- An experimental drug from Seres Therapeutics failed a Phase 2 study of patients with mild or moderate ulcerative colitis in a setback for an emerging class of medicines known as microbiome therapeutics.
- Treatment with Seres' drug didn't lead to meaningfully higher remission rates than did placebo, the study's main goal and a measure of the medicine's ability to curb inflammation associated with the disease. The drug also didn't eliminate patients' symptoms any better than placebo and was associated with more side effects.
- Seres isn't giving up on treating ulcerative colitis, however. The company is exploring a path forward for the drug and has a second treatment in early testing that may work better. Shares still fell by more than half on the news, erasing gains the biotech has made since last year.
Prior to Thursday's news, the past year was a good one for Seres and the field of drugs in which it specializes.
Seres, a pioneering developer of so-called microbiome drugs, last August declared success in a Phase 3 study for a type of recurring bacterial infection. The result, combined with positive findings for similar treatments from Finch Therapeutics and Rebiotix, signaled growing promise for microbiome drugs, which are designed to change the interactions between the body and the microbes that inhabit them.
Seres shares soared to new highs in the ensuing months as the biotech prepared an approval filing that could be the field's first. Partner Nestle Health Science subsequently deepened its ties with Seres by investing $500 million more in the experimental medicine.
Microbiome drugs, though, are viewed as a way to treat a wide range of conditions, from cancer to inflammatory diseases. That made Seres' next test, in ulcerative colitis, an important proof point for the field.
Unlike other ulcerative colitis treatments, Seres' isn't immunosuppressive. Seres hoped to show the drug — a group of gut bacteria packed into a pill — could prove a safer alternative or potential combination partner for existing drugs. Instead, the biotech is dissecting another failure and figuring out its next move.
Seres said two different drug regimens led to remission rates of 10.3% and 10.6%, respectively, versus 11.6% for placebo. Though the majority of treatment-related side effects were mild to moderate, four participants who received Seres' drug experienced serious adverse events — among them congestive heart failure and the formation of abnormal polyps on the colon — compared to only one who received placebo.
As a result of the negative findings, Seres closed the open label and maintenance portions of the trial. On a conference call, company CEO Eric Schaff said Seres was "surprised and disappointed" by the preliminary results, noting how much they diverged from Phase 1.
Seres will have more data by the second half of the year, he added, which may help determine next steps for the drug, known as SER-287, and a successor version called SER-301.
This type of plan has worked for Seres before. After combing through the 2016 failure of its drug for C. difficile infections, Seres identified issues in patient screening and designed a new trial that yielded positive results in 2020.
"While we don't know what drove the differences between the [Phase] 1 and [Phase] 2 today, we do know that taking a similar process is the right next step for us and that's what we're going to do," said Schaff.
Seres can fall back on SER-301, a consortium of bacteria Seres hand-picked, optimized and cultivated, rather than derived from donors like SER-287. The goal is more targeted treatment, which chief scientific officer Matthew Henn said may be necessary for diseases like ulcerative colitis. An early-stage study is underway, though executives wouldn't say when to expect results.
Other companies, among them Finch and Vedanta Biosciences, are developing microbiome drugs for inflammatory bowel disease, too. Vedanta plans to start a Phase 2 trial in ulcerative colitis later this year, while Finch's is still in preclinical testing.