BUSINESS OVERVIEW 6 a new drug or biological product designated for priority review in U.S. Patent Term Restoration and Marketing Exclusivity an effort to facilitate the review. Depending upon the timing, duration and specifics of the FDA Accelerated approval. A product may be eligible for accelerated approval of the use of our product candidates, some of the U.S. approval. Drug or biological products studied for their safety patents that we in-license may be eligible for limited patent term and effectiveness in treating serious or life-threatening illnesses extension under the Drug Price Competition and Patent Term and that provide meaningful therapeutic benefit over existing Restoration Act of 1984, commonly referred to as the Hatch- treatments may receive accelerated approval, which means Waxman Amendments. The Hatch-Waxman Amendments permit that they may be approved on the basis of adequate and wel l- a patent restoration term of up to five years as compensation controlled clinical trials establishing that the product has an effect for patent term lost during product development and the FDA on a surrogate endpoint that is reasonably likely to predict a clinical regulatory review process. However, patent term restoration benefit, or on the basis of an effect on a clinical endpoint other cannot extend the remaining term of a patent beyond a total than survival or irreversible morbidity that is likely to reasonably of 14 years from the product’s approval date. The patent term predict a clinical benefit. As a condition of approval, the FDA may restoration period is general ly one-half the time between the require that a sponsor of a drug or biological product receiving effective date of an IND and the submission date of a BLA plus accelerated approval perform adequate and wel l-control led the time between the submission date of a BLA and the approval post-marketing clinical trials. In addition, the FDA currently of that application. Only one patent applicable to an approved requires as a condition for accelerated approval pre-approval of biological product is eligible for the extension and the application promotional materials, which could adversely impact the timing of for the extension must be submitted prior to the expiration of the commercial launch of the product. the patent. The USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or Breakthrough therapy designation. To qualify for the restoration. In the future, we may apply for restoration of patent breakthrough therapy program, product candidates must be term for one of our currently owned or in-licensed patents to add intended to treat a serious or life-threatening disease or condition patent life beyond its current expiration date, depending on the and preliminary clinical evidence must indicate that such product expected length of the clinical trials and other factors involved in candidates may demonstrate substantial improvement on one or the filing of the relevant BLA. more clinically significant endpoints over existing therapies. The FDA will seek to ensure the sponsor of a breakthrough therapy A biological product can obtain pediatric market exclusivity product candidate receives intensive guidance on an efficient in the United States. Pediatric exclusivity, if granted, adds six development program, intensive involvement of senior managers months to existing exclusivity periods and patent terms. This six- and experienced staff on a proactive, col laborative and cross- month exclusivity, which runs from the end of other exclusivity disciplinary review, and rolling review. protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued Fast Track designation, breakthrough designation, priority “Written Request” for such a study. This is not a patent term review and accelerated approval do not change the standards for extension, but it effectively extends the regulatory period during approval, but may expedite the development or approval process. which the FDA cannot accept or approve a biosimilar application. Biological product manufacturers and other entities involved in The Biologics Price Competition and Innovation Act, or BPCIA, the manufacture and distribution of approved biological products created an abbreviated approval pathway for biological products are required to register their establishments with the FDA and shown to be biosimilar to, or interchangeable with, an FDA-licensed certain state agencies, and are subject to periodic unannounced reference biological product. A reference biologic is granted inspections by the FDA and certain state agencies for compliance twelve years of exclusivity from the time of first licensure of the with GMPs and other laws. Accordingly, manufacturers must reference product. Biosimilarity, which requires that there be no continue to expend time, money and effort in the area of clinically meaningful differences between the biological product production and quality control to maintain GMP compliance. and the reference product in terms of safety, purity and potency, Discovery of problems with a product after approval may result in can be shown through analytical studies, animal studies and a restrictions on a product, manufacturer, or holder of an approved clinical trial or trials. Interchangeability requires that a product BLA, including withdrawal of the product from the market. is biosimilar to the reference product and the product must In addition, changes to the manufacturing process or facility demonstrate that it can be expected to produce the same clinical generally require prior FDA approval before being implemented results as the reference product and, for products administered and other types of changes to the approved product, such as multiple times, the biologic and the reference biologic may be adding new indications and additional labeling claims, are also switched after one has been previously administered without subject to further FDA review and approval. increasing safety risks or risks of diminished efficacy relative to GENSIGHT BIOLOGICS – 2017 Registration Document– 93