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Regeneron Regeneron Pharmaceuticals –Pharmaceuticals –Its history, science Its history, science

and technologyand technology

BIOMAN ConferenceBIOMAN Conference

July 30, 2009July 30, 2009

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Regeneron at the Regeneron at the startstart

Founded in 1988 by Len Schelifer, MD, PhD, Professor Founded in 1988 by Len Schelifer, MD, PhD, Professor of Neurology, Cornell Medical Schoolof Neurology, Cornell Medical School

Four original employeesFour original employees Expertise in neuroscienceExpertise in neuroscience Cutting edge research in neurotropins (CNTF, BDNF, Cutting edge research in neurotropins (CNTF, BDNF,

NGF, NT-3)NGF, NT-3) Commited to the discovery, development and Commited to the discovery, development and

commercialization of drug products for the treatment on commercialization of drug products for the treatment on unmet medical conditionsunmet medical conditions

Initial therapeutic target was treatment of Initial therapeutic target was treatment of neurodegenerative disease (ALS or Lou Gehrig’s disease)neurodegenerative disease (ALS or Lou Gehrig’s disease)

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Regeneron Historical Regeneron Historical Ups and Downs 1989 - 1999Ups and Downs 1989 - 1999

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

New HQ in Tarrytown

BODformedREGN goes public

Rens Mfg site acquired for CNTF

CNTF fails in PIII

BDNF collab. w/ Sumitomo

Axokine collab. w/P&G

Merck toll mfg agreement

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Regeneron Historical Regeneron Historical Milestones 2000 - presentMilestones 2000 - present

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

IL-1 Trap collab. w/ Novartis begins

VEGF Trap collab. w/ Aventis begins

BDNF dropped

Sanofi collab. expandedto mAbs

VEGF Trap –Eye collab w/ Bayer

Axokine poor PIII outcome

Trap molecules begin to emerge

Merck contract ends

IL-1 Trap RA PII releasedNovartiswithdraws

First 2 x 10 kL mfg suite on line

IL-1 Trap appoved in US for CAPS

Second 2x10 kL mfg suite on line

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Regeneron Evolution and Regeneron Evolution and GrowthGrowthHistoricalHistorical CurrentCurrent

Therapeutic Therapeutic AreasAreas

Neurogenerative diseaseNeurogenerative disease VelocImmune turn-VelocImmune turn-key approach:key approach:

CAPSCAPS CancerCancer GoutGout Eye diseaseEye disease ArthritisArthritis PainPain

Drug Drug CandidatesCandidates

Neurotrophic factorsNeurotrophic factors

Cytokine trapsCytokine traps

Monoclonal Antibodies & Fusion ProteinsMonoclonal Antibodies & Fusion Proteins

Production Production SystemsSystems

Bacterial fermentationBacterial fermentation misfolded proteinsmisfolded proteins inclusion bodiesinclusion bodies

Mammalian cell culture (CHO)Mammalian cell culture (CHO) fully folded, functional proteinsfully folded, functional proteins post-translational modificationspost-translational modifications secreted into cell culture fluidsecreted into cell culture fluid

Production Production ScaleScale

300 L bioreactor300 L bioreactor 0.3 m diameter columns0.3 m diameter columns

10,000 L bioreactor10,000 L bioreactor 1.4 m diameter column1.4 m diameter column

IND filingsIND filings 3 in 10 years3 in 10 years 2 – 3 per year2 – 3 per year

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Therapeutic Proteins Therapeutic Proteins TodayToday

Arcalyst, Rilonacept (IL-1 Trap)Arcalyst, Rilonacept (IL-1 Trap)ApprovedApproved

Aflibercept (VEGF Trap)Aflibercept (VEGF Trap) Phase IIIPhase III REGN88 (IL-6R antibody)REGN88 (IL-6R antibody) Phase IIPhase II REGN421 (DLL4 antibody)REGN421 (DLL4 antibody) Phase IPhase I REGN475 (NGF antibody)REGN475 (NGF antibody) Phase IPhase I REGN668 (IL-4R antibody)REGN668 (IL-4R antibody) IND SeptIND Sept REGN727/728 (PCSK9 antibody)REGN727/728 (PCSK9 antibody) IND IND

OctOct

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Regeneron TodayRegeneron Today

Broad clinical development portfolio across Broad clinical development portfolio across all development stages provides multiple all development stages provides multiple “shots on goal”“shots on goal”

Three Phase 3 programs to yield initial data Three Phase 3 programs to yield initial data in 2010in 2010

Potential multiple product launches in next Potential multiple product launches in next few yearsfew years

Nearly 1,000 employees working in a Nearly 1,000 employees working in a science-driven, entrepreneurial culturescience-driven, entrepreneurial culture

Rensselaer facility among the leaders in Rensselaer facility among the leaders in antibody production capacityantibody production capacity

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Regeneron Keys to Regeneron Keys to SuccessSuccess

Commitment to cutting edge science and enabling Commitment to cutting edge science and enabling technologiestechnologies

Neurotrophins, cytokines, angiogenesis, receptor Neurotrophins, cytokines, angiogenesis, receptor chemistry and signalingchemistry and signaling

Cytokine and growth factor TrapsCytokine and growth factor Traps VelociSuite technologiesVelociSuite technologies

Fully integrated biopharmaceutical enterprise Fully integrated biopharmaceutical enterprise World reknown Board of Directors members - 3 nobel World reknown Board of Directors members - 3 nobel

laureates as well as seasoned pharmaceutical professionalslaureates as well as seasoned pharmaceutical professionals Attract and secure investment and favorable corporate Attract and secure investment and favorable corporate

collaborationscollaborations

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Collaboration AgreementsCollaboration Agreements

sanofi-aventis

Bayer HealthCar

esanofi-aventis –

Upfront/milestone payments

$130MM $95MM $85MM –

Development costs paid by partner *

100% ~50% ~100%** –

Profit split — Regeneron share

US 50% 100% 50% 100%

Japan~35%

royalty50% 35-45% 100%

ROW 50% 50% 35-45% 100%

Milestones remaining

Regulatory $400MM $90MM – –

Sales – $135MM $250MM –

Oncology Eye Disease Antibodies Inflammation

* 50% repayment from profits ** plus $475MM of research funding over 5 years

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Trap TechnologyTrap Technology

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Traps: Based on Discovery that Some Traps: Based on Discovery that Some Receptors Must “Heterodimerize” for Receptors Must “Heterodimerize” for

High-affinityHigh-affinity

Ectodomain

Cytodomain

Factor

Conventional Receptor: Receptors “Homo-Dimerize”

+

Many Receptors: Require “Heterodimerization”

Kd = 5 nM Kd ~ pM

R1 R2

Ectodomain

Cytodomain

Factor

+

Conventional “Homodimeric” Soluble

Decoy Receptor (e.g. Enbrel for TNF)

ReceptorEctodomains

Fc Constant (Dimerization & Half-life)

First Generation Heterodimeric TRAP

(subpicomolar affinity)

R2Ectodomain

Fc Constant (Dimerization & Half-life)

R1 Ectodomain

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Conventional “Homodimeric” Soluble

Decoy Receptor (e.g. Enbrel for TNF)

Fc Constant (Dimerization & Half-life)

Antibody Structure

Light Chain

Heavy Chain

Variable Regions (Binding)

Cytokine/Interleukin

ReceptorEctodomains

Fc Constant (Dimerization & Half-life)

First Generation Heterodimeric Interleukin-1

Trap

(subpicomolar affinity)

Receptor 2(IL1 R1)Ectodomain

Fc Constant (Dimerization & Half-life)

Receptor 1(IL1 AcP) Ectodomain

“Single-Chain” Interleukin-1 Trap

(sub-picomolar affinity)

Receptor 2(IL1 R1) Ectodomain

Fc Constant (Dimerization & Half-life)

Receptor 1(IL1 AcP) Ectodomain

Cytokine/Interleukin

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Regeneron’s Traps: Proprietary & Regeneron’s Traps: Proprietary & Turnkey Solutions Turnkey Solutions

for Blocking Well-Validated Cytokine & for Blocking Well-Validated Cytokine & Growth Factor TargetsGrowth Factor Targets

AdvantagesAdvantages Allow targeting of extremely well-Allow targeting of extremely well-

validated cytokines & growth validated cytokines & growth factorsfactors

Can target multiple ligands for Can target multiple ligands for same receptor (e.g., IL1same receptor (e.g., IL1 & & , , VEGF & PLGF)VEGF & PLGF)

All human componentsAll human components Long circulating half-life in Long circulating half-life in

humanshumans In each case, Traps are most In each case, Traps are most

potent blockers described for their potent blockers described for their targets (often by 100-1000 fold) targets (often by 100-1000 fold)

Prior to development of Prior to development of VelocImmuneVelocImmune technology, much technology, much more efficient and higher affinity more efficient and higher affinity than conventional human antibody than conventional human antibody approachesapproaches

Regeneron Traps

2 Receptor’sBinding Regions

… fused to…

IgG Fc region

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ARCALYSTARCALYST®® (rilonacept) (rilonacept) Approved and Launched in 2008Approved and Launched in 2008

ARCALYST® (rilonacept) is approved for treatment of Cryopyrin-Associated Periodic Syndromes (CAPS)*

Rare, inherited, auto-inflammatory diseases Approved for adults and children age 12 and

older Patients with CAPS experience ongoing lifelong

symptoms Intermittent, debilitating exacerbations or flares

can be triggered at any time by exposure to cooling temperatures

Symptoms include rash, fever/chills, joint pain, eye redness/pain and fatigue

Patients often adopt a compromised lifestyle*

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Aflibercept (VEGF Aflibercept (VEGF Trap)Trap)

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Aflibercept Aflibercept DifferentiationDifferentiationAflibercept

All human amino acid sequences~110,000 MWKd = 0.5 pM (tighter than natural receptors)Blocks all mammalian VEGF-A, as well as PlGF and VEGF-BBinds VEGF isoforms as monomer without Immune Complex formation

Bevacizumab

Humanized MAb~160,000 MWKd = 400-1000 pMOnly blocks primate VEGF-AForms Immune Complex with VEGF-A

Figure 1. Structure of VEGF Trap

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VEGF Trap-EyeVEGF Trap-Eye

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0

2

4

6

8

10

12

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76

VEGF Trap – Eye Extension Study: VEGF Trap – Eye Extension Study: Durable Responses in Visual Acuity to 18 Durable Responses in Visual Acuity to 18

Months Months (all 5 dose groups combined, n=117)(all 5 dose groups combined, n=117)

*P < 0.0001 vs. baseline

+7.1 letters*

PRN-dosing phasePRN dosing

2mgFixed-dosing

+7.3 letters*+8.4 letters*

Ch

an

ge in

Vis

ual A

cu

ity (

lett

ers

)

3 12 18Month 1

8

Results Announced May 2009

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Nine Phase 3 Trials Nine Phase 3 Trials Currently UnderwayCurrently Underway

9 Phase 3 Trials9 Phase 3 Trials

Initial Phase 3 data coming in 2010Initial Phase 3 data coming in 2010

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VelociSuiteVelociSuite of Technologies of Technologies

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VelociSuiteVelociSuite of Technologies: of Technologies:Target Identification and ValidationTarget Identification and Validation

Together, used to identify and validate drug targets:Together, used to identify and validate drug targets: Rapidly replaces gene with reporter to see where gene is activeRapidly replaces gene with reporter to see where gene is active Shows the result of deleting or adding extra copies of genesShows the result of deleting or adding extra copies of genes Allows direct testing in mammalian models of whether the gene product Allows direct testing in mammalian models of whether the gene product

is an important target in a disease setting and for therapeutic is an important target in a disease setting and for therapeutic interventionintervention

Selected to play major role in NIH Knockout Mouse ProjectSelected to play major role in NIH Knockout Mouse Project

VelociGene® VelociMouse™

High-throughput generationof almost any desired genetic alteration in mouse embryonic stem cells

High-throughput generationof mouse models directly from embryonic stem cells containing genetically altered target genes

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VelociSuiteVelociSuite of Technologies: Human of Technologies: Human Antibody Generation and Antibody Generation and

ManufacturingManufacturing

GGenetically humanized over enetically humanized over 6 megabases of mouse 6 megabases of mouse immune genomeimmune genome

VelocImmuneVelocImmune mice mount a mice mount a robust immune response robust immune response and generate antibodies as and generate antibodies as efficiently as normal miceefficiently as normal mice

Antibodies with most desirable Antibodies with most desirable characteristics selected and characteristics selected and extracted from B cellsextracted from B cells

Antibodies cloned into high-Antibodies cloned into high-expression manufacturing cell expression manufacturing cell lines, suitable for clinical and lines, suitable for clinical and commercial usecommercial use

VelocImmune®

Rapid generationof high-quality, fully human

antibodies

VelociMab™

High-throughput antibody screening and selection and high-expression,

manufacturing cell line development

human heavy chain Vs Ds Js mouse constants and controlling regions

human kappa chain Vs Js mouse constant and controlling regions

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ImmunogenicityHuman Antibody PlatformsHuman Antibody Platforms

Phage-DisplayPhage-Display AstraZeneca (Cambridge Antibody AstraZeneca (Cambridge Antibody

Technology)Technology) Several companies using technologySeveral companies using technology

Transgenic MouseTransgenic Mouse Amgen Inc. (Abgenics, Inc.)Amgen Inc. (Abgenics, Inc.) Medarex Inc. / Kirin Pharma, Ltd.Medarex Inc. / Kirin Pharma, Ltd.

Regeneron Regeneron VelocImmuneVelocImmune Mouse Mouse Broad-based collaboration with Sanofi-aventisBroad-based collaboration with Sanofi-aventis Licensed to AstraZeneca and Astellas PharmaLicensed to AstraZeneca and Astellas Pharma

Why Fully Human Antibodies? Why Fully Human Antibodies? Evolution of TechnologiesEvolution of Technologies

Murine(0% Human)

Chimeric(66% Human)

Humanized(90 - 95% Human)

Fully Human(100% Human)

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Selection of Antibody Selection of Antibody CandidatesCandidates

Early screening steps focus on: Early screening steps focus on: binding affinitybinding affinity blockingblocking diversitydiversity

Final screening steps focus on:Final screening steps focus on: protein expression/purificationprotein expression/purification protein protein

characterization/qualitycharacterization/quality in vivoin vivo properties properties

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Regeneron Cell Line Regeneron Cell Line TechnologiesTechnologies

FASTRFASTR System System ((FFlow cytometry based low cytometry based AAutologous utologous SSecretion ecretion TrTrap)ap) High-copy system for high-level expressionHigh-copy system for high-level expression Inducible Fc capture protein on cell surface to utilize Inducible Fc capture protein on cell surface to utilize

FACS-based sorting (96-well format)FACS-based sorting (96-well format) Perfect for commercial cell linesPerfect for commercial cell lines

EESYR System EESYR System ((EEnhanced nhanced EExpression and xpression and SStabilittabilitYY RRegion)egion) Provides a common site of integrationProvides a common site of integration High efficiency integration of single copy heavy & High efficiency integration of single copy heavy &

light chainlight chain Perfect for head-to-head comparisonsPerfect for head-to-head comparisons Perfect for providing a speed-to-clinic cell linePerfect for providing a speed-to-clinic cell line

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Selecting High Producing Selecting High Producing Cells Using Fluorescence Cells Using Fluorescence Associated Cell Sorting Associated Cell Sorting

(FACS)(FACS)Key Advantages - Speed and Throughput

• Individually examines 20,000 cells per second

• Up to 100 million transfected cells examined

• Can directly single-cell sort - eliminates subcloning step

Droplet Generator

Detector Electrical Wire

Computer

+

+

-

-+++

++

--

--

-

+ --

-++

Laser

Empty Droplet

Cells In

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Value ofValue of VelocImmune VelocImmune™ ™ MouseMouse

Validated By Multiple Validated By Multiple RelationshipsRelationships

CorporateLicenses

AstraZeneca/Cambridge Antibody Technology (February 2007)

Astellas Pharma(March 2007)

Columbia University (September 2008)

The University of Texas SouthwesternMedical Center(March 2009)

AcademicLicenses

sanofi-aventisCollaboration

Broad profit-sharingprogram todiscover, develop and commercializehuman antibodies(November 2007)

3 antibodies now inclinical trials

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Regeneron is a Fully-Regeneron is a Fully-integrated integrated

Biopharmaceutical Biopharmaceutical Company

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Regeneron Regeneron ManufacturingManufacturing

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State-of-the-Art State-of-the-Art Manufacturing FacilityManufacturing Facility

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Process Area 3 – 1 x 1600 Process Area 3 – 1 x 1600 L BioreactorL Bioreactor

Primarily for PI/II Supply Ten years of operating experience

3 Traps 7 mAbs

Flexible Process Design

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Process Area 1 – 2 x 3000 Process Area 1 – 2 x 3000 L BioreactorL Bioreactor

Primarily for PII/III Supply New facility realized in 14

months (!) Focus on characterizing and

understanding the process

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Red Mill Process AreaRed Mill Process Area

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Currently Doubling Currently Doubling Manufacturing Capacity Manufacturing Capacity

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IL-6R Antibody Formulated Drug Substance IL-6R Antibody Formulated Drug Substance Manufacturing Manufacturing

Upstream Operations, 3,000L Production Upstream Operations, 3,000L Production ScaleScale

Thaw ofthe MCB

2L Wavebag 20L Wavebag 200L Wavebag1,000L Bioreactor

3,000L Bioreactor

CentrifugationDepth and Polish FiltrationHarvest PoolProtein ALow pH Hold

500ml Flask

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Anion ExchangeChromatography

Hydrophobic InteractionChromatography

Viral Clearance Filtration

Concentration andDiafiltration

Transfer to Formulation TankFilling of1 L bottles

Freezing ofFormulated

Drug Substance

< -20C

Addition of concentratedexcipient buffer

IL-6R Antibody Formulated Drug Substance IL-6R Antibody Formulated Drug Substance Manufacturing Manufacturing

Downstream Operations, 3,000L Production Downstream Operations, 3,000L Production ScaleScale

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Regeneron Regeneron Human Human

ResourcesResources

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GroupGroup PersonnelPersonnelQuality (QA, QC, Audit)Quality (QA, QC, Audit) 8888

Facilities Operations Facilities Operations (Maintenance, EH&S, (Maintenance, EH&S, Engineering)Engineering)

4444

Manufacturing (Internal Manufacturing (Internal and External)and External) 7070

Business Operations Business Operations (Finance, Supply Chain, (Finance, Supply Chain, Warehouse)Warehouse)

3535

Process & Analytical Process & Analytical SciencesSciences 2121

Human Resources and Human Resources and TrainingTraining 1010

AdministrativeAdministrative 33

TotalTotal 271271

8%

4%

25%61%

Headcount Totals

IOPS PersonnelIOPS Personnel

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Employee ProfileEmployee ProfileTitleTitle DegreeDegree MajorMajor Yrs of Yrs of

ServiceServiceBiotech Biotech ProdProd

AssociateAssociate

AAS/BA/BSAAS/BA/BS BiologyBiology 44

ProcessProcess

SpecialistSpecialistBA/BSBA/BS ChemicalChemical

EngineeringEngineering2.32.3

QAQA

SpecialistSpecialistBA/BSBA/BS BiologyBiology 4.64.6

QCQC

AnalystAnalystBA/BSBA/BS Chemistry;Chemistry;

BiologyBiology5.85.8

ProcessProcess

ScientistScientistBA/BSBA/BS Biology;Biology;

Chemical Chemical EngEng

3.63.6

AnalyticalAnalytical

ScientistScientistMA/PhDMA/PhD ChemistryChemistry 6.96.9

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BACK-UP SLIDES

BIOMAN 2009BIOMAN 2009

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A Look at the U.S. A Look at the U.S. Biotech IndustryBiotech Industry The biotech industry is a major growth area in the global The biotech industry is a major growth area in the global

healthcare market and due to developments in healthcare market and due to developments in monoclonal antibodies, genomics and proteomics the monoclonal antibodies, genomics and proteomics the biotech market has experienced great expansion since its biotech market has experienced great expansion since its emergence in the 1970semergence in the 1970s

To date, biotechnology has created more than 200 new To date, biotechnology has created more than 200 new therapies and vaccines, including products to treat therapies and vaccines, including products to treat cancer, diabetes, HIV/AIDS and autoimmune disorderscancer, diabetes, HIV/AIDS and autoimmune disorders

There are more than 400 biotech drug products and There are more than 400 biotech drug products and vaccines currently in clinical trials targeting more than vaccines currently in clinical trials targeting more than 200 diseases200 diseases

As of Dec. 31, 2006, there were 1,452 biotechnology As of Dec. 31, 2006, there were 1,452 biotechnology companies in the United States, of which 336 were companies in the United States, of which 336 were publicly heldpublicly heldSource: Biotechnology Industry Organization Guide, “Beyond Borders,“ Ernst & Young Biotechnology Report 2008Source: Biotechnology Industry Organization Guide, “Beyond Borders,“ Ernst & Young Biotechnology Report 2008

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U.S. Biotech Industry U.S. Biotech Industry StatisticsStatistics According to BioWorld, biotechnology attracted more According to BioWorld, biotechnology attracted more

than $24.8 billion in financing in 2007 and raised than $24.8 billion in financing in 2007 and raised more than $100 billion in the five-year span of 2003–more than $100 billion in the five-year span of 2003–20072007

The biosciences employed 1.2 million people in the The biosciences employed 1.2 million people in the U.S. in 2004 and generated an additional 5.8 million U.S. in 2004 and generated an additional 5.8 million related jobsrelated jobs

Revenues of publicly traded biotechs grew 12% to Revenues of publicly traded biotechs grew 12% to $89.7 billion in 2008. The global industry’s net loss $89.7 billion in 2008. The global industry’s net loss improved 53%, from US$3 billion in 2007 to US$1.4 improved 53%, from US$3 billion in 2007 to US$1.4 billion in 2008 billion in 2008

In 2008, the US publicly traded industry posted an In 2008, the US publicly traded industry posted an aggregate net profit for the first time - US$0.4Baggregate net profit for the first time - US$0.4B

Source: Biotechnology Industry Organization Guide, “Beyond Borders,“ Ernst & Young Biotechnology Report 2008Source: Biotechnology Industry Organization Guide, “Beyond Borders,“ Ernst & Young Biotechnology Report 2008

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U.S. Biotechnology U.S. Biotechnology RegionsRegionsThere are 10 thriving clusters of life science industry There are 10 thriving clusters of life science industry

in the U.S., helping to attract investment, talent and in the U.S., helping to attract investment, talent and additional resources to specific geographic areasadditional resources to specific geographic areas

Ranking of Clusters by total number of companies

Biotech BayGenetownBiotech BeachPharm CountryBIO NCBIOMidwestBIOCapitalBIO ForestBIOCanadaSouthernPharmUS Device

The U.S. Biotechnology Regions map can be found on Biospace.com (http://www.biospace.com/biotechhotbeds.aspx).

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A Look at the Pharm A Look at the Pharm Country ClusterCountry Cluster

Regeneron belongs to “Pharm Regeneron belongs to “Pharm Country”Country”

The U.S. Biotechnology Regions map can be found on Biospace.com (http://www.biospace.com/biotechhotbeds.aspx).

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New York State New York State BiotechnologyBiotechnology

In its 2009 annual report, the New York Biotechnology In its 2009 annual report, the New York Biotechnology Association (NYBA) reported that:Association (NYBA) reported that:

In New York State, biopharmaceutical companies In New York State, biopharmaceutical companies directly directly employed 55,446 workers and were employed 55,446 workers and were responsible for a total of 130,464 jobs.responsible for a total of 130,464 jobs.

The industry The industry generated $29.1 billion in total generated $29.1 billion in total economic output in 2006economic output in 2006 and New York State is and New York State is responsible for nearly seven percent of all direct responsible for nearly seven percent of all direct biopharmaceutical output nationallybiopharmaceutical output nationally

New York last year was New York last year was second in the nation with second in the nation with 5,053 clinical testing sites5,053 clinical testing sites for potential new for potential new medicinesmedicines

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Growth of New York Growth of New York Biotechs ContinuesBiotechs Continues

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Opt-in Rights to Novartis IL-1 Opt-in Rights to Novartis IL-1 Antibody Converted to RoyaltyAntibody Converted to Royalty

Regeneron had opt-in rights to canakinumab (Ilaris®, ACZ885) since 2003Regeneron had opt-in rights to canakinumab (Ilaris®, ACZ885) since 2003 Option to share in development, commercialization, and profitsOption to share in development, commercialization, and profits Regeneron would pay upfront, milestones, and 45% of N. American Regeneron would pay upfront, milestones, and 45% of N. American

development costsdevelopment costs Royalty agreement (June 2009)Royalty agreement (June 2009)

Opt-in rights cancelledOpt-in rights cancelled Stepped royalty on worldwide sales in all indicationsStepped royalty on worldwide sales in all indications Initial 4% royalty, reaches 15% of total sales if sales Initial 4% royalty, reaches 15% of total sales if sales >>$1.5B$1.5B No Regeneron financial obligationNo Regeneron financial obligation

Canakinumab statusCanakinumab status Approved in U.S. for CAPS treatmentApproved in U.S. for CAPS treatment In clinical trials for gout, COPD, type 2 diabetes, SJIAIn clinical trials for gout, COPD, type 2 diabetes, SJIA