A Phase 1, Open-Label, Multi-Center, Dose-Escalating, Safety and Tolerability Study of a Single Intravitreal Injection of AAVCAGsCD59 in Patients With Advanced Non-Exudative (Dry) Age-Related Macular Degeneration With Geographic Atrophy

Age related macular degeneration (AMD) is the leading cause of vision loss in individuals over age 60. AMD is classified as wet and dry. Wet AMD constitutes 10 to 15% of all cases of AMD and occurs when an abnormal blood vessel grows in or under the retina leading to central vision loss. Wet AMD is successfully treated with injections in the eye on a monthly basis that stop the blood vessel from growing and leaking. The most common form of AMD is the dry variant or dry AMD that affects 85 to 90% of all patients with AMD. In dry AMD, there is loss of retinal pigment, formation of deposits called drusen, and loss of the vessels in a layer of the retina called the choriocapillaris. In the most severe forms of dry AMD there is loss of retinal tissue called geographic atrophy. Over time retinal tissue degenerates in the area responsible for central vision leading to vision loss leading to legal blindness. Currently no treatment for dry AMD exists so that there is a significant unmet need in patients with this ocular disease.

Recently, evidence has implicated an overactive inflammatory cascade called the complement system as playing a pivotal role in the development of dry AMD. The complement cascade consists of 3 arms that converge to form a pore-like complex on the surface of cells called the membrane attack complex (MAC). Accumulation of MAC on cell surfaces leads to cell damage and death causing the clinical findings seen in AMD. Normal cells within the human body produce a protein on their cell surfaces called CD59 that blocks the MAC from forming. In AMD, the complement cascade is upregulated and leads to more MAC formation than the body can protect itself against leading to cell destruction.

AAVCAGsCD59, an ocular gene therapy product that is injected in to the eye in the physician's office, causes normal retinal cells to increase the expression of a soluble form of CD59 (sCD59). This soluble recombinant version of the naturally occurring CD59 is designed and intended to protect retinal cells that are responsible for central vision by inhibiting the formation of the membrane attack complex (MAC), the terminal step of complement-mediated cell lysis. In gene therapy the cells of the retina are potentially permanently altered to make sCD59 for the life of the patient. With gene therapy only one injection is needed for the drug to be effective for the patient's entire life. This study will evaluate the safety after a single injection of AAVCAGsCD59 administered in an office setting for patients whose enrolled eye has advanced dry AMD with geographic atrophy. The initial study is 26 weeks followed by an additional 18-month safety evaluation.