Innovations in Retinal Gene Therapy: Insights from the BIRD-1 Trial

Opus Genetics has dosed the first patient in the BIRD-1 trial, initiating first-in-human testing of a BEST1-directed gene therapy and confirming operational readiness across trial sites. Initial data are expected in the first quarter of 2026.

The BIRD-1 study is an adaptive, open-label phase 1/2 dose‑exploring trial evaluating safety, tolerability and early signals of efficacy in patients with Best vitelliform macular dystrophy and autosomal-recessive bestrophinopathy. It uses staged cohorts to assess biological activity across functional and anatomical endpoints. The investigational product, OPGx-BEST1, is a programmed gene-replacement construct delivered via a one-time subretinal procedure; the adaptive dose-escalation format balances patient safety with the need to detect early biological effect in small cohorts.

OPGx-BEST1 employs an AAV-based vector to deliver a functional copy of BEST1 directly to retinal pigment epithelium (RPE) cells, aiming to restore bestrophin-mediated RPE function and ion-channel activity. Subretinal administration concentrates transduction in the RPE while limiting systemic exposure. Because the design is a single-dose delivery, expectations center on durable cellular expression rather than repeat dosing, and early monitoring will prioritize surgical and vector-related safety alongside biomarker shifts in RPE physiology.

Early readouts will pair standard functional and structural measures to capture complementary safety and efficacy signals: best-corrected visual acuity for functional change; high-resolution retinal imaging — OCT and fundus autofluorescence — to document outer retinal and RPE changes; electrophysiology where appropriate to detect subtle functional gains; and systematic adverse-event monitoring including immune-response surveillance. OCT may show outer retinal restoration or progressive atrophy, while autofluorescence will reflect RPE health. Adverse-event logs and immunologic assays should help differentiate procedure-related events from vector-related responses. Clinicians can expect initial signals to appear within months, which informs follow-up scheduling and patient counseling about timelines.