Corporate Presentation - · PDF fileCorporate Presentation November 10, 2014 Creating the Next Generation of CNS Drugs . ... • Favorable safety profile provides clear differentiation

Corporate Presentation November 10, 2014

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 and clinical trials involving our product candidates, including NUPLAZID™ (pimavanserin); (ii) the timing of any application for, or receipt of, regulatory clearances and approvals, including any potential expedited path to approval, 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 or PDP; (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, 2013, 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

• Multiple product candidates targeting large commercial markets

• Seeking to establish a leading U.S. specialty neurology franchise

• NUPLAZID™ (pimavanserin) represents a potential new class of psychosis medicine

– Potential to be first drug approved in U.S. for Parkinson’s disease psychosis (PDP)

– Strong Phase III PDP efficacy with favorable safety profile

– Expedited path to NDA filing

– FDA Breakthrough Therapy designation

– Broad expansion opportunities in range of neurology and psychiatric indications

• Worldwide commercialization rights to NUPLAZID

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Compound/

Program Indication Preclinical IND-Track Phase I Phase II Phase III Commercialization Rights

NUPLAZID™

(pimavanserin)

Parkinson’s

Disease Psychosis

ACADIA Schizophrenia

Alzheimer’s Disease

Psychosis

Adrenergic Chronic Pain Allergan

Muscarinic Glaucoma Allergan

ER Chronic Pain, MS,

Parkinson’s

Disease ACADIA

Nurr-1 Parkinson’s

Disease ACADIA

Pipeline Multiple Product and Commercial Opportunities

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ACADIA’s Commercial Strategy for NUPLAZID

• Establish a leading U.S. specialty neurology franchise:

– Building U.S. specialty neurology sales force

– Positioning Parkinson’s disease psychosis as lead indication may provide strong entry into neurology market

– Expanding into other neurological indications, focusing initially on Alzheimer’s disease psychosis

• Pursuing opportunities in schizophrenia and other psychiatric indications

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Psychiatric Neurological

Psychosis Parkinson’s Alzheimer’s LBD, DAT

Schizophrenia Depression

Mania

PDP

NUPLAZID (pimavanserin) A Potential New Class of Psychosis Medicine

• Selective serotonin inverse agonist preferentially targeting 5-HT2A receptors

• NCE with broad IP position (U.S. patents into 2028)

• Phase III data demonstrated strong efficacy, favorable safety profile and additional benefits in Parkinson’s disease psychosis (PDP)

• Favorable safety profile provides clear differentiation from current antipsychotics

• Positioned as potential first-in-class drug for PDP

• Expedited path to NDA filing for PDP

• FDA Breakthrough Therapy designation

• Broad expansion opportunities in neurology/psychiatry indications – Alzheimer’s disease psychosis – Schizophrenia

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Parkinson’s Disease Psychosis An Unmet Medical Need

• Characterized by disturbing hallucinations and delusions

• Progressive and persistent disorder

• Leading cause of nursing home placement of Parkinson’s patients

• No FDA-approved drug for PDP

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• PD is second most common neurodegenerative disease – Affects 4-6 million people worldwide

– Incidence projected to increase with aging population

• PDP occurs in an estimated 40% of Parkinson’s patients

Parkinson’s Disease Psychosis Affects Millions of Patients

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2011 2015

United States 1,055,700 1,151,800

Europe 1,474,300 1,587,500

Japan 742,900 837,900

Expected Prevalence of Parkinson’s Disease

Cognos Study #4. Parkinson’s disease. Cognos, Decision Resources, Inc. Waltham, MA, USA. June 2006

Inadequate Current Standard of Care Existing Antipsychotics Are Unsuitable for PDP

• All existing antipsychotics have a dopaminergic action and are pharmacologically contra-indicated in PDP patients

• Still, antipsychotics are frequently used off-label to treat PDP – Low-dose Seroquel is sedating and not proven effective in PDP

– Low-dose clozapine has shown efficacy, but is not safe

– All antipsychotics have side-effects related to off-target interactions

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

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5-HT2A D2 H1

NUPLAZID™ ― ― ―

Seroquel

Zyprexa

Risperidone ―

Clozapine

Pivotal Phase III PDP Trial (-020 Study): Key Results

• NUPLAZID demonstrated an ideal profile for PDP treatment:

– Highly significant improvement in psychosis on the 9-item SAPS-PD scale (p=0.001)

– Supported by highly significant improvement on CGI-I (p=0.001)

– Met the key secondary endpoint of motoric tolerability as measured by the UPDRS II+III scale

– Showed significant improvements on nighttime sleep, daytime wakefulness and caregiver burden

– Favorable safety and tolerability profile

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Cummings et al., Lancet (2014) 383

-020 Study: Design

Patient Pathway From Screening to Open-Label Treatment

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6-Week Blinded Treatment Period Long-Term Open-Label(1)

40 mg PIM or PBO (1:1)

40 mg PIM

Baseline SAPS-PD

2-Week Visit

4-Week Visit

6-Week Endpoint

BPST Run-In

Screening

NPI

(1) Patients who completed the 6-week treatment period of the -020 Study could roll over into a Phase III open label safety extension trial, the -015 Study, with investigator approval.

Pivotal Efficacy, Tolerability and Safety Study

Region North America

Patients 199, with moderate to severe PDP

Type of design Randomized, double-blind, placebo-controlled

Primary endpoint 9-item SAPS-PD; centralized ratings

Key secondary endpoint UPDRS Parts II and III

-8

-6

-4

-2

0

1 15 29 43

SAP

S-P

D Im

pro

vem

en

t (

LSM

± S

E)

Study Day

Placebo 40 mg PIM

p = 0.001

p = 0.037

-020 Study: NUPLAZID Demonstrated Highly Significant Reduction in Psychosis

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-2.73

-5.79

-7

-6

-5

-4

-3

-2

-1

0

Placebo 40 mg PIM

SAP

S-P

D I

mp

rove

me

nt

Change from Baseline to Day 43 (LSM + SE)

**

*

SAPS-PD (primary endpoint) (ITT, N=185; change from baseline)

-020 Study: NUPLAZID Showed Highly Significant Efficacy as Assessed by Different Raters and Scales

Endpoint Rater p-value*

SAPS-PD Centralized Independent

0.001

SAPS H+D Centralized Independent

0.001

CGI-I Investigator 0.001

CGI-S Investigator <0.001

*ITT, MMRM, OC

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-020 Study: NUPLAZID Showed Significant Efficacy as Assessed by All Supportive Measures

Measure LSM Treatment p-value*

SAPS-PD % Change -23.1% <0.001

SAPS H+D % Change -23.5% <0.001

SAPS H -2.08 0.003

SAPS D -1.16 0.033

CGI-I responder 23.3% 0.002**

* ITT, MMRM, OC **Chi-square test

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-020 Study: NUPLAZID Maintained Motor Control in PDP Patients

• NUPLAZID met key secondary endpoint for motoric tolerability

• Both arms showed improvements in combined UPDRS II+III score (-1.69 for PBO, -1.40 for PIM) – The treatment difference met the pre-specified criteria for

non-inferiority

• NUPLAZID conferred antipsychotic efficacy while maintaining motor control

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-020 Study: NUPLAZID Improved Nighttime Sleep and Daytime Wakefulness

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-3

-2.5

-2

-1.5

-1

-0.5

0

0.5

1 15 29 43

Study Day Placebo 40 mg PIM

p = 0.045 p = 0.001

-3

-2.5

-2

-1.5

-1

-0.5

0

0.5

1 15 29 43

Study Day

Placebo 40 mg PIM

p = 0.012

Daytime Wakefulness (ITT, N=185; change from baseline)

** *

*

Nighttime Sleep (ITT, N=185; change from baseline)

SCO

PA I

mp

rove

me

nt

(LSM

SE

)

SCO

PA I

mp

rove

me

nt

(LSM

SE

)

-020 Study: NUPLAZID Reduced Caregiver Burden

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-6

-5

-4

-3

-2

-1

0

1

2

1 15 29 43

Car

egi

ver

Bu

rde

n Im

pro

vem

en

t (L

SM

SE)

Study Day Placebo 40 mg PIM

p = 0.002 **

Caregiver Burden (ITT, N=185; change from baseline)

NUPLAZID in PDP 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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NUPLAZID – Positive FDA Interactions

• Two major positive FDA decisions:

– FDA has agreed that the pivotal Phase III -020 Study, together with supportive data from other studies, can serve as the basis for NDA filing

– FDA granted Breakthrough Therapy designation to NUPLAZID for PDP

• FDA decisions highlight PDP as a serious condition, reinforce significant unmet need, and further validate the importance of NUPLAZID PDP program

• Target NDA submission in 1st Quarter 2015

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Parkinson’s Disease Psychosis Provides Strategic Entry Into Broader Neurology Market Opportunities

• PDP may be ideal lead specialty neurology indication

• PDP program can be readily leveraged for Alzheimer’s disease psychosis (ADP) development

• Other related expansion opportunities include LBD psychosis, MID psychosis, and psychosis in elderly patients with neurodegenerative diseases

• NUPLAZID may have the ideal profile for indications where existing antipsychotics are unsuitable

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*Charts reflect ACADIA internal estimate of market size.

• ADP afflicts 25% to 50% of the 5.2 million Alzheimer’s disease patients in U.S.

• No FDA-approved drug for ADP

• Current antipsychotics have black box warning for use in ADP

• MOA and safety profile of pimavanserin attractive for ADP

• Development and regulatory synergies with PDP

• Phase II ADP trial initiated in late 2013

Alzheimer’s Disease Psychosis (ADP) Neurology Expansion Opportunity for Pimavanserin

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Phase II ADP Trial (-019 Study): Design

Patient Pathway From Screening to Treatment Period

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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

12-Week Blinded Treatment Period

Baseline 4-Week Visit

6-Week Key Endpoint

12-Week Cognitive Endpoint

Screening

NPI-NH 2-Week Visit

BPST Run-In 40 mg PIM or PBO (1:1)

9-Week Visit

Pimavanserin as a Treatment for Schizophrenia

• 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

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0.0

5.0

10.0

15.0

20.0

25.0

30.0

PA

NS

S I

mp

rovem

en

t Pimavanserin Co-Therapy Phase II Schizophrenia Trial

Pimavanserin co-therapy (PIM/RIS) demonstrated equivalent efficacy with less weight gain

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Weig

ht

Ch

an

ge (

kg

)

Change in Mean PANSS Score from Baseline

Mean Change in Weight from Baseline

p = 0.05 p = 0.007

RIS LD PIM/RIS RIS HD RIS LD PIM/RIS RIS HD

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Meltzer et al., Schizophrenia Research (2012)

NUPLAZID (pimavanserin) Summary

• NCE with ideal clinical profile and broad commercial potential

• Positioned as potential first-in-class drug for PDP by Phase III data – Robust efficacy while maintaining motor control

– Favorable safety profile provides clear differentiation from current antipsychotics

• Expedited path to NDA filing

• FDA Breakthrough Therapy designation

• Life cycle program designed to broaden to other indications – ADP Phase II trial initiated in late 2013

– Planning for additional schizophrenia study

– Planning for additional label-enhancing studies

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Corporate Information

(1)Reflects cash, cash equivalents and investment securities.

Profile:

• Based in San Diego

• 85 employees

Financial:

• Cash position at September 30, 2014(1): $338M

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ACADIA Key Priorities

• Complete and submit NDA for NUPLAZID in PDP

• Continue commercial preparations for planned U.S. launch of NUPLAZID

• Execute on life-cycle management program for pimavanserin:

– Ongoing Phase II ADP trial

– Planning for additional indication expanding and label-enhancing studies

• Complete and submit MAA for NUPLAZID in Europe

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ACADIA A CNS Focused Biopharmaceutical Company

• Multiple product candidates targeting large commercial markets

• Seeking to establish a leading U.S. specialty neurology franchise

• NUPLAZID (pimavanserin) represents a potential new class of psychosis medicine

– Potential to be first drug approved in U.S. for Parkinson’s disease psychosis (PDP)

– Strong Phase III PDP efficacy with favorable safety profile

– Expedited path to NDA filing

– FDA Breakthrough Therapy designation

– Broad expansion opportunities in range of neurology and psychiatric indications

• Worldwide commercialization rights to NUPLAZID

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Creating the Next Generation of CNS Drugs