Cowen and Company 32nd Annual Healthcare...

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Our purpose We enable people with life-altering conditions to lead better lives. Cowen and Company 32 nd Annual Healthcare Conference Shire plc Dr. Jeffrey Jonas SVP, R&D, Specialty Pharmaceuticals and Regenerative Medicine

Transcript of Cowen and Company 32nd Annual Healthcare...

Our purposeWe enable people with life-altering conditions to lead better lives.

Cowen and Company 32nd

Annual Healthcare Conference

Shire plc

Dr. Jeffrey JonasSVP, R&D, Specialty Pharmaceuticals and Regenerative Medicine

To be as brave as the people we help.

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THE “SAFE HARBOR”

STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company’s Specialty Pharmaceuticals, Human Genetic Therapies and Regenerative Medicine products, as well as the ability to secure new products

for commercialization and/or development; government regulation of the Company’s products; the Company’s ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company’s products; the Company’s ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company’s ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company’s filings with the Securities and Exchange Commission.

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Human Genetic Therapies (HGT)Orphan Diseases

Specialty Pharmaceuticals (SP)Attention Deficit Hyperactivity Disorder (ADHD) ,

Gastrointestinal (GI), Renal, Hematology

Advanced BioHealing

(ABH)Regenerative Medicine

Acquisition of ABH adds a strategic platform in Regenerative Medicine

Shire’s balanced product portfolio continues to drive good earnings growth

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KEY

PRODUCTS

LATE STAGE PIPELINE

EARLY STAGE PIPELINE

VALIDATING TECHNOLOGY PLATFORMS

RESOLOR

LIALDA

VYVANSE

ELAPRASE

REPLAGAL

VPRIV

INTUNIV

FIRAZYR

DERMA-

GRAFTREPLAGAL US

Investing to deliver growth now and into the future, supported by strong cash generation

LIALDA DVVYVANSE

MDD

Regen

Medassets

VYVANSEEx-US

Specialty PharmaVyvanse New Uses

CarrierwaveHematology

Movetis

assets

HGT Hunter CNSSanfilippo ASanfilippo B

DMDMLD

Emer

ging

Res

earc

h A

sset

s

INTUNIVEx-US

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8,467,008

6,987,453

0

1,000,000

2,000,000

3,000,000

4,000,000

5,000,000

6,000,000

7,000,000

8,000,000

9,000,000

TRx

Vyvanse

21.2% Growth

20102011

Source: IMS NPA Monthly

VYVANSE TRx

growth outpaced ADHD market growth (10.4%) in 2011

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VYVANSE ADHD Life Cycle Management Objectives

Differentiation

to help physicians and patients make better decisions about treatment while delivering value to payors

and policymakers

Evolution

to provide a stream of new information to support promotional efforts and strengthen positioning

Science

to advance understanding of the disorder

Globalization

to leverage our experience in the US as we prepare to launch in the EU

Our purposeWe enable people with life-altering conditions to lead better lives.

VYVANSE®

Maintenance Treatment in Adults with ADHD

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VYVANSE Adult Maintenance of Efficacy Study Overview

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More Than 90% of Patients Taking VYVANSE Continued to Maintain Symptom Control vs

25% of Patients Taking Placebo

Our purposeWe enable people with life-altering conditions to lead better lives.

VENVANSE®

(VYVANSE®) EUOverview of Study 325 Data

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VENVANSE (VYVANSE) EU

Filed in the EU Dec 2011

Opportunity to grow market and treatment rates

Ph 3 Study SPD489-325 (including methylphenidate as a reference arm) •

Double blinded placebo and active-controlled study in children and adolescents aged 6-17 with ADHD

Conducted at 48 sites across Europe; approximately 200 patients completed trial

Showed that Vyvanse demonstrated robust efficacy on all key endpoints •

Safety profile consistent with the known effects of amphetamine treatment and previous Vyvanse trials

Ph 3 Study 317 (including Strattera

comparator): ongoing

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-5.7

-18.7*-24*-30

-20

-10

0

10

20

30

40

50

Baseline Endpoint LS Mean Change From Baseline

AD

HD

-RS

Mea

n To

tal S

core

*P<0.001FAS=full analysis set (n=332)

Placebo SPD489

(VYVANSE EU)

Concerta

SPD489-325 Mean Change

from

Baseline

in

ADHD-RS-IV

Total

Score

Our purposeWe enable people with life-altering conditions to lead better lives.

Effectiveness of VYVANSE®

Compared to Concerta

in Adolescents With ADHD

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Strategic rationale for trial of VYVANSE versus Concerta

As a leader in ADHD therapy and research, Shire is committed to

expanding our knowledge about ADHD and its treatment. This, first-of-its-kind, head-to-head trial is an example of this commitment.

It is incumbent upon us to continue to demonstrate the clinical

value of our products in a data-driven manner that is backed by rigorous clinical science.

Based on our data from the 325 study where Concerta

was a reference arm, new trials have a good probability of differentiating VYVANSE from Concerta

in ways that will be clinically meaningful to patients, physicians, and payors

• Study design•

2 studies, 6-8 weeks, use of ADHD-RS-IV and CGI-I scales, multiple doses, US sites•

Approximately 1000 patients to be studied•

Completed by 2H 2013

Our purposeWe enable people with life-altering conditions to lead better lives.

VYVANSE®

New Uses Update

This communication describes investigational studies which evaluate the potential use of VYVANSE in treating non-ADHD conditions. These data are presented to inform the medical and financial communities about Shire development programs. No conclusions can be drawn regarding the safety or efficacy of VYVANSE in any of these other conditions without additional studies and review by regulatory authorities. VYVANSE is approved only for the treatment of Attention Deficit Hyperactivity Disorder. Shire does not recommend the use of its products in any way other than as described in the Prescribing Information.

Our purposeWe enable people with life-altering conditions to lead better lives.

VYVANSE®

New Uses Update

Investigation of dopamine-norepinephrine modulation in

Major Depressive Disorder (MDD)

Excessive Daytime Sleepiness (EDS)

Negative Symptoms in Schizophrenia (NSS)

Binge Eating Disorder (BED)

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17Kessler RC et al. Am J Psychiatry 2006;163:716-723; Atlfas

et al. BMC Psychiatry 2002;2:9; Hudson et al. Biol Psychiatry 2007;61:348-358; Ross et al. Schiz. Res 2006;88:90-

95; Wingo

et al. J Clin Psychiatry, 2007, 68:11:1776-1784; Walters et. al. J Clin Sleep Med, 2008, 4:6:591-600; Dunlop & Nemeroff Arch Gen Psych (2007); 64:327-37.

As VYVANSE impacts DA and NE transmission, therapeutic effects may be seen in symptomatic disorders involving these neural pathways

Dopamine Norepinephrine

MOOD

COGNITION

INTEREST

INHIBITION

ENERGY

MOTIVATION

WAKEFULNESS

ADHD

Major Depression

Excessive Daytime Sleepiness

Schizophrenia

Binge Eating

VYVANSE NEW USES

Dopamine (DA) and norepinephrine (NE) dysregulation is implicated in many neuropsychiatric disorders

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VYVANSE New Uses

Dopamine modulation in reward systems across CNS disorders

‘Reward’

thermostatmediates the internal response to

motivational stimuli

Motivational stimuli include food, water, drugs of abuse,

social interaction, emotional experience

Reward tone can be over and under set

(risk judgment, attention imbalance, anhedonia [joy], avolition [will])

Disordered dopamine tone in substance abuse, ADHD, depression, schizophrenia, eating disorders, modulating this tone may produce clinical benefit

Salamone JD et al. Curr Opin Pharm 2004: 5(1); 34-41; Bressan & Crippa. Acta Psych Scand 2005:111(s427);14-21; Martin-Soelch C. Biochem Soc Trans 2009:37;313-7; Volkow ND et al. JAMA 2010: 302(10);1084-91. Buckholtz JW et al. Nature Neurosci 2010:13; 419-21; Wang GJ et al. Obesity 2011;19:1601-8

DopamineDopaminetonetone

Dopamine chemically modulates the level of reward perceived

NORMAL

HighLow Rewardperception

Less reward

Our purposeWe enable people with life-altering conditions to lead better lives.

VYVANSE® Major Depressive Disorder

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VYVANSE NEW USES

Augmentation of first-line anti-depressants for inadequately responsive MDD

Placebo-controlled Phase 2 trial in ‘all comers’

showed clinically meaningful improvement in depressive symptoms (MADRS) and disability (SDS)

‘All comers’

reflects all patients, regardless of which residual symptoms are prominent (e.g., sadness, anxiety, energy, concentration)

Additional Phase 2 trial in MDD patients near or at remission

with persistent cognitive impairment using patient-centric approach

Approximately 20 to 30% of MDD patients have persistent cognitive problems despite improvement in core depressive symptoms

Exploring potential innovative pathway for development and pharmacoeconomic

benefit in targeted patients, given the disability associated with persistent cognitive impairment

Phase 3 program enrolling globally: 3 controlled, short-term trials and 1 open-label long-term trial

Enrollment ~ 24 months, Treatment: 4 to 12 months, depending on trial•

Final submission expected to include ~1,500 subjects

MADRS=Montgomery-Åsberg Depression Rating Scale; SDS=Sheehan Disability Scale; Iverson et al, J Aff Disord (2011); Hasselbalch et al, J Aff Disord (2010): 134 (1-2): 20-31.

Our purposeWe enable people with life-altering conditions to lead better lives.

VYVANSE® Negative Symptoms of Schizophrenia

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VYVANSE NEW USES (NSS)

Market Dynamics

Diagnosis rate = 95%

Treatment rate = 73%

Negative Symptoms = 65%

CAGR [2008-2018] of each rate = 1.04%

Prevalence of Schizophrenia

6,645,156

Prevalence of Schizophrenia

6,645,156 Diagnosed6,312,899

Diagnosed6,312,899 Treated

4,608,416Treated

4,608,416 Negative Symptom Patients

2,995,470

Negative Symptom Patients2,995,470

WHO report, global burden of Disease 2004 (2008), www.who.int, Decision Resources Schizophrenia Report 1/2010, Sartorius N, Schiz. Bulletin: 21-34,1974;Knapp et al., Schiz. Bulletin (30), 2, p279-293, 2004; Wu et al, J Clin

Psych 2005; Sources: Eurostatand

US Census, Commercial Insight: Antipsychotics, October 2009; Decision Resources Shire Estimates

3.0 million candidates for treatment (G7 in 2010)

Estimated Total Societal Cost (G7)

~ $120 Billion per year

Estimated Total Societal Cost (G7)

~ $120 Billion per year

Total Atypical Antipsychotic Market Value (2008)$18.2 Billion per year

Total Atypical Antipsychotic Market Value (2008)$18.2 Billion per year

Potential NSS Market Value

>$1 Billion

Potential NSS Market Value

>$1 Billion

Lifetime disability•

Multiple hospitalizations•

Dependence on public careMedication

Costs

No consensus of approved medication or medications for NSS

Schizophrenia presents substantial societal costs to offset (G7)

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VYVANSE NEW USES (NSS) –

study design

3 week screening

(no VYVANSE)10 week open label

( augmentation with VYVANSE of atypical antipsychotics)4 week double blind,

randomised discontinuation

Patients stable on atypical antipsychotic medication

Stability confirmed over three weeks

No depression (CDSS ≤

9)

No EPS

Mild positive symptoms

10 week open label VYVANSE augmentation of atypical antipsychotics

92 enrolled, 69 completed

Weekly BLINDED assessments

Optimised dose over 20 to 70 mg/d range

4 week double blind discontinuation

35 patients switched to placebo

34 patients continued VYVANSE

Weekly BLINDED assessments

Study 204: A blinded rater

open-label, double blind withdrawal design•

21 sites, mean age = 42, average dose = 52mg•

Entry into open label required SANS Total ≥

55, CDSS ≤

9, SAS Akinesia

<2, and PANSS Positive subscore

< 20

Efficacy Measurements•

Negative symptoms (1º

endpoint)•

Positive symptoms•

Psychiatric symptoms, depression-anxiety•

Global Clinical Assessments•

Cognitive functioning•

Real-world functioning

Safety Measurements•

Movement disorder symptoms•

Suicidal thinking•

Amphetamine cessation symptoms•

Sleep quality •

Vital Signs, Adverse Events•

Fasting laboratories, ECG

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VYVANSE NEW USES (NSS) -

Safety

No new issues in population expected to experience tolerability issues

Disposition•

All cause discontinuation: 25% in OL, 14% in DB (no group differences)•

Most common: ‘withdrawal by subject’

(12 –14%)•

Adverse event discontinuations: 5.4% in OL, 2.2% in DB

Treatment-emergent adverse events (≥

5%)•

Headache

14.1%•

Insomnia

10.9%•

Decreased Appetite

10.9% •

Dizziness

8.7%•

Dry Mouth

6.5% •

Diarrhea

5.4% •

Across both phases, ‘exacerbation of illness’

in 3.2% of subjects receiving Vyvanse and 1.1% of subjects receiving placebo

Vital Sign mean changes (Week 10)•

Systolic BP (mmHg)

2.6 Diastolic BP (mmHg) 2.5•

Pulse (bpm) 5.1 Weight (kg) -0.46 No clinically significant changes in laboratories or ECG measurements

Data Source SPD489-204: Tables 4.2.2.1; 4.2.2.3; 4.6.6.1; 4.7.2 15-Mar-2011; Shire data on file

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25Data Source SPD489-204: Tables 3.1.1.1, 3.1.2.4, 15-Mar-2011; Shire data on file

VYVANSE NEW USES (NSS) –

Clinical Effect on Negative Symptoms

Improvement in open-label, no rebound in randomized discontinuation

40

45

50

55

60

65

-3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 10 11 12 13 14Week

SANS-18TOTAL SCORE

ScreeningNo VYVANSE

OL Augmentationof Atypical Antipsychotics

DB RandomizedDiscontinuation

**VYVANSE n= 35

Placebo n= 34

Enrolled n= 92

Completed n= 69

Of Week 10 completers, 52.9% of subjects categorized as responders (≥

20% improvement from Week 0)

No significant difference between PBO and VYVANSE

at Week 14

Low

er R

efle

cts

Impr

ovem

ent

**p<0.0001 compared to baseline (LOCF)**p<0.0001 compared to baseline (LOCF)

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VYVANSE NEW USES (NSS) –

Clinical Effect on Positive Symptoms

Mean PANSS Total and subscale scores

Data Source SPD489-204: Tables 3.2.4.1 to 10, 15-Mar-2011; Shire data on file

10

15

20

25

30

35

40

-3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 10 11 12 13 14Week

**

**

PANSSSUB-

SCALESCORES

PANSS Negative Score mean (7-items)

PANSS Positive Score mean (7-items)

PANSS General Psychopathology Score mean (14-items)

VYVANSE n= 35

Placebo n= 34

VYVANSE n= 35

Placebo n= 34

VYVANSE n= 35

Placebo n= 34

10 11 12 13 14Week

Decrease in general (non-

psychotic) symptoms

Decrease in negative

symptoms

No increase in positive

symptoms

No significant difference between PBO and VYVANSE at Week 14

In the OL phase, mean PANSS Total Score decreased from 73.8 (Week 0) to 63.9 (Week 10), or

-9.8 points** (95% CI: -11.7 to -8.0)

Low

er R

efle

cts

Impr

ovem

ent

**p<0.0001 compared to baseline (LOCF)**p<0.0001 compared to baseline (LOCF)

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VYVANSE NEW USES

Summary and Next Steps for VYVANSE in NSS

Summary

Improvement with VYVANSE augmentation during OL-blinded rater phase; no worsening/rebound during short DB phase

Slow/little offset of activity over 4 weeks suggests conventional withdrawal designs may suffice

No new or unexpected safety findings across psychiatric (positive symptoms, anxiety, depression) and medical (laboratories, vital sign, ECG) parameters

Negative symptom improvements supported by collateral improvements in other clinical domains

Positive health authority and global thought leader response to current data set

Next Steps

Establish potential/parameters for biomarkers for response, including commercially viable diagnostic and maintenance tools

Given tolerability in previous trial (highest VYVANSE doses), exploring risk-benefit profile of a higher dose range prior to initiating Phase 3 to enable optimal clinical use

Potential to initiate Phase 3 by end 2012

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Indication Status

Excessive Daytime Sleepiness •

Completing health authority interactions regarding potential for comparative labeling to enable optimal commercial positioning

Binge Eating Disorder •

Phase 2 trial enrollment completed•

Expected data availability mid-year 2012

VYVANSE –

Other New Use Programs

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2012 Key newsflow

Lexington manufacturing plant US approval for VPRIVLexington manufacturing plant US approval for VPRIV

Potential REPLAGAL US approvalPotential REPLAGAL US approval

LIALDA diverticular

disease Phase 3 dataLIALDA diverticular

disease Phase 3 data

VYVANSE binge eating disorder Phase 2 dataVYVANSE binge eating disorder Phase 2 data

Potential DERMAGRAFT Canadian approvalPotential DERMAGRAFT Canadian approval

Potential VENVANSE EU approvalPotential VENVANSE EU approval

Sanfilippo A and Hunter Intrathecal

program updatesSanfilippo A and Hunter Intrathecal

program updates

Specialty Pharma Human Genetic Therapies Regenerative Medicine

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Consistent strategy continues to deliver

Balanced product portfolio expected to continue to deliver good earnings growth

Balanced product portfolio expected to continue to deliver good earnings growth

Delivering valuable and innovative treatments to meet the changing healthcare environment

Delivering valuable and innovative treatments to meet the changing healthcare environment

Investing in promising mid and late stage pipeline opportunities

Investing in promising mid and late stage pipeline opportunities

Our purposeWe enable people with life-altering conditions to lead better lives.

Questions and Answers Breakout Room –

Wellesley, 3rd

floor

Our purposeWe enable people with life-altering conditions to lead better lives.

Appendix

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Pipeline (at February 9, 2012)

SPD 535Platelet Reducing

VENVANSE (EU)

ADHD

SPD 557 (M0003)rGERD

VYVANSEMDD

Guanfacine

Carrier WaveDERMAGRAFT

(Canada) DFU

HGT 1410 Sanfilippo A(1)

HGT 2310Hunter CNS(1)

HGT 4510

DMD(2)

HGT 1110 MLD

Phase 1 Preclinical and Discovery Phase 2 Phase 3 Registration

XAGRID (Japan)

Essential Thrombocythaemia

LIALDA

Diverticular

Disease

INTUNIV (EU) ADHD

VYVANSE

NSS/EDS/BED

ADHD/CNSGIHematologyRegenerative Medicine

ERTDMDNew projectsProject advancement

INTUNIV (Canada) ADHD

REPLAGAL (US) Fabry Disease

HGT 3010 Sanfilippo B

RESOLOR (US)

Chronic Constipation (3)

Changes to the pipeline since third quarter 2011Progress•VENVANSE (EU) in ADHD moved from phase 3 to registrationAdditions •Addition of HGT 3010 Sanfilippo B in preclinical•RESOLOR US added post Shire’s acquisition of rights in the USDiscontinued•Carrier Wave for Pain –

phase 1•SPD 556 (M0002) Ascites

phase 2

Note(1)

HGT 1410 and HGT 2310 are currently in Phase 1/2 clinical trials(2)

Currently on clinical hold(3)

Phase 3 ready

Early Research

To be as brave as the people we help.

34Source: IMS NPA Monthly

2011 ADHD market growth primarily driven by Adults

27,499,681

25,689,195

25,553,271

22,642,946

10,000,000

20,000,000

30,000,000

40,000,000

50,000,000

60,000,000

TRx

2011 2010

Ped (6‐17) Adult (18+)

Ped7.6% Growth 

2011

Adult13.5% Growth 

2011

Overall ADHD Market Growth 10.4%