BUSINESS OVERVIEW 6 No Existing Therapies for the Treatment of RP • IVT administration, a straightforward and common approach No treatments for RP have been approved in the United States well-accepted by ophthalmologists, in contrast to subretinal or the European Union. Other gene therapy approaches under injections; development to treat vision loss due to RP are focused on specific • small viral load administered, decreasing the risk of systemic mutations and these therapies, if approved, would be limited immunologic response; to specific patient subpopulations. Another alternative to treat • injection of small volumes, reducing the likelihood of ophthalmic vision loss from RP involves medical devices in the form of retinal complications; and implants, certain of which products have received marketing • small required volumes, resulting in ease of manufacturing. approval in Europe and the United States. Retinal implants have proven to restore some visual perception in patients and are Our primary optogenetics strategy consists of introducing intended for patients with advanced RP who have lost their ChrimsonR, a light-sensitive protein belonging to the channel photoreceptors. Therefore, treatment of RP is considered a rhodopsin family into normal ly light insensitive cel ls present significant unmet medical need. in the inner retinal layer, particularly RGCs, via a gene therapy Market Opportunity in RP product injected into the vitreous of an affected eye. Upon light stimulation, the ChrimsonR protein is activated leading to an RP is the leading cause of hereditary blindness in developed electrical response of the cel l, which in turn carries electrical countries, with a prevalenceof about 1.5 mil lion people signals encoding visual information through the optic nerve into throughout the world. In Europe and the United States, about the visual cortex of the brain. This process mimics the natural 265,000 to 350,000 patients suffer from RP, and every year an function of the retina without the need for the initial step of estimated 10,000 to 15,000 patients with RP lose their sight. the transduction cascade, which normal ly occurs in the outer Some studies of prevalence rates of RP may underestimate segments of the cone. By stimulating RGCs, partial restoration of the number of severely visual ly impaired patients with RP retina performance allowing daily life tasks is expected. because they are based on patients with active follow-up care in ophthalmology clinics. We believe that many patients stop seeing The figure below illustrates our optogenetics strategy aimed at ophthalmologists within a few years after reaching blindness restoring vision in retinal degenerative diseases, which includes because of a perceived lack of treatment and difficulty in traveling the following steps: to medical centers. • The photoswitch gene (gene encoding for ChrimsonR protein) Our Solution: GS030 for the Treatment of Photoreceptor is packaged into an AAV2 7 m8 vector. Degeneration • The AAV2 7 m8 carries the transgene into RGCs, resulting in synthesis of ChrimsonR protein within the membrane of the GS030 is developed through our optogenetics platform and is RGCs. designed to confer light sensitivity to normally light insensitive retinal neurons, specifical ly RGCs, in order to restore vision. • When appropriate light (590 nm wavelength) is shed onto the While there is significant loss of photoreceptor cel ls in these RGCs expressing ChrimsonR, it results in a depolarization of diseases, RGCs are preserved. the cells, creating an action potential which is then transmitted to the visual cortex by the optic nerve. Our novel, proprietary optogenetics platform technology has • The visual cortex will then assemble the signals to form a useful enabled us to develop GS030 with potential advantages over image. other therapies currently in development, including: • potential to address any photoreceptor degenerative disease independent of genotype; GENSIGHT BIOLOGICS – 2017 Registration Document– 77