Opus Genetics (IRD) Study result summary

Program overview, study design, and participant demographics

• 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.

• The Phase 1/2 open-label, ascending-dose trial enrolled six participants (three adults, three pediatric), treating the eye with the worst vision; baseline visual acuity ranged from 0.96 to 2.9 logMAR.

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

• Efficacy was assessed using visual acuity, full-field stimulus test (FST), Multi-Luminance Orientation and Mobility Test (MLoMT), and microperimetry.

• The study 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 observed.

• 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 the surgical procedure.

Efficacy outcomes: visual acuity and functional vision

• Visual acuity improved in 5 of 6 participants, with gains as early as one month and sustained up to 18 months in adults; pediatric participants showed a mean 0.3 LogMAR improvement at three months.

• FST showed improved sensitivity in 5 of 6 participants, with over 1 log unit improvement in cone sensitivity in pediatric participants.

• MLoMT demonstrated improved object identification and navigation in both adults and children, with greater improvements in those with better baseline vision.

• Microperimetry indicated increased foveal sensitivity and improved fixation in eligible participants.