The study (NCT06801067), conducted at MSK, by Principal Investigator David Faleck, M.D., Director of Inflammatory and Immune-Related Bowel Diseases, evaluated SER-155 in 15 patients with moderate-to-severe (Grade 2- 3) irEC, which affects approximately 25% of all immune checkpoint inhibitor (ICI) therapy recipients in the US. Clinical guidelines for these patients stipulate halting of ICI cancer treatment and initiation of systemic immunosuppressive corticosteroids, which are associated with clinically meaningful toxicities and other negative consequences, including: systemic immunosuppression, increased infection risk, metabolic complications, and potential interference with cancer treatment. There remains a significant unmet need for systemic immunosuppressive-free therapeutic approaches that reduce gastrointestinal inflammation and diarrhea and may allow patients who develop irEC to avoid disruption of their life-saving ICI cancer treatment. Participants in the study were on a wide range of ICI types, including PD-1 inhibitors (Keytruda®, Opdivo®, Zynz®), PD-L1 inhibitors (Imfinzi®, Bavencio®), CTLA-4 inhibitors (Yervoy®, Imjudo®), LAG-3 inhibitor (Opdualag®), and combinations thereof. The promising study results support continued development of SER-155 to treat irEC.

Topline Clinical Results

Day 15 Data

  • Following SER-155 dosing, 12 of 15 participants (80%) achieved an immunosuppressive-free clinical response at Day 15, the primary endpoint, defined as at least a 1-grade improvement in diarrhea symptoms without immunosuppressive therapy (i.e., a corticosteroid and/or biologic immunomodulator drug). Notably, 8 of these 12 responders (67%) achieved greater than or equal to a 2-grade improvement in diarrhea symptoms without immunosuppressive therapy at Day 15.

     
  • At Day 15, 5 of 15 participants (33%) achieved immunosuppressive-free complete clinical remission, defined as total resolution of diarrhea symptoms to Grade 0, without immunosuppressive therapy.

     

Day 43 Data

  • At Day 43, 5 of 15 participants (33%) maintained immunosuppressive-free clinical response, and, notably, 2 of 15 participants (13%) maintained immunosuppressive-free complete clinical remission.

     
  • All 12 participants with immunosuppressive-free clinical response at Day 15 had the same, or better, diarrhea grade at Day 43. As noted, 5 maintained immunosuppressive-free clinical response at Day 43. The other 7 were treated with non-systemically acting, gastrointestinal-targeted immunosuppressives after Day 15.

     

Safety

  • SER-155 was generally well tolerated through Day 43, with no safety concerns identified, consistent with the outcome in Seres’ Phase 1b study of SER-155 in participants undergoing allogeneic hematopoietic cell transplantation (allo-HCT). There were no serious adverse events assessed as related to SER-155 and no bloodstream infections reported in the study through Day 43. Two participants experienced 2 non-serious adverse events each, assessed as possibly related to vancomycin and SER-155. All 4 adverse events were moderate in severity and were resolved.

     

Pharmacology

  • SER-155 bacterial strain engraftment (a measure of drug pharmacokinetics and strain growth in the gastrointestinal tract) was robust, with the majority of SER-155 strains observed across the study participants, and with kinetics, magnitude, and durability comparable to that observed in prior Seres clinical studies.

     
  • Translational biomarkers of gastrointestinal inflammation (fecal calprotectin) and of mucosal epithelial barrier integrity (fecal albumin), which were elevated in participants at baseline, prior to SER-155 dosing, both showed decreases post SER-155 treatment, with statistically significant reductions achieved by Day 43, reflecting improvement in two mechanistically linked dimensions of irEC disease. Data suggest that administration of SER-155 led to improvement in mucosal epithelial barrier integrity, providing support for potential further development in multiple other inflammatory and immune diseases.