Acurx Pharmaceuticals Advances Ibezapolstat to Phase 3 Trials for C. difficile Infection

Acurx Pharmaceuticals is advancing its lead antibiotic candidate ibezapolstat to international Phase 3 clinical trials for the treatment of patients with C. difficile infection (CDI), following final regulatory guidance from both the FDA and the European Medicines Agency (EMA). The company has also launched a new clinical trial program for recurrent CDI and presented scientific research findings detailing the mechanism of action of its new class of DNA polymerase IIIC inhibitors.

Acurx announced that the company's clinical program in the broader CDI patient population is ready to advance to Phase 3 international pivotal clinical trials. Both the EMA and FDA provided final advice confirming the non-inferiority study design elements, patient population, primary and secondary endpoints, and size of the registration safety database for the planned trials. The EMA's scientific advice confirmed that the clinical, non-clinical, and CMC information package supports advancement of the Phase 3 program and, if successful, supports the submission of a Marketing Authorization Application (MAA) for regulatory approval in Europe. The information package submitted to the EMA included details on two planned international Phase 3 clinical trials, which will be 1:1 randomized and designed as non-inferiority versus vancomycin.

The company recently announced the launch of a clinical trial program in patients with recurrent CDI (rCDI). This new program begins with an open-label pilot trial in patients with multiply-recurrent CDI, defined as having at least three episodes within the past 12 months. Results from this 20-patient trial will inform a planned active-controlled, Phase 3 registration trial in the rCDI indication. Ibezapolstat's Phase 2 results showed a 96% clinical cure rate in 26 patients with no recurrence in patients while sparing the gut microbiome. 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.

The company also presented scientific research findings from its collaboration with Leiden University Medical Center (LUMC). High-resolution cryo-electron microscopy resolved the structure of ibezapolstat in relationship to the binding pocket of a Gram-positive DNA polymerase IIIC (pol IIIC) to 3.2Å. The active site of the polymerase is conserved in more than 220 Gram-positive species, indicating potential for broad clinical utility. The Nature Communications scientific journal published results from this collaboration demonstrating structural biology research that reveals, for the first time, a DNA pol IIIC inhibitor bound to its target.

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. The antibiotic's unique spectrum of activity, which includes C. difficile but spares other Firmicutes and important Actinobacteria phyla, appears to contribute to the maintenance of a healthy gut microbiome. Ibezapolstat was designated by the FDA as a Qualified Infectious Disease Product (QIDP) for the treatment of patients with CDI and granted "Fast Track" designation. The CDC has designated C. difficile as an urgent threat highlighting the need for new antibiotics to treat CDI.

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. The R&D pipeline includes antibiotic product candidates that target Gram-positive bacteria, including Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and drug-resistant Streptococcus pneumoniae (DRSP). In February 2026, the USPTO granted a new patent for the company's Pol IIIC inhibitors covering composition of matter and method of use, extending to December 2039 subject to extension under US patent rules.

For the full year and fourth quarter ended December 31, 2025, the company ended the quarter with cash totaling $7.6 million, compared to $3.7 million as of December 31, 2024. During the fourth quarter, the company raised approximately $1.5 million of gross proceeds through purchases under the Equity Line of Credit, with gross proceeds totaling approximately $4.0 million for the full year. In October 2025, the company received gross proceeds from the exercise of 170,068 Series F Warrants of approximately $1.4 million.