Jefferies Healthcare Conference June 2, 2015

Jefferies Healthcare Conference June 2, 2015 Creating the Next Generation of CNS Drugs Forward-Looking Statement This presentation contains forward-...
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Jefferies Healthcare Conference June 2, 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.

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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-HT2A 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

NUPLAZID™ (pimavanserin)

Parkinson’s Disease Psychosis Alzheimer’s Disease Psychosis

IND-TRACK

PHASE I

PHASE II

PHASE III

REGULATORY APPROVAL

COMMERCIALIZATION RIGHTS

ACADIA

Schizophrenia

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Adrenergic

Chronic Pain

Allergan

Muscarinic

Glaucoma

Allergan

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

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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.”

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NUPLAZID: Differentiation From Atypical Antipsychotics

5-HT2A

D2

H1



NUPLAZID™









Seroquel









Zyprexa









Risperidone









Clozapine









NUPLAZID’s selective, non-dopaminergic profile enables treatment of PDP without compromising motor control

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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

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SAPS-PD Improvement (LSM ± SE)

-020 Study: NUPLAZID Demonstrated Highly Significant Reduction in Psychosis SAPS-PD (Primary Endpoint)

0 -2 -4 -6

p = 0.037

Placebo

p = 0.001

40 mg NUPLAZID

-8 1

15

Study Day

29

43

CGI-I

-0.5

-1 Placebo 40 mg NUPLAZID

p = 0.022

-1.5 1

15

Study Day 9

p < 0.001

29

43

CGI-Improvement (LSM ± SE)

Change in CGI-Severity Score (LSM ± SE)

CGI-S 0

4

3.5

3

2.5 1

Placebo 40 mg NUPLAZID

p = 0.010

15

29

Study Day

p = 0.001

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-020 Study: NUPLAZID Improved Nighttime Sleep, Daytime Wakefulness and Reduced Caregiver Burden Daytime Wakefulness SCOPA Improvement (LSMSE)

0 -0.5 -1 -1.5 -2 p = 0.001

Placebo

-2.5

p = 0.045

40 mg NUPLAZID

-3 1

15

29

43

0.5 0 -0.5 -1 -1.5 -2 Placebo

-2.5 1

15

29

Study Day

Caregiver Burden

2 0 -2 -4 Placebo

p = 0.002

40 mg NUPLAZID

-6 1

10

p = 0.012

40 mg NUPLAZID

-3

Study Day Caregiver Burden Improvement (LSMSE)

SCOPA Improvement (LSMSE)

Nighttime Sleep 0.5

15

Study Day

29

43

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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

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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

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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.

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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



Commercial

Medicare Part D LIS

Medicaid

Payers responded favorably to NUPLAZID’s target product profile. Most valued attributes: – – – –

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Medicare Part D Standard

Reduction in psychotic symptoms Safety and tolerability profile No worsening of motor function Delaying institutionalization

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 around approval

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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 around 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

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PDP Disease Awareness Campaign

• Neurology journal and digital placements creating over 500,000 impressions • PDP educational website targeting physicians • Educational programs with experts • Strong presence at neurology/psychiatry medical meetings

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Pimavanserin Life Cycle Management PDP Provides Strategic Entry Into Other Indications Neurological

Parkinson’s Alzheimer’s Lewy Body Dementia

Psychiatric

Psychosis

Schizophrenia Depression Mania

Pimavanserin has the potential to be a transformative advancement in the treatment of psychosis 18

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

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Phase II ADP Trial (-019 Study): Design Phase II Efficacy, Tolerability and Safety Study Location

Nursing homes at Biomedical Research Centre for Mental Health, Kings College

Patients

Target enrollment of 200 ADP patients

Type of design

Randomized, double-blind, placebo-controlled

Key efficacy endpoints

NPI-NH, CMAI-SF, ADCS-CGIC

Patient Pathway From Screening to Treatment Period Screening

12-Week Blinded Treatment Period

BPST Run-In NPI-NH

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Baseline

40 mg PIM or PBO (1:1) 2-Week Visit

4-Week Visit

6-Week Key Endpoint

9-Week Visit

12-Week Cognitive Endpoint

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 —



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Phase II PoC demonstrated advantages of co-therapy

Potential use as stand-alone maintenance therapy to improve compliance

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

3.0

p = 0.007

p = 0.05 2.5

Weight Change (kg)

PANSS Improvement

25.0

20.0

15.0

10.0

1.5

1.0

5.0

0.5

0.0

0.0

RIS LD

PIM/RIS

Meltzer et al., Schizophrenia Research (2012)

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2.0

RIS HD

RIS LD

PIM/RIS

RIS HD

Corporate Information

Profile: • Based in San Diego • 130 employees

Financial: • Cash position at March 31, 2015(1): $298M (1) Reflects

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cash, cash equivalents and investment securities

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 24

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-HT2A 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 25

Creating the Next Generation of CNS Drugs

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