Ben Yerxa Opus Genetics
Ben Yerxa, PhD, CEO of Opus Genetics

Opus Genetics has acquired the rights to two adeno-associated virus (AAV)-based gene therapy product candidates for inherited retinal diseases (IRDs) from the public biopharmaceutical company Iveric Bio. This deal adds to Opus’ AAV-based gene therapy portfolio, which has focused on treating pediatric forms of inherited blindness. As part of the deal, Opus will be in charge of researching, developing, and selling new gene therapy candidates to address two adult-onset IRDs: bestrophin-1 (BEST1)-related inherited retinal diseases and rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP).

Ben Yerxa, PhD, CEO of Opus, told GEN Edge that the main reason for acquiring the programs was to bring therapies to more patients. “The first three programs that we brought in to start the company are all pediatric gene therapies, and a couple of them are in pretty small populations—hundreds of patients,” said Yerxa.

“These two new assets are for adult-onset retinal degenerations, and they’re in the mid-thousands of patients (in the United States only). That scales with population. So, it really broadens the portfolio so that we’re not just in pediatrics, and it includes a couple larger populations.”

Eagle eye

Opus was started by the Foundation Fighting Blindness in Research Triangle Park, NC, in 2021. Yerxa, who previously was the CEO at the Foundation and the Retinal Degeneration Fund (RD Fund), the venture arm of the Foundation Fighting Blindness, said that Opus was founded based on the foundation’s work identifying gene therapies that weren’t getting the attention they needed because they were isolated projects.

The RD Fund led the seed financing with $10 million. This funding was supported by $5 million from the Manning Family Foundation and $4 million from Bios Partners, a venture capital firm identifying advanced biotech in overlooked and under-invested markets in the United States.

Co-founder Jean Bennett, MD, PhD, is the F.M. Kirby emeritus professor of ophthalmology at the Perelman School of Medicine at the University of Pennsylvania and also co-founder of Spark Therapeutics (which Roche acquired), GenSight Biologics, and Limelight Bio. With the initial seed funding, Opus was able to advance preclinical research toward the clinic.

Opus’s initial lead programs concentrate on therapies to address gene mutations that result in various forms of Leber congenital amaurosis (LCA)—a group of rare inherited retinal diseases that typically present in infancy and are characterized by degeneration of photoreceptors. The company’s lead program, OPGx-001, is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein. One in 1.7 million people has LCA5, one of the most severe types of the disease. In December 2022, Opus Genetics received FDA clearance of its IND application for OPGx-001, and the company anticipates initiating a Phase I/II clinical trial in early 2023 in the United States.

One IND per year

“We created Opus to essentially put our arms around a number of gene therapies focused on inherited retinal disease only and to build a business model around a stack of assets,” said Yerxa. “When you have a stack, then commercially it actually starts to really work, even if you have some smaller populations, as long as they’re blended with some other larger populations—then the whole portfolio really comes together.”

In the United States, it is estimated that nearly 5,000 patients, or one in 69,000 people, have IRDs linked to BEST1. The goal of BEST1 gene therapy is to give retinal pigment epithelial cells a working copy of the BEST1 gene so that they can make the bestrophin-1 protein and bring the photoreceptors and retinal pigment epithelial cells back into balance.

The RHO-adRP gene therapy approach is going after autosomal dominant retinitis pigmentosa, which is one of the most widespread IRDs and is thought to affect more than 6,000 people in the United States alone, or one in every 51,000 people. This uses what Yerxa calls “knock down and replace” technology—there’s a silencing RNA (siRNA) that knocks down the autosomal dominant rhodopsin gene and replaces that with a functional copy of the gene.

“Our goal from the outset is to be able to file one IND per year,” said Yerxa. “I’m happy to say that we filed and cleared our first IND [in 2022], and we’ll be starting our clinical trial for our first indication in the first quarter of [2023]. For the BEST1 asset, we will be filling the IND in the second half of 2023. Even as a small company, we have the ability to develop even half a dozen assets all at once in staggered fashion, and we can do that with great partnerships.”

Yerxa said to expect a full pipeline update in Spring 2023 showing six programs or more under development, which is quite the load for a company made up of 19 people.

Divide and conquer

In November 2022, Iveric announced that it has submitted to the FDA the first part of its New Drug Application (NDA) for rolling review of avacincaptad pegol (ACP, also known as Zimura®) a novel investigational complement C5 inhibitor, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

“We really just got together with Iveric and said, ‘Look, we are the perfect home for these assets, let’s try to work something out,’” said Yerxa. “They have a tiger by the tail with their geographic atrophy program, so they were willing to be creative with us and find a good home for these assets.”

In exchange, Iveric received an upfront payment of $500,000 and a high single-digit percentage ownership of Opus. Iveric can receive development and regulatory milestone payments, sales milestone payments, and a low single-digit earnout on net sales of the products. In addition, Iveric retains certain rights with respect to the potential future commercialization of gene therapy products for BEST1 or RHO-adRP under certain circumstances.