Health~Holland Awards Another Innovative Research Grant for DNA Pol IIIC Inhibitors to Leiden University Medical Center and Acurx Pharmaceuticals

STATEN ISLAND, N.Y.,Nov. 18, 2025/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, announced today that Health~Holland has awarded another grant of approximately $375,000 USD to Leiden University Medical Center (LUMC) and, through a three-party Consortium Agreement, Acurx Pharmaceuticals. The grant will fund this innovative research project entitled:POLSTOP4MDRO – Assessing conservation in mode-of-action and -resistance for a novel class of antimicrobials.

Acurx Pharmaceuticals (Acurx) has been collaborating with Leiden University Medical Center (LUMC) in Leiden, The Netherlands, to establish medium-throughput assay for biochemical activity of PolC* (pol IIIC) enzymes from various Gram-positive pathogens, as well as to determine the structure of a representative PolC (pol IIIC) enzyme in complex with a novel PolC (pol IIIC) inhibitor from Acurx's portfolio. The results of this work, which include kinetic data for a suite of Acurx lead compounds versus the polymerases of MRSA, VRE and PRSP and three complete structures (apo-PolC, PolC in complex with ibezapolstat and PolC in complex with ACX-801), were 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.

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: "This collaborative new grant opportunity will be a novel scientific accomplishment contributing to Acurx programs by enhancing knowledge of the structure of pol IIIC from different pathogenic, multidrug-resistant organisms. Additionally, we will study the binding of Acurx drug candidates in complex with pol IIIC enzymes to establish a detailed in vitro characterization of polymerase and inhibiting activity." He further stated: "This work will lead to important insights into differences between replicative polymerases of critical drug-resistant Gram-positive pathogens and pave the way for rational design of novel inhibitors based on structure-activity relationships in the future."

Robert J. DeLuccia, Executive Chairman of Acurx, stated "We believe this state-of-the-art structural biology research, which includes crystallography and cryo-electron microscopy, can be translated into chemical synthesis strategies using Artificial Intelligence and Free Energy Perturbation to develop an innovative portfolio of novel inhibitors of DNA polymerases of target organisms with our GPSS®(Gram-positive Selective Spectrum) antibiotic candidates". He further stated: "This could lead to identification of selective inhibitors for serious priority Gram-positive infections, particularly those caused by MRSA, VRE and PRSP, offering more opportunities to enhance our development pipeline and expand the treatment options with new classes of antibiotics for multi-drug-resistant bacterial infections." Additionally, as was previously reported, new experiments provide initial evidence that preservation of beneficial gut microbiota may be a class effect of Acurx's pol IIIC inhibitors."

*"pol C" is alternative nomenclature for "pol IIIC"

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 ofClostridioides difficileInfection in a recently completed Phase 2 clinical trial and is ready to enter Phase 3 clinical trials, but the molecular basis of selective inhibition is not fully characterized as no structural information is available on pol IIIC proteins from pathogens. This research project will determine the structure of pol IIIC from the multidrug-resistant organisms methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococci (VRE) and/or penicillin resistant Streptococcus pneumoniae (PRSP) in the absence and presence of lead compounds. These results will reveal the structural space of inhibitor-binding and guide the rational design of inhibitors with optimal pharmacological properties and organism-specificity that will be demonstrated by in vitro polymerase inhibition assays and in vivo minimal inhibitory concentration determination.

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.

The Research Consortium participants are the Dutch Top Sector Life Sciences and Health ('Topconsortium voor Kennis en Innovatie' or 'TKI' Life Sciences and Health) and is represented by Stichting Life Sciences Health – TKI (aka, Health~Holland) and is tasked by the Dutch government to promote and stimulate new public-private partnerships (PPPs) to undertake R&D projects in the life sciences. To promote such partnerships, the Minister of Economic Affairs and Climate Policy has allocated certain funds to Stichting LSH-TKI, to grant allowances to projects under the TKI-programme Life Sciences & Health. Stichting LSH-TKI has designated the Board of Directors of LUMC as delegated grantor for the PPP allowance allocated to the LUMC.

Together with Acurx Pharmaceuticals the PPP will initiate the research project entitled:POLSTOP4MDRO – Assessing conservation in mode-of-action and -resistance for a novel class of antimicrobials.

The collaboration project is co- funded by the  PPS Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.

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.

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.

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 designatedC. difficileas an urgent threat highlighting the need for new antibiotics to treat CDI.