Opus Genetics (IRD) Study result summary

Study design and objectives

• Phase I/II open-label, adaptive, dose-escalation trial of subretinal OPGX-BEST1 gene therapy in adults with BVMD or ARB, focusing on safety, tolerability, and efficacy endpoints including microperimetry, BCVA, LLVA, contrast sensitivity, autofluorescence, and OCT.

• Cohort 1 (low dose, 1.5E9 vg/eye) included five participants with both ARB and BVMD phenotypes at varying disease stages; Cohort 2 (high dose, 4.5E9 vg/eye) is over-enrolled with eight participants, mostly BVMD, with dosing to complete in Q4 2026.

• Primary objective: safety and tolerability; secondary: efficacy, dose selection for Phase 3, and functional/structural endpoints.

• Study design and pivotal endpoint selection informed by FDA feedback, with potential for pivotal trial adaptation.

• New epidemiology estimates 23,600 symptomatic BEST1 patients in the U.S. and 45,400 globally.

Safety and tolerability results

• OPGX-BEST1 was well-tolerated in all participants, with no serious adverse events, dose-limiting toxicities, or intraocular inflammation.

• All treatment-related adverse events were mild or moderate, with no significant systemic or laboratory safety findings.

• No treatment-related systemic adverse events were reported.

• Independent Data Monitoring Committee recommended advancing to Cohort 2 at a higher dose.

• Principal investigator and investigators expressed strong encouragement with safety and early efficacy at low dose.

Efficacy and functional outcomes

• 100% of participants showed clinically meaningful improvement in at least one functional measure; 80% had structural improvements.

• Microperimetry improved in 75% of evaluable patients, with three out of four showing ≥3 dB gain in at least five loci.

• Best-corrected visual acuity improved in 60%, low luminance visual acuity in 40%, and contrast sensitivity in 40% of participants.

• Mean BCVA improved by 9 letters at 3 months in treated eyes with structural improvement.

• Largest functional gains observed in younger, less advanced participants, supporting earlier intervention.