Theriva Biologics' SYN-004 Passes Key Safety Review In Early Trial For Transplant Patients

Theriva™ Biologics, Inc. (NYSE American: TOVX), a clinical-stage biopharmaceutical company focused on developing innovative cancer therapies for critical unmet medical needs, has announced encouraging results following a review by the Data and Safety Monitoring Committee (DSMC). The review focused on data from the second cohort of Theriva's ongoing Phase 1b/2a clinical trial evaluating SYN-004 (ribaxamase) in patients undergoing allogeneic hematopoietic cell transplants (HCT). This randomized, double-blinded, placebo-controlled study aims to prevent acute graft-versus-host disease (aGVHD) in these high-risk patients.

In Cohort 2, a total of 19 patients were enrolled, each receiving at least one dose of the study treatment (SYN-004 or placebo, in a 2:1 randomization). Eighteen of these participants also received intravenous (IV) piperacillin/tazobactam, and 12 completed sufficient doses for evaluation towards the study’s objectives. Although the trial is still ongoing and blinded, key insights from the blinded data for Cohort 2 are shared below:

Adverse events (AEs) and serious adverse events (SAEs) in Cohort 2 aligned with what is typically seen in allo-HCT patients, and no AEs or SAEs were attributed by investigators to the study drug. Ten patients experienced a total of 15 SAEs, with infections and infestations, including sepsis, being the most common. No deaths occurred within 30 days of the final dose, although one patient died 95 days after the last dose due to cancer relapse, and another passed away 211 days later from pneumonia—neither case was linked to the study drug.

In line with findings from Cohort 1 and earlier studies involving healthy volunteers, SYN-004 was not detected in any blood samples at any point. Additionally, the pharmacokinetics of piperacillin, which can be metabolized by SYN-004, were consistent with expectations for this patient population.

Following an analysis of the safety and pharmacokinetic data, the Data and Safety Monitoring Committee (DSMC) has recommended moving forward with the study. Cohort 3 will now be enrolled, where SYN-004 or placebo will be administered alongside the IV beta-lactam antibiotic cefepime.

Chief Executive Officer of Theriva Biologics, Steven A. Shallcross, said in a statement, “These encouraging data support the clinical advancement of SYN-004 and build on the growing data that underscore its therapeutic potential. The first 2 cohorts have shown that active SYN-004 is not found in the blood of allo-HCT patients after repeated oral doses, in part alleviating the concern that SYN-004 might be absorbed in patients with poor intestinal barrier function and potentially interfere with IV antibiotics. 

He further stated, “We are very grateful for the tremendous support from Dr. Dubberke and his team at Washington University as we pursue additional funding to enable the conduct of the third cohort and continue with the goal of improving standard treatment for these highly susceptible patients by overcoming existing limitations of broad-spectrum IV beta-lactam antibiotics.”