FDA Grants Breakthrough Therapy Designation to Seres Therapeutics’ SER-155 for Bloodstream Infections

Seres Therapeutics, Inc. (Seres or the Company) announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to SER-155, the Company’s lead investigational program, for the reduction of bloodstream infections (BSIs) in adults undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT) for the treatment of hematological malignancies. In September 2024, Seres reported topline clinical data from Cohort 2 of its SER-155 Phase 1b placebo-controlled study in patients undergoing allo-HSCT, in which SER-155 was associated with a significant reduction in BSIs (77% relative risk reduction), a significant reduction in systemic antibiotic exposure, and lower incidence of febrile neutropenia, in each case as compared to placebo, through day 100 post-HSCT. Additionally, SER-155 was generally well tolerated, with no observed treatment-related serious adverse events.

FDA Breakthrough Therapy designation ensures communication and guidance from FDA to expedite the development of medicines which are intended to treat serious or life-threatening diseases, and in which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint over available therapies. The receipt of Breakthrough Therapy designation for SER-155, the Company’s second program to receive such designation, grants Seres access to FDA senior management and a commitment from FDA to work closely with the Company, facilitating an efficient drug development process. In December 2023, SER-155 received FDA Fast Track designation for reducing the risk of infection and GvHD in this patient population.

“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. We are excited to advance the development of SER-155, working diligently to bring this innovative therapeutic to patients in need, while also exploring its potential use in other high-risk patient populations to maximize its impact,” said Eric Shaff, President and Chief Executive Officer of Seres Therapeutics.

Lisa von Moltke, M.D., Chief Medical Officer of Seres Therapeutics continued, “This Breakthrough Therapy designation was supported by compelling clinical data demonstrating the potential of SER-155 to significantly reduce bacterial bloodstream infections and associated complications. We intend to meet with FDA in the first quarter of 2025 to discuss the next clinical study of SER-155 in allo-HSCT, which we believe could be a single registrational study for efficacy. We look forward to working closely with the agency on our development plans for SER-155, aimed at addressing this significant unmet need in patients undergoing allo-HSCT.”

The SER-155 Breakthrough Therapy designation was supported by positive data from our recent SER-155 Phase 1b clinical trial. Patients who received SER-155 experienced a significantly lower incidence of bacterial BSIs as compared with the placebo arm (2/20 (10%) vs. 6/14 (42.9%), respectively; [Odds Ratio: 0.15; 95% CI: 0.01, 1.13, p=0.0423]), representing a 77% relative risk reduction. In addition, while antibiotic starts were similar in each arm, patients administered SER-155 were treated with antibiotics for a significantly shorter duration compared to patients in the placebo arm (9.2 days vs. 21.1 days, respectively, with a mean difference of -11.9 days [95% CI: -23.85, -0.04; p=0.0494]). Further, the incidence of febrile neutropenia was reduced, and gastrointestinal pathogen domination was substantially lower compared to a historical control cohort, providing further evidence of SER-155’s activity in modulating the microbiome to address critical post-transplant complications. SER-155 was well tolerated with no treatment related serious adverse events and engrafted as expected in the gastrointestinal tract.

Bloodstream infections in allo-HSCT patients are frequent, serious, and potentially fatal. In clinical practice, HSCT patients who experience a BSI or febrile neutropenia are aggressively treated, often with broad-spectrum antibiotics, as infections are a leading cause of death in these patients in the first 100 days post-transplant. While prophylaxis of BSIs with antibiotics is common, antibiotics do not address the root cause as SER-155 is designed to do.

Recent market research conducted by Seres characterized a significant commercial opportunity for SER-155 in allo-HSCT. Health Care Providers (HCPs) treating allo-HSCT patients indicated a high level of concern regarding BSIs. Additionally, HCPs stated that they would rapidly add a product providing similar efficacy to what we have observed in our SER-155 study to standard treatment protocols. The approximately 40,000 worldwide allo-HSCT patients are treated in a subset of large oncology centers across the globe, enabling rapid and efficient education of HCPs about SER-155, if approved.

In addition to allo-HSCT, bloodstream infections are a common and serious complication in many other medically vulnerable populations, including autologous-HSCT patients, cancer patients with neutropenia, CAR-T recipients, individuals with chronic liver disease, solid organ transplant recipients, as well as patients in the intensive care unit and long-term acute care facilities. Seres intends to explore development of SER-155 and additional pipeline candidates for these populations. The targeted patient populations for SER-155 and Seres’ other pipeline candidates could represent multiple blockbuster commercial opportunities.

Seres is actively seeking a partner to provide financial resources and other capabilities to support the Company’s goal to maximize the SER-155 program opportunity, while pursuing a capital-efficient development approach.