APLS 2017 Annual Report

10 should continue as planned. All mandated safety monitoring committee meetings have been held and no further safety monitoring committee meetings are scheduled. We submitted a safety report to the FDA in April 2017 regarding these events, and the FDA has not communicated any concern or requested additional information with respect to these findings. We observed a pronounced treatment effect in patients who experienced exudation in the study eye. In a post hoc analysis of the 12-month data, a subset of patients who experienced exudation in the study eye, and for whom images were available at baseline, two, six and 12 months, had pronounced reductions in the growth rate of GA lesion size as shown in the figure below. However, given the small number of patients in these groups, this observation was not statistically significant. Note: Sample size for sham-total includes all sham patients and the sample size for all other groups includes patients who had images at baseline, two, six and 12 months. We also observed a treatment effect in patients who did not experience exudation in their study eye. In a post hoc analysis, when patients who experienced exudation in the study eye were excluded from the analysis, 71 patients receiving administration of APL-2 every month showed a 28% reduction in the growth rate of GA lesion size as compared to 80 sham patients, with a p-value of 0.011, and 73 patients receiving administration of APL-2 every other month showed a 24% reduction in the growth rate of GA lesion size as compared to sham, with a p-value of 0.028. In a post hoc analysis of the 12 month data, after excluding patients with wet AMD in the fellow eye, five patients (10%) receiving monthly administration of APL-2 and two patients (4%) receiving administration every other month of APL-2 experienced exudation in the study eye. In the Phase 2 trial, a total of 93 patients (36%) had wet AMD in the fellow eye at the start of the trial, and we observed that these patients were more likely to show new onset exudation in the study eye than patients without wet AMD in the fellow eye. Wet AMD was present in 27% in the fellow eye of patients with GA in a published third-party study. Phase 1 Clinical Trial We conducted a Phase 1 open label, ascending single-dose clinical trial of APL-2 administered by intravitreal injection in patients with wet AMD who were receiving anti-VEGF therapy. We conducted the trial at multiple clinical sites both within and outside the United States to assess safety, tolerability and PK of APL-2. In this trial, patients received a single dose of APL-2 by intravitreal injection followed by 113 days of monitoring. We originally planned to enroll nine patients in the trial, in three cohorts of three patients each, at doses of 5 mg, 10 mg and 20 mg of APL-2. In August 2015, after completing enrollment of all three cohorts, we expanded the third cohort from three to 12 patients, for a total of 18 patients in this trial. In this trial, APL-2 was well tolerated, and no serious adverse events were reported. Based on the results, we determined to evaluate a dose of 15 mg in our Phase 2 trial.