Acurx Announces Publication in ASM Confirming Data on its DNA pol IIIC Inhibitor Pipeline of Antibiotics Demonstrating a Potential Microbiome-Sparing Class Effect

- Publication of first ever head-to-head comparison of gut microbiome changes associated with novel oral preclinical PolC (pol IIIC*) inhibitors to linezolid in a murine neutropenic thigh infection model

- Structural molecular modification of molecules related to ibezapolstat (IBZ) improved solubility and systemic exposure of novel Pol IIIC inhibitors with all three tested Pol IIIC inhibitors reduced MRSA burden in a neutropenic mouse thigh model

- Pol IIIC inhibitors in this study maintained high gut microbial diversity, as well as preserved microbiome metabolic function, in contrast to the marked disruption shown by linezolid

- Pol IIIC inhibitor compounds specifically preserved anaerobic microbiome components and metabolism, whereas linezolid induced depletion and disruption of healthy anaerobic bacterial communities

- Acurx's DNA pol IIIC inhibitor preclinical product candidates are FDA QIDP and Fast-Track eligible and target Gram-positive infections classified as Serious Threat priorities by CDC

STATEN ISLAND, N.Y., Oct. 21, 2026 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage biopharmaceutical company developing a new class of antibiotics for serious and life-threatening bacterial infections, today announced publication in the ASM (American Society for Microbiology) Microbiology Spectrum journal of results of a study entitled: The effects of novel oral preclinical PolC inhibitor antibiotic candidates on the gut microbiome in a murine thigh infection model. These findings confirm in vivo antibacterial activity at tested doses while suggesting that further structural or dosing optimization may enhance tissue-level efficacy. Compared with oral linezolid, a commonly used oral therapy for gram-positive infections, orally dosed Pol IIIC inhibitors demonstrated a consistent class characterized by preservation of a Bacteroidota-dominant murine gut community and maintenance of anaerobic metabolic pathways. These experiments also highlight the importance of microbiome-informed antibiotic evaluation in preclinical studies.

Kevin Garey, PharmD, MS, FIDSA and Principal Investigator for microbiology and microbiome aspects of Acurx's DNA pol IIIC program and the Robert L. Boblitt, Endowed Professor in Drug Discovery at the University of Houston College of Pharmacy is the lead author and commented on the significance of the data: "Discovering highly selective antibacterial agents that specifically target systemic bacterial pathogens while avoiding the eradication of trillions of health-promoting bacteria in our gut microbiome remains a "Holy Grail" of antibiotic development. 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."

Robert J. DeLuccia, Executive Chairman of Acurx, stated: "Acurx is at the forefront of pioneering Antimicrobial Stewardship with antibiotics by discovering and developing innovative narrow-spectrum antibiotics which cause minimal gut dysbiosis. This Microbiome Stewardship dimension, which we believe should be fundamental to driving today's drug discovery and development process, is emerging as a new standard in the field of human anti-infective research".

Acurx's portfolio of preclinical compounds include clinical applications for infections caused by MRSA such as: ABSSI, Hospital Acquired and Ventilator Acquired Bacterial Pneumonia, bacteremia with or without sepsis and/or endocarditis, bone and joint and diabetic foot infections and B. anthracis (anthrax; a Bioterrorism Category A Threat-Level pathogen).

*Pol IIIC is alternative nomenclature for Pol C

The publication is available on the Acurx Pharmaceuticals website www.acurxpharma.com

ASM publication: https://pubmed.ncbi.nlm.nih.gov/42885945/

About ASM (American Society for Microbiology) Spectrum

Microbiology Spectrum® is an online-only, fully open-access journal that publishes research from all domains of basic, applied, and clinical microbial sciences. Rather than making subjective evaluations of potential impact, Microbiology Spectrum publishes research studies that are of high technical quality and are useful to the community. All decisions are made by an international and diverse editorial board that fully represents the microbiology research community.

About MRSA (Methicillin-Resistant Staphylococcus Aureus)

While ibezapolstat for the treatment of C. difficile Infection (CDI) is ready to advance to Phase 3 international pivotal trials, Acurx's R&D platform has sustainability for additional new product candidates from its pipeline of systemic (oral and IV) antibiotics to treat infections caused by other susceptible and antimicrobial resistant bacteria, including infections caused by MRSA. The CDC estimates ~323,700 hospital cases of MRSA infections annually with ~10,600 deaths. In a recent CDC surveillance study in hospitalized patients in the US, MRSA accounted for 52% of all infections, almost twice as many as MDR Gram-negative infections.

Clinical applications for these infections include: ABSSI, Hospital Acquired and Ventilator Acquired Bacterial Pneumonia, bacteremia with or without sepsis and/or endocarditis, bone and joint, diabetic foot infections. Acurx's DNA pol IIIC inhibitor preclinical product candidates are FDA QIDP and Fast-Track eligible and target Gram-positive infections classified as Serious Threat priorities by CDC.

About the Neutropenic Mouse Model

The purpose of the murine thigh MRSA infection model was to evaluate the in vivo efficacy of the PolC inhibitor compounds using linezolid as a control. Animal experiments were conducted at NeoSome Life Sciences, an American Association for the Accreditation of Laboratory Animal Care-accredited facility. All experiments were approved by the NeoSome Institutional Animal Care and Use Committee (protocol number NLS24-011). Female CD-1 mice (Charles River Laboratories) were rendered neutropenic by two intraperitoneal doses of cyclophosphamide and acclimated for 5 days prior to study initiation. Mice were housed four per cage with ad libitum access to food and water. All animals were inoculated intramuscularly in the right rear thigh with a prepared bacterial suspension containing MRSA strain BAA-1717 (USA 300) at time 0, achieving a final inoculum of 1.8 × 105 colony-forming unit (CFU) per mouse thigh. Antibiotic treatment began 1 h post-infection, with each cage serving as an independent experimental unit receiving a single drug–dose combination.

Acurx previously announced that the first patient has been enrolled in its new clinical trial (PATHFINDER) in patients with multiply recurrent C. difficile Infection (rCDI). This new, fully funded,PATHFINDER clinical trial is a pilot trial in approximately 20 patients with multiply-recurrent CDI (at least three episodes over the past 12 months) and will support filing of a U.S. NDA (New Drug Application) based on a single Phase 3 trial.

The PATHFINDER Phase 2 multicenter, open-label, single-arm study evaluates the efficacy and safety of ibezapolstat in the treatment and reduction of recurrence of CDI in patients who have experienced at least 3 episodes of CDI within the past 12 months. Participants will be treated with IBZ for 14 days and assessed for Clinical Cure (Day 16), Sustained Clinical Cure (Day 42), rate of CDI recurrence (to Week 24), and Extended Clinical Cure (to Week 24).

https://clinicaltrials.gov/study/NCT07513285?term=acurx&viewType=Card&rank=2

Separately, the planned ASPIRE trial is of non-inferiority design with the primary efficacy analysis in the Modified Intent-To-Treat (mITT) population and will result in approximately 550 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin. The ASPIRE trial will be conducted when the Company has sufficient resources from public or private partnership(s) to fund this trial.

Acurx previously announced the successful outcome of a Type C Meeting conducted with FDA on July 13, 2026 to discuss ibezapolstat's Phase 3 clinical program and scope of its planned NDA. The Agency stated that it is open to further discussion at a Pre-NDA Meeting regarding the possibility of submitting an NDA with only a single Phase 3 trial, depending on the totality of the clinical data plus any other supportive data that Acurx may generate by that milestone. The Agency noted that determination of acceptability of one Phase 3 clinical trial for an NDA is made on a case-by-case basis, taking into consideration such factors as the magnitude, consistency, and overall robustness of the efficacy results; generalizability of the results to the US population; relevance of the results to US patient care and clinical practice guidelines; Phase 2 data; and an adequate safety database. The Agency acknowledged Acurx's planned clinical trial in recurrent CDI (rCDI) and noted the data from this rCDI trial, if successful, would support an NDA submission. If the IBZ-ASPIRE trial does not meet these criteria, then a second trial consistent with the agreement reached at the end of Phase 2 (EOP2) meeting on April 27, 2024, is recommended.

The currently planned IBZ-ASPIRE trial is of non-inferiority design with the primary efficacy analysis in the Modified Intent-To-Treat (mITT) population. This will result in approximately 550 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard-of-care vancomycin.