Corporate Presentation May 13, 2015 Creating the Next Generation of CNS Drugs
Forward-Looking Statement This 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 achievements expressed or implied by the 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 statements about (i) the plans for, including timing and progress of, clinical development, clinical trials and commercialization for our product candidates, including NUPLAZID (pimavanserin); (ii) the timing of any submission or application for, or receipt of, regulatory clearances and approvals, any potential approval of NUPLAZID as a first-in-class drug for PDP or potential approval for other indications; (iii) the benefits to be derived from and efficacy of our product candidates, including the clinical benefits of NUPLAZID, in PDP, ADP, schizophrenia or other neurological or psychiatric indications, the potential advantages of NUPLAZID versus existing antipsychotics, the potential for NUPLAZID to represent a new class of psychosis medicine, and the expansion opportunities for NUPLAZID; (iv) estimates regarding the prevalence of PD, PDP, ADP or schizophrenia; (v) the potential market for any of our product candidates, including NUPLAZID; and (vi) our estimates regarding our cash position or capital requirements. In some cases, you can identify forward-looking statements by terms such as may, will, should, could, 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 forward-looking statements. 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, 2014, as well as our subsequent filings with the SEC. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them for future events. 2
ACADIA: A CNS Focused Biopharmaceutical Company Building a leading U.S. specialty CNS franchise NUPLAZID (pimavanserin), a differentiated and potential new class of psychosis therapy Selective serotonin inverse agonist preferentially targeting 5-HT 2A receptors Potential to be first and only drug approved in U.S. for Parkinson s disease psychosis (PDP) NDA planned for 2H 2015 Demonstrated strong efficacy and favorable safety profile in Phase III PDP trial FDA granted Breakthrough Therapy designation in 2014 Opportunity for pimavanserin to expand into broad range of neurological and psychiatric indications Worldwide commercialization rights to NUPLAZID U.S. patents go into 2028 3
Pipeline COMPOUND/ PROGRAM INDICATION IND-TRACK PHASE I PHASE II PHASE III REGULATORY APPROVAL COMMERCIALIZATION RIGHTS NUPLAZID (pimavanserin) Parkinson s Disease Psychosis Alzheimer s Disease Psychosis ACADIA Schizophrenia Adrenergic Chronic Pain Allergan Muscarinic Glaucoma Allergan 4
Parkinson s Disease Psychosis An Unmet Medical Need Characterized by hallucinations and delusions Chronic disorder; worsens over time and severely impacts daily living Afflicts about 40% of the 1 million Parkinson s patients in the U.S. Leading cause of nursing home placement of Parkinson s patients No drug approved by FDA for PDP 5
Current Antipsychotics Not Approved for PDP and Increase Mortality and Morbidity Can counteract PD dopamine replacement therapy resulting in a worsening of motor symptoms Significant side effects are problematic for frail elderly population; sedation, stroke, hematological disorder, cardiovascular events, and cognitive impairment Not approved by the FDA for PDP Black box warning: Increased mortality in elderly patients with dementiarelated psychosis. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. 6
NUPLAZID: Differentiation From Atypical Antipsychotics 5-HT 2A D 2 H 1 NUPLAZID Seroquel Zyprexa Risperidone Clozapine NUPLAZID s selective, non-dopaminergic profile enables treatment of PDP without compromising motor control 7
NUPLAZID: Key Findings From Phase III -020 Study 6-week double blind placebo-controlled study in 199 PDP patients randomized to 40 mg of NUPLAZID or placebo (1:1) Highly significant and clinically meaningful improvement in psychosis Significant improvement on all additional efficacy measures: nighttime sleep, daytime wakefulness and caregiver burden Favorable safety and tolerability profile - no worsening of motor function Source: Cummings et al., Lancet (2014) 383 8
SAPS-PD Improvement (LSM ± SE) SAPS-PD Improvement -020 Study: NUPLAZID Demonstrated Highly Significant Reduction in Psychosis 0 SAPS-PD (primary endpoint) (ITT, N=185; change from baseline) -2-4 -6-8 Change from Baseline to Day 43 (LSM + SE) 0-1 -2-3 -4-5 -6-7 Placebo -2.73 40 mg PIM -5.79 1 15 29 43 Placebo Study Day p = 0.037 40 mg NUPLAZID p = 0.001 9
-020 Study: NUPLAZID Showed Highly Significant Efficacy as Assessed by Different Raters and Scales Endpoint Rater p-value* SAPS-PD SAPS H+D Centralized Independent Centralized Independent 0.001 0.001 CGI-I Investigator 0.001 CGI-S Investigator <0.001 *ITT, MMRM, OC 10
SCOPA Improvement (LSM SE) SCOPA Improvement (LSM SE) -020 Study: NUPLAZID Improved Nighttime Sleep and Daytime Wakefulness 0.5 Nighttime Sleep (ITT, N=185; change from baseline) 0.5 Daytime Wakefulness (ITT, N=185; change from baseline) 0 0-0.5-0.5-1 -1-1.5-1.5-2 p = 0.001 p = 0.045-2 -2.5-2.5-3 1 15 29 43 Study Day Placebo 40 mg NUPLAZID -3 p = 0.012 1 15 29 43 Study Day Placebo 40 mg NUPLAZID 11
Caregiver Burden Improvement (LSM SE) -020 Study: NUPLAZID Reduced Caregiver Burden 2 Caregiver Burden (ITT, N=185; change from baseline) 1 0-1 -2-3 -4-5 -6 p = 0.002 1 15 Study Day 29 43 Placebo 40 mg NUPLAZID 12
NUPLAZID PDP Program Open-Label Safety Extension Studies ~800 patient years of exposure in PDP > 250 patients treated 1 year > 100 patients treated 2 years Longest patient exposure > 9 years Favorable long-term safety and tolerability profile observed to date in fragile, elderly patients Differentiation from off-label use of antipsychotics 13
Parkinson s Disease Psychosis Patient Profile Average age around 74 years Around 60/40 split between men and women Over 70% suffer comorbid sleep disturbances Almost 90% have caregiver support with 74% requiring daily care Source: Based on ACADIA market research with over 800 PDP-treating physicians and over 700 PDP patient chart audits 14
Parkinson s Disease Psychosis ACADIA Market Research Treating physicians surveyed were dissatisfied with use of atypical antipsychotics for PDP patients: Safety and tolerability issues Black-box warning Impact on motor function Physicians top-ranked attributes for PDP product: Does not negatively impact motor symptoms Resolves psychosis fully Low incidence of side effects These top-ranked attributes compare favorably with the profile we have observed with NUPLAZID in the clinic Source: Based on ACADIA market research with over 800 PDP-treating physicians and over 700 PDP patient chart audits. 15
PDP: U.S. Payer Landscape ACADIA has conducted foundational access and reimbursement research with key decision makers for payers covering 168 million lives: Payer Landscape Medicare Part D Standard Commercial Medicare Part D LIS Medicaid Payers responded favorably to NUPLAZID s target product profile. Most valued attributes: Reduction in psychotic symptoms Safety and tolerability profile No worsening of motor function Delaying institutionalization 16
PDP-Treating Physicians Landscape 11,000 PDP-Treating Physicians: - Neurologists comprise the largest group - Psychiatrists - Long-term care physicians 135 Sales Reps will be hired at approval 17
Commercial Preparations for Planned Launch of NUPLAZID Executing on Plan Building out ACADIA commercial organization: Preparing commercial infrastructure and systems, including supply chain distribution Planning to hire 135 sales representatives at approval Completed extensive market research to understand: PDP market landscape Physicians current treatment behaviors, view of unmet medical need and prescribing patterns PDP patients and caregivers needs Conducted national and regional scientific advisory boards Launching PDP disease awareness campaign 18
Pimavanserin Life Cycle Management PDP Provides Strategic Entry Into Other Indications Neurological Psychiatric Parkinson s Alzheimer s Lewy Body Dementia Psychosis Schizophrenia Depression Mania Pimavanserin has the potential to be a transformative advancement in the treatment of psychosis 19
Alzheimer s Disease Psychosis (ADP) Neurology Expansion Opportunity for Pimavanserin ADP afflicts 25% to 50% of the 5.2 million Alzheimer s disease patients in U.S. No drug approved by FDA for ADP Current antipsychotics have black box warning for use in elderly demented patients MOA and safety profile of pimavanserin potentially attractive for ADP Development and regulatory synergies with PDP Phase II ADP trial ongoing 20
Phase II ADP Trial (-019 Study): Design Phase II Efficacy, Tolerability and Safety Study Location Patients Type of design Key efficacy endpoints Nursing homes at Biomedical Research Centre for Mental Health, Kings College Target enrollment of 200 ADP patients Randomized, double-blind, placebo-controlled NPI-NH, CMAI-SF, ADCS-CGIC Patient Pathway From Screening to Treatment Period Screening 12-Week Blinded Treatment Period BPST Run-In 40 mg PIM or PBO (1:1) NPI-NH Baseline 2-Week Visit 4-Week Visit 6-Week Key Endpoint 9-Week Visit 12-Week Cognitive Endpoint 21
Schizophrenia Psychiatric Expansion Opportunity for Pimavanserin A debilitating lifelong disease afflicting 1% of population Current therapies are sub-optimal Pimavanserin profile may allow for an improved schizophrenia therapy Phase II PoC demonstrated advantages of co-therapy Potential use as stand-alone maintenance therapy to improve compliance 22
PANSS Improvement Weight Change (kg) Pimavanserin Co-Therapy Phase II Schizophrenia Trial Pimavanserin co-therapy (PIM/RIS) demonstrated equivalent efficacy with less weight gain Change in Mean PANSS Score from Baseline Mean Change in Weight from Baseline 30.0 25.0 p = 0.007 3.0 2.5 p = 0.05 20.0 2.0 15.0 1.5 10.0 1.0 5.0 0.5 0.0 RIS LD PIM/RIS RIS HD 0.0 RIS LD PIM/RIS RIS HD Meltzer et al., Schizophrenia Research (2012) 23
Corporate Information Profile: Based in San Diego 130 employees Financial: Cash position at March 31, 2015 (1) : $298M (1) Reflects cash, cash equivalents and investment securities 24
ACADIA Key Priorities NUPLAZID - Parkinson s disease psychosis Submit NDA to FDA in 2H 15 Submit MAA to EMA around six to nine months following NDA submission Execute on commercial preparations for successful launch of NUPLAZID in U.S. Pimavanserin - Alzheimer s disease psychosis Complete enrollment in Phase II study around the end of the year Pimavanserin life cycle management Initiate Phase II study with pimavanserin in PD patients with sleep disturbances following NDA submission Initiate Phase II study with pimavanserin in patients with schizophrenia around the end of the year 25
ACADIA: A CNS Focused Biopharmaceutical Company Building a leading U.S. specialty CNS franchise NUPLAZID (pimavanserin), a differentiated and potential new class of psychosis therapy Selective serotonin inverse agonist preferentially targeting 5-HT 2A receptors Potential to be first and only drug approved in U.S. for Parkinson s disease psychosis (PDP) NDA planned for 2H 2015 Demonstrated strong efficacy and favorable safety profile in Phase III PDP trial FDA granted Breakthrough Therapy designation in 2014 Opportunity for pimavanserin to expand into broad range of neurological and psychiatric indications Worldwide commercialization rights to NUPLAZID U.S. patents go into 2028 26
Creating the Next Generation of CNS Drugs