From The Editor | November 17, 2023

The Eye: A Candidate For Modifier Gene Therapy


By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

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Ocugen, Inc. is a clinical stage biotech with a modifier gene therapy platform that has the potential to treat multiple retinal diseases with a single product. The company is also advancing research in infectious diseases to support public health and cell therapy to address unmet medical need in orthopedics. Earlier this year, I talked to Chairman, CEO and Co-founder, Shankar Musunuri ,Ph.D., MBA about preliminary data for OCU400, a therapeutic approach utilizing a modifier gene therapy platform with the potential to address significant unmet medical need for patients affected by Retinitis pigmentosa (RP) and Leber Congenital Amaurosis (LCA). Here, I caught up with Dr. Musunuri for an update on OCU400 and other trials as well as to learn more about inherited retinal disorders (IRDs), the outlook for retinal gene therapy, and more.

Historically, why have IRDs been so difficult to treat?

Inherited retinal diseases (IRDs) represent a broad spectrum of diseases, each with unique genetic characteristics, caused by a genetic mutation that can result in vision loss. IRDs such as retinitis pigmentosa (RP), a complex ocular disease that exhibits considerable genetic variability, and Leber congenital amaurosis (LCA), a form of retinal dystrophy caused by mutations in several different genes, are complex diseases with no currently available treatment options. IRDs are traditionally difficult to treat given the number of potential gene mutations. The importance of other factors, like maintaining homeostasis and healthy cell environments, indicate treatment needs to be more holistic. We are encouraged by recent research into a gene-agnostic approach that has yielded promising developments in restoring retinal integrity and function in these IRDs.

Explain the clinical trials currently underway.

OCU400 is a modifier gene therapy for the treatment of RP and LCA. OCU400 continues to demonstrate a favorable safety and tolerability profile and the most recent clinical study update suggests continued positive trends in Best-Corrected Visual Acuity (BCVA) and Multi-Luminance Mobility Testing (MLMT), as well as positive trends in Low-Luminance Visual Acuity (LLVA) among treated eyes. We believe we have strong clinical evidence to reach an agreement with the FDA to initiate our Phase 3 trial for RP in the first half of 2024. Utilizing a dual-track strategy, we also intend to expand our OCU400 Phase 3 trial in the second half of 2024 to include patients with LCA.

OCU410ST is a modifier gene therapy that utilizes an AAV delivery platform for the retinal delivery of the RORA (RAR Related Orphan Receptor A) gene for the treatment of Stargardt disease. The first patient was dosed Nov. 10, 2023. A GARDian clinical trial update is anticipated in the second half of 2024.

OCU410 is a modifier gene therapy for the treatment of dry age-related macular degeneration (dry AMD). We are working diligently to dose patients in the Phase 1/2 ArMaDa study to assess the safety and efficacy of OCU410 for geographic atrophy secondary to dry AMD. Geographic atrophy, an advanced form of dry AMD, affects approximately 1 million people in the United States alone.   

OCU500 Series is an inhaled mucosal vaccine platform intended to provide protection against severe disease, increase the duration of protection and prevent transmission of viral threats. The National Institute for Allergy & Infectious Disease (NIAID) in October selected OCU500, specifically targeted to fight COVID-19, for inclusion in a Phase 1 trial comparing the administration of OCU500 via different mucosal routes—inhalation into the lungs or up the nose via a nasal spray. OCU500 has the potential to be an inhaled vaccine for COVID-19 with durability up to one year.

NeoCart is Ocugen’s Phase 3-ready autologous regenerative cell therapy (using patients’ own cartilage cells) that received RMAT designation. The Phase 3 clinical trial is planned to start in the second half of 2024.

Explain why the eye is a good target for gene therapy?

The eye’s unique biological features, such as its accessibility and immune privilege, have rendered it an ideal candidate for modifier gene therapy. Ocugen is pioneering a gene-agnostic approach in the treatment of several eye diseases. Rather than replacing a diseased gene with a functional copy, modifier gene therapy introduces the gene for a particular nuclear hormone receptor (NHR) that is then produced in the tissue. Once it is produced, the NHR can regulate multiple gene networks. For diseases like RP and LCA that affect approximately 125,000 people, there are more than 125 associated gene mutations. Developing a single therapy to treat each mutation is not feasible. Ocugen’s gene-agnostic approach has the potential to address many different gene mutations—and in turn multiple rare retinal diseases—with a single product.

As we head into 2024, what is on the horizon for retinal gene therapy?

Heading into 2024, we are very encouraged by the FDA’s support for clinical trials in gene therapy. This approach to medicine is the future of healthcare, as it focuses on the needs and characteristics of the individual patient. We have made so much progress in this area over the past 10 years and I truly believe that we will soon see an acceleration of one-time curative therapies for blindness diseases available for the patients who desperately need them.

Explain the why behind Ocugen’s gene-agnostic approach.  

Our gene-agnostic approach offers an adaptable solution to not just IRDs, but potentially a host of other gene-mutation-related diseases. By identifying a master gene regulator common to several disorders, therapies can be devised to modulate various disease outcomes. The gene-agnostic approach targets a single master gene regulator that dictates various aspects of gene function and expression without the need to replace or edit each individual gene involved in diseases caused by multiple genetic mutations. This approach holds promise in advancing the field towards precision medicine, setting the stage for more targeted and effective treatments. Developing a gene-agnostic approach may prove more broadly applicable and could transcend the limitations of traditional gene therapies that target one gene at a time. In summary, Ocugen’s gene therapies have the potential to address the majority of unmet medical needs in the retinal space—for rare diseases and blindness diseases affecting millions.