From The Editor | April 27, 2023

Ocugen's Modifier Gene Therapy Technology


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


Ocugen is the Malvern, PA-based biotech focused on discovering, developing, and commercializing novel gene and cell therapies, biologics, and vaccines. The company has achieved positive, 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). I talked to Shankar Musunuri, Chairman of the Board, CEO & Co-founder of Ocugen to learn about next steps in the program.

 Briefly explain Ocugen and its mission.

We are dedicated to our mission to develop cutting-edge innovations for people facing serious disease and conditions with a commitment to ensuring global market access. Our modifier gene therapy platform has the potential to treat multiple retinal diseases with a single product, we are advancing vaccine research with next generation inhalation vaccines for flu and COVID-19, and our work in regenerative cell therapy is aimed at orthopedic disease for which no effective treatment options currently exist.

Explain both Retinitis pigmentosa (RP) and Leber Congenital Amaurosis (LCA) and how Ocugen is working to combat these diseases.

Retinitis pigmentosa (RP) is a group of genetic rare eye diseases that people are born with and affect the retina (the light-sensitive layer of tissue in the back of the eye). RP makes cells in the retina break down slowly over time, causing vision loss. Symptoms usually start in childhood, and most people eventually lose most of their sight. Leber congenital amaurosis (LCA) is a group of inherited retinal diseases characterized by severe impairment vision or blindness at birth. LCA is caused by degeneration and/or dysfunction of photoreceptors, the cells in the retina that make vision possible. Despite its prevalence, RP and LCA patients have limited treatment options:

  • U.S.: RP & LCA affect 110,000 and 15,000 people, respectively
  • Worldwide: conditions affect approximately 1.6M people
  • Current approved and in-development gene therapies focus on individual gene:
  • More than 125 mutated genes associated with RP and LCA
  • Developing a single therapy to treat each mutation is not feasible      
  • Modifier gene therapy is designed to fulfill unmet medical needs related to rare retinal diseases, including IRDs, such as RP, LCA, and Stargardt disease; as well as dry AMD that affects hundreds of millions globally. Our modifier gene therapy platform is based on the use of NHRs, master gene regulators, which have the potential to restore homeostasis — the basic biological processes in the retina. Unlike single-gene replacement therapies, which only target one genetic mutation, we believe that our modifier gene therapy platform, through its use of NHRs, represents a novel approach that has the potential to address multiple retinal diseases caused by mutations in multiple genes with one product, and to address complex diseases that are potentially caused by imbalances in multiple gene networks.

To date, what has been uncovered to date via OCU400 data, and what are the next steps in the trial?

Preliminary data on the Phase 1/2 multicenter, open-label, dose ranging study evaluating OCU400 investigational product demonstrated favorable safety and tolerability among patients with RP associated with NR2E3 and Rhodopsin (RHO) mutations and LCA with mutation(s) in the CEP290 gene. Ocugen is the first company to take the modifier approach into clinical trials globally. The positive proof-of-concept data from this study validates our modifier gene approach.

  • Initial clinical data from low and medium dose cohorts indicated a positive trend in Multi-luminance mobility testing and Best-Corrected Visual Acuity scores for OCU400 treated eyes.
  • 100% of treated eyes (pooled analysis, 6/9 months) showed stability or improved MLMT scores
  • 71.4% of treated eyes improved by at least 1 Lux Level in pooled analyses vs ONLY 28.6% of untreated eyes
  • 66.7 % treated eyes (9 months) improved by at least 2 Lux Level in cohort 1 subjects with 9 months follow up vs 0 % of untreated eyes
  • Ocugen will continue to monitor long-term safety and efficacy data from the treated patients, and advance development of OCU400 to bring a potential treatment option to RP and LCA patients

What is the company’s plan for continued innovation throughout 2023?

Currently Ocugen has three modifier gene therapy programs:

  • OCU400 (RP, LCA) is currently in Phase 1/2 trials. We continue to enroll patients with LCA and intend to initiate a Phase 3 trial near the end of 2023.
  • OCU410 (dry AMD) is in IND-enabling studies for the treatment of Dry Age-Related Macular Degeneration (Dry AMD) and we plan to file an IND to initiate the Phase 1/2 trial in Q2.
  • OCU410ST (Stargardt disease) just received broad orphan drug designation from the FDA for the treatment of ABCA4-associated retinopathies including Stargardt, RP19 and CRD3. We also plan to file an IND to initiate the Phase 1/2 trial of OCU410ST in Q2.
  • NeoCart® is a regenerative cell therapy technology that combines bioengineering and cell processing to enhance autologous cartilage repair. It has the potential to accelerate healing and reduce pain through reconstructing damaged knee cartilage. A Phase 3 clinical trial is planned for 1H 2024.
  • Ocugen is developing a novel mucosal vaccine platform—the OCU500 Series—which includes OCU500, a bivalent COVID-19 inhaled vaccine; OCU510, a seasonal quadrivalent flu inhaled vaccine; and OCU520 a combination quadrivalent seasonal flu and bivalent COVID-19 inhaled vaccine. An IND is planned for 4Q 2023.
  • These OCU400 data are particularly exciting as it’s the first modifier gene therapy technology to enter the clinic in the inherited eye disease space.