Seres Reports Positive SER-155 Results in Immune Checkpoint Enterocolitis

Seres Therapeutics has reported encouraging topline results from an investigator-sponsored trial evaluating SER-155 in patients with moderate-to-severe immune checkpoint inhibitor-related enterocolitis (irEC), a serious gastrointestinal toxicity associated with cancer immunotherapy. Conducted at Memorial Sloan Kettering Cancer Center (MSK), the open-label study met its primary endpoint, with 80% of participants achieving an immunosuppressive-free clinical response by Day 15. The findings suggest SER-155 could offer a microbiome-based alternative to systemic corticosteroids, potentially allowing patients to continue life-saving immune checkpoint inhibitor (ICI) therapy without treatment interruption.

Microbiome Therapy Targets a Major Complication of Cancer Immunotherapy

Immune checkpoint inhibitors have transformed the treatment of multiple cancers but frequently trigger immune-related adverse events. Among the most common is immune checkpoint inhibitor-related enterocolitis (irEC), which affects approximately one-quarter of patients receiving ICIs in the United States. Moderate-to-severe cases are typically managed by stopping immunotherapy and initiating systemic corticosteroids or biologic immunosuppressants, therapies associated with infection risk, metabolic complications, and the potential to reduce anti-tumor immune activity.

SER-155 is an investigational live biotherapeutic containing selected bacterial strains intended to restore the intestinal microbiome, strengthen the mucosal epithelial barrier, and reduce gastrointestinal inflammation rather than suppress the immune system broadly.

Study Met Primary Endpoint with Strong Early Clinical Responses

The investigator-sponsored trial (NCT06801067) enrolled 15 immunosuppressive-naïve patients with Grade 2 or Grade 3 irEC. Participants first received two days of oral vancomycin before taking SER-155 at two capsules daily for 12 consecutive days.

By Day 15, 12 of 15 patients (80%) achieved the primary endpoint of immunosuppressive-free clinical response, defined as at least a one-grade improvement in diarrhea without corticosteroids or biologic immunomodulators. Among responders, eight patients (67%) experienced at least a two-grade improvement, while five patients (33%) achieved complete remission of diarrhea without immunosuppressive therapy.

At Day 43, five participants maintained immunosuppressive-free clinical response, including two who remained in complete remission. The remaining Day 15 responders maintained stable or improved diarrhea severity but received gastrointestinal-targeted, non-systemic immunosuppressive therapy after Day 15.

Safety and Biomarker Findings Support the Mechanism

SER-155 was generally well tolerated through Day 43. Investigators reported no drug-related serious adverse events, no bloodstream infections, and only four moderate, non-serious adverse events that resolved during follow-up.

Pharmacology analyses showed robust engraftment of SER-155 bacterial strains across participants. Biomarkers also supported the proposed mechanism, with statistically significant reductions in fecal calprotectin, a marker of gastrointestinal inflammation, and fecal albumin, an indicator of intestinal barrier damage, by Day 43. These findings suggest improved mucosal barrier integrity alongside reduced inflammation and provide a rationale for evaluating SER-155 in additional inflammatory and immune-mediated diseases, including ulcerative colitis and Crohn’s disease.

Leadership Highlights Broader Development Opportunity

Executive Chairman and Interim Chief Executive Officer Richard Kender said the results support SER-155 as a non-immunosuppressive treatment option that may help patients continue immune checkpoint inhibitor therapy. He noted that the company is engaging with potential partners, including companies with established immuno-oncology franchises, while also seeking financing to advance the planned Phase 2 study of SER-155 in allogeneic hematopoietic cell transplantation.

President and Chief Scientific Officer Matthew Henn, Ph.D. said the clinical and pharmacology data reinforce the therapeutic potential of the company’s live biotherapeutic platform to address diseases driven by epithelial barrier dysfunction and gastrointestinal inflammation. Investigators at MSK also stated that the results support continued evaluation of microbiome therapeutics for irEC and plan to present the full study findings at a future medical conference.

Regulatory Path Forward

The positive topline data strengthen the clinical rationale for advancing SER-155 as a first-in-class microbiome therapeutic for immune checkpoint inhibitor-related enterocolitis. Seres is evaluating partnership opportunities to support further clinical development in irEC while continuing efforts to fund broader development of SER-155 across oncology supportive care and other inflammatory gastrointestinal diseases.

What This Means for Patients

For people receiving immune checkpoint inhibitors for cancer, immune checkpoint inhibitor-related enterocolitis (irEC) can cause severe diarrhea and intestinal inflammation, often forcing doctors to stop immunotherapy and prescribe systemic corticosteroids or other immunosuppressive drugs. In this early study, SER-155 improved diarrhea symptoms in most patients without the need for systemic immunosuppression, raising the possibility that some patients could continue their cancer treatment while avoiding steroid-related side effects. Although these findings are encouraging, SER-155 remains an investigational therapy and requires further clinical studies before it becomes available for routine patient care.

Reference

Seres Therapeutics Announces Early Clinical Data Showing Potential for SER-155 in Immune Checkpoint Inhibitor-Related Enterocolitis (irEC), a Frequent Adverse Reaction That Forces Many Patients to Halt Cancer Treatment | Seres Therapeutics