Theriva Biologics Presents Phase 1b/2a Trial Data on SYN-004 in Allogeneic Hematopoietic Cell Transplant Patients

Theriva Biologics, a clinical-stage company focused on developing treatments for cancer and related illnesses, has revealed interim safety and pharmacokinetic data from its ongoing Phase 1b/2a clinical trial of SYN-004 (ribaxamase). This therapy is being tested for its potential to prevent acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic cell transplant (HCT). The findings will be presented at the Congress of the European Society of Clinical Microbiology and Infectious Diseases, to be held in Vienna, Austria, from April 11-15, 2025.

The SYN-004 trial is being conducted at Washington University School of Medicine in St. Louis. This randomized, double-blinded, placebo-controlled study is examining the safety and absorption of oral SYN-004 in HCT recipients who are also receiving intravenous antibiotics to treat fever. The trial seeks to determine whether SYN-004 can protect the gut microbiome from damage caused by antibiotics, thus preventing complications such as Clostridioides difficile infection (CDI), the emergence of antimicrobial resistance (AMR), and aGVHD.

Participants in the trial are divided into three cohorts, each receiving different study-assigned antibiotics. Cohort 1 received meropenem, a carbapenem antibiotic not affected by SYN-004. Cohorts 2 and 3 were given piperacillin/tazobactam and cefepime, respectively, both of which can be metabolized by SYN-004. The trial aims to enroll 36 participants, with an independent Data and Safety Monitoring Committee evaluating the results from each cohort before proceeding to the next group.

SYN-004 is designed as a prophylactic oral therapy to degrade certain IV beta-lactam antibiotics within the gastrointestinal tract, aiming to maintain the gut’s natural microbiome balance. By preventing antibiotic-induced dysbiosis, SYN-004 may reduce the incidence of CDI, colonization by vancomycin-resistant Enterococci (VRE), and potentially fatal bacteremia, as well as the severity of aGVHD in HCT recipients. Previously, a Phase 2b clinical trial involving 412 patients demonstrated that SYN-004 effectively protected the gut microbiome from damage, ensuring better recovery and lower new colonization by harmful microorganisms.

Theriva Biologics is dedicated to developing innovative treatments addressing unmet medical needs in cancer and related diseases. Among its leading clinical-stage candidates is VCN-01, an oncolytic adenovirus designed to selectively target and replicate in tumor cells while breaking down the tumor stroma barrier, enhancing the effectiveness of concurrent cancer therapies and triggering an immune response to fight tumors. Another candidate, SYN-020, is an oral enzyme formulation targeting both gastrointestinal and systemic diseases.

In summary, the presentation of interim data on SYN-004 at the ESCMID Global Congress highlights Theriva Biologics’ efforts to advance novel treatments for severe conditions like aGVHD. The ongoing clinical trial aims to further establish the safety and efficacy of SYN-004 in preserving the gut microbiome and improving outcomes for patients undergoing allogeneic HCT.