Slide 1: Phase 1 First-in-Human Study of VP-001 for Retinitis Pigmentosa Type 11
Phase 1 First-in-Human Study of VP-001 A Peptide Conjugated Oligonucleotide for the Treatment of Retinitis Pigmentosa Type 11 Dr Fred Chen Lions Eye Institute, Perth, Australia ARVO 2024 1
Slide 2: Executive Summary – Update on VP-001 for RP11
Executive Summary – Update on VP-001 for RP11 Introduction to VP-001 for RP11 1. RP11 is a progressive and blinding eye disease for which there are no treatments available for patients 2. RP11 is caused by insufficient expression of one gene (PRPF31) in the retina 3. VP-001 addresses the underlying
Slide 3: RP11 is a progressive and blinding eye disease with no treatments
1. RP11 is a progressive and blinding eye disease for which there are no treatments available for patients Degenerative sight of an RP11 patient Retinitis Pigmentosa (RP)1,2 6 YEARS OLD • A severe and progressive blinding eye disease that begins in childhood 26 YEARS OLD • Affects 1 in every 3,500 p
Slide 4: RP11 is caused by insufficient expression of one gene in the retina
2. RP11 is caused by insufficient expression of one gene in the retina Unaffected individual RP11 patient1 PRPF31 PRPF31 PRPF31 PRPF31 PRPF31 PRPF31 DNA RNA Protein DNA RNA Protein Functional PRPF31 expression = 100% Functional PRPF31 expression = ~50% PYC THERAPEUTICS 4 4 1. Hafler BP, et al. Cours
Slide 5: VP-001 addresses the underlying cause of RP11 in patient-derived models
3. VP-001 addresses the underlying cause of RP11 and leads to functional benefit in patient-derived cell and organoid models 1. VP-001 is capable of completely rescuing the haploinsufficiency responsible for causing the disease in patient-derived models a) Upregulation of PRPF31 mRNA in RP11 iPSC-RP
Slide 6: VP-001 is now generating data as the first drug candidate in clinical trials for RP11
Phase 1 First-in-Human Study of VP-001 VP-001 is now generating data as the first drug candidate in clinical trials for RP11 6
Slide 7: PLATYPUS: Study Design
PLATYPUS: Study Design PYC THERAPEUTICS 7 7
Slide 8: PLATYPUS: Safety and Exploratory Efficacy Endpoints
PLATYPUS: Safety and Exploratory Efficacy Endpoints Safety monitored by evaluation of: Exploratory efficacy evaluated using: • Ocular and non-ocular adverse events (AEs) • Perimetry • Clinical chemistry parameters • Microperimetry • Best-corrected visual acuity (BCVA) • BCVA • Perimetry • SD-OCT • M
Slide 9: VP-001 is safe in all dose cohorts in SAD (no serious adverse events)
4a. VP-001 is safe in all dose cohorts in SAD (no serious adverse events) No Serious Adverse Events (SAEs) were observed (across all dose cohorts) Dose (patient ID) and study eye TEAE Relationship to VP-001 3 mcg (001-1-001) Vitreous floaters (OU) Not Related OS Vitreous opacities (OU) Not Related V
Slide 10: VP-001 is safe in all dose cohorts in SAD (no significant change in ocular measurements)
4b. VP-001 is safe in all dose cohorts in SAD (no significant change in any ocular measurements of safety) No significant changes in any ocular measurements indicating safety (across all cohorts) Retinal Central Subfield Thickness Measurements (used as representative data) All Cohorts Pooled Cohort
Slide 11: Encouraging signs of efficacy signal (microperimetry) in patient treated with 30 µg
5. Encouraging signs of efficacy signal (microperimetry data) in patient treated with 30 µg VP-001 (8 week follow up comparison to fellow eye) Baseline (December 2023) Week 8 Post-Dosing Findings Microperimetry measurements (#005-1-002) Mean threshold (baseline) 12.5 Mean threshold (week 4) 13.1 Stu
Slide 12: Microperimetry – Subject #005-1-002, Study Eye, Week 8 Post-Dosing – FAF & OCT
Microperimetry – Subject #005-1-002, Study Eye, PLATYPUS, Week 8 Post-Dosing – FAF & OCT PYC THERAPEUTICS 12 12
Slide 13: Encouraging signs of efficacy signal in patient treated with 30 µg VP-001
5. Encouraging signs of efficacy signal (microperimetry data) in patient treated with 30 µg VP-001 (8 week follow up comparison to fellow eye) This patient is at earlier stage of disease progression than other patients in SAD 1 Greater microperimetry sensitivity improvements in treated eye (in 15 lo
Slide 14: Protocol amendments filed with FDA to increase dosing of VP-001
6. Protocol amendments filed with FDA to increase dosing of VP-001 • Protocol amendments to increase doses, filed with FDA for: • Addition of Cohort 4 (75 µg) to SAD study • Multiple-Ascending Dose (MAD) study to include repeat dosing of 30 µg and 75 µg • Both protocol amendments have revised inclus
Slide 15: Conclusion
Phase 1 First-in-Human Study of VP-001 Conclusion 15
Slide 16: Conclusion – VP-001 is safe and shows encouraging signs of efficacy
Conclusion – VP-001 is safe and shows encouraging signs of efficacy • VP-001 is safe in all dose cohorts tested to date • No serious adverse events observed, no significant changes in ocular measurements indicating safety • Encouraging signs of efficacy signal observed (microperimetry data) • In a s
Slide 17: Acknowledgements
Acknowledgements Dr. Mark Pennesi Dr. David Birch Dr. Lesley Everett Dr. Thiran Jayasundera Dr. John Chancellor Retina Foundation Retina Foundation OHSU Casey Eye Kellogg Eye Center Alkek Eye Center of Southwest of Southwest Institute University of Michigan Baylor College of Medicine Dr. Fred Chen D