Cowen Healthcare Conference

Shire plc

Michael ColaPresident, Specialty Pharmaceuticals

2

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 affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of pharmaceutical research; product development including, but not limited to, the successful development of JUVISTA®(Human TGFβ3) and GA-GCB (velaglucerase alfa); manufacturing and commercialization including, but not limited to, the launch and establishment in the market of VYVANSE™(lisdexamfetamine dimesylate) (Attention Deficit and Hyperactivity Disorder (“ADHD”)); the impact of competitive products including, but not limited to, the impact of those on Shire’s ADHD franchise; patents including, but not limited to, legal challenges relating to Shire’s ADHD franchise; government regulation and approval including, but not limited to, the expected product approval date of INTUNIV™ (guanfacine extended release) (ADHD); Shire’s ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire plc’s filings with the Securities and Exchange Commission, particularly Shire plc’s Annual Report on Form 10-K for the year ended December 31, 2007.

3

Agenda

Introduction & Product Highlights

VYVANSE Update

Pipeline Review

Concluding Remarks

Q & A

4

Introduction Excellent performance in all areas of the business in 2007

Strong product sales reflecting good results and successful product launches across all areas of our business

Executing our strategy

6 launches in past two years: FOSRENOL, ELAPRASE, DAYTRANA, LIALDA, VYVANSE, DYNEPO

Strong track record of approvals or “approvables” in past four years

Robust intellectual property for key growth driving products

Rich pipeline with a focus on orphan drugs and specialist products treating symptomatic disorders

16+ potential launches from 2008-2015 (9 from new products)

Global expansion into new markets (South America, Russia, Mexico, Australia, Japan)

2008 revenue growth expected to be in the mid to high teens and positive revenue growth through 2010

5

0

5,000

10,000

15,000

20,000

25,000

Rx

Volu

me

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

NRx Volume TRx Volume TRx Share

NRx Volume 722 3,143 5,340 5,896 6,268 7,689 7,594 8,744 8,571 8,513 9,375 9,112

TRx Volume 725 3,427 7,020 9,258 11,583 14,452 15,429 18,575 19,201 20,595 22,685 22,361

TRx Share 0.3% 1.4% 2.7% 3.6% 4.4% 5.4% 6.3% 6.9% 7.5% 8.0% 8.6% 9.2%

March April May June July Aug Sept Oct Nov Dec Jan Feb

Source: IMS Monthly NPA February 2008

LIALDA’s launch continues with 9.2% national monthly TRx share in February 2008

• TRx Share in representative targeted geography ~12% versus ~6% in uncalled on geography (Source: IMS XPonent 2/22/08)

6

Lialda demonstrates strong launch performance, while Pentasa continues to hold share

Cumulatively Monthly TRx share change by product since Lialda launch

-8.0%

-6.0%

-4.0%

-2.0%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan-08

Feb

% S

hare

Cha

nge

Asacol Pentasa Total Balsalazide Lialda

Source: IMS Monthly NPA February 2008

Total Balsalazide includes Branded Colazal and Generic Balsalazide Disodium

9.2%

-6.8%

7

Best in Class Launch

$0

$10

$20

$30

$40

$50

$60

Q3 2006 Q4 2006 Q1 2007 Q2 2007 Q3 2007 Q4 2007Quarter

Elap

rase

Glo

bal S

ales

($M

)

• First & only enzyme replacement therapy for the treatment of Hunter syndrome

• Now approved in 39 countries

• Recent approval in Mexico marks first ELAPRASE approval in Latin America

• Additional geographic expansion planned in Latin America, Russia & Asia Pacific

VYVANSE – Launch Update

9

Introduction

Launch Progress

Adult Indication

Managed Care Update

10

Key attributes of VYVANSE support differentiation as a NCE

The first Pro-drug Stimulant

Consistent time to maximum concentration of d-amphetamine from patient to patient

Significant efficacy throughout the day, even at 6:00 PM

Adverse event profile that is mild to moderate in severity and incidence decreases over time

Significantly lower abuse related liking effect than an equivalent oral dose of d-amphetamine

5

11

Vyvanse Launch Performance

Over 1,000,000 prescriptions since launch

Topped 50,000 prescriptions for the first time in most recent 2 weeks

60% (25,000) of high volume physicians prescribing

Double industry norms for promotional campaign recall and recognition

* Projection based on daily prescription volume

0%

1%

2%

3%

4%

5%

6%

7%

6/22

6/29 7/67/13

7/20

7/27 8/38/10

8/17

8/24

8/31 9/79/14

9/21

9/28

10/5

10/12

10/19

10/2611

/211

/911/1

611

/2311

/3012/7

12/14

12/21

12/28 1/41/1

11/1

81/2

5 2/1 2/82/15

2/22

2/29 3/73/14

TRx

Shar

e

Labor Day

ThanksgivingChristmas/New Year’s

MLK

6.7%*

Spring Break

12

VYVANSE launch has been tracking in line with other blockbuster CNS drug launches

Source: IMS NPA

0

100,000

200,000

300,000

400,000

500,000

600,000

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Launch Month

TRx

Paxil Risperdal Zyprexa Seroquel Lunesta Strattera Vyvanse

13

Highest volume ADHD prescribers are adopting VYVANSE, and trickle down is occurring with lower level prescribers

Source: IMS

Vyvanse TRx Market Share Uptake Comparison

3.4%4.1%

4.8% 5.2% 5.6% 6.2%3.6%

4.7%5.8%

6.7% 7.2% 7.7%8.6%

4.5%5.8%

7.0%7.9%

8.6% 9.1%10.2%

0.1% 1.2%2.6%

0.1%

1.6%0.1%2.0%

0%

2%

4%

6%

8%

10%

12%

Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08Month

TRx M

arke

t Sha

re

All Top 43,000 Top 14,000

VYVANSE Adult Indication

15

The VYVANSE adult claim represents a significant opportunity for growth in 2008

VYVANSE Adult Indication:

Filed on June 29, 2007

PDUFA date is April 28, 2008

Commercial launch planned for Q2 2008

Strong effort to both physicians and consumers

Duration important for adult day

Lower abuse related liking effect compared to equivalent oral dose of d-amphetamine

New opportunity to grow the adult market

Efforts by all companies to expand adult market have been minimal since promotion of AXR was discontinued

No major consumer efforts in several years

* There has been no adult promotion to date

16

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

2003 2004 2005 2006 2007

6-12 13-17 18+

Current ADHD Market Growth is Primarily Driven by Adults

Source: Age Data - Verispan’s Vector One National; Annual Growth – IMS NPA

Tota

l Pre

scrip

tions

(000

)

Percent Market Growth by Age Segment

+20.4%+25.2%

+17.3%

+15.4%

+10.9%

+14.9%

+10.5%

+5.0%

-0.7%

+9.1%

-3.0%

-5.8%

+14.4%

+3.1%

+2.3%

+16.8% +6.1% +3.2% +5.7%Annual Growth: +17.3%

5-Year CAGR:

18+: 16.4%

13-17: 4.8%

6-12: 1.4%

17

Adults represent the largest and fastest growing segment of the ADHD market

% of total ADHD prescriptions by age category

Source: Verispan’s Vector One: MAT 12/07

36%41%

23%

Adult18+

Child0 – 12 yrs

Adolescent13 – 17 yrs

200736.3MM TRx

28%

46%

25%

200223.4MM TRx

Adult18+

Child0 – 12 yrs

Adolescent13 – 17 yrs

28%

23%

36%41%46%

25%

18

The adult ADHD market remains substantially underdeveloped

Popu

latio

n*N

= 29

6.6

MM

Patient Group by Age

% Prevalence** Drug Treated***

81%4.0MM

24%2.4MM

Total Patients

4.9MM

* US Census**Prevalence data calculated from data presented from Kessler, 2006 and CDC/NHIS *** Drug Treated=Number diagnosed * drug treatment rate

9.9MM

School Age (4-17)(24.3%)72 MM

Adults(75.6%)224 MM

6.9%

4.4%

Untreated

0.9MM

7.5MM

19

15%

17%

19%

21%

23%

25%

27%

Jan-04

Mar-04

May-04

Jul-0

4Sep

-04Nov-04Jan

-05Mar-

05May

-05Jul-0

5Sep-05Nov-05Jan

-06Mar-

06May

-06Jul-0

6Sep-06Nov-06

% S

hare

of A

dult

Tota

l Pre

scrip

tions

VYVANSE share in adults will increase with label change/promotion of the indication as did AXR

Source: Verispan Vector One

ADDERALL XR®

Adult Approval

20

Shire already holds the market lead by a wide margin among brands in Adult ADHD

Source: Verispan’s Vector One: National

Monthly Market Share

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07

Adderall XR Concerta Strattera Focalin XR

21

VYVANSE differentiation will increase with release of new clinical data in 2008

Other

2Q08Flexibility3 new dosage strengths

Mid 08Efficacy, Duration311 Classroom Analog

Mid 08Tolerability310 Dose Optimization

TimingParameters of Differentiation

Studies

Managed Care Update

23

VYVANSE Managed Care Coverage in 9 months exceeds 12 month goal!

ADDERALL XR has outstanding managed care formulary coverage

Our goal was to have VYVANSE achieve parity formulary status to AXR within 18 months of launch; 75% to this goal within 12 months

In total, VYVANSE will have ~80% parity formulary status to ADDERALL XR contracted lives by April 1

We have executed agreements with the top 6 managed care organizations

Lives Covered at Tier 2 (MM)

0

20

40

60

80

100

120

140

160

180

200

3Q07 4Q07 1Q08 April 1, 2008

Plan

Rep

orte

d Li

ves

24

DACON holding steady at 1.0, validating and reinforcing Duration message

DACON of ADDERALL XR started out immediately at launch at 1.2 has remained there for many years

DACON of VYVANSE was close to 1.0 at launch and has held steady at 1.0 after 6 months, validating the long duration of effect

Managed Care was skeptical at launch but now is impressed as DACON has held steady and they see this replicated in their own plan level data

0.6

0.8

1

1.2

1.4

1 2 3 4 5 6 7 8 9 10 11 12

Month Post-Launch

DACO

N

Adderall XR Vyvanse

25

Medicaid Coverage is good and has steadily improved since launch

July 31, 2007: 17% Open AccessSept 31, 2007: 38% Open AccessDec 31, 2007: 58% Open Access

RI

MA

CA

FL

NC

NJ34

VA

MS

MD

AL

SC

IN

LA

AZ

WA

WI

KY

OK

MN

CO

AR

PA

NYOR

KS

IA

NVNE

ME

SD

MTND

AK

WY

VT

ID

UTWV

HI

NMGA

IL

MI

MO

NH

TX

OH DE

CT

TN

DC

*Open Access based on % of ADHD Rxs in Medicaid; Note: AZ has varying access by plan

Source: IMS December 2007 ADHD TRx’s

Anticipated April 2008: 75% Open Access*

26

VYVANSE – Positioned for the long term

Outstanding IP protection to 2023 US / 2024 EU

Further investment

Phase IV research to strengthen product profile

Development of the adult market

Penetration into nascent Global markets

Opportunities beyond ADHD

Pipeline Review

28

R&D investment will drive growth

Focus on products for the specialist market and rare genetic diseases where there is low competitive intensity.

New indications and geographic expansion will maximize the return on our currently marketed products

Acquire products with relatively low technical risk of development in areas where we have expertise

Target the acquisition of companies in new areas that form the cornerstone of a new Business

29

Shire R&D portfolio is well-balanced with both short and long term opportunities for growth

Development Phase

ADHDHGT

Intuniv

VYVANSE – Adult-US

Registration

Daytrana - EU

Phase III

Lialda –Diverticulitis

Fosrenol CKD

VYVANSE - EU

Women’sHealth

DaytranaAdolescent

Velaglucerase

Phase II

Women’s Health

Juvista (SPD 538)

Larazotideacetate

(SPD 550)

Amigal

Plicera

AT2220

Phase I

Elaprase IT

Research-Preclinical

Sanfilippo ERT

MLD ERT

GI Renal Other

30

0

100

200

300

400

500

2005 2006 2007 2008

Spec PharmaHGT

R&D investment…

18%18%19%21%Shire Total

13%13%14%19%Spec Pharma

42%45%74%86%HGT

2008200720062005

R&

D In

vest

men

t ($M

)

R&D investment as a percentage of sales

31

Shire has one of the strongest mid to late-stage pipelines in its sector

20102007 20092008 2011-2015

DAYTRANA ADOLESCENT

VELAGLUCER-ASE ALFA

PLICERA

AMIGAL

AT2220

ELAPRASE IT

SANFILIPPO ERT

MLD ERT

VYVANSE EU

JUVISTA

LIALDA DIVERTICULITIS

SPD 550

WOMEN’S HEALTH PORTFOLIO

VYVANSE

DYNEPO

LIALDA / MEZAVANT

FOSRENOLEU

ELAPRASE EU

DAYTRANA EU

INTUNIV**

VYVANSE ADULT

FOSRENOL -CKD

*16+ potential launches from 2008-2015 - 9 from new products

*Subject to regulatory approvals**Approvable letter received

32

Concluding Remarks

Excellent 2007 results

Successful ongoing launches

Accelerating new product sales representing 23% of total sales for full year

2007 and 32% of total sales for Q4 2007

Successful positioning of VYVANSE for continued growth

Good progress in strengthening our pipeline by in-licensing rights to 5 biological and small molecule products

16+ potential launches 2008 - 2015

9 of which are new products

2008 revenue growth expected to be in the mid to high teens range and positive revenue growth through 2010

QUESTIONS AND ANSWERS

APPENDIX

35

Inc FAS123R Exc FAS123R

Revenue growth Mid to high teens

Vyvanse Product Sales $350 - $400m**

R&D $465 - $490m $450 - $475m

SG&A $1,125 - $1,165m $1,080 - $1,120m

Capex $320- $350m

Depreciation Growth ~50%

Non GAAP Tax Rate ~ 23%

Fully diluted share capital 590m

Interest - after tax add back $13m

* Non GAAP net income for 2008 will include FAS123R and will exclude : amortisation(1) , balance of gains on the sale of non-core products ($29m) and upfront payments & milestones in respect of in-licensed products.(1) Amortisation forecast: 25% growth vs 2007.** Assumes the adult indication is launched by mid year 2008.

2008 Non GAAP Guidance*

36

Duration of Patent and Regulatory Exclusivity

^ Currently difficult generic approval pathway for locally acting drugs*Orphan Drug** Regulatory Exclusivity in EU until 2017Revisions as of March 5, 2008

19

2000 2005 2010 2015 2020 2025

20232012

20122012DYNEPO

2013**2019ELAPRASE*

20182009FOSRENOL

20202010LIALDA^

VYVANSE

Patent Term Regulatory Exclusivity

20202011REPLAGAL*

37

Projected Patent^ and Regulatory Exclusivities*For Current Pipeline Products

2019

2021

2019

2018

2018

2010 2015 2020

AMIGAL 2

VELAGLUCERASE 1

ELAPRASE IT 1

PLICERA 2

AT-2220 2

1. Biologic Product2. Orphan Designation Obtained or Being Sought- 7 yr exclusivity in US; 10 year exclusivity in EU^ Last to expire of currently published patent applications, regardless of jurisdiction; applications not yet granted.* Exclusivity for new, approved biologics in EU is 10 years; currently no generic approval pathway in US. Exclusivities for new chemical entities

(non-biologics) are: US 5 yrs; EU 10 yrs.Revisions as of March 5, 2008

JUVISTA 1

INTUNIV

SPD-550 2019

2021

2019