Slide 1: First of a New Class of Antibiotics (DNA pol IIIC Inhibitors)
First of a New Class of Antibiotics (DNA pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority Pathogens Preparing for the Next Pandemic: Antimicrobial Resistance in Gram-positive Bacterial Infections Presenters: Michael H. Silverman, MD, FACP*, Acurx Medical Director Kevin Garey, PharmD, MS*, Profess
Slide 2: AMR: Global Challenge
AMR: GLOBAL CHALLENGE We must prepare our public health systems to fight multiple threats, simultaneously. Now is the time to address our current antimicrobial- resistant threats, while simultaneously preparing for unknown emerging threats in the future.* Unmet Medical Need: CDC/FDA classification:
Slide 3: Acurx Platform Technology and Pipeline
Acurx Platform Technology and Pipeline DNA Polymerase IIIC Inhibition: ▪Innovation criteria1: ✓ New chemical class ✓ New target ✓ New MOA ✓ No cross-resistance ▪Gram-Positive Selective Spectrum (GPSS®) antibiotics target multi-drug-resistant bacterial pathogens (including C. difficile, MRSA, VRE, DR
Slide 4: Factors Informing Ibezapolstat Registration Trials
Factors Informing Ibezapolstat Registration Trials ▪ Nonclinical: ▪ Bactericidal potency vs C. difficile (MIC90 = 4 µg/mL) ▪ Potency maintained against MDR strains ▪ Does not trigger sporulation or toxin release ▪ Reduced flagellar movement; active in biofilms ▪ Microbiome effects similar to FDX in
Slide 5: Systemic GPSS Antibiotic Platform
® Systemic GPSS Antibiotic Platform ▪ Systemic DNA Pol IIIC Inhibitor Platform: Systemic treatment of Staphylococcus, Streptococcus and Enterococcal infections, including MRSA, VRE, and other resistant G+ bacterial infections; WHO/CDC Priority Pathogen Lists 1 ▪ Novel bactericidal mechanism of actio
Slide 6: Systemic GPSS Antibiotic Program Status
® Systemic GPSS Antibiotic Program Status Hit-to-Lead testing of >600 novel compounds has resulted in significant advances of drug-like properties: ▪ In vitro & in vivo safety ▪ Oral and IV efficacy in mouse infection models including in neutropenic mice (MRSA systemic & thigh, VRE thigh, and PRSP l
Slide 7: Structural Biology of DNA pol IIIC Inhibition
Structural Biology of DNA pol IIIC Inhibition Nature Communications IN-PRESS: A unique inhibitor conformation selectively targets the DNA polymerase PolC of Gram-positive priority pathogens (Smits*, Leiden University Medical Center) ▪ Structural biology using cryo-electron microscopy ▪ Mechanistic i
Slide 8: Cladographic Explanation of Ibezapolstat Selectivity
Cladographic Explanation of Ibezapolstat Selectivity February 24, 2025; AAC: The Microbiome-restorative Potential of Ibezapolstat for the Treatment of Clostridioides difficile Infection is Predicted Through Variant PolC-type DNA Polymerase III in Lachnospiraceae and Oscillospiraceae (McPherson et al
Slide 9: Microbiome Selectivity in Other DNA Pol IIIC inhibitors
Microbiome Selectivity in Other DNA Pol IIIC inhibitors MRSA thigh infection model in neutropenic mice (4 mice per group). Microbiome analysis from colon sections. Three representative DNA pol IIIC inhibitor compounds in preclinical development were tested at two doses compared to linezolid. These e
Slide 10: Thank You!
First of a New Class of Antibiotics (DNA pol IIIC Inhibitors) Targeting CDC/FDA/WHO Priority Pathogens Preparing for the Next Pandemic: Antimicrobial Resistance in Gram-positive Bacterial Infections For additional information and/or to express interest in participating as an investigator in our IBZ