Acurx Pharmaceuticals, Inc. · NASDAQ:ACXP
Acurx Pharmaceuticals — ID Week 2022
17 slides from Acurx Pharmaceuticals's conference presentation, October 2022
Slide 1: Development Update on Ibezapolstat for the Treatment of C. difficile infection: Focus on the Microbiome
Development Update on Ibezapolstat for the Treatment of Clostridioides difficile infection: Focus on the Microbiome Kevin W. Garey, PharmD, MS, FASHP, FIDSA Professor and Chair Dept of Pharmacy Practice and Translational Research
Slide 2: Ibezapolstat (IBZ; ACX362E)
Ibezapolstat (IBZ; ACX362E) ACX-362 dGTP • Ibezapolstat: small-molecule inhibitor of DNA pol IIIC enzyme based upon competitive inhibition of dGTP (guanosine analog) • DNA pol IIIC: essential for replication of low G+C content Gram-positive bacteria (Firmicutes) • Novel mechanism of action GPSS™ (Gr
Slide 3: Spectrum of activity: Ibezapolstat vs. vancomycin
Spectrum of activity: Ibezapolstat vs. vancomycin Phylum Antibiotic activity Ibezapolstat Vancomycin (oral) Actinobacteria No Yes Bacteroidetes No Yes Firmicutes Selective Yes Fusobacteria No No Proteobacteria No No
Slide 4: Phase 1 Study design
Phase 1 Study design Stool collected daily for 13 days Healthy volunteers >18 years old (n=22) Ibezapolstat 450 mg BID X 10 days Ibezapolstat 300 mg BID X 10 days Vancomycin 125 mg QID X 10 days Placebo X 10 days Shotgun metagenomics (Illumina NextSeq 500)
Slide 5: IBZ PH1 results: Ideal PK Properties for GI infections (also safe)
IBZ PH1 results: Ideal PK Properties for GI infections (also safe) Ibezapolstat: Well-tolerated in Phase 2a: MAX: <1 ug/mL 7 AEs, 0 serious AEs Plasma: ng/mL Relationship Serious Treatment Adverse event Intensity Outcome to study drug AE required Headache Mild Unrelated No Resolved No Headache Mild
Slide 6: Both IBZ and vanco decreased alpha diversity but resulted in very distinct microbe populations
Both IBZ and vanco decreased alpha diversity but resulted in very distinct microbe populations
Slide 7: IBZ had a more selective change in Firmicutes vs. vanco
IBZ had a more selective change in Firmicutes vs. vanco
Slide 8: Ibezapolstat Phase 1 study showed beneficial effects on bile acids
Ibezapolstat Phase 1 study showed beneficial effects on bile acids
Slide 9: Phase 2a Open-label Clinical Trial
Phase 2a Open-label Clinical Trial Ibezapolstat 450 mg BID X 10 days Day 12: Initial Day 38: Sustained CDI CDI clinical cure clinical cure Stool collected during course of therapy and at follow-up CDI patients with mild/moderate CDI diagnosed via toxin EIA + (n=10) Microbiology, PK and Microbiome an
Slide 10: Ibezapolstat Phase 2a Clinical Trial Results
Ibezapolstat Phase 2a Clinical Trial Results Clinical Cure Sustained Clinical Cure 100% 100% 90% 90% 80% 80% 70% 70% 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% Clinical Cure (n=10) Sustained Clinical Cure (n=10) Clinical cure: resolution of diarrhea in the 24-hour period immediately Susta
Slide 11: Ibezapolstat had potent C. difficile activity (Phase 2a study)
Ibezapolstat had potent C. difficile activity (Phase 2a study) All samples underwent a 48-hour enrichment step with taurocholate prior to plating on CCFA plates. 90% 86% IBZ MIC 80% Sample Ribotype (ug/mL) Percent of samples with C. difficile growth 70% 1 0.25 F078-126 60% 2 1 F014-020 50% 3 0.5 F10
Slide 12: Plasma and stool PK were consistent from the PH1 study, as was the favorable safety profile
Plasma and stool PK were consistent from the PH1 study, as was the favorable safety profile A) Plasma PK B) Stool PK
Slide 13: Increased alpha diversity while on therapy
Increased alpha diversity while on therapy
Slide 14: Increased proportion of Firmicutes was observed on ibezapolstat therapy
Increased proportion of Firmicutes was observed on ibezapolstat therapy, Clostridiales most common taxa
Slide 15: IBZ Phase 2a continued to show beneficial effects on bile acids
IBZ Phase 2a continued to show beneficial effects on bile acids.
Slide 16: Conclusions: IBZ for the treatment of CDI
Conclusions: IBZ for the treatment of CDI • Clinical Trial • IBZ: Ideal PK characteristics (high fecal concentrations / minimal systemic exposure) • Well tolerated in healthy volunteers and CDI patients • Microbiome Results • Added value of an active comparator (vancomycin) control group in PH1 – th
Slide 17: Acknowledgements
Acknowledgements The Garey Lab Acknowledgements Faculty M Jahangir Alam Figures by BioRender Eugenie Basseres Khurshida Begum Other Images — Filtered by Creative Commons Kevin W Garey Anne J Gonzales-Luna Chenlin Hu Funding Jinhee Jo Postdocs NIH (R44AI13676 and U01AI124290) Hubert Chua Taryn Eubank