“What does the letter ‘E’ look like?”
That was the response of an adult patient who had been blind since the age of two when asked whether he could see the letter on the Snellen chart—the familiar poster with rows of letters shrinking in size that hangs in every optometrist’s office.
It wasn’t that he couldn’t see the letter on the chart. It was the first time he had ever seen a letter. His world, until then, had been known through touch and sound. Letters were understood by the ridges of braille beneath his fingers, not by the black shapes against a white background. For that matter, he hadn’t seen anything before—not his food, not the face of a family member, not a game of soccer. He hadn’t been able to cross streets or call an Uber without help. Then, after receiving a one-time injection of an experimental gene therapy, he could suddenly make out the shapes of letters. Within months, neurons that had been dormant for decades flickered to life. The patient could see for the first time.
The patient’s story is part of a larger clinical trial of OPGx-LCA5, Opus Genetics’ investigational augmentation gene therapy for Leber congenital amaurosis type 5 (LCA5). Children born with the ultra-rare inherited retinal disorder experience profound vision loss that progresses to blindness, often before they reach school age. Previously, Opus Genetics had presented promising data of all three adolescents with the rare inherited retinal disease treated with OPGx-LCA5.
Today, Opus Genetics announced that its Phase I/II study has delivered encouraging results for all three pediatric patients treated, showing measurable improvements across multiple visual function tests—including visual acuity, retinal sensitivity, and navigation tasks. These gains are especially meaningful given the severity of their baseline impairment. The pediatric results build on earlier adult data, where three participants regained vision they had lost in early childhood. Even more striking, those benefits have proven durable: adult patients continue to maintain their improvements out to 18 months after treatment.
And while restoring sight is headline-grabbing on its own, equally important is safety. Across all six patients treated so far, OPGx-LCA5 has been well tolerated, with no dose-limiting toxicities or therapy-related serious adverse events reported.
For George Magrath, MD, CEO of Opus Genetics, the data are as moving as they are scientifically significant. “These are people who’ve been blind since early childhood,” Magrath told Inside Precision Medicine. “And then, suddenly, they’re seeing food on their plate, watching their kids play soccer, or finding the right Uber without help. It’s dramatic. It’s not just restoring vision—it’s restoring independence.”
The initial spark
The origins of OPGx-LCA5 trace back to Jean Bennett, MD, PhD, at the University of Pennsylvania. Bennett developed Luxturna, the first FDA-approved gene therapy for an inherited disease, which targeted RPE65 mutations.
After its historic 2017 approval, however, ophthalmic gene therapy seemed to stall. Despite hundreds of known genetic causes of childhood blindness, no new programs have been advanced to patients. “Jean had all these other therapies that were similar to Luxturna, but they were just sitting there,” recalled Magrath. “There are more than 350 genes that can cause inherited blindness. Jean had worked on seven of them. But without a company to move them forward, they were going nowhere.”
To change that, Bennett partnered with Ben Yerxa, PhD, then CEO of the Foundation Fighting Blindness, to launch the company Opus in 2021. The Foundation provided seed funding, ensuring that promising therapies would not remain stranded in academic labs. “The name ‘Opus’ was deliberate,” said Magrath. “It was meant to be Jean Bennett’s opus magnum—her greatest works.”
At the time, Magrath was running Lexitas, a contract research organization overseeing dozens of ophthalmic trials, one of which happened to be the first-in-human LCA5 trial from Opus. That gave Magrath a front-row seat to see the data, and they treated three adults—a 26-year-old, a 19-year-old, and a 30-year-old—who have been blind since age two. “I saw three adults who’d been blind for decades regain their vision,” he recalls. “That experience stayed with me.”
When Lexitas was acquired by Ocuphire Pharma, Magrath took the helm as CEO and began looking at how to expand their commercial ophthalmic products. But when the chance came to merge with Opus and build a public company around Bennett’s gene therapy pipeline, he seized it. In October 2023, OccuFire acquired Opus and rebranded under the name Opus Genetics, with Magrath as CEO, Yerxa as president, and Bennett as scientific founder. “It created a new gene therapy company for the eye,” Magrath said. “And we had a sustainable model—funding from a commercial product to drive the pipeline forward.”
Limiting new variables
The LCA5 program is, in many ways, ideally suited to gene therapy. In affected patients, the retina’s architecture remains present but non-functional. On imaging, the photoreceptors and supporting structures appear intact, but they lack the lebercilin protein necessary for visual signaling. “It’s like having the hardware of a computer but missing a critical piece of software,” said Magrath. “That makes it a perfect target for gene augmentation.”
The treatment involves injecting an AAV8 vector carrying a functional copy of LCA5 directly into the subretinal space, next to the photoreceptors. The vector uses the same promoter as Luxturna, making use of a validated delivery system. “You couldn’t design a more precise therapy,” Magrath said. “We’re not doing CRISPR or gene editing. It’s straightforward gene augmentation using a proven delivery system. The same promoter as Luxturna. The same vector backbone. Manufacturing is relatively simple. A single 150-liter batch could treat the entire global population of LCA5 patients.”
When Opus presented its one-year adult data to the FDA, the agency granted the program RMAT (Regenerative Medicine Advanced Therapy) designation, enabling closer collaboration and accelerated development. Remarkably, the FDA also agreed to co-fund the study—an unprecedented step for Magrath. “The agency then told us: treat three kids and come back,” he recalled. “That’s exactly what we did. And now, all three kids have gotten better.”
The agency then gave Opus a clear challenge: prove the therapy works in children. In May and June 2025, three pediatric patients were treated at the University of Pennsylvania. Their results, reported in September, echoed the adults’—all three improved. “Now we’ve treated six people—three adults, three kids—and all six got better,” Magrath said. “That’s as strong a signal as you could hope for in an ultra-rare disease.”
Behind the clinical endpoints are human stories that defy statistics. One patient described the freedom of being able to call an Uber, recognize the license plate, and get into the right car without assistance. Another marveled at seeing food on his plate for the first time. For families, the impact has been just as profound: children who can now see their parents’ faces, parents who can watch their kids recognize colors or shapes. “These aren’t incremental gains,” said Magrath. “They’re life-changing. Vision doesn’t just improve quality of life—it restores independence and reduces the lifetime burden of care. Blind children can live 70 or 80 years, requiring constant support. Restoring vision changes that entire equation—for patients, families, and society.”
The next step is pivotal: Opus expects to meet with the FDA in Q4 2025 to define the path toward a registration trial.
Data spreadsheets can’t capture
From Wall Street’s perspective, LCA5 is compelling for its science, not so much its scale. The condition affects an estimated 200 patients in the U.S., making is an ultra-rare inherited retinal disorder. To impact more individuals with inherited retinal disorders, Opus has several other programs, including OPGx-BEST1 is being developed for bestrophin-1 (BEST1)-related inherited retinal diseases or bestrophinopathies, a form of macular degeneration found primarily in adults, estimated to affect approximately 9,000 people in the U.S.
But Magrath stresses that Opus’s approach is deliberately lean. “These are small, targeted programs,” he said. “They don’t require massive facilities or billion-dollar investments. It’s more like traditional drug development than risky drug discovery. You can see effects quickly. You don’t have to wait years for endpoints.” That speed and efficiency are key to making rare disease therapies viable. Many gene therapy programs have failed because the economics of ultra-rare conditions couldn’t support traditional development models. Opus aims to prove that lean, focused development can succeed.
The LCA5 trial is currently conducted at the University of Pennsylvania, which sees roughly a quarter of U.S. patients. For the pivotal trial, Opus plans to add a second site, likely in Dallas, to broaden geographic access. Meanwhile, the company is preparing to advance additional programs from Bennett’s lab. At least three more are expected to enter the clinic next year, each addressing a different inherited retinal disease.
And Opus isn’t just chasing approvals. It is trying to restart an entire field that has been stagnant since Luxturna. “Ophthalmology had the first approved gene therapy,” said Magrath. “Then nothing for years. We want to change that. If we can get LCA5 approved, it opens the door for dozens of other programs. This could be the beginning of a new wave in restoring vision.”
For Magrath, the most powerful proof isn’t in the clinical data—it’s in the stories of patients seeing the world for the first time. “I think about that adult patient staring at the Snellen chart, asking, ‘What does the letter E look like?’” he said. “That moment captured everything. He wasn’t just seeing a letter. He was seeing, period. That’s not data on a spreadsheet—that’s life restored.”
As Opus prepares for pivotal discussions with the FDA, the company stands on the threshold of bringing a second gene therapy for blindness to market. For patients with LCA5 and their families, it could mean a future defined not by darkness, but by sight.
