Acurx Pharmaceuticals, Inc. · NASDAQ:ACXP
Acurx Pharmaceuticals — Anaerobe 2024
19 slides from Acurx Pharmaceuticals's conference presentation, July 2024
Slide 1: Microbiome evaluation from the phase 2b study of ibezapolstat compared with vancomycin
Microbiome evaluation from the phase 2b, randomized, double-blind study of ibezapolstat compared with vancomycin for the treatment of Clostridioides difficile infection Kevin W. Garey, M Jahangir Alam, Khurshida Begum, Jacob McPherson, Taryn A. Eubank, Jinhee Jo, Michael H. Silverman for the Ibezapo
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 (Gra
Slide 3: IBZ Clinical Trial Update
IBZ Clinical Trial Update Healthy Adult Volunteers (n=22) Ibezapolstat 450 mg BID x 10 days Ibezapolstat 300 mg BID x 10 days Analysis: • Adverse effects • Pharmacokinetics in plasma Vancomycin 125 mg QID x 10 days and stool • Shotgun metagenomics (Illumina NextSeq 500) Placebo x 10 days Stool colle
Slide 4: Phase 1 Results
Phase 1 Results Safe and effective for GI infections 4
Slide 5: IBZ Phase 2a
IBZ Phase 2a CDI patients with mild/moderate disease Day 12: Initial Day 38: diagnosed via toxin EIA IBZ Therapy clinical cure Sustained (n=10) clinical cure 10/10 patients achieved clinical cure and sustained clinical cure Ibezapolstat 450 mg BID x 10 Stool collected during therapy and at follow up
Slide 6: IBZ shown to have favorable effects on the microbiome
IBZ shown to have favorable effects on the microbiome IBZ Phase 1 Healthy volunteer study in comparison with VAN IBZ Phase 2a. Single arm, no-comparator study of CDI patients (n=10) IBZ: More narrow spectrum IBZ: Increased proportion of Actinobacteriota Increased proportion of Actinobacteriota Incre
Slide 7: IBZ Phase 2b Microbiome Objectives
IBZ Phase 2b Microbiome Objectives • Evaluate IBZ vs vancomycin (VAN) in patients with CDI for fecal microbiome effects: • Microbiologic eradication • Metagenomic proportional change • Quantitative changes in relative taxa 7
Slide 8: Phase 2b Study design
Phase 2b Study design Outcomes Measured Initial clinical cure (day 12 evaluation) Patients with mild/moderate CDI diagnosed using an EIA free toxin Sustained clinical cure (day 38) kit Extended clinical cure (3 months) Ibezapolstat 450 mg BID X 10 days Time to resolution of diarrhea (TTRD) (days 0-1
Slide 9: Consort Diagram
Consort Diagram Patients enrolled (n=32) IBZ VAN (n=18) (n=14) Modified intent to treat population Completed Completed study (n=16*) study (n=14) *One patient given IBZ withdrew consent prior to first dose; one patient given IBZ had a history of underlying irritable bowel disease and was excluded fr
Slide 10: Demographics and Baseline Information
Demographics and Baseline Information IBZ (n=16) VAN (n=14) P value Age, years 64±13 62±10 0.57 >75 y/o 5 (31.2%) 2 (14.3%) Female 13 (81%) 11 (79%) 0.85 White 16 (100%) 13 (93%) 0.27 Hispanic or Latino 11 (69%) 11 (79%) 0.54 Charlson Comorbidity index 2.6±1.5 2.2±1.5 0.47 Number of UBMs at baseline
Slide 11: Efficacy (mIT population) Safety
Efficacy (mIT population) Safety IBZ VAN Drug-related Serious 0 0 Adverse Events Drug-related treatment 0 0 withdrawals Moderate adverse event, Headache 0 possibly (n=1) related Mild adverse GERD (n=2) event, possibly 0 Nausea (n=1) related 5 of 5 (100%) IBZ patients followed for three months experi
Slide 12: Microbiologic Eradication
Microbiologic Eradication 80% 73% 71% 70% IBZ VAN 60% 50% 40% IBZ: RT 106 VAN: RT Other VAN RT 027 VAN RT 106 VAN RT Other 30% 20% 10% 7% 8% 7% 7% 7% 0% 0% 0% 0% 0% 0% Baseline (15,14) Day 3 (15,13) Day 5 (16,14) Day 8 (11,14) Day 10 (15, 14) Day 12 (16, 13) IBZ: One patient with positive C. diffici
Slide 13: Microbiome. Favorable microbiome results were observed with IBZ
Microbiome. Favorable microbiome results were observed with IBZ Phylum Class IBZ VAN IBZ VAN
Slide 14: VAN caused approximately a 2-fold reduction on Actinobacteria compared to IBZ
VAN caused approximately a 2-fold reduction on Actinobacteria compared to IBZ Mallick H et al, Huttenhower C (2021). Multivariable Association Discovery in Population-scale Meta-omics Studies PLoS Computational Biology, 17(11):e1009442. Maaslin2
Slide 15: IBZ qPCR microbiome analysis
IBZ qPCR microbiome analysis ** ** ** ** **p<0.01
Slide 16: CDI recurrence associated with marked microbiome disruption
CDI recurrence associated with marked microbiome disruption
Slide 17: CDI recurrence associated with marked microbiome disruption
CDI recurrence associated with marked microbiome disruption
Slide 18: Conclusions
Conclusions • IBZ had a clinically comparable cure rates and safety profile to VAN • Favorable microbiome results were observed in IBZ-treated patients • More patients given VAN had persistently positive C. difficile cultured • IBZ treated patients had increased proportion of Actinobacteriota • IBZ
Slide 19: Acknowledgements
Acknowledgements The Garey Lab Garey Lab Funding Faculty NIAID R01AI139261 Kevin W. Garey NIAID T32AI141349 Taryn A. Eubank NIAID PO1AI152999 Jinhee Jo Acurx Pharmaceuticals M Jahangir Alam Merck Pharmaceuticals Khurshida Begum Paratek Pharmaceuticals Eugénie Bassères Seres Health Chenlin Hu PhD stu