A New Approach to Treating CDI

Acurx’s lead antibiotic product development candidate is ACX-362E, a DNA polymerase inhibitor with a novel mechanism of action for oral treatment of Clostridium difficile Infections, or “CDI.” The Food and Drug Administration, or “FDA,” granted designation of ACX-362E as a Qualified Infectious Disease Product, or “QIDP” in June 2018 for use as an oral treatment patients with CDI.

Acurx acquired the worldwide rights to ACX-362E from GLSynthesis Inc. in February 2018.

FDA has granted Qualified Infectious Disease Product (QIDP) status under the GAIN Act (section 505E(g) of the FFDCA) for ACX-362E as an oral treatment for patients with CDI.

ACX-362E 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.

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). ACX-362E is a recent example of this class of compounds and is being advanced to clinical trials.

ACX-362E 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 ACX-362E.

Clinical Development Plan

Acurx plans to file the IND and initiate a Phase 1 clinical trial in 4Q2018. Acurx targets top-line data from the Phase 1 clinical trial in mid-2019.

About Clostridium difficile Infections

The CDC has reported that there are nearly 500,000 patients per year treated for Clostridium difficile infections, or CDI, in the U.S. alone, with a recurrence rate approximated at 20% to 30%, with limited antibiotics available to treat patients with CDI.  CDI is also prevalent in Europe, Japan and Canada, which are countries where the Company has patent protection and anticipates further clinical development and commercialization.    

CDI) is a serious and life-threatening disease that is transmitted by the fecal-oral route.

About Clostridium difficile Infections

Publications

Review scientific publications to get a deeper understanding of the disease areas of our product candidates and current treatment guidelines for CDI candidates in our current product pipeline.

View Publications