Safety and Efficacy Results from a Randomized, Double-Blind, Placebo-Controlled Cohort 2 of a Phase 1b Study of an Investigational Live Biotherapeutic, SER-155, in Adults Undergoing Allo-HCT

Background Bloodstream infections (BSI) are common in patients undergoing allo-HCT and often arise following pathogen domination of the intestinal microbiome in the setting of GI-barrier dysfunction. SER-155 is an investigational, oral live biotherapeutic comprised of 16 bacterial strains, designed to prevent BSI and infection-associated events. SER-155-001 (NCT04995653) was a 2-cohort Phase 1b study evaluating the safety, PK, and efficacy of SER-155 in adults undergoing allo-HCT. We present data from the randomized, double-blind, placebo-controlled Cohort 2 through day 100 post-HCT. Study Design and Methods Patients were randomized 1:1 to receive oral vancomycin/SER-155 or placebo/placebo, administered in 2 courses pre-HCT and post-neutrophil engraftment ( Fig. 1 ). The primary endpoints were safety and SER-155 strain engraftment (PK). Secondary efficacy endpoints included incidence of BSI, febrile neutropenia (FN), and aGvHD (MAGIC criteria). Exploratory endpoints included antibiotic and hospital utilization. Results Thirty-four patients (SER-155 = 20; placebo = 14) were treated and received allo-HCT (modified intention to treat [mITT-1] population) (Fig. 2 ). Demographics and transplant characteristics were mostly balanced between arms. The majority of SER-155 strains engrafted after each course. As expected for the HCT population, 98% of patients had at least 1 treatment-emergent adverse event (TEAE). Serious TEAEs were reported in 52% of patients in the SER-155 arm and 42% in the placebo arm; the most common system organ class was infections and infestations (SER-155 = 24%; placebo = 37%). No drug-related serious TEAEs were observed and no SER-155 species were identified in any clinical culture specimens. Three patients (SER-155 = 1; placebo = 2) died prior to Day 100; 1 patient (SER-155 arm) died after Day 100; none were deemed drug-related. Incidence of BSI was lower in SER-155 vs placebo-treated patients (10% vs 42.9%, respectively; [OR: 0.15; 95% CI: 0.01, 1.13, p=0.04); all occurred after HCT and pre-neutrophil engraftment. There was a significant difference between arms for Kaplan-Meier estimates of time to BSI ( Fig. 3 ). Systemic treatment antibiotic utilization was lower in SER-155 vs placebo (9.2 vs 21.1 days, respectively; mean difference -11.9 days [95% CI: -23.85, -0.04; p=0.05]). Mean days in hospital were lower in SER-155 vs placebo (19.7 vs 28.7 days; p=0.05 [ post hoc test]). Incidence of FN was numerically lower in SER-155 vs placebo (65% vs 78.6%, respectively; [OR: 0.51; 95% CI: 0.07, 2.99; p=0.47). There were 2 events of aGvHD Grade 2 observed in each arm and no aGvHD ≥ Grade 3 events. Conclusions SER-155 was generally well-tolerated, and most SER-155 strains engrafted in the GI tract. The lower incidence of BSI, fewer days in hospital, and less antibiotic utilization in SER-155 treated patients are encouraging and support further development in allo-HCT.