BUSINESS OVERVIEW 6 • small viral load administered, decreasing the risk of systemic The fol lowing image depicts the schematic design of GS010, immunologic response; which includes the steps listed below the image. GS010 allows • injection of small volumes, reducing the likelihood of ophthalmic an efficient expression in the cel l nucleus of a mitochondrial complications; and wild-type ND4 gene, encoding for a protein which is normal ly • small required volumes, resulting in ease of manufacturing. produced in the mitochondrion. ITR: Inverted Terminal Region; PCMV: Promoter cytomegalovirus; cDNA: complementary DNA; ND4: NADH Dehydrogenase Subunit 4. • The ND4 transgene is flanked by two oligonucleotide it integrates the complex I of the respiratory chain in order to sequences, referred as MTS1 and MTS2 in the above diagram. restore normal function. • MTS2 allows the ND4 mRNA to be addressed to polysomes Our construction of GS010, that includes the two MTSs and that are attached to the outer mitochondrial membrane, where the functional transgene, is what actively drives this into the it is translated into ND4 protein. mitochondrial matrix, and characterizes the unique nature of our • MTS1, in turn, al lows the ND4 protein to be transported MTS platform, as depicted in the following image. through the mitochondrion membrane into the matrix where Clinical Development Program for GS010 masked, sham-controlled, multi-center clinical trials in Europe We have completed a Phase I/I I clinical trial for GS010 and and the United States, of LHON subjects with the ND4 mutation our two most advanced Phase I I I clinical trials, RESCUE and with vision loss. RESCUE has enrolled 39 subjects with an onset REVERSE, are expected to report top-line results in 2018. Both of vision loss of less than six months in duration and REVERSE of these Phase I I I trials are designed as randomized, double- has enrolled 37 subjects with an onset of vision loss between six 72– GENSIGHT BIOLOGICS – 2017 Registration Document