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
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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