Acurx Pharmaceuticals : ESCMID Poster Presentation “Preclinical Microbiome Evaluation of novel PolC-inhibitor compounds (Begum, et. al., April 2026)"

Published: 2026-04-30 08:41:12 ET ACXP

Published on 04/30/2026 at 08:41 am EDT

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Poster P2839 Abstract: 7529

1University of Houston College of Pharmacy; 2Acurx Pharmaceuticals, LLC

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BACKGROUND

METHODS

PolC inhibition disrupts DNA replication in low GC-content Gram-positive bacteria, including priority pathogens such as Staphylococcus, Enterococcus, and Streptococcus species.1

Ibezapolstat, a first-in-class PolC inhibitor for Clostridiodies difficile infection (CDI), demonstrated strong efficacy in phase 2 trial with microbiome preservation. 2, 3

Next-generation PolC inhibtor compounds, ACX-978, ACX-801, and ACX-728, were developed to enhance systemic exposure and Gram-positive coverage.1

However, their microbiome effects have not been elucidated

Neutropenic CD-1 mice were infected intramuscularly with MRSA

ACX compounds (100, 150 mg/kg, TID) and linezolid (100 mg/kg, BID) were administered orally beginning 1-hour post-infection (n=4/group)

Controls included baseline and infection-only (placebo) groups

Samples collected at 25 hours post-infection: plasma, feces, and thigh and colon tissue.

Microbiome profiling: shotgun metagenomics (MetaPhlAn).

Drug exposure quantified by LC-MS/MS.

RESULTS

Figure 1. Study Design

Figure 2. PolC inhibitors achieve good plasma and fecal levels at 24 hours

Figure 5. PolC inhibitors reduced MRSA burden in neutropenic mouse model

CONCLUSION

PolC inhibitors demonstrate class-consistent microbiome preservation in concert with antibacterial activity (0.5 to 2.0 log10 reduction in CFU/g)

Unlike linezolid, ACX compounds maintain Bacteroidota-dominant community structure and prevent Proteobacteria expansion.

ACX-801 shows favorable systemic exposure with microbiome stability.

PolC compounds represent a targeted strategy to treat resistant Gram-positive infections while preserving microbiome structure, minimizing downstream complications associated with antibiotic-induced dysbiosis

FUNDING

This study was funded by Acurx Pharmaceuticals, LLC

Wolfe TM, Jo J, Pinkham NV, Garey KW, Walk ST. The impact of ibezapolstat and other Clostridioides difficile infection-relevant antibiotics on the microbiome of humanized mice. Antimicrob Agents Chemother. Apr 2 2025;69(4):e0160424. doi:10.1128/aac.01604-24

Garey KW, McPherson J, Dinh AQ, et al. Efficacy, Safety, Pharmacokinetics, and Microbiome Changes of Ibezapolstat in Adults with Clostridioides difficile Infection: A Phase 2a Multicenter Clinical Trial. Clin Infect Dis. Sep 30 2022;75(7):1164-1170. doi:10.1093/cid/ciac096

Eubank TA, Jo J, Alam MJ, et al. Efficacy, safety, pharmacokinetics, and associated microbiome changes of ibezapolstat compared with vancomycin in adults with Clostridioides difficile infection: a phase 2b, randomised, double-blind, active-controlled, multicentre study. Lancet Microbe. Aug 2025;6(8):101126. doi:10.1016/j.lanmic.2025.101126

Disclaimer

Acurx Pharmaceuticals Inc. published this content on April 30, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 30, 2026 at 12:40 UTC.