December, 02 2021 • Articles

Startup spotlight: Opus Genetics, with $19M, works to advance cures for blinding retinal diseases

by Jason Parker, WRAL TechWire

RALEIGH – Opus Genetics recently announced it would open its third preclinical trial, just a few months after the company formed with a $19 million seed financing round led by the venture capital arm of the Foundation Fighting Blindness, the RD Fund.

The company, founded by the RD Fund, also received seed funding from the Manning Family Foundation and Bios Partners, and is the first spin-out company that was internally conceived and launched by the RD Fund to further the mission of the foundation, which is to advance the treatments and cures for blinding retinal diseases.

WRAL TechWire interviewed the company’s acting CEO, Ben Yerxa, PhD, who also serves as CEO of the Foundation Fighting Blindness and the RD Fund, about the company’s origins, mission, and technology.  A lightly edited transcript of that interview follows.

WRAL TechWire (TW): Tell us more about how and why the company was formed?

Ben Yerxa, PhD, acting CEO of Opus Genetics (Yerxa): Opus Genetics is a gene therapy company focused on preserving or potentially improving vision for patients with inherited retinal diseases with a unique model and purpose.  Opus is uniquely positioned to bring experts, resources and patients together to efficiently advance ocular gene therapies for patients that to date have been neglected.

We’re fortunate to have our scientific founders, who have dedicated their lives to working on these diseases.  The timing, founders and financing came together at the right time to advance these therapies toward patients.

Opus scientific founders are Jean Bennett, M.D., Ph.D., the F.M. Kirby Emeritus Professor of Ophthalmology at the Perelman School of Medicine at the University of Pennsylvania, and Junwei Sun, chief administrator of Penn’s Center for Advanced Retinal Ocular Therapeutics (CAROT), and Eric Pierce, M.D., Ph.D., Director of the Ocular Genomics Institute and William F. Chatlos Professor of Ophthalmology at Massachusetts Eye and Ear and Harvard Medical School.

This opportunity was uniquely suited to working together—technology that is de-risked through rigorous preclinical studies in models that emulate human disease, programs hyper focused in genetic retinal disease, relationships with the best scientists and organizations, and groups that all deeply understand the patient experience and the science.

Our  adeno-associated virus (AAV) based gene therapy portfolio tackles some of the most neglected forms of inherited blindness while creating novel orphan manufacturing scale and efficiencies. The company’s lead programs will focus on treatments delivered subretinally to address mutations in genes that cause different forms of Leber congenital amaurosis (LCA), a rare form of pediatric blindness.

TW: What is the scope of the challenge with retinal disease, and why did the founders and company choose to work to address these? 

Yerxa: There is significant unmet need in the treatment of these rare blinding conditions, and we see the opportunity for a proven, de-risked, efficient path to the clinic for these desperately needed new therapies for patients.  This team and scientists have all dedicated their careers to working to improve vision for these devastating blinding conditions.

OPGx-001 is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein.  OPGx-002 will focus on restoring protein expression and halting functional deterioration in patients with retinal dystrophy caused by mutations in the retinal dehydrogenase (RDH12) gene (LCA13).  OPGx-003 is a gene augmentation therapy designed to halt functional deterioration in pediatric patients with retinal degenerative disease caused by mutations in the nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene.

While LCA is a group of rare inherited retinal diseases characterized by degeneration of photoreceptors that affect about 1 in 40,000 newborns, LCA5 affects approximately one in 1.7 million people, retinal dystrophy caused by mutations in the RDH12 gene affects one in 288,000 people, and disease caused by mutations in the NMNAT1 gene affects one 432,000 people in the U.S.

Another way to think about it is in the US and EU combined these indications have hundreds to low thousands of patients.

TW: The company launched with $19 million in seed funding—how do you plan to allocate and invest this capital?

Yerxa: The $19 million in seed financing was led by the RD Fund, which also founded the company, with participation from the Manning Family Foundation and Bios Partners.

This funding provides Opus with the resources to advance our pipeline of three programs, including our first program (OPGx-001) entering the clinic in 2022.  We plan to continue pursuing additional programs and develop our manufacturing plans in parallel.

A core tenet of our approach is to build an engine to bring multiple rare genetic retinal disease therapeutics into the clinic and ultimately to the patients who need them.  We will disclose additional financing and commercialization plans at the appropriate time.

TW: The company launched in Raleigh—why?

Yerxa: The Triangle is a great place to recruit top talent, and to grow biotech companies, especially in the field of gene therapy. Additionally, the RD Fund is based here, so as its first spinout, it just made sense for Opus to be founded here and gain some early operational and resource efficiencies.

As a rapidly evolving company, we anticipate expanding as we advance our programs toward the clinic. We recently filled two cornerstone leadership roles for the company—Chief Operating Officer Joe Schachle and Chief Scientific Officer Dr. Ash Jayagopal—and we plan to hire additional talent for key roles across the organization.

The idea behind Opus is not about one program, it’s about building an engine to solve as many blinding degenerative retinal diseases as possible.  There are currently over 260 genes known to cause inherited retinal diseases, so our opportunities are substantial.  The infrastructure can be used for multiple products to efficiently move validated science and/or well characterized material by preeminent leaders in the field toward patients leveraging scalable, strategic manufacturing and processes.

We see manufacturing as the lynchpin of our success, in developing the capability and strategically managing the cadence of our clinical timelines to produce therapeutics most efficiently, leveraging our founders’ expertise and learnings over a lifetime of research and development in this area.

Because these are small populations and we treat the eye, our strategy is built around high-quality, small-scale manufacturing—it is a scale down problem, not a scale up problem.  We are working to develop our own strategy for the most efficient way to manufacture small batches using high quality GMP material.  In the meantime, we want to work with a CDMO that embraces our model and is willing to produce small batches.

TW: What have people “missed” in the last two years in gene therapy and in the life sciences?  What are the emerging or existing trends in the sector that folks ought to pay attention to in 2022 and beyond?

Yerxa: The rise of the role of venture philanthropy in driving the life sciences discovery engine, and it’s just the tip of the iceberg: we’re excited about furthering the mission of venture philanthropy in this way.  Opus is the RD Fund’s first company which we have conceived, led the financing, and launched ourselves. Patient donations fund the RD Fund so its majority stakeholders are patients themselves.

That ocular gene therapy is really leading the way in gene therapy—LUXTURNA® (Spark Therapeutics, Philadelphia) was the first approved gene therapy and created by Opus scientific founder Dr. Jean Bennett.  There are several advantages of ocular gene therapy vs. other gene therapy areas, including: small dose required; ability to precisely place the dose in the desired location (subretinally); high levels of immune privilege in the back of the eye; and ability to observe the safety and efficacy readily and non-invasively with various imaging techniques and functional assays.

TW: The company announced last week that it would begin its third preclinical trial—tell us more about all three. 

Opus’ first three programs are licensed from the institutions of its scientific founders—OPGx-001 and OPGx-002 from Penn, and OPGx-003 from Harvard MEEI (Mass Eye and Ear).

Opus’s lead program, OPGx-001, is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein.  This first clinical study will be a dose escalation study in a small number of patients in order to establish safety and potentially to obtain initial efficacy readouts.  Opus expects to file an IND for its OPGx-001 program in early 2022 and enter the clinic in mid-2022.

The company’s second program, OPGx-002, will focus on restoring protein expression and halting functional deterioration in patients with retinal dystrophy caused by mutations in the retinal dehydrogenase (RDH12) gene (LCA13).  We are currently working towards an IND in the next 12-18 months.

OPGx-003 is a gene augmentation therapy designed to halt functional deterioration in pediatric patients with retinal degenerative disease caused by mutations in the nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene.  Opus expects to file an IND for OPGx-003 in 2023.

We hope to announce additional programs, partnerships and hirings soon, while building out our earlier stage development and manufacturing work.  Opus is bringing together the best instruments of science—the expertise of pioneers in ocular gene therapy, patient voices, committed investors, and strong research—to create important new therapies for patients.  This will be our greatest work.