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File Number)

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215 First Street

Cambridge, MA

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Exhibits

Exhibit
No.

Description

ZULRESSO: Launch in the U.S. is on track for late June 2019 following scheduling by the U.S. Drug Enforcement Administration (DEA). ZULRESSO will only be available under a Risk Evaluation and Mitigation Strategy (REMS) program called the ZULRESSO REMS. Prior to launch, Sage continues executing against its go-to-market strategy with a focus on activating REMS-certified Centers of Excellence (COEs) and alternate sites of care, with the goal of ensuring broad access for women with PPD.

Sage has identified a targeted list of COEs that the Company believes are capable of providing ZULRESSO to patients at launch and in subsequent periods. These COEs are sites of care that have a PPD healthcare provider champion, ability to secure appropriate payer reimbursement for ZULRESSSO, and the capabilities to operate under the REMS. The commercial field teams are continuing to educate medical and administrative leaders at these COEs on the ZULRESSO REMS, as permitted, and we have been able to initiate the process of REMS-certification at some of these COEs.

The Sage field market access team has completed more than 500 payer engagement meetings during the past several months, as permitted, including meetings with the majority of commercial and Medicaid payers. Since approval, these teams have conducted productive meetings with payers representing 90 percent of covered lives in the U.S.

The Sage patient support organization is launch ready and will provide a range of patient support resources to assist women with PPD and their families, including: dedicated case managers who can provide information to help navigate the treatment journey; personalized support to assist with understanding insurance and coverage options; financial assistance programs for eligible patients; and access to educational resources and assistance through connections to local resources.

Sage is continuing to use digital health technology in its efforts to raise awareness and reduce the stigma of PPD. Initiatives include:

Support of digital PPD education modules, reaching nearly 50,000 healthcare providers in the U.S. through the Medscape platform;

Support of digital health solutions to pregnant women and new moms, resulting in more than 100,000 digital screenings for PPD.

A U.S. patent, exclusively licensed to the Company, was recently issued covering the method of treating PPD using brexanolone injection; this patent will expire in 2033.

SAGE-217: The pivotal program evaluating the potential of SAGE-217 as a short-course episodic, rapidly-acting oral treatment for MDD and PPD is progressing on target. This program includes two completed, positive pivotal studies, one in MDD and one in PPD.

In January 2019, Sage announced statistically significant topline results in primary and secondary endpoints from the Phase 3 ROBIN Study of SAGE-217 in women with severe PPD. These results demonstrated a rapid, stable, and clinically meaningful improvement in depressive symptoms in the SAGE-217 treatment group compared to the placebo group after two weeks of treatment. The effect was maintained through the end of the four-week follow-up period. The most common adverse events in the treatment group were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation. Two subjects experienced serious adverse events, one in each treatment group.

Ongoing or planned studies in the program include:

MOUNTAIN Study: Evaluates a dosing regimen of two weeks of 20mg or 30mg SAGE-217 treatment compared to placebo in approximately 450 patients with MDD, with four weeks of blinded follow-up. Top-line data from the study are expected in Q4 2019 or Q1 2020. As a separate observational phase, the Company will continue to follow patients for up to 6 months.

Retreatment studies: These studies are designed to provide longer-term retreatment and follow-up safety and tolerability data.

MDD-302 will evaluate fixed interval SAGE-217 monotherapy maintenance (treatment without traditional antidepressants) for up to a year. This placebo-controlled trial is expected to commence in 3Q 2019 and, if successful, is intended to help meet the expected requirements for a New Drug Application for SAGE-217, and enable inclusion of maintenance dosing as part of the label.

The SHORELINE Study evaluates 30mg SAGE-217 open-label treatment, treatment-free intervals and as-needed retreatment for return of major depressive episodes over the course of up to a year. Patients will receive an initial two-week course of SAGE-217 therapy and will be assessed every eight weeks for potential relapse of depressive symptoms. Data are expected in 2020.

RAINFOREST Study: Evaluates two weeks of 30mg SAGE-217 treatment compared to placebo in approximately 100 patients with MDD and co-morbid insomnia. Top-line data are expected in 2020.

The Company is also evaluating SAGE-217 in the Phase 2 open-label ARCHWAY Study in approximately 30 patients with bipolar I/II disorder with a current major depressive episode. Primary endpoints are safety and tolerability; secondary endpoints will measure improvements in depressive symptoms and sleep. Sage plans to announce top-line data from this study in July 2019.

The Company is also evaluating the potential for development of SAGE-217 in additional affective disorders and expects to provide an update on those plans in July 2019.

SAGE-324: In a Phase 1 single ascending dose study (SAD), SAGE-324 was generally well-tolerated with no serious adverse events and demonstrated a pharmacokinetic profile consistent with once-daily dosing.

Sage is continuing to evaluate SAGE-324 in a Phase 1 multiple ascending dose (MAD) study in healthy volunteers and a Phase 1 single dose open-label study in patients with ET. These studies are designed to evaluate the safety, tolerability and pharmacokinetics of the compound. Target engagement using pharmaco-EEG (ß-band power) was observed in the SAD study and will continue to be evaluated in the MAD study. Results from these trials are expected to be announced in 2H 2019.

SAGE-718: The completed Phase 1 single and multiple ascending dose studies in healthy volunteers demonstrated a pharmacokinetic profile consistent with once-daily dosing. SAGE-718 was generally well-tolerated in the studies with no serious adverse events.

Results from ongoing Phase 1 target engagement biomarker studies in healthy volunteers, focusing on electrophysiology and imaging, are expected to be announced in July 2019.

Results from an ongoing Phase 1 study to determine the safety, tolerability and pharmacokinetics in patients with early Huntington’s disease are expected to be announced in 2H 2019.

Top-line data readouts:

SAGE-217 Phase 2 ARCHWAY Study in bipolar depression (July 2019)

SAGE-324 Phase 1 MAD study; cohorts 1-4 (July 2019)

SAGE-718 Phase 1 biomarker data (July 2019)

SAGE-718 early Huntington’s disease Phase 1 cohort data (2H 2019)

SAGE-324 essential tremor Phase 1 topline data (2H 2019)

SAGE-217 MDD Phase 3 MOUNTAIN Study (Q4 2019/Q1 2020)

SAGE-217 MDD Phase 3 RAINFOREST and SHORELINE studies (2020)

Regulatory and commercial:

ZULRESSO commercial launch in the U.S., pending DEA scheduling (late June 2019)

Cash Position: Cash, cash equivalents, and marketable securities as of March 31, 2019 were approximately $1.4 billion, compared to $922.8 million at December 31, 2018. The increase was primarily due to proceeds from Sage’s follow-on public offering completed in February 2019.

R&D Expenses: Research and development expenses were $86.4 million, including $20.7 million of non-cash stock-based compensation expense, in the first quarter of 2019, compared to $49.3 million, including $8.9 million of non-cash stock-based compensation expense, for the same period of 2018. The increase in R&D expenses year-over-year was primarily due to advancement of the pivotal program for SAGE-217 in depression; continued research efforts across our early-stage clinical and discovery pipeline; and investments in R&D headcount to support the growth in Sage’s pipeline and operations.

G&A Expenses: General and administrative expenses were $83.9 million, including $23.4 million of non-cash stock-based compensation expense, in the first quarter of 2019, compared to $28.8 million, including $6.9 million of non-cash stock-based compensation expense, for the same period of 2018. The increase in G&A expenses was primarily due to the increase in personnel-related expenses, professional fees to support expanding operations, costs related to continued preparations for the anticipated commercial launch of ZULRESSO, and facilities-related costs to support expanding operations.

Net Loss: Net loss was $163.4 million for the first quarter of 2019 compared to a net loss of $74.6 million, for the comparable period of 2018.

Based on its current operating plan, Sage now anticipates that its balance of cash, cash equivalents and marketable securities will be at least $950 million at the end of 2019.

Sage expects that its operating expenses will increase year-over-year in 2019 to support continued pipeline advancement and anticipated commercialization of ZULRESSO in PPD.

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Excessive sedation and sudden loss of consciousness. ZULRESSO may cause you to feel very sleepy (excessive sedation) or pass out (loss of consciousness). Your healthcare provider should check you for symptoms of excessive sleepiness every 2 hours while you are awake.

During your ZULRESSO infusion, tell your healthcare provider right away if you feel like you cannot stay awake during the time you are normally awake or if you feel like you are going to pass out. Your healthcare provider may lower your dose or stop the infusion until symptoms go away.

You must have a caregiver or family member with you to help care for your child(ren) during your ZULRESSO infusion.

Because of the risk of serious harm resulting from excessive sedation or sudden loss of consciousness, ZULRESSO is only available through a restricted program called the ZULRESSO REMS.

drink alcohol

have kidney problems

are pregnant or think you may be pregnant. It is not known if ZULRESSO will harm your unborn baby.

There is a pregnancy registry for females who are exposed to ZULRESSO during pregnancy. The purpose of the registry is to collect information about the health of females exposed to ZULRESSO and their baby. If you become pregnant during treatment with ZULRESSO, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visit https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

are breastfeeding or plan to breastfeed. ZULRESSO passes into breast milk. Talk to your healthcare provider about the risks and benefits of breastfeeding and about the best way to feed your baby while receiving ZULRESSO.

ZULRESSO may make you feel dizzy and sleepy. Do not drive a car or do other dangerous activities after your ZULRESSO infusion until your feeling of sleepiness has completely gone away. See “What is the most important information I should know about ZULRESSO?”

Do not drink alcohol while receiving ZULRESSO.

See “What is the most important information I should know about ZULRESSO?”

Increased risk of suicidal thoughts or actions. ZULRESSO and other antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.

Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts, or feelings, or if you develop suicidal thoughts or actions.

Tell your healthcare provider right away if you have any new or sudden changes in mood, behavior, thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms.

Attempts to commit suicide, thoughts about suicide or dying, new or worse depression, other unusual changes in behavior or mood

Sleepiness, dry mouth, passing out, flushing of the skin or face.