BUSINESS OVERVIEW 6 In healthy retinas, RGCs fire electric spikes to the visual cortex onto the retina at increasing intensity. As irradiance increases, at frequencies that are proportional to light intensity, which is the electrodes are measuring the increase of the firing frequency referred to as irradiance. In this experiment, monkeys are treated of each transduced RGC. As shown in the chart above, the firing with GS030 and their retina is sampled after one month. Retina frequency of the RGCs increases almost proportionally to the are put on a multielectrode array and 590nm light is then shed light intensity, which is what one would expect in a normal eye. These photographs above show microscopic views of monkey RP retinas based on the following endpoints: histopathology of retinas after receiving treatment with GS030. (A) and (C) show the retina, outer layer thickness, number of RGCs, cell viability that GS030 achieves efficient transfection of the central part of and/or apoptosis. the retina (fovea and peri-fovea region). (B) shows a magnification of one RGC showing that the protein is in the cytoplasm and in GLP Toxicity Study to Evaluate Toxicity and Biodistribution the membrane of the cell, as confirmed in (D) with the view of the This study evaluated the toxicity, biodistribution and shedding RGCs and their axons. of viral particles as well as immunogenicity of GS030 vector and This study confirmed the initial data and supports the expression ChrimsonR protein after IVT injection in non-human primates. of ChrimsonR in the retina of monkeys. Two dose levels of GS030 were injected bilaterally. The study al lowed us to evaluate and confirm at three and six months GLP Toxicity Studies to Assess Phototoxicity the safety and local tolerability of the vector and protein, the This study assessed the phototoxicity of three levels of light biodistribution and shedding of the vector in tissues and fluids, as intensities fol lowing GS030 injection of rd1 mice, a relevant well as systemic and local ocular immunogenicity. model of RP. One dose level of GS030, which was the highest Proof-of-Concept Study Showing Restoration of Retinal Electrical dose, was combined to a single two-hour exposure to 600nm Activity in a Mouse Model of RP light at three levels of intensity in order to cover the intended use in our Phase I/I I clinical setting. The purpose of the study was to An rd1 mouse is affected by the degeneration of rods followed determine the local tolerability of light exposure on transduced by the degeneration of cones, leading to the loss of vision five GENSIGHT BIOLOGICS – 2017 Registration Document– 79