Let’s Chat About … Opus Genetics with Ben Yerxa

Working with preclinical data from multiple Leber congenital amaurosis (LCA) studies at the same time, Opus Genetics hopes to advance research into gene therapy for several forms of LCA at a faster pace.

Ben Yerxa, PhD, and acting Chief Executive Officer of Opus, told a Hope in Focus webinar audience that good preclinical data from Opus Co-Founders Jean Bennett, MD, and Eric Pierce, MD, became the foundation for the company’s first two projects researching LCA5 (Lebercilin) and LCA13 (RDH12).

Yerxa, who also is CEO of the Foundation Fighting Blindness and its Retinal Degeneration Fund (RD fund), explained that while Dr. Bennett researched what came to be the LCA2 (RPE65) gene therapy LUXTURNA®, other projects awaited advancement to preclinical stages. Dr. Pierce’s preclinical work also became part of Opus’ advancing work.

Yerxa discussed biotechnology company’s aspirations as part of the Hope in Focus “Let’s Chat About …” webinar series. Our March episode, moderated by Courtney Coates, Director of Outreach and Development featured Yerxa, acting CEO of Opus based in Raleigh, N.C. Click here to view the webinar.

The Foundation’s RD Fund led the $19 million in seed financing for the company founded last fall, with participation from the Manning Family Foundation and Bio Partners.

The Magic of a One-of-a-Kind Model

Opus is the first spin-out company internally conceived and launched by the RD Fund to further the Foundation’s mission. The RD Fund is investing in projects that are in, or advancing toward, early-stage clinical trials.

“Opus is a first-of-its-kind model for patient-focused therapeutic development,” Yerxa said. “As the first company launched by the Foundation’s venture arm, RD Fund, Opus is uniquely positioned to bring experts, resources, and patients together to efficiently advance ocular gene therapies for small groups of patients that to date have been neglected.”

The company decided to take on the development of multiple gene therapies, regardless of the small treatment population for rare retinal diseases.

“Opus was really born out of necessity,” Yerxa said. “Many gene therapies in preclinical development were just not being developed further.”

The company would even work on programs where only 100 patients have a particular retinal disease, or where the patient population is smaller or larger than the 1,000 to 2,000 people in the United States with LCA2 RPE65, a form of LCA treated with LUXTURNA®. The gene therapy, developed by Spark Therapeutics, is the only federally approved treatment for an inherited gene mutation.

“It evens out as a blend,” he said. “That’s kind of where the magic is.”

The biotech’s lead program, OPGx-001, addresses mutations in the LCA5 gene that encodes the lebercilin protein. LCA5 is one of the most severe forms of LCA and affects about one in 1.7 million people in the United States.

Its second program, OPGx-002, focuses on restoring protein expression and halting functional deterioration in people with retinal dystrophy caused by mutations in the retinal dehydrogenase gene, knowns as RDH12 or LCA13. The disease affects one in 288,000 people in the U.S.

Its third program, OPGx-003, targets LCA9 caused by NMNAT1 mutations and affects about one in 432,000 people in the U.S.

Yerxa said Opus is hoping to raise $70 million or more in the next six to nine months to bring it through 2024-25.

He advised people interested in the research to keep in communication with their physicians because as clinical trials get ready to begin, Opus will be looking for individuals to take part in them.

LCA5 Clinical Trials Planned Later This Year

Opus is looking at filing for an Investigational New Drug (IND) application with the U.S. Food and Drug Administration by the middle of this year before enrolling people for clinical trials by summers’ end at the University of Pennsylvania for LCA5. By filing for an IND, a company is asking for permission to start human clinical trials and to ship an experimental drug across state lines before approving a marketing application for the drug.

“We’re looking forward to getting that started so we’ll be a clinical-stage company.”

Their work also will center on what Yerxa called a tried-and-true approach to delivering the medicine through Adeno-associated virus (AVV) vectors, the leading platform for gene delivery for the treatment of a variety of human diseases.

In today’s world of retinal gene therapy development, AVVs are most often used to deliver therapeutic genes to cells in the retina, according to the Foundation. Gene therapy is administered by injecting a tiny drop of liquid underneath or near the retina. AAVs are safe and able to penetrate cells with their genetic cargo. They naturally occur in humans and don’t cause any known illness. For regulators like the FDA, that excellent safety profile is highly desirable.

Having available multiple inventories for developing therapies and working with the university to license the technology can speed up the pace of research and manufacturing, reducing the average two-year timeline for clinical work.

“I think we can shave off many months of the timeline,” Yerxa said.

In the question-and-answer session following the webinar, one viewer asked about taking on research into a form of LCA caused by a mutation in the IQCB1 gene, and Yerxa replied, “We are aware of that work and interested in this asset.”

He suggested people keep connected with Opus and receive company emails for updates on projects. https://opusgtx.com/contact/