SER-155 is an investigational, oral, 16 strain, cultivated microbiome therapeutic designed to prevent colonization and reduce the abundance of ESKAPE pathogens (e.g., from families such as Enterococcaceae, Enterobacteriaceae, Streptococcaceae, Staphylococcaceae) in the GI tract to reduce the risk of enteric driven bloodstream infections and other downstream consequences, such as GvHD, in patients receiving allo-HSCT. SER-155 has the potential to impact antimicrobial resistance (AMR), including infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE). The development of SER-155 is informed by preclinical data that showed that allo-HSCT patients across multiple study sites had disrupted microbiomes and were susceptible to pathogen overgrowth in the GI tract, as well as in vivo studies that demonstrated SER-155's ability to significantly decolonize VRE and CRE, and further modulate epithelial barrier integrity and T cell biology or relevance to GvHD. Previously published exploratory results from the SER-109 ECOSPOR III Phase 3 study showed decolonization of gut pathogens, including bacteria that carry antibiotic resistance genes, providing clinical proof-of-concept for the SER-155 program. The SER-155 Phase 1b study includes two cohorts, with Cohort 1 designed to assess safety and drug pharmacology, including the engraftment of drug bacteria in the gastrointestinal tract. Cohort 1 included 13 subjects who received any dosing of the SER-155 regimen, with 11 of these subjects subsequently receiving an allo-HSCT. Nine subjects had evaluable samples for microbiome data analyses. The average age in Cohort 1 was 60, and most subjects had acute myeloid leukemia, myelodysplastic syndrome or myeloproliferative neoplasia as their primary disease and received reduced-intensity conditioning pre-transplant. Most subjects received peripheral blood stem cells from a matched unrelated donor. Neutrophil engraftment was observed in all subjects. The majority of subjects received a tacrolimus-based regimen for GvHD prophylaxis. “The Phase 1b data provide important mechanistic insights that support the potential utility of microbiome therapeutics such as SER-155 to individuals receiving allo-HSCT,” said Matthew Henn, Ph.D., Chief Scientific Officer at Seres. “Study data from Cohort 1 suggest that SER-155 administration results in substantially lower incidence rates of gastrointestinal pathogen domination with ESKAPE pathogens of clinical concern, including Enterococcaceae, Enterobacteriaceae, Streptococcaceae and Staphylococcaceae. These are bacteria that can include antibiotic resistant strains such as carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE).” Published data have demonstrated an association between the incidence of GI domination with ESKAPE pathogens in allo-HSCT patients and the risk of serious infections, GvHD, and mortality.1,2,3 Reducing the incidence of domination of ESKAPE pathogens in the GI microbiome through administration of a microbiome therapeutic has the potential to meaningfully reduce enteric infections, enteric driven blood stream infections and GvHD in this medically compromised patient population and more broadly. “Allogeneic hematopoietic stem cell transplantation can be a highly effective approach to treat serious cancers, however, the process results in a high risk of complications, including infections and graft-versus-host disease,” said Marcel van den Brink, M.D., Ph.D., Head, Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center (MSK). “Microbiome therapeutics have the potential to address underlying mechanisms that may be involved in many of the issues faced during allo-HSCT. These encouraging initial SER-155 results, particularly the very low levels of gastrointestinal pathogen domination observed, provide support for the promise of these approaches to lead to important clinical benefits.” Enrollment of Cohort 2 is ongoing, incorporating a randomized, double-blinded placebo-controlled design to further evaluate safety, drug strain engraftment, and incidence of gastrointestinal ESKAPE pathogen domination, as well as the incidence of enteric infections, enteric driven blood stream infections and GvHD. Cohort 2 will enroll approximately 60 subjects administered either SER-155 or placebo at a 1:1 ratio. The Company anticipates obtaining top-line placebo-controlled day-100 data from study Cohort 2 in mid-2024. Seres believes that the medical benefit and commercial potential for SER-155 is substantial. Nearly 30,000 allo-HSCT procedures are performed in the U.S. and Europe per year.4 Complications are frequent and costly, with additional costs for patients with complications averaging approximately $180,000/year.5,6 Infections and GvHD are estimated to result in nearly half of mortality associated with allo-HSCT.4 With the exception of an exclusive license from MSK, Seres fully owns worldwide rights for commercialization of SER-155. In addition to SER-155, the Company is evaluating other microbiome therapeutic preclinical programs for additional medically compromised patient populations who are at risk of life-threatening infections. 來自網(wǎng)站ir.serestherapeutics.