In a Microbiome Setback, Seres Drug Fails in Phase 2, Shares Crushed

Xconomy Boston — 

Seres Therapeutics raised $134 million in an IPO and made history in the process, becoming the first drug developer targeting the microbiome to go public in the U.S. But disappointing news from the Cambridge, MA, company today shows just how much we have yet to understand about the relationship between trillions of bacteria that colonize our bodies and human disease.

Seres (NASDAQ: MCRB) said this morning that a product known as SER-109, a mix of bacterial spores designed to treat patients from recurring infection of the potentially deadly bacterium Clostridium difficile, or C. diff, failed to meet its main goal in a Phase 2 trial. The drug didn’t reduce the relative risk of C. diff recurrence, compared to a placebo, up to eight weeks after treatment. Seres said it will comb through the data, and after talks with the FDA, make “appropriate adjustments” to its development plans for SER-109.

In a statement, Seres CEO Roger Pomerantz called the data “unexpected” and “inconsistent with our expectations.” The same could be said for Seres shareholders, who sent shares free-falling more than 75 percent, to $8.74 apiece in pre-market trading on Friday. Cambridge-based Flagship Ventures, which formed the company in 2010, held 37.3 percent of Seres as of an April proxy filing.

Seres shares had closed Thursday at $35.77 apiece. It went public at $18 per share last June, in part because of early and promising data for SER-109. The drug effectively cured 29 of 30 patients in an early-stage trial who suffered from recurring infection of C. diff.

“Our priority is to complete a full review of the clinical results and microbiome data of the Phase 2 study and to compare it to data from the prior investigator sponsored Phase 1b,” Pomerantz said in a statement.

Seres is one of an emerging number of companies—among them Vedanta Biosciences, Enterome, Second Genome, EpiBiome, and uBiome—trying to understand the relationship between our bodies and the microbiome. That quest picked up steam in June in Washington, when the Obama administration launched the $121 million Microbiome Initiative, adding to a string of high-profile initiatives in cancer, brain research, and precision medicine. SER-109 represented the field’s biggest test to date, a Phase 2 test of its most advanced therapeutic.

In the study, 89 patients with recurrent C. diff—at least three or more recent flare-ups—were randomized two-to-one and given either SER-109 or a placebo after an antibiotics regimen (59 were on SER-109, and 30 were given a placebo). The goal was for SER-109 to improve the relative risk of C. diff recurrence, defined as a need for antibiotics, diarrhea for two or more days, and a positive test for C. diff.

The data Seres reported fell far short of expectations, however. Some 44 percent of patients (26 of 59) on SER-109 had their C. diff recur after 8 weeks, compared to 53 percent (16 of 30) of those on placebo. On the positive side, Seres didn’t see any difference in the rate, types, or severity of side effects—mostly gastrointestinal problems like diarrhea or stomach pain—but now the future of SER-109 is unclear and investors’ faith in the company has been shaken. Leerink Partners’ Joseph Schwartz, for instance, wrote in a note this morning that he expects investors to “grow more cautious on not just SER-109…but the entire microbiome platform.”

Seres will hold a conference call this morning to discuss the news. Meanwhile, check out these stories for more on Seres and microbiome research.