Seres Therapeutics Announces SER-155 Phase 1b Results in Allo-HSCT Patients

Seres Therapeutics, Inc. has announced significant findings from Cohort 2 of its Phase 1b placebo-controlled study of SER-155, a live oral biotherapeutic designed to prevent gastrointestinal-derived bacterial bloodstream infections (BSIs) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This patient group is highly susceptible to severe infections that often lead to life-threatening complications.

The study's results indicate that SER-155 substantially reduced the incidence of BSIs and systemic antibiotic use compared to placebo through day 100 post-transplant. Moreover, there was a lower occurrence of febrile neutropenia in patients treated with SER-155. Importantly, the therapy exhibited a generally well-tolerated safety profile without treatment-related serious adverse events.

SER-155 has been cultivated from clonal master cell banks to prevent BSIs and other related complications. The study divided participants into two cohorts. Cohort 1 focused on safety and drug pharmacology, specifically the drug strain's engraftment in the gastrointestinal tract. This cohort included 13 subjects who received any dosing of the SER-155 regimen, with most subsequently undergoing an allo-HSCT. The results from this cohort, announced in May 2023, showed good tolerability and successful drug strain engraftment, reducing pathogen domination in the GI microbiome compared to historical controls.

Cohort 2 utilized a randomized, double-blinded 1:1 placebo-controlled design to further assess safety and drug strain engraftment, as well as secondary and exploratory endpoints, including the incidence of BSIs and other medical consequences. This cohort included 45 patients in the intention-to-treat (ITT) population, with 20 receiving SER-155 and 14 receiving placebo. Clinical evaluation data were available through day 100, the study's primary observation point.

Key findings from Cohort 2 showed a significant reduction in BSIs in the SER-155 group compared to the placebo group (2/20 vs. 6/14, respectively). Additionally, although the number of antibiotic starts was similar in both groups, patients treated with SER-155 required significantly fewer days of antibiotic treatment (9.2 days vs. 21.1 days). The incidence of febrile neutropenia was also lower in the SER-155 group (65% vs. 78.6%), though this difference was not statistically significant.

The study also noted that recent changes in the allo-HSCT standard of care, including increased use of post-transplant cyclophosphamide for graft-versus-host disease (GvHD) prophylaxis, have generally reduced GvHD rates in this patient population. In the study, GvHD rates were low, with only a few cases of grade 2 GvHD and no instances of higher-grade GvHD.

The promising results from this Phase 1b study support Seres Therapeutics' strategy to advance SER-155 and other live biotherapeutics for the prevention of serious bacterial infections in medically vulnerable populations. The company plans to seek Breakthrough Therapy designation from the FDA to expedite the development and potential approval of SER-155 for allo-HSCT patients. Additionally, Seres aims to explore the use of SER-155 in other patient groups at high risk of severe bacterial infections.

Seres' Chief Medical Officer, Lisa von Moltke, M.D., expressed optimism about the results, emphasizing the importance of addressing bacterial infections in patients undergoing allo-HSCT. Infectious disease expert David Fredricks, M.D., highlighted the potential of live oral biotherapeutics like SER-155 to improve patient outcomes and reduce antibiotic use.

With these results, Seres Therapeutics aims to engage with the FDA and advance the development of SER-155, potentially addressing a broader range of patient populations, including those undergoing autologous stem cell transplants, CAR-T therapy, and organ transplants. The company owns worldwide rights for the commercialization of SER-155 and continues to explore its application in various medically vulnerable groups.