Shire: Repositioned for Growth JP Morgan Healthcare Conference January 14, 2014

Flemming Ornskov, MD, MPH Chief Executive Officer

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THE “SAFE HARBOR” STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included in this announcement that are not historical facts are forward-looking statements. 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, that: • Shire’s products may not be a commercial success; • revenues from ADDERALL XR are subject to generic erosion; • the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payors in a timely manner for Shire's products may

impact future revenues and earnings; • Shire relies on a single source for manufacture of certain of its products and a disruption to the supply chain for those products may result in Shire being

unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis; • Shire uses third party manufacturers to manufacture many of its products and is reliant upon third party contractors for certain goods and services, and any

inability of these third party manufacturers to manufacture products, or any failure of these third party contractors to provide these goods and services, in each case in accordance with its respective contractual obligations, could adversely affect Shire’s ability to manage its manufacturing processes or to operate its business;

• the development, approval and manufacturing of Shire’s products is subject to extensive oversight by various regulatory agencies and regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;

• the actions of certain customers could affect Shire 's ability to sell or market products profitably and fluctuations in buying or distribution patterns by such customers could adversely impact Shire’s revenues, financial conditions or results of operations;

• investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire’s activities in the highly regulated markets in which it operates may result in the distraction of senior management, significant legal costs and the payment of substantial compensation or fines;

• adverse outcomes in legal matters and other disputes, including Shire’s ability to obtain, maintain, enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on Shire’s revenues, financial condition or results of operations;

• Shire’s proposed acquisition of ViroPharma may not be consummated due to the occurrence of an event, change or other circumstances that gives rise to the termination of the merger agreement;

• a governmental or regulatory approval required for the proposed acquisition of ViroPharma may not obtained, or may be obtained subject to conditions that are not anticipated, or another condition to the closing of the proposed acquisition may not be satisfied;

• ViroPharma may be unable to retain and hire key personnel and/or maintain its relationships with customers, suppliers and other business partners pending the consummation of the proposed acquisition by Shire, or ViroPharma’s business may be disrupted by the proposed acquisition, including increased costs and diversion of management time and resources;

• difficulties in integrating ViroPharma into Shire may lead to the combined company not being able to realize the expected operating efficiencies, cost savings, revenue enhancements, synergies or other benefits at the time anticipated or at all;

and other risks and uncertainties detailed from time to time in Shire’s filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K.

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Strategy Shift + Operational Discipline = Continued Growth

Strategy Shift

Operational Discipline

2013 Accomplishments

Focused on specialty areas where innovation still drives differentiation and value

Executed M&A in line with therapeutic area strategy

Kicked off corporate reset, “One Shire”, to simplify structure and reduce costs

Top-line growth delivered through improved execution

Drove customer centricity

Upgraded Non GAAP earnings guidance throughout the year

2014 Priorities

Further refine therapeutic area strategy

Strengthen our portfolio organically and via M&A

Continued growth from in-line portfolio

Maintain discipline to drive further operational leverage

Advance our pipeline

Integrate ViroPharma

Deliver strong cash generation and earnings

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Strategy shift drove four company-wide growth initiatives

• High unmet need • Prioritized investments

• One structure • One purpose

• Lean, scalable base • Efficient allocation of resources

• Patient centric • Performance based

Shire

PROFITABILITY

PORTFOLIO ONE SHIRE

CULTURE

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Strategy shift executed via our In-Line and Pipeline Teams

Drive optimum performance from our

currently marketed products

In-line Pipeline

Build our future assets through both R&D and Business Development

• Increase sales for rare disease treatments through geographic expansion, patient identification and increase awareness through medical education

• Execute on market expansion initiatives (e.g., Neuroscience)

• Optimize the sales performance of GI and Internal Medicine products

• Continuously assess to leverage strengths • Developing promising pipeline • M&A to expand pipeline and on-market

presence (e.g., ViroPharma immediately enhances revenues & earnings)

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Strategy shift drove R&D re-prioritization and significant savings

Current Therapeutic Areas

Research & Preclinical

Pre-Proof of Concept

Post-Proof of Concept

Registration / On-Market

Rare Disease

Neuroscience

Gastrointestinal

Ophthalmology

Hematology

Regenerative Medicine

High priority Medium priority Low priority

Further prioritization in 2014 to be driven by: • Progress of current pipeline • External project additions, including ViroPharma

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We replenished our portfolio in line with our strategic focus

Acquired first and only protein replacement therapy being investigated for Dystrophic Epidermolysis Bullosa (pre-clinical)

Acquired Dry Eye Disease asset (phase 3), which could provide the basis for a larger ophthalmology business

Acquired Retinopathy of Prematurity (ROP) asset (phase 2), providing entry point into neonatology

Announced deal adds significant scale to rare disease portfolio with on- market hereditary angioedema (HAE) product complementary to FIRAZYR®

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Operational excellence helped improve Vyvanse Rx growth

• Attention-Deficit/Hyperactivity Disorder (ADHD) currently affects about 9.5% of US school-age children*

• The worldwide ADHD market is > $8 billion per year

• Vyvanse has 16.9% US market share (IMS monthly November 2013) • US share growth from July is 0.8% (IMS monthly), 0.2% points greater than the same

period in 2012. December IMS weekly data indicates share momentum continues

• Opportunities for continued growth in ex-US markets such as Europe, Canada, LATAM and Australia

• Positive top-line results recently reported from two Phase 3 studies evaluating the efficacy and safety of Vyvanse versus placebo in adults with Binge Eating Disorder (BED)

• Shire plans to file an FDA submission for Vyvanse in the treatment of BED in adults (ages 18 to 55) by Q3 2014

• Major Depressive Disorder (MDD) Phase 3 head line data expected H1 2014

* 2011 National Survey of Children’s Health (NSCH) data (CDC website)

In line with overall market despite continued strong growth of IR formulations

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We also grew LIALDA® and FIRAZYR through greater commercial focus

• 36% Growth in Q3 2013 sales vs. prior year • ASACOL® manufacturing cessation in the US

provided opportunity • Favorable Managed Care formulary positioning • 5-ASA market leadership in the US and worldwide • Further, moderate share growth expected

• Estimated 7,000-8,000 US HAE sufferers • Only around half of sufferers currently treated • Average patient on FIRAZYR is treating 12 – 18

attacks per year • FIRAZYR has the leading market share in US of

HAE attacks treated acutely* • >1,500 patients in US have received FIRAZYR

commercial therapy to date

22.5%

28.2%

15%

20%

25%

30%

LIALDA – US TRx Market Share (Jun 2012 – Nov 2013)

Market Event

Edema attack

Source: US HAEA website http://www.haea.org/patients/what-is-hae/

*based on Shire’s market research

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Simplifying our structure

Resetting our cost base

Pipeline prioritization

Increasing cash generation enabling

continued M&A investment

Commercial excellence

High teens non GAAP EPS growth

Full year 2013 outlook

Strategy Shift + Operational Discipline = Strong Financial Results

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SARcode and Premacure acquisitions in line with strategic focus

• Phase 3 compound lifitegrast • Significant unmet need

• Less than 10% of patients on prescription therapy

• US dry eye disease market ~$1.5 billion in 2012

• First drug to meet pre-specified primary symptom endpoint in a Phase 3 clinical study

• We anticipate meeting with the FDA to discuss totality of our data

• IGF-1 protein replacement therapy • Rare condition retinopathy of

prematurity • Routinely screened for in babies

younger than 30 weeks gestation • Can result in ocular scarring and

blindness • ~30K-40K addressable patients

worldwide per year • Phase 2 studies ongoing with

headline data expected H1 2015

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Going forward, we are focused on integrating ViroPharma in line with our key success factors

5 key success factors: • Drive revenue from marketed

products

• Ensure uninterrupted supply

• Extract value from pipeline programs

• Leverage talent

• Realize cost and revenue synergies

Deal rationale • Adds CINRYZE® – a growing

product complementary to FIRAZYR

• Augments Shire’s strong growth profile

• Annual cost synergies of approximately $150m by 2015

• Immediately accretive to non GAAP EPS upon closing

• Anticipated to deliver ROIC in excess of weighted average cost of capital

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Expected to create a growing ~$2 billion Rare Disease business

Sales estimates based on 2013 consensus sales forecasts(1)

24%

17% 10%

23%

21%

28% 17%

10%

24%

On closing, CINRYZE will make an immediate and significant contribution to the

Rare Disease business…

… supported by a track record of significant growth

Cinryze US sales since launch ($m)

*ViroPharma has guided to North American sales of $395m - $405m for 2013

(1) Shire consensus sales forecasts: based on the most recent consensus sales estimates compiled by Consensus Forecast Ltd, as of the date of this release for the year ending December 31, 2013, available on Shire’s website CINRYZE sales forecasts: based on FactSet consensus for year ended December 31, 2013 (accessed 4 November 2013)

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Future growth will be driven by an innovative pipeline

INTUNIV (Japan) ADHD

LDX* (Japan) ADHD

LDX* MDD

LDX* BED

SHP611 MLD(1)

FIRAZYR (EU) ACE inhibitor-induced

AE(7)

SHP609 Hunter CNS(3)

SHP610 Sanfilippo A(4)

Phase 1 Phase 2 Phase 3 Registration

FIRAZYR (US) ACE inhibitor-induced AE(5)

SHP606 (Lifitegrast)

Dry eye disease

INTUNIV® (EU) ADHD

SHP613

Acute Vascular Repair

SHP555 (US) Chronic

Constipation(6)

Discovery and Preclinical

Discovery and preclinical assets focussed on rare

diseases SHP602

(Ferrokin) Iron overload

VPRIV (Japan) Gaucher

SHP607 (PREMIPLEX®) Prevention of ROP(2)

Notes * Lisdexamfetamine dimesylate, active ingredient in VYVANSE/ELVANSE. (1) SHP611 is currently in a Phase 1/2 clinical trial. (2) Retinopathy of prematurity (ROP) is a Rare Disease. (3) SHP609 has completed its Ph 1/2 clinical trial and preparation is underway for a Ph 3 trial. (4) SHP610 has completed its Ph 1/2 clinical trial and preparation is underway for a Ph 2b trial. (5) Phase 3 study expected to commence in Q4 2013. (6) Discussions are planned with the FDA to determine potential clinical development pathways. (7) Application for EU label change, based on an investigator sponsored trial was filed in December 2012.

Changes since Q3 2013 results: • XAGRID and VPRIV have been filed in Japan

XAGRID® (Japan) Essential

Thrombocythaemia

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We expect to have more to share in 2014 as this pipeline reads out

2014

VYVANSE Head to Head versus Concerta Phase 4 data

INTUNIV EU Phase 3 head line data

FIRAZYR (EU) ACE inhibitor-induced AE approval(1)

SHP607 ROP Phase 2 head line data

SHP613 AVF Phase 2 head line data

Registration and Phase 4 Phase 3 Phase 2

SHP602 Phase 2b iron overload head line data study 203

2015

LDX MDD Phase 3 head line data

(1) Application for EU label change, based on an investigator sponsored trial was, filed in December 2012.

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In 2014, we remain confident in delivering Non GAAP EPS in line with the November 2013 consensus forecast(1) for the year 2014 (which excluded ViroPharma)

Lean and scalable Infrastructure

Capturing additional savings

Pipeline prioritization

Continued earnings growth

Increasing cash generation enabling investment in future

growth

(1) Based on the 2014 consensus estimates compiled by Consensus Forecast Ltd, posted on Shire.com on November 11, 2013, of $8.54 Non GAAP diluted earnings per ADS for the year ended December 31, 2014, included on Shire’s website (http://www.shire.com/shireplc/en/investors/forecasts).

Driving growth through greater commercial focus

Shire will update its 2014 Guidance during the Q4 2013 earnings call on February 13, 2014. During this call Shire will also outline the accretive benefits of the ViroPharma acquisition, if the deal has closed at that point.

Q&A breakout – Borgia Room 100

Investor relations contacts

Europe: Sarah Elton-Farr Souheil Salah T: +44 1256 894157 T: +44 1256 894160 E: seltonfarr@shire.com E: ssalah@shire.com

North America: Eric Rojas T: +1 781 482 0999 E: erojas@shire.com