"Theriva Biologics, a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, announced the presentation of the previously disclosed blinded safety and pharmacokinetic (PK) data from the ongoing phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). These data will be featured in an ePoster Flash Session oral presentation at the Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global), taking place in Vienna, Austria from April 11-15, 2025.
Details on ePoster number E0145 can be found:
Presenting Author: Erik R. Dubberke, MD, Professor of Medicine, Clinical Director, Transplant Infectious Diseases, Washington University School of Medicine in St. Louis -- Title: Safety and tolerability of SYN-004 in allogeneic haematopoietic cell transplant (HCT) recipients receiving meropenem (MER) or piperacillin/tazobactam (P/T) -- Session: Infections in hemato-oncological hosts: from bacterial to viral (ePoster Flash Session) -- Date & Time: Saturday, April 12 at 1:30 p.m. CEST --Location: Arena 1 of the Messe Wien Exhibition and Conference Center, Vienna, Austria.
The ongoing randomized, double-blinded, placebo-controlled phase 1b/2a clinical trial is being conducted at Washington University School of Medicine in St. Louis. The trial is designed to evaluate the safety, tolerability, and potential absorption of oral SYN-004 (150 mg q.i.d. for a maximum of 28 days) into the systemic circulation of allogeneic HCT recipients who receive an IV antibiotic to treat fever. To mitigate risk, Cohort 1 of the study administered meropenem as the study-assigned antibiotic. Meropenem is a carbapenem antibiotic that is not metabolized by SYN-004. Patients in Cohort 2 were administered piperacillin/tazobactam as the study-assigned antibiotic and patients in Cohort 3 will receive cefepime. Piperacillin and cefepime can be metabolized by SYN-004. The trial is also designed to evaluate potential protective effects of SYN-004 on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allogeneic HCT recipients. The trial is expected to enroll up to 36 participants with three sequential cohorts, each evaluating a different study-assigned IV beta-lactam antibiotic. Safety and pharmacokinetic data for each cohort is reviewed by an independent Data and Safety Monitoring Committee that makes a recommendation on whether to proceed to the next IV beta-lactam antibiotic.
SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of Clostridioides difficile infection (CDI), overgrowth of pathogenic organisms, the emergence of antimicrobial resistance (AMR) and acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients. Allogeneic HCT recipients routinely receive long courses of IV beta-lactam antibiotics to treat infection following conditioning therapy. Antibiotic-mediated damage of the gut microbiome in allogeneic HCT recipients may lead to adverse outcomes including CDI, VRE colonization and potentially fatal bacteremia and aGVHD. A previously completed placebo-controlled phase 2b clinical trial of 412 patients demonstrated SYN-004 protected the gut microbiome from antibiotic-mediated dysbiosis. Patients who received SYN-004 also demonstrated significantly better maintenance and recovery of the gut microbiome as well as lower incidences of new colonization by opportunistic and potentially pathogenic microorganisms such as VRE.
Theriva Biologics is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need.
