Theriva™ Biologics Reports Positive DSMC Review for SYN-004 Trial in Allogeneic HCT Recipients

Theriva Biologics, Inc. (NYSE American: TOVX), a clinical-stage company developing cancer and disease therapeutics, recently shared positive outcomes from the Data and Safety Monitoring Committee (DSMC) regarding the second cohort of their Phase 1b/2a trial for SYN-004 (ribaxamase). This trial focuses on preventing acute graft-versus-host-disease (aGVHD) in patients undergoing allogeneic hematopoietic cell transplant (HCT). Cohort 2 included 19 patients receiving the study drug (SYN-004 or placebo) and at least one dose of intravenous (IV) piperacillin/tazobactam. The study remains blinded, but key data from this cohort revealed encouraging findings.

Adverse events (AEs) and serious adverse events (SAEs) in Cohort 2 were consistent with those typically seen in allo-HCT patients. None of the AEs or SAEs were linked to the study drug by the investigators. Among the 15 SAEs reported, the most common were infections and infestations, including sepsis. Importantly, there were no deaths within the 30-day follow-up after the last dose of the study drug. Two patients died later due to unrelated causes—cancer relapse and pneumonia. Consistent with previous studies, no patient blood samples tested positive for SYN-004 at any point.

The DSMC's review of safety and pharmacokinetic data recommended proceeding to Cohort 3, which will involve administering the study drug with the IV beta-lactam antibiotic cefepime. Steven A. Shallcross, CEO of Theriva Biologics, expressed optimism about the study's progress, emphasizing the promising data supporting SYN-004's clinical advancement. He highlighted the drug’s ability to remain undetected in blood samples of allo-HCT patients, addressing concerns about possible absorption and interference with IV antibiotics. Additionally, Shallcross acknowledged the support from Dr. Dubberke and his team at Washington University, as the company seeks further funding to continue the trial.

The ongoing Phase 1b/2a trial is conducted at Washington University School of Medicine in St. Louis. It aims to assess the safety, tolerability, and potential absorption of oral SYN-004 in allogeneic HCT recipients receiving an IV antibiotic. Cohort 1 used meropenem, an antibiotic not metabolized by SYN-004. Cohort 2 utilized piperacillin/tazobactam, and Cohort 3 will use cefepime, both of which can be metabolized by SYN-004. The study also aims to evaluate SYN-004's protective effects on the gut microbiome and gather preliminary data on therapeutic benefits and patient outcomes. The trial plans to enroll up to 36 participants across three sequential cohorts, each testing a different IV beta-lactam antibiotic. Safety and pharmacokinetic data from each cohort are reviewed by an independent DSMC to decide on progressing to the next antibiotic.

SYN-004 (ribaxamase) is an oral therapy designed to degrade certain IV beta-lactam antibiotics in the gastrointestinal tract, maintaining the gut microbiome's balance and preventing Clostridioides difficile infection (CDI), pathogenic overgrowth, antimicrobial resistance (AMR), and aGVHD in allogeneic HCT recipients. These patients often require extended IV antibiotic courses post-conditioning therapy. Antibiotic-induced gut microbiome damage can lead to adverse outcomes such as CDI, VRE colonization, bacteremia, and aGVHD. A previous Phase 2b trial with 412 patients showed that SYN-004 protected the gut microbiome from antibiotic-mediated dysbiosis, with better maintenance and recovery of the microbiome and lower incidences of opportunistic pathogenic colonization.

Theriva Biologics, Inc. is advancing a platform of therapeutics for treating cancer and related diseases. Their lead candidates include VCN-01, an oncolytic adenovirus targeting tumor cells, SYN-004 (ribaxamase), and SYN-020, a recombinant enzyme for treating local GI and systemic diseases.