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With FDA’s Blessing, Seres Preps New “Pivotal” Microbiome Drug Trial

Xconomy Boston — 

Seres Therapeutics wants to become the first company to bring to market a drug that targets the microbiome, the delicate balance of microbes colonizing the human body. The failure of its lead drug in a clinical trial last year put those aspirations in doubt. Now the Cambridge, MA, drug developer is getting another shot.

Seres (NASDAQ: MCRB) plans to test its microbiome drug, SER-109, in a new clinical trial, one that will enroll more patients than the Phase 2 study that failed last summer. If successful, Seres CEO Roger Pomerantz says the FDA agreed that this larger study would be a “pivotal” trial, another way of saying that it should provide enough data for Seres to file for FDA approval.

“One of the reasons a Phase 2 trial can be considered pivotal is that this is a breakthrough drug, and we believe, and the FDA believes, the first microbiome drug,” Pomerantz says.

Seres is developing SER-109 as a treatment for recurrent Clostridium difficile infection, or C. diff., a bacterial infection that can occur in patients who have been treated with antibiotics. The Seres drug is a capsule containing a mix of bacterial spores from healthy human donors. When swallowed, the drug is supposed to help a patient’s gut microbiome return to the healthy balance that keeps c. diff. bacteria from proliferating and causing an infection.

In a Phase 1b study, the Seres drug cured 29 of 30 patients who had recurring C. diff. infection, which helped fuel Seres’s run to a $134 million IPO in 2015—the first ever U.S. IPO for a microbiome drug developer. But in July 2016, SER-109 badly failed its next test, a placebo-controlled Phase 2 trial, and shares spiraled downward. Seres subsequently dug through the data to figure out what happened, and designed a new trial based on its findings.

Pomerantz said in January Seres didn’t find any problems with SER-109, just with the way C. diff. infection was diagnosed in the failed study. Patients in the trial were diagnosed using polymerase chain reaction, or PCR, a test that finds genetic traces of C. diff bacteria. But Seres found that some of those patients had genetic traces of C. diff. without actually having active cases of the infection. The company proposed using an older diagnostic, one that tests for cytotoxins in stool samples. Seres also concluded that the dose given to patients was not high enough.

Pomerantz says the FDA has agreed with the company’s assessment. The new trial will include the stool sample diagnostic, and Seres will use a 10-fold higher dose of SER-109 than it used in the previous study. Patients will also get the drug over three days, rather than two. Pomerantz says the company’s data and analyses suggest the Seres drug works best when the dose is spread over three days. To date, Seres has not reported signs of “safety signals”—indications that the drug is causing dangerous side effects. But the company will need to show that the drug is safe at the higher dose.

Seres will enroll 320 patients—compared to the 89 in the previous trial—and give half the drug and the other half a placebo. The larger patient pool will help Seres build a safety database, Pomerantz says. The study will have the same goals as the failed trial: evaluating the risk of recurrence of C. diff. infection after eight weeks of treatment.

Seres expects to have enough funds to finance the new study. The company had $230 million in cash at the end of the fourth quarter, according to CFO Eric Shaff, in part because of a $120 million, January 2016 deal with Nestle Health Science. Shaff says Seres’ cash should carry the company through 2018.

It’s unclear whether Seres will have data by then. Pomerantz gave no specific details on when the trial would begin, other than to say that Seres wants to start “as rapidly as we can.” He noted that the company already has the 27 sites used in the previous clinical trial, which should allow the study to enroll more quickly. The company will be adding new sites, including locations in Canada, he says.

Image of Clostridium difficile bacterium by the Centers for Disease Control and Prevention.