Seres Therapeutics (NASDAQ:MCRB) reported results from an investigator-sponsored study of SER-155 in immune checkpoint inhibitor-related enterocolitis, or irEC, saying the data support further evaluation of the live biotherapeutic as a potential non-immunosuppressive treatment option for cancer patients experiencing the gastrointestinal toxicity.
The open-label Phase 1b trial was conducted at Memorial Sloan Kettering Cancer Center and evaluated SER-155 in 15 participants with Grade 2 or Grade 3 irEC who had not yet received immunosuppressive therapy for the condition. The study’s main clinical efficacy assessment was immunosuppressive-free clinical response at day 15, defined as at least a one-grade improvement in diarrhea symptoms without corticosteroid or biologic immunosuppressive therapy.
Study Shows 80% Response at Day 15
Kelly Brady, Seres’ executive vice president and chief operating officer, said 12 of 15 participants, or 80%, achieved an immunosuppressive-free clinical response by day 15 after treatment with SER-155. Five participants, or 33% of the total study population, achieved complete clinical remission, defined as resolution of diarrhea symptoms to Grade 0 without immunosuppressive therapy.
Brady said the response was observed quickly, with 11 of 12 responders showing improvement by day eight. Eight of the 12 responders improved by two or more grades by day 15.
At day 43, all 12 day-15 responders remained at the same diarrhea grade or better. Five of the 15 participants maintained an immunosuppressive-free response at day 43, including two who remained in clinical remission and three who remained at Grade 1. The other seven day-15 responders maintained their clinical response at day 43 after receiving non-systemically acting, gastrointestinal-targeted immunosuppressives for mild residual or moderate recurrent symptoms, according to Brady.
Seres said SER-155 was generally well tolerated through day 43. No serious adverse events were assessed as related to SER-155, and no bloodstream infections were reported. Two participants experienced non-serious adverse events assessed as possibly related to vancomycin and SER-155; the events were moderate in severity and resolved.
Company Highlights Need for Alternatives to Steroids
Brady said immune checkpoint inhibitors are increasingly used across a range of solid tumors but can trigger immune-related gastrointestinal toxicity, including diarrhea, abdominal pain, colitis and blood in stool. She said moderate to severe irEC, classified as Grades 2 to 3, occurs in about 25% of all immune checkpoint inhibitor recipients, which Seres estimates would represent about 75,000 patients in the U.S. in 2026.
Current guidelines call for halting immune checkpoint inhibitor therapy and starting immunosuppressive corticosteroids for patients with Grade 2 or higher irEC, Brady said. In the study, 14 of 15 participants, or 93%, had their immune checkpoint inhibitor therapy interrupted before study entry because of irEC.
Brady said a post hoc observation found that a portion of participants returned to immune checkpoint inhibitor therapy through day 43, and Seres expects to analyze immune checkpoint inhibitor administration in a future study.
Biomarker Data Support Biological Activity, Seres Says
Matthew Henn, Seres’ president and chief scientific officer, said the study also produced pharmacology and translational results that supported the observed clinical activity. He said SER-155 strains engrafted across the majority of patients, consistent with prior studies in allogeneic hematopoietic stem cell transplant patients.
Henn said participants entered the study with elevated fecal albumin and fecal calprotectin levels, biomarkers associated with epithelial barrier disruption and gastrointestinal inflammation. After SER-155 treatment, both biomarkers showed reductions over time, with significant reductions by day 43, according to Henn.
He said the results suggest SER-155 may act on disease-relevant biology rather than only producing symptomatic effects. Henn also referenced Seres’ earlier Phase 1b study of SER-155 in allo-HSCT patients, in which the company reported a 77% relative risk reduction in bloodstream infections among participants who received SER-155. He said those results led to FDA breakthrough therapy designation for SER-155 in that setting.
MSK Physician Cites Potential in Cancer Care
Dr. Jonathan Peled, a bone marrow transplant specialist and cellular therapist at Memorial Sloan Kettering, said the gut barrier is a critical area where the microbiome and immune system interact. He said current steroid treatment for irEC is inadequate for many patients because of immunosuppression, infection risk and interruption of cancer therapy.
Peled said the idea of administering a designed consortium of bacterial strains to promote gut barrier function, outcompete pathogens and potentially reset gut homeostasis is “really exciting” because it could help patients manage a serious side effect while avoiding steroid-related immunosuppression.
Seres Discusses Next Development Steps
During the question-and-answer session, Brady said Seres anticipates a modestly sized Phase 2 trial of approximately 100 to 150 patients evaluating SER-155 as a treatment for irEC, using similarly timed endpoints intended to support a timely readout. She said the company would also consider studying SER-155 prophylactically to prevent irEC, though prevention studies can be larger.
Kender said the new data would support Seres’ ongoing engagement with potential strategic counterparties and financial partners, including those focused on oncology outcomes, immune checkpoint inhibitor use and broader inflammatory and immune diseases.
About Seres Therapeutics (NASDAQ:MCRB)
Seres Therapeutics is a clinical?stage microbiome therapeutics company focused on harnessing the power of the human microbiome to treat serious diseases. Headquartered in Cambridge, Massachusetts, Seres applies proprietary microbiome science and manufacturing capabilities to develop a pipeline of living microbial therapies designed to restore healthy gut function. The company’s approach leverages understanding of microbial ecology and human biology to address conditions where the native microbiome is disrupted.
Among its lead candidates is SER-109, an investigational oral microbiome therapeutic for reducing recurrence of Clostridioides difficile infection.
