- 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. The Agency also agreed with the overall trial design and evaluation criteria and further agreed that the trial testing criteria, if successful, could support indications for both the acute treatment and the reduction of recurrence of CDI. In the event non-inferiority of ibezapolstat to vancomycin for Clinical Cure of CDI is demonstrated, further analyses will be conducted to test for superiority for reduction of recurrence and for clinical cure of CDI.
About Ibezapolstat
Ibezapolstat is the Company's lead antibiotic candidate targeting patients with C. difficile infection. The Company has initiated enrollment of a ground-breaking clinical trial in patients with multiply-recurrent CDI (rCDI) with the first patient enrolled in September 2026. This open-label, single arm 20-patient, pilot trial will enroll patients with multiply-recurrent CDI with at least 3 prior episodes of CDI within the past 12 months. If successful, the Company plans to target a Phase 3 regulatory strategy with just one Phase 3 registration trial in rCDI pursuant to FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD Pathway), subject to concurrence with FDA, based on the data generated in the open-label trial. Upon subsequent successful completion of a Ph3 pivotal rCDI trial, and per the operative FDA procedure, Acurx plans to request FDA approval for treatment and prevention of rCDI. Successful trial outcome has the potential to shift the paradigm of treatment and prevention of rCDI from two agents to one.
In addition, subject to receiving appropriate funding, Acurx is planning to advance to international Phase 3 clinical trials to treat patients with acute C. difficile infection. As previously announced, the Company has received final FDA agreement for our ibezapolstat pivotal Phase 3 trial in acute CDI. Their advice included and confirmed the non-inferiority study design elements, the patient population, primary and secondary endpoints, and size of the registration safety database. Acurx also now has a clear roadmap for conduct of its Phase 3 program in acute CDI and, if successful, requirements for US NDA submission.
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 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. (see https://clinicaltrials.gov/ct2/show/NCT04247542). 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 and continue to test for anti-recurrence microbiome properties seen in the Phase 2a trial, including the treatment-related changes in alpha diversity and bacterial abundance and effects on bile acid metabolism. (Data published in Lancet, August 2025 https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(25)00054-0/fulltext).
About Clostridioides difficile Infection (CDI) and Recurrent CDI (rCDI)
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 30,000 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%.
In recent studies, rCDI incidence ranges from 4% to 19.5% following treatment with fidaxomicin and 17 to 27% following treatment with vancomycin. In patients with multiple prior episodes of CDI, rCDI following treatment with vancomycin is even more problematic, with an incidence of up to 40%. Consequently, the principal unmet medical need in this disease is the prevention of recurrence. The estimated annual public health cost burden in the U.S. annually is ~$5 billion annually with ~$2.8 billion due to recurrent CDI.
About the Microbiome in C. difficile Infection (CDI) 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, 8, 200; doi:10.3390/microorganisms8020200.) 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 (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.
About Acurx Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a new class of small molecule antibiotics for serious and life-threatening 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+ 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 (CDI) is Phase 3 ready to advance to international clinical trials subject to obtaining appropriate financing. Acurx has received FDA guidance in meeting minutes from a July 13, 2026 Type C Meeting to discuss ibezapolstat's (IBZ) Phase 3 clinical program, including the potential to submit an NDA (New Drug Application) based on a single Phase 3 trial and a clinical trial design intended to support indications for both treatment and reduction of recurrence of Clostridioides difficile infection (CDI). FDA stated that it is open to further discussion on the totality of evidence from the clinical development program at a pre-NDA meeting after completion of a single Phase 3 trial and any other clinical trials conducted prior to the pre-NDA meeting, particularly if the clinical efficacy results are robust. Additionally, the Agency agreed that a successful clinical outcome from a single IBZ-ASPIRE Phase 3 trial, supported by the open-label IBZ-PATHFINDER Phase 2 trial in multiply-recurrent CDI (rCDI) will allow an NDA filing for both the acute treatment and the reduction of recurrence of CDI. The IBZ-PATHFINDER trial is currently enrolling. https://clinicaltrials.gov/study/NCT07513285? term=acurx&viewType=Card&rank=2
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 prophylaxis of inhaled anthrax is being planned in parallel.
To learn more about Acurx Pharmaceuticals and its product pipeline, please visit www.acurxpharma.com.
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 described in the Company's annual report on Form 10-K for the year ended December 31, 2025 as filed with the Securities and Exchange Commission on March 12 2026, 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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