2 We are currently enrolling a Phase 1b open-label multiple-dose study of KSI-301 at multiple clinical trial sites in the United States. The Phase 1b is in treatment naïve patients with neovascular (wet) age-related macular degeneration (approximately 20 patients), DME (approximately 20 patients), and macular edema due to retinal vein occlusion (approximately 10 patients). The trial is designed such that all patients receive three loading doses once a month, and then are followed monthly, with further KSI-301 treatment determined by disease-specific retreatment criteria. All patients are planned to be evaluated through 36-weeks. Given the results of the Phase 1a study, we intend to evaluate this study for bioactivity and durability signals and look for this study to continue to build our knowledge of KSI-301 as an important new therapeutic candidate. We plan to present on-going Phase 1b data at key medical and investor conferences in 2019 and 2020. The Phase 1a data in DME patients supports our plan to study the potential durability advantage of KSI-301 over other anti-VEGF biologics in wet AMD, because AMD is a more localized retinal disease with typically lower levels of VEGF compared to DME. For this reason, we have enhanced our wet AMD pivotal Phase 2 study design to include evaluation of our top dose of 5mg at 20-week along with 16-week and 12-week dosing intervals in comparison to EYLEA on its 8-week labeled regimen. We believe that, if successful, a regimen which provides nearly all patients with a 12-week or better treatment interval would be unique and a potentially differentiating characteristic. We anticipate that this study will begin enrollment in the second quarter of 2019. Furthermore, the bioactivity and durability profile of the treatment responses seen so far, as well as the observed safety profile, support the evaluation of KSI-301 in earlier forms of diabetic eye disease such as non-proliferative diabetic retinopathy, or NPDR. We believe that identifying and treating the right NPDR patients (those at higher risk of vision- threatening complications) with an infrequent dose regimen before vision loss occurs could have a tremendous public health impact. We expect to be dosing patients in our global Phase 2 study of KSI-301 in the United States in the second quarter of 2019. This randomized, controlled study in approximately 400 treatment naïve wet AMD patients will evaluate the non- inferiority of intravitreal KSI-301 administered as infrequently as every 20 weeks versus EYLEA (aflibercept) administered on its every 8-week labeled regimen. We additionally plan to initiate two Phase 2 studies in China, one in wet AMD and one in DME, and we are planning for these studies to have the same clinical design frameworks as our U.S. and European Union studies. We have submitted a pre-IND package to China’s Center for Drug Evaluation, or CDE, and hope to submit an IND, or Investigational New Drug application, in China later this year with an objective to begin enrollment in 2019. We continue to evaluate the timing and design of the planned global Phase 2 study in DME patients and also our clinical strategy in NPDR patients. At this time, we plan to initiate the global Phase 2 study in DME in the second half of 2019, but we may elect to shift out this study start depending on the tempo of our China Phase 2 study starts as well as our evolving NPDR strategy. As reported earlier and following from potential learnings in our Phase 1b study, in the future, we may also pursue other target indications for KSI-301 such as macular edema due to retinal vein occlusion, choroidal neovascularization due to pathologic myopia, or other diseases for which existing anti-VEGF therapies have been approved or may be beneficial. Target Indications Our initial target indications for KSI-301 are wet AMD and diabetic eye disease. Wet AMD is a chronic and progressive disease of the central portion of the retina, known as the macula, which is responsible for sharp central vision and color perception. It is caused by abnormal blood vessels that grow underneath the retina and leak blood and fluid into the macula, causing visual distortion and acute vision loss, which can be permanent. Wet AMD is the leading cause of severe vision loss in adults over the age of 50 in the United States and the European Union, or EU. We estimate the combined prevalence of wet AMD in the United States and the EU to be approximately 2.9 million people. Diabetic eye disease results from diabetes, in which chronically elevated blood sugar levels and other metabolic abnormalities cause progressive damage to blood vessels in the retina. Diabetic eye disease is the leading cause of blindness in working age adults in the United States and the EU. We estimate that the number of people in the United States and the EU with diabetic eye disease in 2015 was approximately 28.5 million.