Acurx Unveils Ibezapolstat Research Results with Leiden University at C. difficile Symposium

Acurx Pharmaceuticals, Inc., a biopharmaceutical company focusing on new antibiotic treatments, has revealed significant findings from its research on ibezapolstat, developed in collaboration with Leiden University Medical Center (LUMC). The results were presented at the International C. difficile Symposium (ICDS) in Bled, Slovenia. Dr. Wiep Klaas Smits of LUMC discussed the detailed structure and action mechanism of ibezapolstat, highlighting its unique approach to targeting DNA polymerase IIIC (pol IIIC) in combating C. difficile infections.

Dr. Smits emphasized the importance of DNA replication as a therapeutic target, which remains underexploited in the fight against antimicrobial resistance. The research provided a high-resolution understanding of how ibezapolstat interacts with its molecular target, fundamentally differentiating it from other antibiotics by not fostering cross resistance and not encouraging the emergence of vancomycin-resistant Enterococcus strains.

Robert J. DeLuccia, Acurx's Executive Chairman, expressed satisfaction with the productive collaboration with LUMC. He noted that the mechanistic insights into DNA pol IIIC inhibitors are essential for regulatory filings as ibezapolstat moves into its late-stage development phase aimed at commercialization.

Acurx has confirmed key elements for two pivotal Phase 3 clinical trials, including protocol design, patient population, and primary and secondary endpoints. In agreement with FDA guidelines, the primary efficacy analysis will use a Modified Intent-To-Treat (mITT) population, estimating around 450 subjects. These subjects will be randomized to receive either ibezapolstat or standard-of-care vancomycin, with the primary goal being to assess clinical cure and reductions in CDI recurrence.

The research project, funded by Health Holland and conducted in collaboration with Acurx, focused on understanding the 3-dimensional structures of DNA polymerases and their interactions with new inhibitors. Findings from this research are expected to accelerate the selection of lead candidates for Acurx's pre-clinical programs, targeting other high-priority, multi-drug resistant Gram-positive pathogens.

The International C. difficile Symposium is a key platform for discussing advancements in Clostridium difficile research. The 2024 meeting in Bled marked a continuation of the symposium's tradition, providing an opportunity for the scientific community to review progress in various aspects of CDI research.

The Phase 2 clinical trials for ibezapolstat demonstrated promising results. The initial Phase 2a segment involved 20 subjects and showed a 100% cure rate at the end of treatment, leading to the recommendation to advance to Phase 2b. The Phase 2b study, which compared ibezapolstat with vancomycin, was concluded early due to positive outcomes, with a 96% overall clinical cure rate observed in the ibezapolstat group. The trial faced challenges due to COVID-19, but the preliminary findings supported the efficacy of ibezapolstat, paving the way for Phase 3 trials.

Ibezapolstat's unique mechanism involves minimal disruption to the gut microbiome, promoting the production of secondary bile acids which are crucial in preventing C. difficile recurrence. Phase 2 studies indicated a beneficial shift in bile acid metabolism, suggesting a lower likelihood of CDI recurrence compared to vancomycin.

Acurx is now planning to advance ibezapolstat to international Phase 3 clinical trials and is preparing regulatory submissions in various regions including the European Union, the United Kingdom, Japan, and Canada. Ibezapolstat has received FDA's Qualified Infectious Disease Product (QIDP) and Fast-Track Designation, highlighting its potential as a significant advancement in CDI treatment.

Clostridioides difficile remains a significant health issue, causing nearly half a million infections annually in the U.S., with high recurrence rates and significant mortality. Acurx's research into ibezapolstat aims to address these challenges by providing a novel treatment option that spares beneficial gut microbiota and reduces recurrence risks.

Acurx Pharmaceuticals continues to focus on developing antibiotics that target Gram-positive bacteria, contributing to the fight against difficult-to-treat bacterial infections.