BUSINESS OVERVIEW 6 6.1 OVERVIEW Overview mitochondrial protein into the matrix of the mitochondrion. We We are an innovative clinical-stage gene therapy company with believe that our MTS technology is the only existing technology an initial focus on discovering, developing and commercializing that permits missing mitochondrial proteins to be actively shuttled novel therapies for severe retinal neurodegenerative diseases. into the mitochondrion, enabling the restoration of mitochondrial We are developing a pipeline of proprietary product candidates to function necessary to effectively treat LHON. provide patients with a long-lasting cure for severe inherited retinal GS010 has received orphan drug designation for the treatment of diseases for which there are no currently approved treatments. LHON in the United States and the European Union, and is being Our current product candidates are designed to be administered in evaluated in our ongoing Phase I I I clinical trials. We reported top- a single treatment to each eye by intravitreal, or IVT, injection. We line data from our first Phase I I I clinical trial REVERSE in April 2018, are leveraging our expertise in ophthalmology, gene therapy and highlighting the favorable safety and tolerability profile of GS010, drug development to restore vision by combining a gene therapy- and showing a clinically meaningful improvement of visual acuity based approach with our proprietary technology platforms of of +11 ETDRS letters in treated eyes at 48 weeks as compared mitochondrial targeting sequence, or MTS, and optogenetics. We to baseline in all 37 patients. A similar improvement was reported believe our technology platforms have broad applicability both in untreated eyes, and caused the trial not to meet its primary within and outside of ophthalmology as well as central nervous endpoint, defined as a difference of improvement in visual acuity system, or CNS, disorders. Our lead product candidate, GS010, in GS010-treated eyes compared to sham-treated eyes at 48 is a recombinant AAV2-based gene therapy for the treatment of weeks. This bilateral improvement is currently being investigated Leber Hereditary Optic Neuropathy, or LHON, and is currently further, and we expect to communicate additional data and in Phase I I I clinical trials. We reported top-line data from our firstrelevant post-hoc analyses in the second quarter of 2018. The trial Phase I I I clinical trial REVERSE in April 2018, and expect to report also demonstrated a statistically significant relative preservation top-line results of our second Phase I I I trial RESCUE in the third of the structure of the retina in treated eyes, specifical ly the quarter of 2018. Our second most advanced product candidate, volume of the retinal ganglion cells and the thickness of the nerve GS030, for the treatment of Retinitis Pigmentosa, or RP, is currently fiber layers, while untreated eyes continued to deteriorate. We in a Phase I/I I trial. We expect to treat the first subject in this orphananticipate reporting top-line results from our second Phase I I I family of diseases in the second quarter of 2018. trial RESCUE in the third quarter of 2018. Immediately following GS010 for the Treatment of LHON the RESCUE results, if successful, we intend to meet with the FDA and apply for Fast Track Designation, which if granted, LHON is an orphan mitochondrial disease that causes the would al low us to file a BLA and seek an accelerated approval sudden and dramatic loss of vision, leading to bilateral blindness pathway, while we continue to conduct our ongoing REFLECT in less than a year, in teens and young adults and for which we trial pursuant to a special protocol assessment with the FDA. In believe there is currently no effective treatment option. LHON addition, we expect that the results of our Phase I I I REVERSE trial is estimated to have a prevalence of between one in 31,000 and and RESCUE trial, if successful, will be sufficient to support filing one in 40,000 in the United States and the European Union, for marketing authorization in the European Union. We believe respectively. LHON originates mainly from mutations in the three that the benefits of GS010 treatment may prevent further vision NADH dehydrogenase mitochondrial genes: ND1, ND4 and loss and/or restore vision, leading to increased autonomy and ND6. NADH dehydrogenase is an enzyme that acts on NADH overall quality of life for affected individuals. We have completed and is the key enzyme in cellular and mitochondrial metabolism, a Phase I/I I trial for GS010 in France in 15 subjects with long- the complex that supplies energy to cel ls that promote vision. standing vision loss from LHON with the ND4 gene mutation. ND4 and ND1 mutations account for approximately 70% and Results of this trial were published in Ophthalmology, the journal of 15% of the LHON populations, respectively. the American Academy of Ophthalmology. This trial demonstrated Our lead product candidate, GS010, is developed using our that GS010 was well tolerated, with no unexpected treatment- MTS technology platform and is designed to treat LHON by emergent adverse events, no serious adverse events related to restoring the function of NADH dehydrogenase resulting from the treatment or procedure, and no suspected unexpected serious a mutation in the ND4 gene. Our MTS technology platform adverse reactions. We believe that GS010 has the potential to be allows for efficient expression of a mitochondrial gene by active the first therapy approved by the FDA for the treatment of LHON. delivery of messenger ribonucleic acid, or mRNA, to polysomes RESCUE enrol led LHON patients with an onset of vision loss located at the mitochondrial surface. This allows for the synthesis, of less than six months in duration, while REVERSE enrol led translocation, internalization and proper localization of the missing patients with an onset of vision loss between six and 12 months. 66 – GENSIGHT BIOLOGICS – 2017 Registration Document