JPM 2023 Sage.pdf

1、J.P.Morgan Healthcare ConferenceJanuary 2023Sage Therapeutics 2023Safe Harbor Statement2 The slides presented today and the accompanying oral presentations contain forward-looking statements,which may be identified by the use of words such as“may,”“might,”“will,”“should,”“can,”,“expect,”“plan,”“anti

2、cipate,”“believe,”“estimate,”“project,”“intend,”“future,”“opportunity”,“goal”,“mission”,“potential,”“target”,or“continue,”and other similar expressions.Forward-looking statements in this presentation include statements regarding:our clinical development plans,including expected timelines for activit

3、ies and our expectations as to potential results;our belief that our NDA for zuranolone will be accepted and the possibility of priority review;the potential for approval and launch of zuranolone and potential timelines;our belief in the potential benefit and profile of zuranolone and in its potenti

4、al to be successful and to meet an unmet need in the treatment of MDD and PPD;the potential for commercialization of zuranolone and our commercialization plans,including plans to help enable access;our expectations as to the types of MDD patients who may benefit from zuranolone,if approved;the poten

5、tial for success of our other 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 interest to us and that we hope to help and the potential market for our produ

6、ct candidates,if approved;the goals,opportunity,mission and vision for business;and our views with respect our financial strength and potential value creation opportunities.These forward-looking statements are neither promises nor guarantees of future performance,and are subject to a variety of risk

7、s 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 risk that:The FDA may not accept our NDA for zuranolone for review or may accept the filing for review but not gran

8、t 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 other data in order for us to file for or obtain regulatory approval of zuranolone.The FDA may not grant priority review of o

9、ur 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 decide that the design or results of our clinical trials for our product candidates are not sufficient to successfully file for or obtain regulato

10、ry approval.Our clinical trials may not meet their primary endpoints or key secondary endpoints.Success in 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 cand

11、idates.Non-clinical and clinical results from ongoing or future trials may not support further development of the product candidate or filing for or obtaining regulatory approval on the timelines we expect or at all and we may be required to conduct additional clinical trials or nonclinical studies

12、which may not be successful.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 or patients,and such issues with any trial could cause delay in completion of

13、the trial,availability of results and timing of future activities.We may encounter unexpected safety or tolerability issues with respect to any of our product candidates or marketed products;we may encounter different or more severe adverse events at the higher doses,different frequency or length of

14、 dosing or in new indications we are studying or may study in ongoing or planned trials.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 approval.Other de

15、cisions or actions of the FDA or other regulatory authorities may affect the initiation,timing,design,size,progress and cost of clinical trials and our ability to proceed with further development.Even if zuranolone is approved,we may not achieve market acceptance or use of zuranolone in the MDD and

16、PPD patient types we expect and we may not achieve reimbursement of zuranolone at the levels or with the type of access we expect.The benefit and safety profile of zuranolone in clinical practice,if approved,may not meet our expectations.We may not be successful in execution of our planned commercia

17、lization activities or we may change our plans.We may never be successful or achieve our goals with respect to commercialization of zuranolone,if approved.Even if zuranolone or our other product candidates are successfully developed and approved,the number of patients with the diseases or disorders

18、our products treat or the subset of such patients we believe will use our products,the need for new treatment options,and the actual market for such products may be smaller than our current estimates.The anticipated benefits of our collaborations,including our collaboration with Biogen,may never be

19、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

20、.We may not be able to obtain and maintain adequate intellectual property protection or other forms of data and marketing exclusivity for our products,or to defend our patent portfolio against challenges from third parties.We may face competition from others developing products or with approved prod

21、ucts for similar uses as those for which our product candidates are being developed.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 plans.We may need or choose to raise additional

22、funding,which may not be available on acceptable terms,or at all.We may not be able to establish and maintain key business relationships with third parties on acceptable terms or we may encounter problems with the performance of such third parties.We may encounter technical and other unexpected hurd

23、les in the manufacture,development or commercialization of our products.Any of the foregoing or other factors may negatively impact our ability to achieve our goals,mission,opportunities,plans or expectations for our business.For additional disclosure regarding these and other risks Sage faces,see t

24、he disclosure contained in the Risk Factors section of our most recent report,and in our other public filings,with the Securities and Exchange Commission,available on the SECs website at http:/www.sec.gov.Any forward-looking statement represent our views only as of today,and should not be relied upo

25、n as 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.Sage Therapeutics 2023The time is now3SheanteMajor Depressive Disorde

26、r(MDD)KayPostpartum Depression(PPD)SethHuntingtons Disease(HD)LynnEssentialTremor(ET)DanParkinsons Disease(PD)KirstenAlzheimers Disease(AD)Brain health is fundamental to good healthSage Therapeutics 20234Patients,providers,and society can and must be better served Relentless focus on developingnew a

27、nd effective treatments to address brain health disorders Millions of people have been waiting decades for new treatment options Building impact and scaleThe time is nowSage Therapeutics 2023Challenge scientific convention5Starting with our work on GABA and NMDA,we are pursuing breakthroughs that ha

28、ve the potential to advance the treatment of a wide range of brain health disorders.Sage Therapeutics 2023Building a business for the future 6Rich innovative pipeline/product engineDeep expertise in brain circuitrySignificant potential patient impactStrong cash position to fuel growthExciting busine

29、ss momentum into 2023Sage Therapeutics 2023COMPOUNDPARTNERINDICATIONSPRECLINICALPHASE 1PHASE 2PHASE 3REGISTRATIONMARKETEDDEPRESSIONZULRESSO(brexanolone)CIV injectionPostpartum DepressionZuranolone(SAGE-217)Major Depressive DisorderPostpartum DepressionTreatment Resistant DepressionGeneralized Anxiet

30、y DisorderBipolar DepressionNEUROLOGYSAGE-324Essential TremorEpileptiform DisordersParkinsons DiseaseSAGE-689Acute GABA HypofunctionNEUROPSYCHIATRYSAGE-718Huntingtons Disease Cognitive DysfunctionParkinsons Disease Cognitive DysfunctionAlzheimers Disease Mild Cognitive Impairment and Mild DementiaEA

31、RLY DEVELOPMENTSAGE-319GABA HypofunctionSAGE-421NMDA HypofunctionSage has a leading brain health portfolio7Light shades indicate trials in the planning or evaluation stageSage Therapeutics 2023The economic burden of MDD in the United States is an estimated$326 billion in 20182In a survey of MDD pati

32、ents(n=583)conducted by Sage,75%of MDD patients asked about the impact of switching medications reported being frustrated or feeling that no medication was going to work for them1STAR*D Analysis shows that patients who achieve later remission have a 1.5 times higher risk of relapse than those who re

33、mit early1Significant unmet needs remain in the treatment of depression8MDD=major depressive disorder1.Sage Therapeutics.Data on file.2.Greenberg PE,et al.PharmacoEconomics.2021;39:653-665.123Unmet Needs Sage Therapeutics 2023Zuranolone clinical data supports its potential to fulfill unmet needs for

34、 people with MDD and PPDProfile based on data demonstrated in clinical studies with zuranolone to dateNote:Success of zuranolone and the product profile depend on the clinical development program and regulatory approval.1Antonoudiou,P.et al.Allopregnanolone mediates affective switching through modul

35、ation of oscillatory states in the basolateral amygdala.Biological Psychiatry,2021.2003.2008.434156,doi:10.1016/j.biopsych.2021.07.017(2021).MDD=major depressive disorder,PPD=postpartum depression9Rapid&SustainedRapid symptom reduction observedSustained effects lasted beyondcompletion of treatmentFl

36、exible ApproachImprovement seen in depressive symptoms in MDD/PPD patients when used as mono or adjunctive therapyImprovements seen in MDD/PPD patients with or without elevated anxietyNovel MOASelectively modulates GABAARMay help neuronal networks rebalance1Well-ToleratedWell-tolerated profile*Diffe

37、rentiated side effect profile with no evidence of increased sexual dysfunction,weight gain or sleep disruptionShort CourseAs-needed oral therapy2-week treatment courseImproved Feel/FunctioningImprovements seen across domains of quality of life Measured benefits that patients are looking for from dep

38、ression treatmentZuranolone is being developed in collaboration with Biogen.*Zuranolone was generally well-tolerated across clinical studies.The most common adverse events associated with zuranolone included headache,somnolence,dizziness and sedation.Sage Therapeutics 2023In an integrated analysis o

39、f zuranolone data,patients reported overall improvement in functioning and well-being10*LSM treatment difference p-value 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 SHOR

40、ELINE Study interviews.Patient experiences in the SHORELINE Study differed patient-to-patient.Results of the survey are not intended to make claims about zuranolones potential benefit.Survey information does not represent all patients who took zuranolone.Interviews conducted with patients who respon

41、ded 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 pat

42、ients n=32.MDD=major depressive disorder“It was really impressive that the results happened so quickly,and it was so dramatic.It wasnt just a slight improvement,it was night and day.It was a 180 degree turn from how Id been feeling even just the day before.”“.almost like an afterglow of the two week

43、 course of treatment,that then it was just working for several months.I didnt have to think about it constantly.I didnt have to take medication.I wasnt having to think about my depression and try to manage it.”“I felt better both timesI started feeling better right awayand I wasnt as bad when I took

44、 it the second time as I had been before the study.”“Very satisfied becauseits helping me.I feel better about myself now than I did when I first started.I know its goodIm doing more than I used to.Im getting up.Im going to church.Before,I wouldnt be anywhere,I wouldnt go outside,I would just look ou

45、tside the door.It has helped me.”Examples of quotes from surveyed patients who responded to initial treatment cycle of 50 mg zuranolone in the open-label SHORELINE Study(n=32)Rapid OnsetA substantial majority of interviewed patients noticed improvements within the first weekDurabilityMost interviewe

46、d patients reported being satisfied with duration of improvementsRetreatmentA significant majority of interviewed patients who received retreatment reported feeling fine,positive,or neutral about needing to be retreatedSatisfactionAll interviewed patients reported being moderately,quite,or very sati

47、sfied with zuranoloneZuranolone is being developed in collaboration with Biogen.Sage Therapeutics 2023Goal of the planned zuranolone launch strategy is to transform the way MDD and PPD are treated12MDD Partial ResponseMDDwith Elevated AnxietyMDD Adherence ChallengedPPDIf zuranolone is approved,plan

48、to focus on:Priority MDD and PPD patient segmentsTarget High Volume HCPsPsychiatristsNPs/PAsPCPsOBGYNsCollaborate with PayersLead with ValueSage and Biogen Zuranolone Webcast December 6,2022.Accessible via:https:/ depressive disorder,PPD=postpartum depression,NP=nurse practitioner,PA=physician assis

49、tant,PCP=primary care providerZuranolone is being developed in collaboration with Biogen.Sage Therapeutics 2023Cognitive impairment is prevalent and impacts people across the lifespan Executive FunctionPlanning,decision-making,working memory,multitasking,flexibilityLearning&MemoryRecall,recognition.

50、long-term memory,implicit learningAttentionSustained attention,divided attention,selective attention,processing speedLanguageObject naming,word finding,fluency,grammar and syntax,receptive languageVisuospatialVisual perception.Visuo-constructional reasoning,perceptual-motor coordinationCookingDrivin

51、gWorkingListsSources:SSM Popul Health.2020 Aug;11:100577.Published online 2020 Mar 31.doi:10.1016/j.ssmph.2020.100577https:/ LIFE13Sage Therapeutics 2023Sages first-in-class NMDA receptor PAMNovel starting point for understanding NMDA receptor modulation14SAGE-718:NMDA Positive Allosteric Modulator(

52、PAM)SAGE-718 is a novel,positive allosteric modulator derived from our pharmacological understanding of 24S-HCSAGE-718 is believed to bind to a novel neurosteroid site on the NMDA receptorSAGE-718 has the potential to restore NMDA activity and improve cognitive functioning Emerging Science Drives Ne

53、w ThinkingThe neuroactive steroid,24S-hydroxycholesterol(24S-HC),is an endogenous modulator of NMDA receptorsNMDA receptors play a major role in excitatory transmission in the brain and influence cognition and other key brain functionsNMDA receptor hypofunction has been implicated in cognitive impai

54、rment associated with disorders such as Huntingtons disease,Parkinsons disease and Alzheimers diseaseSage Therapeutics 2023Globally,disorders involving cognitive impairment continue to increase 15Cognitive impairment has devastating impacts onpatients,families,and society188KHuntingtons Disease Glob

55、al Prevalence1Cognitive Impairment in HD can occur up to 15 years before motor manifestation&is highly associated with overall functional decline8.8MParkinsons Disease Global Prevalence2Mild cognitive impairment(MCI)is diagnosed in nearly half of people with PD and causes poorer treatment outcomes,g

56、reater medical costs,and caregiver distress134MAlzheimers Disease Global Prevalence3Up to 50%of people with MCI due to AD progress to Alzheimers dementia within 5-10 yearsHD=Huntingtons disease,PD=Parkinsons disease,AD=Alzheimers disease 1.Pringsheim T,Wiltshire K,Day L,Dykeman J,Steeves T,Jette N.T

57、he incidence and prevalence of Huntingtons disease:a systematic review and meta-analysis.Mov Disord.2012 Aug;27(9):1083-91.doi:10.1002/mds.25075.Epub2012 Jun 12.PMID:22692795.2.Sage Therapeutics,Inc.Data on file.3.Sage Therapeutics,Inc.Data on file.Sage Therapeutics 2023SAGE-718 has demonstrated con

58、sistent beneficial effects on cognitive performance in clinical studies to date16HV=healthy volunteers HV on Ketamine&Placebo n=19HV on Ketamine&SAGE-718 n=18n=6 n=16n=24Performance on Executive Functioning Tasks Across SAGE-718 StudiesZ-Transformed Change from Baseline to Last Assessment*(Mean chan

59、ge from baseline plotted)n=13n=17n=23n=25NO CHANGE0.20.40.60.81.01.2-0.2-0.4WORSENINGIMPROVEMENTHuntingtons DiseaseCLP-102BHealthy Volunteers w/Ketamine Challenge EXM-103 Parkinsons DiseasePARADIGM StudyAlzheimers DiseaseLUMINARY StudyPlacebo-controlled Two Back Test Digital Symbol Substitution Test

60、Spatial Working Memory TestSage Therapeutics 202317SAGE-718 clinical development program in Huntingtons diseaseHuntingtons DiseaseFDA Fast-track DesignationDIMENSION(CIH-201)|3-month studyDescription:Robust RCT in patients with HD cognitive impairment,designed to evaluate efficacy Objective:Demonstr

61、ate difference on cognitive performance between drug and placebo at month 3Target enrollment:178SURVEYOR(CIH-202)|1 month studyDescription:Placebo-controlled RCT to demonstrate the clinical meaningfulness of improving cognition in HDObjective:Generate evidence linking change in cognitive performance

62、 to real-world patient functioning,benchmarked against performance of healthy volunteersTarget enrollment:40 people with HD,40 healthy volunteers(assessment-only HV arm)PURVIEW(CIH-301)|13-month studyDescription:Open-label safety study,enrolling participants from DIMENSION,SURVEYOR,and an additional

63、 de novo cohortObjective:Designed to evaluate the long-term safety profile and benchmark performance against HD natural history studies Target enrollment:300 ENROLLINGENROLLINGENROLLINGSage Therapeutics 2023Sages robust portfolio features NCEs with differentiated target profiles that may be suited f

64、or study across the lifespanZULRESSO(brexanolone)CIVzuranolone(Oral)SAGE-324(Oral)SAGE-718(Oral)SAGE-421(Oral)SAGE-319(Oral)SAGE-689(Parenteral)18GABANMDASage Therapeutics 2023Anticipated 2023 Milestones19EarlyMidLate*Early:Q1-Q2;Mid:Q2-Q3;Late:Q3-Q4DEPRESSIONZuranolone(SAGE-217)FDA acceptance of ro

65、lling NDA submission for zuranolone in MDD and PPDPresent additional data from SHORELINE StudyPDUFA date for zuranolone in MDD and PPD,if accepted for review by the FDACommercial availability of zuranolone in MDD and PPD,if priority review is granted and zuranolone is approvedInitiate a lifecycle in

66、novation study with zuranolonePresent additional analyses of data from LANDSCAPE and NEST clinical programs,including health economics and patient reported outcomesNEUROLOGY SAGE-324Complete enrollment in Phase 2b KINETIC 2 StudyPresent additional analyses of data from clinical development program a

67、s well as disease state and burden of disease research in ETNEUROPSYCHIATRYSAGE-718Progress recruitment in the ongoing DIMENSION,SURVEYOR,PURVIEW,PRECEDENT,and LIGHTWAVE StudiesPresent additional analyses of data from clinical development program as well as disease state and burden of disease resear

68、ch in HD,PD and ADADDITIONAL CLINICAL PROGRAMS&MILESTONESAdditional Pipeline ProgramsProvide update on next steps for pipeline programs(e.g.,SAGE-319)Cash BalanceMaintain strong balance sheetMDD=major depressive disorder,PPD=postpartum depression,ET=essential tremor,HD=Huntingtons disease,PD=Parkins

69、ons disease,AD=Alzheimers disease Sage Therapeutics 2023The time is now20SheanteMajor Depressive Disorder(MDD)KayPostpartum Depression(PPD)SethHuntingtons Disease(HD)LynnEssentialTremor(ET)DanParkinsons Disease(PD)KirstenAlzheimers Disease(AD)Brain health is fundamental to good healthSage Therapeutics 202321Seeing the brain differentlymakes a world of difference