Acurx Pharmaceuticals (NASDAQ: ACXP) announced the publication of a preclinical study in the American Society for Microbiology's Microbiology Spectrum journal, reporting results on the effects of its DNA polymerase IIIC (Pol IIIC) inhibitor antibiotic candidates on the gut microbiome in a murine thigh infection model.

The study represents what the company describes as the first head-to-head comparison of gut microbiome changes associated with novel oral preclinical Pol IIIC inhibitors versus linezolid, a commonly used oral therapy for gram-positive infections, in a murine neutropenic thigh infection model.

According to the publication, all three tested Pol IIIC inhibitor compounds reduced MRSA bacterial burden in the neutropenic mouse model. The compounds also maintained higher gut microbial diversity and preserved anaerobic metabolic pathways compared with linezolid, which the study found caused disruption of healthy anaerobic bacterial communities.

Kevin Garey, PharmD, MS, FIDSA, lead author and professor at the University of Houston College of Pharmacy, commented on the findings: "Work in our laboratory with Acurx's novel DNA pol IIIC inhibitors has advanced this work by demonstrating favorable gut microbiome-sparing effects of this novel class of antibiotics. It further emphasizes the value of incorporating microbiome profiling into the earliest phases of new antibiotic clinical research programs."

The preclinical Pol IIIC inhibitor compounds are structurally related to ibezapolstat, Acurx's lead antibiotic candidate targeting C. difficile infection. Structural modifications to these related molecules were reported to improve solubility and systemic exposure. The preclinical candidates are eligible for FDA Qualified Infectious Disease Product (QIDP) and Fast Track designations, according to the company.

Acurx also noted that its PATHFINDER Phase 2 clinical trial, evaluating ibezapolstat in patients with multiply recurrent C. difficile infection, is currently enrolling, with the first patient enrolled in September 2026.