Sage Therapeutics Announces Second Quarter 2023 Financial Results and Highlights Pipeline and Business Progress ZURZUVAE (zuranolone) approved as first-and-only oral treatment specifically indicated for adults with postp

Sage Therapeutics Announces Second Quarter 2023 Financial Results and Highlights Pipeline and Business Progress

ZURZUVAE (zuranolone) approved as first-and-only oral treatment specifically indicated for adults with postpartum depression (PPD) and on-track for planned launch in the fourth quarter of 2023 shortly

after DEA scheduling

Sage brain health pipeline provides potential for significant long-term value creation

Remain well capitalized with $1.0 billion of cash, cash equivalents and marketable securities as of June 30, 2023

CAMBRIDGE, Mass. August 7, 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 second quarter ended June 30, 2023.

We are currently at a tipping point with the burden and prevalence of brain health conditions accelerating at an alarming rate. The need has never been

greater than it is today and our team is singularly focused on changing the trajectory of these devastating diseases through our development efforts and novel pipeline, said Barry Greene, Chief Executive Officer at Sage Therapeutics. We

were delighted to receive U.S. Food and Drug Administration (FDA) approval for ZURZUVAE as the first-and-only oral treatment specifically indicated for adults with

postpartum depression (PPD), the most common medical complication of childbirth. We believe the need for new treatment options for women with PPD is a significant medical need and presents a strong business opportunity. While we were very

disappointed by the recent Complete Response Letter (CRL) we received from the FDA regarding zuranolone in the treatment of major depressive disorder (MDD), we are reviewing the feedback from the FDA and evaluating next steps.

While we believe we are well capitalized, given the impact of the CRL for zuranolone in MDD on our plans, we are currently evaluating resource

allocation, including pipeline prioritization and a workforce reorganization with a goal of extending our cash runway. With a right-sized organization and portfolio, we believe we have an opportunity to emerge

as an even stronger company. We plan to provide greater detail and next steps before the end of the third quarter, continued Mr. Greene.

Second Quarter 2023 Portfolio Updates

advancing a portfolio of clinical-stage programs with internally discovered novel chemical entities that have the potential to address urgent unmet needs in 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

ZURZUVAE was approved by the

FDA in August 2023 as the first-and-only oral treatment specifically indicated for adults with PPD. Zuranolone is a next-generation positive allosteric modulator (PAM) of GABAA receptors being evaluated as a treatment for various affective disorders in collaboration with Biogen Inc. Sage also commercializes

ZULRESSO (brexanolone) CIV injection in the treatment of PPD.

ZURZUVAE is expected to

be commercially available for adults with PPD in the fourth quarter of 2023 shortly following scheduling by the U.S. Drug Enforcement Administration (DEA), which is expected to occur within 90 days.

Sage also announced that the FDA issued a CRL for the New Drug Application (NDA) seeking approval of zuranolone as a treatment for MDD.

In the CRL, the FDA stated that the application did not provide substantial evidence of effectiveness to

support the approval of zuranolone for the treatment of MDD and that an additional study or studies will be needed. Sage and Biogen are reviewing the feedback from the FDA and are evaluating next steps.

Today, Sage also announced additional data from the open-label SHORELINE Study in MDD, specifically from the cohort of patients (n=277) that rolled over into

the SHORELINE Study from the CORAL Study. In this cohort, the adverse event profile and the data generated on repeat treatments were similar to previously reported data from other cohorts of the SHORELINE Study, with no new safety signals

identified. Sage plans to present further analyses from the SHORELINE Study at future medical congresses.

The Company expects the following milestones in

its Depression franchise in late 2023:

Neuropsychiatry Franchise

SAGE-718, the Company 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, including Huntington s disease (HD), Parkinson s disease (PD) and Alzheimer s disease (AD). SAGE-718 has received Fast Track Designation from the FDA and Orphan Drug

Designation from the European Medicines Agency (EMA) for the potential treatment of HD.

Sage is advancing a robust clinical program for SAGE-718 and is currently enrolling in the following studies with data read-outs expected to begin in 2024:

The Company expects the following milestones in neuropsychiatry in 2023:

Sage s lead neurology drug candidates include 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 movement

disorders, such as essential tremor (ET), epilepsy and PD. SAGE-689, a Sage wholly-owned program, is an intramuscular balanced GABAA receptor PAM in

development as a potential therapy for disorders associated with GABA hypofunction.

Sage and its collaborator, Biogen, are actively 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 targeted for completion in late 2023.

Sage is also currently enrolling 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 of the open-label study is incidence of treatment-emergent adverse events.

SAGE-689 continues in Phase 1 development.

The Company expects the following milestones in neurology in 2023:

Sage continues to progress its early development programs, SAGE-319 and

SAGE-421. SAGE-319 is currently in Phase 1 studies and IND-enabling work is underway for

FINANCIAL RESULTS FOR THE SECOND QUARTER

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 completion of DEA scheduling, plans for launch, availability and commercialization of ZURZUVAE as a treatment for women

with PPD, and potential timing of such activities; our belief in the business case in PPD and our readiness for commercial launch of ZURZUVAE in this indication; our plans to review the CRL received with respect to zuranolone for the treatment of

MDD and evaluation of next steps; the potential benefit of ZURZUVAE in the treatment of women with PPD; the number of women with PPD and the potential market for ZURZUVAE for the treatment of women with PPD; our belief in the potential of ZURZUVAE

to be successful and to meet an unmet need in the treatment of women with PPD, anticipated timelines for commencement of trials, completion of enrollment, 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 potential for

value creation opportunities; the mission and goals for our business; our anticipated cash runway and plans to evaluate resource allocation and a reorganization with a goal of extending the cash runway and becoming a stronger company; and our

expectations with respect to potential receipt of milestones from collaborations, potential future revenue, funding of future operations, and a potential decrease 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: our launch and commercialization efforts in the U.S. with respect to ZURZUVAE for the

treatment of women with PPD may not be successful, and we may be unable to generate revenues at the levels or on the timing we expect or at levels or on the timing necessary to support our goals; the number of patients with the diseases or disorders

for which our products are developed and approved, the unmet need for additional treatment options, and the potential market for ZURZUVAE in women with PPD, or for any other future products, if successfully developed, may be significantly smaller

than we expect; ZURZUVAE or any other products that we may successfully develop 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; we may never achieve regulatory approval for zuranolone in MDD; the FDA has taken the position that one or more additional clinical trials of zuranolone are required to support approval in

MDD, and even if we appeal this decision in the future, the FDA may not change that position; such trial or trials could be time-consuming, significantly increase our expenses, and may not be feasible; even if we conduct such clinical trials, they

may not be successful; the FDA may decide that the design, conduct or results of our clinical trials for zuranolone, even if positive, are not sufficient for approval in MDD or may find other deficiencies in our development program, data, processes,

or manufacturing sites; even if we receive regulatory approval of zuranolone for the treatment of MDD, the FDA may approve zuranolone for only a subset of MDD patients or with limitations or restrictions; even if we run additional clinical trials to

try to obtain approval of zuranolone in MDD or with respect to clinical trials for our other product candidates, we may encounter delays in initiation, conduct, completion of enrollment or completion of any such 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 may increase our costs; success in earlier

clinical trials of zuranolone or 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; decisions or actions of the FDA 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 need to align with our collaborators may hamper or delay our development and commercialization efforts or increase our costs; the anticipated

benefits of our ongoing collaborations, including the receipt of milestone payments or the successful development or commercialization of products and generation of revenue, may never be achieved; 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; and 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 to change or curtail some of our plans or both; 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, and our plans to evaluate resource allocation with the goal of extending our cash runway may not be successful or actually extend our cash runway; 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 ZURZUVAE and ZULRESSO; we may not

achieve revenues from other of our products that may be successfully developed in the future, at levels we expect; our expectations as to cash runway, the 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; 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.

Sage Therapeutics, Inc. and Subsidiaries

Condensed Consolidated Balance Sheets

Sage Therapeutics, Inc. and Subsidiaries

Condensed Consolidated Statements of Operations

(in thousands, except share and per share data)

ZURZUVAE (zuranolone) IMPORTANT SAFETY INFORMATION