MEDICAL INNOVATIONTHE VALUE OF

2018 EDITIONSusan Freeman was diagnosed with plaque psoriasis

2

Health is not a commodity, but a humanright and public good. By incentivizinginnovation beyond financial gains, wecan bring effective medicines to everycorner of the globe.

Dr. Jorge BermudezVice-President, Health Production and Innovation,Ministry of Health (Brazil)

3

INTRODUCTION

Chapter 1: Virtuous Cycle of Medical

Innovation

Chapter 2: Living Better and Healthier

Chapter 3: Progress & Prosperity

Chapter 4: Better Healthcare, Better

Outcomes

Chapter 5: Accelerating Innovation in

Immune and Inflammatory Disorders

Chapter 6: Celgene

TABLE OF CONTENTS

4

David Clark was diagnosed with psoriatic arthritis

INTRODUCTIONAmong the technological innovations of the 20th and 21st

centuries, medical innovation has been one of the most

significant contributions to our ability to live longer,

healthier lives.

Medical innovation is turning knowledge about disease

mechanisms at the genetic and cellular level into

breakthrough therapies that address significant unmet

needs. It brings about a virtuous cycle of better health and

greater prosperity which, in turn, stimulates additional

investment in even more advanced innovations for

preventing and treating disease.

In recent years, medical innovation has significantly

improved outcomes and quality of life for patients living

with chronic, life-long immune and inflammatory disorders.

However, more needs to be done to address unmet needs.

This sourcebook will take a close look at the unmet need in

immune disorders, what is driving innovation and how to

ensure the virtuous cycle of innovation continues.

5

Cindy Custodio was diagnosed with psoriasis and psoriatic arthritis

6 | WHO IS CELGENE? 6

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION 6

1

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION

VIRTUOUS CYCLE OF MEDICAL INNOVATIONMEDICAL INNOVATION REQUIRES COMMITMENT, COLLABORATION AND INVESTMENT

Medical innovation is an important contributor to longer and healthier

life. In the 21st century, medical innovation is dramatically improving

health outcomes, reducing the overall cost of healthcare and stimulating

the growth of the global economy – producing a world that may one

day be free from immune disorders.

This virtuous cycle of innovation, in turn, stimulates investment in

biomedical research to further improve health and create economic

value throughout the world.

For people living with chronic diseases, medical innovation success

means lower disability rates, increased work productivity, greater

mobility, and increased well-being, among other factors. Success is

giving people the ability to perform everyday activities. Medical

innovation is increasing in the area of immune and inflammatory

disorders. To accelerate innovation, the pharmaceutical industry,

academia, medical societies, government, patient advocacy groups and

others must work together collaboratively to stimulate investment in

research as well as generate greater public awareness and enhance

patient access.

7

1

Wendy Ryder was diagnosed with psoriatic arthritis

8

8

What is emerging is a more complexunderstanding of the science… We areunderstanding the mechanisms of theimmune response and how it playsout in pathogenic disease.

Kristine Kuus-ReichelDirector, Immunomics Business Unit, Beckman Coulter

9

6 | WHO IS CELGENE? 10

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION

Medical Innovation is a Virtuous Cycle

10

Access and reimbursement for innovative therapies today make possible the investment in research and development that leads to future medical advances

Celgene has invested on average 39.3 percent of revenue in research and development during the past five years

Continuous investment of time and resources by biopharmaceutical companies such as Celgene leads to new medical breakthroughs

Access and reimbursement for innovative therapies fund investment in future medical advances

Virtuous Cycle of Medical

Innovation

Source 4: Celgene. 2015 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/0x0x889847/98954B20-BFA0-4AD4-9649-105595A19800/Celgene_2015_Annual_Report.pdf. Accessed June 2018. Source 5: Celgene. 2017 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6326255878x0x978672/138C3639-1839-499D-8191-34F9E08A0CBD/Celgene_AR_complete_PDF_041718.pdf. Accessed June 2018.

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION

Continued Development in Addressing Unmet Needs (1970-2018)*

11

PUVA shown effective in psoriasis

Human insulin approved

Betaseron approved for multiple sclerosis

First protease inhibitor for

HIV

TNF blockers approved for

rheumatoid arthritis and psoriatic arthritis

Interleukin therapies for

psoriasis

PrEP for HIV

JAK inhibitor for psoriatic

arthritis

Identification of HIV virus

First monoclonal

antibody approved

Human genome sequenced

PDE4 inhibitor for psoriasis and psoriatic arthritis

Anti-integrin therapies for

ulcerative colitis and Crohn’s disease

Gene therapies,

RNAi

Source 6: Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med 1974;291:1207-11. Accessed June 2018. Source 7: Müller D, Ellen M, Duffy M, et al. Timeline: 200 Years of the New England Journal of Medicine. NEJM 2012; 366:e 3. January 5, 2012. DOI: 10.1056/NEJMp1114819. Accessed June 2018.Source 8: Human Insulin. Available at https://www.diabetes.co.uk/insulin/human-insulin.html. Accessed June 2018.Source 9: Company News; F.d.a. Approves a Multiple Sclerosis Drug Milt Freudenheim. Available at https://www.nytimes.com/1993/07/24/business/company-news-fda-approves-a-multiple-sclerosis-drug.html. Accessed June 2018.Source 10: Invirase Prescribing Information. Available at https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Advair_Diskus/pdf/ADVAIR-DISKUS-PI-PIL-IFU.PDF. Accessed June 2018.Source 11: Humalog Prescribing Information. Available at https://pi.lilly.com/us/humalog-pen-pi.pdf. Accessed June 2018.Source 12: Humira Prescribing Information. Available at http://www.rxabbvie.com/pdf/humira.pdf. Accessed June 2018.Source 13: ENBREL ® (etanercept). Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/etanimm011502LB.pdf. Accessed June 2018.Source 14: Tsai, Y., & Tsai, T. Anti-interleukin and interleukin therapies for psoriasis: Current evidence and clinical usefulness. Therapeutic Advances in Musculoskeletal Disease, 9(11), 277-294. doi:10.1177/1759720x17735756. Accessed June 2018.Source 15: Blumenthal, J., & Haubrich, R. Pre-exposure prophylaxis for HIV infection: How antiretroviral pharmacology helps to monitor and improve adherence. Expert Opinion on Pharmacotherapy, 14(13), 1777-1785. doi:10.1517/14656566.2013.812072. Accessed June 2018.Source 16: Harmanjit S. Vedolizumab: A novel, selective Integrin Inhibitor for the treatment of IBD. Inflammatory Bowel Diseases, 15. doi:10.1097/00054725-200912002-00033. Accessed June 2018.Source 17: Celgene. Oral OTEZLA® (apremilast) Approved by the U.S. Food and Drug Administration for the Treatment of Patients with Moderate to Severe Plaque Psoriasis. Available at http://ir.celgene.com/releasedetail.cfm?releaseid=872240. Accessed June 2018. Source 18: Pfizer. Pfizer Announces FDA Approval of XELJANZ® (tofacitinib) and XELJANZ® XR for the Treatment of Active Psoriatic Arthritis. Available at http://press.pfizer.com/press-release/pfizer-announces-fda-approval-xeljanz-tofacitinib-and-xeljanz-xr-treatment-active-psor. Accessed June 2018.Source 19: Almåsbak, H., Aarvak, T., & Vemuri, M. C. CAR T Cell Therapy: A Game Changer in Cancer Treatment. Journal of Immunology Research, 2016, 1-10. doi:10.1155/2016/5474602. Accessed June 2018. Source 20: Zhou, J., & Rossi, J. J. Mechanisms and Barriers to RNAi Delivery. Advanced Delivery and Therapeutic Applications of RNAi, 3-17. doi:10.1002/9781118610749.ch1. Accessed June 2018.

Insulin lispro, first rapid-

acting insulin

*Not an exhaustive list

PUVA = photochemotherapy; HIV = human immunodeficiency virus; TNF = tumor necrosis factor PrEP = pre-exposure prophylaxis; PDE4 = phosphodiesterase-4; JAK = janus kinase; RNAi = ribonucleic acid interface

Human insulin approved

First monoclonal

antibody approved

6 | WHO IS CELGENE? 12

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION

Medicines are Transforming the Treatment of Many Immune and Inflammatory Diseases

12

Source 21: PhRMA. A Decade of Innovation in Chronic Diseases. Available at http://phrma-docs.phrma.org/sites/default/files/pdf/decade-of-innovation-chronic-disease.pdf. Accessed June 2018.Source 22: NICHD NIH. Some Rights Reserved. Available at https://www.flickr.com/photos/nichd/21086425615/in/album-72157652207729612/. Accessed June 2018.Source 23: Matsuoka K, Kobayashi T, Ueno F, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. Journal of Gastroenterology 2018; 53(3). January. DOI: 10.1007/s00535-018-1439-1. Available at https://www.ncbi.nlm.nih.gov/pubmed/29429045. Accessed June 2018.Source 24: Feldman SR, Bernard G, Rice G, et al. The Challenge of Managing Psoriasis: Unmet Medical Needs and Stakeholder Perspectives. American Health & Drug Benefits 2016; 9(9). December. DOI: 10.1056/NEJMp1114819. Available at https://www.ncbi.nlm.nih.gov/pubmed/28465778. Accessed June 2018.Source 25: PhRMA. Pharmaceutical Summit on Business & Compliance Issues in Managed Markets. Available at http://www.ehcca.com/presentations/PharmaMM/hubbard_1.pdf. Accessed June 2018.

Multiple Sclerosis (MS)

With the expansion of treatments, including oral medicines, healthcare professionals may have additional options for treating patients with MS, with a treatment goal of optimizing management and potentially slowing disease progression.

Inflammatory Bowel Disease (IBD)

With the accumulation of new evidence and the approval of new diagnostic and therapeutic agents, it is anticipated that the management guidelines for IBD will change considerably over even the next few years.

Plaque Psoriasis (PsO) & Psoriatic Arthritis (PsA)

New discoveries have led to a broader range of potential treatment options for patients, with varying efficacy-safety profiles, to meet the different needs of patients.

Rheumatoid Arthritis (RA)

Therapeutic advances have transformed the RA treatment paradigm over the past 20 years, shifting from a focus on managing symptoms to aiming for slowed disease progression and even disease remission.

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION

Investment in Healthcare R&D Has Risen*;I&I Treatment Options Have Increased

Source 26: Drug-Development Pipeline. Multiple Sclerosis Discovery Forum. Available at www.msdiscovery.org/research-resources/drug-pipeline. Accessed June 2018.Source 27: Pharmaceutical Research and Manufacturers of America (PhRMA). 2017 PhRMA Annual Membership Survey. Table 1: Domestic R&D and R&D Abroad. Accessed June 2018. Source 28: National Psoriasis Foundation. FDA-Approved. Available at https://www.psoriasis.org/phases/fda-approved?page=2. Accessed June 2018.Source 29: IBD Medication Guide. Crohn’s & Colitis Foundation. Available at http://ibdmedicationguide.org/browse. Accessed June 2018.Source 30: Ultravate Prescribing Information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208183s000lbl.pdf. Accessed June 2018.

$2.0

$8.4

$26.0

$39.9$43.0

$47.9 $47.4

$46.4

$50.7

$48.6

$49.6

$51.6

$53.3 $59.6

$65.5

0

10

20

30

40

50

60

70

1980 1990 2000 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Billions of dollars in

R&D

R&D investment in the U.S.

*R&D spend for PhRMA members only †Domestic R&D: Expenditures within the United States by all PhRMA member companies.‡R&D Abroad: Expenditures outside the United States by US-owned PhRMA member companies, and R&D conducted abroad by US divisions of foreign-owned PhRMA member companies.

3325

New advances in immune and inflammatory diseases

➢ 32 medicines are in development and three oral disease-modifying medicines are now available for the treatment of multiple sclerosis.

➢ In the past 30 years, over 16 medicines have been approved by the FDA for the treatment of psoriasis.

➢ As of 2018, 24 medicines have been developed for the treatment of IBD (ulcerative colitis and Crohn’s disease).

13

6 | WHO IS CELGENE? 14

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION

Innovative HIV treatments lower prevalence and increase life expectancy

Innovation Success Story

14

Source 31: Trickey, Adam et al. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. The Lancet HIV, Volume 0, Issue 0. Available at http://thelancet.com/journals/lanhiv/article/PIIS2352-3018(17)30066-8/fulltext. Accessed June 2018.

Source 32: Cohen, John. HIV Treatment as Prevention. Science. 2011. 34 (6063). doi: 10.1126/science.334.6063.1628. Accessed June 2018.

Our research illustrates a success story of how improved HIV

treatments coupled with screening, prevention and treatment of health

problems associated with HIV infection can extend the life span of

people diagnosed with HIV. - Adam Trickey, Medical Statistician at the University of Bristol2017“A study showed that antiretroviral

therapy prevents the transmission

of the disease, by

as much as 96%,

in heterosexual couples where

one partner has HIV.

A 2017 cohort study found that 20-year-olds who started with antiretroviral therapy in 2013 are predicted to live up to 10 years longer than those who first underwent similar treatment in 1996 – when it first became widely available.

BETWEEN

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010“

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION

Supporting References

15

Source 1: Clinical Trials. Phase 2-Phase 4. Available at clinicaltrials.gov. Accessed March 2018. (Cover Slide)Source 2: Autoimmune Disease List AARDA. Available at https://www.aarda.org/diseaselist/. Accessed March 2018. (Cover Slide)Source 3: TEConomy Partners; for PhRMA. The Economic Impact of the US Biopharmaceutical Industry. Columbus, OH: TEConomy Partners. Available at http://phrma-docs.phrma.org/industryprofile/pdfs/ 2017IndustryProfile_TheBiopharmaceuticalIndustrysRole.pdf. Accessed July 2017. (Cover Slide)Source 4: Celgene. 2015 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/0x0x889847/98954B20-BFA0-4AD4-9649-105595A19800/Celgene_2015_Annual_Report.pdf. Accessed June 2018. Source 5: Celgene. 2017 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6326255878x0x978672/138C3639-1839-499D-8191-34F9E08A0CBD/Celgene_AR_complete_PDF_041718.pdf. Accessed June 2018. Source 6: Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med 1974;291:1207-11. Accessed June 2018. Source 7: Müller D, Ellen M, Duffy M, et al. Timeline: 200 Years of the New England Journal of Medicine. NEJM 2012; 366:e 3. January 5, 2012. DOI: 10.1056/NEJMp1114819. Accessed June 2018.Source 8: Human Insulin. Available at https://www.diabetes.co.uk/insulin/human-insulin.html. Accessed June 2018.Source 9: Company News; F.d.a. Approves a Multiple Sclerosis Drug Milt Freudenheim. Available at https://www.nytimes.com/1993/07/24/business/company-news-fda-approves-a-multiple-sclerosis-drug.html. Accessed June 2018.Source 10: Invirase Prescribing Information. Available at https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Advair_Diskus/pdf/ADVAIR-DISKUS-PI-PIL-IFU.PDF. Accessed June 2018.Source 11: Humalog Prescribing Information. Available at https://pi.lilly.com/us/humalog-pen-pi.pdf. Accessed June 2018.Source 12: Humira Prescribing Information. Available at http://www.rxabbvie.com/pdf/humira.pdf. Accessed June 2018.Source 13: ENBREL ® (etanercept). Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/etanimm011502LB.pdf. Accessed June 2018.Source 14: Tsai, Y., & Tsai, T. Anti-interleukin and interleukin therapies for psoriasis: Current evidence and clinical usefulness. Therapeutic Advances in Musculoskeletal Disease, 9(11), 277-294. doi:10.1177/1759720x17735756. Accessed June 2018.Source 15: Blumenthal, J., & Haubrich, R. Pre-exposure prophylaxis for HIV infection: How antiretroviral pharmacology helps to monitor and improve adherence. Expert Opinion on Pharmacotherapy, 14(13), 1777-1785. doi:10.1517/14656566.2013.812072. Accessed June 2018.Source 16: Harmanjit S. Vedolizumab: A novel, selective Integrin Inhibitor for the treatment of IBD. Inflammatory Bowel Diseases, 15. doi:10.1097/00054725-200912002-00033. Accessed June 2018.Source 17: Celgene. Oral OTEZLA® (apremilast) Approved by the U.S. Food and Drug Administration for the Treatment of Patients with Moderate to Severe Plaque Psoriasis. Available at http://ir.celgene.com/releasedetail.cfm?releaseid=872240. Accessed June 2018. Source 18: Pfizer. Pfizer Announces FDA Approval of XELJANZ® (tofacitinib) and XELJANZ® XR for the Treatment of Active Psoriatic Arthritis. Available at http://press.pfizer.com/press-release/pfizer-announces-fda-approval-xeljanz-tofacitinib-and-xeljanz-xr-treatment-active-psor. Accessed June 2018.Source 19: Almåsbak, H., Aarvak, T., & Vemuri, M. C. CAR T Cell Therapy: A Game Changer in Cancer Treatment. Journal of Immunology Research, 2016, 1-10. doi:10.1155/2016/5474602. Accessed June 2018. Source 20: Zhou, J., & Rossi, J. J. Mechanisms and Barriers to RNAi Delivery. Advanced Delivery and Therapeutic Applications of RNAi, 3-17. doi:10.1002/9781118610749.ch1. Accessed June 2018. Source 21: PhRMA. A Decade of Innovation in Chronic Diseases. Available at http://phrma-docs.phrma.org/sites/default/files/pdf/decade-of-innovation-chronic-disease.pdf. Accessed June 2018.Source 22: NICHD NIH. Some Rights Reserved. Available at https://www.flickr.com/photos/nichd/21086425615/in/album-72157652207729612/. Accessed June 2018.Source 23: Matsuoka K, Kobayashi T, Ueno F, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. Journal of Gastroenterology 2018; 53(3). January. DOI: 10.1007/s00535-018-1439-1. Available at https://www.ncbi.nlm.nih.gov/pubmed/29429045. Accessed June 2018.Source 24: Feldman SR, Bernard G, Rice G, et al. The Challenge of Managing Psoriasis: Unmet Medical Needs and Stakeholder Perspectives. American Health & Drug Benefits 2016; 9(9). December. DOI: 10.1056/NEJMp1114819. Available at https://www.ncbi.nlm.nih.gov/pubmed/28465778. Accessed June 2018.Source 25: PhRMA. Pharmaceutical Summit on Business & Compliance Issues in Managed Markets. Available at http://www.ehcca.com/presentations/PharmaMM/hubbard_1.pdf. Accessed June 2018.Source 26: Drug-Development Pipeline. Multiple Sclerosis Discovery Forum. Available at www.msdiscovery.org/research-resources/drug-pipeline. Accessed June 2018.Source 27: Pharmaceutical Research and Manufacturers of America (PhRMA). 2017 PhRMA Annual Membership Survey. Table 1: Domestic R&D and R&D Abroad. Accessed June 2018. Source 28: National Psoriasis Foundation. FDA-Approved. Available at https://www.psoriasis.org/phases/fda-approved?page=2. Accessed June 2018.Source 29: IBD Medication Guide. Crohn’s & Colitis Foundation. Available at http://ibdmedicationguide.org/browse. Accessed June 2018.Source 30: Ultravate Prescribing Information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208183s000lbl.pdf. Accessed June 2018. Source 31: Trickey, Adam et al. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. The Lancet HIV, Volume 0, Issue 0. Available at http://thelancet.com/journals/lanhiv/article/PIIS2352-3018(17)30066-8/fulltext. Accessed June 2018.Source 32: Cohen, John. HIV Treatment as Prevention. Science. 2011. 34 (6063). doi: 10.1126/science.334.6063.1628. Accessed June 2018.

6 | WHO IS CELGENE? 16

1 | VIRTUOUS CYCLE OF MEDICAL INNOVATION 16

2

2 | LIVING BETTER & HEALTHIER

LIVING BETTER AND HEALTHIERINNOVATION IS OVERCOMING BURDENS,

CREATING NEW VALUE FOR PATIENTS

There are more than 100 types of immune disorders, a cluster of conditions in which the immune system attacks the host’s own body or specific organs.

Immune and inflammatory disorders can manifest at an early age, go undiagnosed for many years, and pose life-long challenges. Their full impact on quality of life can be greatly underappreciated.

We will examine the prevalence and delay in diagnosis associated with several immune disorders, including psoriasis, psoriatic arthritis, multiple sclerosis, Crohn’s disease, ulcerative colitis, and Behçet's disease. At the same time, we will highlight how innovative treatment options can potentially improve the lives of patients living with these conditions.

Greater awareness and research is still needed to help understand the complexity of these disorders. The toll on patients, society, and the healthcare system is significant, but innovative therapies hold promise and opportunity to address these unmet needs, delivering new benefits for patients.

17

Bryan Schmidt was diagnosed with psoriasis and psoriatic arthritis

2 | LIVING BETTER & HEALTHIER

Patient with Moderate-to-Severe Plaque Psoriasis

18

“”

Despite our progress, we recognize that more needs to be done so that we may close the gaps in our knowledge and achieve our overall goal of reducing the rising toll of autoimmune disease.

Elias A. Zerhouni, M.D. Former Director, National Institutes of Health

19

6 | WHO IS CELGENE? 20

2 | LIVING BETTER & HEALTHIER

Autoimmune Disorders are Chronic and May be Disabling

20

Autoimmune disorders are chronic and potentially disabling disorders in which underlying defects in the immune response lead the body to attack its own organs and tissues

Organ-specific autoimmune diseases are localized to a single organ or tissue

Non-organ-specific diseases arecharacterized by autoimmune reactions against many different organs and tissues resulting in widespread injury

Source 1: U.S. Department of Health and Human Services. Autoimmune Diseases Coordinating Committee: Autoimmune Disease Research Plan. Available at http://www.niaid.nih.gov/topics/autoimmune/Documents/adccreport.pdf (no longer live). Accessed June 2018. Source 2: American Autoimmune Related Diseases Association (AARDA). Autoimmune Statistics. Available at http://www.aarda.org/autoimmune-information/autoimmune-statistics/. Accessed June 2018. Source 3: American Autoimmune Related Diseases Association (AARDA). What are the types of autoimmunity? Available at https://www.aarda.org/knowledge-base/what-are-the-types-of-autoimmunity/. Accessed June 2018.

PRODUCTIVITY

REPRESENT A BURDEN TO INDIVIDUALS AND THE

HEALTHCARE SYSTEM

2 | LIVING BETTER & HEALTHIER

There are More Than 100 Autoimmune Disorders*

21

Source 4: Autoimmune and Autoimmune-Related Diseases. List of Diseases. Available at http://www.aarda.org/autoimmune-information/list-of-diseases/. Accessed June 2018. Source 5: Mayo Clinic. Disease and Conditions: Hashimoto’s Disease. Available at http://www.mayoclinic.org/diseases-conditions/hashimotos-disease/basics/definition/con-20030293?p=1. Accessed June 2018.

*Not an exhaustive list

6 | WHO IS CELGENE? 22

2 | LIVING BETTER & HEALTHIER

Over 168 Million People Worldwide Suffer from One of These Immune and Inflammatory Disorders

125

37.5

3.5

2.3

0 20 40 60 80 100 120 140

Psoriasis

Psoriatic Arthritis

IBD*

Multiple Sclerosis

Millions

*IBD = Inflammatory Bowel Disease (Crohn’s Disease & Ulcerative Colitis): Includes those living in North America and Europe

22

Source 6: Browne, P., Chandraratna D., Angood C. Global Perspectives. Neurology. 2014. Accessed June 2018. Source 7: Ng S., Yun Shi H., Nima Hamidi, F. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. The Lancet 2017. Accessed June 2018. Source 8: National Psoriasis Foundation. About Psoriatic Arthritis. Available at https://www.psoriasis.org/about-psoriatic-arthritis. Accessed June 2018. Source 9: Griffiths C., van der Walt J., Ashcroft D. The global state of psoriasis disease epidemiology: a workshop report. British Journal of Dermatology. Accessed June 2018. Source 10: Liu, J. et al. Psoriatic arthritis: Epidemiology, diagnosis, and treatment. World Journal of Orthopedics. DOI: 10.5312/wjo.v5.i4.537. Accessed June 2018.

2 | LIVING BETTER & HEALTHIER

Nearly 1 in 30 People in the U.S. Live with at Least One of These Immune and Inflammatory Disorders

23

7.5

1.5

1

0.6

0.17

Psoriasis†

IBD*

Psoriatic Arthritis

Multiple Sclerosis

Behçet's Disease

0 1 2 3 4 5 6 7 8

Millions

Source 11: National Psoriasis Foundation. Media Kit. Accessed June 2018. Source 12: United States Census Bureau. Idaho is Nation’s Fastest-Growing State, Census Bureau Reports. Available at https://www.census.gov/newsroom/press-releases/2017/estimates-idaho.html?intcmp=s1-popest-state. Accessed June 2018. Source 13: Wallin, M., Culpepper, W., Campbell, J., et al. The Prevalence of Multiple Sclerosis in the United States: A Population-Based Healthcare Database Approach. European Committee For Treatment And Research In Multiple Sclerosis. 2017. Available at https://onlinelibrary.ectrims-congress.eu/ectrims/2017/ACTRIMS-ECTRIMS2017/199999/mitchell.t.wallin.the.prevalence.of.multiple.sclerosis.in.the.united.states.a.html. Accessed June 2018. Source 14: Yazici H., Hatemi G., Yazici Y. Behçet syndrome: a contemporary view. Nature Reviews Rheumatology. 2018. 14. Accessed June 2018. Source 15: Loftus E. Update on the Incidence and Prevalence of Inflammatory Bowel Disease in the United States. Gastroenterology & Hepatology. 2016. 12(11) Accessed June 2018.

*IBD = Inflammatory Bowel Disease (Crohn’s Disease & Ulcerative Colitis): Includes those living in North America†1.9 million people are living with moderate to severe psoriasis

6 | WHO IS CELGENE? 24

2 | LIVING BETTER & HEALTHIER

Immune Disorders are Often Chronic, Life-long Conditions that Present Early in Life

24

Age Range of Symptom Onset

0 10 20 30 40 50 60

Behçet’s Disease

Plaque Psoriasis

Multiple Sclerosis

Psoriatic Arthritis

IBD

*According to the American Academy of Dermatology, psoriasis can happen at any age. Most people get psoriasis between 15 and 30 years of age. About 75% of people who will get psoriasis will have it by age 40. Another time when symptoms appear is between 50-60 years of age.

Source 16: U.S. Department of Health and Human Services. Autoimmune Diseases Coordinating Committee: Autoimmune Disease Research Plan. Available at http://www.niaid.nih.gov/topics/autoimmune/Documents/adccreport.pdf. Accessed June 2018. Source 17: National Psoriasis Foundation. Media Kit. Available at http://www.psoriasis.org/. Accessed June 2018. Source 18: Alroughani, R., Akhtar, S., & Ahmed, S. (2016). Is Time to Reach EDSS 6.0 Faster in Patients with Late-Onset versus Young-Onset Multiple Sclerosis? Plos One, 11(11). doi:10.1371/journal.pone.0165846. Accessed June 2018. Source 19: American Academy of Dermatology. Psoriasis. Available at https://www.aad.org/public/diseases/scaly-skin/psoriasis#causes. Accessed June 2018. Source 20: Crohn’s & Colitis Foundation of America. The Facts About Inflammatory Bowel Diseases. Available at http://www.crohnscolitisfoundation.org/assets/pdfs/updatedibdfactbook.pdf . Accessed June 2018. Source 21: Hatemi G., Seyahi E., Fresko I. One year in review 2017: Behçet’s syndrome. Clinical and Experimental Rheumatology. 2017. Accessed June 2018.

2 | LIVING BETTER & HEALTHIER

There are Often Delays* in Diagnoses

25

Source 22: Paisal, V., Al-Abadi, E., & Protheroe, S., et al. THU0536 Childhood onset of behÇet disease (BD) symptoms in an adult cohort of BD patients. The BMJ. doi:10.1136/annrheumdis-2017-eular.6077. Accessed June 2018. Source 23: Chams, H., Davatchi, F., & Mahmoudi, A., et al. Risk Factors of Blindness in Behcet’s Disease. Iranian Journal of Ophthalmology. 20(2). Available at https://irjo.org/article-1-121-en.pdf. Accessed June 2018. Source 24: Lebwohl, M., Bachelez, H., Barker, J., et al. Patient Perspectives in the Management of Psoriasis: Results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis. Journal of the American Academy of Dermatology. 2014; 70(5): 871-881.e30. Accessed June 2018. Source 25: Thormann, A., Sørensen, P. S., Koch-Henriksen, N., Laursen, B., & Magyari, M. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology, 89(16), 2017. doi:10.1212/wnl.0000000000004508. Accessed June 2018. Source 26: Nyguyen, V., et al. Impact of Diagnostic Delay and Associated Factors on Clinical Outcomes in a U.S. Inflammatory Bowel Disease Cohort. Accessed June 2018.Source 27: Fiorino, G., Danese, S. Diagnostic Delay in Crohn’s Disease: Time for Red Flags. Digestive Diseases and Sciences. DOI 10.1007/s10620-016-4298-8. Accessed June 2018.

0 1 2 3 4 5 6

Ulcerative Colitis (3 months)

Crohn's Disease (~7 months)

Psoriasis (2 years)

Multiple Sclerosis (4 years)

Psoriatic Arthritis (5 years)

Behçet's Disease (~5 years)

Average Delay (Years) in Diagnosis After Symptom Onset

*Diagnostic delays are attributable to differential diagnoses and/or the presence of comorbidities

6 | WHO IS CELGENE? 26

2 | LIVING BETTER & HEALTHIER

Significant Comorbidities That May be Associated with Autoimmune Disorders*

Source 28: The Arthritis Foundation. Arthritis By The Numbers. Available at https://www.arthritis.org/Documents/Sections/About-Arthritis/arthritis-facts-stats-figures.pdf (no longer live). Accessed June 2018. Source 29: Jamnitski A., Symmons D., Peters M. Cardiovascular Comorbidities In Patients With Psoriatic Arthritis: A Systematic Review. Ann Rheum Dis. 2013. doi:10.1136/annrheumdis-2011-201194. Accessed June 2018. Source 30: Husted, J., Thavaneswaran, A., Chandran, V., et al. Incremental Effects of Comorbidity on Quality of Life in Patients with Psoriatic Arthritis. The Journal of Rheumatology. 2013; 40(8): 1349-1356. Accessed June 2018. Source 31: Centers for Disease Control and Prevention. Rheumatoid Arthritis. Available at http://www.cdc.gov/arthritis/basics/rheumatoid.htm. Accessed June 2018. Source 32: Aurangabadkar, S. Comorbidities in Psoriasis. Indian Journal of Dermatology, Venereology and Leprology. 2013; 79(7): 10-17. Accessed June 2018. Source 33: Senusi A, Ola D, Mather J. Behçet’s syndrome and health-related quality of life: influence of symptoms, lifestyle and employment. Clinical and Experimental Rheumatology. 2017. Accessed June 2018. Source 34: Mayo Clinic. Amyloidosis. Available at https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178. Accessed June 2018.

*Not an exhaustive list

26

2 | LIVING BETTER & HEALTHIER

Autoimmune Diseases May Impose a Variety of Heavy Burdens

27

Source 35: Crohn’s & Colitis Foundation of America. The Facts About Inflammatory Bowel Diseases. Available at http://www.crohnscolitisfoundation.org/assets/pdfs/updatedibdfactbook.pdf . Accessed June 2018. Source 36: American Autoimmune Related Diseases Association (AARDA). The Cost Burden of Autoimmune Disease: The Latest Front in the War on Healthcare Spending. Available at http://www.diabetesed.net/page/_files/autoimmune-diseases.pdf. Accessed June 2018. Source 37: Senusi A, Ola D, Mather J. Behçet’s syndrome and health-related quality of life: influence of symptoms, lifestyle and employment. Clinical and Experimental Rheumatology. 2017. Accessed June 2018. Source 38: Dilokthornsakul P., Valuck R., Nair K. Multiple sclerosis prevalence in the United States commercially insured population. Neurology. 2016. Accessed June 2018. Source 39: Armstrong, E., Harskamp, C., Armstrong, A. Psoriasis and Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Observational Studies. Journal of the American Heart Association. 2013; 2: e000062. Accessed June 2018.

6 | WHO IS CELGENE? 28

2 | LIVING BETTER & HEALTHIER

28

Patients with Psoriasis Often Develop Psoriatic Arthritis

28

Source 40: National Psoriasis Foundation. About Psoriatic Arthritis. Available at https://www.psoriasis.org/about-psoriatic-arthritis. Accessed June 2018.

2 | LIVING BETTER & HEALTHIER

Psoriatic Arthritis Patients Experience a Variety of Manifestations of Disease

29

29

Source 41: Ritchlin, C., Colbert, R., Gladman D. Psoriatic Arthritis. The New England Journal of Medicine. Doi: 10.1056/NEJMra1505557. Accessed June 2018. Source 42: Gladman, D., & Chandran, V. Observational cohort studies: Lessons learnt from the University of Toronto Psoriatic Arthritis Program. Rheumatology. 50(1), 25-31. doi:10.1093/rheumatology/keq262. Accessed June 2018. Source 43: Liu, J. Psoriatic arthritis: Epidemiology, diagnosis, and treatment. World Journal of Orthopedics, 5(4), 537. doi:10.5312/wjo.v5.i4.537. Accessed June 2018.

6 | WHO IS CELGENE? 30

2 | LIVING BETTER & HEALTHIER

Crohn’s Disease and Ulcerative Colitis Patients May Experience a Variety of Symptoms During a Flare-Up*

30

Source 44: Crohn’s and colitis UK. Taking the IBD Standards forward in Scotland. Results from Watson, AJM. PTU-288 Taking the ibd standards forward in scotland: a national patient survey. BMJ. Available at https://gut.bmj.com/content/64/Suppl_1/A187.1. Accessed June 2018.

*An online survey of Crohn’s disease and ulcerative colitis patients reporting a flare-up within the last four years to identify key issues facing patients with IBD. There were a total of 777 respondents.

2 | LIVING BETTER & HEALTHIER

Multiple Sclerosis Patients May Suffer a Variety of Comorbidities and the Prevalence Increases with Age

31

96 1 5

28

21

5

10

57

35

2018

0

10

20

30

40

50

60

Hypertension Hyperlipidemia Heart Disease Diabetes

Age group: 20-44 years 45-59 years ≥60 years

Lifetim

e p

reva

lence

(%

) in

2010

Source 45: Marrie R., et al. Nat Rev Neurol. 2017;13:375-382. Accessed June 2018.

Age-Specific Prevalence of Common Comorbidities

6 | WHO IS CELGENE? 32

2 | LIVING BETTER & HEALTHIER

Patients with Autoimmune Disorders are at Increased Risk of Cardiovascular Events

32

32

32Perc

ent

Incr

ease

d R

isk C

om

pare

d t

o G

enera

l Popula

tion

Ris

k c

alc

ula

ted a

s (R

R–1.0

)

Note: In the general population in the U.S., approximately 0.3% of people suffer a coronary attack, and 0.25% experience a stroke each year.

Source 46: Armstrong, E., Harskamp, C., Armstrong, A. Psoriasis and Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Observational Studies. Journal of the American Heart Association. 2013; 2: e000062. Accessed June 2018. Source 47: Singh, S., Singh, H., Loftus, E., et al. Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Patients with Inflammatory Bowel Disease: a Systematic Review and Meta-Analysis. Clinical Gastroenterology and Hepatology. 2014; 2(3): 382-93. Accessed June 2018. Source 48: Polachek, A., Touma, Z., & Anderson, M., et al. Risk of Cardiovascular Morbidity in Patients With Psoriatic Arthritis: A Meta-Analysis of Observational Studies. Arthritis Care & Research. 69(1), 67-74. doi:10.1002/acr.22926. Accessed June 2018. Source 49: Jadidi, E., Mohammadi, M., & Moradi, T. High risk of cardiovascular diseases after diagnosis of multiple sclerosis. Multiple Sclerosis Journal. 19(10), 1336-1340. doi:10.1177/1352458513475833. Accessed June 2018. Source 50: Mozzaffarian, D., et al. Executive Summary: Heart Disease and Stroke Statistics – 2016 Update. AHA. Accessed June 2018.

70

43

85

18

56

22

72

21

0

10

20

30

40

50

60

70

80

90

Severe Psoriasis Psoriatic Arthritis Multiple Sclerosis Inflammatory Bowel Disease

CardiovascularEvent/Ischemic HeartDisease

Cerebrovascular Event

Meta-analysis of 9 studies

Meta-analysisof 11 studies

N=8281 patients from 1987-2009

Meta-analysis of 9 studies

2 | LIVING BETTER & HEALTHIER

Life Expectancy in Patients with Autoimmune Disorders

33

33

Source 51: Scalfari A., Knappertz V., Cutter G. Mortality in patients with multiple sclerosis. Neurology. 2013. 81(2): 184–192. doi: 10.1212/WNL.0b013e31829a3388. Accessed June 2018. Source 52: Gelfand, J., Troxel, A., Lewis, J., et al. The Risk of Mortality in Patients with Psoriasis: Results From a Population‐Based Study. Archives of Dermatology. 2007; 143(12): 1493‐1499. Accessed June 2018. Source 53: Ali, Y., Tom, B., Schentag, C., et al. Improved Survival in Psoriatic Arthritis with Calendar Time. Arthritis & Rheumatology. 2007; 56(8): 2708‐2714. Accessed June 2018.

*From a meta-analysis of large cohort disease registries from countries in Europe and North America†From a retrospective cohort study using the United Kingdom’s General Practice Research Database representing a total of 3,951 patients with severe psoriasis‡From a cohort of 680 psoriatic patients enrolled in a University of Toronto Psoriatic Arthritis Clinic from 1978 to 2004

* † ‡

I tend to put off going to thehairdresser. Some of the women whowash hair wear gloves when I comein; people think it’s contagious.

– Psoriasis Patient“ ”

”It was hard for me to open a marker towrite on a white board, hard to answerthe phone or type, because I couldn'tmake a fist, I couldn't grip anything.

– Psoriatic Arthritis Patient

Crohn's disease has affected every aspect ofmy body and life. Beyond the gastrointestinalpain, it has wreaked havoc on my skin, eyes,hair and joints and destroyed my energy level. Ithas been a driving force behind many family andcareer decisions. Crohn's has impacted my life inways many people could never understand.– Crohn’s Disease Patient

“”“

It often takes me a long time to thinkthrough decisions, and the limitedmobility I do have can feel like I’mmoving my limbs through jelly.– Multiple Sclerosis Patient“ ”

I withdrew into myself. I didn’t want to see anyone, I didn’t want to talk. – Behçet's Disease Patient “ ”

34

2 | LIVING BETTER & HEALTHIER

Emotional Components

Percent of patients† with psoriasis who reported:

83%

87%

87%

89%

89%

0 10 20 30 40 50 60 70 80 90 100

Embarrassment

Helplessness

Anger or Frustration

Self-consciousness

Percent of Patients

Concealed PhysicalManifestation of their Disease

35

†Patients may or may not have psoriatic arthritis

Psoriasis May Substantially Impact Emotional Well-being*

35

Source 54: Armstrong, A., Schupp, C., Wu, J., et al. Quality of Life and Work Productivity Impairment Among Psoriasis Patients: Findings from the National Psoriasis Foundation Survey Data 2003‐2011. PLoS One. 2012; 7(12): e52935. Accessed June 2018.

*Findings from the National Psoriasis Foundation Survey, 2003-2011, with responses from 5604 psoriasis and/or psoriatic arthritis patients in the general US community.

83%

87%

87%

89%

89%

0 10 20 30 40 50 60 70 80 90 100

Embarrassment

Helplessness

Anger or Frustration

Self-consciousness

Percent of Patients

6 | WHO IS CELGENE? 36

2 | LIVING BETTER & HEALTHIER

Psoriatic Arthritis May Exert a Severe Impact on the Working Lives of Patients*

36

Source 55: Kavanaugh, A., Helliwell, P., & Ritchlin, C. T. (2016). Psoriatic Arthritis and Burden of Disease: Patient Perspectives from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey. Rheumatology and Therapy. 3(1), 91-102. doi:10.1007/s40744-016-0029-z. Accessed April 2018.

*The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey included psoriasis and/or psoriatic arthritis patients in North America and Europe, focusing and QoL impacts and unmet treatment needs (N=712 for PsA patients)

0% 5% 10% 15% 20% 25% 30% 35%

Working full-time

Career advancement

Choice of career

Keeping a job

Getting a job

Missed work inpast 12 months

% Psoriatic Arthritis Patients Reporting an Impact of PsAon the Ability to Function and Work Productively

PsA Patients

2 | LIVING BETTER & HEALTHIER

Crohn’s Disease and Ulcerative Colitis May Substantially Impact Overall Well-being

37

Source 56: Lönnfors S., Vermeireb S., Grecoa M. IBD and health-related quality of life — Discovering the true impact. Journal of Crohn's and Colitis. 2014. Available at https://academic.oup.com/ecco-jcc/article/8/10/1281/2392494. Accessed June 2018. Source 57: European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA). The True Impact of IBD: A European Crohn’s and Ulcerative Colitis Patient Life: IMPACT Survey 2010-2011. Available at http://efcca-solutions.net/media/jointhefight/ImpactReport.pdf (no longer live). Accessed June 2018.

HAD GOTTEN IN THE WAY OF THEIR ABILITY TO MAKE OR KEEP FRIENDS

6 | WHO IS CELGENE? 38

2 | LIVING BETTER & HEALTHIER

Multiple Sclerosis Patients May Face Numerous Challenges That Can be Related and Interdependent

38

Adding to the challenge for patients is that these symptoms can occur with regularity or with variable frequency

% F

requency

Seen in M

S P

opula

tion

Source 58: Crayton H, et al. Neurology. 2004;63(11 Suppl 5):S12-8. Accessed June 2018. Source 59: Miller A, Bourdette D, Cohen JA, et al. Multiple sclerosis. Continuum 1999;5:120–133. Accessed June 2018.

0

10

20

30

40

50

60

70

80

90

100Spast

icity

Fatigue

Conce

ntr

ation /

Mem

ory

Dis

turb

ance

s

Bow

el /

Bla

dder

Dysf

unct

ion

Tre

mor

/Im

bala

nce

Pain

Sexual

Dysf

unct

ion

55

40 - 60

84

78 - 90

40 - 50 50.3

48 – 75

2 | LIVING BETTER & HEALTHIER

Source 60: Crow, J. Psoriasis Uncovered. Nature Outlook. 2012; 492(20/27): S50-S51. Accessed June 2018. Source 61: Zuckerman, A. Cyclosporine: A Review. Journal of Transplantation. 2012. doi:10.1155/2012/230386. Accessed June 2018. Source 62: Amgen. FDA Approves Expanded Use Of ENBREL® (etanercept) To Treat Children With Chronic Moderate-To-Severe Plaque Psoriasis. Available at https://www.amgen.com/media/news-releases/2016/11/fda-approves-expanded-use-of-enbrel-etanercept-to-treat-children-with-chronic-moderatetosevere-plaque-psoriasis/. Accessed April 2018. Source 63: Bottrell, John. Let’s Talk Corticosteroids: History, Side effects, and Benefits. Available at https://asthma.net/living/lets-talk-corticosteroids-history-side-effects-benefits/. Accessed June 2018.

Source 64: Myhr, K. M., & Mellgren, S. I. Corticosteroids in the treatment of multiple sclerosis. Acta Neurologica Scandinavica, 120. 73-80. doi:10.1111/j.1600-0404.2009.01213. Accessed June 2018. Source 65: Zeichner, J. Use of Topical Coal Tar Foam for the Treatment of Psoriasis in Difficult-to-treat Areas. The Journal of Clinical and Aesthetic Dermatology. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945847/. Accessed June 2018. Source 66: Boivin, N., Baillargeon, J., Doss, P. M., Roy, A., & Rangachari, M. Interferon-β Suppresses Murine Th1 Cell Function in the Absence of Antigen-Presenting Cells. Plos One. 10(4). doi:10.1371/journal.pone.0124802. Accessed June 2018. Source 67: Gottlieb, A., & Narang, K. Ustekinumab in the treatment of psoriatic arthritis: Latest findings and clinical potential. Therapeutic Advances in Musculoskeletal Disease. 5(5), 277-285. doi:10.1177/1759720x13501021. Accessed June 2018. Source 68: Khatri, B. O. (2016). Fingolimod in the treatment of relapsing–remitting multiple sclerosis: Long-term experience and an update on the clinical evidence. Therapeutic Advances in Neurological Disorders, 9(2), 130-147. doi:10.1177/1756285616628766. Accessed June 2018. Source 69: Schafer, P., Parton, A., Capone, L., Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cellular Signalling, 26(9), 2016-2029. doi:10.1016/j.cellsig.2014.05.014. Accessed June 2018. Source 70: Pfizer. Pfizer Announces FDA Approval of XELJANZ® (tofacitinib) and XELJANZ® XR for the Treatment of Active Psoriatic Arthritis . Available at http://press.pfizer.com/press-release/pfizer-announces-fda-approval-xeljanz-tofacitinib-and-xeljanz-xr-treatment-active-psor. Accessed June 2018. Source 71: Shu S., Wang J., Tao M. Gene Therapy for Autoimmune Disease. Clinical Reviews in Allergy & Immunology. Available at https://link.springer.com/article/10.1007%2Fs12016-014-8451-x. Accessed June 2018. Source 72: Weinblatt, M. Methotrexate in Rheumatoid Arthritis: A Quarter Century of Development. Transactions of the American Clinical and Climatological Association, 2013; 124: 16–25. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715949/. Accessed June 2018. Source 73: Celgene. Oral OTEZLA® (apremilast) Approved by the U.S. Food and Drug Administration for the Treatment of Patients with Moderate to Severe Plaque Psoriasis. Available at http://ir.celgene.com/releasedetail.cfm?releaseid=872240. Accessed June 2018. Source 74: Johnson & Johnson. STELARA® (Ustekinumab) Receives FDA Approval To Treat Active Psoriatic Arthritis. Available at https://www.jnj.com/media-center/press-releases/stelara-ustekinumab-receives-fda-approval-to-treat-active-psoriatic-arthritis. Accessed June 2018. Source 75: Johnson & Johnson. FDA Approves STELARA® (Ustekinumab) for Treatment of Adults With Moderately to Severely Active Crohn’s Disease. Available at https://www.jnj.com/media-center/press-releases/fda-approves-stelara-ustekinumab-for-treatment-of-adults-with-moderately-to-severely-active-crohns-disease. Accessed April 2018. Source 76: FDA Approved Drug Products. Acitretin. Available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019821. Accessed June 2018.

Innovations for Immune and Inflammatory Disorders*

Have Increased Over the Past Decade†

Plaque Psoriasis Psoriatic Arthritis Multiple Sclerosis Inflammatory Bowel DiseasesPSO PSA MS IBD

*Psoriasis, psoriatic arthritis, multiple sclerosis, Crohn’s disease, and ulcerative colitis†Selected agents reflect first-in-class; timeline reflects initial approval of agent, with subsequent indications as notedNote: There are no FDA-approved treatments for Behcet’s Disease.

>100 YEARS AGOCOAL TAR

1960sMETHOTREXATE

1951CORTICOSTEROIDS

UVB LIGHT

PSORALEN AND UVA LIGHT (PUVA)

CYCLOSPORINE

1993INTERFERON

BETA-1B

19962018 and Beyond?

100 YEARS AGO 1920 1940 1960 1980 2000 2020

1998TNF INHIBITOR

2009IL-12/-23 ANTAGONIST

RETINOID

PSO

MS

PSA

PSO

PSO

PSA (2002)

1974 PSO

PSA

MS

PSO PSA(2013)

PSO

MS

PSO (2004)

Gene therapies, RNAi

2014 PSA PSO

PDE4 INHIBITOR

2017JAK INHIBITOR PSA

2010S1P RECEPTOR MODULATOR

IBD (2016)

39

6 | WHO IS CELGENE? 40

2 | LIVING BETTER & HEALTHIER

Rheumatoid Arthritis: An Innovation Story

40

Source 77: Upchurch, K., Evolution of treatment for rheumatoid arthritis. Rheumatology. 2012. doi:10.1093/rheumatology/kes278. Accessed June 2018.

THEN: During the first half of the 20th century, rheumatoid arthritis treatment regimens included drugs that could provide only symptomatic benefit, analgesics, and physical measures such as bed rest, splinting and physical therapy.

NOW: Biologic disease-modifying antirheumatic drugs target the underlying sources of inflammation, which improves physical functioning and prevents irreversible joint damage, making disease remission possible.

2 | LIVING BETTER & HEALTHIER

Multiple Sclerosis: The Evolution of Clinical Value for Patients

41

Source 78: Rolak, L. The History of MS: The Basic Facts. Available at https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-History-of-Multiple-Sclerosis.pdf. Accessed June 2018. Source 79: Multiple Sclerosis Association of America. Timeline – The History of Multiple Sclerosis. Available at https://mymsaa.org/publications/motivator/summer-fall12/cover-story/timeline. Accessed June 2018. Source 80: National Multiple Sclerosis Society. Interferons. Available at https://secure.nationalmssociety.org/site/SPageServer/?NONCE_TOKEN=D1B1C9DADA22CF73012881C883164C18&pagename=HOM_LIB_sourcebook_interferons. Accessed April 2018. Source 81: Kebir, H., Ifergan, I., Alvarez, J., et al. Preferential recruitment of interferon-γ-expressing TH17 cells in multiple sclerosis. Annals of Neurology. 66(3), 390-402. doi:10.1002/ana.21748. Accessed June 2018. Source 82: Deangelis, T., & Lublin, F. Multiple sclerosis: New treatment trials and emerging therapeutic targets. Current Opinion in Neurology. 21(3), 261-271. doi:10.1097/wco.0b013e328300c70d. Accessed June 2018. Source 83: Thormann, A., Sørensen, P. S., Koch-Henriksen, N., et al. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology. 89(16), 1668-1675. doi:10.1212/wnl.0000000000004508. Accessed June 2018. Source 84: National Multiple Sclerosis Society. Disease-Modifying Therapies for MS. Available at http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-The-MS-Disease-Modifying-Medications.pdf. Accessed June 2018.

• Magnetic resonance imaging (MRI) scans further improve diagnostic capabilities

• Steroid treatments common

• Interferon gamma fails clinical trials, but later success with interferon beta

• Distinct clinical patterns of multiple sclerosis are identified

• The role of T-cells in pathology is recognized

• Interferons fully emerge as disease-modifying therapies

• Greater understanding of cell movement across the blood-brain barrier

• The role of Th17 cells is uncovered

• New therapeutic targets in disease begin to emerge

• The first oral disease-modifying therapy is approved in 2010

• Now, the average time between onset of MS symptoms and diagnosis is about 4 years

• For patients, there are now a total of 15 disease-modifying therapies…so far

Since the 1960s, progress has been made in understanding MS and developing treatment options for MS patients

• Diagnosis often took seven years

• Computerized axial tomography (CAT) scans facilitated these diagnoses

• Chemotherapy and corticosteroids were the common treatments

• Growing recognition of the role of the immune system

6 | WHO IS CELGENE? 42

2 | LIVING BETTER & HEALTHIER

Vast Majority of Psoriasis and Psoriatic Arthritis Patients Believe There is a Need for Additional Innovative Therapies*

42

Source 85: Lebwohl, M., Bachelez, H., Barker, J., et al. Patient Perspectives in the Management of Psoriasis: Results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis. Journal of the American Academy of Dermatology. 2014; 70(5): 871-881.e30. Accessed June 2018.

OF PSORIASIS AND PSORIATIC ARTHRITIS PATIENTSREPORTED A NEED FOR NEW INNOVATIVE

THERAPIES

*The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey included psoriasis and/or psoriatic arthritis patients in North America and Europe, focusing and QoL impacts and unmet treatment needs (N=3426)

2 | LIVING BETTER & HEALTHIER

Majority of Psoriatic Arthritis Patients With or Without Psoriasis are Not Receiving Treatment or Only Using Topical Therapy*

Source 86: Lebwohl, M., Bachelez, H., Barker, J., et al. Patient Perspectives in the Management of Psoriasis: Results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis. Journal of the American Academy of Dermatology. 2014; 70(5): 871-881.e30. Accessed June 2018.

†E.g., cyclosporine, methotrexate, acitretin or fumaric acid esters

28%

31%

19%

8%

14%

Biologic ± topical

Oral medications† + biologic

Oral medications ± topical

Topical only

No treatment

(n=712)

Current Treatments

59% % P

atients

59% of patients living with psoriasis +/- PsA, which are systemic diseases, are receiving only topical therapy or no treatment at all

Current Treatments for Patients with Psoriasis and Psoriatic Arthritis

0%

100%

*The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey included psoriasis and/or psoriatic arthritis patients in North America and Europe, focusing and QoL impacts and unmet treatment needs (N=3426)

43

6 | WHO IS CELGENE? 44

2 | LIVING BETTER & HEALTHIER

Source 87: Krupa, L., Kennedy, H., Jamieson, C., et al. The Reasons for Discontinuation of Infliximab Treatment in Patients with Crohn's Disease: A Review of Practice at NHS

Teaching Hospital. ISRN Gastroenterology. Article ID 672017. Accessed June 2018.

Note: Percentages do not add up to 100% as patients could name more than one reason for discontinuing therapy

Patients Discontinue Therapy for a Variety of Reasons*

44

44

*A review of medical notes at the Norfolk & Norwich University Hospital between 2002-2008 to determine reasons for discontinuation (N=65)

2 | LIVING BETTER & HEALTHIER 45

Lois Minta was diagnosed with psoriatic arthritis

6 | WHO IS CELGENE? 46

2 | LIVING BETTER & HEALTHIER

Supporting References

46

Source 1: U.S. Department of Health and Human Services. Autoimmune Diseases Coordinating Committee: Autoimmune Disease Research Plan. Available at http://www.niaid.nih.gov/topics/autoimmune/Documents/adccreport.pdf (no longer live). Accessed June 2018. Source 2: American Autoimmune Related Diseases Association (AARDA). Autoimmune Statistics. Available at http://www.aarda.org/autoimmune-information/autoimmune-statistics/. Accessed June 2018. Source 3: American Autoimmune Related Diseases Association (AARDA). What are the types of autoimmunity? Available at https://www.aarda.org/knowledge-base/what-are-the-types-of-autoimmunity/. Accessed June 2018. Source 4: Autoimmune and Autoimmune-Related Diseases. List of Diseases. Available at http://www.aarda.org/autoimmune-information/list-of-diseases/. Accessed June 2018. Source 5: Mayo Clinic. Disease and Conditions: Hashimoto’s Disease. 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Media Kit. Available at http://www.psoriasis.org/. Accessed June 2018. Source 12: United States Census Bureau. Idaho is Nation’s Fastest-Growing State, Census Bureau Reports. Available at https://www.census.gov/newsroom/press-releases/2017/estimates-idaho.html?intcmp=s1-popest-state. Accessed June 2018. Source 13: Wallin, M., Culpepper, W., Campbell, J., et al. The Prevalence of Multiple Sclerosis in the United States: A Population-Based Healthcare Database Approach. European Committee For Treatment And Research In Multiple Sclerosis. 2017. Available at https://onlinelibrary.ectrims-congress.eu/ectrims/2017/ACTRIMS-ECTRIMS2017/199999/mitchell.t.wallin.the.prevalence.of.multiple.sclerosis.in.the.united.states.a.html. Accessed June 2018. Source 14: Yazici H., Hatemi G., Yazici Y. Behçet syndrome: a contemporary view. Nature Reviews Rheumatology. 2018. 14. Accessed June 2018. Source 15: Loftus E. Update on the Incidence and Prevalence of Inflammatory Bowel Disease in the United States. 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S., Koch-Henriksen, N., Laursen, B., & Magyari, M. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology, 89(16), 2017. doi:10.1212/wnl.0000000000004508. Accessed June 2018. Source 26: Nyguyen, V., et al. Impact of Diagnostic Delay and Associated Factors on Clinical Outcomes in a U.S. Inflammatory Bowel Disease Cohort. Accessed June 2018.Source 27: Fiorino, G., Danese, S. Diagnostic Delay in Crohn’s Disease: Time for Red Flags. Digestive Diseases and Sciences. DOI 10.1007/s10620-016-4298-8. Accessed June 2018. Source 28: The Arthritis Foundation. Arthritis By The Numbers. Available at https://www.arthritis.org/Documents/Sections/About-Arthritis/arthritis-facts-stats-figures.pdf (no longer live). Accessed June 2018. Source 29: Jamnitski A., Symmons D., Peters M. Cardiovascular Comorbidities In Patients With Psoriatic Arthritis: A Systematic Review. Ann Rheum Dis. 2013. doi:10.1136/annrheumdis-2011-201194. Accessed June 2018. Source 30: Husted, J., Thavaneswaran, A., Chandran, V., et al. Incremental Effects of Comorbidity on Quality of Life in Patients with Psoriatic Arthritis. The Journal of Rheumatology. 2013; 40(8): 1349-1356. Accessed June 2018. Source 31: Centers for Disease Control and Prevention. Rheumatoid Arthritis. Available at http://www.cdc.gov/arthritis/basics/rheumatoid.htm. Accessed June 2018.

2 | LIVING BETTER & HEALTHIER

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Source 32: Aurangabadkar, S. Comorbidities in Psoriasis. Indian Journal of Dermatology, Venereology and Leprology. 2013; 79(7): 10-17. Accessed June 2018. Source 33: Senusi A, Ola D, Mather J. Behçet’s syndrome and health-related quality of life: influence of symptoms, lifestyle and employment. Clinical and Experimental Rheumatology. 2017. Accessed June 2018. Source 34: Mayo Clinic. Amyloidosis. Available at https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178. Accessed June 2018. Source 35: Crohn’s & Colitis Foundation of America. The Facts About Inflammatory Bowel Diseases. Available at http://www.crohnscolitisfoundation.org/assets/pdfs/updatedibdfactbook.pdf . Accessed June 2018. Source 36: American Autoimmune Related Diseases Association (AARDA). The Cost Burden of Autoimmune Disease: The Latest Front in the War on Healthcare Spending. Available at http://www.diabetesed.net/page/_files/autoimmune-diseases.pdf. Accessed June 2018. Source 37: Senusi A, Ola D, Mather J. Behçet’s syndrome and health-related quality of life: influence of symptoms, lifestyle and employment. Clinical and Experimental Rheumatology. 2017. Accessed June 2018. Source 38: Dilokthornsakul P., Valuck R., Nair K. Multiple sclerosis prevalence in the United States commercially insured population. Neurology. 2016. Accessed June 2018. Source 39: Armstrong, E., Harskamp, C., Armstrong, A. Psoriasis and Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Observational Studies. Journal of the American Heart Association. 2013; 2: e000062. Accessed June 2018. Source 40: National Psoriasis Foundation. About Psoriatic Arthritis. Available at https://www.psoriasis.org/about-psoriatic-arthritis. Accessed June 2018. Source 41: Ritchlin, C., Colbert, R., Gladman D. Psoriatic Arthritis. The New England Journal of Medicine. Doi: 10.1056/NEJMra1505557. Accessed June 2018. Source 42: Gladman, D., & Chandran, V. Observational cohort studies: Lessons learnt from the University of Toronto Psoriatic Arthritis Program. Rheumatology. 50(1), 25-31. doi:10.1093/rheumatology/keq262. Accessed June 2018. Source 43: Liu, J. Psoriatic arthritis: Epidemiology, diagnosis, and treatment. World Journal of Orthopedics, 5(4), 537. doi:10.5312/wjo.v5.i4.537. Accessed June 2018. Source 44: Crohn’s and colitis UK. Taking the IBD Standards forward in Scotland. Results from Watson, AJM. PTU-288 Taking the ibd standards forward in scotland: a national patient survey. BMJ. Available at https://gut.bmj.com/content/64/Suppl_1/A187.1. Accessed June 2018. Source 45: Marrie R., et al. Nat Rev Neurol. 2017;13:375-382. Accessed June 2018.Source 46: Armstrong, E., Harskamp, C., Armstrong, A. Psoriasis and Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Observational Studies. Journal of the American Heart Association. 2013; 2: e000062. Accessed June 2018. Source 47: Singh, S., Singh, H., Loftus, E., et al. Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Patients with Inflammatory Bowel Disease: a Systematic Review and Meta-Analysis. Clinical Gastroenterology and Hepatology. 2014; 2(3): 382-93. Accessed June 2018. Source 48: Polachek, A., Touma, Z., & Anderson, M., et al. Risk of Cardiovascular Morbidity in Patients With Psoriatic Arthritis: A Meta-Analysis of Observational Studies. Arthritis Care & Research. 69(1), 67-74. doi:10.1002/acr.22926. Accessed June 2018. Source 49: Jadidi, E., Mohammadi, M., & Moradi, T. High risk of cardiovascular diseases after diagnosis of multiple sclerosis. Multiple Sclerosis Journal. 19(10), 1336-1340. doi:10.1177/1352458513475833. Accessed June 2018. Source 50: Mozzaffarian, D., et al. Executive Summary: Heart Disease and Stroke Statistics – 2016 Update. AHA. Accessed June 2018. Source 51: Scalfari A., Knappertz V., Cutter G. Mortality in patients with multiple sclerosis. Neurology. 2013. 81(2): 184–192. doi: 10.1212/WNL.0b013e31829a3388. Accessed June 2018. Source 52: Gelfand, J., Troxel, A., Lewis, J., et al. The Risk of Mortality in Patients with Psoriasis: Results From a Population‐Based Study. Archives of Dermatology. 2007; 143(12): 1493‐1499. Accessed June

2018. Source 53: Ali, Y., Tom, B., Schentag, C., et al. Improved Survival in Psoriatic Arthritis with Calendar Time. Arthritis & Rheumatology. 2007; 56(8): 2708‐2714. Accessed June 2018. Source 54: Armstrong, A., Schupp, C., Wu, J., et al. Quality of Life and Work Productivity Impairment Among Psoriasis Patients: Findings from the National Psoriasis Foundation Survey Data 2003‐2011. PLoSOne. 2012; 7(12): e52935. Accessed June 2018. Source 55: Kavanaugh, A., Helliwell, P., & Ritchlin, C. T. (2016). Psoriatic Arthritis and Burden of Disease: Patient Perspectives from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey. Rheumatology and Therapy. 3(1), 91-102. doi:10.1007/s40744-016-0029-z. Accessed April 2018.Source 56: Lönnfors S., Vermeireb S., Grecoa M. IBD and health-related quality of life — Discovering the true impact. Journal of Crohn's and Colitis. 2014. Available at https://academic.oup.com/ecco-jcc/article/8/10/1281/2392494. Accessed June 2018. Source 57: European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA). The True Impact of IBD: A European Crohn’s and Ulcerative Colitis Patient Life: IMPACT Survey 2010-2011. Available at http://efcca-solutions.net/media/jointhefight/ImpactReport.pdf (no longer live). Accessed June 2018. Source 58: Crayton H, et al. Neurology. 2004;63(11 Suppl 5):S12-8. Accessed June 2018. Source 59: Miller A, Bourdette D, Cohen JA, et al. Multiple sclerosis. Continuum 1999;5:120–133. Accessed June 2018.Source 60: Crow, J. Psoriasis Uncovered. Nature Outlook. 2012; 492(20/27): S50-S51. Accessed June 2018. Source 61: Zuckerman, A. Cyclosporine: A Review. Journal of Transplantation. 2012. doi:10.1155/2012/230386. Accessed June 2018. Source 62: Amgen. FDA Approves Expanded Use Of ENBREL® (etanercept) To Treat Children With Chronic Moderate-To-Severe Plaque Psoriasis. Available at https://www.amgen.com/media/news-releases/2016/11/fda-approves-expanded-use-of-enbrel-etanercept-to-treat-children-with-chronic-moderatetosevere-plaque-psoriasis/. Accessed April 2018.

6 | WHO IS CELGENE? 48

2 | LIVING BETTER & HEALTHIER

Supporting References

48

Source 63: Bottrell, John. Let’s Talk Corticosteroids: History, Side effects, and Benefits. Available at https://asthma.net/living/lets-talk-corticosteroids-history-side-effects-benefits/. Accessed June 2018. Source 64: Myhr, K. M., & Mellgren, S. I. Corticosteroids in the treatment of multiple sclerosis. Acta Neurologica Scandinavica, 120. 73-80. doi:10.1111/j.1600-0404.2009.01213. Accessed June 2018. Source 65: Zeichner, J. Use of Topical Coal Tar Foam for the Treatment of Psoriasis in Difficult-to-treat Areas. The Journal of Clinical and Aesthetic Dermatology. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945847/. Accessed June 2018. Source 66: Boivin, N., Baillargeon, J., Doss, P. M., Roy, A., & Rangachari, M. Interferon-β Suppresses Murine Th1 Cell Function in the Absence of Antigen-Presenting Cells. Plos One. 10(4). doi:10.1371/journal.pone.0124802. Accessed June 2018. Source 67: Gottlieb, A., & Narang, K. Ustekinumab in the treatment of psoriatic arthritis: Latest findings and clinical potential. Therapeutic Advances in Musculoskeletal Disease. 5(5), 277-285. doi:10.1177/1759720x13501021. Accessed June 2018. Source 68: Khatri, B. O. (2016). Fingolimod in the treatment of relapsing–remitting multiple sclerosis: Long-term experience and an update on the clinical evidence. Therapeutic Advances in Neurological Disorders, 9(2), 130-147. doi:10.1177/1756285616628766. Accessed June 2018. Source 69: Schafer, P., Parton, A., Capone, L., Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cellular Signalling, 26(9), 2016-2029. doi:10.1016/j.cellsig.2014.05.014. Accessed June 2018. Source 70: Pfizer. Pfizer Announces FDA Approval of XELJANZ® (tofacitinib) and XELJANZ® XR for the Treatment of Active Psoriatic Arthritis . Available at http://press.pfizer.com/press-release/pfizer-announces-fda-approval-xeljanz-tofacitinib-and-xeljanz-xr-treatment-active-psor. Accessed June 2018. Source 71: Shu S., Wang J., Tao M. Gene Therapy for Autoimmune Disease. Clinical Reviews in Allergy & Immunology. Available at https://link.springer.com/article/10.1007%2Fs12016-014-8451-x. Accessed June 2018. Source 72: Weinblatt, M. Methotrexate in Rheumatoid Arthritis: A Quarter Century of Development. Transactions of the American Clinical and Climatological Association, 2013; 124: 16–25. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715949/. Accessed June 2018. Source 73: Celgene. Oral OTEZLA® (apremilast) Approved by the U.S. Food and Drug Administration for the Treatment of Patients with Moderate to Severe Plaque Psoriasis. Available at http://ir.celgene.com/releasedetail.cfm?releaseid=872240. Accessed June 2018. Source 74: Johnson & Johnson. STELARA® (Ustekinumab) Receives FDA Approval To Treat Active Psoriatic Arthritis. Available at https://www.jnj.com/media-center/press-releases/stelara-ustekinumab-receives-fda-approval-to-treat-active-psoriatic-arthritis. Accessed June 2018. Source 75: Johnson & Johnson. FDA Approves STELARA® (Ustekinumab) for Treatment of Adults With Moderately to Severely Active Crohn’s Disease. Available at https://www.jnj.com/media-center/press-releases/fda-approves-stelara-ustekinumab-for-treatment-of-adults-with-moderately-to-severely-active-crohns-disease. Accessed April 2018. Source 76: FDA Approved Drug Products. Acitretin. Available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019821. Accessed June 2018. Source 77: Upchurch, K., Evolution of treatment for rheumatoid arthritis. Rheumatology. 2012. doi:10.1093/rheumatology/kes278. Accessed June 2018. Source 78: Rolak, L. The History of MS: The Basic Facts. Available at https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-History-of-Multiple-Sclerosis.pdf. Accessed June 2018. Source 79: Multiple Sclerosis Association of America. Timeline – The History of Multiple Sclerosis. Available at https://mymsaa.org/publications/motivator/summer-fall12/cover-story/timeline. Accessed June 2018. Source 80: National Multiple Sclerosis Society. Interferons. Available at https://secure.nationalmssociety.org/site/SPageServer/?NONCE_TOKEN=D1B1C9DADA22CF73012881C883164C18&pagename=HOM_LIB_sourcebook_interferons. Accessed April 2018. Source 81: Kebir, H., Ifergan, I., Alvarez, J., et al. Preferential recruitment of interferon-γ-expressing TH17 cells in multiple sclerosis. Annals of Neurology. 66(3), 390-402. doi:10.1002/ana.21748. Accessed June 2018. Source 82: Deangelis, T., & Lublin, F. Multiple sclerosis: New treatment trials and emerging therapeutic targets. Current Opinion in Neurology. 21(3), 261-271. doi:10.1097/wco.0b013e328300c70d. Accessed June 2018. Source 83: Thormann, A., Sørensen, P. S., Koch-Henriksen, N., et al. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology. 89(16), 1668-1675. doi:10.1212/wnl.0000000000004508. Accessed June 2018. Source 84: National Multiple Sclerosis Society. Disease-Modifying Therapies for MS. Available at http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-The-MS-Disease-Modifying-Medications.pdf. Accessed June 2018. Source 85: Lebwohl, M., Bachelez, H., Barker, J., et al. Patient Perspectives in the Management of Psoriasis: Results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis. Journal of the American Academy of Dermatology. 2014; 70(5): 871-881.e30. Accessed June 2018. Source 86: Lebwohl, M., Bachelez, H., Barker, J., et al. Patient Perspectives in the Management of Psoriasis: Results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis. Journal of the American Academy of Dermatology. 2014; 70(5): 871-881.e30. Accessed June 2018. Source 87: Krupa, L., Kennedy, H., Jamieson, C., et al. The Reasons for Discontinuation of Infliximab Treatment in Patients with Crohn's Disease: A Review of Practice at NHS Teaching Hospital. ISRN Gastroenterology. Article ID 672017. Accessed June 2018.

3

3 | PROGRESS & PROSPERITY

49

49

3 PROGRESS AND PROSPERITYIMMUNE AND INFLAMMATORY DISORDERS POSE A BURDEN FOR BOTH PATIENTS AND SOCIETY

For patients, immune and inflammatory disorders can lead to work-related disability, chronic absenteeism, and losses in overall productivity. These losses are exacerbated when immune and inflammatory diseases strike early in life, with the potential for cumulative, life-long effects on education and careers.

Biopharmaceutical research and development seeks to benefit not only patients, but also society as a whole. Addressing the challenges these disorders pose will benefit the public in a number of ways, including increasing rates of employment and reducing days lost to illness.

As improvements in patient health spur economic growth, these effects are mirrored at a broader level, as jobs in the research arena yield still more jobs in related sectors. Scientific research can serve as an economic engine to drive new opportunities in healthcare and academia.

Ongoing innovation to improve patient treatments simultaneously improves the value these treatments deliver to society.

Alissa Walton was diagnosed with psoriatic arthritis

6 | WHO IS CELGENE? 50

3 | PROGRESS & PROSPERITY 50

The physical manifestations of immune- and inflammatory-related disorders are not only a burden to the patient, but may be to society in different ways

3 | PROGRESS & PROSPERITY

Source 1: Salter, A., Thomas, N., Tyry, T., Cutter, G., & Marrie, R. A. Employment and absenteeism in working-age persons with multiple sclerosis. Journal of Medical Economics, 20(5), 493-502. doi:10.1080/13696998.2016.1277229. Accessed April 2018. Source 2: Tillett, W., de‐Vries, C., McHugh, N. Work Disability in Psoriatic Arthritis: A Systematic Review. Rheumatology. 2012; 51(2): 275‐283. Accessed April 2018. Source 3: De Boer, A. G., Evertsz’, F. B., Stokkers, P. C. Employment status, difficulties at work and quality of life in inflammatory bowel disease patients. European Journal of Gastroenterology & Hepatology, 28(10), 1130-1136. doi:10.1097/meg.0000000000000685. Accessed April 2018.

51

Immune Disorders Have an Impact on Work-Related Disability

51

23%

Source 1: Salter, A., Thomas, N., Tyry, T., Cutter, G., & Marrie, R. A. Employment and absenteeism in working-age persons with multiple sclerosis. Journal of Medical Economics, 20(5), 493-502. doi:10.1080/13696998.2016.1277229. Accessed June 2018. Source 2: Tillett, W., de‐Vries, C., McHugh, N. Work Disability in Psoriatic Arthritis: A Systematic Review. Rheumatology. 2012; 51(2): 275‐283. Accessed June 2018. Source 3: De Boer, A. G., Evertsz’, F. B., Stokkers, P. C. Employment status, difficulties at work and quality of life in inflammatory bowel disease patients. European Journal of Gastroenterology & Hepatology, 28(10), 1130-1136. doi:10.1097/meg.0000000000000685. Accessed June 2018.

I’m unable to provide for myself and my partner. – Crohn’s Disease Patient“ ”

As Immune and Inflammatory Disorders Often Present at a Young Age, the Lifetime Impact on Education, Career Development and Overall Quality of Life May be Substantial

I know someday I will not be able to work, and the time is becoming closer.– Psoriatic Arthritis Patient “ ”

Over the years, I have had no choice but to quit jobs because the pain can get unbearable. – Psoriasis Patient“ ”

I’m sure I am depressed, but I am still functioning. You are working hard to stand still. – Multiple Sclerosis Patient“ ”

52

3 | PROGRESS & PROSPERITY

Nearly a Third of Psoriasis and Psoriatic Arthritis Patients Miss More Than 10 Work Days Per Month*

Source 4: Armstrong, A., Schupp, C., Wu, J., et al. Quality of Life and Work Productivity Impairment Among Psoriasis Patients: Findings from the National Psoriasis Foundation Survey Data 2003‐2011. PLoS One. 2012; 7(12): e52935. Accessed June 2018.

53

53

*A National Psoriasis Foundation survey of 5,604 patients, conducted from 2003-2011.

6 | WHO IS CELGENE? 54

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Work Impairment is Linked to Disease Severity in Plaque Psoriasis Patients

54

PASI = Psoriasis Area Severity Index

*A cross-sectional patient survey and retrospective chart review of 142 patients with a physician-confirmed diagnosis of psoriasis conducted at eight Canadian dermatology clinics

4.2%

15.4%

23.1%

27%

16.2%

0

5

10

15

20

25

30

Mild(n=40)

Moderate(n=41)

Moderate/Severe(n=40)

Severe(n=21)

Total(n=142)

Percent Impairment While Working Due to Plaque Psoriasis

Mean %

Source 5: Lane, S., Szabo, S., & Syed, I., et al. The impact of psoriasis severity on work productivity and daily activities. Journal of the American Academy of Dermatology. 74(5). doi:10.1016/j.jaad.2016.02.1068. Accessed June 2018.

PASI ≤3 3< PASI ≤12 12 PASI ≤2 >20

3 | PROGRESS & PROSPERITY

Psoriatic Arthritis May Decrease Work Productivity*

55

Source 6: Kennedy, M., Papneja A., Thavaneswaran A., et al. Prevalence and Predictors of Reduced Work Productivity in Patients with Psoriatic Arthritis. Clinical and Experimental Rheumatology. 2014; 32(3): 342-8. Accessed June 2018.

*Results from the Work Limitations Questionnaire (WLQ) of 186 eligible psoriatic arthritis patients

6 | WHO IS CELGENE? 56

3 | PROGRESS & PROSPERITY

Source 7: Wilson BS, Lönnfors S, Vermeire S, et al. The True Impact of IBD. A European Crohn's and Ulcerative Colitis Patient Life IMPACT Survey 2010–2011 http://www.efcca.org/index.php/our-activities/latest-news/51-join-the-fight-against-ibd-project (no longer live). Accessed June 2018.

*A total of 4990 IBD patients (63% Crohn’s disease, 33% ulcerative colitis) from 27 countries completed the web-based IMPACT survey.

Nearly 75% of IBD Patients Report Disease-related Absenteeism in the Past Year

56

HAVE TAKEN

TIME OFF IN THE PAST

YEAR DUE TO THEIR CONDITION

OF THOSE PATIENTS HAD

MORE THAN 25 DAYS

ABSENT/YEAR

3 | PROGRESS & PROSPERITY

Employed Multiple Sclerosis Patients May Struggle with Increased Rates of Absenteeism

57

≈25% of MS patients report missed work days; patients with higher PDDS levels miss more days of work*

Source 8: Salter, A., Thomas, N., Tyry, T., Cutter, G., & Marrie, R. A. Employment and absenteeism in working-age persons with multiple sclerosis. Journal of Medical Economics, 20(5), 493-502. doi:10.1080/13696998.2016.1277229. Accessed June 2018.

*As measured by Patient-Determined Disease Steps (PDDS), a validated measure of patient disability with an emphasis on mobility.

0

5

10

15

20

25

30

35

40

Mild Moderate Severe

RMS: Relapsing-Remitting MS PPMS: Primary Progressive MS

% E

mplo

yed M

S P

atients

Mis

sing

Work

Days

in t

he L

ast

6 M

onth

s

6 days missed(mean)

10 days missed(mean)

12 days missed(mean)

10 days missed(mean) 6 days

missed(mean)

PDDS Group

6 | WHO IS CELGENE? 58

3 | PROGRESS & PROSPERITY

Estimated Economic Burden of These Immune and Inflammatory Disorders is Substantial in the U.S.

58

Source 9: American Autoimmune Related Diseases Association (AARDA). The Cost Burden of Autoimmune Disease: The Latest Front in the War on Healthcare Spending. Available at http://www.diabetesed.net/page/_files/autoimmune-diseases.pdf. Accessed June 2018. Source 10: National Multiple Sclerosis Society. Financial Burdens for People with MS, their Families, and Society. Available at https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Documents/Health-Policy-Fact-Sheet-2-Costs.pdf. Accessed May 2018. Source 11: Lee, S., Mendelsohn, A., Sarnes, E. et al. The Burden of Psoriatic Arthritis. Journal of the American Academy of Dermatology. Doi: 10.1016/j.jaad.2015.02.1012. Accessed June 2018.

Multiple Sclerosis

Psoriasis

Psoriatic Arthritis

Ulcerative Colitis

Crohn’s Disease

$28 Billion

$4 Billion$10.9

Billion

$8.1 Billion

$11.2Billion

$62.2Billion

(Annually)

++

+

=

Note: All estimates are inclusive of both direct and indirect annual costs

2 | LIVING LONGER, BETTER & HEALTHIER

*A multicenter, double-blind trial of 1,230 adults who had a diagnosis of plaque psoriasis for at least 6 months, were candidates for phototherapy or systemic therapy, had a baseline Psoriasis Area and Severity Index(PASI) score of 12 or higher, and had at least 10%body surface area (BSA) involvement with psoriasis at baseline.†A randomized study of 504 patients with active psoriatic arthritis. ‡A comprehensive questionnaire distributed to patients in Sweden starting on natalizumab treatment between June 2007 and May 2008, identified via the Swedish National MS registry. §Study utilized data from the Active Ulcerative Colitis Trials 1 and 2 of 728 patients.¶Multicenter, observational study of patients with confirmed diagnosis of CD and initiated anti-TNF treatment.

Source 12: Reich, K. et al. Ustekinumab Decreases Work Limitations, Improves Work Productivity, and Reduces Work Days Missed in Patients with Moderate-to-severe Psoriasis: Results from PHOENIX 2. Journal of Dermatological Treatment 22. doi:10.3109/09546634.2010.499931. Accessed June 2018. Source 13: Zhang F, et al. Work Productivity Improvement Associated With Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients With Psoriatic Arthritis Results Of A Phase 3, Randomized, Controlled Trial. Value Health. 2014 17:A372-3. Accessed June 2018. Source 14: Wickström, A., Nyström, J., & Svenningsson, A. (2012). Improved ability to work after one year of natalizumab treatment in multiple sclerosis. Analysis of disease-specific and work-related factors that influence the effect of treatment. Multiple Sclerosis Journal, 19(5), 622-630. doi:10.1177/1352458512461391. Accessed June 2018. Source 15: Reinisch W, et al. Response and remission are associated with improved quality of life, employment and disability status, hours worked, and productivity of patients with ulcerative colitis. Inflamm Bowel Dis. 2007;13:1135-1140. Accessed June 2018. Source 16: Toruner M, et al. P401 Anti-TNF treatments in Crohn's disease and improvement in work productivity and quality of life: an observational study from Turkey. European Crohn’s and Colitis Organization. Available at http://ecco.sol4.at/index.php/publications/congress-abstract-s/abstracts-2017/item/p401-anti-tnf-treatments-in-crohn-s-disease-and-improvement-in-work-productivity-and-quality-of-life-an-observational-study-from-turkey-2.html. Accessed June 2018.

Treated Patients Have the Potential to Experience Improvements in Workplace Productivity and Attendance

Psoriatic Arthritis

Multiple Sclerosis

PsoriasisUlcerative

Colitis

In patients reporting sickness

at baseline, the number of hours worked weekly nearly doubled following a year

of treatment‡

Crohn’s Disease

After 12 months of treatment,

work time missed decreased by nearly 25%¶

After 16 weeks, treated patients reported ~20% improvement in

productivity compared to

placebo†

After 12 weeks, productivity

improvements were ~70%

greater in treated patients

compared to placebo*

Patients in remission following

treatment report 3X the fully productive

weekly work hours than

patients not in remission§

59

VIRTUOUS

CYCLE1

Over the last half century, improvements in health have been as valuable [for economic growth] as all other sources of economic growth combined.“Kevin Murphy, Ph.D. and Robert Topel, Ph.D.*University of Chicago Economists ”

*Adapted from William D. Nordhaus

60

3 | PROGRESS & PROSPERITY

Biopharmaceutical Sector is a Major Job Generator in the 21st Century

61

OPEN

TOTAL JOBS SUPPORTEDMore than 4.7 million U.S. jobs are

supported by the biopharmaceutical sectorMore than 800,000 jobs in theU.S. biopharmaceutical sector

Each direct biopharmaceutical job

supports nearly 5 additional jobs in other sectors

BIOPHARMA JOBS

Source 17: TEConomy Partners; for PhRMA. The Economic Impact of the US Biopharmaceutical Industry. Columbus, OH: TEConomy Partners. Available at http://phrma-docs.phrma.org/industryprofile/pdfs/ 2017IndustryProfile_TheBiopharmaceuticalIndustrysRole.pdf (no longer live). Accessed June 2018.

6 | WHO IS CELGENE? 62

3 | PROGRESS & PROSPERITY

The Biopharmaceutical Sector is the Most R&D-intensive Industry in the U.S.

62

Source 18: Celgene data on file. Source 19: NDP Analytics. IP-Intensive Manufacturing Industries: Driving U.S. Economic Growth from September 2017. Accessed June 2018.

10,994

16,986

20,098

23,231

47,084

55,717

57,755

147,281

Petroleum & coal

Transportation equipment

Medical equipment

Aerospace*

Computers and electronics

Chemicals

Semiconductors*

Biopharmaceuticals*

Annual Average R&D Investment per Employee by Manufacturing Industry, 2000‐2013

Biopharmaceutical companies invest approximately 12 times the amount of R&D dollars per employee than manufacturing industries overall

Celgene’s 2017 R&D expenditure per employee is ~$792,152

*Manufacturing subsectors

Note: IP-intensive manufacturing industries are defined as those industries that have a higher rate of R&D investment per employee than the average R&D per employee across all manufacturing industries.

3 | PROGRESS & PROSPERITY

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•••••••••••••

•••••••••••••••••••••••••••••••••••••••••

••••••••••••••••••••••••••••••••

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••••••••••••••••••••••••••••••••

The Human Genome Project: An Example of High Return on Investment in Basic Science

63

Why Incentivize the Innovators?

$3.8 billionU.S. Investment in the Human Genome Project

The Human Genome Project supported more than 310,000 jobs and generated $67 billion in U.S. economic output

Source 20: Tripp S, Grueber M; Battelle Memorial Institute, Technology Partnership Practice. Economic Impact of the Human Genome Project. May, 2011. Available at http://www.battelle.org/docs/default-document-library/economic_impact_of_the_human_genome_project.pdf?sfvrsn=2. Accessed June 2018.

6 | WHO IS CELGENE? 64

3 | PROGRESS & PROSPERITY

Understanding the Human Genome Leads to More Precise TargetingThe Human Genome Project maximizes the potential of innovative medicines via more precise targeting that can improve lives and meaningfully contribute to society.

64

Are now packaged with genomic information that tells doctors to test their patients for genetic

variants linked to efficacy, dosages or side-effects

DISORDERS

DIFFERENT FDA-APPROVED MEDICINES

MORE THAN

100Before the

Human Genome Project,

researchers knew

the genetic basis of about

Today, they know

the basis of nearly

60

CONDITIONS

5,000

Source 21: Young Rojahn S. MIT Technology Review. A Decade of Advances Since the Human Genome Project. 2013. Available at: https://www.technologyreview.com/s/513666/a-decade-of-advances-since-the-human-genome-project/. Accessed June 2018.

3 | PROGRESS & PROSPERITY

Across the U.S., Scientific Research Contributes to Significant Economic Activity

65

In 2013, the biopharmaceutical sector sponsored approximately 6,200 clinical trials of medicines around the United States, involving 1.1 million participants and supporting an estimated $25 billion in economic activity across all 50 states and the District of Columbia.*

*Estimates reflect only those activities occurring at clinical trial sites and exclude more centralized, cross-site functions such as coordination and data analysis. Also excluded are nonclinical R&D such as basic and preclinical research and the significant economic contribution from non-R&D activities of the industry such as manufacturing and distribution.

Source 22: Battelle Technology Partnership Practice; for PhRMA. Biopharmaceutical industry-sponsored clinical trials: impact on state economies. Available at http://phrma-docs.phrma.org/sites/default/files/ pdf/biopharmaceutical-industry-sponsored-clinical-trials-impact-on-state-economies.pdf (no longer live). Accessed June 2018.

Output Total Impact

$1,000+ million

$500 to $999 million

$100 to $499 million

Up to $100 million

6 | WHO IS CELGENE? 66

3 | PROGRESS & PROSPERITY

Scientific Research Contributes to Economic Activity in the U.S. and Around the World

66

Source 23: U.S. National Library of Medicine. ClinicalTrials.gov. Available at https://clinicaltrials.gov/. Accessed June 2018.

10,700+active clinical trials

the U.S. biopharmaceutical sector is sponsoring

In 2018

supporting tangible economic activity including jobs in research, healthcare, academia, and industry

Advances in the life sciences will have applications that extend even beyond the improvement of human health. We must do all we can to pave the way for these advances – and we must do it now.“Elias Zerhouni, M.D.Former Director, National Institutes of Health ”

67

6 | WHO IS CELGENE? 68

3 | PROGRESS & PROSPERITY

Supporting References

68

Source 1: Salter, A., Thomas, N., Tyry, T., Cutter, G., & Marrie, R. A. Employment and absenteeism in working-age persons with multiple sclerosis. Journal of Medical Economics, 20(5), 493-502. doi:10.1080/13696998.2016.1277229. Accessed June 2018. Source 2: Tillett, W., de‐Vries, C., McHugh, N. Work Disability in Psoriatic Arthritis: A Systematic Review. Rheumatology. 2012; 51(2): 275‐283. Accessed June 2018.

Source 3: De Boer, A. G., Evertsz’, F. B., Stokkers, P. C. Employment status, difficulties at work and quality of life in inflammatory bowel disease patients. European Journal of Gastroenterology & Hepatology, 28(10), 1130-1136. doi:10.1097/meg.0000000000000685. Accessed June 2018. Source 4: Armstrong, A., Schupp, C., Wu, J., et al. Quality of Life and Work Productivity Impairment Among Psoriasis Patients: Findings from the National Psoriasis Foundation Survey Data 2003‐2011. PLoSOne. 2012; 7(12): e52935. Accessed June 2018. Source 5: Lane, S., Szabo, S., & Syed, I., et al. The impact of psoriasis severity on work productivity and daily activities. Journal of the American Academy of Dermatology. 74(5). doi:10.1016/j.jaad.2016.02.1068. Accessed June 2018. Source 6: Kennedy, M., Papneja A., Thavaneswaran A., et al. Prevalence and Predictors of Reduced Work Productivity in Patients with Psoriatic Arthritis. Clinical and Experimental Rheumatology. 2014; 32(3): 342-8. Accessed June 2018. Source 7: Wilson BS, Lönnfors S, Vermeire S, et al. The True Impact of IBD. A European Crohn's and Ulcerative Colitis Patient Life IMPACT Survey 2010–2011 http://www.efcca.org/index.php/our-activities/latest-news/51-join-the-fight-against-ibd-project (no longer live). Accessed June 2018. Source 8: Salter, A., Thomas, N., Tyry, T., Cutter, G., & Marrie, R. A. Employment and absenteeism in working-age persons with multiple sclerosis. Journal of Medical Economics, 20(5), 493-502. doi:10.1080/13696998.2016.1277229. Accessed June 2018. Source 9: American Autoimmune Related Diseases Association (AARDA). The Cost Burden of Autoimmune Disease: The Latest Front in the War on Healthcare Spending. Available at http://www.diabetesed.net/page/_files/autoimmune-diseases.pdf. Accessed June 2018. Source 10: National Multiple Sclerosis Society. Financial Burdens for People with MS, their Families, and Society. Available at https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Documents/Health-Policy-Fact-Sheet-2-Costs.pdf. Accessed May 2018. Source 11: Lee, S., Mendelsohn, A., Sarnes, E. et al. The Burden of Psoriatic Arthritis. Journal of the American Academy of Dermatology. Doi: 10.1016/j.jaad.2015.02.1012. Accessed June 2018. Source 12: Reich, K. et al. Ustekinumab Decreases Work Limitations, Improves Work Productivity, and Reduces Work Days Missed in Patients with Moderate-to-severe Psoriasis: Results from PHOENIX 2. Journal of Dermatological Treatment 22. doi:10.3109/09546634.2010.499931. Accessed June 2018. Source 13: Zhang F, et al. Work Productivity Improvement Associated With Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients With Psoriatic Arthritis Results Of A Phase 3, Randomized, Controlled Trial. Value Health. 2014 17:A372-3. Accessed June 2018. Source 14: Wickström, A., Nyström, J., & Svenningsson, A. (2012). Improved ability to work after one year of natalizumab treatment in multiple sclerosis. Analysis of disease-specific and work-related factors that influence the effect of treatment. Multiple Sclerosis Journal, 19(5), 622-630. doi:10.1177/1352458512461391. Accessed June 2018. Source 15: Reinisch W, et al. Response and remission are associated with improved quality of life, employment and disability status, hours worked, and productivity of patients with ulcerative colitis. InflammBowel Dis. 2007;13:1135-1140. Accessed June 2018. Source 16: Toruner M, et al. P401 Anti-TNF treatments in Crohn's disease and improvement in work productivity and quality of life: an observational study from Turkey. European Crohn’s and Colitis Organization. Available at http://ecco.sol4.at/index.php/publications/congress-abstract-s/abstracts-2017/item/p401-anti-tnf-treatments-in-crohn-s-disease-and-improvement-in-work-productivity-and-quality-of-life-an-observational-study-from-turkey-2.html. Accessed June 2018. Source 17: TEConomy Partners; for PhRMA. The Economic Impact of the US Biopharmaceutical Industry. Columbus, OH: TEConomy Partners. Available at http://phrma-docs.phrma.org/industryprofile/pdfs/ 2017IndustryProfile_TheBiopharmaceuticalIndustrysRole.pdf (no longer live). Accessed June 2018. Source 18: Celgene data on file. Source 19: NDP Analytics. IP-Intensive Manufacturing Industries: Driving U.S. Economic Growth from September 2017. Accessed June 2018. Source 20: Tripp S, Grueber M; Battelle Memorial Institute, Technology Partnership Practice. Economic Impact of the Human Genome Project. May, 2011. Available at http://www.battelle.org/docs/default-document-library/economic_impact_of_the_human_genome_project.pdf?sfvrsn=2. Accessed June 2018. Source 21: Young Rojahn S. MIT Technology Review. A Decade of Advances Since the Human Genome Project. 2013. Available at: https://www.technologyreview.com/s/513666/a-decade-of-advances-since-the-human-genome-project/. Accessed June 2018. Source 22: Battelle Technology Partnership Practice; for PhRMA. Biopharmaceutical industry-sponsored clinical trials: impact on state economies. Available at http://phrma-docs.phrma.org/sites/default/files/ pdf/biopharmaceutical-industry-sponsored-clinical-trials-impact-on-state-economies.pdf (no longer live). Accessed June 2018. Source 23: U.S. National Library of Medicine. ClinicalTrials.gov. Available at https://clinicaltrials.gov/. Accessed June 2018.

3 | PROGRESS & PROSPERITY 69

6 | WHO IS CELGENE? 70

3 | PROGRESS & PROSPERITY 70

4

4 | BETTER HEALTHCARE, BETTER OUTCOMES

BETTER HEALTHCARE, BETTER OUTCOMES

71

FOR THE LONG-TERM HEALTH OF THE HEALTHCARE SYSTEM

While healthcare spending continues to grow, relative spending on

medicines has decreased, representing only a fraction of total

healthcare costs. Further savings might be realized through

improvements in access or adherence, resulting in both patient

benefits and broader societal savings that go beyond drug costs.

Improved access to affordable healthcare has already shown

reductions in projected Medicare spending, and the percentage of

U.S. healthcare dollars spent on prescription medications is predicted

to remain fairly stable in the coming years. In addition, there is a

continuous shift in the market. The savings that occur as medicines

become generic can be used towards new innovative therapies that

come to market, allowing for the current system to be sustainable in

the long term.

At the same time, however, patients face rising costs and other

barriers to care that can adversely affect their adherence to therapy.

This may drive downstream impact on costs in the healthcare system,

as patients become sicker and require additional care. Innovative and

efficacious medicines that are accessible to as many patients as

possible benefit the long-term health of the healthcare system.Kara Errington was diagnosed with plaque psoriasis

6 | WHO IS CELGENE? 72

4 | BETTER HEALTHCARE, BETTER OUTCOMES 72

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Total Healthcare Expenditure Has Seen Constant Growth Globally, While Spending on Medicines Has Decreased

73

Pharmaceutical expenditure growth has substantially decreased since 2010 while total healthcare expenditure has continued to grow across developed markets from 1990–2013

-4.0%

-2.0%

0.0%

2.0%

4.0%

6.0%

8.0%

1990 1995 2000 2005 2010 2013

Annual G

row

th in P

harm

ace

utica

l and

Tota

l H

ealth E

xpenditure

per

Capita

Total Health Expenditure Growth Pharmaceutical Expenditure Growth

Note: Average annual growth in pharmaceutical and total health expenditure per capita, in real terms, average across OECD countries, 1990 to 2013 (or nearest year). Countries include Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Israel, Italy, Japan, Korea, Luxembourg, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States.

Source 1: EFPIA 2015, H&G evidence compendium. Available at http://efpia.morris-chapman.net/documents/160/138/2015-Health-amp-Growth-evidence-compendium-Slide-decks (no longer live). Accessed July 2017. Calculated at OECD (2015), Average annual growth in pharmaceutical and total health expenditure per capita, in real terms, average across OECD countries, 1990 to 2013 (or nearest year), in Health at a Glance 2015, OECD Publishing, Paris. Available at http://dx.doi.org/10.1787/health_glance-2015-graph8-en. Accessed June 2018.

6 | WHO IS CELGENE? 74

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Call to Action: Across the Healthcare Landscape, Responsible Use of Medicines Can Lead to Potential Savings

74

Based on estimates from 2012, responsible use of medicines could eliminate up to $213 billion in U.S. healthcare costs annually, which represents 8% of US healthcare spending.

$1

$20

$87

$105

$213

$0 $50 $100 $150 $200 $250

Mismanaged Polpharmacy in the Elderly

Medication Errors

Suboptimal Prescribing*

Nonadherence

Total Avoidable Costs

Avoidable Annual U.S. Healthcare Cost Estimates (in Billions, 2012)

Source 2: IMS Institute for Healthcare Informatics. Avoidable costs in US healthcare: the $200 billion opportunity from using medicines more responsibly. Available at http://www.imshealth.com/files/web/IMSH%20Institute/Reports/Avoidable_Costs_in%20_US_Healthcare/IHII_AvoidableCosts_2013.pdf. Published June 2013. Accessed June 2018.

*Category includes delayed evidence-based treatment practice ($40 billion), antibiotic misuse ($35 billion), and suboptimal generic use ($12 billion)

4 | BETTER HEALTHCARE, BETTER OUTCOMES

*Retrospective cohort study involving patients with psoriasis adherent and non-adherent to the prescribed treatment regimen.†A phase 3, double-blind, placebo-controlled trial of 409 patients with active psoriatic arthritis. ‡A study of 16, 2018 patients with MS who initiated a DMT in a US administrative claims database were followed for 1 year. §Study included approximately 3.6 million patients enrolled in the Maryland CareFirst BlueCross BlueShield program.

¶Analysis of patients with CD who had at least four infliximab infusions (with the time between consecutive infusions ≤12 weeks for the first four infusions) during the first year following infliximab initiation (index date) were identified from the Integrated Health Care Information Service claims database (2002-2006).

Source 3: Jevtic, T., Bukumiric, Zoran., Jankovic, S. Effects of treatment adherence on clinical and economic outcomes in patients with psoriasis. Med Glas Ljek komore Zenicko-doboj kantona. 2013. 10(1). Accessed June 2018. Source 4: Kavanaugh, A., Gladman, D., & Heijde, D., et al. Improvements In Productivity At Paid Work And Within Household, And Increased Participation In Daily Activities After 24 Weeks Of Certolizumab Pegol Treatment Of Patients With Psoriatic Arthritis: Results Of A Phase 3 Double Blind Randomized Placebo-Controlled Study. Value in Health. 16(3). doi:10.1016/j.jval.2013.03.1158. Accessed June 2018. Source 5: Thomas, N., Curkendall, S., Farr, A., et al. The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis. The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis. 19(5):497-505. doi: 10.3111/13696998.2015.1134546. Accessed June 2018. Source 6: Kane, S., & Shaya, F. Medication Non-adherence is Associated with Increased Medical Health Care Costs. Digestive Diseases and Sciences. 53(4), 1020-1024. doi:10.1007/s10620-007-9968-0. Accessed June 2018. Source 7: Kane, S., Chao, J., & Mulani, P. Adherence to infliximab maintenance therapy and health care utilization and costs by Crohn’s disease patients. Advances in Therapy. 26(10), 936-946. doi:10.1007/s12325-009-0069-7. Accessed June 2018.

Studies Show Substantial Value from Improved Use of Medicines

Adherence leads

to faster clinical

improvement,

with a more rapid

decrease in the

costs of

treatment and

diminished

overall

expenditures*

Psoriatic Arthritis

Multiple Sclerosis

PsoriasisUlcerative

ColitisCrohn’s Disease

After 24 weeks,

treated patients

who did not

report workplace

absenteeism

increased by

12-19%,

compared with

only 1% in the

placebo group†

Improved

persistence to

medications

reduces the

likelihood of a

patient’s hospital

admission and

emergency room

visits by up to

50%‡

Adherence was

associated with

62% lower costs

for hospital

admissions and

49.8% lower

overall total

health care costs§

Adherent

patients resulted

in savings of

73% and 90%

for all-cause and

CD-related

medical costs,

respectively¶

75

There are advanced technologies which can dramatically lower health care costs andimprove quality. The technologies are proven. The associated benefits are known. But there are barriers in the system which impede their implementation. We can change that.

“Mitchell AdamsFormer Executive Director,Massachusetts Technology Collaborative ”

76

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Decreases in Overall Spending for Medicare Beneficiaries are Largely Attributable to Part D Spending on Prescription Drugs

77

Since 2012Between 2011-2014

OF THE SLOWDOWN IN OVERALL MEDICARE BENEFITS

SINCE 2011

MORE THAN

60%

OF TOTAL MEDICARE

SPENDING IS TOWARD PART D

BUT THIS ACCOUNTED

FOR

Source 8: Adler L., Rosenberg. A. The $500 Billion Medicare Slowdown: A Story About Part D. Health Affairs Blog. Available at http://healthaffairs.org/blog/2014/10/21/the-500-billion-medicare-slowdown-a-story-about-part-d/. Accessed June 2018. Source 9: Congressional Budget Office. Competition and the Cost of Medicare’s Prescription Drug Program. Accessed June 2018.

APPROX.

10%

6 | WHO IS CELGENE? 78

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Improved Access to Healthcare Through the Affordable Care Act Has Slowed the Projected Growth of Medicare Spending

$0

$200

$400

$600

$800

$1,000

$1,200

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025

Medic

are

Spendin

g P

roje

ctio

ns

($ in B

illio

ns)

January 2010

January 2011

January 2012

February 2013

February 2014

March 2015

78

Source 10: Blumenthal, D. The Affordable Care Act at Five Years. The New England Journal of Medicine. doi:10.15868/socialsector.25102. Accessed June 2018.

Congressional Budget Office estimates for Medicare spending in 2020 have been reduced more than $200 billion since January of 2010

Projected Medicare Spending in 2020:As of January 2010: $1,038 Billion

As of March 2015: $829 Billion

4 | BETTER HEALTHCARE, BETTER OUTCOMES

32%

19%

3%

29%

11%

1%

5%

U.S. National Health Expenditure Dollars: Increased Spending, but Projected Allocations Remain Consistent

79

32%

20%

3%

29%

10%

1%

5%

Hospital Care

Physician & Clinical

Home Health

Other

Prescription Drugs

R&D

Nursing Care

2016 NHE: $3,337.2 Billion (Projected) 2026 NHE: $5,696.2 Billion

Source 11: CMS National Health Expenditure Accounts, January 2017. National Health Expenditure Amounts and Annual Percent Change by Type of Expenditure: Calendar Years 2010-2026. Available at https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/index.html. Accessed June 2018.

6 | WHO IS CELGENE? 80

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Prescription Growth Has Been Lower or on Par with Other Components of Healthcare Spending

-4%

-2%

0%

2%

4%

6%

8%

10%

12%

14%

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

80

National Health Expenditures

Retail Medicine Prescriptions

Hospital Care

Net Cost of Health Insurance

Professional Services

Year-Over-Year Growth in Spending

Source 12: CMS National Health Expenditure Accounts, January 2017. National Health Expenditures; Aggregate, Annual Percent Change, Percent Distribution and Per Capita Amounts, by Type of Expenditure: Selected Calendar Years 1960-2016. Available at https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nationalhealthaccountsprojected.html. Accessed June 2018. Source 13: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018.

4 | BETTER HEALTHCARE, BETTER OUTCOMES

6.2

20.717.3

14.312

7

6.7

3.75.7

5.23.9

2.19.9

3.6

1.52.7

1.73.1

1.4

-0.5

2.2

5.32.7

-0.7-5

-18.8

-10.2 -11.3-12.2

-12.5

0

Net Spending Growth by Product Type US $Bn

LOE

Generics Price

Generics Volume

Protected Brands Volume

Protected Brands Price

New Brands

Total Net Spending Growth on Medicines is Falling Due to Decreased Spending on New Brands and Increased Generic Competition

81

Total

2013 2014 2015 2016 2017

Source 14: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018.

6 | WHO IS CELGENE? 82

4 | BETTER HEALTHCARE, BETTER OUTCOMES

602 606 605 579 536 513 512 522 505 469

198 215 232 239238 253

310358 391 407

0

100

200

300

400

500

600

700

800

900

1000

Declining Medicine Costs Due to Patent Expirations

82

Real Net Per Capita Medicine Spending and Growth by Product Type (U.S.$)

Specialty % growth Real Net Per Capita Spending Growth % Traditional % growth

20172008 2009 2010 2011 2012 2013 2014 2015 2016

$800 $822 $837 $818$774 $766

$823$896 $876

25%

20%

15%

10%

5%

0%

-5%

-10%

-15%

-20%

Real 2017 U

S$ N

et

Per

Capita M

edic

ine S

pendin

g

$880

Traditional Specialty

Gro

wth

Traditional medicine costs are declining due to patent expirations, creating room for new specialty medicines

Total

Source 15: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018.

4 | BETTER HEALTHCARE, BETTER OUTCOMES

240 255 260 270 255 257 280 312 325 325 337 345 355 375 395

4045

60 60 65 80100

117125 130

33

145158

170192

0

100

200

300

400

500

600

700

Net Spending Growth on Medicines was 0.6% in 2017; Expected to Average 2-5% Through 2022

83

Total Spending on Medicines, Growth and Outlook to 2022, US$Bn

Growth will be driven by innovation and offset by slower price growth and patent expirations

Invoice Spending growth Net Spending Growth

20172008 2009 2010 2011 2012 2013 2014 2015 2016

15%

10%

5%

0%

-5%

-10%

Spendin

g U

S$Bn

Net Spending Invoice to Net Difference

Gro

wth

2022*2018* 2019* 2020* 2021*

Source 16: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018.

0.6%

*Projected growth

6 | WHO IS CELGENE? 84

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Multiple Sources Show Medicine Spending Growth Slowed in 2017

84

+1.5%Express Scripts

+0.6%IQVIA

+1.9%CVS

-0.2%Prime Therapeutics

(Commercial Plans) (Commercial Plans)

(Commercial Plans)(Net Spending Growth)

Source 17: Express Scripts. Express Scripts 2017 Drug Trend Report. (n.d.). Available at http://lab.express-scripts.com/lab/drug-trend-report/2017-dtr. Accessed June 2018.Source 18: Prime Therapeutics. Focus on Trend. Retrieved from: https://www.primetherapeutics.com/content/dam/corporate/Documents/Newsroom/Pressreleases/2018/document-commercial-trendspring-2018.pdf. Accessed June 2018.Source 19: QuintileslMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018.Source 20: CVS. Drug Trend Report 2017. Available at https://payorsolutions.cvshealth.com/sites/default/files/cvs-health-payor-solutions-2017-drug-trend-report-feature-april-2017.pdf. Accessed June 2018.

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Forecasts of Specialty Drug Spending Have Been Overstated

85

An analysis of annual drug trend reports found that inconsistent definitions of specialty medicines can bias spending projections

24% 27%

19%

27%17%

18%

2011 2012 2013

Forecast vs. Actual Growth in Specialty Medication SpendingFrom a Major Pharmacy Benefits Management Company*

Forecasted 2 years prior Forecasted 1 year prior As reported for year

17% 18%

14%

*As reported in annual Drug Trend Reports from Express Scripts.

Source 21: Dieguez G, et. al. Milliman, Inc. Understanding Specialty Drug Forecasts. Available at http://phrma-docs.phrma.org/sites/default/files/pdf/milliman-specialty-drug-forecasts.pdf. Accessed June 2018.

6 | WHO IS CELGENE? 86

4 | BETTER HEALTHCARE, BETTER OUTCOMES 86

DRUG DEVELOPMENT BRAND DRUG LIFESPAN* GENERICS

FDAApproval

Generics Enter Market

Most brand medicines face

competition from other brands

Average time to develop a new medicine:

at least 10 years

Average time on market before generic entry:

12.5 years†

*Brand drug market share generally declines rapidly after generic entry†For brand medicines with more than $250 million in annual sales in 2008 dollars, which account for 82% of the brand medicines analyzed

FOREVER

Source 22: Pharmaceutical Research and Manufacturers of America. Drug Discovery and Development: Understanding the R&D Process. Available at http://www.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf. Accessed June 2018. Source 23: Grabowksi H, Long G, Mortimer R, Boyo A. Updated trends in US brand-name and generic drug competition. J Med Economics. 2016;19(9):836-844. Available at http://www.tandfonline.com/doi/abs/10.1080/13696998.2016.1176578?journalCode=ijme20. Accessed June 2018.

Additional Cost Savings to the Healthcare System are Realized Once New Medicines Become Generic

4 | BETTER HEALTHCARE, BETTER OUTCOMES

As Innovator Brands Lose Exclusivity, Generics Account for an Increasing Percentage of Total Prescriptions

87

46% 43% 40% 37%33%

28% 26%22%

27%22% 20% 18% 17% 16% 14%

54% 57% 60% 63%67%

72% 74%78%

73%78% 81% 82% 83% 84% 86%

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017*

Percent Share of Prescriptions

Innovator Brands Generics

Chart Notes: Includes all prescriptions dispensed through retail pharmacies, including independent and chain drug stores, food store pharmacies and mail order as well as long-term care facilities. Generics include branded and unbranded generic medicines. Prescription counts are not adjusted for length of therapy. 90-day and 30-day prescriptions are both counted as one prescription.

*Data is from IQVIA 2018; All other data from IMS 2017

Source 24: IMS Institute for Health Informatics Declining Medicine Use and Costs: For Better or Worse? A Review of the Use of Medicines in the United States in 2012. Available at http://static.correofarmaceutico.com/docs/2013/05/20/usareport.pdf. Accessed June 2018. Source 25: Long D. Global Generic and Biosimilars Trends and Insights. Available at https://accessiblemeds.org/sites/default/files/2018-02/Doug%20Long.pdf. Accessed June 2018.

6 | WHO IS CELGENE? 88

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Generic Medicines Generated $253 Billion in Savings for Patients and the Health System in 2016

88

– Pharmaceutical Research and Manufacturers of

America (PhRMA)

“The savings created by generic copies free up resources to invest in new treatments –creating headroom for innovation – and resulting in significant progress against some of the most costly and challenging diseases.”

Recent generic entries have exhibited steeper and faster

price reductions compared to earlier generic entries

Monthly price reductions for oral medicines after loss of exclusivity

2002-2004

2005-2007

2008-2010

2011-2013

2002-2014

0%

-20%

-40%

-60%

-80%

-100%

0 6 12 18 24 30 36

Price

Reduct

ions

Months Since Loss of Exclusivity

Source 26: IMS Health. Price Declines after Branded Medicines Lose Exclusivity in the U.S. Available at https://www.imshealth.com/files/web/IMSH%20Institute/Healthcare%20Briefs/PhRMA%20Generic%20Price%20Brief%20January%202016.pdf. Accessed June 2018. Source 27: IMS Health, National Sales Perspectives, March 2015. Available at http://stateofreform.com/featured/2017/06/generic-drugs-generated-253-billion-savings-2016/. Accessed June 2018.

4 | BETTER HEALTHCARE, BETTER OUTCOMES 89

Innovator Brands that Become Generics Reduce Costs for the Healthcare System

GenericsInnovator Brands

Mental Health

Hypertension

Cholesterol

Antiulcerants

Nervous System Disorders

Pain

Cancer Anti-Nauseants

Oncology

Anticoagulants

Antibacterials

Respiratory

Diabetes

2016 Savings from Generics in Billions

Generic mental health,

hypertension, cholesterol

and ulcer medications

account for half of the

savings in the last 10 years

INCREASEDCOMPETITION

AMONG INNOVATOR

BRANDS

FROM NEW HEPATITIS C THERAPIES

FROM WHEN HEPATITIS C TREATMENT FIRST REACHED THE MARKET

RESULTED IN

~50%DECREASE

IN TREATMENT COST

Generic competition

saved the U.S.

healthcare system

$1.67 trillion from

2007-2016

$44 Billion

$29 Billion

$28 Billion

$22 Billion

$16 Billion

$8.8 Billion

$5.5 Billion

$13 Billion

$11.8 Billion

$10 Billion

$9.1 Billion

$7.4 Billion

Source 28: 2017 Association for Accessible Medicines Generic Drug Access & Savings Report. Available at https://accessiblemeds.org/sites/default/files/2017-07/2017-AAM-Access-Savings-Report-2017-web2.pdf. Accessed June 2018. Source 29: Britt R. MarketWatch. Gilead to discount its pricey Sovaldi drug. Available at http://www.marketwatch.com/story/gilead-to-discount-its-pricey-sovaldi-drug-2015-02-04. Accessed June 2018. Source 30: Gilead FDA Approval Timeline. Available at http://www.gilead.com/medicines/productapprovaltimeline (no longer live). Accessed August 2017.

6 | WHO IS CELGENE? 90

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Loss of Exclusivity Continues to Drive Substantial Price Decreases and Projected Savings in the Next Five Years

90

Lower Brand Invoice Spending Due to Loss of Exclusivity

-0.1 -1.2 -1.2 -0.9 -5.0 -5.7

-9.4-6.9

-2.3

-17.3-11.5 -13.3

-12.5

-16.0 -10.5-20.4

-16.7

-11.9

-15.9

Biologics Small Molecules

-$74 billion

-$105 billion

2022*2013 2014 2015 2016 2017 2018* 2019* 2020* 2021*

Chart notes: Lower brand spending based on invoice prices. Historic impacts from QuintilesIMS National Sales Perspectives, forecast impacts are modeled by projecting individual products sales growth to the point of patent expiry and then modeling expected impact based on historical analogues and actual data for in-progress events.

*Estimated numbers based on projections

Source 31: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018.

-17.3

-11.6

-14.5 -13.7

-16.9-15.5

-26.1

-18.8 -18.2

-26.0

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Patients in the U.S. are Facing Rising Out-of-pocket Costs and Other Barriers to Care

23%

46%

2012 2015

Percent of Plans with Deductibles on Prescription Medicines

The Use of Four or More Cost Sharing Tiers is Becoming More Common on Employer Plans

3% 5%

7%

13%14%

20%

23%

2004 2006 2008 2010 2012 2014 2015 2016

32%

Source 32: PWC, Health and Well-Being Touchstone Survey, June 2016. Available at https://www.pwc.com/us/en/hr-management/publications/assets/pwc-touchstone-2017.pdf. Accessed June 2018. Source 33: Kaiser Family Foundation/Health Research & Educational Trust, Employer Health Benefits: 2015 Annual Survey. Available at http://files.kff.org/attachment/Report-Employer-Health-Benefits-2016-Annual-Survey. Accessed June 2018. Source 34: IMS Institute for Healthcare Informatics. Emergence and Impact of Pharmacy Deductibles: Implications for Patients in Commercial Health Plans. Accessed June 2018.

91

6 | WHO IS CELGENE? 92

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Plans Often Charge Patients a Percentage of a Medicine’s Total Cost Rather Than Fixed-dollar Copays

92

Coinsurance

74%

Fixed-DollarCopays26%

In the most frequently purchased type of Health Insurance Exchange plan, coinsurance for certain medicines is common

COINSURANCEcan make a patient’s out-of-pocket costs difficult to predict

– and potentially much higher – than fixed-dollar copays.

* Silver Plans are shown here because they account for a majority of Health Insurance Exchange enrollment. Plans subject different medicines to different levels of cost sharing, or “tiers”. Medicines assigned to a “specialty tier” typically require the highest level of cost sharing.

Source 35: Pearson C F. Avalere Health Release Majority of Drugs Now Subject to Coinsurance in Medicare Part D Plans. Available at http://avalere.com/expertise/managed-care/insights/majority-of-drugs-now-subject-to-coinsurance-in-medicare-part-d-plans data conducted using Avalere Health’s Data Frame database accessed here http://avalere.com/business-intelligence. Accessed June 2018. Source 36: Pharmaceutical Research and Manufacturers of America. Biopharmaceuticals in Perspective. Spring 2016. Available at http://phrma-docs.phrma.org/sites/default/files/pdf/chart-pack-biopharmaceuticals-in-perspective.pdf. Calculated with Avalere Health PlanScape©, http://go.avalere.com/acton/fs/blocks/showLandingPage/a/12909/p/p-00ed/t/page/fm/0 a proprietary analysis of exchange plan features, December 2015. This analysis is based on data collected by Managed Markets Insight & Technology, LLC. Accessed June 2018.

Cost Sharing in Specialty Tiers of 2016 Silver Plans*

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Cost-sharing Shifts an Increasing Burden to Patients

93

0

2

4

6

8

10

12

14

16

Co-payments for non-preferred-brand drugs

General annual deductibles Out-of-pocket limits

7.1

10.3

13.6

Source 37: The Commonwealth Fund. Changes in Consumer Cost-Sharing for Health Plans Sold in the ACA’s Insurance Marketplaces, 2015 to 2016. Available at http://www.commonwealthfund.org/publications/issue-briefs/2016/may/cost-sharing-increases. Accessed June 2018.

% c

hange

Average Changes in Consumer Cost-sharing for Health Plans Sold in the Affordable Care Act Insurance Marketplaces 2015–2016

6 | WHO IS CELGENE? 94

4 | BETTER HEALTHCARE, BETTER OUTCOMES

High Cost-sharing is Associated with Reductions in Use of Medicine

94

-45% -44%

-34% -33% -32%

-26% -26% -25%

-50%

-45%

-40%

-35%

-30%

-25%

-20%

-15%

-10%

-5%

0%

Perc

ent

change in d

ays

supplie

d o

f m

edic

ines

Percentage Change in Adherence from Doubling Medicine Copays from 1997–2000*

*Based on information from claims database

Source 38: Goldman D P, Joyce G F, Escarce J , et al. Pharmacy benefits and the use of drugs by the chronically ill. JAMA. 2004;291(19):2344-2350. Available at http://jamanetwork.com/journals/jama/fullarticle/198761. Accessed June 2018.

4 | BETTER HEALTHCARE, BETTER OUTCOMES

58% 60% 59% 32%94%

40%of those:

of patients were required to fail two or more drugs before having access to the originally prescribed drug

indicated they had been subject to step therapy

Step Therapy May Further Limit Access to Prescribed Medicines: A Case Study in IBD

95

In a survey* of 2,600 IBD patients:

*National survey performed by the Crohn’s & Colitis Foundation. 2,602 respondents were surveyed in December 2016.

were unable to have a doctor intervene to stop the step therapy process on their behalf

were delayed from their optimal treatment plan for over three months

were delayed for over 7 months

believe step therapy to be a barrier to timely and appropriate care

Step therapy: An obstacle course to optimal health

Source 39: Crohn’s and Colitis Foundation. Step Therapy. Available at http://www.crohnscolitisfoundation.org/steptherapy/state-content/infographic1.pdf. Accessed June 2018.

Medicines should reach as many people as possible; we need ideas from stakeholders in the fields of health and innovation to make this a reality.“Shiba PhurailatpamDirector of the Asia Pacific Network of People Living with HIV ”

96

4 | BETTER HEALTHCARE, BETTER OUTCOMES 97

6 | WHO IS CELGENE? 98

4 | BETTER HEALTHCARE, BETTER OUTCOMES

Source 1: EFPIA 2015, H&G evidence compendium. Available at http://efpia.morris-chapman.net/documents/160/138/2015-Health-amp-Growth-evidence-compendium-Slide-decks (no longer live). Accessed July 2017. Calculated at OECD (2015), Average annual growth in pharmaceutical and total health expenditure per capita, in real terms, average across OECD countries, 1990 to 2013 (or nearest year), in Health at a Glance 2015, OECD Publishing, Paris. Available at http://dx.doi.org/10.1787/health_glance-2015-graph8-en. Accessed June 2018. Source 2: IMS Institute for Healthcare Informatics. Avoidable costs in US healthcare: the $200 billion opportunity from using medicines more responsibly. Available at http://www.imshealth.com/files/web/IMSH%20Institute/Reports/Avoidable_Costs_in%20_US_Healthcare/IHII_AvoidableCosts_2013.pdf. Published June 2013. Accessed June 2018. Source 3: Jevtic, T., Bukumiric, Zoran., Jankovic, S. Effects of treatment adherence on clinical and economic outcomes in patients with psoriasis. Med Glas Ljek komore Zenicko-doboj kantona. 2013. 10(1). Accessed June 2018. Source 4: Kavanaugh, A., Gladman, D., & Heijde, D., et al. Improvements In Productivity At Paid Work And Within Household, And Increased Participation In Daily Activities After 24 Weeks Of Certolizumab Pegol Treatment Of Patients With Psoriatic Arthritis: Results Of A Phase 3 Double Blind Randomized Placebo-Controlled Study. Value in Health. 16(3). doi:10.1016/j.jval.2013.03.1158. Accessed June 2018. Source 5: Thomas, N., Curkendall, S., Farr, A., et al. The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis. The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis. 19(5):497-505. doi: 10.3111/13696998.2015.1134546. Accessed June 2018. Source 6: Kane, S., & Shaya, F. Medication Non-adherence is Associated with Increased Medical Health Care Costs. Digestive Diseases and Sciences. 53(4), 1020-1024. doi:10.1007/s10620-007-9968-0. Accessed June 2018. Source 7: Kane, S., Chao, J., & Mulani, P. Adherence to infliximab maintenance therapy and health care utilization and costs by Crohn’s disease patients. Advances in Therapy. 26(10), 936-946. doi:10.1007/s12325-009-0069-7. Accessed June 2018. Source 8: Adler L., Rosenberg. A. The $500 Billion Medicare Slowdown: A Story About Part D. Health Affairs Blog. Available at http://healthaffairs.org/blog/2014/10/21/the-500-billion-medicare-slowdown-a-story-about-part-d/. Accessed June 2018. Source 9: Congressional Budget Office. Competition and the Cost of Medicare’s Prescription Drug Program. Accessed June 2018. Source 10: Blumenthal, D. The Affordable Care Act at Five Years. The New England Journal of Medicine. doi:10.15868/socialsector.25102. Accessed June 2018. Source 11: CMS National Health Expenditure Accounts, January 2017. National Health Expenditure Amounts and Annual Percent Change by Type of Expenditure: Calendar Years 2010-2026. Available at https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/index.html. Accessed June 2018. Source 12: CMS National Health Expenditure Accounts, January 2017. National Health Expenditures; Aggregate, Annual Percent Change, Percent Distribution and Per Capita Amounts, by Type of Expenditure: Selected Calendar Years 1960-2016. Available at https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nationalhealthaccountsprojected.html. Accessed June 2018. Source 13: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018. Source 14: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018. Source 15: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018. Source 16: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018. Source 17: Express Scripts. Express Scripts 2017 Drug Trend Report. (n.d.). Available at http://lab.express-scripts.com/lab/drug-trend-report/2017-dtr. Accessed June 2018.Source 18: Prime Therapeutics. Focus on Trend. Retrieved from: https://www.primetherapeutics.com/content/dam/corporate/Documents/Newsroom/Pressreleases/2018/document-commercial-trendspring-2018.pdf. Accessed June 2018.Source 19: QuintileslMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018.Source 20: CVS. Drug Trend Report 2017. Available at https://payorsolutions.cvshealth.com/sites/default/files/cvs-health-payor-solutions-2017-drug-trend-report-feature-april-2017.pdf. Accessed June 2018.Source 21: Dieguez G, et. al. Milliman, Inc. Understanding Specialty Drug Forecasts. Available at http://phrma-docs.phrma.org/sites/default/files/pdf/milliman-specialty-drug-forecasts.pdf. Accessed June 2018. Source 22: Pharmaceutical Research and Manufacturers of America. Drug Discovery and Development: Understanding the R&D Process. Available at http://www.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf. Accessed June 2018. Source 23: Grabowksi H, Long G, Mortimer R, Boyo A. Updated trends in US brand-name and generic drug competition. J Med Economics. 2016;19(9):836-844. Available at http://www.tandfonline.com/doi/abs/10.1080/13696998.2016.1176578?journalCode=ijme20. Accessed June 2018. Source 24: IMS Institute for Health Informatics Declining Medicine Use and Costs: For Better or Worse? A Review of the Use of Medicines in the United States in 2012. Available at http://static.correofarmaceutico.com/docs/2013/05/20/usareport.pdf. Accessed June 2018. Source 25: Long D. Global Generic and Biosimilars Trends and Insights. Available at https://accessiblemeds.org/sites/default/files/2018-02/Doug%20Long.pdf. Accessed June 2018. Source 26: IMS Health. Price Declines after Branded Medicines Lose Exclusivity in the U.S. Available at https://www.imshealth.com/files/web/IMSH%20Institute/Healthcare%20Briefs/PhRMA%20Generic%20Price%20Brief%20January%202016.pdf. Accessed June 2018. Source 27: IMS Health, National Sales Perspectives, March 2015. Available at http://stateofreform.com/featured/2017/06/generic-drugs-generated-253-billion-savings-2016/. Accessed June 2018. Source 28: 2017 Association for Accessible Medicines Generic Drug Access & Savings Report. Available at https://accessiblemeds.org/sites/default/files/2017-07/2017-AAM-Access-Savings-Report-2017-web2.pdf. Accessed June 2018. Source 29: Britt R. MarketWatch. Gilead to discount its pricey Sovaldi drug. Available at http://www.marketwatch.com/story/gilead-to-discount-its-pricey-sovaldi-drug-2015-02-04. Accessed June 2018. Source 30: Gilead FDA Approval Timeline. Available at http://www.gilead.com/medicines/productapprovaltimeline (no longer live). Accessed August 2017.Source 31: QuintilesIMS, IQVIA National Sales Perspectives, IQVIA Institute, April 2018. Available at https://www.iqvia.com/institute/reports/medicine-use-and-spending-in-the-us-review-of-2017-outlook-to-2022. Accessed June 2018. Source 32: PWC, Health and Well-Being Touchstone Survey, June 2016. Available at https://www.pwc.com/us/en/hr-management/publications/assets/pwc-touchstone-2017.pdf. Accessed June 2018. Source 33: Kaiser Family Foundation/Health Research & Educational Trust, Employer Health Benefits: 2015 Annual Survey. Available at http://files.kff.org/attachment/Report-Employer-Health-Benefits-2016-Annual-Survey. Accessed June 2018. Source 34: IMS Institute for Healthcare Informatics. Emergence and Impact of Pharmacy Deductibles: Implications for Patients in Commercial Health Plans. Accessed June 2018.Source 35: Pearson C F. Avalere Health Release Majority of Drugs Now Subject to Coinsurance in Medicare Part D Plans. Available at http://avalere.com/expertise/managed-care/insights/majority-of-drugs-now-subject-to-coinsurance-in-medicare-part-d-plans data conducted using Avalere Health’s Data Frame database accessed here http://avalere.com/business-intelligence. Accessed June 2018. Source 36: Pharmaceutical Research and Manufacturers of America. Biopharmaceuticals in Perspective. Spring 2016. Available at http://phrma-docs.phrma.org/sites/default/files/pdf/chart-pack-biopharmaceuticals-in-perspective.pdf. Calculated with Avalere Health PlanScape©, http://go.avalere.com/acton/fs/blocks/showLandingPage/a/12909/p/p-00ed/t/page/fm/0 a proprietary analysis of exchange plan features, December 2015. This analysis is based on data collected by Managed Markets Insight & Technology, LLC. Accessed June 2018. Source 37: The Commonwealth Fund. Changes in Consumer Cost-Sharing for Health Plans Sold in the ACA’s Insurance Marketplaces, 2015 to 2016. Available at http://www.commonwealthfund.org/publications/issue-briefs/2016/may/cost-sharing-increases. Accessed June 2018. Source 38: Goldman D P, Joyce G F, Escarce J , et al. Pharmacy benefits and the use of drugs by the chronically ill. JAMA. 2004;291(19):2344-2350. Available at http://jamanetwork.com/journals/jama/fullarticle/198761. Accessed June 2018. Source 39: Crohn’s and Colitis Foundation. Step Therapy. Available at http://www.crohnscolitisfoundation.org/steptherapy/state-content/infographic1.pdf. Accessed June 2018.

Supporting References

98

5

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

WHAT MUST BE DONE TO REALIZE THE FULL PROMISE OF INNOVATION?

Although the pace of progress is accelerating, scientists are just beginning to understand immune and inflammatory disorders. Additional research is needed to unravel the complexities of these conditions, but clues from genetics and the immune system have yielded a global pipeline rich in potential first-in-class therapies, with the promise of precision medicines tailored to individual patient needs.

However, even though progress has been made, there remains a need to accelerate medical innovation throughout the world. This is critical to ensuring further progress in medicine and innovation in immune and inflammatory disorders, with subsequent improvements in quality of life, prosperity and progress.

Life science companies, academic institutions, government, medical societies, patient advocacy groups, and the media, among others, need to work as a collaborative ecosystem to foster greater understanding about immune and inflammatory disorders and stimulate investment in the virtuous cycle of medical innovation.

99

Jennifer Spear was diagnosed with psoriasis and psoriatic arthritis

“ ”Today, no area in biomedical research is more vibrant than immunology and those who suffer from autoimmune diseases stand to benefit.

Sam Hawgood, MBBSChancellor, University of California, San Francisco

100

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

We are at a Critical Crossroads for Medical Innovation

101

R&D Investment Longer, Better, Healthier Lives

AMAJOR PARADOXThe potentialof science is

greater than ever …

but the outlook for

investment has

never been more

uncertain

101

6 | WHO IS CELGENE? 102

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Pace of Medical Progress in Immune and Inflammatory Disorders is Accelerating

Genomic and proteomic technology

The development of genomic and proteomic technologies provides an ability to identify novel bio-signatures to diagnose, classify and guide therapeutic decision making in patients with immune and inflammatory disorders.

Identification of genes that cause the diseases

Researchers are identifying genes that predispose individuals to develop immune and inflammatory disorders and studying how these genes initiate disease process or exacerbate symptoms, including the impact of environmental factors on genes. Epigenetic strategies to modify the expression of specific genes is an emerging tool to alter the course of pathologies driven by the dysregulation of gene expression.

Biomarkeridentification and development

Identification of biomarkers (i.e., clinical signs or lab tests) will allow for earlier and more accurate diagnosis, better prediction of disease flare-ups, and improved monitoring of disease progression and response to treatment. Identification of many biomarkers is needed as some biomarkers may be common in a variety of immune and inflammatory disorders, while others may be unique and disease-specific.

Identification of cellular pathways and new drug targets)

Researchers have been exploring inter- and intracellular pathways that decrease the production of anti-inflammatory mediators, as well as identifying novel drug targets in an effort to discover and develop innovative treatments for immune and inflammatory diseases and their related sequelae.

102

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Maximizing the Promise of Science: 7,000+ Medicines in Development Globally in 2016

103

*Defined as single products that are counted exactly once regardless of the number of indications pursued

Source 1: Biopharmaceuticals in Perspective, Spring 2017. Available at http://phrma-docs.phrma.org/files/dmfile/Biopharmaceuticals-in-Perspective-2017.pdf. Calculated from Adis R&D Insight Database. Accessed June 2018.

836

566

420

311

190 171 13577

0

400

800

1,200

Cancer Rare Diseases NeurologicalDisorders

AutoimmuneDiseases

Heart Disease &Stroke

Diabetes Mental HealthDisorders

Alzheimer'sDiseases

Number of medicines

Biopharmaceutical researchers are working on new medicines* for many diseases, including:

6 | WHO IS CELGENE? 104

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

An Average of 74% of Drugs in the Biopharmaceutical Industry Clinical Pipeline are Potential First-in-class Medicines

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

HIV and Related Conditions

Immunology

Diabetes

Psychiatry

Cardiovascular

Cancer

Neurology

Alzheimer's

Percentage of Products in Clinical Development and Regulatory Review That are Potentially First-in-Class in Selected Therapeutic Areas, 2017

Source 2: Analysis Group. Biopharmaceutical Pipeline Full Report. Available at http://www.analysisgroup.com/uploadedfiles/content/insights/publishing/the_biopharmaceutical_pipeline_report_2017.pdf. Accessed June 2018.

104

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

The Biopharmaceutical Industry Pipeline is Active with Numerous Treatments* in Development for Immune and Inflammatory Disorders

8

25

32

33

48

0

0 10 20 30 40 50 60

Psoriatic Arthritis

Ulcerative Colitis

Multiple Sclerosis

Psoriasis†

Crohn's Disease(as of Match 2015)

Source 3: National Psoriasis Foundation. Drug Pipeline (PsO). Available at http://services.psoriasis.org/drug-pipeline/index.php. Accessed June 2018.Source 4: National Psoriasis Foundation. Drug Pipeline (PsA). Available at http://services.psoriasis.org/drug-pipeline/index.php. Accessed June 2018.Source 5: Drug-Development Pipeline. Multiple Sclerosis Discovery Forum. Available at www.msdiscovery.org/research-resources/drug-pipeline. Accessed June 2018.Source 6: Amiot A. and Peyrin-Biroulet L. Current, new and future biological agents on the horizon for the treatment of inflammatory bowel diseases. Therapeutic Advances in Gastroenterology. 2014;8(2):66-82. doi:10.1177/1756283x14558193. Accessed June 2018.

Number of Treatments in Development

*Some of the treatments are being studied in multiple indications

† Includes topical treatments

105

(as of April 2018)

(as of March 2015)

(as of January 2018)

(as of April 2018)

6 | WHO IS CELGENE? 106

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Biopharmaceutical Companies Conduct the Vast Majority of Research to Translate Early Research into New Medicines

106

While basic research is often initiated in government and academia, it is biopharmaceutical firms that provide the necessary critical mass, expertise and experience needed to develop new medicines.

2015* Biopharmaceutical R&D Investment:

$75.3 Billion (est.)

Applied Research

Basic

ResearchApplied

Research

Basic Research

Management &

Administration

2015 NIH Research Spending:

$29.6 Billion

In addition to basic research and biopharmaceutical related

research, NIH supports applied research on

medical devices, diagnostics, prevention and other areas.

Source 7: Pharmaceutical Research and Manufacturers of America. Biopharmaceuticals in Perspective, Spring 2017. Available at http://phrma-docs.phrma.org/files/dmfile/Biopharmaceuticals-in-Perspective-2017.pdf. Calculated from Tufts CSDD, TEConomy Partners and NIH. Accessed June 2018. Source 8: Chakravarthy R, Cotter K, DiMasi J, Milne C-P, Wendel N; Tufts Center for the Study of Drug Development (CSDD). Public and private sector contributions to the research & development of the most transformational drugs of the last 25 years. Available at http://csdd.tufts.edu/files/uploads/PubPrivPaper2015.pdf (no longer live). Accessed June 2018.

*Latest public data available for biopharmaceutical R&D investment

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Biopharmaceutical Companies are Committed to Advancing Precision Medicine

107

In recent years, we have seen remarkable advances in targeted therapy, and the R&D

pipeline has never been more promising.

42%OF NEW MEDICINES

Source 9: Precision Medicine Coalition. The Personalized Medicines Report 2017. Available at http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/The-Personalized-Medicine-Report1.pdf. Calculated with Tufts Center for the Study of Drug Development (CSDD). Personalized medicine gains traction but still faces multiple challenges. Tufts CSDD Impact Rep. 2015;17(3). Accessed June 2018.

IN THE PIPELINE*2016

25%

PRECISIONMEDICINES

OF NEW MEDICINES

MORE THAN

approved by FDA were

PRECISIONMEDICINES

have potential to be

*Across the entire biopharmaceutical industry

6 | WHO IS CELGENE? 108

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Over Time, Ongoing Research and Use of a Medicine May Reveal Additional Value

108

1ST MAJOR MILESTONE

FOR PATIENTS

AN FDAand

KNOWLEDGEThrough

continued research and

real-world clinical practice

MEDICINE’Sof a

- Earlier use- Use in combination with other agents- Use in specific sub-populations of patients using diagnostics- Use in other disease indications+

With additional research and approvals, greater value may be realized over time

AND SOCIETY

EMERGESOVER TIME

FULL POTENTIAL

– American Society of Clinical Oncology

APPROVAL

INTRODUCTION OF NEW THERAPY IS A

Source 10: Sweeney N Gross T F. Boston Associates. The Value of Innovation in Oncology: Recognizing Emerging Benefits Over Time White Paper May 2015. Available at http://studyres.com/doc/2762501/cancer-medicines. Accessed June 2018.

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Increasing Competition Within Therapeutic Categories

109

The pace of competition has substantially increased and, as a result, the time that a medicine is the

only therapy available in its pharmacologic class has declined.

Source 11: Biopharmaceuticals in Perspective, Spring 2016. Available at https://www.phrma.org/report/chart-pack-biopharmaceuticals-in-perspective. Calculated from Adis R&D Insight Database. Accessed June 2018. Source 12: 1970s data: Tufts Center for the Study of Drug Development, unpublished data, March 2010; 2005‐2011 data: Tufts Center for the Studyof Drug Development. First‐in‐class drugs in competitive development races with later entrants. Tufts CSDD Impact Rep. 2015;17(6). Accessed June 2018.

Source 13: Statista.com. Time between approval of first and second drugs in a therapeutic class. Available at https://www.statista.com/statistics/215468/time-taken-for-approval-of-drugs-in-a-therapeutic-class-in-the-us/. Accessed June 2018.

10.2

2.30

2

4

6

8

10

12

1970s 2005-2011

Me

dia

n N

um

be

r o

f Y

ea

rs

Year of Approval of First-in-Class Medicine

Time Between Approval of First- and Second-in-class Medicines in a Pharmacologic Class

of second medicines in a class

were approved within 2.3 years

of the first medicine’s approval

were approved within just

4 months

6 | WHO IS CELGENE? 110

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Drug Development Costs Continue to Climb

110

The average cost to develop one new approved therapy

more than tripled between the late 1990s and 2014

$140m$320m

$800m$1.2b

Drug Development Costs $2.6b

110

Source 14: Pharmaceutical Research and Manufacturers of America. 2013 Profile: biopharmaceutical research industry. Available at http://www.phrma.org/sites/default/files/pdf/PhRMA%20Profile%202013.pdf. Accessed June 2018. Source 15: DiMasi J. et al. Innovation in the pharmaceutical industry: New estimates of R&D costs. Journal of Health Economics. Available at http://csdd.tufts.edu/news/complete_story/pr_tufts_csdd_2014_cost_study (no longer live). Accessed June 2018.

Note: Drug development costs data from various sources

Drug Development Costs

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Society Benefits from New Treatments and Lower Costs in the Future

Source 16: DiMasi J. et al. Innovation in the pharmaceutical industry: New estimates of R&D costs. Journal of Health Economics. Available at http://csdd.tufts.edu/news/complete_story/pr_tufts_csdd_2014_cost_study (no longer live). Accessed June 2018. Source 17: Pharmaceutical Research and Manufacturers of America. Drug Discovery and Development: Understanding the R&D Process. Available at http://www.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf. Accessed June 2018. Source 18: Grabowksi H, Long G, Mortimer R, Boyo A. Updated trends in US brand-name and generic drug competition. J Med Economics. 2016;19(9):836-844. Available at http://www.tandfonline.com/doi/abs/10.1080/13696998.2016.1176578?journalCode=ijme20. Accessed June 2018.

Innovative therapies have a limited time in their lifecycle to recapture investment and fund future

innovation.

1APPROXIMATELY

5,000to

10,000COMPOUNDS

5COMPOUNDS

DISCOVERY ANDDEVELOPMENT

FDAREVIEW

~$2.6 BILLION

~3-6 YEARSPreclinical

~0.5-2 YEARSFDA Review

INNOVATOREXCLUSIVITY

~5 - 10.5 YEARSFDA-Approved

Therapy

GENERIC

FOREVER~6-7 YEARSClinical Trials

111

6 | WHO IS CELGENE? 112

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

A Collaborative Ecosystem is Necessary to Accelerate Innovation in Immune and Inflammatory Disorders

Media

AcademicInstitution

s

Government

Research

Medical Societies

Continued commitment to R&D, collaboration withacademic researchers, public awareness efforts,unmet needs assessment

LIFE SCIENCES COMPANIES

ACADEMICINSTITUTIONSIncreased focus on collaboration to identify gene markers, new cellular pathways, etc.

GOVERNMENTRESEARCHGreater allocation offunding for research

MEDIAGreater public awareness

and recognition

MEDICAL SOCIETIESBest practice

sharing

PATIENT ADVOCACY ORGANIZATIONS

Awareness and unmet needs clarification

MEDICALINNOVATION

112

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS

Promise and Progress in Immune and Inflammatory Disorders

113

We’re making progress but much more needs to be done to accelerate innovation in immune and inflammatory disorders. Today’s investments in healthcare and R&D can create a better,

more healthy and potentially disease-free world in some conditions.

Personalized medicine

Cellulartherapies

Genetherapy

Genemapping

Immune modifiers

OFFER HOPE

“Eric Topol, M.D.Author, The Creative Destruction of Medicine ”This is the most exciting time in the historyof medicine. If we can make some radicalchanges to accommodate the enormousopportunities, there will be better health atlower costs for many generations to come.

114

5 | WORKING TOWARD A WORLD FREE FROM IMMUNE-INFLAMMATORY DISEASES

Source 1: Biopharmaceuticals in Perspective, Spring 2017. Available at http://phrma-docs.phrma.org/files/dmfile/Biopharmaceuticals-in-Perspective-2017.pdf. Calculated from Adis R&D Insight Database. Accessed June 2018. Source 2: Analysis Group. Biopharmaceutical Pipeline Full Report. Available at http://www.analysisgroup.com/uploadedfiles/content/insights/publishing/the_biopharmaceutical_pipeline_report_2017.pdf. Accessed June 2018. Source 3: National Psoriasis Foundation. Drug Pipeline (PsO). Available at http://services.psoriasis.org/drug-pipeline/index.php. Accessed June 2018.Source 4: National Psoriasis Foundation. Drug Pipeline (PsA). Available at http://services.psoriasis.org/drug-pipeline/index.php. Accessed June 2018.Source 5: Drug-Development Pipeline. Multiple Sclerosis Discovery Forum. Available at www.msdiscovery.org/research-resources/drug-pipeline. Accessed June 2018.Source 6: Amiot A. and Peyrin-Biroulet L. Current, new and future biological agents on the horizon for the treatment of inflammatory bowel diseases. Therapeutic Advances in Gastroenterology. 2014;8(2):66-82. doi:10.1177/1756283x14558193. Accessed June 2018. Source 7: Pharmaceutical Research and Manufacturers of America. Biopharmaceuticals in Perspective, Spring 2017. Available at http://phrma-docs.phrma.org/files/dmfile/Biopharmaceuticals-in-Perspective-2017.pdf. Calculated from Tufts CSDD, TEConomy Partners and NIH. Accessed June 2018. Source 8: Chakravarthy R, Cotter K, DiMasi J, Milne C-P, Wendel N; Tufts Center for the Study of Drug Development (CSDD). Public and private sector contributions to the research & development of the most transformational drugs of the last 25 years. Available at http://csdd.tufts.edu/files/uploads/PubPrivPaper2015.pdf (no longer live). Accessed June 2018. Source 9: Precision Medicine Coalition. The Personalized Medicines Report 2017. Available at http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/The-Personalized-Medicine-Report1.pdf. Calculated with Tufts Center for the Study of Drug Development (CSDD). Personalized medicine gains traction but still faces multiple challenges. Tufts CSDD Impact Rep. 2015;17(3). Accessed June 2018. Source 10: Sweeney N Gross T F. Boston Associates. The Value of Innovation in Oncology: Recognizing Emerging Benefits Over Time White Paper May 2015. Available at http://studyres.com/doc/2762501/cancer-medicines. Accessed June 2018. Source 11: Biopharmaceuticals in Perspective, Spring 2016. Available at https://www.phrma.org/report/chart-pack-biopharmaceuticals-in-perspective. Calculated from Adis R&D Insight Database. Accessed June 2018. Source 12: 1970s data: Tufts Center for the Study of Drug Development, unpublished data, March 2010; 2005‐2011 data: Tufts Center for the Studyof Drug Development. First‐in‐class drugs in competitive development races with later entrants. Tufts CSDD Impact Rep. 2015;17(6). Accessed June 2018.

Source 13: Statista.com. Time between approval of first and second drugs in a therapeutic class. Available at https://www.statista.com/statistics/215468/time-taken-for-approval-of-drugs-in-a-therapeutic-class-in-the-us/. Accessed June 2018. Source 14: Pharmaceutical Research and Manufacturers of America. 2013 Profile: biopharmaceutical research industry. Available at http://www.phrma.org/sites/default/files/pdf/PhRMA%20Profile%202013.pdf. Accessed June 2018. Source 15: DiMasi J. et al. Innovation in the pharmaceutical industry: New estimates of R&D costs. Journal of Health Economics. Available at http://csdd.tufts.edu/news/complete_story/pr_tufts_csdd_2014_cost_study (no longer live). Accessed June 2018. Source 16: DiMasi J. et al. Innovation in the pharmaceutical industry: New estimates of R&D costs. Journal of Health Economics. Available at http://csdd.tufts.edu/news/complete_story/pr_tufts_csdd_2014_cost_study (no longer live). Accessed June 2018. Source 17: Pharmaceutical Research and Manufacturers of America. Drug Discovery and Development: Understanding the R&D Process. Available at http://www.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf. Accessed June 2018. Source 18: Grabowksi H, Long G, Mortimer R, Boyo A. Updated trends in US brand-name and generic drug competition. J Med Economics. 2016;19(9):836-844. Available at http://www.tandfonline.com/doi/abs/10.1080/13696998.2016.1176578?journalCode=ijme20. Accessed June 2018.

Supporting References

115

6 | WHO IS CELGENE? 116

5 | ACCELERATING INNOVATION IN IMMUNE AND INFLAMMATORY DISORDERS 116

6

6 | CELGENE

CELGENE

Passion, innovation, and courage have been in the company’s genes since its founding. Celgene’s unwavering focus on medical innovation underscores its position in a healthcare ecosystem that has delivered longer, healthier lives to patients.

From helping patients obtain their medications to using cutting-edge scientific technology to discover new treatments, Celgene’s entrepreneurial spirit, collaborative culture, and commitment to rare diseases creates a unique platform for transforming patient outcomes. At every level, it is growing and evolving.

Celgene has become a leader in discovering, developing, and delivering innovative medicines to patients with unmet needs, by digging deeper to resolve unanswered scientific questions, and working tirelessly to improve the lives of patients worldwide.

117

ENHANCING THE FUTURE THROUGH MEDICAL INNOVATION

6 | WHO IS CELGENE? 118

6 | CELGENE 118

6 | WHO IS CELGENE?

“Celgene exemplifies what it means to put patientsfirst. From its research and development focused on

bringing innovative therapies to those with highunmet disease needs, to its continued commitmentto support patients and their families through theirjourneys, the patient has and continues to be thefocal point of Celgene.

Susan GorkyPatient Advocacy ”

119

6 | WHO IS CELGENE? 120

6 | CELGENE

Delivering on Our Commitment to Bringing New Treatment Options to Patients in Need

120

Source 1: Celgene. Form 10-K (Annual Report). 2006. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6295570566x0xS930413%2D06%2D2083/816284/filing.pdf. Accessed June 2018. Source 2: Celgene. Form 10-K (Annual Report). 2009. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6295570566x0xS1362310%2D09%2D2329/816284/filing.pdf. Accessed June 2018. Source 3: Celgene. Form 10-K (Annual Report). 2012. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6295570566x0xS1047469%2D12%2D1293/816284/filing.pdf. Accessed June 2018. Source 4: Celgene. Celgene 2017 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6117887751x0x978672/138C3639-1839-499D-8191-34F9E08A0CBD/Celgene_AR_complete_PDF_041718.pdf. Accessed June 2018. Source 5: Celgene. Celgene 2015 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6117887751x0x889847/98954B20-BFA0-4AD4-9649-105595A19800/Celgene_2015_Annual_Report.pdf. Accessed June 2018. Source 6: The 2017 EU Industrial R&D Investment Scoreboard. Available at http://iri.jrc.ec.europa.eu/scoreboard17.html. Accessed June 2018.

*Based on U.S. Generally Accepted Accounting Principles.†R&D intensity is defined as the ratio between R&D investment and net sales of a given company or group of companies‡In Generally Accepted Accounting Principles.

$0

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

$7,000

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

Celgene R&D investmentin millions of dollars‡

Over the past 5 years, Celgene has invested an average of 39.3 percent* of total revenue on research and development. In fact, over the same period, Celgene committed $18.7 billion to research and development (R&D). Celgene also ranked #3 in R&D intensity† according to the 2017 EU Industrial R&D Investment Scoreboard.

6 | CELGENE

Sustaining a Deep and Diverse Group of Innovative Centers of Excellence

121

Research Informatics/ Knowledge Utilization;EU Clinical Operations;Tissue BankSeville, Spain (CITRE)

Immuno-Oncology Research; Research Informatics/ Knowledge UtilizationSeattle, WA

Protein Homeostasis; BiologicsSan Diego, CA

Nonclinical & EarlyClinical DevelopmentSummit, NJ

Medicinal Chemistry;Inflammation & Immunology Cambridge, MA

Inflammation & ImmunologySan Diego, CA

Translational DevelopmentEpigenetics;Quanticel ResearchSan Francisco, CA

6 | WHO IS CELGENE? 122

6 | CELGENE 122

Scientific knowledge has now advanced to the point where it is possible to create medicines that have the potential to modify the

immune and inflammatory systems.

Instead of developing treatments that represent incremental improvements over current standards of care, we

are looking to take on diseases where, many times, patients are

faced with limited treatment options.

For many conditions, normal activities and routines can help change their

outlook on life, to say nothing of the productivity that results from those

patients who are able to return to the workplace as active contributors to the

economy.

Celgene remains committed to supporting patients by not just

developing cutting-edge therapies, but also by addressing other

potential barriers that can prevent patients from fully realizing the

benefits of innovation.

Changing the Course of Immune and Inflammatory Disorders by Focusing on the Drivers of Disease and Supporting Patient Access

6 | CELGENE

Source 7: Celgene. Product Pipeline. Available at http://media.celgene.com/content/uploads/product-pipeline.pdf. Accessed June 2018.

The Celgene Immune and Inflammatory Pipeline is Deep and Robust

123

LEGEND

Post-Approval Research

Ph I

Behçet's Diseaseapremilast

Psoriasisapremilast

Relapsing Multiple Sclerosis

ozanimodEosinophilic EsophagitisRPC4046

Psoriatic Arthritisapremilast

Ulcerative Colitisozanimod

Inflammation &

Immunology

Systemic Lupus Erythematosus

CC-220

Idiopathic Pulmonary Fibrosis

CC-90001

PsoriasisCC-90006

Crohn’s Diseaseozanimod

Ulcerative Colitisapremilast

Ph 2 Ph 3

The best way to predictthe future is to invent it.“ Alan KayAmerican Computer Scientist ”

124

6 | CELGENE

Supporting References

125

Source 1: Celgene. Form 10-K (Annual Report). 2006. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6295570566x0xS930413%2D06%2D2083/816284/filing.pdf. Accessed June 2018. Source 2: Celgene. Form 10-K (Annual Report). 2009. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6295570566x0xS1362310%2D09%2D2329/816284/filing.pdf. Accessed June 2018. Source 3: Celgene. Form 10-K (Annual Report). 2012. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6295570566x0xS1047469%2D12%2D1293/816284/filing.pdf. Accessed June 2018. Source 4: Celgene. Celgene 2017 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6117887751x0x978672/138C3639-1839-499D-8191-34F9E08A0CBD/Celgene_AR_complete_PDF_041718.pdf. Accessed June 2018. Source 5: Celgene. Celgene 2015 Annual Report. Available at http://files.shareholder.com/downloads/AMDA-262QUJ/6117887751x0x889847/98954B20-BFA0-4AD4-9649-105595A19800/Celgene_2015_Annual_Report.pdf. Accessed June 2018. Source 6: The 2017 EU Industrial R&D Investment Scoreboard. Available at http://iri.jrc.ec.europa.eu/scoreboard17.html. Accessed June 2018. Source 7: Celgene. Product Pipeline. Available at http://media.celgene.com/content/uploads/product-pipeline.pdf. Accessed June 2018.

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