Acurx’s Ibezapolstat Shows Favorable Gut Microbiome Impact In CDI Study Compared To Other Antibiotics

Acurx Pharmaceuticals, a late-stage biopharmaceutical company, is advancing its lead antibiotic candidate, ibezapolstat, into international Phase 3 clinical trials for Clostridioides difficile infection (CDI). The company recently announced the results of a humanized mouse study, which has been published in the Journal of Antimicrobial Agents and Chemotherapeutics. Led by Trenton Wolfe, a PhD student at the University of Montana, the study was funded by multiple institutions, including the National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute (NCI), along with Acurx itself.

The co-author Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program, and Acurx Scientific Advisory Board member, commented, "This study provides critical evidence to begin to distinguish ibezapolstat from other C. difficile directed antibiotics, especially fidaxomicin. Although both ibezapolstat and fidaxomicin were narrower spectrum than vancomycin or metronidazole, ibezapolstat's effect on the microbiome was distinctly different from fidaxomicin. How this translates into beneficial health effects or emergence of antimicrobial resistance will be an area of further study."

The study compared ibezapolstat’s effects on the gut microbiome with those of other CDI antibiotics, a first-of-its-kind head-to-head analysis in non-clinical, in vivo models. The findings showed that ibezapolstat caused fewer disruptions in gut microbiome diversity compared to vancomycin (VAN) and metronidazole (MET). By the end of treatment, ibezapolstat increased beneficial bacteria such as Bacteroidota and Actinomycetota, while microbiome-humanized mice exhibited a milder impact on gut diversity with ibezapolstat and fidaxomicin (FDX) compared to VAN and MET.

Acurx's Executive Chairman, Bob DeLuccia, said, "These results of this first ever direct comparison of the gut microbiome effects of ibezapolstat in a validated humanized mouse model set the stage for potential competitive advantage of IBZ over all commonly used anti-CDI antibiotics, including fidaxomicin". He added: "These data also serve as a foundation upon which to build future planned preclinical and clinical studies at the appropriate time to clarify further ibezapolstat's favorable effect on the microbiome known to confer health benefits to patients with CDI."

The analysis suggests that ibezapolstat has a narrower microbiome impact, similar to FDX, but with notable differences. One key distinction was an increased presence of Actinomycetota, including Bifidobacteria, which are linked to human health benefits. These results highlight ibezapolstat’s potential as a targeted therapy for CDI with a reduced risk of microbiome disruption, which could differentiate it from existing CDI treatments in future research.