BUSINESS OVERVIEW 6 • Rapidly advance clinical development of our second most orphan nature of LHON, we believe a targeted sales and marketing advanced product candidate, GS030, using our optogenetics organization would be able to reach specialized ophthalmology technology for the treatment of RP. centers and their patients. We have built, and continue to expand upon, key relationships with ophthalmic experts and patients GS030 has demonstrated that it can restore light sensitivity in the of severe retinal neurodegenerative diseases around the globe, retina in animal models. In late 2017, we received MHRA approval since we anticipate that a large majority of patients suffering from to conduct a Phase I/I I clinicaltrial of GS030 in blind RP subjects. this disease will be referred to a limited number of large, well- We expect to treat the first subject in the second quarter of equipped neuro-ophthalmologists and retina specialists in each 2018. We anticipate receiving interim data within one year after country. Due to the broad patient populations that GS030 may the last subject is treated. GS030 has received orphan drug address, we may enter into strategic partnerships to maximize designation for the treatment of RP in the United States and the commercial value of our product candidate. European Union. We believe that due to its ability to introduce a gene encoding for light-sensitive protein into target cells, GS030 • Acquire or in-license complementary technologies and has the potential to be the first therapy that partial ly or ful ly product candidates. restores sight to RP patients. In addition to our current product candidates, we will evaluate • Expand our pipeline by leveraging our proprietary MTS acquisition or in-licensing opportunities with the potential to technology platform. expand and diversify our pipeline in ophthalmology and other neurodegenerative disorders. We believe that our management Mitochondrial defects are associated with several severe team’s expertise in the gene therapy field and the broad degenerative diseases of the optic nerve as well as diseases of the applicability of our proprietary technology platforms provide us central nervous systems. We believe our discovery capabilities with a competitive advantage in evaluating product opportunities. and clinical experience will allow us to pursue the preclinical and clinical development of treatments using our MTS technology platform to more broadly target degenerative diseases such as other forms of LHON or diseases of the central nervous system. 6.4 For example, while our later stage Phase I I I LHON trials are GENE THERAPY IN THE EYE: A WELL-VALIDATED designed to treat subjects with the mutation in the ND4 gene, APPROACH we plan to initiate preclinical development for GS011 using our The eye is a validated target organ for gene therapy due to its MTS technology to treat LHON due to mutation in the ND1 accessibility, small size, compartmentalization and relative immune gene. In addition, our MTS technology platform has the potential privileged status. In addition to having a validated manufacturing to address neurodegenerative diseases of the central nervous process, vectors based on adeno-associated virus, or AAV, are system caused by mitochondrial defects, such as Kearns-Sayre believed to be especially well suited for treating severe retinal syndrome, Alpers disease, Parkinson’s disease and ALS. diseases because AAV is a small, replication-deficient virus that • Pursue preclinical development of other indications using is non-pathogenic and has a well-documented safety profile. The our optogenetics technology platform. vectors can be directly injected into the diseased tissue and their The initial focus of our optogenetics technology platform using effects can be non-invasively observed for efficacy and safety. GS030 is for disorders of the photoreceptor cells, in particular RP. The blood-ocular barrier prevents the widespread dissemination However, because GS030 can address diseases of photoreceptor of locally administered vectors throughout the body. Given the degeneration regardless of the type of mutation, we believe that small volume of the eye, the amount of vector needed to achieve a GS030 may be extended to address patients suffering from dry therapeutic effect is low, reducing the amount of vector required AMD and GA, both areas of significant unmet medical need. to be administered to the patient and reducing potential systemic We plan to explore other indications outside of ophthalmology side effects or immune response. In addition, the reduced where we are able to use light to stimulate the neurons, such as volume requirement provides us with the advantage of smal l- congenital deafness, pain treatment and vagus nerve stimulation. scale manufacturing requirements for clinical trials and potential commercialization. • Directly commercialize our lead product candidate, GS010, in key geographies and retain the option to commercialize Our Gene Therapy Approach GS030 by ourselves. Building on our scientific expertise and clinical experience of our We hold worldwide commercialization rights to our platform team, we have developed two proprietary technology platforms, technologies, product candidates and development programs. MTS and optogenetics. These technologies are combined with a If approved, we intend to commercialize GS010, initially in the gene therapy based approach and have the potential to reverse United States and the European Union, ourselves. Due to the vision loss, thereby improving the quality of their lives. GENSIGHT BIOLOGICS – 2017 Registration Document– 69