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Safe Harbor Statement The slides presented today and the
accompanying oral presentations contain forward-looking - At any stage, regulatory authorities may ask for additional clinical trials, nonclinical studies or other data in order for us to proceed further in development or to file for or obtain
regulatory statements, which may be identified by the use of words such as "may," "might," "will," "should," "can,","expect," "plan," "anticipate,"
"believe," "estimate," "project," "intend," "future," "opportunity", approval. Other decisions or actions of the FDA or other regulatory authorities may affect the
"goal", "mission", "potential," "target", or "continue," and other similar expressions. initiation, timing, design, size, progress and cost of clinical trials and our ability to proceed
with further development. Forward-looking statements in this presentation include statements regarding: our clinical development plans, including expected timelines for activities and our expectations as to potential - Even if
zuranolone is approved, we may not achieve market acceptance or use of zuranolone in results; our belief that our NDA for zuranolone will be accepted and the possibility of priority the MDD and PPD patient types we expect and we may not achieve
reimbursement review; the potential for approval and launch of zuranolone and potential timelines; our belief in the of zuranolone at the levels or with the type of access we expect. The benefit and safety profile of potential benefit and profile of
zuranolone and in its potential to be successful and to meet an unmet zuranolone in clinical practice, if approved, may not meet our expectations. We may not need in the treatment of MDD and PPD; the potential for commercialization of zuranolone and
our be successful in execution of our planned commercialization activities or we may change our commercialization plans, including plans to help enable access; our expectations as to the types of plans. We may never be successful or achieve our
goals with respect to commercialization MDD patients who may benefit from zuranolone, if approved; the potential for success of our other of zuranolone, if approved. product candidates in various indications, including the potential profile and
benefit of our other product candidates; our estimates as to the number of patients with disorders and diseases of - Even if zuranolone or our other product candidates are successfully developed and approved, the number of patients with the
diseases or disorders our products treat or the subset of such interest to us and that we hope to help and the potential market for our product candidates, if approved; the goals, opportunity, mission and vision for business; and our views with
respect our patients we believe will use our products, the need for new treatment options, and the actual financial strength and potential value creation opportunities. market for such products may be smaller than our current estimates. - The
anticipated benefits of our collaborations, including our collaboration with Biogen, may never 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 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
could cause actual results to differ materially from those contemplated in these forward-looking statements, including the risk that: costs may increase if any of our key collaborators fails to perform its obligations or terminates our
collaboration. - The FDA may not accept our NDA for zuranolone for review or may accept the filing for review - We may not be able to obtain and maintain adequate intellectual property protection or other but not grant approval or may
grant approval for a narrower indication than we expect or with unexpected limitations. The FDA may ask for additional clinical trials, nonclinical studies or forms of data and marketing exclusivity for our products, or to defend our patent
portfolio against challenges from third parties. other data in order for us to file for or obtain regulatory approval of zuranolone. The FDA may not grant priority review of our NDA for zuranolone. Our expectations for timing of review of our NDA
and of launch of zuranolone, if approved, may not be accurate. The FDA may ultimately - We may face competition from others developing products or with approved products for similar uses as those for which our product candidates are being
developed. decide that the design or results of our clinical trials for our product candidates are not sufficient to successfully file for or obtain regulatory approval. - Our operating expenses may be higher than forecasted, our revenues may
be lower than we expect, or we may face unexpected expenditures, which could cause us to change our - Our clinical trials may not meet their primary endpoints or key secondary endpoints. Success in plans. We may need or choose to raise
additional funding, which may not be available on non-clinical studies or in prior clinical trials of our product candidates may not be repeated or observed in ongoing, planned or future studies involving the same compound or other product
acceptable terms, or at all. candidates. Non-clinical and clinical results from ongoing or future trials may not support further - We may not be able to establish and maintain key business relationships with third parties on development of the
product candidate or filing for or obtaining regulatory approval on the acceptable terms or we may encounter problems with the performance of such third parties. timelines we expect or at all and we may be required to conduct additional clinical
trials or nonclinical studies which may not be successful. - We may encounter technical and other unexpected hurdles in the manufacture, development or commercialization of our products. - We may experience slower than expected
enrollment in our clinical trials or may encounter other delays or problems, including in analyzing data or requiring the need for additional analysis, data - Any of the foregoing or other factors may negatively impact our ability to achieve
our goals, or patients, and such issues with any trial could cause delay in completion of the trial, availability mission, opportunities, plans or expectations for our business. of results and timing of future activities. For additional
disclosure regarding these and other risks Sage faces, see the disclosure contained - We may encounter unexpected safety or tolerability issues with respect to any of our product in the Risk Factors section of our most recent report, and in
our other public filings, with the candidates or marketed products; we may encounter different or more severe adverse events at Securities and Exchange Commission, available on the SEC's website at http://www.sec.gov. Any the higher doses, different
frequency or length of dosing or in new indications we are studying or forward-looking statement represent our views only as of today, and should not be relied upon as may study in ongoing or planned trials. representing our views as of any
subsequent date. We undertake no obligation to update or revise the information contained in this presentation, whether as a result of new information, future events or circumstances or otherwise. 2 Sage Therapeutics 2023
The time is now Kay Lynn Seth Postpartum Huntington's
Essential Depression (PPD) Disease (HD) Tremor (ET) Sheante Dan Kirsten Major Depressive Parkinson's Alzheimer's Disorder (MDD) Disease (PD) Disease (AD) Brain health is fundamental to good health 3 Sage Therapeutics
Building impact and scale Millions of people have been Patients,
providers, and society Relentless focus on developing waiting decades for new can and must be better served new and effective treatments to treatment options address brain health disorders The time is now 4 Sage Therapeutics
Challenge scientific convention Starting with our work on GABA and NMDA,
we are pursuing breakthroughs that have the potential to advance the treatment of a wide range of brain health disorders. 5 Sage Therapeutics 2023
Building a business for the future Rich innovative pipeline/product
engine Deep expertise in brain circuitry Significant potential patient impact Strong cash position to fuel growth Exciting business momentum into 2023 6 Sage Therapeutics 2023
Sage has a leading brain health portfolio PRECLINICAL REGISTRATION
MARKETED COMPOUND PARTNER INDICATIONS PHASE 1 PHASE 2 PHASE 3 DEPRESSION ZULRESSO Postpartum Depression (brexanolone) CIV injection Major Depressive Disorder Postpartum Depression Zuranolone Treatment Resistant Depression (SAGE-217)
Generalized Anxiety Disorder Bipolar Depression NEUROLOGY Essential Tremor Epileptiform Disorders SAGE-324 Parkinson's Disease SAGE-689 Acute GABA Hypofunction NEUROPSYCHIATRY Huntington's Disease Cognitive Dysfunction Parkinson's
Disease Cognitive SAGE-718 Dysfunction Alzheimer's Disease Mild Cognitive Impairment and Mild Dementia EARLY DEVELOPMENT SAGE-319 GABA Hypofunction NMDA Hypofunction SAGE-421 7 Sage Therapeutics 2023 Light shades indicate trials in the
planning or evaluation stage
Significant unmet needs remain in the treatment of depression Unmet
Needs In a survey of MDD patients (n=583) STAR*D Analysis shows that patients The economic burden of MDD in the conducted by Sage, 75% of MDD who achieve later remission have a United States is an estimated $326 2 patients asked about the impact of
1.5 times higher risk of relapse than billion in 2018 1 switching medications reported being those who remit early frustrated or feeling that no medication 1 was going to work for them 1 2 3 MDD = major depressive disorder 8 Sage Therapeutics
2023 1. Sage Therapeutics. Data on file. 2. Greenberg PE, et al. PharmacoEconomics. 2021; 39: 653-665.
Zuranolone clinical data supports its potential to fulfill unmet needs
for people with MDD and PPD Rapid & Sustained Short Course Rapid symptom reduction observed As-needed oral therapy Sustained effects lasted beyond 2-week treatment course completion of treatment Well-Tolerated
Novel MOA Selectively modulates GABA R Well-tolerated profile* A May help neuronal networks Differentiated side effect profile with no 1 rebalance evidence of increased sexual dysfunction, weight gain or sleep
disruption Flexible Approach Improved Feel/Functioning Improvement seen in Improvements seen across depressive symptoms in domains of quality of life MDD/PPD patients when used Measured benefits that patients as mono or
adjunctive therapy are looking for from depression Improvements seen in treatment MDD/PPD patients with or *Zuranolone was generally well-tolerated across clinical studies. The most common adverse events associated with zuranolone included
headache, somnolence, dizziness and sedation. without elevated anxiety Profile based on data demonstrated in clinical studies with zuranolone to date Note: Success of zuranolone and the product profile depend on the clinical development program and
regulatory approval. 1 Antonoudiou, P. et al. Allopregnanolone mediates affective switching through modulation of oscillatory states in the basolateral amygdala. Biological Psychiatry, 2021.2003.2008.434156, doi:10.1016/j.biopsych.2021.07.017
(2021). Sage Therapeutics 2023 9 MDD = major depressive disorder, PPD = postpartum depression Zuranolone is being developed in collaboration with Biogen.
In an integrated analysis of zuranolone data, patients reported overall
improvement in functioning and well-being * Mental Health * Clinically meaningful * improvements were observed Role-Emotional * across mental health, physical * * Social Functioning and general health domains * Vitality * of SF-36 * *
General Health * Bodily Pain * Role-Physical * * Physical Functioning 0 3 6 9 12 15 18 Day 42 Day 15 Zuranolone Day 42 Zuranolone Day 15 Placebo Day 42 Placebo Day 15 *LSM treatment difference p-value <0.05 (nominal); Integrated analyses
combine doses from the ROBIN Study, MDD- 201B Study, MOUNTAIN Study ( 24 HAMD-17 subgroup), and WATERFALL Study. For the ROBIN study, data were 10 collected at Day 45.; SF-36 = 36-Item Short Form Health Survey (version 2). Sage
Therapeutics 2023 Zuranolone is being developed in collaboration with Biogen.
Selected responder interviews from SHORELINE Study in MDD Examples of
quotes from surveyed patients who responded to initial treatment cycle of 50 mg zuranolone in the open-label SHORELINE Study (n=32) "Very satisfied because "...almost like an afterglow of "It was really impressive it's
helping me. I feel better the two week course of that the results happened about myself now than I did treatment, that then it was just "I felt better both times so quickly, and it was so when I first started. I know it's working
for several months. I started feeling better right dramatic. It wasn't just a slight good I'm doing more than I I didn't have to think about it away and I wasn't as bad improvement, it was night and used to.
I'm getting up. I'm going constantly. I didn't have to take when I took it the second time day. It was a 180 degree turn to church. Before, I wouldn't be medication...I wasn't having as I had been before the
study." from how I'd been feeling anywhere, I wouldn't go outside, to think about my depression even just the day before." I would just look outside the and try to manage it." door. It has helped me." Rapid Onset
Durability Retreatment Satisfaction A substantial majority of interviewed Most interviewed patients reported A significant majority of interviewed All interviewed patients reported patients noticed improvements within being satisfied with duration
of patients who received retreatment being moderately, quite, or very the first week improvements reported feeling fine, positive, or satisfied with zuranolone neutral about needing to be retreated Among patients treated in the ongoing open-label
Phase 3 SHORELINE Study, the most common TEAEs (>5%) observed in the 30 and 50 mg cohorts were headache, somnolence, dizziness, and sedation. Patient experiences are provided solely to help illustrate the data collected from the SHORELINE Study
interviews. Patient experiences in the SHORELINE Study differed patient-to-patient. Results of the survey are not intended to make claims about zuranolone's potential benefit. Survey information does not represent all patients who took zuranolone.
Interviews conducted with patients who responded to the first 50 mg zuranolone treatment cycle and had been participants in the SHORELINE Study for at least six months. Interviews were conducted at various timepoints for each patient. Based on
SHORELINE Study design, patients were allowed to be on background therapy. Sample size of interviewed patients n = 32. 11 Sage Therapeutics 2023 MDD = major depressive disorder Zuranolone is being developed in collaboration with
Goal of the planned zuranolone launch strategy is to transform the way
MDD and PPD are treated MDD - MDD Partial with Elevated If zuranolone is approved, plan to focus on: Response Anxiety Priority MDD and PPD patient segments Target High Volume HCPs Psychiatrists NPs / PAs PCPs MDD
- Adherence PPD OBGYNs Challenged Collaborate with Payers Lead with Value Sage and Biogen Zuranolone Webcast [December 6, 2022]. Accessible via:
https://investor.sagerx.com/events/event-details/sage-therapeutics-and-biogen-webcast-discuss- potential-commercialization-plans MDD = major depressive disorder, PPD = postpartum depression, NP = nurse practitioner, PA = physician assistant, PCP =
primary care provider 12 Sage Therapeutics 2023 Zuranolone is being developed in collaboration with Biogen.
Cognitive impairment is prevalent and impacts people across the
lifespan Executive Function Learning & Memory Attention Language Visuospatial Planning, decision- Recall, recognition. Sustained attention, Object naming, word Visual perception. making, working long-term memory, divided attention, finding,
fluency, Visuo-constructional memory, multitasking, implicit learning selective attention, grammar and syntax, reasoning, perceptual- flexibility processing speed receptive language motor coordination DAILY LIFE Cooking Driving Lists Working
Finances Sources: SSM Popul Health. 2020 Aug; 11: 100577. Published online 2020 Mar 31. doi: 10.1016/j.ssmph.2020.100577 https://altoida.com/blog/defining-the-6-key-domains-of-cognitive-function/ 13 Sage Therapeutics 2023
Sage's first-in-class NMDA receptor PAM Novel starting point for
understanding NMDA receptor modulation Emerging Science SAGE-718: NMDA Positive Drives New Thinking Allosteric Modulator (PAM) The neuroactive steroid, 24S- SAGE-718 is a novel, positive hydroxycholesterol (24S-HC), is an allosteric
modulator derived from our endogenous modulator of NMDA pharmacological understanding of receptors 24S-HC NMDA receptors play a major role in SAGE-718 is believed to bind to a excitatory transmission in the brain novel neurosteroid
site on the NMDA and influence cognition and other receptor key brain functions SAGE-718 has the potential to NMDA receptor hypofunction has restore NMDA activity and improve been implicated in cognitive cognitive functioning
impairment associated with disorders such as Huntington's disease, Parkinson's disease and Alzheimer's disease 14 Sage Therapeutics 2023
Globally, disorders involving cognitive impairment continue to increase
Cognitive impairment has devastating impacts on patients, families, and society ~188K ~8.8M ~134M Huntington's Disease Parkinson's Disease Alzheimer's Disease 1 2 3 Global Prevalence Global Prevalence Global Prevalence Cognitive
Impairment in HD can Mild cognitive impairment (MCI) is Up to 50% of people with MCI due occur up to 15 years before motor diagnosed in nearly half of people to AD progress to Alzheimer's manifestation & is highly associated with PD and
causes poorer treatment dementia within 5-10 years with overall functional decline outcomes, greater medical costs, and caregiver distress HD = Huntington's disease, PD = Parkinson's disease, AD = Alzheimer's disease 1. Pringsheim
T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington's disease: a systematic review and meta-analysis. Mov Disord. 2012 Aug;27(9):1083-91. doi: 10.1002/mds.25075. Epub 15 Sage Therapeutics 2023 2012
Jun 12. PMID: 22692795. 2. Sage Therapeutics, Inc. Data on file. 3. Sage Therapeutics, Inc. Data on file.
SAGE-718 has demonstrated consistent beneficial effects on cognitive
performance in clinical studies to date Placebo-controlled Two Back Test Performance on Executive Functioning Tasks Across SAGE-718 Studies Digital Symbol Substitution Test Z-Transformed Change from Baseline to Last Assessment* (Mean change from
baseline plotted) Spatial Working Memory Test IMPROVEMENT 1.2 Healthy Volunteers Huntington's Parkinson's Disease Alzheimer's Disease w/ Ketamine Disease PARADIGM Study LUMINARY Study Challenge CLP-102B 1.0 EXM-103 0.8 0.6 0.4 0.2
NO CHANGE HV on Ketamine n = 6 n = 13 n = 16 n = 17 n = 23 n = 24 n = 25 & SAGE-718 -0.2 n = 18 -0.4 HV on Ketamine WORSENING & Placebo n = 19 HV = healthy volunteers 16 Sage Therapeutics 2023
SAGE-718 clinical development program in Huntington's disease