Opus Genetics (IRD) Study result summary

Program overview and study design

• OPGx-LCA5 is an AAV8-based gene therapy for Leber congenital amaurosis type 5 (LCA5), an ultra-rare inherited retinal disease affecting about 200 patients in the U.S. and accounting for about 2% of all LCA cases.

• The therapy is delivered via subretinal injection, aiming to restore lebercilin protein function in retinal photoreceptors.

• The Phase 1/2 open-label, ascending-dose study enrolled six participants (three adults, three pediatric) with biallelic LCA5 mutations, treating the eye with the worst vision.

• Baseline visual acuity ranged from 0.96 to 2.9 logMAR; efficacy was assessed using visual acuity, full-field stimulus testing, MLOMT, and microperimetry.

• The trial is co-funded by the FDA and has received Rare Pediatric Disease, Orphan Drug, and RMAT designations.

Safety and tolerability

• OPGx-LCA5 was well-tolerated in all six participants, with no ocular serious adverse events or dose-limiting toxicities.

• All ocular adverse events were mild, anticipated, and unrelated to the study drug; one pediatric participant experienced a worsening of a pre-existing cataract due to surgery, not the drug.

Efficacy results: visual acuity and functional outcomes

• Visual acuity improved in 5 of 6 participants, with gains as early as 1 month and sustained up to 18 months in adults; pediatric participants showed a mean 0.3 logMAR improvement at 3 months, with individual gains from 0.2 to 0.7 logMAR.

• FST showed improved sensitivity in 5 of 6 participants, with over 1 log unit improvement in cone sensitivity and durable effects in adults.

• MLOMT demonstrated improved object recognition and navigation in both cohorts, with all pediatric participants identifying more objects at three months.

• Microperimetry indicated increased foveal sensitivity and fixation movement toward the fovea in eligible participants.