Key Takeaways:
A live biotherapeutic from Seres Therapeutics resolved immunotherapy-related gastrointestinal toxicity in 80% of patients without systemic immunosuppression, offering a potential alternative to steroids that often force cancer patients to halt treatment.
Seres Therapeutics (NASDAQ: MCRB) reported results from an investigator-sponsored Phase 1b trial of SER-155 in immune checkpoint inhibitor-related enterocolitis, or irEC, a frequent side effect of PD-1, PD-L1 and CTLA-4 inhibitors that affects about 25% of all immune checkpoint inhibitor recipients. The open-label study, conducted at Memorial Sloan Kettering Cancer Center, enrolled 15 patients with Grade 2 or Grade 3 irEC who had not yet received immunosuppressive therapy.
"These results suggest SER-155 may offer a promising, novel approach to managing irEC, with the potential to reduce reliance on systemic immunosuppressive therapies, while also helping patients continue ICI treatment," Dr. David Faleck, the trial's principal investigator and a gastroenterologist at MSK, said.
Twelve of 15 participants, or 80%, achieved the primary endpoint of immunosuppressive-free clinical response at day 15, defined as at least a one-grade improvement in diarrhea symptoms without corticosteroid or biologic therapy. Five patients, or 33%, reached complete clinical remission with diarrhea resolution to Grade 0. Among the 12 responders, eight improved by two or more grades by day 15, and 11 showed improvement as early as day eight. At day 43, all 12 day-15 responders maintained the same or better diarrhea grade, though seven received non-systemically acting, gastrointestinal-targeted immunosuppressives after day 15 for mild residual or recurrent symptoms.
The current standard of care for moderate-to-severe irEC requires halting immune checkpoint inhibitor therapy and starting systemic corticosteroids, which carry risks of immunosuppression, infection and potential interference with antitumor activity. In the study, 14 of 15 participants had their cancer therapy interrupted before enrollment because of irEC. Seres estimates the addressable US patient population at about 75,000 in 2026.
Biomarker Data Support Mechanism of Action
Translational biomarker results reinforced the clinical findings. Patients entered the study with elevated fecal calprotectin and fecal albumin, markers of gastrointestinal inflammation and epithelial barrier disruption. Both biomarkers showed statistically significant reductions by day 43 after SER-155 treatment, suggesting the therapy acts on disease-relevant biology rather than producing only symptomatic effects, according to Matthew Henn, Seres' president and chief scientific officer.
SER-155 is a cultivated multi-strain oral live biotherapeutic designed to restore gut barrier function, outcompete pathogens and reset gut homeostasis. The bacterial strains engrafted across the majority of patients, with kinetics and durability consistent with prior studies in allogeneic hematopoietic stem cell transplant recipients. In that earlier Phase 1b placebo-controlled study, SER-155 showed a 77% relative risk reduction in bloodstream infections, earning the drug breakthrough therapy and fast track designations from the FDA.
Safety Profile and Path Forward
SER-155 was generally well tolerated through day 43, with no serious adverse events assessed as related to the study drug and no bloodstream infections reported. Two participants experienced non-serious adverse events possibly related to vancomycin and SER-155, both moderate in severity and resolving.
Richard Kender, Seres' executive chairman and interim chief executive officer, said the data expand the opportunity for the company's live biotherapeutics platform in cancer care and support ongoing discussions with potential strategic and financial partners. Seres plans to advance SER-155 into a Phase 2 trial of about 100 to 150 patients in irEC and is also considering prophylactic use to prevent the condition, though prevention studies would be larger.
The company, headquartered in Cambridge, Massachusetts, also counts SER-109, an investigational oral microbiome therapeutic for reducing recurrence of Clostridioides difficile infection, among its lead candidates. Seres did not disclose its current cash runway, but the Phase 2 planning and partnership discussions suggest the company is positioning SER-155 as a potential non-immunosuppressive cornerstone of immune checkpoint inhibitor supportive care — a market with no approved microbiome-based alternatives today.
This article is for informational purposes only and does not constitute investment advice.
