Seres Therapeutics' investigational live biotherapeutic, SER-155, is showing promise in reducing bloodstream infections (BSIs) in adults undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT) for hematological malignancies. The FDA has granted Breakthrough Therapy designation to SER-155, based on positive Phase 1b clinical trial data. This designation aims to expedite the development and review of drugs intended to treat serious conditions where preliminary evidence indicates significant improvement over existing therapies.
The Phase 1b study demonstrated a 77% relative risk reduction in bacterial BSIs compared to placebo in patients receiving SER-155. The study also showed a significant reduction in systemic antibiotic exposure and a lower incidence of febrile neutropenia through day 100 post-transplant. SER-155 was generally well tolerated, with no treatment-related serious adverse events reported.
Biomarker Data Supports Mechanism of Action
New translational biomarker results from the Phase 1b study further support SER-155's mechanism of action. Data showed that SER-155 promoted epithelial barrier integrity, as indicated by a statistically significant decrease in fecal albumin, a biomarker of intestinal permeability. Additionally, SER-155 had a positive impact on biomarkers of systemic inflammation and immune homeostasis compared to placebo.
Wendy Garrett, M.D. Ph.D., Professor of Immunology and Infectious Diseases at Harvard T.H. Chan School of Public Health, commented, "The SER-155 translational biomarker data, combined with the promising clinical results demonstrating an impressive reduction in bloodstream infection rates, provide strong biological evidence supporting Seres’ live biotherapeutic candidates as a novel potential therapeutic approach to improve epithelial barrier integrity and to positively modulate multiple inflammatory pathways."
Addressing Unmet Needs in Allo-HSCT
Bloodstream infections are a major complication in allo-HSCT patients, often leading to aggressive treatment with broad-spectrum antibiotics. Current antibiotic prophylaxis strategies do not address the root cause of these infections. SER-155 is designed to decolonize GI pathogens, improve epithelial barrier integrity, and induce immune tolerance, potentially preventing BSIs and antimicrobial-resistant infections.
Future Development Plans
Seres Therapeutics is planning to meet with the FDA in the first quarter of 2025 to discuss the next clinical study of SER-155 in allo-HSCT, which the company believes could be a single registrational study for efficacy. The company is also seeking a strategic partner to provide financial resources and expertise to maximize the SER-155 program and explore its potential in other high-risk patient populations, including autologous-HSCT patients, cancer patients with neutropenia and CAR-T recipients.
Eric Shaff, President and Chief Executive Officer of Seres Therapeutics, stated, "We are thrilled that the FDA has granted Breakthrough Therapy designation to SER-155, underscoring the strength of our Phase 1b clinical data and the potential of this live biotherapeutic candidate to address one of the most significant complications faced by patients undergoing allo-HSCT."
