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43rd Annual JP Morgan Healthcare Conference Catherine Owen Adams Chief Executive Officer January 14, 2025
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This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements other than statements of historical fact and can be identified by terms such as “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “outlook,” “potential” and similar expressions (including the negative thereof) intended to identify forward-looking statements. Forward-looking statements contained in this presentation, include, but are not limited to, statements about: (i) our business strategy, objectives and opportunities; (ii) plans for, including timing, development and progress of commercialization or regulatory timelines for, NUPLAZID, DAYBUE and our product candidates; (iii) benefits to be derived from and efficacy of our products, including the potential advantages of NUPLAZID and DAYBUE and expansion opportunities for NUPLAZID and DAYBUE in other indications, and for DAYBUE in jurisdictions outside the U.S. and Canada; (iv) estimates regarding the prevalence of the diseases targeted by our products and product candidates; (v) potential markets for any of our commercial products; and (vi) our estimates regarding our future financial performance, cash position, profitability or capital requirements. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. Such risks, uncertainties and other factors include, but are not limited to: our dependency on the continued successful commercialization of NUPLAZID and DAYBUE and our ability maintain or increase sales of NUPLAZID or DAYBUE; the costs of our commercialization plans and development programs, and the financial impact or revenues from any commercialization we undertake; our ability to obtain necessary regulatory approvals for our product candidates and, if and when approved, market acceptance of our products; our dependence on third-party collaborators, clinical research organizations, manufacturers, suppliers and distributors; the impact of competitive products and therapies; our ability to generate or obtain the necessary capital to fund our operations; our ability to grow, equip and train our specialized sales forces; our ability to manage the growth and complexity of our organization; our ability to maintain, protect and enhance our intellectual property; and our ability to continue to stay in compliance with applicable laws and regulations. Given the risks and uncertainties, you should not place undue reliance on these forward- looking statements. For a discussion of these and other risks, uncertainties 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, 2023 as well as our subsequent filings with the Securities and Exchange Commission from time to time, including our quarterly report on Form 10-Q for the period ended September 30, 2024. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them after this date, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Projections, assumptions and estimates of the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Forward-Looking Statements 2
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2025 expected to be first full year of $1 billion+ revenue Filing of DA YBUE MAAwith EMA with expected approval in Q1 2026 Anticipated timelines for last patient in and top line results for: ACP-101 Phase 3 study in Prader-Willi Syndrome ACP-204 Phase 2 study in Alzheimer's Disease Psychosis Plans to initiate a Phase 2 of ACP-204 in Lewy Body Dementia with Psychosis Plans to host first R&D day in company history in mid-2025 Announced Today 3 MAA: marketing authorization application EMA: European Medicines Agency
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2025-2026 Anticipated Milestones Corporate 2026 Q1 Q2 Q3 Q4 2025 Filed MAA with EMA Managed Access Programs available in select EU countries Phase 3 LAST PATIENT IN Phase 2 in LBDP FIRST PATIENT IN R&D Day (MID -2025) Annual Sales >$1B P otential Approval Q1 Q2 Q3 Q4 Expected Approval in EMA Two late-stage pipeline programs anticipated to have topline results in 2026 ACP-204 (ADP/LBDP) ACP-101 (PWS) 4 Phase 2 in ADP LAST PATIENT IN Phase 2 in ADP TOPLINE RESULTS Phase 3 TOPLINE RESULTS
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Neuro Psych Building Long Term Growth in CNS & Rare Disease Neuro Rare ADP ACP-204 (new 5-HT2A) Essential T remor ACP-711 (selective GABAA-α3 modulator) TRD/MDD/Other ACP-211 (NMDA receptor antagonist) PWS ACP-101 (Intranasal carbetocin) Rett/Fragile X ACP-2591 (cGP analogue) 5 LBDP ACP-204 (new 5-HT2A) PRECISION MEDICINE | DATA INNOVATION | GLOBALIZATION | PATIENT EMPOWERMENTPOWERED BY Core Franchise Core Pipeline Expansion Areas Expansion to other Rare Disease areas under evaluation Endocrine Metabolic Cardiovascular Immunology Nephrology
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Neuropsychiatric Franchise 6
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Disease Awareness Campaign 7
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Overview of Parkinson's Related Hallucinations and Delusions ~1M patients with Parkinson’s Disease (PD) in U.S. Around 50% may develop hallucinations and/or delusions at some point during course of their disease1 Low awareness Market research indicated that at the start of 2024 less than 10% of caregivers and patients were aware that hallucinations and delusions are associated with PD2 ~130,000 PD patients are treated with an atypical antipsychotic annually3 ▷ Seeing, hearing or experiencing things that others don’t ▷ Believing things that are not true SYMPTOMS 1 Elin B Forsaa, et al. A 12-year population-based study of psychosis in Parkinson disease Arch. Neurol.. 2010; Aug;67(8):996-1001 2 Source: Acadia confidential market research 3 Acadia estimate as of June 2024 based on claims data 8
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NUPLAZID for the Treatment of Parkinson's Related Hallucinations and Delusions NUPLAZID is the first and only FDA-approved drug for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. 9 CLINICALLY PROVEN Over 82,000 patients treated Most studied Rx in PD- Psychosis, with no negative impact on motor function or cognition1 GROWTH ACCELERATING ~10% YTD net sales growth Q1-Q3 in 2024 DTC campaign driving increased referrals in Q4 2024 OPPORTUNITY REMAINS ~20% share of 130,000 patients on atypical antipsychotics Composition of matter to Oct. 2030; formulation to Feb. 2038 ANTICIPATED >$325M IN INCREASING ANNUAL CASH FLOW FUELING CORPORATE GROWTH 1 J Wu et al, Global research trends and hotspots in Parkinson’s disease psychosis: a 25-year bibliometric and visual analysis, Frontiers in Aging Neuroscience, November 2024, DOI 10.3389/fnagi.2024.1480234
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NUPLAZID Commercial Strategy & Outlook Pull through interested consumers from branded DTC campaign Activate Consumers Further leverage real world evidence to drive prescriber decisions Drive Market Share Leverage AI and data to call on the right prescribers at the right time Maximize field force efficiency NUPLAZID 2025 OUTLOOK Accelerating sales growth Increasing market share Additional data publications Additional real world evidence out to 5 years 10
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DAYBUE 11
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~9,000 - 12,000 prevalent population in EU3 Overview of Rett Syndrome Debilitating Symptoms of Rett Syndrome1 ~5,500 - 5,800 diagnosed patients in U.S.2 with a prevalent population of ~6,000 - 9,000 ▷ Fine and gross motor impairment ▷ Loss of verbal and nonverbal communication ▷ Hand stereotypies ▷ Loss of independence and require 24/7 support ▷ GI symptoms including severe constipation ▷ Seizures T ypically caused by mutations in the MECP2 gene disrupting the function of MECP2 protein crucial for brain development and function 12 1 Acadia market research, Neul JL et al, Annal Neurol. 2010;68;944-50 and https://www.rettsyndrome.org/about- rett-syndrome/what-is-rett-syndrome/. 2 Based on Acadia Pharmaceuticals analysis of claims data as of 2024 claims data. 3 Based on Acadia internal estimates.
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DA YBUE is the first and only FDA-approved drug for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older. GROWING CLINCIAL EXPERIENCE Over 1,600 patients treated to date 66% of active patients have been on treatment ≥10 months FAVORABLE ACCESS ENVIRONMENT 90% of DAYBUE families pay <$10 per month EVOLVING PATIENT EXPERIENCE Management of common adverse events (diarrhea and vomiting) further informed by real world experience and engagement DAYBUE for the Treatment of Rett Syndrome 13 EMA FILING SUBMITTED AND EU MANAGED ACCESS PROGRAMS AVAILABLE IN 2025
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- ▷ Substantially increasing our field force and use of predictive analytics ▷ Launching branded Direct-to-Consumer campaigns ▷ Omni-channel strategy to bring DAYBUE clinical data to life 14 DAYBUE 2025 OUTLOOK Maintaining stable persistency Increasing new patient growth in the U.S. Initial revenues from Managed Access Programs in select EU countries Growing body of real world experience, including updated data from LOTUS study DAYBUE Commercial Strategy & Outlook Deepening clinical experience and increasing awareness Pursuing targeted filings and launches EUROPEAN UNION | Est 9,000-12,000 patientsUNITED STATES | Est 6,000-9,000 patients Building out EU launch team for potential Q1:2026 approval JAPAN | Est 1,000-2,000 patients PMDA discussions ongoing; study start anticipated by Q3:2025 CANADA | Est 600-900 patients Approval granted; first sales anticipated in Q3:2025
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Pipeline 15
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CNS/RARE DISEASE ACP-211 TRD/MDD/Other NMDA receptor antagonist ACP-271 Neurology GPR88 agonist PROGRAM INDICATION MECHANISM OF ACTION CNS NUPLAZID Parkinson's Disease Psychosis 5HT2A inverse agonist ACP-204 Alzheimer's Disease Psychosis New 5HT2A inverse agonist ACP-204 Lewy Body Dementia w/ Psychosis New 5HT2A inverse agonist ACP-711 Essential Tremor Selective GABAA-α3 modulator Deep and Diverse Pipeline Across CNS and Rare Disease DISCOVERY IND ENABLING PHASE 1 PHASE 2 PHASE 3 LAUNCHED 16 RARE DISEASE DAYBUE Rett Syndrome Analogue of GPE ACP-101 Hyperphagia in Prader-Willi Syndrome Intranasal Carbetocin ACP-2591 Rett Syndrome; Fragile X Syndrome cGP analogue STOKE ASO 1 Rett Syndrome Antisense oligonucleotide (ASO) STOKE ASO 2 SYNGAP1 Antisense oligonucleotide (ASO) STOKE ASO 3 Not disclosed Antisense oligonucleotide (ASO) + Multiple undisclosed discovery programs in CNS and rare disease NUPLAZID (pimavanserin) is only approved in the U.S. by the FDA for the treatment of hallucinations and delusions associated with Parkinson's disea se psychosis. DAYBUE (trofinetide) is only approved in the U.S. and Canada for the treatment of Rett syndrome in adults and pediatric patients two years of ag e and older.
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CNS/RARE DISEASE ACP-211 TRD/MDD/Other NMDA receptor antagonist ACP-271 Neurology GPR88 agonist PROGRAM INDICATION MECHANISM OF ACTION CNS NUPLAZID PDP 5HT2A ACP-204 Alzheimer's Disease Psychosis New 5HT2A inverse agonist ACP-204 Lewy Body Dementia w/ Psychosis New 5HT2A inverse agonist ACP-711 Essential Tremor Selective GABAA-α3 modulator Pipeline Program Spotlights DISCOVERY IND ENABLING PHASE 1 PHASE 2 PHASE 3 LAUNCHED 17 RARE DISEASE DAYBUE Rett Syndrome Analogue of GPE ACP-101 Hyperphagia in Prader-Willi Syndrome Intranasal Carbetocin ACP-2591 Rett Syndrome; Fragile X Syndrome cGP analogue STOKE ASO 1 Rett Syndrome Antisense oligonucleotide (ASO) STOKE ASO 2 SYNGAP1 Antisense oligonucleotide (ASO) STOKE ASO 3 Not disclosed Antisense oligonucleotide (ASO) + Multiple undisclosed discovery programs in CNS and rare disease
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ACP-101 in Prader-Willi Syndrome
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Prader-Willi Syndrome (PWS) Hyperphagia is a defining characteristic of PWS distinguished by unrelenting hunger due to impaired neural response to food intake and inability to regulate food intake in line with energy needs ~30 years average life expectancy1 with obesity and obesity-related complications leading to mortality 1 Causes of Death in Prader-Willi Syndrome: Prader-Willi Syndrome Association (USA) 40-Year Mortality Survey. Genet Med. 2017. June; 19(6): 635–642. 19 Affecting ~8,000 – 10,000 patients in the U.S . Rare genetic disorder caused by a deletion or mutation on chromosome 15 Typically diagnosed during infancy based on characteristic lack of muscle tone Complex neurobehavioral disease most often managed by pediatric endocrinologists
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ACP-101 Intranasal Carbetocin ACP-101 (carbetocin) is a long-acting analogue of human oxytocin Selectively binds to oxytocin receptors (more so than oxytocin itself) Intended to overcome the functional deficit in oxytocin receptor agonism in Prader Willi Syndrome Drug-device combination product for intranasal administration 20
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COMPASS-PWS Phase 3 Study Trial design builds on previous Phase 3 clinical trial experience 3.2 mg dose was observed to reduce hyperphagia-related behaviors PHASE 3 STUDY DESIGN ACP-101 (Intranasal carbetocin) 3.2 mg Placebo Screening Visit Double-blind 12 Weeks ~170 Subjects Primary Endpoint: Change in HQ-CT1 Ages 5-30 1 Hyperphagia Questionnaire for Clinical Trials (HQ-CT) is an observer-reported outcome measure that has been widely used in interventional studies to assess changes in hyperphagia behaviors individuals with PWS. Global, placebo-controlled, double-blind Phase 3 enrolling 21 ▷ Q4:2025: COMPASS PWS last patient in expected ▷ Q1:2026: COMPASS PWS topline results expected ▷ Q4:2026: Potential approval Q1 Q2 Q3 Q4 2025 2026 Q1 Q2 Q3 Q4 Phase 3 LAST PATIENT IN P otential Approval Phase 3 TOPLINE RESULTS Phase 3 CONTINUED ENROLLMEN T
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ACP-204 Development Plans 22
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Alzheimer’s Disease Psychosis (ADP) Approximately 30% of patients with Alzheimer’s disease experience psychosis commonly consisting of hallucinations and delusions1. Affecting 800,000 to 850,00 Alzheimer's patients in U.S. currently treated with antipsychotics, antidepressants or mood stabilizers2. There are no approved treatments for hallucinations and delusions associated with Alzheimer’s disease psychosis. 1 Cummings J. et al. Criteria for Psychosis in Major and Mild Neurocognitive Disorders: International Psychogeriatric Associations (IPA) Consensus Clinical and Research Definition. Am J of Geriatric Psychiatry. 2020; 28 (12); 1256-1269 2 Based on Acadia internal estimates. 23
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ACP-204 Pimavanserin ACP-204 Builds Upon but is Structurally Distinct from Pimavanserin • >200 patients received ACP-204 in Phase 1 trials • lower hERG vs. pimavanserin; No signs of QT prolongation • Wide dose range established supporting potential for ~2x pimavanserin 34 mg equivalent • Steady state PK achieved in 5 days vs pimavanserin 12 days RESULTS TO DATE Planned publications throughout 2025 ACP-204 FEATURES A COMBINATION OF STRUCTURAL CHANGES VS PIMAVANSERIN, AND REDUCED OFF-TARGET EFFECTS ALONG WITH EQUAL OR INCREASED POTENCY Mitigate or eliminate QT prolongation Enable doses higher than pimavanserin 34 mg equivalent Improve time to onset of action 24 ACP-204 TARGET PRODUCT PROFILE
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RADIANT Phase 2 / Phase 3 Pimavanserin experience supports P2/P3 program Global, placebo-controlled, double-blind Phase 2 enrolling 25 ▷ Q1:2026: Phase 2 in ADP last patient in expected ▷ Mid-2026: Phase 2 in ADP topline results expected Q1 Q2 Q3 Q4 2025 2026 SEAMLESS ENROLLMENT PHASE 2 TWO PHASE 3 STUDIES N=318, double-blind, randomized 1:1:1 of similar size and design ACP-204 (60mg) Placebo 6-week treatment period ACP-204 (30mg) ACP-204 (60mg) Placebo 6-week treatment period ACP-204 (30mg) ACP-204 (60mg) Placebo 6-week treatment period ACP-204 (30mg) Primary Endpoint for Phase 2: SAPS-H+D total score change from baseline to Week 6 Q1 Q2 Q3 Q4 Phase 2 in ADP LAST PATIENT IN Phase 2 in ADP TOPLINE RESULTS Phase 2 in ADP CONTINU ED ENR OLLMEN T
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1 Simuni T, Chahine LM, Poston K, et al. A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. Lancet Neurol. 2024 Feb;23(2):178-190. doi: 10.1016/S1474-4422(23)00405-2. PMID: 38267190. 2 Cummings et al 2018. 3 Based on IQVIA data and Acadia internal estimates. LBD is a progressive brain disorder that affects thinking, movement, mood, and behavior Lewy Body Dementia (LBD) Associated with abnormal deposits of alpha-synuclein in the brain1 No therapies approved for LBD with psychosis and some traditional antipsychotics that are commonly used in other diseases can be harmful >1 million people in the U.S may be living with LBD; 50% -75% of people with LBD experience psychosis (LBDP)2 ▷ Approximately 200,000 patients living with LBD are being treated with antipsychotics 3 26
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Plan to Initiate Phase 2 Study in LBDP in Q3 2025 Phase 2 program will enroll both PDD and DLB patients with psychosis Relapse data from pimavanserin withdrawal study suggest potential utility of targeting 5HT2A % of patients experiencing relapse: • 5.3% (1 of 19) patients receiving pimavanserin • 55.0% (11 of 20) receiving placebo Alpha-synuclein and other biomarkers will be evaluated to characterize patient population 27 Parkinson’s Disease Dementia (PDD) Lewy Body Dementia with Psychosis (LBDP) Dementia with Lewy Bodies (DLB)
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ACP-711 for Essential Tremor 28
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Essential Tremor 1. https://www.mayoclinic.org/ 2. Gerbasi ME, Nambiar S, Reed S, et al. Front Neurol. 2022. doi: 10.3389/fneur.2022.891446. 3. Shanker V. BMJ. 2019. doi: 10.1136/bmj.l4485. 4. Louis ED, Ottman R. Tremor Other Hyperkinet Mov (N Y). 2014. doi: 10.7916/D8TT4P4B. Shaking or trembling movements of the hands (and beyond)1 Associated with physical and cognitive impairments, social avoidance, and other challenges that significantly impact patients' lives2-3 ~ 7 million people affected in the United States ~ 1 million currently receiving Rx4 ▷ Can be debilitating, with significant impact on quality of life2 Innovation needed only approved pharmaceutical treatment is more than 50 years old Aligns with Acadia’s customer–facing footprint and focus on movement disorder specialists/centers of excellence 29
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ACP-711 is a Natural Fit with Acadia’s Commitment to Innovation in CNS GABAA α3 subunit is expressed in key regions involved in essential tremor (cerebellar dentate, thalamus, and cortex)1-4 ACP-711 is a selective GABAA α3 positive allosteric modulator (PAM) with potential to treat ET 2025 activities planned to support Acadia’s desired Phase 2 trial Inclusion of elderly cohort in ongoing Phase 1 to inform future development, given importance of treating the whole patient population Phase 2 trial planned for 2026 30 Highly selective activity for alpha-3 subunit 1. Waldvogel HJ, Munkle M, van Roon-Mom W, et al. J Chem Neuroanat. 2017. doi: 10.1016/j.jchemneu.2017.04.006. 2. Sperk G, Kirchmair E, Bakker J, et al. J Comp Neurol. 2020. doi: 10.1002/cne.24910. 3. Stojanovic T, Capo I, Aronica E, et al. J Comp Neurol. 2016. doi: 10.1002/cne.23923. 4. Schaefer SM, Vives Rodriguez A, Louis ED. Expert Rev Neurother. 2018. doi: 10.1080/14737175.2018.1413353. % modulation relative to reference Log [SAN711] (M) High activity Low activity No activity
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In Closing 31
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LPI: Last Patient In Acadia Believes More is Possible Advancing breakthroughs in neuroscience and rare diseases to elevate life. Growing pipeline in CNS and rare disease with late-stage readouts expected in 2026 Hosting first-ever R&D Day in mid-2025 R&D 32 2025 expected to be first full year of $1 billion+ U.S. total revenues Strong growth for both brands; initial revenues from Managed Access Programs in select EU countries TWO GROWING BRANDS COMMERCIAL FINANCIAL Strong balance sheet with positive, growing cash flow to reinvest for growth LATE -STAGE PIPELINE ACP-101 (P3-PWS) LPI expected Q4:2025 ACP-204 (P2-ADP) LPI expected Q1:2026 PRECISION MEDICINE | DATA INNOVATION | GLOBALIZATION | PATIENT EMPOWERMENTPOWERED BY
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43rd Annual JP Morgan Healthcare Conference Catherine Owen Adams Chief Executive Officer January 14, 2025