OCU200 is a novel fusion protein consisting of two naturally occurring molecules that are present normally in retinal tissues. Tumstatin is the active component of OCU200 and plays a pivotal role in regulating ocular neovascularization through the inhibition of several key signaling pathways, including VEGF and inhibits endothelial cell proliferation and migration. In addition, it also plays an important role in reducing oxidative stress and inflammation through downregulation of COX-2. Importantly, tumstatin selectively targets the actively dividing epithelial cells of expanding blood vessels, leaving healthly existing vasculature unharmed. Transferrin is a protein involved in regulating free iron levels in biological fluid which binds to a receptor that is highly expressed in the retina, particularly by deeper retinal pigment epithelial cells and in the sub-retinal choroidal layer, where wet-AMD first occurs before spreading inward. Transferrin enables transcytosis, targeting of tumstatin to the disease site, and enhances the pharmacodynamic effects of OCU200 in the area primarily impacted by neovascular diseases.
In preclinical studies, OCU200 demonstrated superior efficacy compared to anti-VEGF therapies in reducing choroid neovascularization (CNV) lesion areas in laser-induced rats and mice CNV models. These encouraging results highlight the potential for OCU200 to deliver true disease modification for wet-AMD and other high-need ocular neovascular diseases, such as diabetic macular edema (DME) and diabetic retinopathy (DR).
Ocugen is continuing to advance OCU200 in late-preclinical studies and expects to commence human clinical trials as a treatment for wet-AMD in the next one to two years.
About 10-15% of patients with age-related macular degeneration (AMD) progress to the advanced “wet” form, which is characterized by penetration of abnormal blood vessels in the retina that leak blood and proteins. The result can be irreversible damage to photoreceptor cells and rapid, severe vision loss, particularly in the center of the field of vision, causing significant functional impairment. Wet-AMD accounts for 90% of all AMD-related blindness.
Market-leading drugs used to treat wet-AMD include anti-VEGF injections Eylea® and Lucentis®, however, about 75% of patients on anti-VEGF therapy fail to achieve significant improvement in vision after two years of treatment, with about 25% of patients continuing to lose vision. Only approximately 50% of patients achieve driving vision of 20/40 or better. These treatments are also associated with rebound neovascularization, macular atrophy, and in some cases, severe adverse reactions. There remains significant need for new therapies that are rapidly effective in a larger patient population and can have a significant and lasting impact on the progression of wet-AMD.
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