Sage Therapeutics Announces Fourth Quarter and Full Year 2020 Financial Results and Highlights Pipeline and Business Progress Reported positive interim data from Phase 3 open-label SHORELINE Study showing that more than

Sage Therapeutics Announces Fourth Quarter and Full Year 2020 Financial Results and

Highlights Pipeline and Business Progress

Reported positive interim data from Phase 3 open-label SHORELINE Study showing that more than 70% of patients successfully treated with

zuranolone 30 mg needed two or fewer treatment courses over one year

Progressed WATERFALL Study now closed to enrollment -

investigating zuranolone for as needed treatment of major depressive disorder with data anticipated in the first half of 2021

Entered into global collaboration with Biogen worth up to $3.1 billion, enabling planned expansion and acceleration of the Sage

pipeline and increasing the potential patient reach to more than 450 million, if successful

Initiated six late-stage clinical

trials in 2020, including four Phase 3 trials

Ended 2020 with cash balance of $2.1 billion

Conference call today at 8:00 a.m. ET

CAMBRIDGE, Mass. Feb. 24, 2021 Today, Sage Therapeutics, Inc. (NASDAQ: SAGE), a biopharmaceutical company committed to developing novel

therapies with the potential to transform the lives of people with debilitating disorders of the brain, reported business highlights and financial results for the fourth quarter and full year ended December 31, 2020.

Although 2020 was a challenging year, Sage s commitment to rigorous science, innovation and disciplined execution resulted in significant progress

across all of our brain health franchises, strongly positioning us in our efforts to deliver revolutionary medicines to millions of patients, said Barry Greene, chief executive officer at Sage Therapeutics. Our collaboration with Biogen

enhances our strategic, financial, and operational flexibility, enabling our plans to expand and accelerate our pipeline and extending the potential impact of our product candidates, if we re successful, to more than 450 million patients

worldwide. In the first months of 2021, we ve already begun to realize this expansion and acceleration with the progression of multiple early-stage programs. I believe 2021, with 10 expected data readouts, will be a transformational year for

Sage in our mission to become the leading brain health company in the next five years.

Collaboration with Biogen: In November 2020, Sage and Biogen entered into a global collaboration and license agreement to jointly develop and

commercialize zuranolone (SAGE-217) for major depressive disorder (MDD), postpartum depression (PPD) and other disorders, and SAGE-324 for essential tremor (ET) and

Zuranolone SHORELINE Study data: In October 2020, Sage reported positive, interim topline results from

a July data cut of the ongoing Phase 3 open-label SHORELINE Study of zuranolone in MDD. The SHORELINE Study is designed to evaluate the safety and tolerability of zuranolone in adults for up to one year.

Interim topline data from the SHORELINE Study showed:

Corporate restructuring: In April 2020, Sage completed a restructuring intended to enable the Company to advance its corporate strategy and pipeline

throughout the COVID-19 pandemic and beyond.

Sage is advancing a portfolio of clinical programs featuring internally discovered novel chemical entities with the potential to become differentiated products

designed to improve brain health by targeting the GABAA and NMDA receptor systems. Dysfunction in these systems is thought to be at the core of numerous neurological and neuropsychiatric

Depression Franchise

depression franchise features zuranolone, Sage s next-generation positive allosteric modulator (PAM) of GABAA receptors being evaluated in clinical development as a treatment for

various affective disorders, and ZULRESSO (brexanolone) CIV injection, approved by the U.S. Food and Drug Administration (FDA) as the first treatment specifically indicated for

PPD. Zuranolone has received breakthrough therapy designation from the FDA for the treatment of MDD.

Zuranolone is being evaluating as a potential

rapid-acting, short-course treatment for PPD and MDD in the NEST and LANDSCAPE clinical trial programs. Sage initiated three Phase 3 clinical studies in 2020. If successful, these studies, along with the rest of the program, may support paths to

approval with three distinct opportunities to address patient needs: PPD, acute rapid response therapy (RRT) in MDD when co-initiated with a new standard antidepressant, and

as-needed treatment of MDD.

The Company expects the following zuranolone data readouts in 2021:

Sage is also evaluating the ongoing zuranolone clinical pharmacology and safety program and plans to align with FDA on data to support a potential future new

drug application (NDA) with the FDA. Additional development plans for zuranolone will be confirmed and announced as part of the Company s strategic collaboration with Biogen.

Additionally, Sage s collaboration with Shionogi & Co., Ltd. is progressing. In 2020, Shionogi initiated a Phase 2 trial with zuranolone

in Japan for the treatment of MDD. Shionogi anticipates that this Phase 2 study will finish in the third quarter of 2021. Under the terms of the collaboration, Shionogi is responsible for all clinical development, regulatory filings and

commercialization of zuranolone for MDD, and potentially other indications, in Japan, Taiwan and South Korea.

SAGE-324, a next-generation PAM of

GABAA receptors and Sage s lead neurology program, is in development as a potential oral therapy for neurological conditions, such as ET, epilepsy and Parkinson s disease (PD).

The following milestones are expected for the neurology franchise in 2021:

Additional development plans for SAGE-324 will be confirmed and announced as part of the Company s strategic

collaboration with Biogen.

Neuropsychiatry Franchise

SAGE-718, Sage s first-in-class

NMDA receptor PAM and lead neuropsychiatric drug candidate, is in development as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction, potentially including Huntington s disease (HD), PD and

Alzheimer s disease (AD).

Positive data with SAGE-718 to date include results from a Phase 1 open-label

study evaluating the safety and pharmacokinetics of SAGE-718 in a cohort of patients with early HD. In that study, SAGE-718 was well tolerated with no serious adverse

events or adverse events leading to treatment discontinuation and patients demonstrated improved performance, compared to baseline, on assessments of executive functioning, a core feature of early HD.

Ongoing trials with SAGE-718:

milestones are expected for the neuropsychiatry franchise in 2021:

Additionally, the Company expects to

initiate a placebo-controlled Phase 2 trial with SAGE-718 in late 2021. Details of this trial will be informed by results from the Phase 2a studies and earlier work.

Sage expects to complete certain Phase

1 clinical studies for two programs in its early development pipeline in 2021, SAGE-689 (single ascending dose) and SAGE-904 (single ascending dose and multiple

Results from the Phase 1 studies

will inform further development of these programs.

Additionally, the Company recently announced plans to advance

SAGE-319 and SAGE-421 to preclinical studies.

Other Development Opportunities

Sage initiated a Phase 3 trial with brexanolone in patients with advanced COVID-19 related acute respiratory

distress syndrome (ARDS) in the fourth quarter of 2020 under the Coronavirus Treatment Acceleration Program (CTAP). The Company expects topline data from this trial in 2021.

ANTICIPATED 2021 MILESTONES

FINANCIAL RESULTS FOR THE FOURTH QUARTER AND FULL YEAR 2020

Conference Call Information

will host a conference call and webcast today, Wednesday, February 24, at 8:00 am ET to discuss its fourth quarter and full year 2020 financial results and recent corporate updates. The live webcast can be accessed on the

investor page of Sage s website at investor.sagerx.com. A replay of the webcast will be available on Sage s website approximately two hours after the completion of the event and will be archived for up to 30 days.

About Sage Therapeutics

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: our views and expectations

regarding our planned research and development activities and related timelines, including plans for reporting data, initiation of new activities, and acceleration and expansion of our pipeline; our belief in the potential profile and benefit of our

product candidates, and the opportunity to help patients, in various indications; the potential benefit and success of our collaborations; our goal to deliver medicines that we hope will help patients and the number of patients we hope our medicines

will help; our mission to become the leading brain health company; our statements regarding the vision, opportunity and potential for our business; and our expectations with respect to 2021 year-end cash.

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: success in non-clinical studies or in earlier clinical trials or at interim time periods 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 the product without further development work or may not support further development at all; we may

encounter 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 doses 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; the impact of the COVID-19 pandemic on our clinical development timelines may be more significant than we expect and may

negatively impact expected site initiation, enrollment or conduct in our clinical trials, or cause us to pause trials or not be able to use data, in each case which may significantly impact our ability to meet our expected timelines or may

significantly impact the integrity or sufficiency of the data from our

trials or increase our costs or cause us to have to change our plans; we may encounter other delays in initiation, conduct or completion of our ongoing and planned clinical trials, including as a

result of slower than expected site initiation or enrollment, the need or decision to expand the trials or other changes, that may impact our ability to meet our expected timelines and increase our costs; the FDA may ultimately decide that the

design or results of our completed and planned clinical trials for any of our product candidates, 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 anticipated benefits of our ongoing collaborations may never be

achieved; the internal and external costs required for our ongoing and planned activities, and the resulting impact on expense and use of cash, may be higher than expected which may cause us to use cash more quickly than we expect or change or

curtail some of our plans or both; we may never be able to generate meaningful revenues from sales of ZULRESSO or to generate revenues at levels we expect or at levels necessary to justify our investment; we may not be successful in our development

of any of our product candidates in any indication we are currently pursuing or may in the future pursue; our expectations as to year-end cash may prove not to be correct for other reasons such as changes in

plans or actual events being different than our assumptions; we may be opportunistic in our future financing plans even if available cash is sufficient; the number of patients with the diseases or disorders for which our products are developed or

the unmet need for additional treatment options may be significantly smaller than we expect; and we may encounter technical and other unexpected hurdles in the development and manufacture of our product candidates which may delay our timing or

change our plans or increase our costs; 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