APLS 2017 Annual Report

6 The following table summarizes key information about our clinical program for APL-2: Indication Clinical Trials Trial Participants Estimated Timeline Ophthalmology (intravitreal) Phase 1 single ascending dose trial Patients with wet AMD Completed GA Phase 2 trial Patients with GA Completed Wet AMD Planned Phase 3 trials Planned Phase 1b/2 trial Patients with GA Patients with wet AMD Initiate 2H 2018 Initiate 2Q 2018 Hematology (systemic) Phase 1 single ascending dose trial Healthy volunteers Completed Phase 1 multiple ascending dose trial Healthy volunteers Completed Phase 1b trial Eculizumab-treated patients with PNH Additional data 2Q 2018 Phase 1b trial Treatment-naïve patients with PNH Additional data 2Q 2018 PNH Planned Phase 3 trial Patients with PNH Initiate 2H 2018 AIHA Planned Phase 2 trial Patients with AIHA Initiate 1H 2018; data 2Q 2018 Nephrology (systemic) Complement-dependent Nephropathies Planned Phase 2 trial Patients with complement- dependent nephropathies Initiate 1H 2018; data 2H 2018 Ophthalmology (intravitreal APL-2) Geographic Atrophy Background GA is a type of advanced age-related macular degeneration, or AMD. AMD is a disorder of the central portion of the retina in the eye, known as the macula, which is responsible for central vision and color perception. AMD affects vision in one or both eyes and results in progressive and chronic degeneration of the macula, often resulting in irreversible vision loss. AMD is a disease of aging, typically occurring after the age of 50. In the early stage of the disease, yellow deposits, or drusen, appear under the retina. Over time, the disease can progress to an intermediate stage where drusen deposits grow larger and other changes reflective of disease progression appear. Patients with intermediate AMD are at risk of progressing to GA or wet AMD. In contrast to intermediate AMD, these advanced forms are associated with progressive and often severe vision loss. GA is characterized by a degenerative process resulting in the progressive loss of retinal cells, which over the course of several years results in blindness. Wet AMD is characterized by the rapid abnormal growth of blood vessels beneath the retina and leakage. If left untreated, wet AMD rapidly progresses to severe vision loss. Wet AMD is typically treated with anti-VEGF therapies. Some wet AMD patients require only a few anti-VEGF injections to resolve the condition and do not require further treatment. These patients have good long- term visual outcomes. Other patients become dependent on chronic and repetitive anti-VEGF injections. In a third-party study of wet AMD patients in clinical trials of an anti-VEGF therapy, known as the SEVEN-UP study, 98% of patients dependent on chronic and repetitive anti-VEGF injections developed GA within seven years and GA affected central vision in 90% of these patients. Based on the SEVEN-UP study, we believe that patients with wet AMD who receive chronic anti-VEGF treatments may suffer from significant long-term vision loss as the result of the development of GA. According to the Brightfocus Foundation, over 10 million people in the United States have some form of AMD. Based on published studies, we believe that at least one million people in the United States have GA. The mechanism by which complement activation is upregulated and can damage the retina is poorly understood. However, we believe that the upregulation of complement activation due to immune dysregulation damages retinal cells in two ways. First, retinal cells are damaged by inflammation caused by increased levels of C3a and C5a. Second, the increased deposition of C3b on the cell surface of retinal cells caused by complement activation, combined with the limited ability of cells to remove C3 activated fragments such as C3b, leads to the accumulation of C3 fragments on the retinal cells. The presence of C3a and C5a, as well as C3 fragment deposition on retinal cells, activates macrophages and microglia. Macrophages are large white blood cells that form part of the immune system that engulf and digest cells, debris and foreign substances. Macrophages also play an important role in modulating other parts of the immune system. Microglia are a type of tissue-residing macrophage located in the brain, spinal cord and retina.