About retinal disease
There are several forms of common retinal disease: Age-related macular degeneration (AMD), Geographic Atrophy (GA), Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR).
Age-related macular degeneration (AMD) is typically categorized as either dry or wet.
In the dry form of AMD (sometimes referred to as intermediate AMD), the light-sensitive cells in the macula slowly break down over time. Drusen, which are yellow deposits made of proteins and lipids, build up under the retina. This leads to gradual central vision loss over time. There are currently no approved treatments for dry/intermediate AMD.
In the wet form of AMD, abnormal blood vessels grow under the macula (choroidal neovascularization, or CNV). These vessels leak fluid or blood, damaging the macula quickly. The leads to rapid and severe vision loss if untreated. Wet AMD is typically treated with drugs that target vascular endothelial growth factor, or VEGF, which is involved in the formation of blood vessels that cause leakage.
Geographic Atrophy (GA) is the advanced form of dry age-related macular degeneration (AMD). It causes permanent loss of central vision due to the gradual death of cells in the macula, particularly retinal pigment epithelium (RPE) cells, photoreceptors (light-sensing cells) and choriocapillaris (tiny blood vessels under the retina). Geographic atrophy involves the growth of clearly defined patches or lesions in the retina and results in blurry or missing spots in central vision, difficulty seeing in low light and gradual but irreversible vision loss. Recently approved drugs (complement inhibitors) have been shown to reduce the growth of these lesions, or atrophic zones.
Unmet needs in the treatment of wet AMD and Geographic Atrophy
Wet AMD is typically treated with anti-VEGF therapies, which have been shown to preserve vision over time. However, it has been demonstrated that treatment with anti-VEGF therapy does not prevent the onset of concurrent atrophy. In fact, as many as 30-35% of patients treated with VEGF may develop atrophy after two years, and more than 40% of patients may develop atrophy after five years. (RIVAL study, Journal of Ophthalmology, 2020).
Likewise, patients treated with complement inhibitors for geographic atrophy can develop choroidal neovascularization, a symptom typically associated with wet AMD. The rate of neovascularization in patients treated with complement inhibitors may be up to 4x higher than in patients not receiving therapy.
There is no drug approved to treat both neovascularization and macular atrophy.
Diabetic retinal diseases
Diabetic retinopathy (DR) is an ocular condition caused by damage to the blood vessels in the retina due to chronic high blood sugar in people with diabetes. It’s one of the leading causes of vision loss in adults. Long-term high blood sugar can weaken and damage tiny blood vessels in the retina, causing them to leak fluid or blood. It can result in poor oxygen delivery (ischemia), as well as the formation of new, fragile blood vessels to grow which are prone to bleeding.
Diabetic macular edema (DME) is a complication of diabetic retinopathy where fluid builds up in the macula, the central part of the retina responsible for sharp, straight-ahead vision — like reading, driving, or recognizing faces. High blood sugar damages retinal blood vessels, causing them to leak fluid, lipids, and blood into the surrounding retinal tissue. The macula may swell, disrupting the clear, focused vision it normally provides. This leads to blurry or distorted central vision, and if untreated, can cause permanent vision loss.
Unmet needs in the treatment of diabetic retinal diseases
Diabetic retinopathy and diabetic macular edema are typically treated with anti-VEGF therapy. About 30–40% of DME patients show suboptimal response or little vision improvement, and many still have persistent fluid in the retina despite regular injections. Many patients with DR also do not respond adequately to these therapies, and as they act by suppressing abnormal blood vessel growth, the effect is not permanent.
About TAV-002
TAV-002 is a bispecific antibody that targets both VEGF as well as a receptor that is involved in upstream signaling. The particular pathway that this therapy targets promotes a cascade of inflammation that produces multiple cytokines that are involved in retinal disease pathology including IL-6, IL-8, IL-1b, TNFa and VEGF. We are advancing TAV-002 in pre-IND development activities.