Theriva Biologics announced the presentation of safety and pharmacokinetic data from its ongoing Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant recipients for the prevention of acute graft-versus-host-disease. The 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) in Vienna, Austria from April 11-15, 2025.
Dr. Erik R. Dubberke, Professor of Medicine and Clinical Director of Transplant Infectious Diseases at Washington University School of Medicine in St. Louis, will present the findings titled "Safety and tolerability of SYN-004 in allogeneic haematopoietic cell transplant (HCT) recipients receiving meropenem (MER) or piperacillin/tazobactam (P/T)" on Saturday, April 12 at 1:30 p.m. CEST.
Phase 1b/2a Trial Design and Objectives
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 evaluates the safety, tolerability, and potential absorption of oral SYN-004 administered at 150 mg four times daily for a maximum of 28 days into the systemic circulation of allogeneic hematopoietic cell transplant recipients who receive IV antibiotics to treat fever.
The study employs a sequential cohort design with up to 36 participants across three cohorts, each evaluating a different study-assigned IV beta-lactam antibiotic. To mitigate risk, Cohort 1 administered meropenem as the study-assigned antibiotic, a carbapenem antibiotic that is not metabolized by SYN-004. Patients in Cohort 2 received piperacillin/tazobactam, while patients in Cohort 3 will receive cefepime. Both piperacillin and cefepime can be metabolized by SYN-004.
Safety and pharmacokinetic data for each cohort is reviewed by an independent Data and Safety Monitoring Committee that makes recommendations on whether to proceed to the next IV beta-lactam antibiotic. The trial is also designed to evaluate potential protective effects of SYN-004 on the gut microbiome and generate preliminary information on potential therapeutic benefits and patient outcomes.
SYN-004 Mechanism and Clinical Rationale
SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the gastrointestinal tract and maintain the natural balance of the gut microbiome. The therapy aims to prevent Clostridioides difficile infection, overgrowth of pathogenic organisms, the emergence of antimicrobial resistance, and acute graft-versus-host-disease in allogeneic hematopoietic cell transplant recipients.
Allogeneic hematopoietic cell transplant recipients routinely receive long courses of IV beta-lactam antibiotics to treat infection following conditioning therapy. Antibiotic-mediated damage of the gut microbiome in these patients may lead to adverse outcomes including Clostridioides difficile infection, vancomycin-resistant Enterococci colonization, potentially fatal bacteremia, and acute graft-versus-host-disease.
Previous Clinical Evidence
A previously completed placebo-controlled Phase 2b clinical trial of 412 patients demonstrated SYN-004's protective effects on the gut microbiome from antibiotic-mediated dysbiosis. Patients who received SYN-004 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 vancomycin-resistant Enterococci.
Company Pipeline
Theriva Biologics is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. The company's lead clinical-stage candidates include VCN-01 (zabilugene almadenorepvec), an oncolytic adenovirus designed to replicate selectively within tumor cells, SYN-004 (ribaxamase), and SYN-020, a recombinant oral formulation of the enzyme intestinal alkaline phosphatase produced under cGMP conditions.
