Preliminary Results of the Open-Label Phase of a 2-Part Phase 1b Study That Evaluates Safety, Tolerability, Pharmacokinetics, and Efficacy of Investigational Microbiome Therapeutic SER-155 in Adults Undergoing Allogeneic Hematopoietic Cell Transplantation (allo-HCT)

Background In patients undergoing allo-HCT, low gastrointestinal (GI) microbial diversity is associated with adverse outcomes including bloodstream infections (BSIs) and acute graft-versus-host disease (aGvHD). SER-155 is an investigational cultivated oral microbiome therapeutic designed to engraft in the GI tract, promote GI barrier integrity, and reduce pathogen domination. SER-155-001 is a 2-part, Phase 1b study evaluating the safety, pharmacokinetics (PK), and efficacy of SER-155 in adults undergoing allo-HCT. We present preliminary data from the open-label Cohort 1 through Day 100 post-HCT. Study Design and Methods Adult recipients of allo-HCT were eligible. HCT conditioning and aGvHD prophylaxis were as per investigator discretion. Key exclusion criteria included use of umbilical cord blood or ex vivo T-cell depleted HCT, receipt of fecal microbiota transplant/live biotherapeutic product ≤3 months before screening, CAR-T therapy, ANC <500 on the day of treatment, and/or evidence of relapse/progression of hematologic malignancy.Patients received 2 treatment courses (pre-HCT conditioning and after neutrophil engraftment) consisting of 4 days of oral vancomycin followed by 10 days of oral SER-155 (Fig. 1). The primary endpoint was safety. Stool samples collected pre- and post-HCT were used to evaluate engraftment of SER-155 strains post-treatment (PK) and GI pathogen domination, defined as a relative abundance of ≥30%). A post hoc comparison of GI domination was made using a historical cohort of HCT patients with similar characteristics from study site, MSKCC. Results Fifteen patients enrolled, 13 received any amount of study drug (median age 67; 54% male), and 11 received allo-HCT. Acute myeloid leukemia was the most common underlying disease (6 patients).SER-155 was generally well-tolerated. Treatment-emergent AEs were reported in all patients, with GI AEs the most common. No SAEs were deemed related to SER-155. Most SAEs and adverse events of special interest (i.e., BSI, invasive, or GI infections) occurred between HCT and the 2nd course of SER-155. There were no deaths before Day 100. No BSIs were reported as attributable to SER-155 strains.The majority of the 16 strains in SER-155 were detected in evaluable patients (median = 11 strains in 8 patients before conditioning; median = 12 strains in 7 patients after neutrophil engraftment). Between transplantation (Day 0) and Day 30, GI domination with potentially pathogenic bacteria occurred in 11% (1/9 patients) vs 64% (294/459 patients) in the historical cohort (Fig. 2). Conclusions SER-155 was well-tolerated through Day 100. SER-155 strains engrafted, and GI pathogen domination after transplant through Day 30 was low relative to the historical cohort. Although sample size is limited, these preliminary observations are consistent with the design and preclinical evaluation of SER-155.