Slide 1: Initial Results from Cohort 1 of a Phase 1b/2a Clinical Study of OPGx-BEST1 Gene Therapy
Initial Results from Cohort 1 of a Phase 1b/2a Clinical Study of OPGx-BEST1 Gene Therapy for the Treatment of BVMD and ARB Due to BEST1 Mutations Mark E Pennesi, MD, PhD, FARVO Co-authors: Chief Medical Officer Kaylie Jones, BS1 Steve and Debbie Gray Inherited Retinal Degeneration Endowed Chair Raji
Slide 2: Disclosures
Disclosures • MP: Consultant & Research Support, Opus Genetics, Inc. • KJ: None • RA: None • AN: Consultant & Research Support, Opus Genetics, Inc. • CW: Consultant & Research Support, Opus Genetics, Inc. • RS: Research Support, Opus Genetics, Inc. • CK: Consultant & Research Support, Opus Genetics,
Slide 3: BEST1 Mutations are Associated with Retinal Degeneration
BEST1 Mutations are Associated with Retinal Degeneration • BEST1 mutations are associated with at Three Main BEST1 Phenotypes least five clinically distinct retinal BVMD degenerative diseases1 • Prevalence – 1:15,000 • Dominant Inheritance • Characterized by retinal lesions, with • Haploinsuffiency
Slide 4: BIRD-1: Ongoing Phase 1/2 Study of OPGx-BEST1 Subretinal Gene Therapy
BIRD-1: Ongoing Phase 1/2 Study of OPGx-BEST1 Subretinal Gene Therapy Adaptive, open-label, dose-escalation, safety and tolerability study of a subretinal injection of OPGx-BEST1 gene therapy in adult (≥18 years old) participants with autosomal dominant BVMD or autosomal recessive ARB Cohort 1: low
Slide 5: Participant Demographics: Cohort 1, Low-dose (1.5x10^9 vg/eye)
Participant Demographics: Cohort 1, Low-dose (1.5x109 vg/eye) 101-101 101-104 102-101 102-102 101-106 Age 63 59 50 45 31 Sex Female Female Male Male Male BEST phenotype ARB ARB BVMD BVMD BVMD End-stage with Advanced stage Earlier stage Severity of End-stage with End-stage with sub-foveal, vitello-er
Slide 6: OPGx-BEST1 Demonstrated a Favorable Safety Profile
OPGx-BEST1 Demonstrated a Favorable Safety Profile OPGx-BEST1 was well-tolerated in all 5 No anterior chamber or vitreous participants: cells observed in any patient at any study visit • No anterior chamber or vitreous cells • No serious AEs 101-101 101-104 (ARB) (ARB) • No dose-limiting toxicities
Slide 7: Summary of 3-month Safety and Efficacy Results from Low-Dose Cohort 1
Summary of 3-month Safety and Efficacy Results from Low-Dose Cohort 1 Safety • OPGx-BEST1 was well-tolerated in 5/5 participants, with no SAEs or DLTs • 80% of participants (4/5) had structural improvements: Structural • BVMD: 67% of participants (2/3) had a decrease in vitelliform material Endpoint
Slide 8: Participant 101-106 (BVMD): Vitelliform Material Reduction Co-localized with Microperimetry Improvements
Participant 101-106 (BVMD): Vitelliform Material Reduction Co-localized with Microperimetry Improvements Baseline Vitelliform lesions reduced Month 3 Baseline Month 3 Lesion reduction was consistent with improved function of RPE cells and treatment activity as indicated in microperimetry improvement
Slide 9: Participant 102-102 (BVMD): Microperimetry Improved in the Treated RPE Transitional Zone
Participant 102-102 (BVMD): Microperimetry Improved in the Treated RPE Transitional Zone Baseline Baseline Month 3 Month 3 Baseline Month 3 Fixation moved to a more natural location in the fovea Yellow box represents treated transitional zone. BVMD, best vitelliform macular dystrophy; RPE, retinal p
Slide 10: Participant 101-104 (ARB): IRF Improvement Co-localized with Microperimetry Improvement
Participant 101-104 (ARB): IRF Improvement Co-localized with Microperimetry Improvement Baseline Month 6 Fixation moved to a more Two areas of baseline natural location in the fovea intraretinal fluid Yellow circles denote pockets of intraretinal fluid. Total macular intraretinal fluid volume: Basel
Slide 11: Summary and Next Steps
Summary and Next Steps • 3-month results in the ongoing, low-dose Cohort 1 (N=5) demonstrated: • OPGx-BEST1 was well-tolerated with with no SAEs, no DLTs, and no intraocular inflammation; • Signs of efficacy observed on both functional and structural endpoints • IDMC recommended the Phase 1/2 trial