Opus Genetics Announces Presentation of OPGX-LCA5 Gene Therapy Data at ARVO

 Opus Genetics announced 1-year results from adult patients treated in the ongoing phase 1/2 Study of its lead gene therapy candidate OPGx-LCA5. These results were presented at the 2025 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), taking place May 4-7, 2025 in Salt Lake City, Utah. The presentation, entitled “Recovery of Cone-Mediated Vision in a Severe Ciliopathy after Gene Augmentation: One Year Results of a Phase I/II Trial for LCA5-LCA,” was delivered by Tomas Aleman, MD, of the Scheie Eye Institute, University of Pennsylvania.

“The preliminary data emerging from this phase 1/2 study of OPGx-LCA5 are very encouraging. We are pleased to see evidence of durable efficacy, with the treatment benefits observed at 6 months being sustained out to 1 year,” Dr. Aleman said in a company news release. “Unquestionable gains in cone-mediated vision (daytime) confirmed 1 year after treatment have been associated with improvements in patients’ reading vision and ability to recognize objects, which are meaningful to these patients with severely impaired visual function. These findings support continued development of this gene therapy, which offers potentially groundbreaking opportunities, as we look forward to enrolling additional patients into the study.”

“Presentation of the 12-month data at ARVO underscores the growing interest in this program, and if approved, OPGx-LCA5 could potentially offer a life changing treatment for these patients," said George Magrath, MD, CEO of Opus Genetics. "The new data, while in a limited number of adults patients, give us even more conviction that our initial success with OPGx-LCA5 has the potential to translate to the rest of our pipeline, which contains gene therapy treatments for six additional inherited retinal diseases, as we plan to enter phase 1/2 with our BEST-1 program later this year. Additionally, we have been in discussions with the U.S. Food and Drug Administration (FDA) regarding the registration trial design for OPGx-LCA5, with the goal of initiating the study in 2026.

Highlights of 12-month Phase 1/2 Study Results

• The goal of this clinical trial is to evaluate the safety and preliminary efficacy results of subretinal gene therapy with OPGx-LCA5 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene.
• The results presented comprised three adult patients (ages 19, 26 and 34 years old), all of whom received subretinal (SR) injections in a single eye of up to 300 µl of low dose (1x1010 vector genome (vg) per eye) OPGx-LCA5. Each patient had severe disease at baseline, with limited but detectable photoreceptors and disease that had progressed to the central retina.
• A further two adolescent patients have now also been treated with promising preliminary data that were not included in this presentation.

Efficacy and functional endpoints

• Multi-Luminance orientation and Mobility Test (MLoMT): This is a virtual reality-based test designed to measure changes in functional vision. Similar to 6 months, the results at 12 months showed that all treated subjects identified more objects compared to baseline. Two out of the three participants showed a clinically meaningful improvement in the MLoMT with a three-object recognition threshold (ORT) or more improvement and with the last participant going from being unable to complete the MLoMT course to being able to complete it (although without an increase in the ORT).
• Visual Acuity (VA): Continued VA improvements out to 12 months (averaging 0.35 logMAR, equivalent to a 3.5 line improvement across the three participants).
• Full-field Stimulus Testing (FST): FST is a measure of retinal sensitivity. Improvements were seen at multiple time points post treatment. Study eyes showed larger improvements in sensitivity from baseline, with a 0.86 log improvement being observed at 12 months vs 0.16 log units for the control eyes. For interocular difference, there was an average of 0.7 log units better sensitivity when compared to the control eyes.
• Pupillary Light Reflex (PLR) : PLR is a natural reflex that controls the diameter of the pupil, in response to the intensity (luminance) of light. Pupil responses increased at 12 months in the study eyes compared to both control eyes and baseline. The treated eyes demonstrated a shift in response toward dimmer intensities compared to baseline. These results are supportive of improved cone-mediated vision through 12 months.
• Microperimetry: Microperimetry is a visual field test that incorporates perimetry and retinal imaging. It allows for the direct mapping of a stimulus in specific parts of the retina, thereby correlating functional information (visual field testing) with structural/anatomical data (retinal imaging). Data were collected from one patient (not possible in the other two participants at the baseline visit due to poor fixation), who saw substantial improvements in macular sensitivity. At 12 months, fixation in this patient stabilized and shifted toward the foveal center, suggesting improved central vision with improved fixation.

Safety

• The results provided evidence that OPGx-LCA5 was well tolerated with no reports of dose-limiting toxicities or serious adverse events out to 12 months. Anticipated adverse events were mild and unrelated to treatment, mostly related to the use of systemic steroids or with the surgical procedure. No major changes in the retinal structure of treated eyes were observed. All early adverse events resolved within 30 days of the procedure.