Opus Reports BEST1 Retinal Sensitivity Gains and Sustained LCA5 Vision Improvements

Opus Genetics reported clinical findings from its investigational OPGx-BEST1 and OPGx-LCA5 gene therapy programmes at Retina in Rio 2026 in Rio de Janeiro, Brazil. The results included improved retinal sensitivity in BEST1-associated disease and sustained visual-function improvements in participants with Leber congenital amaurosis type 5 (LCA5), alongside progress towards Phase 3 development of OPGx-LCA5.

OPGx-BEST1 Shows Early Retinal Sensitivity Improvements

The Phase 1/2 BIRD-1 study (NCT07185256) is evaluating OPGx-BEST1, an investigational gene therapy designed to restore bestrophin-1 function in patients with BEST1-associated inherited retinal diseases, including Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB).

In the low-dose Cohort 1, five participants received treatment, with follow-up ranging from three to six months. Three of the four participants evaluable for retinal sensitivity showed improvements in the treated transitional zone, representing 75% of those assessed.

Microperimetry, which measures the retina’s ability to detect light at specific locations, was used to assess sensitivity. The transitional zone surrounds damaged retinal tissue and may contain cells that retain functional potential. Among participants with improved sensitivity, the changes were also associated with reductions in intraretinal fluid, a feature of BEST1-associated disease.

Additional analyses suggested that optical coherence tomography (OCT) and other imaging techniques may help identify retinal regions associated with treatment response. Natural-history analyses also indicated that sensitivity can decline in the transitional zone even when measurements across the entire retina remain relatively stable.

These findings may help refine functional assessments in future studies, although the small evaluable group limits conclusions about treatment effects. The association between reduced intraretinal fluid and improved sensitivity does not establish causation. Opus Genetics also reported completion of enrolment in the high-dose Cohort 2, which includes 11 participants.

OPGx-LCA5 Shows Sustained Visual-Function Signals

OPGx-LCA5 is an investigational adeno-associated virus serotype 8 (AAV8)-based gene therapy designed to deliver a functional copy of the LCA5 gene to retinal photoreceptors. Mutations in LCA5 disrupt production of lebercilin, a protein essential for retinal function, causing severe vision loss that typically begins in childhood.

The company presented findings from six participants receiving the low dose of (1 \times 10^{10}) vector genomes per eye in its ongoing Phase 1/2/3 clinical programme (NCT05616793). The group included three adults and three adolescents.

The three adults demonstrated sustained visual acuity improvements through 24 months. The three adolescents showed evidence of restored cone-mediated vision, with sensitivity measurements reaching the normal range through six months, according to the company. Both groups also showed improved light sensitivity on full-field stimulus testing (FST) compared with their untreated eyes.

Microperimetry assessments showed increased retinal sensitivity and movement of visual fixation towards the central retina. Participants also reported improvements in everyday activities, including recognising family members, identifying objects, seeing colours and navigating independently, including without a cane.

These reports provide context for the potential functional relevance of the measured changes. However, the findings involve only six participants, and follow-up differs between adults and adolescents. The results do not establish the magnitude or durability of benefit across the wider LCA5 population.

Phase 3 Development Advances

Opus Genetics reported that OPGx-LCA5 had advanced to Phase 3 using the low dose without further dose escalation. The company stated that the natural-history and treatment cohorts were fully enrolled, with dosing expected to begin in the fourth quarter of 2026.

The primary efficacy endpoint will assess retinal sensitivity across 16 central retinal test locations. This approach is intended to quantify changes at predefined retinal locations. The Phase 3 results will determine whether the functional improvements reported in the earlier programme can be demonstrated consistently.

Clinical Interpretation

The findings provide early signals of functional improvement across two inherited retinal disease programmes. For OPGx-BEST1, improved retinal sensitivity in three of four evaluable participants, alongside associated reductions in intraretinal fluid among responders, supports further investigation of structural and functional changes following treatment. Imaging analyses may also inform the selection of outcome measures, although their predictive value remains unestablished.

For OPGx-LCA5, visual acuity improvements through 24 months in adults and encouraging findings through six months in adolescents support continued evaluation. However, small participant groups and differing follow-up periods limit conclusions about the consistency and durability of benefit. Neither programme’s reported findings establish definitive efficacy.

References

Opus Genetics, Inc. Opus Genetics Presents Positive Clinical Data from OPGx-BEST1 and OPGx-LCA5 Gene Therapy Programs at Retina in Rio 2026. October 15, 2026.

 Safety and Tolerability of Subretinally Injected OPGx-BEST1 in Patients with Best Vitelliform Macular Dystrophy (BVMD) or Autosomal-Recessive Bestrophinopathy (ARB) (BIRD-1), ClinicalTrials.gov ID NCT07185256

Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm with Untreated Patients, ClinicalTrials.gov ID NCT05616793