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

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