Benzinga | Jul 1, 2021 08:02AM EDT

Acurx Highlights New Ibezapolstat Data On Anti-Recurrence Mechanisms In Clostridiodes Difficile Infection At Int'l. Conference

- Ibezapolstat, the first of a novel class of antibiotics, DNA polymerase IIIC inhibitors, is currently commencing a Phase 2b clinical trial in patients with CDI

- Using samples from Phase 1 healthy volunteers and a novel OMICS analysis approach, ibezapolstat differed favorably from vancomycin in microbiota abundance including a marked increase in Proteobacteria and Fusobacterium and concentration of primary bile acids

- These results form the basis for our scientific advisors to predict an anti-recurrence effect for ibezapolstat in future CDI trials

STATEN ISLAND, N.Y., July 1, 2021 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (Nasdaq ACXP) ("Acurx" or the "Company"), a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today that using specimens from a Phase 1 healthy volunteer trial and a novel analysis technique, beneficial changes potentially predictive of lower risk of CDI (Clostridioides difficile Infection) recurrence were associated with ibezapolstat compared to vancomycin. These results were presented by Dr. Kevin Garey, Professor and Chair, University of Houston College of Pharmacy and the Principal Investigator for microbiome aspects of the clinical trial program for ibezapolstat. The I-Poster and Abstract presented during the World Microbe Forum 2021 virtual conference held June 20-24, 2021 was entitled: OMICS Evaluation of the Gram-positive Selective Spectrum (GPSS) Antibiotic, ibezapolstat, using Phase 1 Clinical Samples, Predicts a Possible Anti-recurrence Effect in Future Clostridioides difficile Infection Studies.

This novel OMICS approach which is a comprehensive study to characterize and quantify biological molecules to better understand structure, function and dynamics of an organism or organism community, involved both microbiome analysis using shotgun metagenomics sequencing and determination of bile acid concentrations and may enable better and earlier prediction of anti-CDI recurrence effects for antibiotics in the clinical development pipeline. This hypothesis will be tested in the Phase 2b trial of ibezapolstat in the treatment of patients with CDI. According to Dr. Garey, "Ibezapolstat's unique spectrum of activity targeting low G+C content Gram-positive bacteria, which includes C. difficile, spares the important Actinobacteria phylum; while at the same time killing C. difficile but not other Firmicutes necessary for maintaining a healthy microbiome." He also stated "Similarly, ibezapolstat's effect on bile acids is dramatically different than that seen with vancomycin and may emerge as another factor that predicts an anti-recurrence effect. Having such potentially predictive data so early in development could create a new paradigm for CDI drug development."

Robert J. DeLuccia, Executive Chairman of Acurx, stated, "We are very excited by these results showing a very distinctive microbiome signature which enhances the population of Actinobacteria without promoting Proteobacteria overgrowth, suggesting the potential for ibezapolstat to have a "restorative" effect on the microbiome." He further stated that "Additional data from our recently completed Phase 2a clinical trial in CDI patients using the same analytics will be forthcoming and are expected to validate the hypothesis as well as give us further confidence of a successful outcome in our Phase 2b trial planned to start later this year."

About the Study Data and Analysis.

Background Reduction in likelihood of Clostridioides difficile infection (CDI) recurrence is an essential endpoint for antibiotics in development for CDI although it is often not evaluated until Phase 3 trials. Advancing knowledge of microbiome, functional metagenomics, and metabolomics may enable predictions of anti-recurrence effects earlier in the drug development process. The purpose of this project was to use an OMICS approach to predict the potential anti-CDI recurrence effect of ibezapolstat, a DNA polymerase IIIC inhibitor in Phase 2 clinical development for the treatment of C. difficile infections using clinical stool samples from the Phase 1 healthy volunteer study.

Methods As part of the completed Phase 1 clinical study of ibezapolstat, stool samples were collected daily from healthy volunteers given ten days of ibezapolstat (300 or 450 mg given twice daily) or vancomycin (125 mg given four times daily). Stool samples were evaluated for microbiome and functional metagenomics changes using shotgun metagenomics (Illumina HiSeq) and bile acid concentrations using mass spectroscopy (LC-MS-MS).

Results: Eighteen subjects (female: 33%) aged 30?8 years were enrolled. Baseline microbiota, functional metagenomics, and bile acid concentrations were similar between study groups. Samples from vancomycin-treated patients displayed significant changes in microbiota abundance including a marked increase in Proteobacteria and Fusobacterium, a significantly lower abundance of bile salt biotransformation genes, and a marked increase in primary compared to secondary bile acids. In contrast, samples from ibezapolstat treated patients did not have as profound a shift in the microbiome with the exception of increased proportion of Actinobacteria, and a less marked relative reduction in bile salt biotransformation genes and secondary bile acids.