Seres Therapeutics Reports SER-155 Phase 1b Cohort 1 Results Showing Successful Drug Bacteria Engraftment and Substantial Reduction in Pathogen Domination in the Gastrointestinal Microbiome
– Tolerability profile observed supports continued development in Cohort 2, with no treatment attributed serious adverse events –
– Reduction in incidences of microbiome pathogen domination provides support for intended SER-155 clinical activity –
–SER-155 Phase 1b placebo-controlled Cohort 2 data readout anticipated in mid-2024 –
– Conference call at
“We are pleased with these initial SER-155 Phase 1b study results from Cohort 1, which provide encouraging evidence to support our clinical objective of reducing enteric-derived infections, resulting bloodstream infections, and graft-versus-host disease in individuals undergoing allo-HSCT for cancers and other serious conditions,” said
SER-155 Phase 1b Study Design and Summary of Cohort 1 Results
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
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
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
Conference Call Information
Seres’ management will host a conference call today,
To access the conference call, please dial 800-715-9871 (domestic) or 646-307-1963 (international) and reference Conference ID 5098595. To join the live webcast, please visit the ‘Investors and News’ section of the Seres website at www.serestherapeutics.com.
A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.
SER-155 is a consortium of bacterial species selected using Seres’ reverse translation discovery and development platform technologies. The design incorporates microbiome biomarker data from human clinical data and nonclinical human cell-based assays and in vivo disease models. The SER-155 composition aims to decrease the colonization and abundance of bacterial pathogens that can harbor antibiotic resistance and to enhance epithelial barrier integrity in the GI tract to both reduce the likelihood of pathogen translocation and decrease the incidence of bloodstream infections. Further, SER-155 is designed to modulate host immune responses to decrease GvHD.
Forward-Looking Statements and Disclosures
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including the timing of additional clinical data, the ability of microbiome therapeutics to prevent or reduce infections, the ultimate safety and efficacy data of SER-155, final study results, and other statements which are not historical fact.
These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding; our limited operating history; the impact of the COVID-19 pandemic; our unproven approach to therapeutic intervention; our reliance on third parties and collaborators to conduct our clinical trials, manufacture our product candidates and develop and commercialize VOWST or any other product candidates, if approved; the unknown degree and competing factors of market acceptance for VOWST; the competition we will face; our ability to protect our intellectual property; and our ability to retain key personnel and to manage our growth. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K filed with the
SER-155 is covered by certain intellectual property exclusively licensed to Seres from MSK. Drs.
- Peled, J, Gomes, A, Devlin, S, et al. (2020). Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med. 382(9), 822–834. DOI: 10.1056/nejmoa1900623
- Stein-Thoeringer, C, Nichols, K, Lazrak, A, et al. (2019). Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science. 366(6469), 1143–1149. DOI: 10.1126/science.aax3760
- Taur, Y, Xavier, J, Lipuma, L, et al. (2012). Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Clinical Infectious Diseases. 55(7), 905–914. DOIL 10.1093/cid/cis580
Center for International Blood and Marrow Transplant Research
Broder, M, Quock, T, Chang, E, et al. (2017). The Cost of Hematopoietic Stem-Cell Transplantation in
the United States. American Health & Drug Benefits. 10(7), 366–374. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726064/
- Seres internal estimates
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