Seres Therapeutics (MCRB) Study Result summary

Study background and rationale

• SER-155 is a live oral biotherapeutic with 16 bacterial strains, designed to reduce GI-derived bloodstream infections and related complications in allo-HSCT patients.

• Allo-HSCT patients are highly immunocompromised and at significant risk for serious infections, with up to 45% experiencing bloodstream infections during transplant.

• The study aimed to address unmet needs in this population, with potential expansion to other high-risk groups.

• SER-155 was developed using Seres' reverse translation platform, incorporating human biomarker and nonclinical data.

• Early SER-155 development was supported by CARB-X, a global partnership against drug-resistant bacteria.

Study design and patient population

• Phase 1b, randomized, double-blind, placebo-controlled study in allo-HSCT patients; Cohort 2 included 45 patients (20 SER-155, 14 placebo) with data through day 100 post-transplant.

• Most patients had AML, ALL, MDS, or myeloproliferative neoplasia and received reduced-intensity conditioning and matched unrelated donor stem cells.

• Majority received post-transplant cyclophosphamide for GVHD prophylaxis; median age was 63 and gender distribution was balanced.

• The study included an open-label cohort (n=15) and a placebo-controlled cohort (n=45), focusing on safety, pharmacology, and efficacy.

• Primary endpoints were safety and tolerability; key secondary endpoints included incidence of bloodstream infections, GI infections, acute GVHD, febrile neutropenia, and bacterial pathogen abundance.

Safety and tolerability

• SER-155 was generally well tolerated, with diarrhea and nausea as the most common AEs, slightly higher than placebo.

• No treatment-related serious adverse events, SUSARs, or drug-related deaths occurred.

• Three deaths occurred before day 100 (one in SER-155, two in placebo), none related to SER-155.

• 48% of subjects experienced an SAE, with infections and infestations being the most common; none were related to SER-155.

• Adverse events of special interest were lower in the SER-155 arm (29%) compared to placebo (42%).