Opus Genetics’ OPGx-LCA5 Shows Sustained Vision Improvement at One Year in Phase 1/2 Study

RESEARCH TRIANGLE PARK, N.C., May 05, 2025 (GLOBE NEWSWIRE) — Opus Genetics, Inc. (Nasdaq: IRD), a clinical-stage ophthalmic biotechnology company dedicated to developing innovative gene therapies for inherited retinal diseases (IRDs), today announced compelling one-year results from the adult patient cohort of its ongoing Phase 1/2 study evaluating the AAV-delivered OPGx-LCA5. This lead gene therapy candidate targets Leber congenital amaurosis type 5 (LCA5), a severe form of inherited retinal degeneration.  The encouraging data, presented yesterday by Dr. Tomas Aleman at the prestigious 2025 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Salt Lake City, Utah, underscore the potential for OPGx-LCA5 to provide a durable and meaningful benefit to individuals with this debilitating condition.

Dr. Aleman of the Scheie Eye Institute, University of Pennsylvania, who delivered the presentation titled “Recovery of Cone-Mediated Vision in a Severe Ciliopathy after Gene Augmentation: One Year Results of a Phase I/II Trial for LCA5-LCA,” commented, “The preliminary data observed in this Phase 1/2 study of OPGx-LCA5 are highly promising. The sustained efficacy seen at the one-year mark, building upon the encouraging six-month findings, is particularly noteworthy. The clear improvements in cone-mediated vision, which is crucial for daytime sight, have translated into tangible benefits for patients, enhancing their reading capabilities and ability to recognize objects. These are significant gains for individuals with severely impaired visual function, reinforcing the potential of this gene therapy as a groundbreaking treatment option. We eagerly anticipate the enrollment of additional patients to further explore its potential.”

George Magrath, M.D., Chief Executive Officer of Opus Genetics, added, “The presentation of this 12-month data at ARVO highlights the increasing interest and excitement surrounding the OPGx-LCA5 program. If ultimately approved, this therapy has the potential to be a life-changing treatment for individuals affected by LCA5-related inherited retinal disease. While these initial findings are based on a limited number of adult patients, they significantly bolster our confidence in the potential of our gene therapy approach. We believe the success we are seeing with OPGx-LCA5 could have implications for the rest of our pipeline, which includes gene therapy treatments for six other inherited retinal diseases. We are on track to initiate a Phase 1/2 study for our BEST-1 program later this year. Furthermore, we have been actively engaged in discussions with the U.S. Food and Drug Administration (FDA) regarding the design of the pivotal registration trial for OPGx-LCA5, with the aim of commencing this crucial study in 2026.”

Key Highlights of the 12-Month Phase 1/2 Study Results:

This Phase 1/2 clinical trial is designed to assess the safety and preliminary efficacy of a single subretinal administration of OPGx-LCA5 in patients experiencing inherited retinal degeneration due to biallelic mutations in the LCA5 gene. The presented results encompass data from three adult patients (aged 19, 26, and 34) who each received a subretinal injection of up to 300 µl of a low dose (1×10¹⁰ vector genome (vg) per eye) of OPGx-LCA5 in one eye. At the start of the study, all patients exhibited severe disease with limited but detectable photoreceptors and disease progression affecting the central retina. Notably, promising preliminary data from an additional two adolescent patients, treated more recently, were not included in this initial presentation.

Efficacy and Functional Endpoints:

• Multi-Luminance orientation and Mobility Test (MLoMT): This innovative virtual reality-based test evaluates changes in functional vision. Consistent with the six-month data, the 12-month results demonstrated that all treated subjects could identify a greater number of objects compared to their baseline performance. Importantly, two of the three participants showed a clinically meaningful improvement, achieving a three-object recognition threshold (ORT) or more improvement. The third participant, who was initially unable to complete the MLoMT course, was able to complete it at 12 months, indicating a functional improvement even without a measured increase in ORT.
• Visual Acuity (VA): Patients continued to experience improvements in visual acuity out to the 12-month mark. On average, the three participants showed a 0.35 logMAR improvement in the treated eye, which translates to approximately a 3.5-line gain on a standard eye chart.
• Full-field Stimulus Testing (FST): This test measures the overall sensitivity of the retina to light. Improvements in retinal sensitivity were observed at multiple time points following treatment. At 12 months, the treated eyes showed a substantial average improvement of 0.86 log units from baseline, compared to a minimal 0.16 log unit change in the untreated control eyes. The interocular difference in sensitivity, comparing the treated eye to the control eye, averaged a significant 0.7 log units in favor of the treated eye.
• Pupillary Light Reflex (PLR): The pupillary light reflex, a natural response to changes in light intensity, showed increased responses in the treated eyes at 12 months compared to both the untreated eyes and baseline measurements. Notably, the treated eyes demonstrated a shift in their response towards dimmer light intensities compared to their initial baseline, providing further evidence of improved cone-mediated vision persisting through 12 months.
• Microperimetry: This advanced visual field test maps light sensitivity to specific areas of the retina. Data were available for one patient (fixation issues prevented baseline data collection in the other two). This patient demonstrated substantial improvements in macular sensitivity at the 12-month assessment. Furthermore, the patient’s fixation, which was initially unstable, stabilized and shifted towards the foveal center, suggesting an improvement in central vision and the ability to focus.

Safety:

The one-year safety data continue to support the favorable profile of OPGx-LCA5. The therapy was well-tolerated, with no reports of dose-limiting toxicities or serious adverse events observed throughout the 12-month follow-up period. Any adverse events reported were mild and considered unrelated to the gene therapy itself, primarily associated with the use of systemic steroids administered post-surgery or related to the surgical procedure. Importantly, no significant changes in the retinal structure of the treated eyes were observed. All early adverse events resolved within 30 days of the surgical procedure.

Study Design:

This open-label, Phase 1/2 clinical trial is evaluating the safety and preliminary efficacy of a single subretinal injection of OPGx-LCA5 in patients with inherited retinal degeneration caused by biallelic mutations in the LCA5 gene. The trial is actively enrolling both adult and pediatric patients, with dosing of the first pediatric patients commencing in February 2025. Key efficacy endpoints include assessments of functional vision using the Multi-Luminance orientation and Mobility Test (MLoMT), retinal sensitivity through Full-Field Stimulus Testing (FST), and localized retinal function via microperimetry.