Announcement • Jun 16
Acurx Pharmaceuticals, Inc. Announces Presentation Of Results From Leiden University Medical Center Public-Private Partnership For Its DNA Pol IIIC Inhibitors At The Leiden Early Drug Discovery & Development Scientific Conference
Acurx Pharmaceuticals, Inc. announced that a presentation was given by Mia Urem, PhD, from Leiden University Medical Center in the Netherlands entitled: "A unique inhibitor conformation selectively targets Gram+ Bacterial DNA Replication" at the Leiden Early Drug Discovery & Development Scientific Conference on June 11, 2026. Results are from Acurx's ongoing scientific collaboration with Leiden University Medical Center partially under a grant from Health Holland to further study the mechanism of action of DNA pol IIIC inhibitors. LUMC highlighted Acurx's new class of promising antimicrobials, ibezapolstat and related analogues specifically target Gram-positive bacteria. High-resolution cryo-electron microscopy resolved the structure of ibezapolstat in relationship to the binding pocket of a Gram-positive DNA pol IIIC to the level of 3.2Å. The Company's preclinical pipeline includes development of an oral product candidate for treatment of ABSSSI (Acute Bacterial Skin and Skin Structure Infections), with a development program for post-exposure prophylaxis of inhalation anthrax being planned in parallel. Ibezapolstat has previously been granted FDA QIDP and Fast-Track Designations and has received SME (Small and Medium-sized Enterprise) designation by the EMA. Dr. Urem's group utilized high-resolution cryo-electron microscopy to resolve the structure of ibezapolstat in relationship to the binding pocket of a Gram-positive DNA pol IIIC to the level of 3.2Å. The active site of the polymerase is conserved in >220 Gram-positive species, indicating potential for broad clinical utility of this bactericidal inhibitory mechanism of action of Acurx compounds. The distinctive non-planar conformation of IBZ and chemically related molecules, together with high conservation of the binding pocket in DNA pol IIIC, suggests that this is a general mechanism for this class of inhibitor and that a wide range of Gram-positive infections, including those caused by high-priority pathogenic Gram-positive bacteria, may be susceptible to treatment with Acurx pipeline antibiotics. Acurx's 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). 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. The presentation is posted on the Acurx website. 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 as a Qualified Infectious Disease Product 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 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. 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. The primary efficacy analysis will be performed using a Modified Intent-To-Treat population. This will result in an estimated 450 subjects in the Modified Intent-To-Treat 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. 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 recent Phase 2a clinical trial, but the molecular basis of selective inhibition is not fully characterized as no structural information is available on pol IIIC proteins from pathogens. Ongoing 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. The presented research was performed in part as a public-private partnership that includes the Dutch Top Sector Life Sciences and Health and is represented by Stichting Life Sciences Health – TKI (aka, Health~Holland). This foundation is tasked by the Dutch government to promote and stimulate public-private partnerships 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.
