Two Gene Therapy Candidates for Inherited Retinal Diseases are Acquired by Opus Genetics

 

With the agreement, Opus' targeted patient group for its cutting-edge therapies of uncommon hereditary retinal illnesses will grow from paediatric to adult-onset.

Written on January 3, 2023, by Jonathan D. Grinstein, Ph.D.

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Iveric Bio, a publicly traded biopharmaceutical firm, sold Opus Genetics the rights to two adeno-associated virus (AAV)-based gene therapy product candidates for inherited retinal disorders (IRDs). With a focus on treating paediatric types of hereditary blindness, Opus' AAV-based gene therapy portfolio has grown with the addition of this transaction. Opus will be in charge of investigating, creating, and marketing innovative gene therapy candidates to treat two adult-onset IRDs: rhodopsin-mediated autosomal dominant retinitis pigmentosa and bestrophin-1 (BEST1)-related inherited retinal disorders (RHO-adRP).

The primary goal of acquiring the programmes, according to Ben Yerxa, PhD, CEO of Opus, was to make medicines available to more people. The company's initial three initiatives, which all involve paediatric gene therapy, were all started with just a few hundred patients, according to Yerxa.

These two new resources are for adult-onset retinal degenerations, and there are around 20,000 individuals with them (in the United States only). That grows as the population rises. As a result, it significantly broadens the portfolio and includes a few larger groups, allowing us to move beyond paediatrics.

Hawk eye

The Foundation Fighting Blindness launched Opus in 2021 at Research Triangle Park, North Carolina. Yerxa, who formerly served as the CEO of the Foundation and the Retinal Degeneration Fund (RD Fund), the venture arm of the Foundation Fighting Blindness, claimed that the foundation's work in identifying gene therapies that weren't receiving the attention they required because they were standalone projects led to the founding of Opus.

With $10 million, the RD Fund took the lead in the seed funding. $5 million from the Manning Family Foundation and $4 million from Bios Partners, a venture capital business that seeks for advanced biotech in underserved and untapped markets in the United States, helped to support this investment.

The F.M. Kirby emeritus professor of ophthalmology at the Perelman School of Medicine at the University of Pennsylvania and co-founder Jean Bennett, MD, PhD, also founded GenSight Biologics, Limelight Bio, and Spark Therapeutics, which Roche later bought. Opus was able to push preclinical research toward the clinic with the help of the initial seed investment.

The initial focus of Opus's lead initiatives is on treatments for gene abnormalities that cause various types of Leber congenital amaurosis (LCA), a category of uncommon hereditary retinal illnesses that often manifest in infancy and are marked by photoreceptor degradation. The LCA5 gene, which codes for the lebercilin protein, is the target of the company's primary programme, OPGx-001. LCA5, one of the most severe forms of the illness, affects one in every 1.7 million individuals. Opus Genetics expects to begin a Phase I/II clinical study in the United States in early 2023 after receiving FDA clearance of their IND application for OPGx-001 in December 2022.

Each year, one IND

The purpose of Opus, according to Yerxa, was to "basically wrap our arms around a variety of gene treatments targeted exclusively at hereditary retinal illness and to construct a business model around a stack of assets." If you have a stack, then commercially it really begins to work, even if you have some smaller populations, as long as they are mixed with some other larger populations—when that's the whole portfolio really comes together."

One in 69,000 Americans, or close to 5,000 patients, are thought to have IRDs connected to BEST1 in the US. Giving retinal pigment epithelial cells a functional copy of the BEST1 gene will enable them to produce the bestrophin-1 protein and restore the balance between photoreceptors and retinal pigment epithelial cells.

Autosomal dominant retinitis pigmentosa, one of the most common IRDs, is thought to affect more than 6,000 people in the United States alone, or one in every 51,000 people. The RHO-adRP gene therapy strategy targets this condition. In this, the autosomal dominant rhodopsin gene is knocked down and replaced with a functioning copy of the gene using a technique that Yerxa refers to as "knock down and replace."

Our first objective is to be able to submit one IND annually, according to Yerxa. "I'm pleased to report that in 2022 we submitted and received clearance for our first IND, and in the first quarter of [2023] we will begin our clinical study for our first indication. In the second half of 2023, we will fill the IND for the BEST1 asset. With the help of fantastic collaborations, even as a small business, we are able to develop even a dozen assets at simultaneously in a staggered approach.

A comprehensive pipeline update showing six or more items in development is anticipated in the spring of 2023, according to Yerxa, which is a lot for a firm with only 19 employees.

"Divide and rule"

The first portion of Iveric's 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 was submitted to the FDA in November 2022, according to the company's announcement (AMD).

Yerxa stated, "We actually simply sat with Iveric and said, Look, we are the right home for these assets, let's try to work something out. With their geographic atrophy initiative, they "had the tiger by the tail," thus they were open to working with us to come up with a decent home for these assets.

Iveric was compensated with a $500,000 up-front payment and a high single-digit ownership stake in Opus in return. In addition to sales milestone payments and a low single-digit earnout on net sales of the goods, Iveric may also receive development and regulatory milestone payments. Additionally, under specific conditions, Iveric retains some rights with regard to the prospective future marketing of gene therapy products for BEST1 or RHO-adRP.