Table of Contents
Dr. Shankar Musunuri, Chairman, CEO, and Co-founder of Ocugen, sat down with Onyx for a feature length interview.
What makes Ocugen’s approach to gene therapies so different?
Traditional gene therapies and gene editing focus on replacing or repairing a single defective gene, and they often overlook the broader genetic network. In retinitis pigmentosa (RP) alone, more than 150 genes have been linked to the disease. With traditional approaches, you would need over 150 different products to address the entire patient population. Instead, we use modifier genes—master gene regulators—that target the network, not just the defective gene.
For instance, OCU400 is our modifier gene therapy that uses NR2E3, which boosts the functioning of other genes and helps stabilize photoreceptors in the retina to restore homeostasis. This is crucial because vision loss in diseases like RP is often due to the loss of these photoreceptors. Our modifier gene therapy approach is also gene-agnostic. In the Phase 1/2 clinical trial of OCU400, most patients (78%) with mutations in RHO—an entirely different gene than NR2E3—experienced stabilization or improvement in treated eyes, which supports the gene-agnostic mechanism of action.
Currently, there is only one therapy on the market to treat one mutation associated with RP—leaving approximately 98% of patients untreated. Given the roughly 310,000 RP patients in the United States, Canada, and Europe, this provides a sizable market for a rare disease.
How do you see the future of gene therapies, especially when it comes to access and affordability?
The cost of gene therapies can reach millions of dollars per patient. This pricing limits access, particularly outside developed regions like the U.S. and EU. Our goal is to work with government agencies and payers to affect a paradigm shift in the reimbursement model and arrive at cost-effective treatments that can be accessible globally.
One way to drive affordability is to create regional centers of excellence for gene therapy manufacturing. By building manufacturing capacity globally, we can lower costs and ensure these therapies reach more patients, faster.
What’s in Ocugen's pipeline?
Our primary focus is to be a leader in ophthalmology gene therapy by developing first-in-class treatment approaches for blindness due to RP, geographic atrophy (GA), and Stargardt disease. Our modifier gene therapy platform shows great promise in stabilizing and improving vision across inherited retinal diseases, as well as multi-factorial diseases that affect millions.
We’re in the Phase 3 clinical trial for OCU400 with sites in the U.S. and Canada, where we’re actively recruiting patients. The trial has a sample size of 150 participants: One arm has 75 participants with RHO gene mutations, and the other arm has 75 participants with mutations in any of several other genes associated with RP. The Luminance Dependent Navigation Assessment (LDNA) is the primary endpoint for the study. In this assessment, a participant navigates an obstacle course that constitutes a more sensitive and specific measurement of visual function than the mobility test used in previous Phase 3 clinical trials.
Our Phase 3 liMeliGhT trial will focus on the proportion of responders, in treated and untreated groups, who achieve an improvement of at least 2 Lux (light) levels from baseline in the study eyes. More than 60% of the intent-to-treat patients from the Phase 1/2 clinical trial, including patients with the RHO mutation, meet the responder criteria established for Phase 3. The Phase 3 mobility test responder rate for the only FDA-approved product to treat one mutation in RP was 52%. Assuming only a 50% responder rate, our Phase 3 trial is powered greater than 95%. OCU400 remains on track for the 2026 BLA and MAA approval targets.
Our second big focus is GA, a severe form of dry age-related macular degeneration (dAMD) that affects millions of people. GA is caused by a variety of dysfunctional biological pathways, but current treatments address only the complement system, require multiple injections per year, are accompanied by various safety concerns, and only slow disease progression by about 30% over two years. Ocugen’s approach targets all the key pathophysiological pathways implicated in dAMD—oxidative stress, lipid metabolism, and inflammation, as well as the complement system—using another modifier gene called RORA.
The Phase 1 trials went extremely well from a safety perspective, and we’re already in Phase 2 trials for GA. Our goal is to offer a one-time gene therapy that not only slows the progression of GA but could potentially stabilize it altogether with good safety. It would be a game-changer for patients.
OCU410ST, also utilizing the RORA gene, has received an Orphan Drug Designation from the FDA for the treatment of Stargardt disease, which has no approved treatment and affects approximately 100,000 people in the U.S. and Europe combined. OCU410ST has the potential to be the first one-time gene therapy for Stargardt disease.
We licensed our modifier gene therapy platform from Dr. Neena Haider’s lab at Harvard Medical School. Her research spans 20 years and offers groundbreaking, distinct approaches to gene therapy.
Our goal with all our therapies is to do more than just treat symptoms. We focus on addressing the underlying causes of disease, and our gene therapies have the potential to significantly alter disease progression.
What has your career journey looked like, and how did you come to lead Ocugen?
Well, I started in biotech, and it was a surprise to me to end up in big pharma. That opportunity provided me with a broad range of experiences, from R&D to operations and business roles. I eventually found my passion for entrepreneurship, wanting to be closer to decisions that affect patients directly. I realized how much more I could do for global health, particularly in developing countries. I wanted to be part of that change.
That’s how I started Ocugen in 2013 with my co-founder, Dr. Uday Kompella, who invented OCU200—now entering Phase 1. Our mission today is to bring game-changing gene and cell therapies and vaccines to market and working even harder to provide access to patients globally.
