Opus Genetics’ OPGx-LCA5 Gene Therapy Shows Sustained Vision Gains Ahead of Phase 3

Opus Genetics has reported interim phase 1/2 data from two adeno-associated virus (AAV) gene therapy programs for inherited retinal diseases (IRDs), including sustained visual improvements with OPGx-LCA5 that support the program’s move into phase 3 at its lowest tested dose.¹ The data were presented at Retina in Rio 2026.¹

“The data presented at Retina in Rio highlight meaningful progress across our gene therapy pipeline, with sustained improvements in visual function observed through 24 months in adults treated with OPGx-LCA5 and encouraging early evidence of improved retinal sensitivity in participants receiving OPGx-BEST1,” said George Magrath, MD, chief executive officer of Opus Genetics.

What is OPGx-LCA5, and what did the data show?

OPGx-LCA5 is an AAV8-based gene therapy designed to deliver a functional copy of the LCA5 gene to retinal photoreceptors.¹ Mutations in LCA5 disrupt production of lebercilin, a protein needed for normal retinal function, causing Leber congenital amaurosis type 5, a rare inherited retinal disease that leads to severe vision loss beginning in childhood.¹ In one large screening study of patients with childhood retinal dystrophy, LCA5 mutations accounted for approximately 2% of disease.² The therapy is given as a one-time subretinal administration, as BioPharm International® previously reported.

Six patients, three adults and three children or adolescents, received the low dose of 1 × 10¹⁰ vector genomes per eye in the phase 1/2 study.¹ According to Opus, the adult patients showed visual acuity improvements sustained through 24 months, while cone-mediated vision in pediatric patients reached normal ranges by six months.¹

Both groups showed improved light sensitivity on full-field stimulus testing compared with their untreated eyes.¹ Microperimetry showed increased retinal sensitivity and a shift in fixation toward the central retina.¹ Opus also said participants reported functional gains, such as navigating without a cane and recognizing family members.¹

What did OPGx-BEST1 show?

OPGx-BEST1 targets IRDs caused by mutations in the BEST1 gene, including Best vitelliform macular dystrophy and autosomal recessive bestrophinopathy.¹ It is being evaluated in the ongoing Phase 1/2 BIRD-1 trial.¹

In the low-dose Cohort 1, five patients were treated, with three to six months of follow-up.¹ Of the four patients who could complete retinal sensitivity testing, three (75%) showed improved retinal sensitivity by microperimetry in the treated transitional zone.¹ Responders also showed reduced intraretinal fluid, a feature of BEST1-associated disease.¹ The high-dose Cohort 2 has completed enrollment with 11 participants.¹

Opus did not report safety findings for either program in its announcement, and both data sets come from small cohorts with interim follow-up.¹

Why does the LCA5 dose matter?

Opus is advancing OPGx-LCA5 into phase 3 at the phase 1/2 low dose without further dose escalation.¹ Dose is a central consideration in AAV gene therapy. In a BioPharm International interview on next-generation AAV approaches, Erik Wiklund, chief executive officer of Circio, described the potential benefit of lowering AAV doses. “If you can bring down the dose of an AAV by 50-fold, it would really help alleviate some of the toxicity challenges,” Wiklund said.

What happens next?

The natural history and treatment cohorts of the OPGx-LCA5 Phase 3 trial are fully enrolled, and dosing is expected in the fourth quarter of 2026.¹ The trial’s primary efficacy endpoint is change in retinal sensitivity across 16 central retinal test locations.¹ As BioPharm International reported when the trial completed enrollment, the design includes a six-month run-in period in which patients serve as their own baseline comparators, and the program holds Rare Pediatric Disease, Orphan Drug, and Regenerative Medicine Advanced Therapy designations.

For OPGx-BEST1, Opus said the findings are informing its development strategy, including more targeted retinal sensitivity assessments and imaging approaches to measure treatment response.¹

“Importantly, these findings strengthen our understanding of how to measure treatment response in IRDs and support the continued advancement of both programs,” McGrath said.¹

References

1. Opus Genetics. Opus Genetics Presents Positive Clinical Data from OPGx-BEST1 and OPGx-LCA5 Gene Therapy Programs at Retina in Rio 2026. Press release. Published October 15, 2026. Accessed October 16, 2026.
2. Mackay DS, Borman AD, et al. Screening of a large cohort of Leber congenital amaurosis and retinitis pigmentosa patients identifies novel LCA5 mutations and new genotype-phenotype correlations. Hum Mutat. 2013;34(11):1537-1546.