Sage Therapeutics Announces Second Quarter 2022 Financial Results and Highlights Pipeline and Business Progress Rolling NDA submission for zuranolone in MDD and PPD remains on track, with completion expected in the secon

Sage Therapeutics Announces Second Quarter 2022 Financial Results and Highlights Pipeline and Business

Rolling NDA submission for zuranolone in MDD and PPD remains on track, with completion expected in the second half of 2022

Announced positive topline data from the Phase 3 SKYLARK Study evaluating 50 mg zuranolone for PPD

Enrolling multiple Phase 2 studies across neuropsychiatry and neurology franchises, additional trials expected to initiate throughout 2022

Cash and cash equivalents, anticipated funding from ongoing collaborations, and potential revenue, expected to support operations

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

CAMBRIDGE, Mass. August 2, 2022 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 second quarter ended June 30, 2022.

The first half of 2022 has been marked by important clinical and regulatory achievements across our entire pipeline, paving the way for continued

focused execution throughout the remainder of the year, said Barry Greene, Chief Executive Officer at Sage Therapeutics. We are making progress on the NDA submission for zuranolone and building our organization to support a potential

launch. Based on the consistent clinical profile of zuranolone, we believe it has the potential, if approved, to address the significant unmet need for people suffering from MDD and PPD and we are working with a sense of urgency toward our goal of

bringing zuranolone to them. Beyond zuranolone, we are continuing to advance our pipeline, with the presentation of multiple data sets at key upcoming scientific congresses. I believe our progress this year, combined with the strong foundation

we ve built, supports our growth as a leader in brain health and a top-tier biopharmaceutical company.

Second Quarter 2022 Portfolio Updates

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 disorders.

Depression Franchise

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 U.S. Food and Drug Association (FDA) as the first treatment specifically indicated for postpartum depression (PPD). Zuranolone has received Breakthrough Therapy and Fast Track Designation for the treatment of major

depressive disorder (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 in the LANDSCAPE and NEST clinical development programs, respectively. Across seven positive clinical trials, zuranolone has demonstrated rapid

and sustained relief of depressive symptoms in people with MDD and PPD. In the second quarter of this year, Sage and its collaborator, Biogen, announced that the SKYLARK Study of zuranolone in PPD met its primary and all key secondary endpoints.

In June 2022, Sage and Biogen announced that the rolling NDA submission that was previously initiated will seek approval for both MDD and PPD in one

filing. The Companies plan to complete submission of the single NDA for zuranolone for the treatment of both MDD and PPD to the FDA in the second half of this year, accelerating previously planned timelines for PPD.

The Company also shared insights from the terminated RAINFOREST and REDWOOD Studies today. The RAINFOREST

Study was designed to investigate the efficacy and safety of 30 mg zuranolone in comorbid MDD and insomnia. The REDWOOD Study was designed to study fixed schedule intermittent dosing of 30 mg zuranolone throughout the course of a year. Both studies

were terminated in 2020 based on the Company s plans to advance the program with the 50 mg dose of zuranolone.

The RAINFOREST Study, which enrolled

87 patients, was terminated prior to achieving the planned sample size. As the study was not fully enrolled, the statistical analysis plan was invalid. The study directionality showed that zuranolone may benefit sleep efficiency, with numerical

improvement in objective measures of quality of sleep, including wake after sleep onset, total sleep time, latency to persistent sleep, median number of awakenings, and mean duration of awakenings, and differences on endpoints involving REM sleep.

The REDWOOD Study did not enroll enough patients for efficacy analyses to be performed. There were no new safety findings from the study. In the open-label SHORELINE Study, a large naturalistic study in the zuranolone development program, 80% of

patients who responded to initial treatment with zuranolone 50 mg received only 1 or 2 treatment courses during their time in the year-long study, with a median time to the second treatment course of 249 days also with no new safety findings.

Additionally, Sage today announced that the SUNBIRD Study evaluating the safe-use administration of ZULRESSO as a

treatment for PPD in a woman s home has completed enrollment. Sage does not plan any label changes from this study.

The Company expects to achieve

the following milestones across its depression franchise in 2022:

Neuropsychiatry Franchise

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 development as a potential treatment for HD.

advancing a robust clinical program for SAGE-718 with multiple ongoing or planned Phase 2 studies, including the DIMENSION and SURVEYOR Studies in people with HD cognitive impairment, the lead indication for SAGE-718, the PRECEDENT Study in people with mild cognitive impairment (MCI) associated with PD and a Phase 2 study in people with MCI and mild dementia due to AD.

The Company expects to achieve the following milestones across its neuropsychiatry franchise in 2022:

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 people 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 and frequency 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.

Sage also recently initiated a Phase 2 long-term open label safety study with SAGE-324, designed to evaluate the

long-term safety and tolerability of SAGE-324 in ET, with incidence of treatment-emergent adverse events as the primary endpoint.

SAGE-689 continues in Phase 1 development.

The Company expects to achieve the following milestones across its neurology franchise in 2022:

Sage is progressing its early

development programs with IND-enabling work underway for SAGE-319 and SAGE-421.

FINANCIAL RESULTS FOR THE SECOND QUARTER

Conference Call Information

Sage will host a conference call and webcast today, Tuesday, August 2, at 8:00 a.m. ET to discuss its second quarter 2022 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

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. www.sagerx.com.

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

statements regarding: plans and potential timing for completion of our rolling NDA submission for zuranolone in MDD and PPD; our belief in the regulatory filing pathway for zuranolone in MDD and PPD; the potential profile and benefit of zuranolone

in MDD and PPD; the potential for regulatory approval and commencement of commercialization of zuranolone; other planned next steps for the zuranolone program; anticipated timelines for commencement of trials, 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 2022 year-end cash, no receipt of milestones from collaborations in 2022, funding of future

operations and expectations for 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

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: we may experience delays or unexpected hurdles in our efforts to complete our rolling NDA

submission for zuranolone in MDD and PPD and we may not be able to complete the submission on the timeline we expect or at all; the FDA may find inadequacies and deficiencies in our NDA for zuranolone, including in the data we submit, despite prior

discussions, and may decide not to accept the NDA for filing; even if the FDA accepts the NDA for filing, the FDA may find that the data included in the NDA are not sufficient for approval and may not approve the NDA; 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; even if our NDA is successfully filed and accepted, 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 or results; 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 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 or that require additional nonclinical and clinical work which may not yield positive results; we may encounter 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; 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 and, even if successfully developed and approved, we may not achieve revenues from such products at the levels we expect; our expectations as to year-end cash and 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 our products are developed, the unmet need for additional treatment options

and the potential market for our current or future products may be significantly smaller than we expect; any of our products that may be approved in the future may not achieve market acceptance 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 our 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.

Sage Therapeutics, 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