1、Steve Davis,CEO42nd Annual J.P.Morgan Healthcare ConferenceJanuary 9,2024NUPLAZID(pimavanserin)is only approved in the U.S.by the FDA for the treatment of hallucinations and delusions associated with Parkinsons disease psychosis.DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treat

2、ment of Rett syndrome in adults and pediatric patients two years of age and older.Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.2Forward-Looking StatementsThi

3、s presentation contains forward-looking statements.These statements relate to future events and involve known and unknown risks,uncertainties and other factors which may cause our actual results,performance or achievements to be materially different from any future results,performances or achievemen

4、ts expressed in or implied by such forward-looking statements.Each of these statements is based only on current information,assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties.Forward-looking statements include,but are not limited to,sta

5、tements about(i)plans for,including timing and progress of commercialization or regulatory timelines for,DAYBUE;(ii)benefits to be derived from and efficacy of our product candidates,including the potential advantages of DAYBUE and expansion opportunities for DAYBUE;(iii)estimates regarding the prev

6、alence of Rett syndrome;(iv)potential markets for any of our products,including NUPLAZID and DAYBUE;(v)our estimates regarding our future financial performance,cash position or capital requirements.In some cases,you can identify forward-looking statements by terms such as“may,”“will,”“should,”“could

7、,”“would,”“expects,”“plans,”“anticipates,”“believes,”“estimates,”“projects,”“predicts,”“potential”and similar expressions(including the negative thereof)intended to identify forward-looking statements.Given the risks and uncertainties,you should not place undue reliance on these forward-looking stat

8、ements.For a discussion of the risks and other factors that may cause our actual results,performance or achievements to differ,please refer to our annual report on Form 10-K for the year ended December 31,2022 as well as our subsequent filings with the SEC.The forward-looking statements contained he

9、rein are made as of the date hereof,and we undertake no obligation to update them for future events.3DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treatment of Rett syndrome in adults and pediatric patients two years of age and older.NUPLAZID(pimavanserin)is only approved in the

10、U.S.by the FDA for the treatment of hallucinations and delusions associated with Parkinsons disease psychosis.Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.In

11、vestment ThesisThree late-stage assets with strong early-stage pipelineTwo successful commercial franchises driving record revenuesCash flow positiveSuccessful Launch of DAYBUE forRett SyndromeCaregiver testimonials are sourced from AnovoRx as well as from poster titled Assessing Experiences With Tr

12、ofinetide for Rett Syndrome:Interviews With Caregivers of Patients in LAVENDER,LILAC,and LILAC-2 Studies.DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treatment of Rett syndrome in adults and pediatric patients two years of age and older.Provided January 9,2024 as part of an oral

13、 presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.5DAYBUE Real World Experience“She knows that she can get her answers out quicker and that shes answering accurately,and shes getting more reciprocation fr

14、om peers.People around her are able to communicate with her more effectively.”“Picking up things a lot more(mostly her cup),happens daily and she is now trying to drink by herself.”“It was her engagement level with the world outside of her to me and to friends in school;it just blossomed,and it was

15、like a light was turned on.”“Her verbalization definitely improved,and she started sayingmore things.”“Improved cognitive ability,and the parents are hearing new words or words they have not heard in a while.”“Better at following directions and listening to what someone tells her,better with recepti

16、ve language.”1Based on guidance range provided on November 2,2023 combined with YTD actual results through September 30,2023.DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treatment of Rett syndrome in adults and pediatric patients two years of age and older.Provided January 9,202

17、4 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.6Successful DAYBUE Launch Continuingto expand breadth and depth in Rett community leveraging:Current demand tracking to typical rare d

18、isease launch trajectoryEarly surge in demand from centers of excellenceExpect$170 to$177.5 million in FY 2023 product sales(first 8 months of launch)15,000 diagnosed Rett syndrome patients 800 patients on DAYBUE,as of end of 3Q23Real world benefitsPhysician experienceCaregiver familiarityEstablishe

19、d broad payor access DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treatment of Rett syndrome in adults and pediatric patients two years of age and older.Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual re

20、sults may vary materially;Acadia disclaims any duty to update.7DAYBUE Performance Metrics6-month real world persistency vs.clinical trial experienceHeader text here76%68%58%Based on confirmed discontinuations onlyBased on confirmed discontinuations and patients who were 60 days past their scheduled

21、refill LILAC-1 persistency at month 6Compliance to dose estimated 75-80%Formal payor policies in place for 80%of Rett covered lives8Worldwide DAYBUE Opportunity Expanding globally beginning in 2024Header text here NDS filing 1Q24 Potential approval around YE24Prevalence Estimated 600 to 900 patients

22、 Engaging with EMA in 1Q24 MAA filing in 1H25Prevalence Estimated 9,000 to 14,000 patients(Europe and UK)Engaging Japanese regulatory agency(PMDA)in 2024Prevalence Estimated 1,000 to2,000 patientsCANADAEUROPEJAPANNDS:New Drug Submission;EMA:European Medical Authority;MAA:Marketing Authorization Appl

23、ication;PMDA:Pharmaceuticals and Medical Devices AgencyPrevalence numbers estimated by Acadia based on information available.DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treatment of Rett syndrome in adults and pediatric patients two years of age and older.Provided January 9,202

24、4 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.NUPLAZIDProvides StrongFoundationNUPLAZID Strategy:Optimize Cash Flow Franchise generates$300 million in annual cash flowReal world ev

25、idence has grown new patient starts and net salesReduced NUPLAZID SG&A spend by$100M on an annualized basis(21 vs.23)NUPLAZID(pimavanserin)is only approved in the U.S.by the FDA for the treatment of hallucinations and delusions associated with Parkinsons disease psychosis.Provided January 9,2024 as

26、part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.10Positioning Acadia for Further GrowthNUPLAZID(pimavanserin)is only approved in the U.S.by the FDA for the treatment of hallucinations and

27、 delusions associated with Parkinsons disease psychosis.DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treatment of Rett syndrome in adults and pediatric patients two years of age and older.1 Safety and efficacy of pimavanserin for the treatment of negative symptoms of schizophren

28、ia have not been established or approved by the FDA.2 Acadia acquired Levo Therapeutics and its rights/licenses to ACP-101.3 The safety and efficacy of these investigational agents have not been established.There is no guarantee these investigational agents will be filed with or approved by any regu

29、latory agency.Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.Deep CNS Pipeline12ProgramIndicationPreclinical Phase 1 Phase 2Phase 3MarketedNUPLAZID(pimavanseri

30、n)Parkinsons Disease PsychosisDAYBUE(trofinetide)Rett SyndromePimavanserin1Negative Symptoms of SchizophreniaACP-1012,3Hyperphagia in Prader-Willi SyndromeACP-2043Alzheimers Disease PsychosisACP-25913Rett Syndrome;Fragile X SyndromeASO Programs3 SYNGAP1;Rett;UndisclosedMultiple Undisclosed ProgramsN

31、europsychiatric and Rare DisordersNegative Symptoms of Schizophrenia Negative Symptoms of Schizophrenia1Studies suggest that 40-50%of schizophrenia patients experience predominant negative symptoms;Patel et al.2015,Haro et al.,2015,Bobes et al.2010,and Chue and Lalonde,2014.Provided January 9,2024 a

32、s part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to updateChronic,persistent negative symptoms include social withdrawal,restricted speech,lack of emotion,loss of motivation,and blunted affect and

33、 can lead to:No FDA-approved treatment700,000 patientsin the U.S.have persistent negative symptoms1Low social functioningLong-term disabilitySignificant caregiver burden14.Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual resu

34、lts may vary materially;Acadia disclaims any duty to update.15Addressing Unmet Need in Predominant,Chronic Negative Symptoms of SchizophreniaTopline results from ADVANCE-2 Phase 3 study of pimavanserin expected 1Q24Completed one positive pivotal study,ADVANCE-1ADVANCE-2 leverages optimal therapeutic

35、 dose of 34 mg 6-month study designed to evaluate impact on persistent negative symptoms beyond acute psychosis periodDesigned to treat patients whose positive psychotic symptoms are adequately controlled,but still suffer from predominant and uncontrolled negative symptoms,inhibiting their ability t

36、o live a normal,productive lifeACP-101 for the Treatment of Prader-Willi Syndrome(PWS)17Prader-Willi Syndrome OpportunityRare and complex neurobehavioral genetic disorder that often leads to social isolationHyperphagia is a defining characteristic of PWS and commonly begins between the ages of 3-8Hy

37、perphagia is characterized by unrelenting hunger Often leads to obesity and behavioral challenges including anxiety and aggression Extremely distressing for patients,parents and caregivers30 years average life expectancy1 1Causes of Death in Prader-Willi Syndrome:Prader-Willi Syndrome Association(US

38、A)40-Year Mortality Survey.Genet Med.2017 June;19(6):635642.Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.Significant Unmet Need 8,000-10,000 patients in the

39、U.S.No FDA approved medicine to treat hyperphagia in PWSProvided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.18Initiated Phase 3 Study of ACP-101 forthe Treatment of

40、 Hyperphagia in PWSPhase 3 Study Design Primary Endpoint:Change in HQ-CTScreening VisitCarbetocin3.2 mgPlaceboDouble-blind Treatment Period12 WeeksSame primary endpoint as previousPhase 3 studyTrial builds on previousPhase 3 clinical trial experience 3.2 mg dose was observed to significantly reduce

41、hyperphagia-related behaviorsACP-204 for the Treatment of Alzheimers Disease Psychosis(ADP)Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.20ACP-204 in ADPTarge

42、t Product ProfilePhase 1 ResultsMitigate or eliminate QT prolongationNo sign of QT prolongationExplore doses higher than pimavanserin 34 mg equivalent Wide dose range established supporting potential for 2x pimavanserin 34 mg equivalentImproved time to onset of actionSteady state PK achieved in less

43、 than half the time of pimavanserinACP-204 is a next generation 5HT2A blocker that builds on the learnings of pimavanserin Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty

44、 to update.21Seamless EnrollmentPhase 2N=318,double-blind,randomized 1:1:1Two Phase 3 StudiesEach study sized equivalent to Phase 2 double-blind,randomized 1:1:1ACP-204(60 mg)ACP-204(30 mg)PlaceboACP-204(60 mg)ACP-204(30 mg)PlaceboACP-204(60 mg)ACP-204(30 mg)PlaceboPhase 2/Phase 3 Program for the Tr

45、eatment of ADP6-weektreatment period6-weektreatment period6-weektreatment periodOur experience with pimavanserin supports seamless P2/P3 program1Based on mid-point of guidance ranges for 4Q23 sales of DAYBUE and FY23 sales of NUPLAZID provided on November 2,2023.2 Excluding one-time payment of$100 m

46、illion to Neuren to secure worldwide rights to trofinetide.NUPLAZID(pimavanserin)is only approved in the U.S.by the FDA for the treatment of hallucinations and delusions associated with Parkinsons disease psychosis.DAYBUE(trofinetide)is only approved in the U.S.by the FDA for the treatment of Rett s

47、yndrome in adults and pediatric patients two years of age and older.Provided January 9,2024 as part of an oral presentation and is qualified by such;contains forward-looking statements;actual results may vary materially;Acadia disclaims any duty to update.22Building On Our SuccessHeader text hereLau

48、nched second commercial drug,DAYBUE38%revenue growth from two commercial franchises,DAYBUE and NUPLAZID1Acquired worldwide rights to trofinetideCompleted enrollment in ADVANCE-2Reached cash flow positivity2Capitalize on successful DAYBUE launchStrong revenue streams from DAYBUE and NUPLAZID franchis

49、esGlobal expansion of trofinetide into Canada,Europe and JapanTopline results from ADVANCE-2 in 1Q24Sustainable and growing cash flow from operationsInitiated Phase 3 trial of ACP-101Potential new therapy for Prader-Willi syndrome2023 Recap2024 and BeyondInitiated seamless Phase 2/Phase 3 of ACP-204Potential new therapy for Alzheimers disease psychosis