SER-155 / Memorial Sloan-Kettering Cancer Center, Seres Therap - LARVOL DELTA

Preliminary Safety Results of the Open-Label Phase of a 2-Part Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of an Investigational Microbiome Therapeutic, SER-155, in Adults Undergoing Hematopoietic Cell Transplantation (ASH 2023) - "Following screening, patients received two treatment courses (before conditioning and after neutrophil engraftment) comprised of microbiome conditioning with 4 days of oral vancomycin (to facilitate engraftment of SER-155 strains) followed by 10 days of oral SER-155 (see study design schematic, Figure 1)...8%) received tacrolimus/methotrexate-based GvHD prophylaxis... In patients enrolled in this open-label Cohort 1 of this Phase 1b study, SER-155 was well-tolerated through Day 100. Although sample size is limited, the observed safety and tolerability profile of SER-155 in this patient population is consistent with multiple preclinical assessments supporting the safety of SER-155 for therapeutic use. Enrollment in the double-blind, randomized, placebo-controlled second cohort to assess safety, efficacy, and changes in microbiome composition and function is ongoing."

Clinical • P1 data • PK/PD data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Classical Hodgkin Lymphoma • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation

Impact of Investigational Microbiome Therapeutic SER-155 on Pathogen Domination: Initial Results from a Phase 1b Study in Adults Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT) (ASH 2023) - P1 | " Study patients received two treatment courses of SER-155 (before conditioning and after neutrophil engraftment), each comprised of microbiome conditioning with 4 days oral vancomycin (to facilitate engraftment of SER-155 strains into the GI microbiome) followed by 10 days of oral SER-155. The observation of SER-155 strain engraftment before transplant and low incidence of GI pathogen domination after transplant through Day 30 are encouraging, although these preliminary data are limited by the small size of this open-label cohort of HCT patients. These observations are consistent with the design and preclinical evaluation of SER-155, supporting further development of this investigational cultivated microbiome therapeutic. Enrollment in the second double-blind, randomized, placebo-controlled cohort (approximately 60 participants) has initiated following a preplanned review by the Data Safety Monitoring Committee."

Clinical • P1 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Transplantation

Following recent constructive FDA feedback, Seres anticipates finalizing SER-155 Phase 2 study protocol for the prevention of bloodstream infections in adults undergoing allogeneic hematopoietic stem cell transplant for the treatment of hematological malignancies (The Manila Times) - "The study is planned to enroll approximately 248 participants, and the interim data analysis is expected when approximately half of the enrolled participants have reached the primary endpoint. This interim analysis, which is projected to be within 12 months following study initiation, will facilitate timely engagement with the FDA on the design of a Phase 3 study and inform development in adjacent medically vulnerable patient populations."

Clinical protocol • FDA event • Hematological Malignancies • Transplantation

Clinical and Microbiology Outcomes of Bloodstream Infections (BSI) in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplant (allo-HCT) in a Randomized, Double-blind, Placebo-controlled Cohort 2 of a Phase 1b Study of SER-155, an Investigational Live Biotherapeutic (IDWeek 2025) - No abstract available

Clinical • P1 data • Infectious Disease

Financial Results (Seres Therapeutics Press Release) - "Research and development (R&D) expenses for the second quarter of 2025 were $12.9 million, compared with $15.8 million for the second quarter of 2024. The decrease in R&D expenses was primarily driven by a decrease in expenses resulting from completion of the SER-155 Phase 1b study, lower personnel and related expenses, and a decrease in platform investments."

Commercial • Transplantation

Seres engaging with multiple parties regarding various deal structures, including potential business development and partnerships, intended to secure additional capital and other resources to enable the clinical advancement of SER-155 and additional live biotherapeutic product candidates (The Manila Times) - "Further development of SER-155 is supported by previously disclosed Phase 1b placebo-controlled study results that showed a significant reduction (77% relative risk reduction) in bloodstream infections in a high-risk patient population: adults undergoing allogeneic hematopoietic stem cell transplant...In addition to allo-HSCT, the Company intends to evaluate SER-155 and other cultivated live biotherapeutic candidates in other medically vulnerable patient populations including autologous-HSCT patients, cancer patients with neutropenia, CAR-T recipients, individuals with chronic liver disease, solid organ transplant recipients, as well as patients in the intensive care unit and long-term acute care facilities."

Commercial • Chemotherapy-Induced Neutropenia • Immunology • Transplantation

Exploratory analyses of immune reconstitution biomarkers from a Ph1b study of an investigational, oral, live biotherapeutic, SER-155, in adult allo-HCT. (ASCO 2025) - P1 | " Participants were randomized 1:1 to receive 4 days of oral vancomycin (for microbiome conditioning) and 10 days of SER-155 or placebo/placebo administered pre-HCT (course 1) and post-neutrophil engraftment (course 2). The significantly higher concentrations of IL7 with SER-155 treatment and observed frequency of CD4+ T cells support the potential role of the GI microbiome in promoting homeostatic expansion of peripheral T cells and immune reconstitution important for successful HCT. Median plasma IL7 and IL15 (pg/mL), SER-155 vs. placebo (generalized linear model)."

Biomarker • Clinical • Infectious Disease • Inflammation • CD4 • IL15 • IL7

Seres Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Updates (GlobeNewswire) - "Anticipated Upcoming Milestones and Events: Provide updates regarding SER-155 partnership discussions; Submit to FDA a protocol for a SER-155 Phase 2 study in allo-HSCT in the coming weeks; Present additional SER-155 clinical results at the American Society of Clinical Oncology (ASCO) 2025 conference taking place from May 30 to June 3, 2025....Research and development (R&D) expenses for the first quarter of 2025 were $11.8 million, compared with $19.5 million for the first quarter of 2024. The decrease in R&D expenses was primarily driven by lower personnel expenses, a decrease in platform investments, and a decrease in expenses related to SER-155 Phase 1b study."

Clinical protocol • Commercial • New P2 trial • P1 data • Immunology • Infectious Disease • Transplantation

PHARMACOKINETIC (PK) AND PHARMACODYNAMIC (PD) RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED COHORT 2 OF A PHASE 1B STUDY OF AN INVESTIGATIONAL, ORAL, LIVE BIOTHERAPEUTIC, SER-155, IN ADULTS UNDERGOING ALLO-HCT (DDW 2025) - P1 | "Patients were randomized 1:1 to receive vancomycin/SER-155 or placebo/placebo administered pre-HCT and post-neutrophil engraftment ( Fig. Demographics were balanced between treatment arms. Of 45 patients randomized, 34 (SER-155, 20; placebo, 14) were treated and received allo-HCT; 28 received treatment course 2 after neutrophil engraftment (SER-155, 19; placebo, 9). SER-155 was generally well tolerated: serious TEAEs were similar between arms (SER-155, 52%; placebo, 42%) with no drug-related serious TEAEs observed."

Clinical • P1 data • PK/PD data • Gastrointestinal Disorder • Infectious Disease • Inflammation • IL10 • IL17A • TNFA

Seres Therapeutics Presents Data at the 2025 Digestive Disease Week Conference Highlighting the Potential for Live Biotherapeutics to Treat Inflammatory and Immune Diseases (GlobeNewswire) - "Seres Therapeutics, Inc...today announced that it will present three related posters at the upcoming 2025 Digestive Disease Week (DDW) Conference being held May 3-6, 2025, in San Diego, CA....New results presented at the DDW conference could help identify candidate biomarkers to support the further clinical development of live biotherapeutics to treat inflammatory and immune diseases, including ulcerative colitis and Crohn’s disease."

Biomarker • Clinical data • Crohn's disease • Ulcerative Colitis

SAFETY AND EFFICACY OF SER-155, AN INVESTIGATIONAL LIVE BIOTHERAPEUTIC: RESULTS FROM A RANDOMIZED, PLACEBO-CONTROLLED COHORT 2 OF A PHASE 1B STUDY IN ADULTS UNDERGOING ALLO-HCT (EBMT 2025) - P1 | " Participants were randomized 1:1 to receive 10 days of SER-155 (preceded by 4 days of vancomycin) or placebo/placebo, administered in 2 courses (pre-HCT and post-neutrophil engraftment)...Demographics and transplant characteristics were mostly balanced between arms, though fewer participants in the SER-155 arm received post-transplant cyclophosphamide (PTCy)-based GvHD prophylaxis (70% and 93%, respectively) (Table).Table... SER-155 was generally well-tolerated and the majority of SER-155 strains engrafted in the GI tract. The lower incidence of BSI and reduced antibiotic utilization for SER-155 treated participants support further development in allo-HCT. Clinical Trial Registry: NCT04995653"

Clinical • P1 data • Febrile Neutropenia • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Neutropenia

INVESTIGATIONAL LIVE BIOTHERAPEUTIC SER-155 : BIOMARKER INSIGHTS FROM A PHASE 1B STUDY IN ADULTS UNDERGOING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLO-HCT) (EBMT 2025) - P1 | " Subjects were randomized 1:1 to receive vancomycin/SER-155 (oral vanc for microbiome conditioning) or placebo/placebo administered in 2 courses, one pre-HCT and one following neutrophil engraftment. The SER-155 live biotherapeutic engrafted in the GI tract, was generally well-tolerated, and is associated with a reduction in BSI incidence, and with a decrease in both fecal albumin and systemic inflammatory markers compared to placebo in the window between treatment course 1 and transplant. These data are consistent with SER-155 MoA design targets of 1) reducing BSIs by improving GI barrier integrity and preventing bacterial translocation, and 2) regulation of systemic inflammatory responses. These results support further development in allo-HCT."

Biomarker • Clinical • P1 data • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Systemic Inflammatory Response Syndrome • Transplantation • CXCL8 • IL10 • IL17A • TNFA

INVESTIGATIONAL LIVE BIOTHERAPEUTIC SER-155 : BIOMARKER INSIGHTS FROM A PHASE 1B STUDY IN ADULTS UNDERGOING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (ALLO-HCT) (EBMT 2025) - P1 | " Subjects were randomized 1:1 to receive vancomycin/SER-155 (oral vanc for microbiome conditioning) or placebo/placebo administered in 2 courses, one pre-HCT and one following neutrophil engraftment. The SER-155 live biotherapeutic engrafted in the GI tract, was generally well-tolerated, and is associated with a reduction in BSI incidence, and with a decrease in both fecal albumin and systemic inflammatory markers compared to placebo in the window between treatment course 1 and transplant. These data are consistent with SER-155 MoA design targets of 1) reducing BSIs by improving GI barrier integrity and preventing bacterial translocation, and 2) regulation of systemic inflammatory responses. These results support further development in allo-HCT."

Biomarker • Clinical • P1 data • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Systemic Inflammatory Response Syndrome • Transplantation • CXCL8 • IL10 • IL17A • TNFA

Seres Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Present SER-155 Phase 1b clinical and exploratory translational biomarker data as a Top 100 abstract at the European Bone Marrow Transplant meeting in March 2025, facilitating engagement with potential European investigators in support of the Company’s planned global study. Additionally, exploratory translational biomarker data from across Seres’ programs, including in allo-HSCT and IBD, have been accepted for poster presentations at Digestive Disease Week (DDW) in May 2025."

Biomarker • Clinical data • P1 data • Bone Marrow Transplantation • Immunology • Inflammatory Bowel Disease • Transplantation

Seres Therapeutics Receives Feedback From FDA on SER-155 Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT) Development Approach (GlobeNewswire) - "Seres Therapeutics, Inc...today announced that it has received constructive feedback from a Type B Breakthrough Therapy designation engagement with the U.S. Food and Drug Administration (FDA or the agency) regarding the Company’s development strategy for its lead live biotherapeutic, SER-155 in patients undergoing allo-HSCT. The FDA provided feedback on important elements of the next study that included a recommendation that it be a Phase 2 and support for a reduction in bloodstream infections as of 30 days post HSCT as the primary endpoint; and confirmed their expectations for the manufacture and control of SER-155. Further interaction with FDA is expected in the coming weeks as the Company has submitted questions to clarify certain feedback received. Seres is evaluating the next study design...anticipates submitting a proposed protocol, incorporating FDA’s feedback, for the next study of SER-155 in allo-HSCT to the agency in the second quarter of this year."

Clinical protocol • FDA event • Immunology • Transplantation

Pharmacokinetic (PK) and Pharmacodynamic (PD) Results from a Randomized, Double-Blind, Placebo-Controlled Cohort 2 of a Phase 1b Study of an Investigational, Oral, Live Biotherapeutic, SER-155, in Adults Undergoing Allo-HCT (TCT-ASTCT-CIBMTR 2025) - P1 | "Study Design and Patients were randomized 1:1 to receive vancomycin/SER-155 or placebo/placebo administered pre-HCT and post-neutrophil engraftment ( Fig. SER-155 engraftment was robust with a majority of strains detected after the 1st and 2nd courses, and SER-155 species represented >10% of the GI microbiome during the peri-transplant period. These PK and PD data are consistent with the SER-155 design targets and support further development in allo-HCT."

Clinical • P1 data • PK/PD data • Gastrointestinal Disorder • Infectious Disease • Inflammation • IL10 • IL17A • TNFA

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 (TCT-ASTCT-CIBMTR 2025) - P1 | "Study Design and 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. 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."

Clinical • P1 data • Febrile Neutropenia • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Infectious Disease • Neutropenia

A Study of SER-155 to Treat Diarrhea in People on Immunotherapy (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • Gastrointestinal Disorder • Oncology

Seres Therapeutics Announces New Translational Biomarker Results from SER-155 Phase 1b Clinical Study and Provides Corporate Updates (GlobeNewswire) - P1 | N=60 | NCT04995653 | Sponsor: Seres Therapeutics, Inc. | "Following SER-155 administration, there was a statistically significant decrease in fecal albumin, an established biomarker of epithelial barrier integrity, and a positive impact on biomarkers of systemic inflammation and immune homeostasis...The lower concentrations of plasma biomarkers of systemic inflammation, and changes in immune homeostasis observed following SER-155 dosing reinforce the positive impact in allo-HSCT patients...Seres’ SER-155 Phase 1b clinical study results have been accepted for an oral presentation in the Best Abstracts in Infectious Diseases track and the related drug pharmacology results have been accepted as a poster presentation at the February 2025 TANDEM Meeting...The Company submitted a Briefing Book in support of its planned interaction with FDA on a potential next registrational study of SER-155 in allo-HSCT and expects feedback from the agency this quarter."

FDA event • P1 data • Transplantation

FDA Grants Breakthrough Therapy Designation to Seres Therapeutics’ SER-155 for Reduction of Bloodstream Infections in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT) (Seres Therapeutics Press Release) - "Seres Therapeutics, Inc...announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to SER-155...for the reduction of bloodstream infections (BSIs) in adults undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT) for the treatment of hematological malignancies...The SER-155 Breakthrough Therapy designation was supported by positive data from our recent SER-155 Phase 1b clinical trial (NCT04995653)."

Breakthrough therapy • Transplantation

Seres Therapeutics to Participate in 2025 J.P. Morgan Healthcare Conference (Seres Therapeutics Press Release) - "Seres will highlight its plans to advance its biotherapeutics pipeline, focusing on SER-155, the Company’s lead program...Seres is actively seeking a partner to provide financial resources and other capabilities to more fully explore the development of SER-155 and additional pipeline candidates for these populations."

Commercial • Graft versus Host Disease • Transplantation

SER-155-001: A Multiple Dose Study to Evaluate Safety, Tolerability, PK, and Efficacy of SER-155 in Adults Undergoing HSCT (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: Seres Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Infectious Disease • Transplantation

Biomarkers in a phase 1b study of investigational microbiome therapeutic SER-155 in adults undergoing allogeneic hematopoietic cell transplantation (allo-HCT). (ASCO 2024) - P1 | "Patients received 2 courses of SER-155 (pre-HCT and post-neutrophil engraftment, each comprised of 4 days of microbiome conditioning with oral vancomycin followed by 10 days oral SER-155. In this small open-label cohort, SER-155 was generally well-tolerated through Day 100 without drug-related SAEs and no severe aGvHD. Plasma biomarkers were not elevated at HCT Day 0 or neutrophil recovery. These preliminary observations align with the design and preclinical evaluation of SER-155."

Biomarker • Clinical • P1 data • Acute Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Oncology • Transplantation • IFNG • IL6 • REG3A • ST2 • TNFA

SER-155-001: A Multiple Dose Study to Evaluate Safety, Tolerability, PK, and Efficacy of SER-155 in Adults Undergoing HSCT (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: Seres Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Infectious Disease • Transplantation

SERES THERAPEUTICS ANNOUNCES COMPLETION OF PATIENT ENROLLMENT FOR SER-155 PHASE 1B COHORT 2 CLINICAL TRIAL IN ALLOGENIC HSCT - "Seres Therapeutics, Inc...announced today that enrollment is complete in the placebo-controlled Cohort 2 of its Phase 1b trial of SER-155 in patients who received Allogeneic Hematopoietic Stem Cell Transplantation...The SER-155 Phase 1b study (NCT04995653) is being conducted across 13 clinical centers in the US, including Memorial Sloan Kettering . Study Cohort 1, which included 13 participants, was designed to assess safety and drug pharmacology, including the engraftment of drug bacteria in the gastrointestinal tract...Study Cohort 2, which includes 45 participants, incorporates a randomized, double-blinded placebo-controlled 1:1 design to further evaluate safety and engraftment, as well as clinical outcomes."

Enrollment closed • Transplantation