Cowen Healthcare Conference Shire plc March 8, 2011 Sylvie Grgoire - - PowerPoint PPT Presentation

Our purpose

We enable people with life-altering conditions to lead better lives

Cowen Healthcare Conference

Shire plc March 8, 2011

Sylvie Grégoire President, Human Genetic Therapies

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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, Shire’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 Shire’s Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure new products for commercialization and/or development; government regulation of Shire’s products; Shire’s ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on Shire’s products; Shire’s ability to register, maintain and enforce patents and other intellectual property rights relating to its products; Shire’s ability to obtain and maintain government and other third-party reimbursement for its products; and

• ther risks and uncertainties detailed from time to time in Shire’s filings with the

Securities and Exchange Commission.

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Agenda

• ADHD Business Update
• Business Model | Financial Performance
• Recent Highlights | Growth Drivers
• Insight into Orphan Diseases
• Q&A

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Shire’s Business Model Has Been the Key to Our Financial Growth

Growth Growth CAGR CAGR

Total revenues 235% 16% EBITDA 198% 15%

• Specialty biopharmaceutical

company with expanding global reach

• Treatment of symptomatic

diseases

• Operating leverage through

efficient commercial infrastructure

• Growth through licensing and

acquisition

• Focus on projects with

relatively low risk and strong IP protection Financial Impact 2003-2010 Business Model

Note: data covers timeframe of 1/1/2003 through 12/31/2010

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Strong top-line and EPS growth in 2010

2009 2010

Product Sales Royalties and Other Revenues $2.7 billion $3.1 billion Total revenues $3.5 billion Total revenues $3.0 billion

Total revenues 15% to $3.5 billion Product sales 16% to $3.1 billion Non GAAP Earnings per ADS 21% to $4.23 Financial results support our aspirational target of mid-teens growth

15%

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Recent Highlights

Self-administration label for the treatment of acute HAE attacks approved by the European Commission  Complete response filed with the FDA  Positive efficacy and safety US Phase 3 results included  Approved by FDA as adjunctive therapy to stimulants for the treatment of ADHD in children and adolescents

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Drivers for Future Growth

Launching new products and new indications Advancing the pipeline Investing in biologic manufacturing and global operations

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• Brazil; Adolescent launch

(US & Canada); Adult launch in Canada

• File MAA in Europe
• Continue development of new uses
• Progress EU Phase 3
• Brazil; Adolescent launch

(US & Canada); Adult launch in Canada

• File MAA in Europe
• Continue development of new uses
• Progress EU Phase 3

Launching new products and new indications Launching new products and new indications

• US launch*
• Maintenance indication*
• Continue European launches
• US launch*
• Maintenance indication*
• Continue European launches

*Pending regulatory approval

Drivers for Future Growth

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• SPD 535 - Platelet reduction
• Guanfacine Carrier Wave
• Movetis programs
• HGT IT programs – Hunter CNS,

Sanfilippo A, MLD

• HGT 4510 - DMD
• SPD 535 - Platelet reduction
• Guanfacine Carrier Wave
• Movetis programs
• HGT IT programs – Hunter CNS,

Sanfilippo A, MLD

• HGT 4510 - DMD

Advancing the pipeline Advancing the pipeline Investing in biologic manufacturing and global

• perations

Investing in biologic manufacturing and global

• perations

Drivers for Future Growth

Continue build-out of EU hub in Switzerland Complete REPLAGAL and VPRIV submissions for new plant approval

Our purpose

We enable people with life-altering conditions to lead better lives

Insight Into Orphan Diseases

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Past year completes series of transformational events for Shire’s rare disease business

VPRIV US/EU Launch REPLAGAL market leader in Fabry Acceleron deal VPRIV acceleration and early access LTP-300 Roller Bottle Facility completed Santaris (LNA) collaboration Jerini Acquisition, HAE EU market Lexington Campus, Atlas facility Metazym acquisition Amicus deal

HGT Profitability

Market Expansion Hunter US/ EMEA/LatAm markets Fabry Ex-US market

2005 2006 2007 2008 2009 2010 HGT has transformed into a global business with leading marketed products and a focused pipeline

2010 Rev $909M

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• Rare diseases with

unmet need

• High impact Rx /

high margin products

• Global development/

commercialization

• 4 Marketed products
• 4 potential new

product launches by 2017

• Multiple platform

technologies (incl. Santaris LNA)

• #1 or #2 in our markets
• Pipeline growth via

internal Research and Business Development to drive sales growth

• Strong RoW growth with

minimal infrastructure PATIENT-CENTRIC BUSINESS MODEL PORTFOLIO STRENGTH FUTURE GROWTH

Shire HGT Business Model Supports Strong Growth

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Adding to the Portfolio through Internal Research Engine: Three Technology Horizons - Core, Emerging, Future

Lysosomal Storage Diseases

• Enzyme Replacement Therapy
• Optimized Protein Production

Extend Core Capabilities CNS Lysosomal Storage Diseases

• Enzyme Replacement Therapy
• Intrathecal Delivery
• Optimized protein production

Build New Capability Orphan Diseases

• Novel Disease Space
• Novel Therapeutic Modalities
• Novel Delivery Technologies
• Patient-Centric Focus

Build The Future

• Hunter Syndrome
• Fabry Disease
• Gaucher Disease

CNS Platform

• Hunter CNS
• Sanfilippo A
• Metachromatic

Leukodystrophy Internal R&D External Collaborations

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Prioritization Criteria

• Unmet Patient Need
• Prevalence
• Commercial Fit
• Scientific Validity
• Unmet Patient Need
• Competition
• Proof of Concept
• Development Feasibility
• IP/Exclusivity

>500 Genetic Disorders Disease Criteria Product Criteria New Programs for R&D or BD Augmenting the HGT Portfolio through R&D and Business Development

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Disease Prevalence

• 10,000

20,000 30,000 40,000 50,000 60,000 DMD HAE Gaucher Fabry Hunter MLD Sanfilippo Global Disease Prevalence

HGT Rare Diseases Range 2,000 to 50,000 Patients Globally Concentrated in Centers of Excellence

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HGT Portfolio Maintains Strategic Focus on Rare Diseases

Product Animal POC Preclinical IND Tox Phase I/II Phase II/III Commercial Launch

2001 2006 2008 2010 Research

Expand pipeline through internal research capability

HGT 1410

Sanfilippo ERT

HGT 1110

MLD ERT IT

Growth Drivers

Retention and additional switch (ex-US) Revenue growth from ROW US approval, Self-Administration, Global launches Retention and additional switches, continued global launches Ph II/III Proof of Concept in DMD Differentiation within the sector Novel technology: ERT's delivered into CNS

HGT 4510 (ACE 031)

DMD

HGT 2310

Hunter CNS

Replagal

Fabry disease

Elaprase

Hunter syndrome

Firazyr

HAE

VPRIV

Gaucher disease

IV ERT AE Peptide SC Protein IT Platform Research

Our purpose

We enable people with life-altering conditions to lead better lives

ADHD Business Update and VYVANSE New Uses

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EU Only

“School Day Control”

Children and adolescent patients that:

• Can’t or won’t take a stimulant
• Sub-optimal responders to their

current stimulant treatment

Shire ADHD

Equasym Vyvanse Intuniv Global ADHD Portfolio

US ADHD market TRx volume grew 12.2% in 2010

For the majority of children, adolescent and adult ADHD patients based on efficacy and duration of symptom control

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• NEW adolescent indication for VYVANSE
• Increase recognition of the importance of inattentive

symptoms with HCPs in adolescent & young adult patients

• Establish VYVANSE as a preferred treatment option within
• ur target audience for adolescents and adults with ADHD

VYVANSE Priorities

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INTUNIV Near Term Drivers of Growth

• Continued acceptance and uptake of monotherapy indication
• New indication for adjunctive therapy to stimulants
• Fastest growing segment of non-stimulant market
• Significant off-label use of unapproved products (clonidine,

atypical antidepressants, SSRI) as adjunctive therapy

• Direct To Mom (DTM) Television
• March Launch – monotherapy
• Q3 - adjunctive therapy

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(5)

Mood Cognition Wakefulness Reward-Impulsivity

Dopamine-dependent symptoms

Kessler 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.

Dopamine dysregulation implicated in many neuropsychiatric disorders

Schizophrenia

ADHD Major Depression Excessive Daytime Sleepiness Bipolar Disorder Binge Eating Disorder

VYVANSE should only be used to treat ADHD

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Solid foundation for future growth

Sustaining growth in a challenging macroeconomic environment Sustaining growth in a challenging macroeconomic environment Continuing to build our global presence Continuing to build our global presence Meeting the needs of patients and families with innovative, truly valued products Meeting the needs of patients and families with innovative, truly valued products

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Our purpose

We enable people with life-altering conditions to lead better lives

Questions and Answers

Our purpose

We enable people with life-altering conditions to lead better lives

APPENDIX

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Replenishing our pipeline

SPD 535

Platelet Reducing

Carrier Wave for Pain VYVANSE (EU) ADHD SPD 557 (M0003) GERD VYVANSE MDD Guanfacine Carrier Wave

ADHD

LIALDA (US)

Maintenance of Remission

HGT 1410 Sanfilippo A VYVANSE EDS HGT 2310 Hunter CNS VYVANSE

Negative symptoms and cognitive impairment in schizophrenia

FIRAZYR (US) HAE SPD 556 (M0002) Ascites HGT 4510 DMD HGT 1110 MLD Phase 1 Preclinical and earlier Phase 2 Phase 3 Registration LIALDA

Diverticular Disease

INTUNIV (EU)

ADHD

Undisclosed Programs VYVANSE

Other Non-ADHD uses

ADHD/CNS GI Hematology Pain ERT DMD Angioedema Early Research XAGRID (Japan)

Essential Thrombocythaemia

RESOLOR (EU)

Chronic Constipation (Males)

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+9% +9% 314 343 Royalties and other revenues +17% +16% 2,694 3,128 Product sales +48% 917 1,353 Cash generation (2) Like for Like Growth (1) Growth 2009 $m 2010 $m +21% $3.49 $4.23 EPS - ADS (2) +21% +19% 982 1,165 EBITDA (2) +16% +15% 3,008 3,471 Total revenues

2010 Full Year performance summary

(1) ‘Like for Like Growth' excludes movements in exchange rates by applying 2009 exchange rates to 2010 results. (2) These are Non GAAP financial measures. See appendix for a list of items excluded from the US GAAP equivalent used to calculate these measures.

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• 2%
• 5%

45 <1%

• 1%

184 182 FOSRENOL Like for Like Growth(2) Growth 2010 $m Like for Like Growth(2) Growth 2009 $m 2010 $m +33% +30% 763 +35% +34% 2,067 2,767 CORE PRODUCT SALES

• 27%
• 29%

73

• 4%
• 5%

366 347 OTHER +59% +48% 3 +91% +82% 6 11 FIRAZYR n/a(3) n/a(3) 59 n/a(3) n/a(3) 3 143 VPRIV n/a(3) n/a(3) 43 n/a(3) n/a(3) 5 166 INTUNIV +3% +3% 60 +10% +10% 215 236 PENTASA +27% +27% 84 +24% +24% 236 293 LIALDA / MEZAVANT +88% +80% 109 +87% +81% 194 351 REPLAGAL +17% +13% 106 +16% +14% 353 404 ELAPRASE +25% +25% 181 +26% +26% 505 634 VYVANSE Fourth Quarter Financial Year

2010 Portfolio strength and diversity – Core product sales(1)

(1) Core product sales represent Shire’s product sales excluding ADDERALL XR. (2) 'Like for Like Growth' excludes movements in exchange rates by applying 2009 exchange rates to 2010 results. (3) INTUNIV was launched in the US in Q4 2009 (2009 sales $5.4m). In 2009 VPRIV generated sales from early access programs (2009 sales $2.5m).

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2010 Core product sales up $700m

Core products(2) growth 2010 +34% 2009 2010

• $233m

+$161m +$129m +$57m +$157m +$140m AXR(1)

(1) Product sales and royalties (2) Core product sales represent Shire’s product sales excluding ADDERALL XR.

$3,008m Total revenues $3,471m Total revenues INTUNIV VYVANSE LIALDA REPLAGAL VPRIV ELAPRASE Other +$4m Royalties (excluding AXR) &

• ther

revenues

• $3m

+$51m

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Operating leverage emerging – key financial ratios

86.5% 86.5% Gross margin(1) 25% 26% EBITDA(1) (2) 19% 19% R&D(1) Ratios: +10% +14% R&D(1) +25% +34% Core product sales

• 2%

+16% Product sales 42% 41% SG&A(1) % of product sales

• 3%

+13% SG&A(1) 2009 2010 Year on Year:

(1) These are Non GAAP financial measures. See appendix for a list of items excluded from the US GAAP equivalents used to calculate these measures. (2) Excluding royalties and other revenues

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Dynamics beyond 2010

• Movetis acquisition
• DAYTRANA divestment

ABSORBING THE IMPACT OF RECENT TRANSACTIONS

• Expanded operating margins
• Earnings growth
• Strong cash generation

DELIVERING FINANCIAL PERFORMANCE

• Progressing the pipeline
• Optimising the global reach of our products
• Infrastructure to sustain future growth

INVESTING IN FUTURE GROWTH

• Young growing portfolio
• Significant diversification of sources of growth

SUSTAINED PRODUCT SALES GROWTH

KEY ELEMENTS DRIVERS

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Good Earnings growth Reported EPS-ADS 22-24% tax rate cemented by Swiss operations

≈

Tax rate 10-13% growth R&D and SG&A

≈

Product gross margins Generic erosion (Total royalties & other revenue -10%) Royalties Growth continuing at 2010 rate Product sales

Direction versus FY 2010

Full year 2011 dynamics

Shire 2011 outlook

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Fourth Quarter Financial Year

• 36%

n/a

• 43%
• 73%
• 11%

Growth 74 13 8 14 39 2010 $m

• 13%

48 42 REMINYL +48% 68 100 ADDERALL XR +12% 293 328 Total Royalties +146% 13 32 Other

• 6%

164 154 3TC and ZEFFIX Growth 2009 $m 2010 $m

2010 Royalties

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Non GAAP net debt

499 550 Cash and cash equivalents 33 27 Restricted cash (1,100) (1,100) Convertible bonds (615) (531) Net debt (47) (8) Building finance obligation December, 31 2009

$m

December, 31 2010

$m

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• This presentation contains financial measures not prepared in accordance with US GAAP.
• These Non GAAP financial measures are used by Shire’s management to make operating

decisions because they facilitate internal comparisons of the Company’s performance to historical results and to competitors’ results. They should not be considered in isolation from, as substitutes for, or superior to financial measures prepared in accordance with US GAAP.

• The following items are excluded from these non-GAAP financial measures:

Amortization and asset impairments:

• Intangible asset amortization and impairment charges; and
• Other than temporary impairment of investments.

Acquisitions and integration activities:

• Upfront payments and milestones in respect of in-licensed and acquired products;
• Costs associated with acquisitions, including transaction costs, fair value adjustments on contingent

consideration and acquired inventory;

• Costs associated with the integration of companies; and
• Non-controlling interest in consolidated variable interest entities.

Divestments, re-organizations and discontinued operations:

• Gains and losses on the sale of non-core assets;
• Costs associated with restructuring and re-organization activities;
• Termination costs; and
• Income / (losses) from discontinued operations.

Non GAAP measures