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Acurx Pharmaceuticals, Inc., a clinical stage biopharmaceutical company developing a new class of antibiotics for difficult-to-treat bacterial infections, 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] [https://rdcu.be/fxMVQ]. 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."
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 programme 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.
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] [https://rdcu.be/fxMVQ]. 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.
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.
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).
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