Phase 1/2 clinical trial of OPGx-BEST1 shows positive results for inherited retinal diseases

Opus Genetics announced positive 3- and 6-month results from the low-dose cohort 1 of BIRD-1, the ongoing phase 1/2 open-label trial of OPGx-BEST1, an investigational gene therapy, for BEST1-related retinal diseases, according to a press release issued by the company.

BEST1-related inherited retinal diseases, which include Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathies (ARB), are described as rare forms of inherited macular degeneration resulting from BEST1 gene mutations. The normal function of retinal pigment epithelial (RPE) cells is disrupted in these diseases with resultant development of retinal lesions, progressive degeneration, and visual loss. No currently approved therapies exist to address the underlying genetic cause of BEST1-related diseases.

OPGx-BEST1 uses an adeno-associated virus vector to deliver a functional copy of the BEST1 gene to the RPE cells. The ongoing BIRD-1 clinical trial is evaluating the safety and efficacy of subretinal administration of OPGx-BEST1 in one eye of adults with BVMD or ARB.

About the trial

Cohort 1 was comprised of five patients treated with 1.5 x 10⁹ vg/eye. Of these, three participants with BVMD reached 3 months of follow-up and two with ARB reached 6 months of follow-up.

According to the press release, the five patients had clinically meaningful improvements in visual function in one or more of the following parameters: best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), and contrast sensitivity or microperimetry. The greatest functional gains occurred in the treated transitional zone in patients with less advanced disease, supporting the potential benefit of treating patients with viable retinal tissue.

Mark Pennesi, MD, PhD, said, “We are encouraged by the localization of functional gains to areas of viable, compromised retina and by the opportunity to apply these insights prospectively as OPGx-BEST1 is advanced into cohort 2 and potential pivotal development.” He is clinical trial investigator and Professor of Ophthalmology, Casey Eye Institute, Oregon Health & Science University School of Medicine, Portland.

The press release reported that the BCVA improved in 60% of participants and the low- LLVA and the contrast sensitivity improved in 40% of participants. Among four patients who were evaluated, 75% had clinically meaningful improvement in the retinal sensitivity.

Four patients had structural improvements that included reductions in vitelliform material, ie, in 67% of participants with BVMD and reductions in intraretinal fluid in all with ARB. The third BVMD participant had a possible reduction in vitelliform material.

The company expects to announce 6-month data for the three patients with BVMD in the second quarter of 2027.

OPGx-BEST1 also showed a favorable safety and tolerability profile; no serious adverse events, dose-limiting toxicities, intraocular inflammation, and vital-sign or safety-laboratory findings developed. All treatment-related adverse events were mild or moderate.

Christine Nichols Kay, MD, clinical trial investigator and Director of Clinical Research and Retinal Genetics at Vitreo Retinal Associates, Gainesville, FL, commented, “The cohort 1 data provide encouraging evidence that OPGx-BEST1 can be delivered safely and may improve retinal structure and visual function in patients with advanced BEST1-related retinal disease.”

George Magrath, MD, Chief Executive Officer of Opus Genetics, also expressed confidence in the findings. “The functional and structural improvements across cohort 1, particularly the greater functional gains observed in patients with viable retinal tissue, reinforce our confidence in OPGx-BEST1’s potential to have a positive impact on the lives of patients with BEST disease. Together with our recent FDA interaction and rapid enrollment of cohort 2, we believe these data provide a clear path toward pivotal development, which we plan to begin next year.”

Regulatory status

In August 2026, the company met with the FDA to discuss OPGx-BEST1 development and potential endpoints for a pivotal clinical trial. The company aligned with the FDA on a potential pivotal endpoint based on a 3-decibel or greater microperimetry improvement in five or more prespecified loci, in conjunction with a patient-reported outcome in a randomized, controlled trial. The company also aligned with the FDA on phase 3 and commercial manufacturing requirements, which it expects to be completed in early 2027. Planning for the phase 3 trial is expected to begin immediately, with participant dosing expected to begin in 2027.

Based on the safety profile and positive proof-of-concept findings from cohort 1, the company has advanced to the higher dose cohort 2, with dosing at 4.5 x 10⁹ vg/eye; this expected to be completed in the fourth quarter of 2026 and topline 3-month data are expected in the second quarter of 2027. Originally designed to enroll five participants, Cohort 2 is comprised of eight participants, most of whom have BVMD. The results should inform the design of a potential pivotal clinical trial.