RISK FACTORS 4 reproducible and scalable manufacturing process or transferring CBER and its advisory committee, and any new guidelines they that process to commercial partners, which may prevent us promulgate, may lengthen the regulatory review process, require from completing our clinical trials, meeting the obligations of our us to perform additional preclinical studies or clinical trials, col laborations or commercializing our products on a timely or increase our development costs, lead to changes in regulatory profitable basis, if at all. For example, we, a collaborator or another positions and interpretations, delay or prevent approval and group may uncover a previously unknown risk associated with commercialization of our current or future product candidates the adeno-associated virus, or AAV, which is the vector currently or lead to significant post-approval limitations or restrictions. used in our gene therapy approaches, and this may prolong the As we advance our product candidates, we will be required to period of observation required for obtaining regulatory approval consult with these regulatory and advisory groups and comply or may necessitate additional clinical testing. with applicable guidelines. If we fail to do so, we may be required Because human gene therapy is a relatively new and expanding to delay or discontinue development of our product candidates. area of novel therapeutic interventions, and because we are These additional processes may result in a review and approval developing product candidates for the treatment of mitochondrial process that is longer than we otherwise would have expected. and neurodegenerative diseases of the eye and central nervous Delay or failure to obtain, or unexpected costs in obtaining, the system for which there are no or limited therapies and/or regulatory approval necessary to bring a potential product to treatments, and for which there is little clinical trial experience, market could decrease our ability to generate sufficient product there is an increased risk that the FDA, EMA or other regulatory revenue, and our business, financial condition, results of authorities may not consider the endpoints of our clinical trials operations and prospects would be harmed. Even if our product to be sufficient for marketing approval. In addition, ethical, candidates are approved, we expect that the FDA wil l require social and legal concerns about gene therapy, genetic testing us to submit follow-up data regarding our clinical trial subjects and genetic research could result in additional regulations for a number of years after approval. If these fol low-up data restricting or prohibiting the processes we may use. The product show negative long-term safety or efficacy outcomes for these specifications and the clinical trial requirements of the FDA, patients, the FDA may revoke its approval or change the label of EMA and other regulatory authorities and the criteria these our products in a manner that could have an adverse impact on regulators use to determine the safety and efficacy of a product our business. candidate vary substantially according to the type, complexity, In addition, adverse developments in clinical trials of gene therapy novelty and intended use and market of such product candidate. products conducted by others may cause the FDA or other The regulatory approval process for novel product candidates oversight bodies to change the requirements for approval of our such as ours is unclear and may be lengthier and more expensive product candidates. Similarly, the EMA may issue new guidelines than the process for other, better-known or more extensively concerning the development and marketing authorization for studied product candidates. For example, clinical trial protocols gene therapy products and require that we comply with these for some gene therapies are potentially subject to review by the new guidelines. Recombinant DNA Advisory Committee, or RAC, a committee of the U.S. National Institutes of Health, or NIH, and the RAC As a result, it is difficult to determine how long it wil l take or review process can delay the initiation of a clinical trial, even if how much it will cost to obtain regulatory approvals for GS010, the FDA has approved the initiation of the trial. In addition, the GS030, or any other new product candidates in either the FDA generally requires multiple well- controlled clinical trials to United States or the European Union or how long it will take to provide the evidence of effectiveness necessary to support a commercialize our other product candidates. Approvals by the BLA, although FDA guidance provides that reliance on a single EMA may not be indicative of what the FDA may require for pivotal trial may be appropriate if the trial has demonstrated a approval and vice versa. clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potential serious outcome, The regulatory approval process of the FDA, the EMA and other and where confirmation of the result in a second trial would be regulatory authorities and the clinical trials that our product practically or ethically impossible. candidates will need to undergo, are time-consuming and expensive, the outcomes of which are unpredictable, and for which Regulatory requirements governing gene and cell therapy products there is a high risk of failure. have changed frequently and may continue to change in the future. The FDA has established the Office of Tissues and Advanced The regulatory approval process for novel product candidates Therapies within its Center for Biologics Evaluation and Research, such as ours can be more expensive and take longer than for other, or CBER, to consolidate the review of gene therapy and related better known or more extensively studied product candidates. As products, and has established the Cel lular, Tissue and Gene of the date of this Registration Document, only one gene therapy Therapies Advisory Committee to advise CBER in its review. product, Luxturna, has received marketing approval by the FDA, GENSIGHT BIOLOGICS – 2017 Registration Document– 21