Oral Presentation

Restoration of Cone-Mediated Vision After Gene Augmentation in Children with LCA5

The oral presentation, delivered by Tomas S. Aleman, M.D., primary study investigator, reported 6-month results from the ongoing Phase 1/2/3 study of OPGx-LCA5 in pediatric patients with Leber congenital amaurosis type 5 (LCA5), a severe, early-onset, inherited retinal degeneration.

Despite advanced disease and very poor baseline vision, patients treated with OPGx-LCA5 demonstrated robust and consistent restoration of cone-mediated function following a single subretinal injection.

Key findings include:

• Well tolerated, with no dose-limiting toxicities and adverse events that were mild, expected, and resolved
• Over 30-fold improvements in cone sensitivity across all treated patients, representing recovery of primary photoreceptor function
• Improvement in visual acuity in treated eyes relative to baseline and untreated control eyes
• Objective confirmation of efficacy across multiple independent readouts, including dark-adapted pupillary light responses showing improved amplitude and latency thresholds
• Early and durable improvements in functional vision in an orientation and mobility test
• Consistent patient-reported improvements in daily functional vision

"These results indicate that even in severe, early-onset disease, there remains a possible window of opportunity to restore cone function and meaningfully improve vision," said Dr. Tomas S. Aleman. "Gene augmentation in LCA5 demonstrated dramatic recovery of daytime vision in adolescents, paving the path for use in younger patients with theoretically greater treatment potential. Importantly, these results build on prior adult data and demonstrate that in severe pediatric disease, viable cone photoreceptors may be rescued, supporting a broader therapeutic window."

Poster Presentations

Preliminary Results from Adult Participant in a Phase 1b/2a Clinical Study of OPGx-BEST1 Gene Therapy for ARB and BVMD Due to BEST1 Mutations

• Well tolerated through three months with no ocular inflammation or treatment-related adverse events
• Up to 12-letter improvement in visual acuity in the treated eye
• ~23% reduction in central subfield thickness, indicating improved retinal structure
• Early patient-reported improvements, including reduced perception of progressive vision dimming

These findings provide early clinical evidence for BEST1 gene augmentation in a large inherited retinal disease population. Opus Genetics has completed enrollment in Cohort 1 of its ongoing Phase 1/2 study of OPGx-BEST1 gene therapy, and expects to announce 3-month topline data from Cohort 1 in September 2026.

Development of Cell-Based Expression and Functional Potency Assays for OPGx-BEST1 Gene Therapy

• Developed robust, reproducible assays (RT-dPCR, western blot, ELISA) to quantify gene expression and protein production
• Demonstrated consistent potency across manufacturing lots within expected ranges (50–150%)
• Established a functional assay to measure BEST1 channel activity, supporting mechanism-driven validation
  
   

These capabilities support scalable development and regulatory readiness.

Nonclinical Efficacy and Toxicity Study of GMP-Grade Vector OPGx-RHO Delivered by Subretinal Injection in a Canine Model of RHO-adRP

• Established no-observed-adverse-effect-level (NOAEL) to guide clinical dosing
• Demonstrated preservation of retinal structure and function in treated regions
• Observed dose-dependent structural rescue, supporting clinical translation
  
   

Therapeutic Efficacy of a Mutation-Independent AAV Knockdown and Replacement Approach in a Swine Animal Model of Autosomal-Dominant Retinitis Pigmentosa (RHO)

• Mutation-independent approach demonstrated:
  • Restoration of rod-driven visual responses
  • Maintenance of cone function over time
  • Preservation of retinal structure, including outer retinal thickness and photoreceptor morphology
• Identified minimal effective dose and evidence of durability across timepoints
• Data also suggest interocular vector transfer, indicating potential systemic distribution dynamics

These results support a differentiated strategy to treat genetically heterogeneous retinal diseases with a single therapeutic approach.