RISK FACTORS 4 and GlaxoSmithKline plc’s Strimvelis is the only gene therapy Union, for combination products such as GS030 poses unique product currently approved by the EMA, which makes it difficult challenges because they involve components that are regulated to determine how long it wil l take or how much it wil l cost to under different types of regulatory requirements, and, in the obtain regulatory approvals for our product candidates in either United States, by different FDA evaluation centers. As a result, the United States or the European Union or how long it will take such products raise regulatory, policy and review chal lenges. to commercialize our product candidates. Approvals by the EMA For example, in the European Union, GS030 has been classified may not be indicative of what the FDA may require for approval, by the EMA Committee for Advanced Therapies, or CAT, as an and vice versa. advanced therapy medicinal product, even though it consists of two components, as its primary mode of action is linked to the In addition, we believe that certain of our product candidates gene therapy component. Because the biomimetic goggles are not and certain of our underlying technology platforms may be incorporated in, or combined with, the drug product itself, they immediately transferable to the treatment of other diseases, are considered an external device. In the United States, because including dry age-related macular degeneration, or dry AMD, divisions from both the CBER and FDA’s Center for Devices and and geographic atrophy, or GA, as wel l as diseases outside of Radiological Health must review our submissions concerning ophthalmologoy, including central nervous system, or CNS, GS030, the regulatory review and approval process for GS030 may disorders. These other indications, as well as additional potential be lengthened. In addition, differences in regulatory requirements product candidates, will require additional, time-consuming and for each component of a combination product can impact the costly development efforts prior to commercial sale, which may regulatory processes for all aspects of product development and be unpredictable and may differ significantly from those of our management, including preclinical testing, clinical investigation, initial product candidates. marketing applications, manufacturing and quality control, adverse Changes in regulatory requirements, guidance from regulatory event reporting, promotion and advertising, user fees, pricing and authorities or unanticipated events during our clinical trials of reimbursement, and post-approval modifications. our product candidates could necessitate changes to clinical trial protocols or additional clinical trial requirements, which would To be successful in developing and commercializing GS030, result in increased costs to us and could delay our development we would need to address a number of scientific, technical timeline. and regulatory chal lenges. We have limited experience in the development of biologic-device combinations and may not be Changes in regulatory requirements, FDA guidance or guidance successful in developing GS030. Given our limited experience from the EMA or other European regulatory authorities, or in developing devices, we expect to rely in part on third parties unanticipated events during our clinical trials, may force us to for the design and manufacture of the biomimetic goggles. As amend clinical trial protocols. The regulatory authorities could a result, we have entered into a consortium agreement and also impose additional clinical trial requirements. Amendments to related agreements for the financing and conduct of research and our clinical trial protocols would require resubmission to the FDA, development activities with Pixium Vision S.A., or Pixium Vision, EMA, national clinical trial regulators and Institutional Review and Fondation Voir et Entendre, or FVE, a scientific foundation Boards, or IRBs, and ethics committees for review and approval, that funds scientific programs in the field of ophthalmic diseases. which may adversely impact the cost, timing or successful See Section 11.4, “Col laboration, Partnership and Related completion of a clinical trial. If we experience delays completing, Agreements” of this Registration Document. or if we terminate, any of our clinical trials, or if we are required to conduct additional clinical trials, the commercial prospects for our Success in preclinical studies or early clinical trials may not be product candidates may be harmed and our ability to generate indicative of results obtained in later trials. product revenue will be delayed. Results from preclinical studies or previous clinical trials are not The complexity of a combination product that includes a biological necessarily predictive of future clinical trial results, and interim product and a medical device presents additional, unique results of a clinical trial are not necessarily indicative of final development and regulatory challenges, which may adversely results. Our product candidates may fail to show the desired impact our development plans and our ability to obtain regulatory safety and efficacy in clinical development despite demonstrating approval of GS030. positive results in preclinical studies or having successful ly advanced through initial clinical trials. GS030 relies on the combination of two components: a gene therapy to restore light sensitivity in retinal cells, and biomimetic We have no clinical data demonstrating either the safety or goggles that stimulate the reengineered retinal cells by projecting efficacy of GS030 in humans, and we have limited clinical data light-amplified images onto the retina. Developing and obtaining demonstrating efficacy of GS010 in humans. There can be no regulatory approval, in the United States and in the European assurance that the results demonstrated in the Phase I/I I clinical 22 – GENSIGHT BIOLOGICS – 2017 Registration Document