Opus Genetics, Inc. announced positive 3- and 6-month results from the low-dose Cohort 1 of its Phase 1/2 clinical trial evaluating OPGx-BEST1. The trial targets patients with BEST1-related retinal diseases, specifically Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). Cohort 1 enrolled five participants treated at a dose of 1.5 x 10^13 vg/eye. Three participants with BVMD reached the three-month follow-up mark, while two participants with ARB reached the six-month mark.
According to the filing, all five participants demonstrated clinically meaningful improvement in visual function. Improvements were measured via best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), contrast sensitivity (CS), or microperimetry. Specifically, BCVA improved in 60% of participants (3 out of 5), LLVA improved in 40% (2 out of 5), and contrast sensitivity improved in 40% (2 out of 5). Additionally, 75% of evaluable participants showed improvement in retinal sensitivity by microperimetry.
Structural improvements were observed in four of the five participants. Reductions in vitelliform material, the hallmark of BVMD, were seen in 67% of participants with BVMD (2 out of 3). Reductions in intraretinal fluid were observed in 100% of participants with ARB (2 out of 2). The company reported a favorable safety profile, with no serious adverse events, dose-limiting toxicities, or intraocular inflammation observed. All treatment-related adverse events were mild or moderate in severity.
Based on these findings, Opus Genetics has advanced to Cohort 2, which is evaluating a higher dose of 4.5 x 10^13 vg/eye. Originally designed for five participants, Cohort 2 is over-enrolled with eight participants. The company expects dosing to be completed in the fourth quarter of 2026, with topline three-month data expected in the second quarter of 2027.
In August 2026, the company met with the U.S. Food and Drug Administration (FDA) to discuss development plans. The company aligned with the FDA on a potential pivotal endpoint based on a microperimetry improvement of at least 3 dB in at least 5 prespecified loci, in conjunction with a patient-reported outcome. The company also aligned on Phase 3 and commercial manufacturing requirements, expecting to complete these by early 2027. Additionally, new epidemiology research estimates approximately 23,600 symptomatic BEST1 patients in the U.S. and approximately 45,400 globally.
