ACX-375C Program with GPSS™
Acurx’s second antibiotic program now in lead optimization stage of preclinical development seeks to develop innovative, systemic Gram-positive selective spectrum (GPSS™) bactericidal antibiotics which target all multi-drug resistant (MDR) and sensitive Gram-positive bacterial pathogens. This previously unexploited mechanism of action is the same as ibezapolstat where recent Phase 2 clinical results in CDI (Clostridioides difficile Infection) have validated the therapeutic effect of DNA pol IIIC as a bacterial target. DNA pol IIIC occurs only in low G+C Gram-positive bacteria, and not in Gram-negative bacteria or in healthy cells; inhibition is expected to be highly selective for Gram-positive bacteria and unaffected by current mechanisms of resistance.
Drug-resistant Gram-positive infections are substantial societal, public health, and economic burdens worldwide with significantly greater incidence than drug-resistant Gram-negative infections. The U.S. Centers for Disease Control (CDC) classifies methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP) as “Serious Threats” and Group A/B Streptococcus are “Concerning Threats” https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.
|Enterococcus / VRE||Staph aureus / MRSA^||Strep pneumoniae / PRSP^^|
|ACX-375C MIC (μg/mL)||0.63-2.5||1.25-2.5||1.25-5.0|
|No. of US infections/yr*||66,000/20,000||~2,000,000/80,500||4,000,000/1,200,000|
|No. of US deaths/yr*||Unknown/1,300||Unknown/11,300||22,000/7,000|
*Antibiotic Resistance Threats in the United States, CDC, 2013,
https://www.cdc.gov/drugresistance/biggest_threats.html, Accessed 22 January 2019;
^Estimated from Tong, Clin Microbiol Rev 2015; ^^Huang, Vaccine 2011
US Infections per Year: Selected Gram-positive Organisms
Recently published data (Jernigan, 2020) show that MRSA accounts for 52% of US inpatient infections, almost twice the incidence of carbapenem-resistant (CR) Enterobacteriaceae infections. Furthermore, VRE infections exceed CR Acinetobacter, MDR Pseudomonas aeruginosa and CR Enterobacteriaceae infections combined.
Based upon advice from our scientific advisors, we believe ACX-375C, our second antibiotic candidate, will also be eligible for FDA’s QIDP and Fast Track designations and we plan to file for these FDA designations at the appropriate time in the drug development cycle.