Sage Therapeutics, Inc. reported complete 12-month data from the 30 mg cohort and interim data from the 50 mg cohort of the ongoing Phase 3 open-label SHORELINE Study. This clinical study was designed to naturalistically follow patients with major depressive disorder (MDD) and evaluate the safety and tolerability of zuranolone 30 mg and 50 mg in adults for up to one year. For the primary endpoint of safety and tolerability, the data analyzed to date show that zuranolone was generally well-tolerated in both the 30 mg and 50 mg dose cohorts. Adverse events reported in the trial during the period analyzed were generally consistent with results seen in previous zuranolone clinical trials. Secondary endpoints included response and remission as evaluated by the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the number of times a patient received retreatment. Patients with a clinical response (decrease in HAMD-17 baseline score of =50%) to the initial 14-day course of zuranolone 30 mg required a mean of 2.2 treatments in the 12-month study. As the first naturalistic, longitudinal, clinical development trial conducted in MDD, the SHORELINE Study provides real-world insight into the potential use of zuranolone, if successfully developed and approved, as an as-needed treatment for MDD, and builds on the data assembled in the LANDSCAPE clinical program to date. The Company plans to report additional data from patients in the 50 mg dose cohort in late 2021. Additionally, the Company plans to present additional data from the SHORELINE Study at medical and scientific conferences and in peer-reviewed journal articles. Zuranolone 30 mg: Summary of Complete 12-Month Results from SHORELINE Study: The Phase 3 SHORELINE Study is evaluating the safety and tolerability of zuranolone 30 mg and 50 mg in adults 18-75 who have MDD with a baseline HAMD-17 total score =20; 725 people with MDD (HAM-D =20 and Montgomery Asberg Depression Rating Scale (MADRS) =28) were treated with a first dose of zuranolone 30 mg once nightly for 14 days; The mean baseline HAM-D score (± SD) at entry into the study was 25.3 ± 4.1 (n=725); 173 (23.9%) did not achieve response to the first course and exited the study. Subjects were required by protocol to achieve response to continue into the naturalistic follow-up period; At Day 15, the mean change from baseline was -15.2 ± 7.1 (n=687); 505 (73.5%) patients achieved response and 276 (40.2%) achieved remission (HAM-D =7); 304 (42%) patients were on pre-existing antidepressant therapy (ADT) which was continued, while 421 (58%) were on no ADT; there were no meaningful differences in efficacy outcomes between the two groups. Safety and tolerability of initial treatment: In the first course of treatment (n=725), the adverse events reported were similar in nature and frequency to those previously reported for completed zuranolone studies, with 368 (51%) patients reporting at least one adverse event; The most common treatment emergent adverse events (TEAEs) (reported =5%) were somnolence (86; 11.9%), headache (103; 14.2%), and dizziness (54; 7.4%). Most adverse events were mild or moderate; Similar adverse events were reported regardless of the presence or absence of ADT; Causes of adverse event-related discontinuations during the 14-day course of treatment were varied. The overall rate of study drug discontinuation due to TEAEs was 2.6%; No events of loss of consciousness were reported at any time during the study. Zuranolone 50 mg Dosing Cohort Initial Treatment Course: Since May 2020, all newly enrolled patients in the SHORELINE Study received zuranolone 50 mg; In the 199 patients who received zuranolone 50 mg only (n=199), the mean HAM-D baseline score was 25.1 ± 3.3; At Day 15 of the initial treatment course in this group, the mean HAM-D change from baseline was -16 ± 6.0; 149/185 (80.5%) achieved response and 80/185 (43.2%) achieved remission; In this cohort the adverse event profile was similar to that seen in patients who received 30 mg zuranolone, with 62.8% (125/199) subjects reporting at least one AE. Events >5% of somnolence, dizziness, and sedation were observed to be more frequent in the 50 mg cohort, but were similar in severity to the events seen with 30 mg. Most adverse events were mild or moderate; The 50 mg cohort completed course one and is due for completion of the full 12-month follow-up in late 2021.