World Preview 2016-Evaluatepharma

EvaluatePharma® - helping you to find value in the pharma and biotech sector

World Preview 2016 “Beyond the Patent Cliff”

June 2011

Welcome to the EvaluatePharma® World Preview 2016 The fourth edition of EvaluatePharma®’s World Preview brings together many of our analyses to provide a top level insight, from the world’s financial markets, into the expected performance of the industry between now and 2016. Based on EvaluatePharma®’s coverage of the world’s leading 3,000 pharmaceutical and biotech companies, the World Preview highlights trends in prescription drug sales, patent risk, R&D spend, global brand sales and market performance by therapy area. Also included in the report is a brief review of 2010 performance. In this year’s edition of the World Preview we have updated the analysis of the market to 2016 and focused on how the forecast to 2016 has changed compared to the last edition in May 2010.

About EvaluatePharma® Since 1998 EvaluatePharma® has been providing senior decision makers within the pharmaceutical industry with an essential service that models the sector from the viewpoint of the world’s financial markets. EvaluatePharma®’s forward looking view of the market is hugely influential as it displays the consensus of expectations, which influence company stock market valuations. The forecasts of equity analysts reveal their perspectives on individual company performance, industry trends and the macro economic environment. EvaluatePharma® has captured the consensus forecasts of equity analysts and seamlessly integrated them with the historic results, as reported by companies. From this comprehensive view of the industry, its past and expected future performance emerges and can be analysed using EvaluatePharma®. Analyses range from total market trends and therapeutic overviews to individual company performance and product progress. Whatever your view on the future of the industry, EvaluatePharma® can help you find value in the pharma and biotech sector. To find out more about this report and EvaluatePharma® services contact us: North America: Debbie Paul Tel: 1-617-573-9453 Email: [email protected]

Rest of the World: Will Hau Tel: +44 (0)20 7377 0800 Email: [email protected]

General Enquiries: [email protected] Disclaimer This report may not be relent, resold, hired out or otherwise disposed of by way of trade in any form of binding or cover other than that in which it is published, without the prior consent of EvaluatePharma Ltd. While all reasonable steps have been taken to ensure that the data presented are accurate, EvaluatePharma Ltd cannot accept responsibility for errors or omissions. Neither does EvaluatePharma Ltd warrant the accuracy, merchantability or fitness of use for a particular purpose of the data.

World Preview to 2016

June 2011

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

2

EvaluatePharma® Foreword: Last year’s edition of the World Preview highlighted that prescription drug sales were forecast to increase by 2.9% per year between 2010 and 2016. In this edition, we can report an upward revision in growth to 4.0% per year between 2010 and 2016. The uplift can be attributed to an upward revision in consensus product forecasts (see page 19) due to favourable news events (page 26), the continuing weakness in the dollar vs. major currencies and a general improvement in sentiment over the last 12 months. Does this signal anything of substance? Despite the upward revision, prescription sales growth is still forecast to lag world economic growth, predicted by the IMF to be 4.4% per year over 2011 and 2012. Underlying this is a two speed world, with developed economies growing at 2.4% and emerging economies growing at 6.5% per year over the period. In a business world increasingly obsessed with emerging markets, it is often overlooked that the ultimate prize for global majors is to sell innovative patented products to the wealthy sub-populations in emerging markets who can afford private healthcare and to convince governments to pay for patented products, rather than selling generic drugs listed on reimbursement lists. Struggling global majors may talk-up the Chinese market, but it cannot be viewed as a substitute for innovation. The shift in the pharmaceutical industry’s focus from the dominant US market towards emerging markets is a symptom of patent expirations coupled with poor R&D productivity, rather than any fundamental economic weakness in the US market. GlaxoSmithKline’s decline, to be outside of the world’s Top 5 biggest sellers of prescription medicines in 2010 (page 22), is a prime example. Its failure to replace ageing blockbusters has seen its US pharmaceutical sales decline from $19.1bn in 2006 to $11.8bn in 2010, despite spending more than $30bn on R&D over the same period. On R&D productivity, 2010 did register a bumper year for new drug approvals in the US in terms of quality. Despite the number of new drugs approved declining 24% in 2010 to 26, the quality of the approved products (based on US sales 5 years post-launch) more than doubled to $13.3bn (page 12), easily the best year since 2004 (when Avastin was approved). This year’s increase in quality, coupled with flat (declining in real terms) industry R&D investment over the last 3 years, is a positive step towards rebalancing R&D output to investment. The imbalance remains huge with the average Net Present Value (NPV) of new products averaging $70bn per year between 2008-10, versus R&D investment at $127bn per year. The Industry as a whole is not yet generating a return on R&D investment. Even if all R&D was successful it is unlikely governments would be capable of reimbursing all new products. It is telling that when Pfizer announced the removal of $1.5bn from its 2012 R&D spend, its stock price rose 5%. In an age of austerity who will be next to wield the axe to their R&D budget? In terms of patent expiries 2011 and 2012 are forecast to be the worst years, with $54bn of sales set to be lost. With small molecule patent expiries relatively priced-in and given a more balanced R&D output to investment, the financial markets may start to re-evaluate global majors as having a more positive long term growth prospect beyond the patent cliff. The analysis we present here is a snapshot of an evolving picture so please view it as such. But whatever the outlook, EvaluatePharma® is there to help you find value in the pharma and biotech sector. Anthony Raeside, Head of Research World Preview to 2016

June 2011

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

3

EvaluatePharma® World Preview 2016 – Analysis Highlights







2016 forecasts for the top 50 products have increased by $21.7bn (+13% upgrade) since April 2010; Worldwide prescription drug sales total $853bn in 2016; Since April 2010 growth revised up from 2.9% to 4.0% (CAGR) over 2010 – 2016;




Over $255bn of sales at risk from patent expirations in 2011-16;




Humira world's largest selling product in 2016;




Pfizer, Novartis and Sanofi competing for top spot in 2016;
















Biotech products fail to overtake small molecule sales within top 100 drugs by 2016; Global pharmaceutical R&D spend returns to growth in 2010 following unprecedented decline in 2009; still over investment; Pfizer’s 2016 R&D spend revised down by $1.2bn since April 2010; Anti-coagulants set to record highest growth of major therapy categories to 2016; Best year for NME approvals since 2004 as sales potential doubles; number of new drugs approved down 24%;




GSK falls out of top 5 in 2010; first time since late 1980s;




Teva continues to dominate generic drug market in 2010;







Roche’s company value slumps in 2010 due to setbacks to Avastin and taspoglutide; Novo Nordisk’s share price soars in 2010 following series of positive events within anti-diabetic business

World Preview to 2016

June 2011

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

4

Table of Contents




Worldwide Prescription Drug Sales (2002-16)




Worldwide Prescription Drug Sales in 2016: Top 20 Companies

7




Worldwide Prescription & OTC Sales by Technology (2002-16)

8




Top 20 Most Valuable R&D Projects (Ranked by Net Present Value)

9




Worldwide R&D Spend by Pharma & Biotech Companies (2002-2016)

10




Pharmaceutical R&D Spend in 2016: Top 20 Companies

11




FDA New Drug Approval Analysis (NMEs & Biologicals): 1997 to 2010

12




Worldwide Rx & OTC Sales by Therapy Area in 2016

13




Oncology Market to 2016

14




Anti-Diabetic Market to 2016

15




Anti-Rheumatics Market to 2016

16




Vaccine Market to 2016

17




Anti-Virals Market to 2016

18




2016: Top 50 Selling Products in the World

19




2016: Top 50 Selling Products in the USA

20




Worldwide Rx & OTC Sales by Therapy Area in 2010

21




Worldwide Prescription Drug Sales in 2010

22




Worldwide Generic Drug Sales in 2010

23




M&A Analysis: 2006 to 2010




6

24

Venture Financing Analysis: 2006 to 2010

New Analysis

25 New Analysis




Key Product Events Positively Impacting Shareholder Value in 2010




Key Product Events Negatively Impacting Shareholder Value in 2010




Enterprise Value Analysis: 2009 to 2010

28




Net Income in 2010: Top 20 Companies

29




Net Income Margin in 2010: Top 20 Companies

30




2010: Top 50 Selling Products in the World

31




2010: Top 50 Selling Products in the USA

32




About EvaluatePharma®

33

World Preview to 2016

New Analysis

June 2011

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

26 27

5

Worldwide Prescription Drug Sales (2002-16) Worldwide Prescription Drug Sales Forecast to Grow by 4.0% (CAGR) to $853bn by 2016 EvaluatePharma® finds that the market for prescription drugs, based on the consensus forecast for the leading 500 pharmaceutical and biotechnology companies, will grow by 4.0% per year (CAGR) between 2010 and 2016 to $853bn. This represents an upward revision on industry growth, given the comparable 2.9% growth per year predicted in last year's edition of the World Preview. This upward revision can be attributed to a number of positive event outcomes (see page 26), which led to product forecasts adding $39bn in 2016 (page 19), and the continuing weakness in the dollar, which raised the currency translated value of sales outside of the USA. The key dynamic limiting future growth from returning to the high single digit level experienced prior to 2009 is the sharp increase in sales at risk from patent expirations, which sees $255bn of sales at risk between 2011 and 2016 ($139bn predicted to be lost).

+16.0%

+15%

+4.0% CAGR 2010-16

800

+12%

700 600

+10%

+10%

+9% +8%

500

+12.0% +10.0%

539

+8.0%

+8%

406 300

640

+14.0%

592

493

454

400

656

757

730

711

675

853

820

791

+5%

+4%

+4%

+4%

+3%

200

+6.0%

+5%

354

+4.0%

+3%

+3%

2016

2015

2014

2013

2012

2011

2009

2008

2007

2006

+0.0% 2005

0 2004

+2.0%

2003

100

2002

WW Sales Growth %

900

2010

WW Prescription Sales ($bn)

Worldwide Total Prescription Drug Sales 2002-16 Source: EvaluatePharma® (25 MAY 2011)

10% Expected Key Patent Expiries in 2012: Plavix (SNY/ BMS) Seroquel (AZN), Diovan (NVS), Singulair (MRK), Actos (TAK), Lexapro (FRX) & Viagra (PFE).

Total Sales at Risk

60

Expected Sales Lost % of Rx Market At Risk

50

30

4%

4%

4%

7

8

33

13 12

13

11

47 6%

6% 5% 31

24

21 13

5% 41

33 32

21 20 21

19

18 9

4%

26

2% 13

3% 4%

8% 7%

41

3%

20 10

4%

9%

6%

5%

40

9% 63

4%

4% 3%

22

19

20

13

10

% At Risk

WW Sales ($bn)

Worldwide Sales At Risk from Patent Expiration 2002-16 70

2% 1%

2016

2015

2014

2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

2003

0% 2002

0

Patent Analysis: 'Total Sales at Risk' represent the worldwide product sales in the year prior to patent expiry but allocated to the year of expiry. E.g. Lipitor had sales of $10.7bn in 2010, this is shown above as 'At Risk' in 2011. Worldwide Prescription Drug Sales (2002-16) Swine Flu Contribution*

WW Prescription Sales ($bn) Year 2002 2003 2004 2005 Prescription (Rx) Growth per Year Change vs. April 2010**

354 +9.6%

406

454

+14.8% +11.8%

1.0

8.4

5.8

2.0

1.9

2.0

2.0

2.0

2.0

2016

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

493

539

592

640

656

675

711

730

757

791

820

853

+8.4%

+9.4%

+10.0%

+8.0%

+2.5%

+2.9%

+5.3%

+2.7%

+3.7%

+4.5%

+3.7%

+4.0%

+12

+13

+28

+31

+34

+45

+54

+68

Source: EvaluatePharma® (25 MAY 2011) CAGR 10-16 +4.0% Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Sales to 2010 based on company reported sales data. Sales forecasts to 2016 based on a consensus of leading equity analysts' estimates for company product sales and segmental sales. *Swine Flu products include vaccines and influenza treatments Tamiflu and Relenza **EvaluatePharma® expanded company coverage added $12bn to 2009 vs. April 2010.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

6

Worldwide Prescription Drug Sales in 2016: Top 20 Companies Pfizer, Sanofi and Novartis Contesting Top Spot in 2016 EvaluatePharma® finds that Pfizer, Sanofi and Novartis will be competing for the position of largest pharma company in the world in 2016 (based on prescription drug sales); all predicted to have prescription sales in the region of $50bn in 2016. Novo Nordisk is set to climb 5 ranking positions to 12th with sales growing 9% per year to $18.4bn in 2016, due to strong insulin franchise sales (including the potential new longer-acting insulin product, Degludec) and growth of its new GLP-1 agonist, Victoza. Teva is forecast to climb 4 ranking positions to number 9 in the world, partly aided by the acquisition of German generic company ratiopharm in 2010. Eli Lilly is set to plunge 6 ranking positions to 14th in 2016 following patent expiration of Zyprexa in 2011 and Cymbalta in 2013, which leads to a 4% decline per year in prescription sales between 2010 and 2016.

60

40

51.2 -1%

50.2 +5%

49.7 45.0

+3%

+4%

43.6

42.3

+3%

+1%

30

27.0

20

24.4

23.9

+3%

+9%

+2

+4 Teva Pharmaceutical

50

Sales ($bn) CAGR 2010-16 (%) Ranking Chg. 2010-16

Abbott Laboratories

WW Prescription Sales ($bn)

WW Prescription Drug Sales in 2016: Top 10 Companies Source: EvaluatePharma® (25 MAY 2011)

-3%

-3

(-) AstraZeneca

(-)

Merck & Co

+2

Roche

Sanofi

-1

GlaxoSmithKline

+2

Novartis

(-) Pfizer

10

21.9 +1%

-1 Johnson & Johnson

0

WW Prescription Drug Sales (2010/16): Top 20 Companies & Total Market

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Pfizer Sanofi Novartis GlaxoSmithKline Roche Merck & Co AstraZeneca Abbott Laboratories Teva Pharmaceutical Johnson & Johnson Bayer Novo Nordisk Bristol-Myers Squibb Eli Lilly Amgen Takeda Boehringer Ingelheim Daiichi Sankyo Astellas Pharma Baxter International Total Top 20 Other Total

WW Prescription Sales ($bn) 2010 2016 % CAGR 10-16

2016 Change vs. Apr-2010

2010

WW Market Share 2016 Chg. (+/-)

Rank Chg. (+/-)

54.1

51.2

-1%

+4.0

8.0%

6.0%

-2.0%

-

36.6

50.2

+5%

+11.2

5.4%

5.9%

+0.5%

+2

41.4

49.7

+3%

+2.6

6.1%

5.8%

-0.3%

-1

35.6

45.0

+4%

+6.3

5.3%

5.3%

+0.0%

+2

35.6

43.6

+3%

-0.3

5.3%

5.1%

-0.2%

-

40.4

42.3

+1%

-4.0

6.0%

5.0%

-1.0%

-3

32.1

27.0

-3%

+4.9

4.7%

3.2%

-1.6%

-

19.9

24.4

+3%

-1.7

2.9%

2.9%

-0.1%

+2

14.5

23.9

+9%

+3.1

2.1%

2.8%

+0.7%

+4

20.7

21.9

+1%

-2.9

3.1%

2.6%

-0.5%

-1

14.2

18.8

+5%

+1.3

2.1%

2.2%

+0.1%

+3

10.8

18.4

+9%

+3.6

1.6%

2.2%

+0.5%

+5

15.5

17.5

+2%

+1.8

2.3%

2.0%

-0.3%

-2

20.8

16.8

-4%

-0.3

3.1%

2.0%

-1.1%

-6

14.7

15.3

+1%

-3.3

2.2%

1.8%

-0.4%

-3

12.6

15.0

+3%

+2.9

1.9%

1.8%

-0.1%

-

12.6

13.7

+1%

-0.8

1.9%

1.6%

-0.3%

-2

10.8

12.8

+3%

+1.6

1.6%

1.5%

-0.1%

-

10.3

11.9

+2%

+1.3

1.5%

1.4%

-0.1%

-1

8.1

11.0

+5%

-1.1

1.2%

1.3%

+0.1%

-1

461.1

530.3

+2%

+30.4

68.3%

62.2%

-6.2%

213.7

322.5

+6%

+37.8

31.7%

37.8%

674.8

852.8

+3%

+68.2

100.0%

100.0%

Source: EvaluatePharma® (25 MAY 2011) Note: Prescription drug sales include generic drug sales. Excludes alliance revenue and royalties where possible.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

7

Worldwide Prescription & OTC Sales by Technology (2002-16) Biotech Products Fail to Overtake Small Molecule Sales within Top 100 Drugs by 2016 EvaluatePharma® finds that the percentage of sales from biotechnology products (bioengineered vaccines + biologics), within the world's top 100 drugs, is set to increase from 33% in 2010 to 45% by 2016. This is a downward revision on the 48% contribution forecast in April 2010. In the broader market, sales from biotechnology products are set to capture 21% of the world pharmaceutical market by 2016, versus its current share of 18% in 2010. The total value of biotechnology sales is set to grow 48% between 2010 and 2016 from $130bn to $192bn.

100% Biotechnology

90%

Conventional/ Unclassified

88%

87%

86%

85%

84%

83%

82%

70% 15 %

60% 50%

Biotech Within Top 100 Products Biotechnology's rapid increase in share within Top 100 products: 2002 (15%), 2010 (33%) & 2016 (45%)

85 %

40%

67 %

2003

12%

13%

2005

11%

2004

10%

2002

20%

15%

17%

16%

80%

79%

79%

33 %

30%

14%

81%

18%

79%

55 %

19%

20%

21%

21%

21%

79%

45 %

21%

2016 Split: Biotech: n=41 (avg. $2.78bn) Conv.: n=59 (avg. $2.35bn)

10% 2012

2011

2010

2009

2008

2007

2006

0%

2016

89%

2015

90%

2014

80%

2013

Technology % of Rx & OTC Sales

Percentage of Worldwide Rx & OTC Pharmaceutical Sales from Biotech vs. Conventional Technology Source: EvaluatePharma® (25 MAY 2011)

Worldwide Prescription & OTC Sales by Technology (2002-2016) 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Technology Biotechnology 10% 11% 12% 13% 14% 15% 16% 17% 18% 19% 20% 21% 21% 21% 21% Conventional/ Unclassified 90% 89% 88% 87% 86% 85% 84% 83% 82% 81% 80% 79% 79% 79% 79% Total Rx & OTC Sales 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% 100% WW Sales ($bn) 2004

2002 2003 Technology Biotechnology 38 46 Conventional 261 301 Other Unclassified Sales 75 82 Total Rx & OTC Sales 374 429 Source: EvaluatePharma® (25 MAY 2011)

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

56

66

79

96

110

119

130

140

151

163

175

184

192

331

347

371

396

418

429

431

444

437

440

450

454

465

91

105

115

128

142

140

146

162

178

191

205

221

237

478

518

565

620

670

688

707

745

765

794

829

860

894

WW Prescription Drug Sales from Biotechnology in 2016: Top 10 Companies

1 2 3 4 5 6 7 8 9 10

Company Roche Novo Nordisk Sanofi Amgen Pfizer GlaxoSmithKline Abbott Laboratories Merck & Co Eli Lilly Johnson & Johnson

WW Sales ($bn) WW Market Share 2010 2016 % CAGR 10-16 2010 2016 23.7

30.6

+4%

9.9

17.6

+10%

Chg. (+/-)

Rank Chg.

18.3% 15.9%

-2.3%

-

7.7%

9.2%

+1.5%

+1

9.8

15.5

+8%

7.6%

8.1%

+0.5%

+1

13.9

14.6

+1%

10.7%

7.6%

-3.1%

-2

9.3

12.3

+5%

7.2%

6.4%

-0.7%

-

5.5

9.3

+9%

4.3%

4.8%

+0.6%

+3

6.7

9.2

+6%

5.2%

4.8%

-0.3%

-

7.0

9.1

+4%

5.4%

4.8%

-0.7%

-2

4.7

6.1

+5%

3.6%

3.2%

-0.4%

+1

5.6

5.7

+0%

4.3%

3.0%

-1.4%

-2

Note: Company drug sales from undisclosed products are presumed to be from conventional (small molecule) technology.

Note: Sanofi results for 2010 are not pro-forma for the acquisition of Genzyme. Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

8

Top 20 Most Valuable R&D Projects (Ranked by Net Present Value) Value of Industry Pipeline Declines only 8% Despite Approvals; Degludec Most Valuable Product EvaluatePharma® NPV Analyzer finds that the value of the Industry's pipeline declined 8% to $250bn, vs. $272bn as calculated in April 2010. The decrease is a negative indicator for the Industry but masks the positive fact that since April 2010, 8 of last year's top 20 R&D products (by NPV value) have been approved, thus partly crystallizing shareholder value as the risk of failure is reduced and cash flows start to be realised. Approvals include the 4 most valuable products: Prolia/Xgeva (Amgen), Provenge (Dendreon), Benlysta (HGS/GSK) and Incivek (Vertex), which currently have a combined NPV of $30.2bn. Novo Nordisk's Degludec is the most valuable R&D product in the industry based on NPV, with a value of $5.8bn. Top 20 Most Valuable R&D Projects (Ranked by Net Present Value) WW Product Sales ($m) Rank

Product

Today's NPV ($m)

2016

1 Degludec

Company Novo Nordisk

Phase (Current) Phase III

Pharmacological Class Insulin

1,389

new entry

5,807

2 Tofacitinib (CP-690550)

Pfizer

Phase III

JAK-3 inhibitor

1,651

new entry

4,953

3 BG-12

Biogen Idec

Phase III

Fumarate

1,224

new entry

4,666

4 Incivek

Johnson & Johnson

Filed

2,243

4,332

5 Relovair

Theravance

Phase III

Hep C protease inhibitor Beta 2 adrenoreceptor agonist & corticosteroid Lysosomal transport modulator

-

4,241

3,231

new entry

4,155

Omega-3 fatty acid

2,289

new entry

4,052

6 DR Cysteamine

Undisclosed Partner

Phase III

7 AMR101 8 Eliquis

Undisclosed Partner

Phase III

Bristol-Myers Squibb

Filed

Factor Xa inhibitor

2,150

9 Eliquis

Pfizer

Filed

Factor Xa inhibitor

-

Novartis

Filed

Meningococcal B vaccine

10 Bexsero 11 12 13 14 15 16 17 18 19

Elvitegravir + GS 9350 + Truvada Reolysin Ruxolitinib (INC424) DegludecPlus VEGF Trap-Eye Xarelto Varespladib (A-002) Ivacaftor (VX-770) Crizotinib (PF-02341066)

20 Trastuzumab-DM1

3,836 new entry

3,592

1,085

3,250

879

3,210

Undisclosed Partner

Phase III

NRTI, HIV integrase inhibitor & CYP3A inhibitor Oncolytic virus

Incyte

Phase III

JAK-1/2 inhibitor

758

Novo Nordisk

Phase III

Insulin

629

new entry

2,334

Regeneron

Filed

VEGFr kinase inhibitor

663

new entry

2,310

Johnson & Johnson

Filed

Factor Xa inhibitor

Anthera

Phase III

sPLA2 inhibitor

724

new entry

2,196

Vertex

Phase III

CFTR potentiator

541

new entry

2,142

Pfizer

Phase III

c-Met & ALK inhibitor

554

new entry

2,123

Roche

Phase III

Anti-HER2 MAb-DM1 conjugate

423

new entry

1,974

Gilead Sciences

Phase III

Top 20 Other Total

1,358

new entry

2,618 2,468

1,215

2,257

23,005

66,517

59,093

182,948

82,098

249,466 -8%

NPV of R&D Pipeline APR 2010:

Source: EvaluatePharma® (25 MAY 2011)

271,836

Most Valuable R&D Projects (Ranked by NPV) in April 2010 Which Have Since Been Approved or Suffered Setbacks Status Change

April 2010

Today's

Company Amgen

Status (April 2010) Filed

Since April10 Approved

NPV ($m)

NPV ($m) Apr-10 (%)

17,892

12,265

Dendreon

Filed

Approved

5,990

5,873

-2%

HGS

Phase III

Approved

5,884

4,645

-21%

Vertex

Phase III

Approved

5,558

7,434

34%

GlaxoSmithKline

Phase III

Approved

3,071

3,692

20%

AstraZeneca

Filed

Approved

2,623

2,947

12%

InterMune

Filed

Approved

2,590

3,942

52%

Forest

Filed

Approved

2,458

930

-62%

46,066

41,728

-9%

AstraZeneca

Filed

Setback

5,135

-

-100%

Merck & Co

Phase III

Setback

4,342

504

-88%

Amylin

Filed

Setback

2,988

1,150

-62%

Roche

Phase III

Setback

2,298

-

-100%

14,763

1,654

-89%

60,829

43,382

-29%

Change vs. APR 10 Approved

Product

Prolia/Xgeva Provenge Benlysta Incivek Benlysta Brilinta* Esbriet* Viibryd

Sub-Total Setback

Numax Vorapaxar (SCH 530348) Bydureon Taspoglutide (RG1583)

Sub-Total

Total

Change vs. -31%

Source: EvaluatePharma® (25 MAY 2011) Note: Theravance to receive royalty payments from GSK on Relovair. DR Cysteamine, AMR101 and Reolysin NPVs based on assumption of future out-licensing, currently being developed by Raptor Pharmaceutical, Amarin and Oncolytics Biotech, respectively. Analysts assume Pfizer to receive co-promotion revenues on Eliquis (apixaban) from BMS. *Brilinta and Esbriet have been approved in the EU but suffered setbacks in the US.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

9

Worldwide R&D Spend by Pharma & Biotech Companies (2002-2016) Global Pharmaceutical R&D Spend Set to Grow by 2.5% (CAGR) to $147bn by 2016; Industry Reinvestment Rate Declining EvaluatePharma® estimates that worldwide pharmaceutical R&D totalled $127bn in 2010, a 1.5% increase on 2009. Despite this representing a return to nominal growth compared to the unprecedented 3.0% decline in 2009, the rate of growth has not returned to the double-digit increases seen in R&D spend between 2002 and 2008 and R&D budgets are now forecast to grow at 2.5% per year, to reach $147bn by 2016. Industry reinvestment, measured by R&D spend as a percentage of prescription sales is set to decline from 18.8% in 2010 to 17.3% in 2016. The decline can be attributed to the fact that R&D spend is growing by less than prescription drug sales as global majors streamline and downsize R&D operations after major patent expiries and historically poor R&D investment returns. The other factor is the change in product mix of the prescription drug industry towards generics, which requires a fraction of the R&D spend.

160

16%

+13.7%

140

+2.5% CAGR 2010-16

+12.1%

+11.4%

120

+10.4% +9.4% 119

100

129 +8.9%

127

125

133

134

144

147

10% 8%

96

6%

+4.5%

88 79 69

14% 12%

107

80 60

137

141

+8.9% CAGR 2002-09

R&D Spend Growth %

WW Pharma R&D Spend ($bn)

Worldwide Total Pharmaceutical R&D Spend in 2002-16 Source: EvaluatePharma® (25 MAY 2011)

+2.2% +2.7% +2.2% +2.4% 4%

+1.5%

+1.0%

2%

40 0% 20

-3.0%

-2%

0 2010

2011

2012

2013

2014

2015

2016

2009

2008

2007

2006

2005

2004

2003

2002

-4%

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

107.5

118.7

129.2

125.3

127.1

132.9

134.1

137.1

140.8

143.9

147.4

+13.7% +11.4% +9.4% +12.1% +10.4% +8.9%

-3.0%

+1.5%

+4.5%

+1.0%

+2.2%

+2.7%

+2.2%

+2.4%

Worldwide R&D Spend by Pharma & Biotech Companies (2002-2016) WW Prescription Sales ($bn) Year 2002 2003 2004 2005 Pharma R&D Spend Growth per Year WW Prescription Sales R&D as a % of WW Rx Sales

69.2

78.7

87.7

95.9

2016

354

406

454

493

539

592

640

656

675

711

730

757

791

820

853

19.6%

19.4%

19.3%

19.5%

19.9%

20.0%

20.2%

19.1%

18.8%

18.7%

18.4%

18.1%

17.8%

17.6%

17.3%

Source: EvaluatePharma® (25 MAY 2011)

CAGR 10-16 on Pharma R&D Spend +2.5% Cumulative R&D Spend (2002-10) $939 bn Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Forecast pharmaceutical research and development spend based on a consensus of leading equity analysts' estimates for company level R&D spend, extrapolated to pharmaceutical R&D when a company has non-pharmaceutical R&D activity.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

10

Pharmaceutical R&D Spend in 2016: Top 20 Companies

R&D Spend ($bn)

Novartis Tops Pharmaceutical R&D Spend in 2016 EvaluatePharma®'s consensus forecast finds Novartis spending the most on pharmaceutical research and development by 2016, with a spend of $9.9bn. In 2010 Pfizer had the largest pharmaceutical R&D budget but falls to the 6th biggest spender by 2016. It is the only global major forecast to cut R&D spend between 2010 and 2016. Since April 2010 consensus analyst forecasts for Pfizer's R&D spend have been revised down by $1.2bn in 2016.

10

Pharmaceutical R&D in 2016: Top 10 Companies Source: EvaluatePharma® (25 MAY 2011) R&D Spend ($bn) CAGR 2010-16 (%)

9.9 8

+4%

8.5

8.4

+1%

+1%

7.6 +5%

6

7.4

7.2

+4%

-4%

4

5.2

5.0

+2%

+1%

4.4 +1%

3.8 +2%

2

Takeda

AstraZeneca

Eli Lilly

Johnson & Johnson

Pfizer

Sanofi

GlaxoSmithKline

Roche

Merck & Co

Novartis

0

Pharmaceutical R&D Spend (2010/16): Top 20 Companies & Total Market

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Novartis Merck & Co Roche GlaxoSmithKline Sanofi Pfizer Johnson & Johnson Eli Lilly AstraZeneca Takeda Bayer Bristol-Myers Squibb Boehringer Ingelheim Amgen Novo Nordisk Abbott Laboratories Daiichi Sankyo Astellas Pharma Otsuka Holdings Merck KGaA Total Top 20 Other Total

Pharma R&D ($bn) 2016 2010

CAGR 10-16

2016 Change vs Apr-10

R&D As a % of Rx Sales 2010 2016

Chg. (+/-)

7.9

9.9

+4%

-0.1

19.0%

19.9%

+0.9%

8.1

8.5

+1%

-0.3

20.1%

20.1%

-0.0%

7.8

8.4

+1%

-1.0

22.0%

19.3%

-2.7%

5.7

7.6

+5%

+0.2

16.0%

17.0%

+1.0%

5.8

7.4

+4%

+1.4

15.9%

14.7%

-1.3%

9.1

7.2

-4%

-1.2

16.8%

14.0%

-2.7%

4.5

5.2

+2%

-0.9

21.7%

23.6%

+1.9%

4.7

5.0

+1%

-0.5

22.8%

29.6%

+6.7%

4.2

4.4

+1%

-0.1

13.2%

16.4%

+3.3%

3.4

3.8

+2%

+0.1

26.9%

25.3%

-1.6%

2.3

3.6

+8%

+1.0

16.3%

19.1%

+2.8%

3.3

3.4

+1%

+0.1

21.3%

19.7%

-1.6%

3.1

3.4

+2%

+0.1

24.3%

24.5%

+0.2%

2.8

3.2

+2%

-0.0

19.3%

21.1%

+1.8%

1.7

2.9

+9%

+0.4

15.8%

15.8%

+0.0%

2.3

2.7

+3%

-0.1

11.4%

11.1%

-0.3%

2.3

2.6

+2%

+0.3

21.1%

20.3%

-0.9%

2.5

2.3

-2%

+0.3

24.7%

19.0%

-5.7%

1.8

1.9

+1%

+0.9

25.2%

36.0%

+10.8%

1.6

1.9

+3%

-0.1

22.0%

21.9%

-0.1%

85.0

95.2

+1.9%

+0.6

18.4%

18.0%

-0.5%

42.2

52.2

+3.6%

+1.3

127.1

147.4

+2.5%

+1.9

Source: EvaluatePharma® (25 MAY 2011) Note: Forecast pharmaceutical R&D spend based on a consensus of leading equity analysts' estimates for company level R&D spend.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

11

FDA New Drug Approval Analysis (NMEs & Biologicals): 1997 to 2010 Best Year for Approvals since 2004 as Sales Potential Doubles; Number of New Drugs Approved Down 24% EvaluatePharma® found that the FDA approved 26 new drugs in 2010, a decrease of 24% from the 2009 figure of 34. The 2010 approvals included 15 new molecular entities (down 4) and 11 biologicals (down 4 on 2009). Despite this decrease in new drug approvals, the quality of the approvals improved significantly over 2009 thanks to the approval of several potential blockbusters: Prevnar 13 (Pfizer), Prolia/Xgeva (Amgen), Provenge (Dendreon), Victoza (Novo Nordisk) and Gilenya (Novartis). Indeed, the quality of the NMEs in 2010 is the highest since 2004, with anticipated USA sales 5 years post launch of $13.3bn, a 119% increase over 2009.

USA Sales 5 Yrs after Launch ($bn)

25

20

49 39

40

1998 Remicade (JNJ) Singulair (MRK) Celebrex (PFE) Enbrel (AMGN/ WYE) Viagra (PFE) Celexa (FRX)

2002 Neulasta (AGMN) Abilify (BMY/ Otsuka) Zetia (SGP/ MRK) Humira (ABT) Eloxatin (SNY)

15

33 $14bn

2004 Avastin (Roche) Cymbalta (LLY) Lyrica (PFE) Spiriva (BI/ PFE)

50

40

38

35

34

32

$14bn $13bn

28

26

10

60

2010 Prevnar 13 (PFE) Prolia/Xgeva (AMGN) Provenge (DNDN) Victoza (Novo N) Gilenya (NVS)

31

29

$13bn

26

20

$8bn $7bn

30

26

Average 5th Year USA Sales Potential: $8.8bn

$7bn

No. of New Drugs

Product name (company ticker) of products in good years (>$1bn) sales)

FDA Approval Count vs. Total USA Product Sales 5 Years After Launch Source: EvaluatePharma® (25 MAY 2011)

$8bn

$7bn

$8bn

5

$7bn

$6bn

$5bn

$5bn

2007

2008

10

0

0 1997

1998

1999

2000

2001

2002

2003

2004

USA Sales 5yrs Post Launch $bn

2005

2006

2009

2010

No. of NMEs Approved

FDA Approval Count (NMEs & Biologicals) vs. 5th Year after Launch USA Product Sales Year No. of NMEs Approved No. of Biologicals Approved Total NMEs + Biologicals % Chg. USA Sales 5yrs Post Launch $bn % Chg.

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

39

30

35

27

24

17

21

31

18

18

16

21

19

15

10

9

5

6

8

9

14

7

10

11

10

10

15

11

49 7.4

2010

39

40

33

32

26

35

38

28

29

26

31

34

26

-20%

+3%

-18%

-3%

-19%

+35%

+9%

-26%

+4%

-10%

+19%

+10%

-24%

6.1

13.3

13.5

7.1

7.4

8.5

12.7

8.3

14.1

6.5

8.1

5.1

5.0

+82%

-48%

+4%

+14%

+50%

-34%

+69%

-54%

+25%

-37%

-2%

+20% +119%

Top 10 New Molecular Entities in 2010: Ranked on USA Consensus Sales in 2015

Product Company Pfizer 1 Prevnar 13 Amgen 2 Prolia/Xgeva Dendreon 3 Provenge Novo Nordisk 4 Victoza Novartis 5 Gilenya Boehringer Ingelheim 6 Pradaxa Sanofi 7 Jevtana Dainippon Sumitomo Pharma 8 Latuda Roche 9 Actemra Eisai 10 Halaven Other Total Source: EvaluatePharma® (25 MAY 2011)

Approved

US Sales 2010 2015

Feb 2010

1,761

2,329

Jun 2010

34

1,864

Apr 2010

48

1,818

Jan 2010

207

1,165

Sep 2010

15

1,077

Oct 2010

-

883

Jun 2010

109

657

Oct 2010

-

631

Jan 2010

56

560

Nov 2010

26

423

170

1,898

Note: Sales forecasts based on a consensus of leading equity analysts' estimates. 5th year USA sales for products approved before 2005 are based on actual company reported sales. E.g. Erbitux (BMS), approved in FEB 2004 has company reported US sales in 2009 (5th year post US launch) of $671m.

2,425 13,306

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

12

Worldwide Rx & OTC Sales by Therapy Area in 2016 Oncology Remains Largest Segment; Anti-coagulants Set to Record Highest Growth to 2016 Oncology remains the largest segment to 2016, with strong growth from in-line products and new products, off-setting a number of major patent expiries over the period. Over the period 2010 to 2016, EvaluatePharma® finds that sales from anti-coagulants are set to grow at an annual rate of 13.5%. This strong growth is being driven by new oral treatments for the prevention of stroke, MI and thrombosis. Analysis on Top 10 Therapy Areas in 2016, Market Share & Sales Growth (2010-16)

WW Market Share %

Analysis on Source: Top 10EvaluatePharma® Therapy Sales 2012, (25in MAY 2011)Market Share & Sales Growth (2007-12) 14%

Key Drivers Avastin (Roche), Rituxan (Roche) Tasigna (NVS), Afinitor (NVS) Provenge (DNDN), Revlimid (CELG) Key Patent Expiries Taxotere (SAN), Arimidex (AZN) Gleevec (NVS), Gemzar (LLY) Femara (NVS)

12% 10%

Key Patent Expiries Angiotensin II antagonists segment Diovan (NVS) in 2012, Avapro (BMY/ SAN) in 2012, Micardis (BI) in 2014.

Oncology*

8%

Key Drivers: New oral treatments Xarelto (BAY/ J&J) Eliquis (BMS / PFE) Pradaxa (BI)

Vaccines

Bronchodilators 4%

Anti-diabetics

Anti-rheumatics

6%

Anti-hypertensives Anti-virals Anti-hyperlipidaemics

2% 0% -10.0%

-5.0%

Anti-coagulants

Dermatologicals

Key Patent Expiry Lipitor (PFE) in 2011

+0.0%

+5.0%

+10.0%

+15.0%

+20.0%

% Sales Growth: CAGR 2010-16

Note: Bubble = WW Sales in 2016 WW Rx & OTC Sales by EvaluatePharma® Therapy Area (2010/16): Top 15 Categories & Total Market WW Sales ($bn) Therapy Area 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Oncology* Anti-diabetics Anti-rheumatics Vaccines Anti-virals Anti-hypertensives Bronchodilators Anti-hyperlipidaemics Dermatologicals Anti-coagulants Sensory organs MS therapies Anti-bacterials Anti-fibrinolytics Bone calcium regulators Top 15 Other Total WW Rx & OTC Sales

2010

2016

% Growth

CAGR

2016 Change vs. Apr-2010

60.0

90.5

+7.1%

+17.7

8.5%

10.1%

+1.6%

-

30.6

47.3

+7.5%

+2.8

4.3%

5.3%

+1.0%

+3

32.7

42.8

+4.6%

+0.0

4.6%

4.8%

+0.2%

+1

25.3

36.5

+6.3%

-0.5

3.6%

4.1%

+0.5%

+3

22.1

32.5

+6.6%

+0.2

3.1%

3.6%

+0.5%

+3

40.9

32.1

-4.0%

+4.6

5.8%

3.6%

-2.2%

-4

32.8

30.7

-1.1%

+5.6

4.6%

3.4%

-1.2%

-4

29.8

25.2

-2.8%

+4.9

4.2%

2.8%

-1.4%

-2

12.4

16.2

+4.6%

+4.4

1.7%

1.8%

+0.1%

+2

WW Market Share 2010 2016

Chg. (+/-)

Rank Chg. (+/-)

7.4

15.8

+13.5%

+1.7

1.0%

1.8%

+0.7%

+5

13.8

15.5

+2.0%

-0.9

2.0%

1.7%

-0.2%

-1

11.1

14.5

+4.5%

+2.3

1.6%

1.6%

+0.0%

-

15.4

14.1

-1.4%

+1.9

2.2%

1.6%

-0.6%

-4

9.1

12.1

+4.9%

-0.3

1.3%

1.4%

+0.1%

-

9.9

11.3

+2.2%

-2.7

1.4%

1.3%

-0.1%

-2

353

437

+3%

+41.6

50.0%

48.9%

-1.1%

354

457

+4%

50.0%

51.1%

+1.1%

707

894

+4%

100.0%

100.0%

61.2

96.2

+8%

8.7%

10.8%

+2.1%

31.9

41.4

+4%

4.5%

4.6%

+0.1%

Total 'Rx & OTC Sales' includes: WW Unbranded Generic Sales OTC Pharmaceuticals Source: EvaluatePharma® (25 MAY 2011)

Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Sales in 2010 based on company reported data. Sales forecasts to 2016 based on a consensus of leading equity analysts' estimates for product sales and segmental sales. *Compared to April 2010, EvaluatePharma® now classifies Revlimid (Celgene, 2016 Sales: $5,550m) and Afinitor (Novartis, 2016 Sales: 2,058) as oncology products (previously classified as immunostimulants).

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

13

Oncology Market to 2016 Roche Set to Continue Domination of Oncology Market EvaluatePharma® found that Roche commanded an impressive 33.8% market share of the worldwide oncology market in 2010. Roche's dominance is set to continue with consensus forecasts predicting a 28.5% share of the $90.5bn oncology market in 2016. Dendreon is set to enter the top 10 by 2016 owing to the 2010 launch of its cancer vaccine (Provenge), which is forecast to achieve sales of $2.6bn in 2016. Bristol-Myers Squibb's oncology sales are forecast to grow by 18% between 2010 and 2016, moving the company to 4th spot in the company rankings, due to strong performances from Sprycel (dasatinib), Yervoy (ipilimumab) and Ixempra (ixabepilone). Patent expiries on Arimidex and Casodex are set to hit AstraZeneca which drops 5 ranking positions to 8th spot in 2016.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16) WW Market Share %

Source: EvaluatePharma® (25 MAY 2011) 40% Roche: Set to control world's top 3 leading oncology products by 2016 with Avastin, Rituxan and Herceptin. Few patent concerns.

35% 30%

Roche

25% 20%

NVS: Tasigna set to replace lost Gleevec sales by 2016 (Gleevec patent expiry JUL 2015). Femara patent expiry JUN 2011.

BMS: Strong growth from Sprycel, Yervoy and Ixempra.

15% 10% Novartis*

Celgene*

5%

Bristol-Myers Squibb

Pfizer

0% -5%

+0%

+5%

+10%

+15%

+20%

+25%

% Sales Growth: CAGR 2010-16

Note: Bubble = WW Sales in 2016

Top 10 Companies & Total Worldwide Oncology Sales 2010-16 WW Sales ($m) Rank Company 1 Roche

2016 Change

CAGR

2010

2016

vs. Apr-2010

20,256

25,803

+1466

2010-16 +4%

2010 33.8%

WW Market Share 2016 28.5%

Rank Chg. 2010-16 -

2 Novartis*

6,321

7,463

+2218

+3%

10.5%

8.2%

-

3 Celgene*

3,480

7,354

+6455

+13%

5.8%

8.1%

+2

4 Bristol-Myers Squibb

1,800

4,899

+1038

+18%

3.0%

5.4%

+4

5 Pfizer

2,682

4,225

+21

+8%

4.5%

4.7%

+2

6 Eli Lilly

3,338

4,046

-362

+3%

5.6%

4.5%

-

7 Sanofi

3,740

3,696

+1224

-0%

6.2%

4.1%

-3

8 AstraZeneca

4,045

3,171

+138

-4%

6.7%

3.5%

-5

9 GlaxoSmithKline

1,064

2,993

+432

+19%

1.8%

3.3%

+5 +31

10 Dendreon

48

2,617

+954

+95%

0.1%

2.9%

Top 10

46,775

66,269

+13584

+5%

78.0%

73.2%

Other

13,188

24,217

Total Industry

59,963

90,486

+17660

+9%

22.0%

26.8%

+6%

100.0%

100.0%

Source: EvaluatePharma® (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Oncology Products Worldwide in 2016 WW Sales ($m) Rank

Product 1 Avastin

Generic Name bevacizumab

2 Rituxan

rituximab

3 Herceptin

trastuzumab

4 Revlimid

lenalidomide pemetrexed disodium

5 Alimta

Company Roche Roche + Biogen Idec Roche Celgene Eli Lilly

WW Market Share

Current

Pharma Class Anti-VEGF MAb

2010 6,214

2016 7,831

2010-16 +3%

2010 10.4%

2016 8.7%

Status Marketed

Anti-CD20 MAb

6,113

7,684

+3%

10.2%

8.5%

Marketed

5,221

6,466

+3%

8.7%

7.1%

Marketed

2,469

5,550

+12%

4.1%

6.1%

Marketed

2,209

2,891

+4%

3.7%

3.2%

Marketed

Anti-HER2 (ErbB-2) MAb Immunomodulator Thymidylate synthase inhibitor

CAGR

Note: Oncology Includes: Alkaloids, Alkylating agents, Anti-metabolites, Anti-neoplastic MAbs, Cancer vaccines, Cytotoxic antibiotics, Hormone therapies, Platinum compounds and other anti-cancer. Excludes anti-emetics and anti-anaemics used in chemotherapy-induced anaemia. Also excludes: Interferons, immunostimulants & immunosuppressants. *Compared to April 2010, EvaluatePharma® now classifies Revlimid (Celgene, 2016 Sales: $5,550m) and Afinitor (Novartis, 2016 Sales: $2,058m) as oncology products (previously classified as immunostimulants).

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

14

Anti-Diabetic Market to 2016 Novo Nordisk to Extend Dominance in Anti-Diabetic Market EvaluatePharma® finds Novo Nordisk will continue as the market leader in anti-diabetic products, increasing market share from 26.6% to 30.8% between 2010 and 2016 due to strong growth from its insulin franchise (including the potential new longer-acting insulin product, Degludec) and Victoza (GLP-1). Indeed, positive news flow on Victoza and Degludec helped increase 2016 forecasts for the company's anti-diabetic sales by $3.0bn compared to April 2010. Bristol-Myers Squibb and AstraZeneca are set to become significant players in the diabetes market with strong growth forecast from their new DPP-IV inhibitor, Onglyza, over the period.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16) WW Market Share %

Source: EvaluatePharma® (25 MAY 2011) 40% Novo: Solid growth in its core insulin franchise (including Degludec) and GLP-1 Victoza.

35% Novo Nordisk

30% 25% Takeda: Actos generic competition expected 2012. New DPP-IV inhibitor Nesina set to cushion the blow.

20%

Sanofi

15%

Merck & Co

10% Takeda

Eli Lilly

5%

MRK: Strong growth in DPP-IV inhibitor franchise Januvia/Janumet.

0% -10%

-5%

+0%

+5%

+10%

+15%

Note: Bubble = WW Sales in 2016

+20%

% Sales Growth: CAGR 2010-16

Top 10 Companies & Total Worldwide Anti-Diabetic Sales 2010-16 WW Sales ($m) Rank Company 1 Novo Nordisk

2016 Change

CAGR

2010

2016

vs. Apr-2010

8,144

14,575

+3008

2010-16 +10%

WW Market Share 2010 26.6%

2016 30.8%

Rank Chg. 2010-16 -

2 Sanofi

5,704

7,595

+1030

+5%

18.6%

16.1%

-

3 Merck & Co

3,369

6,691

+630

+12%

11.0%

14.2%

+1

4 Takeda

4,975

3,801

+355

-4%

16.2%

8.0%

-1

5 Eli Lilly

3,294

3,774

-427

+2%

10.8%

8.0%

-

6 Bristol-Myers Squibb

264

2,470

+326

+45%

0.9%

5.2%

+7

7 Amylin Pharmaceuticals

651

1,139

-1376

+10%

2.1%

2.4%

-

8 Novartis

500

1,079

+419

+14%

1.6%

2.3%

+1

9 Servier 10 Bayer Top 10

610

645

+16

+1%

2.0%

1.4%

-2

463

522

+91

+2%

1.5%

1.1%

-1

27,975

42,291

+4072

+6%

91.4%

89.4%

+9%

8.6%

10.6%

+2797

+6%

100.0%

100.0%

Other

2,644

4,989

Total Industry

30,619

47,280

Source: EvaluatePharma® (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Anti-Diabetic Products Worldwide in 2016 WW Sales ($m) Rank

Product

Generic Name

2010

DPP-IV inhibitor Insulin

WW Market Share

Current

2010

Status

1 Januvia/Janumet

sitagliptin

2 Lantus

insulin glargine

3 NovoRapid

insulin aspart

Novo Nordisk

Insulin

2,120

3,672

+10%

6.9%

7.8%

Marketed

4 Human insulin & devices

insulin recombinant Novo Nordisk human

Insulin

2,502

2,507

+0%

8.2%

5.3%

Marketed

5 Humalog

insulin lispro

Insulin

2,054

2,223

+1%

6.7%

4.7%

Marketed

Eli Lilly

Pharma Class

CAGR

Company Merck + Ono + Almirall Sanofi

2016

2010-16

2016

3,503

6,800

+12%

11.4%

14.4%

Marketed

4,658

5,585

+3%

15.2%

11.8%

Marketed

Note: Bristol-Myers Squibb to book worldwide end-user sales on Onglyza, co-promoted worldwide (ex Japan) with AstraZeneca.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

15

Anti-Rheumatics Market to 2016 Abbott Laboratories Set to be Clear No. 1 in 2016 EvaluatePharma®'s consensus forecast predicts Abbott Laboratories will remain the world's number 1 player in anti-rheumatic sales in 2016. Abbott Laboratories' strong performance is driven by strong growth from Humira (adalimumab), which is set to achieve global sales of $9.7bn in 2016. This makes the product the leading Anti-TNF product in 2016, ahead of Merck/J&J's Remicade/Simponi franchise which is forecast to reach $8.0bn by 2016 and Pfizer/Amgen's Enbrel which is forecast to sell $7.2bn in 2016. Strong forecast growth from Cimzia and Actemra is set to propel UCB and Roche, respectively, to positions 8 and 9 in the company rankings.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16) WW Market Share %

Source: EvaluatePharma® (25 MAY 2011) 30% ABT: Continued growth for Humira (adalimumab) in the TNF inhibitor market to 2016.

25%

Abbott Laboratories 20% AMGN: Enbrel sales forecast to decline owing to increased competition in both RA and psoriasis.

15%

Pfizer*

10%

Merck & Co

Johnson & Johnson Amgen 5%

0% -6%

-4%

-2%

+0%

+2%

+4%

+6%

+8%

% Sales Growth: CAGR 2010-16

Note: Bubble = WW Sales in 2016

Top 10 Companies & Total Worldwide Anti-rheumatic Sales 2010-16 WW Sales ($m) Rank Company 1 Abbott Laboratories

2016 Change

CAGR

2010

2016

vs. Apr-2010

6,548

8,959

-679

2010-16 +5%

2010 20.0%

2016 20.9%

WW Market Share

Rank Chg. 2010-16 -

2 Pfizer*

6,496

7,125

+1885

+2%

19.9%

16.6%

-

3 Merck & Co

3,209

4,096

+70

+4%

9.8%

9.6%

+2

4 Johnson & Johnson

3,491

3,591

-854

+0%

10.7%

8.4%

-

5 Amgen

3,534

2,977

-311

-3%

10.8%

7.0%

-2

6 Bristol-Myers Squibb

733

1,709

-89

+15%

2.2%

4.0%

+3

7 Bayer

917

1,381

+343

+7%

2.8%

3.2%

+1

8 UCB

263

1,354

-105

+31%

0.8%

3.2%

+7

9 Roche

221

1,181

-618

+32%

0.7%

2.8%

+8

707

1,111

+171

+8%

2.2%

2.6%

+2

26,119

33,484

-186

+4%

80.0%

78.2%

10 Mitsubishi Tanabe Top 10 Other

6,541

9,324

Total Industry

32,660

42,807

+4

+5%

20.0%

21.8%

+4%

100.0%

100.0%

Source: EvaluatePharma® (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Anti-rheumatic Products Worldwide in 2016 WW Sales ($m) Rank

Product 1 Humira

Generic Name adalimumab

2 Enbrel

etanercept

3 Remicade**

infliximab

Company Abbott + Eisai Amgen + Pfizer + Takeda

WW Market Share

Current

Pharma Class Anti-TNFa MAb

2010 6,742

2016 9,696

2010-16 +5%

2010 20.6%

2016 22.6%

Status Marketed

TNFa inhibitor

7,257

7,190

-0%

22.2%

16.8%

Marketed

6,520

6,107

-1%

20.0%

14.3%

Marketed

324

1,942

+29%

1.0%

4.5%

Marketed

-

1,651

n/m

-

3.9%

Phase III

J&J + Merck + Anti-TNFa MAb Mitsubishi Tanabe

4 Simponi**

golimumab

Merck + J&J

5 CP-690550

tofacitinib citrate

Pfizer

Anti-TNFa MAb Janus kinase-3 (JAK-3) inhibitor

CAGR

Note: Anti-rheumatic sales include TNF inhibitors, COX-2 inhibitors, NSAIDs and new treatments in development. TNF inhibitor sales include RA, Crohn's and Psoriasis. Pfizer books US co-promotion revenues on Enbrel. *Compared to April 2010, EvaluatePharma® now classifies CP-690550 (Pfizer, 2016 Sales: $1,651m) as an Other Anti-rheumatic (previously classified as an immunosuppressant). **Combined Remicade and Simponi sales $8.0bn. Simponi (golimumab) is Merck and J&J's next generation product to Remicade (infliximab). Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

16

Vaccine Market to 2016 GlaxoSmithKline Retains Number 1 Spot in 2016 EvaluatePharma® finds that GSK retains the number 1 spot in vaccines in 2016, despite seeing its market share drop from 26.4% in 2010 to 22.0% in 2016. Pfizer is set to have the fastest growing vaccines division within global majors between 2010 and 2016, with predicted average annual growth of 9%, driven by its pneumococcal vaccines, including the switch from Prevnar to Prevnar 13, the company's new vaccine which protects against an additional 6 strains of pneumococcal bacteria. .

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16) WW Market Share %

Source: EvaluatePharma® (25 MAY 2011) 30% Pfizer Strong growth from newly acquired pneumococcal vaccines (Prevnar & Prevnar 13).

25% GlaxoSmithKline 20%

Sanofi + 50% Sanofi Pasteur MSD

Pfizer

15% Merck & Co + 50% Sanofi Pasteur MSD

10%

Novartis

Novartis Strong contribution expected from new meningococcal vaccines. Bexsero (2016 sales: $1.0bn) and Menveo sales (2016 sales: $643m).

5%

0% +0%

+2%

+4%

+6%

+8%

+10%

+12%

% Sales Growth: CAGR 2010-16

Note: Bubble = WW Sales in 2016

Top 10 Companies & Total Worldwide Vaccine Sales 2010-16 WW Sales ($m) Rank Company 1 GlaxoSmithKline 2

Sanofi + 50% Sanofi Pasteur MSD

2016 Change

CAGR

2010

2016

vs. Apr-2010

6,689

8,034

-139

2010-16 +3%

WW Market Share 2010 26.4%

2016 22.0%

Rank Chg. 2010-16 -

5,662

7,984

+1439

+5%

19.9%

19.1%

-

3,669

6,217

+38

+9%

14.5%

17.0%

+1

4,093

5,472

+389

+4%

13.7%

12.2%

-1

2,101

3,395

-59

+8%

8.3%

9.3%

-

6 CSL

504

934

+190

+11%

2.0%

2.6%

-

7 Baxter International

296

440

-76

+7%

1.2%

1.2%

+1

8 Abbott Laboratories

231

407

-16

+10%

0.9%

1.1%

+3

9 Takeda

234

404

n/m

+10%

0.9%

1.1%

+1

346

351

+77

+0%

1.4%

1.0%

-3

23,825

33,638

+1844

+5%

89.2%

86.5%

3 Pfizer Merck & Co + 50% Sanofi 4 Pasteur MSD 5 Novartis

10 Mitsubishi Tanabe Top 10 Other

1,521

2,861

Total Industry

25,346

36,498

-464

+9%

10.8%

13.5%

+5%

100.0%

100.0%

Source: EvaluatePharma® (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Vaccine Products Worldwide in 2016 WW Sales ($m) Rank

Product 1 Prevnar 13 2 PENTAct-HIB

Generic Name pneumococcal vaccine DTPw, Hib & polio vaccine

3 Fluzone

influenza vaccine

Hepatitis Vaccine 4 Franchise

hepatitis A & B vaccine DTP, hepatitis B & polio vaccine

5 Pediarix

WW Market Share

Current

Company

2010

2016

2010-16

CAGR

2010

2016

Status

Pfizer

2,416

5,805

+13%

9.5%

15.9%

Marketed

Sanofi

1,306

1,922

+6%

5.2%

5.3%

Marketed

Sanofi + Sanofi Pasteur MSD

1,341

1,806

+4%

5.3%

4.9%

Marketed

GlaxoSmithKline

1,113

1,318

+2%

4.4%

3.6%

Marketed

GlaxoSmithKline

1,082

1,310

+3%

4.3%

3.6%

Marketed

Note: Sanofi Pasteur MSD is a European joint venture between Merck & Co and Sanofi. Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

17

Anti-Virals Market to 2016 Gilead Sciences to Dominate Anti-Virals to 2016 EvaluatePharma® finds Gilead Sciences commands a 29.9% market share of the anti-virals area by 2016, with sales set to increase 7% annually between 2010 and 2016. Conversely, GSK is set to fall from 2nd to 5th spot over the same period, due to continued sales decline of its once marketleading herpes treatment, Valtrex, and the expected poor performance from its previously market-dominating HIV franchise. Merck, Vertex and Johnson & Johnson are expected to benefit from the introduction of new treatments for hepatitis C over the period.

Analysis on Worldwide Sales, Market Share & Sales Growth (2010-16) WW Market Share %

Source: EvaluatePharma® (25 MAY 2011) 40%

Gilead: Set to continue dominance in innovative HIV combinational therapy.

35% 30%

MRK: Strong growth from HIV integrase inhibitor Isentress (raltegravir) and new hep C protease inhibitor Victrelis (boceprevir).

Gilead Sciences

25% GSK: Hit by patent expiries (Valtrex - DEC 2009). Weak performance predicted from HIV franchise.

20% 15%

Johnson & Johnson

10%

Merck & Co

Bristol-Myers Squibb GlaxoSmithKline

J&J: Growth driven by new hep C protease inhibitor Incivek (telaprevir).

5% 0% -20%

-10%

+0%

+10%

+20%

+30%

+40%

% Sales Growth: CAGR 2010-16

Note: Bubble = WW Sales in 2016

Top 10 Companies & Total Worldwide Anti-virals Sales 2010-16 2016 Change

CAGR

2010

WW Sales ($m) 2016

vs. Apr-2010

6,537

9,694

-1072

2010-16 +7%

2010 29.6%

2016 29.9%

2010-16 -

2 Johnson & Johnson

1,133

4,514

-762

+26%

5.1%

13.9%

+5

3 Merck & Co

1,517

3,430

+449

+15%

6.9%

10.6%

+3

4 Bristol-Myers Squibb

2,748

3,217

+128

+3%

12.4%

9.9%

-1

5 GlaxoSmithKline

4,897

2,687

+309

-10%

22.2%

8.3%

-3

-

1,730

+848

n/m

0.0%

5.3%

New Entry

7 Abbott Laboratories

1,619

1,068

-722

-7%

7.3%

3.3%

-3

8 Roche

1,607

938

-61

-9%

7.3%

2.9%

-3

-

612

+432

n/m

-

1.9%

New Entry -2

Rank Company 1 Gilead Sciences

6 Vertex Pharmaceuticals

9 SIGA Technologies 10 AstraZeneca Top 10

WW Market Share

646

563

-898

-2%

2.9%

1.7%

20,704

28,453

-1350

+5%

93.7%

87.7%

Other

1,404

3,999

Total Industry

22,107

32,452

+195

+16%

6.3%

12.3%

+6%

100.0%

100.0%

Rank Chg.

Source: EvaluatePharma® (25 MAY 2011); Consensus sales from equity analysts' reports

Top 5 Anti-viral Products Worldwide in 2016 WW Sales ($m) Rank

Product 1 Incivek 2 Atripla 3 Truvada 4 Isentress 5 Reyataz

Generic Name telaprevir efavirenz; emtricitabine; tenofovir emtricitabine; tenofovir

WW Market Share

Current

Company J&J + Vertex + Mitsubishi

Pharma Class Hepatitis C protease inhibitor

2010

2016

2010-16

2010

2016

Status

-

4,226

n/m

-

13.0%

Approved

Gilead Sciences

NNRTI & NRTI

2,927

3,687

+4%

13.2%

11.4%

Marketed

Gilead + Torii

NRTI

2,746

3,345

+3%

12.4%

10.3%

Marketed

HIV integrase inhibitor

1,090

2,222

+13%

4.9%

6.8%

Marketed

Protease inhibitor

1,479

1,883

+4%

6.7%

5.8%

Marketed

raltegravir potassium Merck & Co atazanavir sulfate

Bristol-Myers Squibb

CAGR

Note: GlaxoSmithKline consolidates 100% of the revenues from ViiV Healthcare, a joint venture with Pfizer for the marketing of the two companies' HIV anti-virals.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

18

2016: Top 50 Selling Products in the World 2016 Forecasts Upgraded by $33.8bn (+5% Upgrade) Since April 2010; Humira No.1 in 2016 EvaluatePharma® finds that total 2016 forecasts for the individual products have increased by $33.8bn (+5.4%)* since April 2010. In the top 10 products the largest upward revisions since April 2010 are Crestor (AstraZeneca) and Seretide/Advair (GSK), which saw their 2016 forecasts increase by $1.2bn and $1.8bn, respectively, due to announcements which indicated a reduced generic threat to 2016. The largest global brand in 2016 is predicted to be Humira, sold by Abbott Laboratories and Eisai (Japan), which is forecast to reach $9.7bn in 2016 WW Product Sales ($m) % Growth

Market Status

2016 Change

Product 1 Humira

Generic Name adalimumab

Company Abbott + Eisai

Pharmacological Class Anti-TNFa MAb

2010

2016

6,742

9,696

+5%

Marketed

-405

vs Apr-10 -4%

2 Avastin

bevacizumab

Roche

Anti-VEGF MAb

6,214

7,831

+3%

Marketed

-1078

-12%

3 Rituxan

rituximab

Roche + Biogen Idec

Anti-CD20 MAb

6,113

7,684

+3%

Marketed

+897

+13%

4 Crestor

rosuvastatin calcium

AstraZeneca + Shionogi + Chiesi

Statin/ HMG CoA reductase inhibitor

6,106

7,518

+3%

Marketed

+1242

+20%

5 Enbrel

etanercept

Amgen + Pfizer + Takeda

TNFa inhibitor

7,257

7,190

-0%

Marketed

-119

-2%

6 Seretide/Advair

fluticasone propionate; salmeterol xinafoate

GSK + Almirall + Faes

Beta 2 adrenoreceptor agonist & corticosteroid

8,067

6,953

-2%

Marketed

+1768

+34%

7 Januvia/Janumet

sitagliptin

Merck + Ono + Almirall

DPP-IV inhibitor

3,503

6,800

+10%

Marketed

+791

+13%

8 Herceptin

trastuzumab

Roche

Anti-HER2 (ErbB-2) MAb

5,221

6,466

+3%

Marketed

+300

+5%

9 Remicade

infliximab

J&J + Merck + Mitsubishi Tanabe

Anti-TNFa MAb

6,520

6,107

-1%

Marketed

+380

+7% +237%

10 Prevnar 13

pneumococcal vaccine

Pfizer

Pneumococcal vaccine

2,416

5,805

+13%

Marketed

+4081

11 Lantus

insulin glargine

Sanofi

Insulin

4,658

5,585

+3%

Marketed

+292

+6%

12 Revlimid

lenalidomide

Celgene

Immunomodulator

2,469

5,550

+12%

Marketed

+702

+14%

13 Incivek

telaprevir

J&J + Vertex + Mitsubishi

Hepatitis C protease inhibitor

+15%

14 Lyrica

pregabalin

Pfizer + Eisai

Alpha 2 delta ligand

15 Xarelto

rivaroxaban

Bayer + J&J

Factor Xa inhibitor

16 Atripla

efavirenz; emtricitabine; tenofovir

Gilead Sciences

17 NovoRapid

insulin aspart

Novo Nordisk

0

4,226

Approved

+554

3,077

3,998

+4%

Marketed

-78

-2%

100

3,991

+69%

Marketed

+366

+10%

NNRTI & NRTI

2,927

3,687

+3%

Marketed

+165

+5%

Insulin

2,120

3,672

+8%

Marketed

+415

+13%

3,558

3,442

-0%

Marketed

+344

+11%

41

3,361

+88%

Marketed

-1799

-35%

2,746

3,345

+3%

Marketed

-52

-2%

-

3,231

Phase III

+3231

n/m

3,799

3,223

-2%

Marketed

-1366

-30%

18 Neulasta

pegfilgrastim

Amgen + Kyowa Hakko

Colony stimulating factor

19 Xgeva/Prolia

denosumab

Amgen + GSK + Daiichi Sankyo

Anti-RANKL MAb

20 Truvada

emtricitabine; tenofovir

Gilead + Torii

NRTI

21 DR Cysteamine

cysteamine bitartrate

Raptor Pharmaceutical

Lysosomal transport modulator

22 Spiriva

tiotropium

Boehringer Ingelheim + Pfizer Muscarinic antagonist

23 Micardis

telmisartan

Boehringer + Astellas + Bayer Angiotensin II antagonist

3,258

3,070

-1%

Marketed

+708

+30%

24 Lucentis

ranibizumab

Novartis + Roche

Anti-VEGF MAb

2,935

3,062

+1%

Marketed

-367

-11%

25 Benicar/Olmetec

olmesartan

Daiichi Sankyo + Forest

Angiotensin II antagonist

2,487

3,035

+3%

Marketed

+260

+9%

26 Symbicort

budesonide; formoterol fumarate dihydrate

AstraZeneca + Sigma-Tau

Beta 2 adrenoreceptor agonist & corticosteroid

2,760

2,992

+1%

Marketed

+638

+27%

27 Benlysta

belimumab

Human Genome Sciences + GSK

Anti-B lymphocyte stimulator (BLyS) MAb

-

2,892

Marketed

+151

+6%

28 Alimta

pemetrexed disodium

Eli Lilly

Thymidylate synthase inhibitor

2,209

2,891

+4%

Marketed

-384

-12%

11,968

2,791

-19%

Marketed

+118

+4%

1,565

2,620

+8%

Marketed

+745

+40% +57%

29 Lipitor

atorvastatin calcium

Pfizer + Astellas + Almirall

Statin/ HMG CoA reductase inhibitor

30 Privigen

immune globulin (human)

CSL

Immunoglobulin

31 Provenge

sipuleucel-T

Dendreon

Prostate cancer vaccine

48

2,617

+77%

Marketed

+955

32 Advate

factor VIII (procoagulant)

Baxter International

Factor VIII

1,800

2,612

+5%

Marketed

-362

-12%

33 Botox

botulinum toxin type A

Allergan + GSK

Botulinum toxin

1,435

2,596

+9%

Marketed

+244

+10%

34 Gilenya

fingolimod

Novartis

S1P receptor modulator

15

2,587

+109%

Marketed

+1825

+239%

35 Human insulin & devices

insulin recombinant human

Novo Nordisk

Insulin

2,502

2,507

+0%

Marketed

+392

+19%

36 Zetia

ezetimibe

Merck & Co

Cholesterol absorption inhibitor

2,297

2,502

+1%

Marketed

+247

+11%

37 Copaxone

glatiramer acetate

Teva + Sanofi

MS agent

3,300

2,444

-4%

Marketed

-222

-8%

38 Plavix

clopidogrel bisulfate

Sanofi + BMS

Platelet ADP antagonist

9,148

2,443

-17%

Marketed

+772

+46%

39 Pradaxa

dabigatran etexilate

Boehringer Ingelheim

Thrombin inhibitor

265

2,384

+37%

Marketed

+1210

+103%

40 Lovenox/Clexane

enoxaparin sodium

Sanofi

Heparin, low molecular weight (LMWH)

3,724

2,376

-6%

Marketed

-369

-13%

41 Aranesp

darbepoetin alfa

Amgen + Kyowa Hakko

Erythropoietin

2,974

2,348

-3%

Marketed

-224

-9%

42 Gleevec/Glivec

imatinib mesylate

Novartis

Tyrosine kinase inhibitor

4,265

2,293

-8%

Marketed

-216

-9%

43 AMR101

icosapent ethyl

Amarin

Omega-3 fatty acid

-

2,289

Phase III

+2289

n/m

44 Cialis/Adcirca

tadalafil

Eli Lilly + United Therapeutics Phosphodiesterase V (PDE5) + Nippon Shinyaku inhibitor

1,784

2,273

+4%

Marketed

+254

+13%

45 Tasigna

nilotinib

Novartis

BCR-ABL, PDGFr & c-kit tyrosine kinase inhibitor

399

2,272

+28%

Marketed

+166

+8%

46 Erbitux

cetuximab

Merck KGaA + BMS

Anti-EGFr MAb

1,751

2,237

+4%

Marketed

-276

-11%

47 Humalog

insulin lispro

Eli Lilly

Insulin

2,054

2,223

+1%

Marketed

-97

-4%

48 Isentress

raltegravir potassium

Merck & Co

HIV integrase inhibitor

1,090

2,222

+11%

Marketed

+132

+6%

49 Victoza

liraglutide

Novo Nordisk

GLP-1 agonist

50 Velcade

bortezomib

Takeda + J&J

Proteasome inhibitor

Total Total WW Individual Products Forecast in EvaluatePharma®

413

2,220

+27%

Marketed

+1261

+131%

1,801

2,208

+3%

Marketed

+1173

+113%

151,899

190,364

+3%

+21653

+13%

562,232

656,072

+2%

+39493

+6%

Impact of increased company coverage in EvaluatePharma® +5667 Impact of consensus forecasts added since April 2010 for companies completing IPOs in 2010 and 2011 +3642 Estimated change in 2016 consensus forecast for all products forecast in EvaluatePharma® +30184

Source: EvaluatePharma® (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates. *$33.8bn is the sum of newly IPO'd companies ($3.6bn), plus estimated change in 2016 consensus forecast for all products forecast ($30.2bn). Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

19

2016: Top 50 Selling Products in the USA Rituxan Edges Ahead of Avastin and Humira; AMR101 Highest Ranking R&D Product EvaluatePharma® finds that Roche and Biogen Idec's Rituxan is set to become the top selling USA product in 2016, with sales of $3.6bn, narrowly beating Abbott's Humira, Roche's Avastin and Merck & Co's Januvia/Janumet to the No. 1 spot. Amarin's AMR101, a new Omega-3 fatty acid for dyslipidaemia, is the highest ranked R&D product, at number 13 in the list, with USA sales of $2.3bn in 2016. In total, 2016 forecasts for the top 50 products have increased by $7.0bn since April 2010, whilst all product forecasts have declined $5.8bn, signifying a shift in the concentration of value to the Top 50 products. USA Product Sales ($m)

WW Market

Generic Name rituximab

Company Roche + Biogen Idec

Pharmacological Class Anti-CD20 MAb

2010

2016

% Growth

2,910

3,570

+3%

Marketed

+27

+1%

2 Humira

adalimumab

Abbott Laboratories

Anti-TNFa MAb

2,872

3,538

+3%

Marketed

-257

-7%

3 Avastin

bevacizumab

Roche

Anti-VEGF MAb

3,068

3,450

+2%

Marketed

-141

-4%

4 Januvia/Janumet

sitagliptin phosphate

Merck & Co

2,139

3,417

+7%

Marketed

-116

-3%

5 Advair

fluticasone propionate; salmeterol xinafoate

GlaxoSmithKline

6 Revlimid

lenalidomide

Celgene

7 Lantus

Dipeptidyl peptidase IV (DPPIV) inhibitor & biguanide Beta 2 adrenoreceptor agonist & corticosteroid

Status

2016 Change

Product 1 Rituxan

vs Apr-10

4,026

3,266

-3%

Marketed

+848

+35%

Immunomodulator

1,433

2,949

+11%

Marketed

+266

+10%

insulin glargine recombinant Sanofi

Insulin

2,832

2,801

-0%

Marketed

-355

-11%

8 Enbrel

etanercept

Amgen

TNFa inhibitor

3,304

2,777

-2%

Marketed

-439

-14%

9 Remicade

infliximab

Johnson & Johnson

Anti-TNFa MAb

3,099

2,621

-2%

Marketed

+5

+0%

10 Atripla

efavirenz; emtricitabine; tenofovir

Gilead Sciences

NNRTI & NRTI

1,909

2,562

+4%

Marketed

+569

+29%

11 Prevnar 13

pneumococcal vaccine

Pfizer

Pneumococcal vaccine

1,761

2,450

+5%

Marketed

+1556

+174%

12 Neulasta

pegfilgrastim

Amgen

Colony stimulating factor

2,654

2,383

-2%

Marketed

+985

+70%

13 AMR101

icosapent ethyl

Amarin

Omega-3 fatty acid

-

2,289

Phase III

+2289

n/m

14 Herceptin

trastuzumab

Roche

Anti-HER2 (ErbB-2) MAb

1,530

2,150

+5%

Marketed

+394

+22%

15 Xgeva/Prolia

denosumab

Amgen

Anti-RANKL MAb

34

2,063

+80%

Marketed

-1067

-34%

16 Provenge

sipuleucel-T

Dendreon

Prostate cancer vaccine

48

1,993

+70%

Marketed

+330

+20%

17 Crestor

rosuvastatin calcium

AstraZeneca

2,640

1,981

-4%

Marketed

-189

-9%

18 Benlysta

belimumab

Human Genome Sciences

Marketed

-210

-10%

19 Copaxone

glatiramer acetate

-4%

Marketed

+330

+23%

20 Incivek

telaprevir

21 Truvada

Statin/ HMG CoA reductase inhibitor Anti-B lymphocyte stimulator (BLyS) MAb

-

1,980

2,287

1,743

-

1,730

Approved

+848

+96%

1,309

1,719

+4%

Marketed

+163

+11%

1,424

1,589

+2%

Marketed

+11

+1%

830

1,536

+9%

Marketed

+28

+2%

3,594

1,509

-12%

Marketed

-763

-34%

Insulin

847

1,469

+8%

Marketed

+166

+13%

Insulin

516

1,395

+15%

Marketed

+324

+30%

lisdexamfetamine dimesylate Shire

Psychostimulant

634

1,338

+11%

Marketed

+268

+25%

28 Lucentis

ranibizumab

Roche

Anti-VEGF MAb

1,402

1,314

-1%

Marketed

-171

-12%

29 Victoza

liraglutide recombinant

Novo Nordisk

Glucagon-like peptide 1 (GLP1) agonist

207

1,288

+30%

Marketed

+869

+207%

30 Eliquis

apixaban

Bristol-Myers Squibb

Factor Xa inhibitor

-

1,271

Filed

+151

+13%

31 Gammagard

immune globulin (human)

Baxter International

Immunoglobulin

921

1,238

+4%

Marketed

-278

-18%

32 Varivax

varicella vaccine

Merck & Co

Varicella vaccine

929

1,228

+4%

Marketed

+308

+33%

33 Zetia

ezetimibe

Merck & Co

Cholesterol absorption inhibitor

1,227

1,227

+0%

Marketed

-105

-8%

+87%

Teva Pharmaceutical Industries Vertex Pharmaceuticals

Hepatitis C protease inhibitor

emtricitabine; tenofovir disoproxil fumarate

Gilead Sciences

NRTI

22 Lyrica

pregabalin

Pfizer

Alpha 2 delta ligand

23 Botox

botulinum toxin type A

Allergan

Botulinum toxin

24 Epogen/Procrit

epoetin alfa

Amgen + J&J

Erythropoietin

25 NovoRapid

insulin aspart recombinant

Novo Nordisk

26 Levemir

insulin detemir recombinant

Novo Nordisk

27 Vyvanse

MS agent

34 Gilenya

fingolimod

Novartis

Sphingosine 1-phosphate (S1P) receptor modulator

15

1,220

Marketed

+804

+193%

35 Xarelto

rivaroxaban

Johnson & Johnson

Factor Xa inhibitor

-

1,215

Filed

-387

-24%

36 Brilinta

ticagrelor

AstraZeneca

P2Y12 antagonist

-

1,170

Marketed

-135

-10%

37 Humalog

insulin lispro recombinant

Eli Lilly

Insulin

1,222

1,155

-1%

Marketed

-195

-14%

38 Isentress

raltegravir potassium

Merck & Co

HIV integrase inhibitor

554

1,147

+11%

Marketed

+137

+14%

39 Alimta

pemetrexed disodium

Eli Lilly

Thymidylate synthase inhibitor

957

1,093

+2%

Marketed

-175

-14%

40 NovoSeven

eptacog alfa

Novo Nordisk

Factor VII

774

1,067

+5%

Marketed

+70

+7%

41 Premarin

estrogens, conjugated

Pfizer

Oestrogen agonist

949

1,062

+2%

Marketed

+208

+24%

42 Orencia

abatacept

Bristol-Myers Squibb

B7 integrin antagonist

547

1,034

+10%

Marketed

-42

-4%

43 Byetta/Bydureon

exenatide

Amylin + Eli Lilly

559

1,033

+9%

Marketed

-1048

-50%

Glucagon-like peptide 1 (GLP1) agonist Dipeptidyl peptidase IV (DPPIV) inhibitor

44 Onglyza

saxagliptin hydrochloride

Bristol-Myers Squibb

45 Avonex

interferon beta-1a

Biogen Idec

Interferon beta

119

1,020

+36%

Marketed

+132

+15%

1,492

1,016

-5%

Marketed

-407

46 Xifaxan

rifaximin

Salix Pharmaceuticals

-29%

Ansamycin

250

1,001

+22%

Marketed

-227

47 Velcade

bortezomib

Takeda

-18%

Proteasome inhibitor

594

998

+8%

Marketed

+888

+807% +84%

48 Tysabri

natalizumab

Elan

Anti-VLA-4 MAb

593

990

+8%

Marketed

+451

49 Advate

factor VIII (procoagulant)

Baxter International

Factor VIII

682

989

+5%

Marketed

-73

-7%

Pfizer

Janus kinase-3 (JAK-3) inhibitor

-

987

Phase III

+379

+62%

+7023

+9%

-5849

-2%

50 CP-690550

tofacitinib citrate

Total Total USA Individual Products Forecast in EvaluatePharma®

61,694

88,028

245,150

251,741

+5% +2%

Source: EvaluatePharma® (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

20

Worldwide Rx & OTC Sales by Therapy Area in 2010 Oncology Segment Largest Segment in 2010 EvaluatePharma® found that sales from products within the oncology therapeutic category grew by 6% in 2010 to $60.0bn, maintaining its lead over anti-hypertensives as the largest therapeutic category. 2009's fastest growing category, anti-virals, saw the biggest decline amongst the top 15 categories, as sales fell by 11% to $22.1bn. This decline was driven by a sharp drop in sales of GSK's Valtrex following patent expiration in December 2009, as well as a decline in H1N1 (swine flu) treatments following stockpiling in 2009.

Analysis on Top 10 Therapy Sales in 2010, Market Share & Sales Growth (2009-10)

WW Market Share %

Source: EvaluatePharma® (25 MAY 2011) 12%

Key Drivers Avastin (Roche) Alimta (Lilly) Revlimid (Celgene)

10%

8%

Patent Expiries Eloxatin (Sanofi) Arimidex (AZN)

Oncology

Key Growth Breaks (H1N1) Tamiflu (Roche) Relenza (GSK)

Anti-hypertensives

6%

Bronchodilators Anti-diabetics

4%

Anti-hyperlipidaemics Anti-virals

2%

Antacids and Antiulcerants

Anti-rheumatics

Vaccines

Anti-psychotics

Key Drivers Humira (Abbott) Enbrel (Amgen/Pfizer) Remicade (J&J/ Merck)

0% -15%

-10%

-5%

+0%

+5%

+10%

+15%

+20%

% Sales Growth: 2009-10

WW Rx & OTC Sales by Therapy Area: Top 15 Categories

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

WW Sales ($bn) 2010 % Growth

WW Market Share 2010 Chg. (+/-)

Rank Chg. (+/-)

Therapy Area

2009

Oncology Anti-hypertensives Bronchodilators Anti-rheumatics Anti-diabetics Anti-hyperlipidaemics Vaccines Anti-virals Anti-psychotics Antacids and Anti-ulcerants Anti-bacterials Sensory organs Antidepressants Platelet aggregation inhibitors Dermatologicals Top 15 Other Total WW Rx & OTC Sales

56.4

60.0

+6%

8.2%

8.5%

+0.3%

42.0

40.9

-2%

6.1%

5.8%

-0.3%

-

30.9

32.8

+6%

4.5%

4.6%

+0.1%

-

29.0

32.7

+13%

4.2%

4.6%

+0.4%

+1

27.4

30.6

+12%

4.0%

4.3%

+0.3%

+1

29.3

29.8

+2%

4.3%

4.2%

-0.0%

-1

23.4

25.3

+8%

3.4%

3.6%

+0.2%

+1

24.7

22.1

-11%

3.6%

3.1%

-0.5%

-1

18.3

19.2

+5%

2.7%

2.7%

+0.0%

-

17.7

16.9

-5%

2.6%

2.4%

-0.2%

-

16.1

15.4

-5%

2.3%

2.2%

-0.2%

-

12.4

13.8

+12%

1.8%

2.0%

+0.2%

+2

13.9

13.7

-1%

2.0%

1.9%

-0.1%

-1

12.8

12.6

-2%

1.9%

1.8%

-0.1%

-1

11.1

12.4

+11%

1.6%

1.7%

+0.1%

-

365.3

378.0

+3.5%

53.1%

53.5%

+0.3%

322.3

329.1

+2.1%

46.9%

46.5%

-0.3%

687.5

707.1

+2.8%

100.0%

100.0%

+194.6

54.1

61.2

+13.2%

7.9%

8.7%

+0.8%

30.9

31.9

+3.3%

4.5%

4.5%

+0.0%

2009

-

Total 'Rx & OTC Sales' includes: WW Unbranded Generic Sales OTC Pharmaceuticals

Note: Industry sales based on Top 500 pharmaceutical and biotech companies. Sales in 2010 based on company reported data.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

21

Worldwide Prescription Drug Sales in 2010 GSK Out of Top 5; First Time Since Late 1980s. Pfizer Maintain No.1 Positions EvaluatePharma® found that GSK dropped out of the World's Top 5 companies in 2010, based on booked end-user prescription drug sales, which represents the first time GSK has been out of the top 5* since the late 1980s. GSK sales declined 2% to $35.6bn in 2010. Pfizer maintained its number one position, in terms of worldwide prescription drug sales, as it benefited from the first full year of consolidating Wyeth, acquired in October 2009. Teva continues to rise up the ranking from 15th to 13th in the World. Sanofi was the worst performing global major, recording a 4% decline in worldwide prescription drug sales as it was hit by generic competition on Lovenox, Eloxatin, Plavix and Allegra. In 2010, despite the decline in sales of vaccines and treatments for swine flu in 2010, prescription drug sales growth increased to 2.9% in 2010 vs. 2.5% in 2009.

60 Sales ($bn) Growth rate % Ranking Chg. 2009-10

54.1 28%

40

41.4

40.4

12%

30

45%

36.6

35.6

35.6

-4%

-1%

-2%

32.1

GlaxoSmithKline

-1

AstraZeneca

-2

Roche

-2

Sanofi

+4

Merck & Co**

Pfizer**

0

+1

Novartis

10

20.8

20.7

19.9

+6%

-2%

+21%

+1

-1

Johnson & Johnson

+1%

20

Abbott Laboratories**

50

Eli Lilly

WW Prescription Sales ($bn)

Global Ranking on WW Prescription Drug Sales in 2010 Source: EvaluatePharma® (25 MAY 2011)

WW Prescription Sales in 2010: Top 20 Companies

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Pfizer** Novartis Merck & Co** Sanofi Roche GlaxoSmithKline AstraZeneca Eli Lilly Johnson & Johnson Abbott Laboratories** Bristol-Myers Squibb Amgen Teva Pharmaceutical Industries Bayer Boehringer Ingelheim Takeda Novo Nordisk Daiichi Sankyo Astellas Pharma Baxter International Total Top 20 Other Total

WW Prescription Sales ($bn) 2009 2010 % Growth

2009

WW Market Share 2010 Chg. (+/-)

42.4

54.1

+28%

6.5%

8.0%

+1.6%

-

37.0

41.4

+12%

5.6%

6.1%

+0.5%

+1

27.8

40.4

+45%

4.2%

6.0%

+1.8%

+4

38.3

36.6

-4%

5.8%

5.4%

-0.4%

-2

36.0

35.6

-1%

5.5%

5.3%

-0.2%

-

36.3

35.6

-2%

5.5%

5.3%

-0.3%

-2

31.6

32.1

+1%

4.8%

4.7%

-0.1%

-1

19.7

20.8

+6%

3.0%

3.1%

+0.1%

+1

21.2

20.7

-2%

3.2%

3.1%

-0.2%

-1

16.5

19.9

+21%

2.5%

2.9%

+0.4%

-

14.8

15.5

+5%

2.3%

2.3%

+0.0%

-

14.4

14.7

+2%

2.2%

2.2%

-0.0%

-

12.5

14.5

+16%

1.9%

2.1%

+0.2%

+2

14.3

14.2

-0%

2.2%

2.1%

-0.1%

-1

13.8

12.6

-9%

2.1%

1.9%

-0.2%

-1

11.9

12.6

+5%

1.8%

1.9%

+0.0%

-

9.6

10.8

+13%

1.5%

1.6%

+0.1%

+1

9.2

10.8

+17%

1.4%

1.6%

+0.2%

+1

9.7

10.3

+6%

1.5%

1.5%

+0.0%

-2

7.8

8.1

+4%

1.2%

1.2%

+0.0%

-

424.7

461.1

+9%

64.7%

68.3%

+3.6%

231.4

213.7

-8%

35.3%

31.7%

656.1

674.8

+2.9%

100.0%

100.0%

Rank Chg. (+/-)

Source: EvaluatePharma® (25 MAY 2011) Note: Sales in 2010 based on company reported data. Excludes alliance revenue and royalties where possible. *GSK and Glaxo have consistently been in the Top 5 since late 1980s. **Abbott, Merck & Co and Pfizer based on reported data for 2009/10, not pro-forma. (Abbott acquired Solvay Pharmaceuticals in Feb 2010, Merck & Co acquired Schering-Plough in Nov 2009 and Pfizer acquired Wyeth in Oct 2009.) Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

22

Worldwide Generic Drug Sales in 2010 Teva Dominates Generic Segment in 2010; Generic Market Expands 13%* EvaluatePharma® found that Teva Pharmaceutical continued to dominate the rapidly expanding generic drug market in 2010 with a global market share of 18%. Teva benefited from the consolidation of sales from its $5.3bn acquisition of German generics company ratiopharm, in August 2010. Sanofi experienced strong growth of 44% in 2010 as it benefited from the first full year consolidation of sales from its acquisitions of Zentiva, Medley and Kendrick in 2009. Overall the generic drug market expanded 13% in 2010 based on EvaluatePharma® coverage*.

Sales ($bn) Growth rate % Ranking Chg. 2009-10

11.0 +17%

7 6 5

7.7 15%

+12%

2.3

2.0

2.6

+2

+27%

+55%

-5%

2.0

2.0

1.8

1.5

+2

-1

+3

Watson Pharmaceuticals

Actavis

Mylan

Novartis

Teva Pharmaceutical Industries

0

+44%

STADA Arzneimittel

+38%

Daiichi Sankyo

+5%

+6%

Aspen Pharmacare

5.0

4 3 2 1

Sanofi

12 11 10 9 8

Hospira

WW Generic Sales ($bn)

Global Ranking on WW Generic Drug Sales in 2010 Source: EvaluatePharma® (25 MAY 2011)

WW Unbranded Generic Drug Sales in 2010: Top 20 Companies

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Teva Pharmaceutical Industries Novartis Mylan Actavis Watson Pharmaceuticals Hospira Sanofi Daiichi Sankyo Aspen Pharmacare STADA Arzneimittel Apotex Sun Pharmaceutical Industries Cipla ratiopharm Fresenius Krka Dr. Reddy's Laboratories Lupin Abdi Ibrahim Par Pharmaceutical Companies Total Top 20 Other Total

WW Generic Sales ($bn) 2009 2010 % Growth

2009

WW Market Share 2010 Chg. (+/-)

Rank Chg. (+/-)

9.4

11.0

+17%

17.4%

18.0%

+0.6%

-

6.7

7.7

+15%

12.3%

12.5%

+0.2%

-

4.7

5.0

+6%

8.7%

8.2%

-0.5%

-

2.4

2.6

+5%

4.5%

4.2%

-0.3%

-

1.6

2.3

+38%

3.0%

3.7%

+0.7%

+2

1.8

2.0

+12%

3.4%

3.3%

-0.0%

-

1.4

2.0

+44%

2.6%

3.3%

+0.7%

+3

1.6

2.0

+27%

2.9%

3.3%

+0.4%

-

1.2

1.8

+55%

2.2%

3.0%

+0.8%

+2

1.6

1.5

-5%

2.9%

2.4%

-0.5%

-1

1.0

1.3

+21%

1.9%

2.1%

+0.1%

+3

0.8

1.2

+45%

1.6%

2.0%

+0.4%

+7

1.0

1.2

+19%

1.9%

2.0%

+0.1%

+2

2.3

1.2

-49%

4.3%

1.9%

-2.4%

-9

0.9

1.1

+29%

1.6%

1.9%

+0.2%

+2

1.1

1.1

-0%

2.0%

1.8%

-0.2%

-4

1.0

1.1

+14%

1.8%

1.8%

+0.0%

-1

0.8

1.1

+24%

1.6%

1.7%

+0.1%

-

0.8

0.9

+8%

1.5%

1.5%

-0.1%

+1 -7

1.1

0.9

-19%

2.0%

1.4%

-0.6%

43.3

48.9

+13%

80.2%

79.9%

-0.2%

10.7

12.3

+14%

19.8%

20.1%

54.1

61.2

+13%

100.0%

100.0%

Source: EvaluatePharma® (25 MAY 2011) Note: Sales in 2010 based on company reported data. ratiopharm sales for 2010 reflect the period January 2010 to August 2010, when the company was acquired by Teva. Abdi Ibrahim, Actavis, Apotex, Aspen, Cipla, Dr. Reddy's, Lupin, and Sun based on forecast data for 2010. *EvaluatePharma® coverage: 66 generic companies. Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

23

M&A Analysis: 2006 to 2010 M&A Deal Value Slumps in 2010, Following Bumper 2009 EvaluatePharma® found that total deal values from M&A involving pharmaceutical companies declined by 60% to $75bn in 2010, compared to $188bn in 2009, which was a bumper year for M&A with 3 mega-mergers completed; Pfizer-Wyeth, Merck-Schering-Plough and Roche-Genentech. The number of deals increased marginally (+5%) to 152 deals closing in 2010. The biggest deal of the year was Novartis acquiring a majority stake in Alcon for $28.1bn. This followed an acquisition of a minority stake back in 2008. 2010 also saw further consolidation in the generic sector, with Teva acquiring ratiopharm, Endo acquiring Qualitest, Cephalon acquiring Mepha and Mylan acquiring Bioniche Pharma. Count of Pharma M&A Deals vs. Total Pharma M&A Value (2006 (2005 - 2010) 2009) Source: EvaluatePharma® (25 (30 MAY APR 2010) 2011)

Target [Acquiror] (Deal Value)

DealDeal Value ($bn) Value ($bn)

300

300 2005 2006 FUJ SCH[YAM] [BAY]($20.8bn) ($21.3bn) PFE SAN Cons [DAI][JNJ] ($15.4bn) ($16.6bn)

2008 2007 Alcon [NVS] ($10.4bn) Organon [SGP] ($15.6bn) MEDI [AZN] ($15.6bn) Serono [Merck] ($13.8bn)

2009 WYE [PFE] ($68.0bn) 2008 DNA ($46.8bn) Alcon[Roche] [NVS] ($10.4bn) SGP [MRK] ($41.1bn)

2007 2006 Organon [SGP]($21.3bn) ($15.6bn) SCH [BAY] MEDI [AZN] ($15.6bn) PFE Cons [JNJ] ($16.6bn) Serono [Merck] ($13.8bn)

250

200

153 150

2010 2009 Alcon[PFE] [NVS]($68.0bn) ($28.1bn) WYE DNA [Roche] ($46.8bn) SGP [MRK] ($41.1bn)

145

250

200

152

150

134

124

173% Growth

100

Count DealDeal Count

350

100

50

50 $101bn

$86bn

$69bn

$188bn

$75bn

2006

2007

2008

2009

2010

0

0 Deal Value

Deal Count

Count of Pharma M&A Deals vs. Total Pharma M&A Value (2006 - 2010) Year Deal Count % Chg. Deal Value ($bn) % Chg.

2006

2007

2008

2009

2010

124

134

153

145

152

8%

14%

-5%

5%

86

69

188

75

-15%

-20%

171%

-60%

101

Top 10 M&A Deals in 2010: Ranked on Deal Value Target 1 2 3 4 5 6 7 8 9 10

Target Location USA Belgium Germany USA USA India USA USA USA Japan

Alcon Solvay Pharma ratiopharm Valeant OSI Pharmaceuticals Piramal (Solutions) Abraxis BioScience Chattem Qualitest SSP Other Total Source: EvaluatePharma® (25 MAY 2011)

Target Focus Specialty Regional Major Generic Specialty Biotechnology Generic Specialty Specialty Generic Regional Major

Acquiror Novartis Abbott Laboratories Teva Biovail Astellas Pharma Abbott Laboratories Celgene Sanofi Endo Pharmaceuticals Boehringer Ingelheim

Completion Deal Date Value ($bn) 26 Aug 10 28.1 15 Feb 10 6.6 10 Aug 10 5.0 28 Sep 10 4.5 09 Jun 10 4.0 08 Sep 10 3.8 15 Oct 10 2.9 09 Feb 10 1.9 01 Dec 10 1.2 14 Apr 10 0.8 15.9 74.6

Note: Analysis based on closing date of deal.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

24

Venture Financing Analysis: 2006 to 2010 New Analysis Venture Financing Deals Fall in 2010 EvaluatePharma® found that in 2010 both the number of venture financing deals, down 10% to 298, and the total deal value, down 7% to $4.9bn, fell vs. 2009. The value of venture financing deals can be viewed as a indicator of R&D investment in the private Biotech sector. At $4.9bn it represents a mere 4% of the total pharmaceutical R&D spend of $127bn. The trend in venture financing has been flat for the last 3 years. Of the top 10 venture financing deals in 2010, 7 were for US-based companies, with the biggest being Alvogen, a company focused on the development of complex generics, which raised $200m in November 2010. Count of Venture Financing Deals vs. Total Venture Financing Value (2006 - 2010) Source: EvaluatePharma® (25 MAY 2011) 700

7000

6000

600

$6,210m

500

$5,251m $4,909m

$4,893m 4000

400 333

3000

330 300

298

291

286

Deal Count

Deal Value ($m)

$5,604m 5000

2000

200

1000

100

0

0 2006

2007

2008 Deal Value

2009

2010

Deal Count

Count of Pharma Venture Financing Deals vs. Total Pharma Venture Financing Value (2006 - 2010) Year Deal Count % Chg. Deal Value ($m) % Chg.

2006

2007

2008

2009

286

333

291

330

298

16%

-13%

13%

-10%

6,210

4,893

5,251

4,909

11%

-21%

7%

-7%

5,604

2010

Top 10 Venture Financing Deals in 2010: Ranked on Deal Value Company 1 2 3 4 5 6 7 8 9 10

Listed / Private Private Listed Listed Private Private Private Private Private Private Private

Alvogen Group Lexicon Pharmaceuticals Theravance Archimedes Pharma Reata Pharmaceuticals AiCuris Relypsa immatics biotechnologies Pearl Therapeutics TESARO Other Total Source: EvaluatePharma® (25 MAY 2011)

Country

Company Type USA Generic USA Biotechnology USA Biotechnology UK Biotechnology USA Biotechnology Germany Biotechnology USA Biotechnology Germany Biotechnology USA Specialty USA Biotechnology

Financing Round Undisclosed PIPE PIPE Undisclosed Series G Series B Series B Series C Series C Series A

Date 19 Nov 10 19 Mar 10 29 Nov 10 02 Mar 10 12 Jul 10 14 Apr 10 13 Sep 10 21 Sep 10 19 Oct 10 26 May 10

Deal Value ($m) 200 181 129 100 78 75 70 70 69 60 3,877 4,909

Note: Includes investments in pharmaceutical and biotech companies only. Does not include genomics or medical devices companies. Includes Private Investment in Public Equity (PIPE).

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

25

Key Product Events Positively Impacting Shareholder Value in 2010 New Analysis Crestor Ruling Largest Positive Event in 2010 The analysis below highlights the top 15 product events which positively impacted shareholder value on the day of announcement (measured by change in market capitalization) in 2010. The largest event was a US court ruling on Crestor, which removed the threat of generics prior to 2016. This event initially added $5.8bn in value, +9% share price gain, to AstraZeneca. The approval of Prolia (denosumab) was the second biggest event, adding $5.1bn to the market cap. of Amgen, reflecting a 11% share price gain.

Event Type

Product

Therapy Area

1 AstraZeneca

Litigation

Crestor

Anti-hyperlipidaemics

2 Amgen

FDA Approval (PDUFA)

Prolia

3 Pfizer

Phase III Trial Results

4 GlaxoSmithKline

Company

Date

Commentary on Share Price Change

29 Jun 10 29 Jun: A US court rules that the patent on the company's cholesterol-lowering drug Crestor is valid, removing the threat of generic versions of the drug entering the US market until the patent expires in 2016.

% Share Market Cap Price Change Change +9%

+5,760

Bone calcium regulators 02 Jun 10 1 Jun [post market]: Company receives FDA approval for its key growth driver, osteoporosis drug Prolia, nearly two months ahead of the expected action date of 25 Jul.

+11%

+5,106

Eliquis

Anti-coagulants

11 Jun 10 10 Jun [post-market]: Company and partner BristolMyers Squibb end phase III trial of anti-coagulant drug apixaban early, after clear efficacy is seen in a trial attempting to demonstrate a lower risk of stroke in patients with atrial fibrillation.

+4%

+4,436

Competitor Announcement

Advair

Other bronchodilators

18 Mar 10 18 Mar: Shares rise on news that Novartis' generics division, Sandoz, has returned the US rights to lung drug, VR315, a potential generic competitor to GlaxoSmithKline's asthma drug, Advair, back to Vectura, due to potential difficulties in getting the drug to market in the US.

+4%

+4,003

5 Novo Nordisk

Competitor Announcement

Victoza

Anti-diabetics

20 Oct 10 20 Oct: Shares rise following the FDA's complete response letter for Amylin's diabetes drug, Bydureon, a potential competitor for Novo Nordisk's diabetes treatment, Victoza, which received FDA approval in January.

+9%

+3,834

6 Pfizer

Litigation

Protonix

Antacids & antiulcerants

23 Apr 10 23 Apr: A US federal court rules in the company's favour in a patent lawsuit with Teva over acid reflux drug, Protonix, stating that Pfizer's patent is valid and has been infringed by Teva.

+3%

+3,470

7 Teva

Phase III Trial Results

Laquinimod MS Therapies

09 Dec 10 9 Dec: Company and partner Active Biotech announce positive headline data from first of two phase III trials for their oral MS drug, laquinimod, meeting primary and secondary efficacy endpoints as well as demonstrating a comparable safety profile to placebo.

+7%

+3,145

8 Novartis

Competitor Announcement

Gilenya

MS Therapies

24 Sep 10 24 Sep: The CHMP issues rival Merck KGaA with a negative opinion for its oral MS treatment, cladribine, stating that the drug's benefits do not outweigh its risks.

+2%

+2,708

9 Amgen

Phase III Trial Results

Xgeva

Bone calcium regulators 14 Dec 10 13 Dec [post market]: Top-line phase III results for the company's bone drug, Xgeva (denosumab), demonstrate that the drug significantly improved median bone metastasis-free survival by 4.2 months compared to placebo.

+5%

+2,506

10 Bristol-Myers

Phase III Trial Results

Yervoy

Anti-neoplastic MAbs

07 Jun 10 7 Jun: Phase III trial results for company's melanoma treatment, ipilimumab, presented at ASCO on 5 Jun, show that the drug prolongs life and survival of patients by 34%.

+6%

+2,442

11 GlaxoSmithKline

FDA Advisory Committee

Benlysta

Immunosuppressants

17 Nov 10 16 Nov: An FDA advisory panel votes 13 to 2 in favour of approving company and partner, Human Genome Sciences' lupus drug, Benlysta; final FDA decision due on 9 Dec.

+2%

+2,389

12 Bayer

Phase III Trial Results

Xarelto

Anti-coagulants

15 Nov 10 15 Nov: Company and partner, Johnson & Johnson, report phase III data for anti-clotting drug, Xarelto, which show that the drug is better at preventing stroke than standard treatment, warfarin, with lower risk of intracranial bleeding.

+4%

+2,372

13 GlaxoSmithKline

Broker Upgrade

Potiga

Anti-epileptics

12 Aug 10 11 Aug [post market]: An FDA advisory panel unanimously recommends approval of the company and partner Valeant Pharmaceuticals' epilepsy drug, ezogabine (Potiga); final FDA decision due by 30 Aug.

+3%

+2,322

14 AstraZeneca

FDA Advisory Committee

Brilinta

Platelet aggregation inhibitors

28 Jul 10 28 Jul: An FDA advisory panel votes 7-1 in favour of recommending approval for the company's blood thinner, Brilinta; final FDA decision due by 16 Sep.

+3%

+2,274

15 GlaxoSmithKline

FDA Advisory Committee

Avandia

Anti-diabetics

06 Jul 10 6 Jul: Shares likely to remain volatile ahead of FDA meetings on 13-14 July to review cardiovascular safety issues for Avandia.

+3%

+2,229

Top 15 Total

+48,996

Total Events Positively Impacting Shareholder Value in 2010

+366,102

Source: EvaluatePharma®'s EventAnalyzer (25 MAY 2011) Note: EvaluatePharma®'s EventAnalyzer contains a back catalogue of events which had the greatest impact on company valuations dating back to December 2007. Events can be viewed by Company, Product, Therapy Area and Peer Group to see instantly the impact of events on company valuation and the news flow driving share price movement. Events are categorized into 100 unique Event Type classifications, allowing you to track the market impact of key types of news flow (e.g. regulatory approvals, financial results, patent litigation, broker sentiment and competitor announcements, etc).

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

26

Key Product Events Negatively Impacting Shareholder Value in 2010 New Analysis Avastin Hit by Double Setback in 2010 The analysis below highlights the largest 15 product events negatively impacting shareholder value on the day of announcement (measured by change in market capitalization) in 2010. The largest two events both relate to Roche's Avastin, which saw its consensus forecast tumble over the year following negative PIII results in prostate cancer and a negative opinion from an FDA Advisory Committee on breast cancer. Together these events wiped $9.2bn off Roche's market cap., a 7% decline in its share price.

Product

Therapy Area

Phase III Trial Results

Avastin

Anti-neoplastic MAbs

12 Mar 10 12 Mar: Avastin (bevacizumab) fails to meet its primary phase III endpoint of extending overall survival in prostate cancer patients, compared with chemotherapy and prednisone alone.

-+3%

-+4,724

2 Roche

FDA Advisory Committee

Avastin

Anti-neoplastic MAbs

21 Jul 10 20 Jul [post market]: An FDA advisory panel votes 121 in favour of revoking Avastin's approval for breast cancer, stating that studies show insufficient benefit for patients; final FDA decision due 17 Sep.

-+4%

-+4,500

3 Teva

Competitor Announcement

Copaxone

MS Therapies

23 Jul 10 23 Jul: Momenta Pharmaceuticals receives FDA approval for its generic version of Sanofi' blood thinner, Lovenox, raising fears that the FDA may soon approve a generic version of Copaxone; Momenta confirms in a conference call that it is working with the FDA on its Copaxone application.

-+9%

-+4,323

4 Merck & Co

Pricing Issues

Vytorin

Anti-hyperlipidaemics

21 Apr 10 21 Apr: Bloomberg reports that UnitedHealth Group, the US' biggest medical insurer by sales, plans to double the amount it will charge for company’s cholesterol pills, Vytorin and Zetia, from 1 Jul, raising concerns that the move will deter patients from using the medicines.

-+4%

-+4,115

5 AstraZeneca

Complete Response Letter

Brilinta

Platelet aggregation inhibitors

17 Dec 10 16 Dec [post market]: Company receives an FDA complete response letter for its heart drug, Brilinta, requesting further analyses of phase III trial data, but not additional clinical studies, potentially delaying US approval of the drug by a further nine months.

-+6%

-+4,023

6 Roche

Phase III Trial Results

Taspoglutide Anti-diabetics

18 Jun 10 18 Jun: Company announces the implementation of a risk mitigation plan in its phase III programme for diabetes drug, taspoglutide, following cases of hypersensitivity in patients, leading to a potential delay in filing of at least 12-18 months.

-+2%

-+3,490

7 Pfizer

Product Suspended

Tanezumab

Non-narcotic analgesics 24 Jun 10 23 Jun [post market]: Company suspends phase III trials of its osteoarthritis drug, tanezumab, after some patients taking the drug experienced a worsening of their condition that required joint replacement surgery.

-+3%

-+3,388

8 Sanofi

New Company Financial Guidance

Lovenox

Anti-coagulants

23 Jul 10 23 Jul: Company cuts its 2010 financial outlook after Momenta Pharmaceuticals receives FDA approval for its generic version of Lovenox.

-+4%

-+3,323

9 Merck & Co

Pricing Issues

Vytorin

Anti-hyperlipidaemics

22 Apr 10 Shares continue to fall after Bloomberg reported on 21 Apr that UnitedHealth Group, the US' biggest medical insurer by sales, plans to double the amount it will charge for Vytorin and Zetia from 1 Jul, raising concerns that the move will deter patients from using the medicines.

-+3%

-+3,024

10 Pfizer

FDA Filing

Sutent

Anti-angiogenics

13 May 10 13 May: Mylan files for FDA approval of its generic version of Pfizer's cancer drug, Sutent, challenging several patents on the drug which expire in 2021.

-+2%

-+2,743

11 GlaxoSmithKline

Safety Concerns Avandia

Anti-diabetics

22 Feb 10 22 Feb: The FDA begins reviewing data on possible heart risks linked to Avandia following the release of FDA documents on 20 Feb which included a 2008 memo from FDA drug safety reviewers who recommended withdrawing the drug from the US market due to safety concerns.

-+3%

-+2,713

12 Sanofi

Side Effect Risk/ Lantus Negative Label

Anti-diabetics

18 Jun 10 18 Jun: A new study published in the Diabetes Care journal suggests that company's diabetes drug, Lantus, raises the risk of cancer versus other insulins.

-+3%

-+2,707

13 Roche

Side Effect Risk/ Avastin Negative Label

Anti-neoplastic MAbs

03 May 10 3 May: German newspaper Handelsblatt, states that the company's cancer drug, Avastin, is only marginally effective and has significant toxicity.

-+2%

-+2,487

14 AstraZeneca

Litigation

Crestor

Anti-hyperlipidaemics

30 Jun 10 Shares fall back slightly after rising 9% on 29 Jun after a US court rules that the patent on Crestor is valid, removing the threat of generic versions of the drug entering the US market until the patent expires in 2016.

-+3%

-+2,350

15 Novo Nordisk

Competitor Announcement

Novolin

Anti-diabetics

18 Oct 10 18 Oct: Shares fall on news that Pfizer has signed a deal with Biocon to sell its biosimilar versions of insulin, which will compete with Novo's brands, Novolin and Novolog.

-+5%

-+2,343

Company

Date

Commentary on Share Price Change

% Share Market Cap Price Change Change

Event Type

1 Roche

Top 15 Total

-+50,253

Total Events Positively Impacting Shareholder Value in 2010

-+321,620

Source: EvaluatePharma®'s EventAnalyzer (25 MAY 2011) Note: EvaluatePharma®'s EventAnalyzer contains a back catalogue of events which had the greatest impact on company valuations dating back to December 2007. Events can be viewed by Company, Product, Therapy Area and Peer Group to see instantly the impact of events on company valuation and the news flow driving share price movement. Events are categorized into 100 unique Event Type classifications, allowing you to track the market impact of key types of news flow (e.g. regulatory approvals, financial results, patent litigation, broker sentiment and competitor announcements, etc).

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

27

Enterprise Value Analysis: 2009 to 2010 Johnson & Johnson Maintains No.1 Position in Enterprise Value Rankings in 2010 EvaluatePharma® found that despite losing 7% of its value in 2010 Johnson & Johnson retained its No.1 ranking in terms of enterprise value in 2010, with a valuation of $159bn. Novo Nordisk demonstrated an impressive 59% increase in enterprise value and 70% increase in share price following approval of Victoza, positive pipeline developments for Degludec, clinical setbacks for potential competitor taspoglutide and safety scares for Sanofi’s long-acting insulin, Lantus. Roche's enterprise value fell 16% to $142bn, primarily on setbacks to Avastin and taspoglutide. Global Ranking on Enterprise Value in 2010 Source: EvaluatePharma® (31 DEC 2010) 180

+80% $158bn

$156bn

$150bn

+70% $142bn

+40%

100

$85bn

+30%

$85bn

+20%

$71bn

80

$61bn

60

+12% -0%

-10%

-10%

-11%

-20%

-10%

-30%

Novo Nordisk

Sanofi

-17% GlaxoSmithKline

Novartis

Pfizer

Johnson & Johnson

Roche

-17%

0

Bayer

-2%

Abbott Laboratories

-3%

+10% +0%

40 20

+60% +50%

$114bn

120

Merck & Co

Market Cap ($bn)

140

+70%

$135bn

Share Price Performance (%)

160

Top 20 Companies in 2010: Ranked by Enterprise Value (based on valuation on 31 DEC 10)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Company Johnson & Johnson Pfizer Novartis Roche Merck & Co GlaxoSmithKline Sanofi Abbott Laboratories Bayer Novo Nordisk AstraZeneca Teva Pharmaceutical Amgen Alcon Reckitt Benckiser Bristol-Myers Squibb Eli Lilly Baxter International Gilead Sciences Takeda Total Top 20

Enterprise Value ($bn) 2009 2010 % Growth

Share Price ($ ADR) 2009 2010 % Growth

Enterprise Value Ranking 2009 2010 Chg. (+/-)

171.0

158.5

-7%

63.92

61.85

-3%

1

1

-

166.6

156.4

-6%

17.83

17.51

-2%

3

2

+1

115.6

149.8

+30%

52.48

58.95

+12%

6

3

+3

168.8

141.7

-16%

170.66

141.50

-17%

2

4

-2

136.7

134.6

-2%

36.16

36.04

-0%

4

5

-1

124.0

114.4

-8%

42.25

39.22

-10%

5

6

-1

105.5

85.3

-19%

39.27

32.23

-17%

7

7

-

89.1

85.0

-5%

53.15

47.47

-11%

8

8

-

81.9

71.1

-13%

79.80

73.36

-10%

9

9

-

38.6

61.3

+59%

63.85

112.57

+70%

17

10

+7

65.7

58.2

-11%

46.94

46.19

-4%

10

11

-1

53.0

52.4

-1%

55.81

52.13

-7%

12

12

-

53.4

47.1

-12%

56.57

54.90

-3%

11

13

-2

46.4

46.2

-1%

164.35

163.40

-1%

13

14

-1

39.0

43.1

+10%

54.48

55.01

+1%

16

15

+1

40.6

42.7

+5%

24.95

26.15

+5%

15

16

-1

42.1

40.6

-4%

34.72

35.04

+1%

14

17

-3

36.6

31.0

-15%

58.39

50.62

-13%

19

18

+1

38.4

30.5

-21%

43.27

36.24

-16%

18

19

-1

26.3

28.1

+7%

45.35

20

-

1,577.7

-4%

+8% -1%

20

1,639.3

48.93 avg.

Source: EvaluatePharma® (31 DEC 2010)

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

28

Net Income in 2010: Top 20 Companies Pfizer No. 1 in Terms of Net Income in 2010 EvaluatePharma® found that Pfizer reported the industry’s largest net income (normalised) in 2010, recording $18bn. Of the Top 20 Teva recorded the largest improvement in net margin, up 3.9% to 25.6%, whilst benefiting from one of the lowest tax rates. GlaxoSmithKline's net income (normalised) fell 23% to $7.3bn, with the net margin falling 4.8% to 16.7%.

Net Income ($bn)

Global Ranking on Net Income Normalised: Top 10 Companies Source: EvaluatePharma® (25 MAY 2011) 20 Net income normalised ($bn) Growth rate %

18 16 14

18.0 +27% +27%

12

13.3 +3%

10 8

12.2 +2%

11.8 +24% +13%

6

10.7

10.5

+45% +45%

+7%

9.6 +5%

4

7.3 -23%

2

6.5 +12%

5.2 +8%

Eli Lilly

Abbott Laboratories*

GlaxoSmithKline

AstraZeneca

Roche

Merck & Co*

Novartis

Sanofi

Johnson & Johnson

Pfizer*

0

Net Income in 2010: Top 20 Companies

Company 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Pfizer* Johnson & Johnson Sanofi Novartis Merck & Co* Roche AstraZeneca GlaxoSmithKline Abbott Laboratories* Eli Lilly Amgen Bayer Teva Pharmaceutical Industries Bristol-Myers Squibb Gilead Sciences Takeda Reckitt Benckiser Novo Nordisk Baxter International Alcon Top 20

Net Margin

Net Income Normalised ($bn) 2009 2010 % Growth

2009

2010

14.2

18.0

+27%

28.4%

26.5%

-1.9%

12.9

13.3

+3%

20.9%

21.6%

+0.7%

Chg. (+/-)

12.0

12.2

+2%

29.4%

30.3%

+0.9%

9.5

11.8

+24%

21.0%

22.8%

+1.9%

7.4

10.7

+45%

27.0%

23.3%

-3.7%

9.8

10.5

+7%

21.7%

23.1%

+1.4%

9.2

9.6

+5%

27.9%

29.0%

+1.1%

9.5

7.3

-23%

21.4%

16.7%

-4.8%

5.8

6.5

+12%

18.9%

18.5%

-0.4%

4.9

5.2

+8%

22.2%

22.7%

+0.5%

4.9

4.9

+0%

33.5%

32.6%

-0.9%

4.2

4.6

+10%

9.6%

9.9%

+0.2%

3.0

4.1

+36%

21.8%

25.6%

+3.9%

3.6

3.7

+4%

19.1%

19.2%

+0.0%

2.7

3.1

+13%

38.8%

38.7%

-0.2%

3.9

2.9

-24%

24.5%

17.7%

-6.8%

2.2

2.6

+16%

18.3%

19.6%

+1.4%

2.0

2.6

+27%

21.1%

23.7%

+2.6%

2.3

2.4

+2%

18.5%

18.2%

-0.4%

2.1

2.1

+2%

31.6%

29.0%

-2.6%

126.1

138.2

+10%

23.8%

23.4%

Average

Source: EvaluatePharma® (25 MAY 2011) Measure: Net Income Normalised The accounting profit a company made during 2010, adjusted to exclude any one-off items, such as restructuring charges and disposal gains/ losses. *Abbott, Merck & Co and Pfizer based on reported data for 2009/10, not pro-forma.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

29

Net Income Margin in 2010: Top 20 Companies

60%

Global Ranking on Net Income Margin in 2010: Top 10 Companies Source: EvaluatePharma® (25 MAY 2011)

50% 49%

31%

31%

30%

30%

29%

Forest Laboratories

33%

Warner Chilcott

34%

Sanofi

36%

Sun Pharmaceutical

39% 30%

Celgene

40%

Amgen

Net Margin %

PDL BioPharma Continues to be the Most Profitable Pharma-Biotech Company in 2010 EvaluatePharma® found that for the third year running PDL BioPharma achieved the highest net income normalised margin at 48.8% in 2010, based on a net income of $168m and royalty revenues of $345m. PDL is the first company to spin-out its R&D unit (Facet Biotech) and effectively be run as listed royalty company, with no active R&D operations.

20% 10%

ViroPharma

Valeant Pharmaceuticals

Gilead Sciences

PDL BioPharma

0%

Net Margin in 2010: Top 20 Companies Net Margin

Company

2009

2010

Chg. (+/-)

Net Income - Normalised 2009 2010 % Growth

1 PDL BioPharma 59.3% 48.8% -10.5% 189 168 -10.7% 2 Gilead Sciences 38.8% 38.7% -0.2% 2,724 3,073 +12.8% 3 Valeant Pharmaceuticals 47.1% 35.6% -11.5% 387 421 +8.9% 4 ViroPharma 23.8% 34.1% +10.4% 74 150 +103.2% 5 Amgen 33.5% 32.6% -0.9% 4,899 4,900 +0.0% 6 Celgene 32.2% 31.3% -0.9% 862 1,129 +30.9% 7 Sun Pharmaceutical 34.4% 31.2% -3.1% 283 374 +32.1% 8 Sanofi 29.4% 30.3% +0.9% 12,027 12,229 +1.7% 9 Warner Chilcott 33.1% 29.9% -3.2% 475 890 +87.2% 10 Forest Laboratories 26.0% 29.3% +3.4% 1,067 1,284 +20.3% 11 Alcon 31.6% 29.0% -2.6% 2,051 2,082 +1.5% 12 AstraZeneca 27.9% 29.0% +1.1% 9,159 9,642 +5.3% 13 Biogen Idec 26.8% 27.3% +0.5% 1,175 1,288 +9.6% 14 Pfizer 28.4% 26.5% -1.9% 14,202 17,983 +26.6% 15 Teva Pharmaceutical 21.8% 25.6% +3.9% 3,029 4,134 +36.5% 16 Alexion Pharmaceuticals 20.6% 25.0% +4.4% 80 135 +69.5% 17 Pharmstandard 27.0% 24.0% -3.0% 206 235 +14.0% 18 Endo Pharmaceuticals 22.9% 23.9% +1.0% 334 410 +22.8% 19 Novo Nordisk 21.1% 23.7% +2.6% 2,016 2,566 +27.3% 20 Gedeon Richter 19.1% 23.4% +4.3% 254 311 +22.4% Source: EvaluatePharma® (25 MAY 2011) Measure: Net Margin A ratio measuring company profitability based on net income normalised divided by total revenue. Note: Analysis only includes companies with two consecutive years of profit and with 2010 profit in excess of $50m. Sun Pharmaceutical is based on forecast data for 2010.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

30

2010: Top 50 Selling Products in the World Lipitor is World's Largest Selling Product in 2010 EvaluatePharma® found that global brand sales of Lipitor, primarily sold globally by Pfizer and co-marketed with Astellas in Japan, recorded sales of $12.0bn in 2010, down 6% on $12.7bn in 2009. WW Product Sales ($bn) 2010

12,669

11,968

-6%

14.3

Chiral chemistry

Platelet ADP antagonist

9,492

9,148

-4%

13.2

Small molecule chemistry

GSK + Almirall + Faes

Beta 2 adrenoreceptor agonist & corticosteroid

7,920

8,067

+2%

12.7

Small molecule chemistry

etanercept

Amgen + Pfizer + Takeda

TNFa inhibitor

6,295

7,257

+15%

12.6

Recombinant product

5 Humira

adalimumab

Abbott + Eisai

Anti-TNFa MAb

5,584

6,742

+21%

8.4

Monoclonal antibody

6 Remicade

infliximab

J&J + Merck + Mitsubishi Tanabe

Anti-TNFa MAb

5,923

6,520

+10%

12.8

Monoclonal antibody

7 Avastin

bevacizumab

Roche

Anti-VEGF MAb

5,744

6,214

+8%

7.2

Monoclonal antibody

8 Diovan

valsartan

Novartis + Ipsen

Angiotensin II antagonist

6,091

6,126

+1%

14.7

Small molecule chemistry

Generic Name

Company

1 Lipitor

atorvastatin calcium

Pfizer + Astellas + Almirall

2 Plavix

clopidogrel bisulfate

BMS + Sanofi

3 Seretide/Advair

fluticasone propionate; salmeterol xinafoate

4 Enbrel

9 Rituxan

Pharmacological Class Statin/ HMG CoA reductase inhibitor

% Growth

Products

2009

Product

Age (Yrs)

Technology

rituximab

Roche + Biogen Idec

Anti-CD20 MAb

5,620

6,113

+9%

13.5

Monoclonal antibody

10 Crestor

rosuvastatin calcium

AstraZeneca + Shionogi + Chiesi

Statin/ HMG CoA reductase inhibitor

4,836

6,106

+26%

8.3

Small molecule chemistry

11 Seroquel

quetiapine fumarate

AstraZeneca + Astellas

5-HT2 (serotonin) & dopamine D2 antagonist

5,121

5,611

+10%

13.7

Small molecule chemistry

12 Singulair

montelukast sodium

Merck + Kyorin + Sigma-Tau

Leukotriene D4 antagonist

4,985

5,401

+8%

13.3

Small molecule chemistry

13 Herceptin

trastuzumab

Roche

Anti-HER2 (ErbB-2) MAb

4,862

5,221

+7%

12.7

Monoclonal antibody

14 Zyprexa

olanzapine

Eli Lilly

Atypical anti-psychotic

4,916

5,026

+2%

14.7

Small molecule chemistry

15 Nexium

esomeprazole magnesium

AstraZeneca

Proton pump inhibitor (PPI)

4,959

4,969

+0%

10.8

Chiral chemistry

16 Lantus

insulin glargine recombinant

Sanofi

Insulin

4,293

4,658

+9%

10.9

Recombinant product

17 Actos

pioglitazone hydrochloride

Takeda + Abbott

PPAR gamma agonist

4,194

4,601

+10%

11.8

Small molecule chemistry

18 Epogen/Procrit/Eprex

epoetin alfa

Amgen + J&J + Kyowa Hakko Erythropoietin Kirin

4,963

4,584

-8%

22.4

Recombinant product

19 Abilify

aripiprazole

Otsuka + BMS

5-HT1A & D2 partial agonist & 5-HT2 receptor antagonist

4,039

4,279

+6%

8.5

Small molecule chemistry

20 Gleevec/Glivec

imatinib mesylate

Novartis

Tyrosine kinase inhibitor

3,944

4,265

+8%

10.0

Small molecule chemistry

21 Aricept

donepezil hydrochloride

Eisai + Pfizer

Acetylcholinesterase inhibitor

3,913

3,814

-3%

14.3

Small molecule chemistry

22 Spiriva

tiotropium bromide monohydrate

Boehringer Ingelheim + Pfizer Muscarinic antagonist

3,351

3,799

+13%

9.0

Small molecule chemistry

23 Lovenox/Clexane

enoxaparin sodium

Sanofi

4,241

3,724

-12%

23.4

Small molecule chemistry

Heparin, low molecular weight (LMWH)

24 Neulasta

pegfilgrastim

Amgen

Colony stimulating factor

3,355

3,558

+6%

9.1

Recombinant product

25 Januvia/Janumet

sitagliptin phosphate

Merck + Ono + Almirall

Dipeptidyl peptidase IV (DPPIV) inhibitor

2,611

3,503

+34%

4.7

Small molecule chemistry

26 Cymbalta

duloxetine hydrochloride

Eli Lilly + Shionogi

SNRI

3,075

3,491

+14%

6.8

Small molecule chemistry

27 Lexapro/Cipralex

escitalopram oxalate

Forest + Lundbeck + Others

SSRI

3,403

3,467

+2%

9.2

Chiral chemistry

28 Copaxone

glatiramer acetate

Teva + Sanofi

MS agent

2,826

3,300

+17%

14.4

Small molecule chemistry

29 Blopress/Atacand

candesartan cilexetil

Takeda + AstraZeneca + Almirall

Angiotensin II antagonist

2,935

3,283

+12%

13.5

Small molecule chemistry

30 Micardis

telmisartan

Boehringer + Astellas + Bayer

Angiotensin II antagonist & thiazide

2,959

3,258

+10%

12.5

Small molecule chemistry

31 Avapro

irbesartan

Sanofi + BMS + Dainippon + Shionogi

Angiotensin II antagonist

3,087

3,119

+1%

13.7

Small molecule chemistry

32 Lyrica

pregabalin

Pfizer + Eisai

Alpha 2 delta ligand

2,840

3,077

+8%

6.7

Small molecule chemistry

33 Aranesp

darbepoetin alfa

Amgen + Kyowa Hakko Kirin

Erythropoietin

2,930

2,974

+2%

9.9

Recombinant product

34 Lucentis

ranibizumab

Novartis + Roche

Anti-VEGF MAb

2,338

2,935

+26%

4.9

Monoclonal antibody

35 Atripla

efavirenz; emtricitabine; tenofovir

Gilead Sciences

NNRTI & NRTI

2,382

2,927

+23%

4.8

Small molecule chemistry

36 Taxotere

docetaxel

Sanofi

Taxane

3,034

2,816

-7%

15.4

Plant extract

37 Symbicort

budesonide; formoterol fumarate dihydrate

AstraZeneca + Sigma-Tau

Beta 2 adrenoreceptor agonist & corticosteroid

2,309

2,760

+20%

10.7

Small molecule chemistry

38 Truvada

emtricitabine; tenofovir disoproxil fumarate

Gilead + Torii

NRTI

2,556

2,746

+7%

6.8

Small molecule chemistry

39 Celebrex

celecoxib

Pfizer + Astellas

COX-2 inhibitor

2,575

2,668

+4%

12.3

Small molecule chemistry

40 Avonex

interferon beta-1a

Biogen Idec

Interferon beta

2,323

2,518

+8%

15.0

Recombinant product

41 Human insulin & devices

insulin recombinant human

Novo Nordisk

Insulin

2,488

2,502

+1%

88.2

Recombinant product

42 Benicar/Olmetec

olmesartan medoxomil

Daiichi Sankyo + Forest

Angiotensin II antagonist

2,363

2,487

+5%

9.0

Small molecule chemistry

1,706

2,469

+45%

5.4

Small molecule chemistry

-

2,416

n/m

1.4

Bioengineered vaccine Small molecule chemistry

43 Revlimid

lenalidomide

Celgene

Immunomodulator

44 Prevnar 13

pneumococcal vaccine

Pfizer

Pneumococcal vaccine

45 Zetia

ezetimibe

Merck & Co

Cholesterol absorption inhibitor

2,413

2,297

-5%

8.5

46 Rebif

interferon beta-1a

Merck KGaA + Pfizer

Interferon beta

2,142

2,214

+3%

13.4

Recombinant product

47 Alimta

pemetrexed disodium

Eli Lilly

Thymidylate synthase inhibitor

1,706

2,209

+29%

7.2

Small molecule chemistry

48 Cozaar

losartan potassium

Merck + Sigma-Tau

Angiotensin II antagonist

3,598

2,141

-41%

16.3

Small molecule chemistry

49 NovoRapid

insulin aspart recombinant

Novo Nordisk

Insulin

1,825

2,120

+16%

11.7

Recombinant product

50 Humalog

insulin lispro recombinant

Eli Lilly

Insulin

1,959

2,054

+5%

15.0

Recombinant product

195,689

209,521

+7%

12.8

Total

Source: EvaluatePharma® (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

31

2010: Top 50 Selling Products in the USA Plavix Overtakes Lipitor to become USA No. 1 EvaluatePharma® found that sales of Plavix (clopidogrel), co-promoted by BMS and Sanofi in the US, expanded 11% to $6.2bn, making it the biggest product in the US in 2010. Conversely the biggest product in 2009, Pfizer's cholesterol lowering treatment, Lipitor, fell 6% in the USA, with 2010 sales of $5.3bn. The patents on both Plavix and Lipitor are set to expire in November 2011. USA Product Sales ($bn) Product 1 Plavix

Generic Name clopidogrel bisulfate

Company Bristol-Myers Squibb + Sanofi

2 Lipitor

atorvastatin calcium

Pfizer

3 Seretide/Advair

fluticasone propionate; salmeterol xinafoate

GlaxoSmithKline

4 Seroquel

quetiapine fumarate

AstraZeneca

5 Epogen/Procrit

epoetin alfa

Amgen + J&J

USA Age Company

Pharmacological Class

2009

2010

% Growth

(Yrs)

Strategy

Platelet ADP antagonist

5,556

6,154

+11%

13.5

In-licensed

5,667

5,329

-6%

14.4

Company acquisition

4,057

4,026

-1%

10.8

Organic

3,416

3,747

+10%

13.7

Organic

3,827

3,594

-6%

22.0

Statin/ HMG CoA reductase inhibitor Beta 2 adrenoreceptor agonist & corticosteroid 5-HT2 (serotonin) & dopamine D2 antagonist Erythropoietin

6 Actos

pioglitazone hydrochloride

Takeda

PPAR gamma agonist

3,207

3,582

+12%

11.9

Organic

7 Abilify

aripiprazole

Otsuka + BMS

5-HT1A & D2 partial agonist & 5-HT2 receptor antagonist

3,296

3,348

+2%

8.5

Organic

8 Enbrel

etanercept

Amgen + Pfizer

TNFa inhibitor

3,283

3,304

+1%

12.6

Company acquisition

9 Singulair

montelukast sodium

Merck & Co

Leukotriene D4 antagonist

3,044

3,219

+6%

13.3

Organic

10 Remicade

infliximab

Johnson & Johnson

Anti-TNFa MAb

3,088

3,099

+0%

12.8

Company acquisition

11 Avastin

bevacizumab

Roche

Anti-VEGF MAb

3,061

3,068

+0%

7.2

Company acquisition

12 Rituxan

rituximab

Roche + Biogen Idec

Anti-CD20 MAb

2,784

2,910

+5%

13.5

Company acquisition

13 Humira

adalimumab

Abbott Laboratories

Anti-TNFa MAb

2,519

2,872

+14%

8.4

Company acquisition

14 Lantus

insulin glargine recombinant Sanofi

Insulin

2,661

2,832

+6%

11.1

Company acquisition

15 Cymbalta

duloxetine hydrochloride

Eli Lilly

SNRI

2,552

2,772

+9%

6.8

Organic

16 Nexium

esomeprazole magnesium

AstraZeneca

Proton pump inhibitor (PPI)

2,835

2,695

-5%

10.3

Organic

17 Neulasta

pegfilgrastim

Amgen

Colony stimulating factor

2,527

2,654

+5%

9.3

Joint venture

18 Crestor

rosuvastatin calcium

AstraZeneca

Statin/ HMG CoA reductase inhibitor

2,100

2,640

+26%

7.8

In-licensed

19 Diovan

valsartan

Novartis

Angiotensin II antagonist

2,492

2,520

+1%

14.4

Organic

20 Zyprexa

olanzapine

Eli Lilly

Atypical anti-psychotic

2,332

2,496

+7%

14.7

Organic

21 Lexapro

escitalopram oxalate

SSRI

2,270

2,300

+1%

8.8

In-licensed

22 Copaxone

glatiramer acetate

Forest Laboratories Teva Pharmaceutical Industries

MS agent

1,917

2,287

+19%

14.4

In-licensed

Dipeptidyl peptidase IV (DPPIV) inhibitor Heparin, low molecular weight (LMWH)

23 Januvia/Janumet

sitagliptin phosphate

Merck & Co

24 Lovenox/Clexane

enoxaparin sodium

Sanofi

1,876

2,139

+14%

4.6

Company acquisition

2,539

1,910

-25%

18.2

Company acquisition

25 Atripla

efavirenz; emtricitabine; tenofovir

Gilead Sciences

26 OxyContin

oxycodone hydrochloride

Purdue Pharma

NNRTI & NRTI

1,646

1,909

+16%

4.9

Joint venture

Opioid agonist

2,895

1,800

-38%

15.5

Organic

27 Aricept

donepezil hydrochloride

Eisai

28 Spiriva

tiotropium bromide monohydrate

Acetylcholinesterase inhibitor

2,099

1,795

-15%

14.5

Organic

Boehringer Ingelheim + Pfizer Muscarinic antagonist

29 Prevnar 13

pneumococcal vaccine

Pfizer

1,518

1,766

+16%

7.3

Organic

-

1,761

n/m

1.2

Company acquisition

Pneumococcal vaccine

30 Celebrex

celecoxib

Pfizer

COX-2 inhibitor

1,697

1,580

-7%

12.4

Company acquisition

31 Herceptin

trastuzumab

Roche

Anti-HER2 (ErbB-2) MAb

1,446

1,530

+6%

12.7

Company acquisition

32 Avonex

interferon beta-1a

Biogen Idec

Interferon beta

1,406

1,492

+6%

15.0

Organic

33 Revlimid

lenalidomide

Celgene

Immunomodulator

1,039

1,433

+38%

5.4

Organic

34 Lyrica

pregabalin

Pfizer

Alpha 2 delta ligand

1,504

1,424

-5%

6.4

Company acquisition

35 Lucentis

ranibizumab

Roche

Anti-VEGF MAb

1,106

1,402

+27%

4.9

Company acquisition

36 Levaquin

levofloxacin

Johnson & Johnson

Quinolone

1,478

1,312

-11%

14.4

In-licensed

37 Truvada

emtricitabine; tenofovir disoproxil fumarate

Gilead Sciences

NRTI

1,178

1,309

+11%

6.8

Company acquisition

38 Namenda

memantine hydrochloride

Forest Laboratories

NMDA antagonist

1,115

1,300

+17%

7.6

In-licensed

39 Gleevec/Glivec

imatinib mesylate

Novartis

Tyrosine kinase inhibitor

1,088

1,285

+18%

10.0

Organic

40 Zetia

ezetimibe

Merck & Co (SGP)

Cholesterol absorption inhibitor

1,264

1,227

-3%

8.6

Company acquisition Company acquisition

41 Effexor

venlafaxine hydrochloride

Pfizer (Wyeth)

SNRI

2,398

1,226

-49%

17.4

42 Humalog

insulin lispro recombinant

Eli Lilly

Insulin

1,208

1,222

+1%

15.0

Organic

43 Aranesp

darbepoetin alfa

Amgen

Erythropoietin

1,251

1,103

-12%

9.7

Joint venture

44 Vytorin

ezetimibe; simvastatin

Merck & Co (SGP)

Statin/ HMG CoA reductase inhibitor & cholesterol absorption inhibitor

1,230

1,077

-12%

6.8

Company acquisition

45 Provigil

modafinil

Cephalon

Anti-narcoleptic

961

1,060

+10%

12.4

Company acquisition

46 Taxotere

docetaxel

Sanofi

Taxane

1,153

1,043

-10%

15.0

Company acquisition

47 Viagra

sildenafil citrate

Pfizer

Phosphodiesterase V (PDE5) inhibitor

48 TriCor

fenofibrate

Abbott Laboratories

Fibrate

49 Alimta

pemetrexed disodium

Eli Lilly

Thymidylate synthase inhibitor

50 Premarin

estrogens, conjugated

Pfizer (Wyeth)

Oestrogen agonist

Total

962

992

+3%

13.2

Organic

1,108

984

-11%

9.7

Company acquisition

816

957

+17%

7.3

In-licensed

1,046

949

-9%

69.1

Company acquisition

107,517

110,434

+3%

12.1

Source: EvaluatePharma® (25 MAY 2011) Note: Sales represent company reported sales where available, otherwise based on an average of equity analyst estimates. EvaluatePharma® endeavours to treat the sales from patent protected new formulations of existing products as distinct entities where possible. Epogen/ Neulasta/ Aranesp developed via Kirin-Amgen joint venture.

Copyright © 2011 EvaluatePharma Ltd. All rights reserved.

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