Ibezapolstat

This new partnership builds on the previously reported successful results from the innovative research grant received in November 2025 from Health-Holland to Leiden University and Acurx This prior work included high-resolution elucidation of the interaction of ibezapolstat with its molecular target, DNA polymerase IIIC (pol IIIC, also known as PolC), with mechanistic findings that explain its properties of lacking cross-resistance with other antibiotics and not fostering the emergence of vancomycin-resistant Enterococcus strains, a unique differentiation among anti-CDI antibiotics The new research partnership aims to generate the first-ever 3D structure of PolC from methicillin-resistant Staphylococcus aureus (MRSA) in complex with DNA and an Acurx inhibitor to advance discovery of new antibiotics to treat infections caused by this high-priority pathogen This partnership will extend mechanistic research into PolC inhibition to accelerate the development of novel agents for the systemic treatment of infections caused by a range of Gram-positive pathogens resistant to currently available antibiotics STATEN ISLAND, N.Y., Aug. 10, 2026 /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, today announced a new scientific partnership with Leiden University Medical Center (LUMC) in the Netherlands. Prior work under the November 2025 research grant from Health-Holland to Leiden University Medical Center and Acurx for DNA pol IIIC Inhibitors included detailed three-dimensional structures for three poI IIIC complexes from Enterococcus and was published in Nature Communications in 2025 [A unique inhibitor conformation selectively targets the DNA polymerase PolC of Gram-positive priority pathogens]* []. These results have yielded valuable insights into the structure-function relationship for the PolC class of inhibitors. This new partnership aims to generate the first-ever 3D structure of PolC from MRSA in complex with DNA and an Acurx inhibitor to advance discovery of new antibiotics to treat this high-priority clinical pathogen. This new partnership will extend mechanistic research into PolC inhibition to accelerate the development of novel new agents that are systemically active against a range of Gram-positive pathogens resistant to currently available antibiotics. Wiep Klaas Smits, PhD, Associate Professor, LUMC Department of Medical Microbiology will be the lead researcher in collaboration with Meindert Lamers, PhD, Associate Professor, LUMC Department of Cell and Chemical Biology and Mia Urem, PhD, from Leiden University Medical Center in the Netherlands. Dr. Smits stated: "Whereas the previous work established a conserved mode of action for this novel class of antibiotics, the new project will allow us to investigate more subtle differences between PolC's from different Gram-positive organisms and will improve our understanding of how these different novel antibiotics interact with their target beyond their inhibitory group." Robert J. DeLuccia, Executive Chairman of Acurx, stated: "This work is very important, when coupled with the recently reported initial data from laboratory experiments in MRSA-infected neutropenic mice at the University of Houston School of Pharmacy demonstrating that Acurx DNA pol IIIC antibiotics showed favorable gut-sparing effects to be a class effect while maintaining systemic antibacterial activity . It will pave the way for further rational design of novel DNA pol IIIC inhibitors based on new structure-activity relationships." He further stated: "Treating systemic infections, like those caused by MRSA, without promoting antibiotic-induced gut dysbiosis has the potential for a transformational shift in the treatment paradigm for antibacterial therapy." The scientific poster presented at ESCMID Global in April 2026 is available on our website: Acurx's portfolio of preclinical compounds includes 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. Additionally, Acurx intends to leverage its preclinical development program for S.aureus infections for the treatment of post-exposure inhalational anthrax caused by B. anthracis, a Bioterrorism Category A Threat-Level pathogen. Acurx's DNA PolC 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 Prior Research Project, Leiden University Medical Center, the Research Consortium and the New Scientific Partnership between LUMC and Acurx Antimicrobial resistant microorganisms are a major threat to global health and pose a significant economic burden. Increasing resistance to multiple agents and resistance to so called last-resort antibiotics underscore the necessity to develop therapeutics that have a novel mode of action. DNA replication is a process that can be successfully targeted by small molecules. Ibezapolstat, an inhibitor of the replicative DNA polymerase pol IIIC from Gram- positive bacteria identified by screening library of dGTP analogues, has shown promising results for the treatment of Clostridioides difficile Infection in a recently completed Phase 2 clinical trial and is ready to enter Phase 3 clinical trials. Prior work under the November 2025 research grant from Health-Holland to Leiden University Medical Center and Acurx for DNA pol IIIC Inhibitors included detailed three-dimensional structures for three poI IIIC complexes from Enterococcus and was published in Nature Communications [A unique inhibitor conformation selectively targets the DNA polymerase PolC of Gram-positive priority pathogens] []. These results have yielded valuable insights into the structure-function relationship for the PolC (pol IIIC) class of inhibitors. This new partnership builds on the previously reported successful results from the innovative research grant received in November 2025 from Health-Holland to Leiden University and Acurx. The partnership aims to generate the first-ever 3D structure of Pol C from methicillin-resistant Staphylococcus aureus (MRSA) in complex with DNA and an Acurx inhibitor to advance discovery of new compounds to treat this high-priority clinical pathogen. This new partnership will extend mechanistic research into pol IIIC inhibition to accelerate the development of novel new agents that are systemically active against a range of Gram-positive pathogens resistant to currently available antibiotics. Leiden University was the first university to be established in the Netherlands. Its motto is praesidium libertatis – bastion of freedom. The University wishes to create an increasingly attractive and challenging working climate for top academics and young researchers that is guided by quality and excellence. Leiden University Medical Center (LUMC) research aims to meet the highest international standards of quality and academic integrity. LUMC promotes excellent research through greater collaboration, both disciplinary and interdisciplinary; stronger positioning and greater scope for top talent; and better supervision and more support for young researchers. About Acurx Pharmaceuticals, Inc. 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+ 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 NDA filing for both the acute treatment and the reduction of recurrence of CDI. Trial start-up activities for the IBZ-PATHFINDER ground-breaking clinical trial in patients with rCDI have been initiated with patient enrollment to begin in the next few months. 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. To learn more about Acurx Pharmaceuticals and its product pipeline, please visit . About MRSA 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. 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 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: [email protected] SOURCE Acurx Pharmaceuticals, Inc. 21% more press release views with Request a Demo

Data demonstrated beneficial bacterial taxa persist in fecal samples from patients with rCDI despite multiple prior CDI treatments with the antibiotic standards of care, vancomycin (VAN) and/or fidaxomicin (FDX) Following acute treatment with ibezapolstat (IBZ), these beneficial microorganisms will have the opportunity to repopulate the microbiome in a beneficial way that may prevent recurrence IBZ and FDX were superior in biofilm experimental models with IBZ significantly more effective at killing C. difficile than VAN and FDX Trial start-up activities for a ground-breaking clinical trial in patients with multiply-recurrent CDI (rCDI) have been initiated with the first patient expected to enroll in the next quarter; a successful trial outcome has the potential to shift the paradigm of treatment and prevention of rCDI from two agents to one With mutually consistent feedback from both EMA and FDA, Acurx is well positioned to commence its international Phase 3 registration program in the broader CDI patient population ("acute CDI") Acurx has previously been granted FDA QIDP and Fast-Track Designation and has received SME (Small and Medium-sized Enterprise) designation by the EMA STATEN ISLAND, N.Y., July 14, 2026 /PRNewswire/ -- Acurx Pharmaceuticals, Inc. (NASDAQ: ACXP) a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, announced today that a poster presentation entitled: Microbiome Restoration Potential of Ibezapolstat vs. Comparator Antibiotics in Patients with Multiply-recurrent Clostridioides difficile Infection (CDI) was presented by Kevin Garey, PharmD, MS, FIDSA, Professor and Chair, University of Houston College of Pharmacy, Principal Investigator for microbiology and microbiome aspects of the IBZ clinical trial program at the 18th Biennial Congress of the Anaerobe Society of the Americas held at Columbia University Irving Medical Center in New York City from July 8 to 10, 2026. Studies were performed at the University of Houston to determine whether beneficial gut microbes are present in patients with multiple (≥2) recurrences of Clostridioides difficile infection (rCDI). The objectives of this study were to determine whether beneficial microbes identified in the IBZ Phase 2 studies in patients with initial and 1st recurrent CDI are still present in patients with multiple (≥2) recurrent CDI and to assess killing effects of IBZ vs. comparators in planktonic (non-biofilm) and biofilm mono- and duo-culture studies; specifically, measuring killing of VRE by VAN, FDX, and IBZ in planktonic and biofilm cultures. Commenting on the poster presentation, Dr. Garey stated: "Until now, it has not been known whether repeated courses of VAN and/or FDX destroyed the gut microbiome population of beneficial organisms, namely, those bacterial species that are responsible for metabolizing bile acids and protecting against recurrent episodes of CDI. Our new data indicate that sufficient numbers of such bacteria are preserved to allow regrowth when rCDI treatment consists of an antibiotic like ibezapolstat, which has been shown in our laboratory to be highly selective and preserves the beneficial gut flora." He further stated, "We also showed in our laboratory studies that ibezapolstat was highly effective at killing C. difficile when grown in co-culture with Enterococcus in liquid, planktonic cultures or as part of a biofilm. Ibezapolstat actually outperformed fidaxomicin in biofilm killing effects without causing VRE overgrowth observed with vancomycin." Robert J. DeLuccia, Executive Chairman of Acurx, stated: "These new data provide scientific support for our upcoming trial of ibezapolstat to treat patients with multiply-recurrent CDI which begins with a 20-patient, open-label pilot trial in patients with at least 3 episodes of CDI in the past 12 months and will inform elements of a planned active-controlled, Phase 3 registration trial in rCDI. 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 under the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs (Guidance for Industry, 2020). He added: "Along with results from IBZ's international Phase 3 registration program in patients with acute CDI, we believe IBZ has the potential to be the first agent to demonstrate clinical success in both the treatment of acute CDI and reduction of recurrence in rCDI and such success would shift the paradigm of treatment and prevention of rCDI from two agents to one." The poster is available on the Acurx Pharmaceuticals website About the Anaerobe Society of the Americas Founded in 1992, The Anaerobe Society of the Americas is an international organization, promoting the study and application of knowledge of anaerobic bacteriology. The primary activity of the society is organizing the biennial Anaerobe Congress for researchers, clinicians, and laboratory scientists from around the world to engage in presentations, exchanges, and dialogues related to anaerobes. Acurx previously announced it has received mutually consistent positive feedback from both FDA and EMA which included details on Acurx's two planned international Phase 3 clinical trials in patients with acute CDI. Accordingly, if successful, these trials will support the submission of a U.S. New Drug Application (NDA) and a Marketing Authorization Application (MAA) for regulatory approval in Europe. 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. The primary efficacy analysis will be performed using a Modified Intent-To-Treat (mITT) population. 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 ). 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 (25)00054-0/fulltext). 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 (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 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 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 preparing to advance into international Phase 3 trials. Additionally, the Company has initiated start-up activities for a ground-breaking clinical trial in patients with rCDI with the first patient expected to enroll in the fourth quarter this year. This trial is a 20-patient, open-label pilot trial in patients with multiply-recurrent CDI with at least 3 episodes of CDI in the past year and will inform elements of a planned active-controlled, Phase 3 registration trial in the rCDI. 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 under the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs (Guidance for Industry, 2020). Successful trial outcome has the potential to shift the paradigm of treatment and prevention of rCDI from two agents to one. 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 post-exposure prophylaxis of inhalation anthrax is being planned in parallel. Learn more about Acurx Pharmaceuticals and its product pipeline, please visit 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 quarterly report on Form 10-Q for the quarter ended March 31, 2026, as filed with the Securities and Exchange Commission on May 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: [email protected] SOURCE Acurx Pharmaceuticals, Inc. 21% more press release views with Request a Demo