'By no means are we deterred': Seres' stock spirals after PhII microbiome fail in ulcerative colitis
Almost five years after Seres Therapeutics slammed into a Phase II failure with its lead candidate, the microbiome pioneer is reporting another massive flop in ulcerative colitis. But like the last time, the company isn’t throwing in the towel just yet.
Patients who took SER-287 — a consortia of bacteria found in the gastrointestinal tracts of healthy individuals — showed no difference in clinical remission compared to those given a placebo, Seres said of the Phase IIb trial. The news sent the biotech’s shares $MCRB spiraling more than 50% on Thursday morning, pricing in at just under $10 apiece.
As a result, Seres is closing the open label and maintenance portions of the study — but that doesn’t mean the drug is dead.
“Pioneering a new space is seldom a straight line from point A to point B,” CEO Eric Shaff told Endpoints News. “We’ve been here before as a team and as a company, and we’re disappointed, but by no means are we deterred.”
Shaff compared the failure to the company’s lead candidate, SER-109, which flopped in a Phase II trial for C. difficile infection back in 2016 and diminished investor interest in the field for years afterward. But after bidding adieu to former CEO and Merck vet Roger Pomerantz, the company soldiered on, claiming positive topline Phase III results last summer. Nestlé Health Science put down $175 million upfront earlier this month to co-commercialize the candidate, and has promised Seres another $125 million if the FDA follows through with an approval.
“After our Phase IIb study results in SER-109 for recurrent C diff., we were in a situation where we had a surprising and disappointing result,” Shaff said. “We went through a rigorous scientifically objective analysis, and ultimately, at the end of that we came up with adjustments that we thought could improve our probability of success.”
CMO Lisa von Moltke says microbiome analyses for SER-287 should be ready in the second half of 2021.
“I can’t tell you where that analysis will go, but we certainly do feel that that type of approach is appropriate here,” Shaff said.
The Phase IIb trial, dubbed ECO-RESET, enrolled 203 UC patients who received either a full induction or step-down induction dose of SER-287, or a placebo. Patients in the full induction dose cohort saw an absolute clinical remission rate of 10.3%, compared to 10.6% for the step-down dose and 11.6% for the placebo group.
Those on the drug also showed no differences in endoscopic improvement, endoscopic remission, or symptomatic remission, Seres said.
Back in March, Seres announced its partnered program with the Parker Institute for Cancer Immunotherapy in metastatic melanoma was being shelved due to “challenges” presented by running the study during the pandemic.
When asked during a call with investors whether the pandemic had any effect on the SER-287 trial results, von Moltke responded, “Based on the topline data we’ve seen so far, it looks like the execution was really smooth throughout, and we’ll be looking of course for any kind of pattern as we dig deeper into it, but I think we were quite pleased with the way the sites and the clinical team executed, and we’re quite thankful for their efforts.”
In the meantime, the company seems to be shifting its focus to SER-301, its Phase 1b candidate for UC. SER-301 is also made up of a consortia of healthy bacteria — but it’s cultivated in a lab, unlike SER-287, which is donor-derived.
“It really is focused,” Shaff said. “It allows us to think about the organisms that we know have the most beneficial effects for disease, including anti-inflammatory properties (and) promoting gut barrier integrity.”
The company has not announced when it will read out those Phase Ib results, but Shaff says the company will consider making adjustments to the trial based on results from the microbiome analysis of the SER-287 study.
“As always, what we’ll do is follow the data,” he said.