Opus Genetics Reports Pediatric Data From OPGx-LCA5 Phase 1/2 Trial in LCA5

Opus Genetics announced positive 3-month data from the pediatric cohort of its ongoing phase 1/2 clinical trial (OPGx-LCA5-1001) evaluating OPGx-LCA5, an investigational gene augmentation therapy for Leber congenital amaurosis type 5 (LCA5).

“These pediatric results are particularly exciting, as they provide evidence that OPGx-LCA5 can potentially restore cone-mediated vision in teenagers who had already experienced profound vision loss,” said George Magrath, MD, CEO of Opus Genetics. “These outcomes, alongside observed durable improvements observed in adults out to 18 months, give us confidence in the potential for OPGx-LCA5 to deliver meaningful and lasting benefit to patients. We expect to meet with the US FDA in the fourth quarter of this year to discuss these results and the next steps for our LCA5 program targeting this ultra-rare disease.”

Three pediatric participants aged 16-17 with severe baseline vision impairment received a single subretinal injection of OPGx-LCA5. All three participants had improvements across multiple measures of visual function, as described below:

• Visual Acuity (VA): For the pediatric cohort, early data showed a group average of a 0.3 logMAR improvement which is greater than was observed in the adult cohort
• Full-Field Stimulus Testing (FST): All three participants showed improvements in the treated eyes from 1 month. Participants showed greater than 1 log unit improvement in cone sensitivity to both red and blue light. These changes provide evidence of recovery in retinal sensitivity.
• Multi-Luminance Orientation and Mobility Test (MLoMT): All participants identified more objects through 3 months compared to baseline. Two out of the three participants had greater improvement in the treated eye compared to the control eye.
• Microperimetry: Two of the three pediatric participants could not conduct a microperimetry test due to their poor visual acuity and nystagmus at screening. However, microperimetry data was obtained on one participant, for whom early signs of improved fixation stability were observed, consistent with functional retinal recovery.

In addition, combined adult data support that improvements in visual acuity were sustained through 18 months, both in terms of mean change from baseline and mean interocular difference.

OPGx-LCA5 has been well-tolerated in all six participants treated to date (three adults and three pediatric participants). No ocular serious adverse events or dose-limiting toxicities have been observed. All ocular adverse events were mild in severity and were anticipated. No events were related to the study drug. One pediatric participant had a pre-existing cataract that worsened at 3 months, which was attributed to the surgical procedure itself and did not obscure improvements in retinal sensitivity.

“Seeing pediatric participants achieve measurable improvements in visual acuity, retinal sensitivity, and real-world navigation tasks within 3 months and adult participants maintaining those improvements is a remarkable step forward,” said Tomas S. Aleman, MD, of the Scheie Eye Institute, University of Pennsylvania and principal investigator of the study. “This is important evidence supporting that gene augmentation therapy can potentially restore cone function in patients with LCA5.”