio.com
http://www.vedantabio.com/07-10-2013
http://www.the-scientist.com/?articles.view/articleNo/36433/title/Gut-Microbes-Treat-Illness/
https://www.wired.com/2016/11/microbiome-therapy-making-fecal-transplants-better/
https://www.forbes.com/sites/luketimmerman/2016/06/06/microbiome-startup-vedanta-gets-50m-to-make-rationally-defined-bugs-into-drugs/#47af0e32528a