The infectious disease doctor mining the microbiome for drugs
When Roger Pomerantz left Merck in 2013, he told his wife that that was it—with the exception of sitting on a few company boards, he was going to retire.
Retirement didn't last long.
In 2014, he joined Seres Pharmaceutical as its chief executive. On the surface, it was a non-linear move. An infectious disease physician by training, much of Pomerantz's career has been spent overseeing ways to kill harmful microorganisms. (Before coming to Merck, he was the global head of infectious diseases at Johnson & Johnson.)
Seres Pharmaceutical takes the opposite approach: instead of creating drugs to wipe out bad microbes, it creates drugs from the good ones. Pomerantz got interested in the microbiome, the name for the collective trillions of microorganisms that reside within us, around five years ago back when he was running Merck's licensing and acquisitions department.
One of the last drugs he developed at the pharma giant was a treatment for clostridium difficile (or C.diff), a serious infection that causes dehydration, diarrhea, and other intestinal conditions. It often occurs after a course of broad spectrum antibiotics, which wipe out much of the bacteria in the gut enabling bad strains to flourish.
“No one knew why until we discovered the microbiome,” he says.
Since then, the microbiome has entered the popular imagination. Few areas of study are as frothy. It's easy to understand the excitement: until relatively recently, we didn't know the microbiome existed. Now, researchers believe it influences everything from metabolism, to mood, to cancer. “Without your microbiome, you cannot control your immune system, cholesterol levels, blood sugar. You cannot live,” Pomerantz says. “It's really an organ, it just happens to be made up of 120 trillion microorganisms.”
And yet, we still have a lot to learn. The microbiome is bursting with potential, but we have little more than a series of intriguing, non-linear connections. The hype might be justified, but it could be years before it's translated into treatments.
With Seres, Pomerantz wants to be at the vanguard of the drug discovery process. The company is seeking FDA approval for its microbiome-based treatment for C.diff. Although often caused by broad spectrum antibiotics, the infection has traditionally been treated with antibiotics. “That never made any sense,” said Pomerantz. “The question became, ‘Why don't we use the microbiome instead?'”
There was some precedent for this. Patients with recurrent C.diff infections receive fecal transplants, which, it's believed, help repopulate the gut with good bacteria. Using genomics analysis, Seres compared the microbiomes of people with recurrent C.diff to those of healthy individuals, isolating the strains missing from the former group. It isolated these strains—notably firmicutes, which replicate through spores—purified them, and “put them into Tylenol-size capsules,” Pomerantz says.
In 2016, the company ran into a major roadblock when findings from a mid-stage clinical trial failed to reduce the risk of recurrent C.diff, sending its stock into a tailspin. But after reviewing the results and changing the diagnostic criteria and dosage, Seres developed a new Phase III trial in collaboration with the FDA.
Microbiome research is still in its infancy, said Pomerantz. That's why, despite the vast amount of intriguing links, he's focused on developing drugs from the few that have been validated in trials on animals or that involve human fecal transplants—hence, pills with fecal matter to treat C.diff. As the research progresses, more links will justify drug development. But for now, the questions continue to surface faster than answers.
“If you look at human blood, there are more metabolites from your microbiome than from your own cells,” he says. “The startling thing is, you are more ‘them' than you are ‘you.'”
In other words, we're just beginning to scratch the microbial surface.