RISK FACTORS 4 regulatory authorities, as we may need to conduct additional as well as conditions that did not occur or went undetected in preclinical studies or clinical trials and may experience delay in previous trials, wil l be reported by patients. Many times, side testing or obtaining marketing approvals, or may fail to obtain effects are only detectable after investigational products are marketing approvals at all. Moreover, significant preclinical study tested in large-scale, Phase I I I clinical trials or, in some cases, or clinical trial delays could shorten any periods during which after they are made available to patients on a commercial scale we may have the exclusive right to commercialize our product after approval. If additional clinical experience indicates that our candidates or allow our competitors to bring products to market product candidates cause serious or life-threatening side effects, before we do, which could impair our ability to successful ly the development of our product candidates may fail or be delayed, commercialize our product candidates and may harm our or, if the product candidate has received regulatory approval, business, financial condition, results of operations and prospects. such approval may be revoked, which would harm our business, We have not completed the evaluation of our lead product prospects, operating results and financial condition. candidate, GS010, in clinical trials, and we are currently conducting Our product candidates may lead to undesirable side effects or a Phase I/II clinical trial for our second lead product candidate, adverse reactions. In previous studies involving gene therapy GS030. treatments, some subjects experienced significant adverse side We have initiated two Phase I I I clinical trials in GS010, for which effects, including reported cases of leukemia and death seen in we expect to report data for both in 2018, and for our current other clinical trials using other vectors. While new recombinant Phase I/I I clinical trial in GS030, we expect to treat the first vectors have been developed to reduce these side effects, gene patient in the second quarter of 2018 and report data in 2019. therapy is stil l a relatively new approach to disease treatment However, neither GS010 nor GS030, nor our other product and additional adverse side effects could develop. Insertional candidates, have ever been fully evaluated in human clinical trials, oncogenesis, where the vector is inserted near a cancer causing and we may experience unexpected results in the future. We gene, or an oncogene, may cause adverse immunologic reactions or any of our future development partners wil l be required to and we cannot assure that such reactions will not occur in any demonstrate through adequate and well-controlled clinical trials of our planned or future studies. There also is the potential risk that our product candidates containing our proprietary vectors of delayed adverse events following exposure to gene therapy are safe and effective, with a favorable benefit-risk profile, for products due to persistent biologic activity of the genetic material use in their target indications before we can seek regulatory or other components of products used to carry the genetic approvals for their commercial sale. Drug development is a long, material. expensive and uncertain process, and delay or failure can occur at Possible adverse side effects that could occur with treatment any stage of development, including after commencement of any with gene therapy products include an immunologic reaction of our clinical trials. shortly after administration which, while not necessarily adverse Our product candidates and the process for administering our to the patient’s health, could substantially limit the effectiveness product candidates using AAV vectors may cause undesirable of the treatment. In previous clinical trials involving AAV vectors side effects or have other properties that could delay or prevent for gene therapy, some patients experienced the development of their regulatory approval, limit their commercial potential or a T-cell response, whereby after the vector is within the target result in significant negative consequences following any potential cell, the cellular immune response system triggers the removal of marketing approval. transduced cells by activated T-cells. If our products demonstrate a similar effect, we may decide or be required to halt or delay During the conduct of clinical trials, patients report changes in further clinical development of our product candidates. There are their health, including illnesses, injuries and discomforts, to their also risks inherent in intravitreal injections, including those used to study doctor. Often, it is not possible to determine whether the administer GS010 and GS030, such as intraocular inflammation, product candidate being studied caused these conditions. Various cataract, sterile and culture-positive endophthalmitis, retinal illnesses, injuries and discomforts have been reported from time detachment and retinal tear. to time during clinical trials of our product candidates. Regulatory authorities may draw different conclusions or require additional In addition to any potential side effects caused by our product testing to confirm these determinations. candidates, the administration process or related procedures also can cause adverse side effects. If any such adverse events occur, In addition, it is possible that as we test our product candidates our clinical trials could be suspended or terminated. in larger, longer and more extensive clinical programs, or as use of these product candidates becomes more widespread if If in the future we are unable to demonstrate that such adverse they receive regulatory approval, illnesses, injuries, discomforts events were not caused by the product candidate, the FDA, the and other adverse events that were observed in earlier trials, EMA or other regulatory authorities could deny approval or order GENSIGHT BIOLOGICS – 2017 Registration Document– 25