Slide 1: Preliminary Results from an Adult Participant in a Phase 1b/2a Clinical Study of OPGx-BEST1
Preliminary Results from an Adult Participant in 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 Coauthors: Chief Medical Officer Aaron Nagiel, MD/PhD1 Steve and Debbie Gray Inherited Retinal Degeneration
Slide 2: Disclosures
Disclosures • MP: Consultant & Research Support, Opus Genetics, Inc. • AN: Consultant & Research Support, Opus Genetics, Inc. • KJ: None • RA: None • CW: Consultant & Research Support, Opus Genetics, Inc. • AJ, S Tucker, S Tuller: Employee, Opus Genetics, Inc. 2
Slide 3: BEST1-Related Retinopathy Represents One of the Largest IRD Patient Populations Globally
BEST1-Related Retinopathy Represents One of the Largest IRD Patient Populations Globally Middle East/ China United EU4 + UK North Africa Japan United States ~4,900 ~4,900 ~3,600 Japan States ~8,400 ~250 Approximately 22,050 patients worldwide are affected by BEST1-associated IRD BEST1, bestrophin 1;
Slide 4: 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 – 1:60,000 • Dominant Inheritance • Characterized by retinal lesions, with • Haploinsuffiency
Slide 5: AF and OCT Findings in ARB and BVMD
AF and OCT Findings in ARB and BVMD Best Vitelliform Macular Dystrophy Autosomal Recessive Bestrophinopathy 5
Slide 6: OPGx-BEST1 Gene Therapy
OPGx-BEST1 Gene Therapy • Leverages AAV2 capsid (employed in voretigene) to AAV2.VMD2.hBEST1 Vector deliver functional copy of BEST1 gene ITR VMD2/BEST1 BEST1 SV40 Poly A ITR Promoter • RPE-specific promoter • Approach aims to augment the mutated gene and Produces healthy wildtype BEST1 protein rest
Slide 7: OPGx-BEST1 Reduces Outer Retinal Thickness in a Canine Model
OPGx-BEST1 Reduces Outer Retinal Thickness in a Canine Model OS+ thickness is a collective measurement of pathologies; Reduction in retinal thickness indicates resolution of vitelliform deposits, edema, and detachments OS+ Thickness of Treated Eye (OD) Pre-dose and 12 Weeks Post-dose (one eye from o
Slide 8: BIRD-1: Phase 1/2 Study of OPGx-BEST1 Subretinal Gene Therapy is Ongoing
BIRD-1: Phase 1/2 Study of OPGx-BEST1 Subretinal Gene Therapy is Ongoing Adaptive, open-label, dose-escalation, safety and tolerability study of a subretinal injection of OPGx-BEST1 in adult (≥18 years old) participants with autosomal dominant BVMD or autosomal recessive ARB Cohort 1: low dose Not C
Slide 9: Demographics of Sentinel Participant
Demographics of Sentinel Participant Age 63 Sex Female Diagnosis year 2015 BEST phenotype ARB Study (treated) OS eye VA at Baseline LogMAR 1.66 (CF) (OS) CST at Baseline Atrophic macula (OS) Follow-up 3 months (to date) duration 9 Worse eye deemed study (treated) eye. ARB, autosomal recessive bestri
Slide 10: Sentinel Participant: Surgical Notes
Sentinel Participant: Surgical Notes • 2 major blebs created that surgeon believed were connected • Estimated >80% of macula was treated with SR blebs • Areas of chorioretinal atrophy did not elevate intraoperatively, but were adjacent to the blebs above and below • 2-3 clock hours of macula between
Slide 11: Sentinel Participant: Preliminary Safety Summary
Sentinel Participant: Preliminary Safety Summary • Day 14 • Few pigmented cells in vitreous • No AC inflammation • Steroid taper initiated • Postop Month #1 The Independent Data Monitoring • No ocular inflammation Committee (IDMC) meeting resulted in the unanimous consensus to dose • No ocular AEs r
Slide 12: BCVA in the Treated Eye Improved Over Months
BCVA in the Treated Eye Improved Over 3 Months Change from Baseline in BCVA 14 12 12-letter 10 gain BCVA (Letters) 9-letter 8 gain 6 5-letter 5-letter 4 gain gain 4-letter 2 gain 0 -2 Baseline Day 14 Month 1 Month 3 BCVA - Control Eye BCVA - Study Eye Early signal of functional improvement (12 lette
Slide 13: CST in Treated Eye Improved Over 3 Months
CST in Treated Eye Improved Over 3 Months Change from Baseline in CST 10 5 0 CST CST (μm) -5 -10 -15 -20 -25 -30 23% decrease -35 Baseline Day 14 Month 1 Month 3 CST - Control Eye CST - Study Eye Structural improvement (23% decrease ) observed in the study eye BCVA: equivalent letters 13 BCVA, best-
Slide 14: Untreated Area Remained Unchanged Over 3 Months
Untreated Area Remained Unchanged Over 3 Months Untreated Area Remained Unchanged Over 3 Months Baseline Subretinal fibrosis In areas of absent RPE and severe atrophy outside the 1 Month bleb, there was no change over time 3 Month OCT, optical coherence tomography; OS, left eye; RPE, retinal pigment
Slide 15: Treated Area Improved Over 3 Months
Treated Area Improved Over 3 Months Treated Area Improved Over 3 Months Area of fluid Baseline Reduction of intraretinal fluid as 1 Month early as 1 month in areas with less atrophy 3 Month OCT, optical coherence tomography; OS, left eye. 15
Slide 16: Conclusions and Next Steps
Conclusions and Next Steps • OPGx-BEST1 is a targeted gene augmentation approach designed to restore RPE function and address the underlying cause of BEST1-related IRD • 3-month results in the sentinel participant show OPGx-BEST1 is well-tolerated with no ocular inflammation, no ocular or treatment-