Acurx Pharmaceuticals announced that a new paper has been published in Nature Communications detailing the first structural biology study of its lead antibiotic, ibezapolstat, bound to its target DNA polymerase IIIC (Pol IIIC). The study, conducted in partnership with Leiden University Medical Center, was released on November 10, 2025 and provides the first high‑resolution view of how ibezapolstat engages the Pol IIIC enzyme in Gram‑positive bacteria.
The crystal structure shows that ibezapolstat occupies a unique pocket adjacent to the active site of Pol IIIC, locking the enzyme in an inactive conformation that blocks DNA synthesis. The authors report that the inhibitor’s binding mode explains the drug’s selective activity against priority pathogens such as Clostridioides difficile, methicillin‑resistant Staphylococcus aureus (MRSA) and vancomycin‑resistant enterococci (VRE). The collaboration with LUMC also confirmed that the binding geometry is conserved across multiple Pol IIIC variants, supporting the hypothesis that the drug’s spectrum is driven by a single, highly conserved target.
For Acurx, the structural data reinforce the scientific foundation of the Phase 3 program for CDI and provide a roadmap for future Pol IIIC‑targeted candidates. By demonstrating a clear mechanism of action, the study may ease regulatory discussions and accelerate the design of next‑generation inhibitors that retain microbiome‑sparing properties. The findings also validate the company’s strategy to develop a new class of antibiotics that could address the growing threat of antimicrobial resistance in Gram‑positive pathogens.
The publication comes at a time when the World Health Organization and the CDC have highlighted C. difficile, MRSA and VRE as urgent threats. Ibezapolstat’s novel mechanism—targeting an enzyme absent in humans—offers a first in over three decades of antibiotic development and may reduce the risk of cross‑resistance. Early clinical data already show a 96 % initial cure rate in CDI patients, and the drug has received FDA QIDP and Fast‑Track designations as well as EMA SME status.
While the study itself has not yet triggered a market reaction, it precedes Acurx’s scheduled Q3 2025 earnings release on November 12, 2025. Investors and analysts will likely view the structural confirmation as a positive signal for the company’s pipeline, though the company’s balance sheet remains heavily funded by R&D and it has no current revenue streams. The announcement underscores Acurx’s progress toward a potentially transformative antibiotic platform, but the company’s commercial success will depend on the continued performance of its Phase 3 program and the broader market acceptance of Pol IIIC inhibitors.
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