A New Approach to Treating CDI

Ibezapolstat (formerly named ACX-362E) is our lead antibiotic candidate.  Ibezapolstat is a first-in-class of a new class of Pol IIIC inhibitors which is in clinical development to treat C. difficile infections or CDI.  Current treatments for CDI infections utilize other mechanisms of action while ibezapolstat is the first antibiotic candidate intended to work by blocking the Pol IIIC enzyme in C. difficile.  This enzyme is necessary for replication of the DNA of the DNA of the bacterial cell.

Acurx has worked closely with the FDA to obtain FDA “Fast track” designation as well as designation of ibezapolstat as a qualified infectious disease product, or QIDP, which provides incentives through the GAIN Act including priority review by the FDA, “fast-track” eligibility and extension of statutory exclusivity periods in the U.S. for an additional 5 years upon FDA marketing approval of the product to treat patients with CDI.

Acurx acquired the worldwide rights to ibezapolstat from GLSynthesis Inc. in February 2018.

Ibezapolstat is active against the GAIN Pathogen Clostridium difficile

C. difficile, or CDI, is a pathogen listed in the GAIN Act as a pathogen that causes serious or life-threatening infections and the CDC identifies CDI as an urgent need in terms of generating new antibiotics to treat these infections.

The GAIN Act, Title VIII (Sections 801 through 806) of the FDA Safety and Innovation Act, seeks to provide pharmaceutical and biotechnology companies with incentives to encourage the development of new drugs to treat, prevent, detect and diagnose antibiotic-resistant infections. Qualifying pathogens are defined by the GAIN Act to include multi-drug resistant Gram-negative bacteria, including Pseudomonas, Acinetobacter, Klebsiella, and Escherichia coli species; resistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus (VRE); multi-drug resistant tuberculosis; and Clostridium difficile. It extends the length of time an approved drug is free from competition and clarifies the regulatory pathway for new antibiotics.

Mechanism of Action

DNA polymerase IIIC (pol IIIC) has been shown to be essential for replicative DNA synthesis in aerobic, low G-C Gram-positive bacteria, i.e. those with a low guanine-cytosine (G-C) ratio relative to their adenine-thymine (A-T) ratio. Pol IIIC-specific genes of several such Gram-positive bacteria have been cloned and expressed, and these enzymes share a unique capacity to be inhibited by 6-anilinouracils (AU), 2-phenylguanines (PG) and related compounds which are analogs of 2'-deoxyguanosine 5'-triphosphate (dGTP). Ibezapolstat is a recent example of this class of compounds and is being advanced to clinical trials.

Ibezapolstat has been demonstrated to inhibit purified C. difficile pol IIIC with a Ki of 0.325 µM, confirming the ternary complex hypothesis. In addition, a whole cell study involving the measurement of chromosomal DNA replication demonstrated the expected gene dosage results that suggest inhibition of DNA replication by ibezapolstat.

Clinical Development Program

Acurx completed its Phase 1 clinical trial of ibezapolstat in August 2019 and is targeting initiation of enrollment of its Phase 2 clinical trial in Q1 2020.