Opus Gene Therapy Shows Early Vision Improvements in BEST1 Retinal Disease Trial

Key Points

• Opus Genetics reported positive early data from five patients treated with OPGx-BEST1 in a Phase 1/2 study of inherited BEST1-related retinal diseases.
• All five patients showed clinically meaningful improvement in at least one vision measure, while four showed retinal structural improvements.
• The low-dose cohort reported no serious adverse events, dose-limiting toxicities, or intraocular inflammation.
• Opus said the FDA aligned on a potential Phase 3 endpoint using microperimetry and patient-reported outcomes.
• Higher-dose Cohort 2 dosing is expected to finish in the fourth quarter of 2026, with three-month data anticipated in the second quarter of 2027.

Opus Genetics (Nasdaq: IRD) has reported early Phase 1/2 results suggesting that its investigational gene therapy, OPGx-BEST1, may improve vision and retinal structure in patients with BEST1-related inherited retinal disease.

The BIRD-1 study is evaluating OPGx-BEST1 in patients with Best vitelliform macular dystrophy, or BVMD, and autosomal recessive bestrophinopathy, or ARB. Both conditions are linked to mutations in the BEST1 gene and can cause progressive vision loss.

Low-Dose Cohort Reports Improvements in Vision Measures

The first cohort included five patients treated with a lower vector genomes per eye.

Three patients with BVMD had reached three months of follow-up, while two patients with ARB had reached six months. All five showed clinically meaningful improvement in at least one measure of visual function.

The study reported:

• Best-corrected visual acuity improved in three of five patients.
• Low-light visual acuity improved in two of five patients.
• Contrast sensitivity improved in two of five patients.
• Microperimetry showed improved retinal sensitivity in three of four evaluable patients.

The company said the largest functional improvements occurred in patients with less advanced disease and viable, but impaired, retinal tissue.

Retinal Imaging Shows Reduced Disease-Related Changes

Four of the five patients also showed structural improvements on retinal imaging.

Two of three BVMD patients had reduced vitelliform material, a buildup in the retina that is a defining feature of the disease. The third patient showed a possible but unconfirmed reduction.

Both ARB patients showed reductions in intraretinal fluid, a key disease feature in that condition.

Opus said the early findings support the idea that treatment may work best in retinal areas where cells remain viable. The results are from a small, early-stage study and do not establish that OPGx-BEST1 is safe or effective.

FDA Provides Direction for Potential Phase 3 Trial Design

Opus met with the FDA in August to discuss the potential pivotal development path for OPGx-BEST1.

The company said the FDA aligned on a potential Phase 3 endpoint requiring at least a 3-decibel improvement in microperimetry at five or more prespecified retinal locations, combined with a patient-reported outcome measure in a randomized, controlled study.

The FDA also indicated that best-corrected visual acuity, low-light visual acuity, and contrast sensitivity could serve as acceptable endpoints. Opus said it also aligned with the agency on Phase 3 and commercial manufacturing requirements, which it expects to complete in early 2027.

Higher-Dose Cohort Could Shape 2027 Pivotal Plans

Opus is now dosing a higher-dose second cohort, with more vector genomes per eye. The cohort enrolled eight patients, above the original plan of five, with most participants having BVMD.

The company expects to complete Cohort 2 dosing during the fourth quarter of 2026 and report three-month topline data in the second quarter of 2027. It also expects to report six-month data for the three BVMD participants from Cohort 1 in the second quarter of 2027.

Opus plans to begin preparing for a Phase 3 trial, with patient dosing expected to start in 2027.

Larger BEST1 Population Could Expand Opportunity

Opus cited research from Triangle Insights Group estimating that approximately 23,600 symptomatic BEST1 patients live in the U.S., including 13,000 diagnosed and 10,600 undiagnosed individuals. The research estimated about 45,400 symptomatic BEST1 patients globally.

The company said it has cash runway into 2029, which it expects will support multiple clinical milestones and potential opportunities related to priority review vouchers.

OPGx-BEST1 remains investigational and has not received FDA approval. Future progress will depend on higher-dose data, Phase 3 trial execution, manufacturing readiness, regulatory review, and the treatment’s ability to show a meaningful benefit in larger controlled studies.