Acurx Announces New Data on its DNA pol IIIC Inhibitor Antibiotics Demonstrating a Potential Class Effect of Gut Microbiome Selectivity Presented at IDWeek 2025 Scientific Conference

Rhea-AI Summary

Acurx Pharmaceuticals (NASDAQ: ACXP) presented new data at IDWeek 2025 (Oct 19-22, 2025) showing its Phase 3-ready DNA pol IIIC inhibitor ibezapolstat (IBZ) exhibits selective antibacterial activity in the gut that spares bile acid-metabolizing bacteria, a profile linked to IBZ's anti-recurrence effect in C. difficile infection where no patient cured in Phase 2 experienced recurrence.

New preclinical colonic microbiome data in a mouse model suggest representative DNA pol IIIC inhibitor compounds may share this microbiome-sparing class effect compared with linezolid. Ibezapolstat has FDA QIDP and Fast-Track designation; Acurx's preclinical candidates are QIDP/Fast-Track eligible for systemic Gram-positive infections.

Positive

• Phase 2 CDI result: no cured patient experienced recurrence
• FDA QIDP and Fast-Track designation for ibezapolstat
• Preclinical data show potential microbiome-sparing class effect versus linezolid

Negative

• Class-effect evidence is described as initial/preclinical and not yet confirmed clinically

• Pioneering data demonstrate that Acurx's U.S. and EU Phase 3-ready DNA pol IIIC inhibitor, ibezapolstat (IBZ), has unique selective antibacterial activity in the gut which spares beneficial bile acid-metabolizing bacteria
• The favorable gut bile acid profile contributes to ibezapolstat's anti-recurrence effect in patients with C. difficile Infection (CDI)
• New data presented on representative novel compounds from Acurx's DNA pol IIIC inhibitor preclinical pipeline provide initial evidence that microbiome selectivity, when compared to the comparator antibiotic, linezolid, may be a class effect
• Ibezapolstat has previously received FDA QIDP and Fast-Track Designation from FDA; Acurx's preclinical antibiotic candidates are FDA QIDP/Fast track eligible for systemic treatment of infections caused by other Gram-positive priority pathogens

STATEN ISLAND, N.Y., Oct. 28, 2025 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) ("Acurx" or the "Company"), is a late-stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections. It announced today that a presentation was given by Michael Silverman, MD, FACP, Acurx's Medical Director, and Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, Principal Investigator for microbiology and microbiome aspects of the ibezapolstat clinical trial program at the Infectious Diseases Society of America (IDSA) IDWeek™ 2025 Scientific Conference held on October 19-22, 2025 in Atlanta, GA.

Acurx was one of five companies invited to present at the New Antimicrobials in the Pipeline session on October 20. The presentation entitled: First of a New Class of Antibiotics (DNA pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority Pathogens; Preparing for the Next Pandemic: Antimicrobial Resistance in Gram-positive Bacterial Infections. The Company's presentation included an update on ibezapolstat and its microbiome sparing properties. Also, presented were new colonic microbiome data from a mouse infection model showing a potential microbiome-sparing class effect of representative compounds from the Company's DNA pol IIIC inhibitor preclinical pipeline.

In describing the work performed at his laboratory at the University of Houston, Dr. Garey stated: "Initial work on novel, lead DNA pol IIIC inhibitor compounds indicate that the positive microbiome-sparing results from our ibezapolstat studies may be a class effect. This is an important finding because microbiome sparing likely contributed to IBZs sustained efficacy in the Phase 2 trial where no patient cured of CDI experienced a recurrence. In our recent experiments, mice given the comparator antibiotic, linezolid, demonstrated an over-abundance of uncommon and harmful Gram-negative bacteria called Pseudomonadota, previously known at Proteobacteria. He further stated: "These data indicate a low probability for DNA pol IIIC inhibitors to increase the risk of causing a Clostridioides difficile infection, vancomycin-resistant Enterococcus, or other gut-microbiome related infections."

Robert J. DeLuccia, Executive Chairman of Acurx, stated: "As leaders in the field in developing a class of antibiotics that effectively treat infections caused by Gram-positive priority pathogens, preserving the healthy microbiome is a hallmark of differentiation compared to currently available antibiotics." He further commented: "These new data providing initial evidence that microbiome selectivity may be a class effect has the potential to create a transformational paradigm shift for treatment of serious and potentially life-threatening infections. These include acute bacterial skin and skin-structure infections (including those caused by MRSA), community-acquired bacterial pneumonia, hospital and/or ventilator-associated bacterial pneumonia, anthrax and bacteremia with or without sepsis and/or infectious endocarditis; bone/joint infections & diabetic foot infections".

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

About IDWeek and the IDSA

The Infectious Diseases Society of America (IDSA) is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases. IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP).

About Acurx Pharmaceuticals, Inc. and Its DNA pol IIIC Discovery Program

Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for difficult-to-treat bacterial infections. The Company's approach is to develop antibiotic candidates with a Gram-positive selective spectrum (GPSS®) that blocks the active site of the Gram-positive specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication and leading to Gram-positive bacterial cell death. Its R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin- resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), drug- resistant Streptococcus pneumoniae (DRSP) and B. anthracis (anthrax; a Bioterrorism Category A Threat-Level pathogen). Acurx's lead product candidate, ibezapolstat, for the treatment of C. difficile Infection is Phase 3 ready with plans in progress to begin international clinical trials. The Company's preclinical pipeline includes development of an oral product candidate for treatment of ABSSSI (Acute Bacterial Skin and Skin Structure Infections), upon which a development program for treatment of inhaled anthrax is being planned in parallel.

DNA pol IIIC inhibitors have been clinically validated with the first-generation inhibitor ibezapolstat (IBZ), now entering Phase 3 clinical trials for Clostridioides difficile infection. IBZ has intended poor oral bioavailability and is only appropriate for treatment of gut-associated C. difficile infection. Acurx is advancing novel inhibitors for oral and IV administration for treatment of systemic infections caused by CDC-priority gram-positive pathogens. Furthermore, DNA pol IIIC inhibitors have a defined regulatory pathway with transformative clinical use potential. Acurx uses new AI-driven FEP technologies to rapidly identify and advance novel DNA pol IIIC inhibitors and deliver IND lead candidates representing a new class of systemic antibiotics in >30 years to treat infections caused by gram-positive bacteria. Acurx's proposed innovation offers a disruptive solution that delivers a therapeutic effect with high precision and minimal off-target effects. By leveraging structural insights gained through previous studies and utilizing new FEP studies along with AI/ML approaches, the Acurx program aims to produce a systemically active antibiotic with a new mechanism of action (MOA), no cross resistance with existing antibiotics, and a gut microbiome sparing property that potentially supports long-term dosing for serious infections such as prosthetic joint infection, bacteremia, and osteomyelitis.

Acurx previously announced that it had received positive regulatory guidance from the EMA during its Scientific Advice Procedure which confirmed that the clinical, non-clinical and CMC (Chemistry Manufacturing and Controls) information package submitted to EMA supports advancement of the ibezapolstat Phase 3 program and if the Phase 3 program is successful, supports the submission of a Marketing Authorization Application (MAA) for regulatory approval in Europe. The information package submitted to EMA by the Company to which agreement has been reached with EMA included details on Acurx's two planned international Phase 3 clinical trials, 1:1 randomized (designed as non-inferiority vs vancomycin), primary and secondary endpoints, sample size, statistical analysis plan and the overall registration safety database. With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence our international Phase 3 registration program.

The primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population. This will result in an estimated 450 subjects in the mITT population, randomized in a 1:1 ratio to either ibezapolstat or standard- of-care vancomycin, enrolled into the initial Phase 3 trial. The trial design not only allows determination of ibezapolstat's ability to achieve Clinical Cure of CDI as measured 2 days after 10 days of oral treatment but also includes assessment of ibezapolstat's potential effect on reduction of CDI recurrence in the target population. In the event non-inferiority of ibezapolstat to vancomycin is demonstrated, further analysis will be conducted to test for superiority.

About the Ibezapolstat Phase 2 Clinical Trial

The completed multicenter, open-label single-arm segment (Phase 2a) study was followed by a double-blind, randomized, active-controlled, non-inferiority, segment (Phase 2b) at 28 US clinical trial sites which together comprise the Phase 2 clinical trial. This Phase 2 clinical trial was designed to evaluate the clinical efficacy of ibezapolstat in the treatment of CDI including pharmacokinetics and microbiome changes from baseline. from study centers in the United States. In the Phase 2a trial segment,10 patients with diarrhea caused by C. difficile were treated with ibezapolstat 450 mg orally, twice daily for 10 days. All patients were followed for recurrence for 28± 2 days. Per protocol, after 10 patients of the projected 20 Phase 2a patients completed treatment (100% cured infection at End of Treatment (10 of 10).

In the Phase 2b trial segment, 32 patients with CDI were enrolled and randomized in a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or vancomycin 125 mg orally every 6 hours, in each case, for 10 days and followed for 28 ± 2 days following the end of treatment for recurrence of CDI. The two treatments were identical in appearance, dosing times, and number of capsules administered to maintain the blind. In this Phase 2b trial segment, 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population experienced Clinical Cure (CC) and all 15 of 15 (100%) remained free of C. difficile infection (CDI) recurrence through one month after EOT.

When Phase 2b results are combined with Phase 2a results, the Clinical Cure rate in patients with CDI was 96% (25 out of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a in the Modified Intent to Treat Population, plus 15 out of 16 (94%) patients in Phase 2b in the Per Protocol Population, who experienced Clinical Cure during treatment with ibezapolstat. Notably, in the combined Phase 2 trial, 100% (25 of 25) ibezapolstat-treated patients) who had Clinical Cure at EOT) (End of Treatment) remained cured through one month after EOT, as compared to 86% (12 of 14) for the vancomycin patient group. Ibezapolstat was well-tolerated, with no serious adverse events assessed by the blinded investigator to be drug- related. The Company is confident that based on the pooled Phase 2 ibezapolstat Clinical Cure rate of 96%, Sustained Clinical Cure Rate of 100% and the historical vancomycin Clinical Cure Rate range of 70% to 92% and a Sustained Clinical Cure historical range of 42% to 74%, we will demonstrate non-inferiority of ibezapolstat to vancomycin in Phase 3 trials, in accordance with the applicable FDA Guidance for Industry (October 2022), with favorable differentiation in both Clinical Cure and Sustained Clinical Cure.

In the Phase 2 clinical trial (both trial segments), the Company also evaluated pharmacokinetics (PK) and microbiome changes and test for anti-recurrence microbiome properties, including the change from baseline in alpha diversity and bacterial abundance, especially overgrowth of healthy gut microbiota Actinobacteria and Firmicute phylum species during and after therapy. Phase 2a data demonstrated complete eradication of colonic C. difficile by day three of treatment with ibezapolstat as well as the observed overgrowth of healthy gut microbiota, Actinobacteria and Firmicute phyla species, during and after therapy. Very importantly, emerging data show an increased concentration of secondary bile acids during and following ibezapolstat therapy which is known to correlate with colonization resistance against C. difficile. A decrease in primary bile acids and the favorable increase in the ratio of secondary-to-primary bile acids suggest that ibezapolstat may reduce the likelihood of CDI recurrence when compared to vancomycin. The company also reported positive extended clinical cure (ECC) data for ibezapolstat (IBZ), its lead antibiotic candidate, from the Company's recently completed Phase 2b clinical trial in patients with CDI. This exploratory endpoint showed that 5 of 5 IBZ patients followed for up to three months following Clinical Cure experienced no recurrence of infection. Furthermore, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.

About Ibezapolstat

Ibezapolstat is the Company's lead antibiotic candidate planning to advance to international Phase 3 clinical trials to treat patients with C. difficile infection. Ibezapolstat is a novel, orally administered antibiotic, being developed as a Gram-Positive Selective Spectrum (GPSS®) antibacterial. It is the first of a new class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Ibezapolstat's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and the important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome.

In June 2018, ibezapolstat was designated by the U.S. Food and Drug Administration (FDA) as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and will be eligible to benefit from the incentives for the development of new antibiotics established under the Generating New Antibiotic Incentives Now (GAIN) Act. In 2019, FDA granted "Fast Track" designation to ibezapolstat for the treatment of patients with CDI. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.

About Clostridioides difficile Infection

According to the 2017 Update (published February 2018) of the Clinical Practice Guidelines for C. difficile Infection by the Infectious Diseases Society of America (IDSA) and Society or Healthcare Epidemiology of America (SHEA), CDI remains a significant medical problem in hospitals, in long-term care facilities and in the community. C. difficile is one of the most common causes of health care- associated infections in U.S. hospitals (Lessa, 2015, NEJM). Recent estimates suggest C. difficile approaches 500,000 infections annually in the U.S. and is associated with approximately 20,000 deaths annually. (Guh, 2020, NEJM. Based on internal estimates, the recurrence rate for the antibiotics currently used to treat CDI is between 20% and 40% among approximately 150,000 patients treated. We believe the annual incidence of CDI in the U.S. approaches 600,000 infections and a mortality rate of approximately 9.3%.

About the Microbiome in C. difficile Infection and Bile Acid Metabolism

C. difficile can be a normal component of the healthy gut microbiome, but when the microbiome is thrown out of balance, the C. difficile can thrive and cause an infection. After colonization with C. difficile, the organism produces and releases the main virulence factors, the two large clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou, Microorganisms 2020.) TcdA and TcdB are exotoxins that bind to human intestinal epithelial cells and are responsible for inflammation, fluid and mucous secretion, as well as damage to the intestinal mucosa. Bile acids perform many functional roles in the GI tract, with one of the most important being maintenance of a healthy microbiome by inhibiting C. difficile growth. Primary bile acids, which are secreted by the liver into the intestines, promote germination of C. difficile spores and thereby increase the risk of recurrent CDI after successful treatment of an initial episode. On the other hand, secondary bile acids, which are produced by normal gut microbiota through metabolism of primary bile acids, do not induce C. difficile sporulation and therefore protect against recurrent disease. Since ibezapolstat treatment leads to minimal disruption of the gut microbiome, bacterial production of secondary bile acids continues which may contribute to an anti-recurrence effect. Beneficial effects of bile acids include a decrease in primary bile acids and an increase in secondary bile acids in patients with CDI, which was observed in the Company's Ph2a trial results and previously reported (Garey, CID, 2022). In the Ph2b trial, ibezapolstat-treated patients showed lower concentrations of fecal primary bile acids, and higher beneficial ratio of secondary to primary bile acids than vancomycin-treated patients.

Forward-Looking Statements

Any statements in this press release about our future expectations, plans and prospects, including statements regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether ibezapolstat will benefit from the QIDP designation; whether ibezapolstat will advance through the clinical trial process on a timely basis; whether the results of the clinical trials of ibezapolstat will warrant the submission of applications for marketing approval, and if so, whether ibezapolstat will receive approval from the FDA or equivalent foreign regulatory agencies where approval is sought; whether, if ibezapolstat obtains approval, it will be successfully distributed and marketed; and other risks and uncertainties described in the Company's annual report filed with the Securities and Exchange Commission on Form 10-K for the year ended December 31, 2024, and in the Company's subsequent filings with the Securities and Exchange Commission. Such forward- looking statements speak only as of the date of this press release, and Acurx disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances after the date of such statements, except as may be required by law.

Investor Contact:
Acurx Pharmaceuticals, Inc.,
David P. Luci, President & CEO
Tel: 917-533-1469,
Email: davidluci@acurxpharma.com

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SOURCE Acurx Pharmaceuticals, Inc.

FAQ

What did Acurx (ACXP) announce at IDWeek 2025 on October 20, 2025 about ibezapolstat?

Acurx presented data showing ibezapolstat spares bile acid-metabolizing gut bacteria and that this profile likely contributed to its anti-recurrence effect in CDI.

Does ibezapolstat (ACXP) have FDA designations that speed development?

Yes. Ibezapolstat has FDA QIDP and Fast-Track designation, and Acurx's preclinical candidates are QIDP/Fast-Track eligible.

What evidence did Acurx present that DNA pol IIIC inhibitors may be a class that spares the microbiome?

Acurx presented mouse colonic microbiome data showing representative DNA pol IIIC inhibitors had microbiome-sparing effects compared with linezolid, described as initial evidence of a class effect.

How did linezolid compare to DNA pol IIIC inhibitors in the IDWeek 2025 data?

In the mouse experiments, mice treated with linezolid showed an over-abundance of Pseudomonadota, while DNA pol IIIC inhibitors showed microbiome-sparing profiles.

What clinical benefit is linked to ibezapolstat's gut microbiome profile for CDI patients?

The gut bile acid profile that ibezapolstat preserves is linked to its anti-recurrence effect; no patient cured in the Phase 2 trial experienced recurrence.

Where can investors view Acurx's IDWeek 2025 presentation for ACXP?

The presentation is available via the company website at www.acurxpharma.com.