Where is the microbiome-based therapeutics market headed? A Charles River Think Tank explores the possibilities for changing how we treat disease.  

In the 16 years since Nobel Laureate Joshua Lederberg coined the term microbiome—defined as the genes harboring a vast ecosystem of mostly indwelling bacteria—we’ve seen an explosion in research.

In 2000, there were just 28 published papers on the microbiome, as of last year 7,102 appeared in the scientific literature, noted Sudeep Basu from the industry consultant Frost & Sullivan. Basu, who kicked off a microbiome symposium at the Molecular Medicine Tri-C symposium last Thursday, threw out another stat that revealed even more about the state of the microbiome market: the rapid rise in patent filings—from 9 in 2012 to 833 in 2017.

There is no doubt that the microbiome is tomorrow’s hot drug development story. A year ago, we blogged about how several microbiome-focused start-ups have been raising cash and signing deals with larger pharma partners focused on gastro-intestinal problems, such as irritable bowel syndrome, Crohn’s disease and Clostridium difficile.

There are also numerous studies that suggest the microbiome also heart disease, diabetes, dementia, obesity and autism, with the list of potential associate keeps growing, sparking the imagination on how probing our microbes might lead to better health.

So what are leading scientists in the microbiome space eyeing in this developing industry. At a Charles River Microbiome Think Tank held during the Tri-C meeting and chaired by Vice President Iva Morse and Senior Vice President John Ho of Charles River, nine experts from the academic, government and commercial sectors largely agreed that fecal microbiota transplants to treat recurrent C. diff. would likely be the first microbiome-related targeted therapy approved. (A double-blind randomized study of C. diff patients that appeared in the New England Journal of Medicine demonstrated 94% efficacy of fecal microbiota transplantation compared with 31% after conservative treatment with the antibiotic vancomycin.)

But the immune system is also a hot topic among developers of microbiome therapeutics, particularly in the area of immuno-oncology.

Mohan S. Iyer, Chief Business Officer of the biotech Second Genome in San Francisco, said 30-40 years ago we barely knew or understood the functions of the various subtypes of T cells. Diseases like AIDS and cancer have changed that. “I really believe what we are coming to is that the adult human immune system is really centered on the gut,” says Iyer. “This is the place to really track the immune system in a way we haven’t before.”

Consider immune-oncology and the realm of checkpoint inhibitors, a new class of drugs that temporarily releases the brakes on proteins that sit on the surface of T cells in order to provide a more robust immune response.

David Cook, Executive Vice President and Chief Scientific Officer of the Cambridge, MA biotech Seres Health and a panelist at the Think Tank said researchers from MD Anderson Cancer Center in Houston reported at a conference in Florida last week that they had found a link between microbes in the gut and response to immunotherapy. This observation had already been demonstrated in mice over a year ago, but the human studies made the connection and even bigger story because of the size of the cancer drug market and the clinical need to improve the efficacy of immune checkpoint inhibitors.

Autoimmune diseases are another area microbiome researchers are interested in probing. Lyn Bry, an associate professor of pathology at Brigham and Women’s Hospital in Boston and Director of the Massachusetts Host-Microbiome Center, said her group is interested in the effects of the microbiota on immunomodulation and how microbes might be used as a kind of Swiss Army Knife that can trigger multiple immune pathways. “Perhaps then we could then skew a patient from allergy and autoimmunity to a phenotype that is tolerant or that can otherwise modulate the disease on its own or in combination with other therapies,” says Bry.