A Poopy Pill to Treat Hospital Infections
In the Cambridge (Mass.) basement of startup Seres Health sits a series of benches shrouded in rectangular vinyl tents. They’re essentially clear, vacuum-sealed cages for microbes that live without air. Seres says the organisms hold the key to a new class of biological medicine—pills that can fight the antibiotic-resistant infections sweeping U.S. hospitals. The microbial treatments come from within the human body—deep within. This is, as a whiteboard in the Seres basement puts it, the “Strategic Poop Reserve.”
It’s not as crazy, or gross, as it sounds. In the last few years, one of the most promising therapies for antibiotic-resistant infections has been the transplantation of healthy fecal matter into a patient’s gastrointestinal tract. Antibiotics kill gut bacteria indiscriminately, including healthy strains; the idea with the transplant is to wipe out antibiotic-resistant germs with healthy bacteria reinfused into the patient from donor stool. The transplant procedure, however, is difficult, invasive, and time-consuming, and the U.S. Food and Drug Administration has been slow to approve it for wide use because the long-term effects are unknown.
Seres and a handful of competitors have used a centrifuge to isolate healthy bacteria from fecal matter and put it in a capsule. It’s a simpler treatment that may be just as effective, and it almost certainly has a faster path to FDA approval. “We are eager to move forward as quickly as possible,” says David Berry, a Seres co-founder and director. “This is an important, unmet medical need.”
Berry’s first target is Clostridium difficile, or C. diff, an infection that the Centers for Disease Control and Prevention estimates sickens about 526,000 Americans, kills 14,000, and costs the U.S. health-care system about $1 billion per year. C. diff often looks like flu for a while, but the severe diarrhea eventually caused by the spore-forming bacteria also gives it some resemblance to colitis. The standard treatment for C. diff, like most antibiotic-resistant infections, has been more antibiotics, which often exacerbate the problem. Seres’s 10-milligram pill, called Ecobiotics, combines 5 to 15 purified bacterial strains into a two- to three-pill, once-a-day dose that appears to restore the equilibrium of the microbiome—the collection of organisms that live inside humans—and the health of the gut.
This summer two-year-old Seres published clinical data showing that its capsules successfully treated 97 percent of C. diff infections in its first two phases of 30-person clinical trials. The 22-employee company has raised about $21 million in venture capital, including a $10 million funding round that closed in June. Seres says it’s nearing third-phase testing (typically the last before a drug goes to market), and Chief Executive Officer Roger Pomerantz says the pills will be on sale by 2016.
In Roseville, Minn., three-year-old startup Rebiotix raised $25 million in August on the strength of early trials for its RBX2660, which treats C. diff “in a ready-to-use enema format.” CEO Lee Jones says Rebiotix has completed its Phase II trials and received orphan-drug status from the FDA, which reduces its hurdles to approval. “The market size is relatively small,” says Jones, estimating that about 100,000 Americans are potential candidates. She adds that experimental microbial therapies for other diseases may yield far greater interest. Cipac, an Australian startup affiliated with the University of Minnesota, is testing a gut bacteria treatment for C. diff and for autism, and it’s preparing to test one for metabolic syndrome, a disorder that contributes to diabetes, strokes, and heart attacks.
Berry says Seres is also testing drugs for other diseases, including diabetes. The Harvard M.D., who also has a Ph.D. in biological engineering from MIT, has worked on unconventional projects before. His previous undertakings include efforts to make fuels from sunlight, carbon dioxide, saltwater, and E. coli bacteria. (Biofuels company Renewable Energy Group bought the E. coli business in January for $61.5 million.) Seven years ago, Berry learned that researchers decoding the genetic sequences of stool samples found almost 100 times more genes in the microbiome than in human DNA. “You hear that,” he says, “and you have to think, ‘There’s something important here.’ ”
Only recently have researchers begun to seriously examine how the creatures living inside people affect disease, says Peter DiLaura, CEO of biotech startup Second Genome. “We’ve been so focused on the host side of the biology,” says DiLaura, whose Bay Area company is working with Pfizer. “If we’re going to understand any of these diseases, we have to look at it in the context of the microbiome.”