Sage Therapeutics Announces Continued Positive Zuranolone Data for Both 30 mg and 50 mg Doses in Open-Label SHORELINE Study in Patients with MDD In the now completed 30 mg zuranolone cohort, approximately 70% of particip

Sage Therapeutics Announces Continued Positive Zuranolone Data for Both

30 mg and 50 mg Doses in Open-Label SHORELINE Study

in Patients with MDD

the now completed 30 mg zuranolone cohort, approximately 70% of participants with positive response to an initial 2-week treatment required at most one additional zuranolone treatment during the 12-month study

After the initial 2-week zuranolone

treatment, more than 70% of patients who received 30 mg and 80% of patients who received 50 mg achieved positive response at Day 15

In both 30 mg and 50 mg cohorts, zuranolone was generally well-tolerated with an adverse event profile consistent with data reported earlier

CAMBRIDGE, Mass. March 17, 2020 Sage Therapeutics, Inc. (Nasdaq: SAGE) today 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.

Sage embarked on the LANDSCAPE clinical program to evaluate the safety and efficacy of zuranolone with the ambition of reimagining the treatment for

depression with the goal of a rapid-acting, durable, treat-as-needed option in a disease where innovation is lacking and the incidence rate has unfortunately increased

exponentially in the last 20 years, said Barry Greene, Chief Executive Officer at Sage Therapeutics. Today we are announcing additional positive data from the SHORELINE Study that demonstrate continued strong results from the 30 mg dose

and strengthens our confidence in the potential of the 50 mg dose. Designed as a naturalistic study, these data approximate real-world evidence of use of zuranolone at 30 mg and 50 mg doses. We look forward to the results of the WATERFALL and CORAL

Phase 3 pivotal data readouts in MDD this year.

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.

Safety and tolerability of initial treatment:

489 patients were responders to

initial 30 mg treatment and continued in the study beyond the first treatment course.

Zuranolone 50 mg Dosing Cohort Initial Treatment Course:

Since May 2020, all newly enrolled patients in the SHORELINE Study received zuranolone 50 mg.

The SHORELINE Study (217-MDD-303) is a Phase 3, open-label, 1-year longitudinal study evaluating the safety, tolerability, and need for repeat dosing with zuranolone in adults with MDD. The study comprises

two cohorts, one with zuranolone 30 mg as a starting dose and one with zuranolone 50 mg as a starting dose both administered once nightly for 14 days. The need for repeated dosing is assessed

every 14 days based on the results of a patient-reported PHQ-9 ( 10) and HAMD-17

( 20) assessment. There was a minimum of 56 days between zuranolone 14-day courses, to allow for a maximum of five treatments for the

12-month study period.

About Major Depressive Disorder

Major depressive disorder (MDD) is a common but serious mood disorder in which people experience depressive symptoms that impair their social, occupational,

educational or other important functioning, such as a depressed mood or loss of interest or pleasure in daily activities, consistently for at least a two-week period. It is estimated that approximately

17 million people in the U.S. suffer from MDD each year. While antidepressants are widely used to treat MDD, large-scale studies have demonstrated the need for additional therapies.

Zuranolone (SAGE-217) is a once-daily, two-week therapy in development for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an

investigational oral neuroactive steroid (NAS) GABAA receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous

system and contributes significantly to regulating brain function.

We are jointly developing zuranolone in the U.S. with Biogen under a Collaboration and

License Agreement that became effective in December 2020, and will jointly commercialize zuranolone with Biogen in the U.S. if our development efforts are successful and it is approved in the U.S. We have granted Biogen sole rights to develop and

commercialize zuranolone outside the U.S., other than in Japan, South Korea and Taiwan where we have granted rights to Shionogi.

granted Breakthrough Therapy Designation by the U.S. Food & Drug Administration.

About Sage Therapeutics

Sage Therapeutics is a biopharmaceutical company committed to developing novel therapies with the potential to transform the lives of people with debilitating

disorders of the brain. We are pursuing new pathways with the goal of improving brain health, and our depression, neurology and neuropsychiatry franchise programs aim to change how brain disorders are thought about and treated. Our mission is to

make medicines that matter so people can get better, sooner. For more information, please visit www.sagerx.com.

Forward-Looking Statements

Various statements in this release concern Sage s future expectations, plans and prospects, including without limitation statements regarding:

our belief and confidence in the potential profile and benefit of zuranolone and in future results; the potential for successful development and approval of zuranolone; our planned timing for reporting of data from ongoing clinical trials; our

estimates as to the number of patients with MDD; and the goals, opportunity and potential for zuranolone and for our business. These statements constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform

Act of 1995. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, which could cause actual results to differ

materially from those contemplated in these forward-looking statements, including the risks that: results from interim data cuts from a clinical study may not be reflective of the results that will be achieved in the full study once completed;

success in earlier clinical trials may not be repeated or observed in ongoing or future studies, and ongoing and future non-clinical and clinical results may not meet their primary or key secondary endpoints

or be sufficient to file for or gain regulatory approval to market a product without further development work or may not support further development at all; we may encounter adverse results or adverse events at any stage of development

that negatively impact further development or that require additional nonclinical and clinical work which may not yield positive results; we may encounter different or more severe adverse events

at the higher dose of zuranolone we are studying in our ongoing trials; we may encounter issues with the efficacy or durability of short-term treatment, or co-initiated treatment with zuranolone or safety and

efficacy concerns with respect to retreatment that require additional studies be conducted; we may encounter delays in conduct of our clinical trials, including slower than expected site initiation or enrollment, that may impact our ability to meet

our expected time-lines; the FDA may ultimately decide that the design or results of our completed and planned clinical trials for zuranolone, even if positive, are not sufficient for regulatory approval in the indications that are the focus of our

development plan; other decisions or actions of the FDA or other regulatory agencies may affect the initiation, timing, design, size, progress and cost of clinical trials and our ability to proceed with further development; the actual size of the

MDD patient population may be significantly lower than our estimates and, even if zuranolone is approved, it will only be approved or used to treat a subset of the relevant patient populations; we may encounter technical and other unexpected hurdles

in the development and manufacture of zuranolone or our other product candidates which may delay our timing or change our plans; as well as those risks more fully discussed in the section entitled Risk Factors in our most recent Annual

Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. In addition, any

forward-looking statements represent our views only as of today, and should not be relied upon as representing our views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements