Opus Genetics Reports Positive Low-Dose Cohort 1 Data for OPGx-BEST1 in BEST1-Related Retinal Diseases, Aligns With FDA on Pivotal Endpoint
核心洞察
All five participants in the low-dose Cohort 1 of the Phase 1/2 BIRD-1 trial showed clinically meaningful visual function improvement, with structural improvements in four of five.
OPGx-BEST1 showed no serious adverse events, dose-limiting toxicities or intraocular inflammation, with all treatment-related adverse events mild or moderate.
The FDA aligned on at least 3 decibels of microperimetry improvement in at least five prespecified loci plus a patient-reported outcome as a potential pivotal endpoint.
Opus Genetics, Inc. (Nasdaq: IRD) reported positive 3- and 6-month results from the low-dose Cohort 1 of BIRD-1, its ongoing adaptive, open-label Phase 1/2 clinical trial of OPGx-BEST1 in patients with BEST1-related retinal diseases (搜索), including Best vitelliform macular dystrophy (搜索) (BVMD) and autosomal recessive bestrophinopathy (搜索) (ARB). The company also disclosed alignment with the U.S. Food and Drug Administration (搜索) on a potential pivotal endpoint following an August 2026 Type C meeting, and said it plans to begin Phase 3 planning immediately, with participant dosing expected to begin in 2027.
Cohort 1 enrolled five participants treated at 1.5 x 10⁹ vg/eye via single-eye subretinal administration: three participants with BVMD who have reached three months of follow-up and two with ARB who have reached six months of follow-up. All five demonstrated clinically meaningful improvement in visual function, measured as one or more of best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), contrast sensitivity (CS) or microperimetry, an advanced eye test that maps how well the central part of the retina sees light. Structural improvements were observed in four participants.
Functional and Structural Outcomes
BCVA improved in 60% of participants (3/5), LLVA improved in 40% (2/5), and contrast sensitivity improved in 40% (2/5). Among evaluable participants, 75% (3/4) demonstrated clinically meaningful improvement in retinal sensitivity by microperimetry. The company reported that these gains were concentrated in the treated retinal pigment epithelial (RPE) Transitional Zone, where viable photoreceptors remain, with the greatest functional improvements observed in participants with less advanced disease.
Structural improvements were observed in four of five participants, including reductions in vitelliform material — the hallmark of BVMD — in 67% of participants with BVMD (2/3) and reductions in intraretinal fluid in 100% of participants with ARB (2/2). The third BVMD participant had possible, but not definitive, reduction in vitelliform material. Opus Genetics noted that in BVMD, vitelliform material accumulates early and is the defining structural feature of the disease, while subretinal fluid appears late and pools in areas of established atrophy; reduction of vitelliform material is therefore the more direct measure of restored RPE function in this population and corresponded with functional improvement in those participants. In ARB, where intraretinal fluid is the dominant structural manifestation, fluid reduction was substantial and consistent in both participants.
"These positive results provide important evidence of OPGx-BEST1's potential to improve both visual function and retinal structure in patients with BEST1 (搜索)-related retinal disease, which we believe has a significantly larger underserved patient population than we previously thought," said George Magrath, M.D., Chief Executive Officer of Opus Genetics. "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."
Christine Nichols Kay, M.D., clinical trial investigator and Director of Clinical Research and Retinal Genetics at Vitreo Retinal Associates, said the Cohort 1 data "provide encouraging evidence that OPGx-BEST1 can be delivered safely and may improve both retinal structure and visual function in patients with advanced BEST1 (搜索)-related retinal disease."
Safety Profile
OPGx-BEST1 demonstrated a favorable safety and tolerability profile, with no serious adverse events or dose-limiting toxicities, no intraocular inflammation and no vital-sign or safety-laboratory findings of note. All treatment-related adverse events were mild or moderate in severity.
Regulatory Alignment on Pivotal Endpoints
In August 2026, the company met with the FDA to discuss OPGx-BEST1 development and potential endpoints for a pivotal clinical trial. Opus Genetics aligned with the FDA on a potential pivotal endpoint based on ≥3 dB microperimetry improvement in ≥5 prespecified loci, in conjunction with a patient-reported outcome in a randomized, controlled trial. BCVA, LLVA and CS may also be acceptable endpoints. The company also aligned with the FDA on Phase 3 and commercial manufacturing requirements, which it expects to complete in early 2027.
"We are encouraged by the localization of functional gains to areas of viable, but compromised retina and by the opportunity to apply these insights prospectively as OPGx-BEST1 is advanced into Cohort 2 and potential pivotal development," said Mark Pennesi, M.D., Ph.D., clinical trial investigator and Chief Medical Officer at the Retina Foundation and Adjunct Professor of Ophthalmology, Casey Eye Institute, Oregon Health & Science University. "From a regulatory perspective, it is particularly exciting to align with the FDA on a >3 decibels change from baseline in microperimetry anchored to patient reported outcomes as a potential pivotal endpoint."
Cohort 2 Advancement and Upcoming Readouts
Based on the safety profile and positive proof-of-concept findings from Cohort 1, the company has advanced to the higher-dose Cohort 2, evaluating OPGx-BEST1 at 4.5 x 10⁹ vg/eye. Originally designed to enroll five participants, Cohort 2 has been over-enrolled with eight participants, most of whom have BVMD. Dosing is expected to be completed in Q4 2026, with topline three-month data expected in Q2 2027. Opus Genetics also expects to announce 6-month data for the three participants with BVMD in Cohort 1 in Q2 2027. Data from Cohort 2 are expected to further characterize safety, functional and structural responses at the higher dose and inform the design of a potential pivotal trial.
Epidemiology Points to Larger Addressable Population
New epidemiology research conducted by Triangle Insights Group (搜索), based on a survey of more than 150 eye care professionals, estimates approximately 23,600 symptomatic BEST1 (搜索) patients in the U.S. — including 13,000 diagnosed and 10,600 undiagnosed patients — and approximately 45,400 symptomatic BEST1 patients globally. The company said these findings suggest a substantially larger addressable patient population and unmet need than previously estimated.
Mechanism and Disease Context
BEST1 (搜索)-related inherited retinal diseases, or bestrophinopathies, are rare forms of inherited macular degeneration caused by mutations in the BEST1 gene. These mutations disrupt the normal function of RPE cells, leading to retinal lesions, progressive degeneration and vision loss. BEST1-related diseases include BVMD and ARB, and there are currently no approved therapies that address the underlying genetic cause of these diseases.
OPGx-BEST1 is an investigational gene therapy designed to address the underlying genetic cause of BEST1 (搜索)-related inherited retinal diseases. It uses an AAV vector to deliver a functional copy of the BEST1 gene to retinal pigment epithelial cells. Opus Genetics is a clinical-stage biopharmaceutical company developing gene therapies to restore vision and prevent blindness in patients with inherited retinal diseases, with a pipeline of seven AAV-based programs led by OPGx-LCA5 for LCA5-related mutations and OPGx-BEST1 for BEST1-related retinal degeneration, plus additional candidates targeting RDH12 (搜索), MERTK (搜索), RHO (搜索), CNGB1 (搜索) and NMNAT1 (搜索). The company is based in Research Triangle Park, N.C.
The company noted that the BIRD-1 trial is ongoing and the reported data are interim, subject to change, and based on data available as of a specified date; as enrollment continues and additional follow-up data are obtained, reported data and other clinical outcomes may change materially.