3:20 PM
 | 
Mar 01, 2018
 |  BC Innovations  |  Targets & Mechanisms

Checking out the microbiome

How academics are helping companies harness the microbiome for immuno-oncology

What started out as a potential use in stratifying patients is growing into a new avenue for turning non-responders to responders, as evidence continues to emerge linking the microbiome to immuno-oncology. While the data are handing microbiome companies a welcome but unanticipated path to the clinic, their progress might depend on academic deals to discover the targets and unravel the biology.

The latest data come from three Science papers in the last four months that each analyzed differences in gut microbiota among cancer patients who did or didn’t respond to treatment with checkpoint inhibitors. The studies identified distinct, non-overlapping groups of “good” bacteria prevalent in responders, and “bad” bacteria among the non responders.

By showing fecal transplants from responsive patients could more potently suppress tumors in mice treated with checkpoint inhibitors than transplants from non-responders, the three teams provided independent lines of evidence suggesting the gut microbiome -- or specific bacterial species within it -- can play an active role in determining treatment outcomes.

While a link between the microbiome and cancer had long been suspected, the immuno-oncology connection was sparked by a pair of preclinical Science papers published in late 2015 associating specific bacterial species with CTLA-4 or PD-L1 blockade.

Since then, academic groups have been working to identify the bacterial species in humans that predict or improve response to cancer immunotherapies.

“Every single factor that makes a tumor ‘hotter’ or ‘colder’ is affected by microbiome signals.”

Bernat Olle, Vedanta

Companies are taking note. At least nine have programs spanning the interface between the microbiome and immuno-oncology, and though most drug development in the microbiome space has focused on C. difficile, inflammatory bowel disease (IBD) and other autoimmune indications, the findings are giving the biotechs a foot in the door to a potentially much larger revenue stream.

“Immuno-oncology is such a lucrative field. The fact that there are so many fantastic drugs that only work for a third of patients at best, and that we now know the microbiome may be able to change that, is attracting a lot of interest,” said Jonathan Solomon, CEO of microbiome company BiomX Ltd.

David Cook, CEO of Seres Therapeutics Inc., added that moving towards cancer is an “extension of the idea that the microbiome educates and directs the immune system,” given the known connection with inflammation and immunity.

Still, he said, “five years ago we certainly weren’t thinking the microbiome would play a major role in cancer and that so much of the drug development would focus on cancer. It’s a big opportunity.”

At least three companies have clinical trials in sight. Seres, through a partnership with the University of Texas MD Anderson Cancer Center and the Parker Institute for Cancer Immunotherapy, plans to test SER-401 with an anti-PD-1 therapy next year.

Vedanta Biosciences Inc. plans to file an IND for VE800 this year, which will be tested with an undisclosed checkpoint inhibitor. And Evelo Biosciences Inc. plans to bring a program into the clinic next half in combination with a checkpoint inhibitor. The therapy comprises a single microbiome-derived species delivered to gut-associated lymphoid tissues to spark an immune response without colonizing the gut.

But the data thus far are primarily phenomenological.

To get a better handle on the underlying biology, eight microbiome companies have signed deals with academics, and three have deals with cancer companies (see “Microbiome Oncology Deals”).

The goals are to discover the mechanisms behind bacteria-driven antitumor immunity, uncover the targets, and determine whether the microbiome’s effects extend past checkpoint inhibitors to other cancer immunotherapies.

Table: Microbiome oncology deals

At least nine biotech companies are developing microbiome-based cancer...

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