Sage Therapeutics Announces Fourth Quarter and Full Year 2022 Financial Results and Highlights Pipeline and Business Progress U.S. Food and Drug Administration (FDA) accepts filing of New Drug Application (NDA) for zuran

Sage Therapeutics Announces Fourth Quarter and Full Year 2022 Financial Results and Highlights Pipeline

and Business Progress

U.S. Food and Drug Administration (FDA) accepts filing of New Drug Application (NDA) for zuranolone and grants

Priority Review in the treatment of Major Depressive Disorder (MDD) and Postpartum Depression (PPD) following submission of rolling NDA in December 2022

Robust pipeline advancing nine studies across neuropsychiatry and neurology in 2023

Year-end 2022 cash, cash equivalents and marketable securities of $1.3 billion along with

ongoing collaboration funding, and potential revenue, expected to support operations into 2025

CAMBRIDGE, Mass. Feb. 16, 2023

Sage Therapeutics, Inc. (Nasdaq: SAGE), a biopharmaceutical company leading the way to create a world with better brain health, today reported business highlights and financial results for the fourth quarter and full year ended

We set out in 2022 to deliver on a bold agenda; starting with the goal of transforming the treatment of depression.

We have been laser focused on the opportunity to help millions of people who are desperate for new treatment options and the recent acceptance of the NDA filing for zuranolone in MDD and PPD puts us one step closer to that goal, said Barry

Greene, Chief Executive Officer at Sage Therapeutics. We are also progressing a promising and targeted pipeline with the goal of being able to launch new drugs or indications for years to come. This momentum puts us in a position of strength

as we kick off 2023 and progress in our plan to become the leader in brain health and a top tier biopharmaceutical company.

Advanced Regulatory Path and Commercialization Plans for Zuranolone: In December 2022, Sage and its collaborator Biogen

announced the completion of the rolling NDA submission for zuranolone in MDD and PPD. Sage and Biogen recently announced that the FDA accepted the filing of the NDA for zuranolone and that the application was granted Priority Review, with a

Prescription Drug User Fee Act (PDUFA) action date of August 5, 2023.

Reported Positive Topline Data from Phase 3 SKYLARK Study in 2022 and Multiple Data Presentations Supporting Zuranolone Potential: Sage and its

collaborator Biogen announced positive topline data from the SKYLARK Study in 2022. The companies also presented multiple datasets from the LANDSCAPE and NEST clinical development programs that support the potential efficacy and safety of zuranolone

for the treatment of MDD and PPD, respectively.

Presented Encouraging Data from Phase 2 Open

Label LUMINARY and Open Label PARADIGM Studies of SAGE-718: SAGE-718 demonstrated improvements across multiple domains of cognition, including executive performance

and learning and memory, in patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer s disease (AD) in the Phase 2 open-label LUMINARY Study and in patients with mild cognitive impairment (MCI) due to

Parkinson s disease (PD) in the Phase 2 open-label PARADIGM Study.

Strengthened Executive Leadership Team: In 2022, the Company strengthened its leadership team with several key appointments

including Laura M. Gault, M.D., Ph.D. as Chief Medical Officer and Mark Pollack, M.D. as Senior Vice President, Medical Affairs. Sage also made key leadership hires, further building out the commercial team.

Fourth Quarter 2022 Portfolio Updates

advancing a portfolio of clinical-stage 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 disorders.

Sage s 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 FDA as the first treatment specifically indicated for PPD. Zuranolone has received Breakthrough Therapy and Fast Track Designation for the treatment of MDD and Fast Track Designation for the treatment of PPD from the FDA.

Zuranolone is being evaluated as a potential rapid-acting, once-daily, oral two-week treatment for MDD

and PPD. Across the LANDSCAPE and NEST clinical development programs to date, zuranolone has demonstrated rapid and sustained relief of depressive symptoms in people with MDD and PPD. In December 2022, Sage and its collaborator Biogen completed the

rolling NDA submission for zuranolone in MDD and PPD. The companies recently announced the NDA for zuranolone was accepted for filing by the FDA and granted priority review with a PDUFA action date of August 5th.

The Company expects the following milestones across the depression franchise in 2023:

Sage s neuropsychiatry franchise features SAGE-718, the Company s first-in-class NMDA receptor PAM and lead neuropsychiatric drug candidate, in development as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction, potentially including

Huntington s disease (HD), Parkinson s disease (PD) and Alzheimer s disease (AD). SAGE-718 received Fast Track Designation from the FDA for the potential treatment of HD.

Sage is advancing a robust clinical program for SAGE-718 with multiple ongoing or planned Phase 2 studies across

multiple disease areas, including its potential lead indication, cognitive impairment associated with HD, as well as cognitive impairment due to AD and PD. The Company recently initiated LIGHTWAVE (CNA-202), a

Phase 2 study of SAGE-718 in people with mild cognitive impairment and mild dementia due to AD and PURVIEW (CIH-301), a Phase 3 extension study in people with cognitive

impairment due to HD.

Sage is currently enrolling in the following studies:

The Company expects the following milestones across the neuropsychiatry franchise in 2023:

Sage s neurology franchise features SAGE-324 and SAGE-689. 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 essential tremor (ET), epilepsy and PD. SAGE-689 is an intramuscular GABAA receptor PAM in development as a potential therapy for

disorders associated with acute GABA hypofunction.

Sage and its collaborator, Biogen, are currently enrolling participants in the Phase 2b

KINETIC 2 placebo-controlled study of SAGE-324 in ET following positive results from the KINETIC Study. The KINETIC 2 Study is a Phase 2b dose-ranging study with the primary goal of defining the dose for SAGE-324 in ET with a good tolerability profile and a dosing schedule to maintain plasma concentrations needed for sustained tremor symptom control in treating ET. Enrollment in the KINETIC 2 Study is expected to be

completed in late 2023.

Sage is also currently dosing patients in a Phase 2 long-term open label safety study, to evaluate the long-term safety and

tolerability of SAGE-324 in ET. The primary endpoint is incidence of treatment-emergent adverse events.

SAGE-689 continues in Phase 1 development.

The Company expects the following milestones across the neurology franchise

Sage is progressing its early development programs, SAGE-319 and SAGE-421. IND-enabling work is underway for SAGE-421 and the Company plans to move SAGE-319 to Phase 1 studies.

FINANCIAL RESULTS FOR THE FOURTH QUARTER

Sage will host a conference call and webcast today, Thursday, February 16, at 8:00 a.m. ET to review its

fourth quarter and full year 2022 financial results and discuss 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 following the completion of the event and will be archived for up to 30 days.

About Sage Therapeutics

Sage Therapeutics is a biopharmaceutical company fearlessly leading the way to create a world with better brain health. Our mission is to pioneer solutions to

deliver life-changing brain health medicines, so every person can thrive. For more information, please visit http://www.sagerx.com.

Forward-Looking Statements

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

potential profile and benefit of zuranolone in MDD and PPD; the potential for regulatory approval and commencement of launch and commercialization of zuranolone and potential timing of such activities; our belief in our readiness for commercial

launch of zuranolone, if approved; other planned next steps for the zuranolone program and planned commercialization activities; anticipated timelines for commencement of trials, completion of dosing, initiation of new activities and other plans for

our other programs and early stage pipeline; our belief in the potential profile and benefit of our product candidates; potential indications for our product candidates; the potential for success of our programs, and the opportunity to help patients

in various indications; the mission and goals for our business; and our expectations with respect to potential receipt of milestones from collaborations, funding of future operations and increases in expenses. 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: the FDA may find that the data included in our NDA for

zuranolone are not sufficient for approval and may not approve the NDA in MDD or PPD, or both, or may approve zuranolone for only a subset of such patients; the FDA may decide that the design, conduct or results of our completed and ongoing clinical

trials for zuranolone, even if positive, are not sufficient for approval in MDD or PPD and may require additional trials or data which may significantly delay and put at risk our efforts to obtain approval and may not be successful; the FDA may not

meet expected review timelines for our NDA; other decisions or actions of the FDA or other regulatory agencies may affect our efforts with respect to zuranolone and our plans, progress, results and expected timelines; results of ongoing or future

studies may impact our ability to obtain approval of zuranolone or impair the potential profile of zuranolone; success in earlier clinical trials of any of our other product candidates may not be repeated or observed in ongoing or future studies,

and ongoing and future clinical trials may not meet their primary or key secondary endpoints which may substantially impair development; unexpected concerns may arise from additional data, analysis or results from any of our completed studies; we

may encounter adverse events at any stage that negatively impact further development, the potential for approval or the potential for successful commercialization of any our product candidates or that require additional nonclinical and clinical work

which may not yield positive results; we may encounter delays in initiation, conduct, completion of enrollment or completion of our ongoing and planned clinical trials, including as a result of slower than expected site initiation, slower than

expected 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; 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 or may impair the potential for successful development; the anticipated benefits of our ongoing collaborations, including the

achievement of events tied to milestone payments or the successful development or commercialization of products and generation of revenue, may never be achieved; the need to align with our collaborators may hamper or delay our development and

commercialization efforts or increase our costs; our business may be adversely affected and our costs may increase if any of our key collaborators fails to perform its obligations or terminates our collaboration; 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 efforts to gain regulatory approval of products beyond

ZULRESSO; we may not achieve revenues from zuranolone, if approved, or any other of our products that may be successfully developed, at the levels we expect; our expectations as to sufficiency of cash to fund future operations and expense levels may

prove not to be correct for these and 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; additional funding may

not be available on acceptable terms when we need it; the number of patients with the diseases or disorders for which zuranolone or any of our other products are developed, the unmet need for additional treatment options, and the potential market

for zuranolone, if approved, or any other future products, if successfully developed, may be significantly smaller than we expect; zuranolone, if approved or any of our other products that may be successfully developed in the future may not achieve

the clinical benefit, clinical use or market acceptance we expect or we may encounter reimbursement-related or other market-related issues that impact the success of our

commercialization efforts; and we may encounter technical and other unexpected hurdles in the development and manufacture of our product candidates or the commercialization of any current or

future marketed product which may delay our timing or change our plans, increase our costs or otherwise negatively impact our business; as well as those risks more fully discussed in the section entitled Risk Factors in our most recent

quarterly report, 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.

Inc. and Subsidiaries

Condensed Consolidated Statements of Operations

(in thousands, except share and per share data)

Sage Therapeutics, Inc. and Subsidiaries

Condensed Consolidated Balance Sheets

ZULRESSO (brexanolone) SELECT IMPORTANT SAFETY INFORMATION

This does not include all the information needed to use ZULRESSO safely and effectively. See full prescribing information for ZULRESSO.

WARNING: EXCESSIVE SEDATION AND SUDDEN LOSS OF CONSCIOUSNESS