Key Takeaways

  • All 5 participants in the low-dose BIRD-1 cohort demonstrated clinically meaningful improvement in at least 1 measure of visual function, while structural improvements were observed in 4 participants
  • OPGx-BEST1 was reported to have a favorable safety profile, with no serious adverse events in Cohort 1
  • Opus Genetics has advanced to a higher-dose cohort and is preparing for potential pivotal development, with Phase 3 participant dosing targeted to begin in 2027

Opus Genetics announced positive 3- and 6-month results from the low-dose cohort of its ongoing phase 1/2 BIRD-1 clinical trial evaluating OPGx-BEST1 in patients with BEST1-related retinal diseases, including Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB).

According to the company, all 5 participants in Cohort 1 demonstrated clinically meaningful improvement in at least 1 measure of visual function after receiving OPGx-BEST1 at a dose of 1.5 × 10⁹ vg/eye. Structural improvements were also observed in 4 of the 5 participants.

Cohort 1 included 3 participants with BVMD who have reached 3 months of follow-up and 2 participants with ARB who have reached 6 months. Opus Genetics said the largest functional gains occurred among participants with less advanced disease and viable retinal tissue, a finding that could help guide patient selection in subsequent development.

“These positive results provide important evidence of OPGx-BEST1’s potential to improve both visual function and retinal structure in patients with BEST1-related retinal disease, which we believe has a significantly larger underserved patient population than we previously thought,” George Magrath, MD, chief executive officer of Opus Genetics, said in a statement.

Dr. Magrath added that the Cohort 1 findings, along with recent discussions with the FDA and enrollment in Cohort 2, support the company’s plans to move the program toward pivotal development in 2027.

All 5 participants experienced clinically meaningful improvement in 1 or more assessments of visual function, including best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), contrast sensitivity, and microperimetry. BCVA improved in 3 of 5 participants (60%), while LLVA and contrast sensitivity each improved in 2 of 5 participants (40%). Among participants evaluable by microperimetry, 3 of 4 (75%) demonstrated clinically meaningful improvements in retinal sensitivity.

According to Opus Genetics, microperimetry gains were concentrated in the treated retinal pigment epithelium transitional zone, where viable photoreceptors remained. The greatest functional improvements were seen in participants with less advanced disease.

Structural changes were reported in 4 of 5 participants. Among the 3 participants with BVMD, 2 (67%) experienced reductions in vitelliform material. The third participant had a possible but not definitive reduction. Both participants with ARB experienced reductions in intraretinal fluid.

The company noted that vitelliform material is a defining structural feature of BVMD and said its reduction corresponded with functional improvement in the responding participants. In ARB, where intraretinal fluid is a predominant structural manifestation, reductions were observed in both treated participants.

OPGx-BEST1 demonstrated what the company characterized as a favorable safety and tolerability profile. No serious adverse events, dose-limiting toxicities, or intraocular inflammation were reported, and there were no notable vital-sign or safety-laboratory findings. All treatment-related adverse events were mild or moderate in severity.

Based on the Cohort 1 findings, Opus Genetics has advanced BIRD-1 into Cohort 2, which is evaluating a higher dose of 4.5 × 10⁹ vg/eye.

Although Cohort 2 was initially designed to enroll 5 participants, the company said it has over-enrolled the cohort with 8 participants, most of whom have BVMD. Dosing is expected to be completed during the fourth quarter of 2026, with topline 3-month results anticipated in the second quarter of 2027. Six-month data for the 3 Cohort 1 participants with BVMD are also expected in the second quarter of 2027.

Opus Genetics also provided additional details about an August 2026 meeting with the FDA regarding the clinical development of OPGx-BEST1 and potential endpoints for a pivotal trial. According to the company, discussions with the agency identified a potential pivotal endpoint based on an improvement of at least 3 dB from baseline by microperimetry in at least 5 prespecified loci, in conjunction with a patient-reported outcome in a randomized, controlled trial. BCVA, LLVA, and contrast sensitivity may also represent acceptable endpoints, the company said.

Opus said it also reached alignment with the FDA regarding phase 3 and commercial manufacturing requirements, which it expects to complete in early 2027. The company plans to begin phase 3 planning immediately, with participant dosing targeted for 2027.

Separately, Opus reported new epidemiologic estimates suggesting the population potentially affected by symptomatic BEST1-related disease may be larger than previously estimated.

Research conducted by Triangle Insights Group, based on a survey of more than 150 eye care professionals, estimated approximately 23,600 symptomatic patients with BEST1-related disease in the United States. The estimate includes approximately 13,000 diagnosed and 10,600 undiagnosed patients. Globally, the research estimated approximately 45,400 symptomatic patients with BEST1-related disease.