IR Thematic Call on Alirocumab. March 31 st, 2014

IR Thematic Call on Alirocumab March 31 st, 2014

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Regeneron Forward Looking Statements This presentation includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ( Regeneron or the Company ), and actual events or results may differ materially from these forward-looking statements. Words such as anticipate, expect, intend, plan, believe, seek, estimate, variations of such words and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of Regeneron's products, product candidates, and research and clinical programs now underway or planned; unforeseen safety issues resulting from the administration of products and product candidates in patients, including serious complications or side effects in connection with the use of Regeneron s product candidates in clinical trials, including without limitation the Phase 3 ODYSSEY MONO study and the ODYSSEY global Phase 3 trial program for alirocumab; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron's late-stage product candidates and new indications for marketed products, including without limitation alirocumab; ongoing regulatory obligations and oversight impacting Regeneron s research and clinical programs and business, including those relating to patient privacy; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's products and product candidates; competing drugs and product candidates that may be superior to Regeneron's products and product candidates; uncertainties relating to market acceptance, competitive position, and commercial success of Regeneron's products and product candidates, such as alirocumab; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; coverage and reimbursement determinations by third-party payers, including Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer HealthCare, to be cancelled or terminated without any further product success; and risks associated with third party intellectual property and pending or future litigation relating thereto. These statements are made based on management s current beliefs and judgment, and you are cautioned not to rely on any such statements. In evaluating such statements, shareholders and potential investors should specifically consider the various factors identified under Part I, Item 1A. Risk Factors of Regeneron s Annual Report on Form 10- K for the fiscal year ended December 31, 2013 filed with the Securities and Exchange Commission on February 13, 2014, which could cause actual events and results to differ materially from those indicated by such forward-looking statements. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial or other projection or guidance, whether as a result of new information, future events, or otherwise. 3

Agenda PCSK9 Inhibitor Potential Market Opportunity Robert Terifay, Senior VP, Commercial, Regeneron Alirocumab Clinical Development Jay Edelberg, M.D., Ph.D. VP, Head of the PCSK9 Development & Launch Unit, Sanofi Q&A Session Robert Terifay, Jay Edelberg and Bill Sasiela, VP, Program Direction, Regeneron 4

PCSK9 INHIBITOR POTENTIAL MARKET OPPORTUNITY Robert Terifay Senior Vice President, Commercial Regeneron 5

Despite Current Therapies, There Exists a Significant Population of Patients at High Cardiovascular Risk 62.1 Patient Flow Projections for 2016 (Million Patients) US & EU5 (1) 57% 30.2 (US) 35.7 Diabetics 0/1 Risk Factor 11.0 21.6 31.9 (EU5) Diabetes + 2 Risk Factors with or w/o CV events Secondary Prevention w/o Diabetes Statin Intolerant 11.1 7.6 5.8 11.1 7.6 2.7 Diabetes + 2 Risk Factors with or w/o CV events Secondary Prevention w/o Diabetes Statin Intolerant High CHD Risk Total Population Adults >70mg/dL On Statins + Statin Intolerant HeFH (250K) Increasing CV Risk HeFH (200K) Very High CV Risk Sources: 1) Universe & population growth = US NHANES & Decision Resources 2012; 2) HeFH: Adult prevalence = 1/500 ; 25% of them are diagnosed, 80% are above 70mg/dl; 3) Statin Intolerant: IPSOS Chart Audit, Sept 2012; 4) High Risk: EVD Analysis, Dec 2012; 5) Diabetes Only: EVD Analysis, Dec 2012 6

Diabetics Represent a Significant Portion of The Population Who Are at High Risk ~22M Diabetes Patients With LDL-C >70 mg/dl on Statins Projections for 2016 (Million Patients) US & EU5 (1) Illustrative Example Diabetes + 2 Risk Factors with or w/o CV Events Diabetes + 0/1 Risk Factors 11.0M 11.1M Very High CV Risk 52 year-old male Diagnosis: Primary Hypercholesterolemia Patient history: Type II diabetes & CHD (stented 2 years ago) Current LDL-C: 98mg/dL Current treatment: atorvastatin 40mg (1) US (NHANES, OPTUM, IPSOS SI); EU (NHANES, Decision Resources, Cegedim, IPSOS SI) Besides Diabetes and LDL-C: UA, MI, Stroke, PAD, bypass surgery, PCI w/wo stent, diagnostic non-invasive evidence of chronic heart disease such as angiogram, stress echocardiogram or exercise electrocardiogram, chronic kidney disease (CKD), hypertension, retinopathy, neuropathy, microalbuminuria, family history of chronic heart disease (CHD) 7

Secondary Prevention Patients Are at Higher Risk of Cardiovascular Events 7.6M Secondary Prevention Patients w/o Diabetes And Not at Goal on Statins Projections for 2016 (Million Patients) US & EU5 (1) Illustrative Example History of ACS 44% 31% History of CHD 58 year-old male Diagnosis: Primary Hypercholesterolemia Patient history: established coronary heart disease (CHD) and acute coronary syndrome (ACS), hypertension, previous myocardial infarction (MI) at age 46 9% 16% Current LDL-C: 140mg/dL Diagnosed PAD History of Stroke Current treatment: rosuvastatin 40mg, ezetimibe 10mg 7.6M Patients With Very High CV Risk (1) US (NHANES, OPTUM for PAD); EU (NHANES, Cegedim for PAD) PAD = Peripheral arterial diseases ACS = Acute coronary syndrome 8

Significant Number of HeFH Patients Remain Undiagnosed or Far From Desired LDL-C Goals Heterozygous Familial Hypercholesterolemia (HeFH) Number of patients - Projections for 2016 US & EU5 (1) Illustrative Example Diagnosed Undiagnosed 250K 750K 44 year-old female Diagnosis: Primary Hypercholesterolemia Family history of cardiovascular disease Sustained LDL-C >190mg/dL Current treatment: simvastatin 40mg, ezetimibe 10mg HeFH Patients 200K Treated HeFH Patients ~80% of treated patients are unable achieve LDL-C goal (1) PijlmanAH et al. Atherosclerosis 209 (2010) 189 194; Ned RM at al. PLOS Currents Evidence on Genomic Tests. 2011 Jul 1. Edition 1. doi: 10.1371/currents.RRN1238, PCK9 team assumptions, Optum & Cegedim 9

A Large Number of Statin-Intolerant Patients Are at High Risk For Cardiovascular Diseases 5.8M Patients Intolerant to Statins Projections for 2016 (Million Patients) US & EU5 (1) Very High CV Risk Illustrative Example 58 year-old male Statin Intolerant Patients 3.1M Statin Intolerant High CHD Risk 2.7M Diagnosis: Primary Hypercholesterolemia Patient history: Myocardial Infarction two years ago Current LDL-C: 125mg/dL History of statin intolerance: experienced muscle pains with simvastatin 20mg, and recently had upper back and bilateral leg pains with atorvastatin 10mg Current treatment: ezetimibe 10mg (1) US: NHANES, OPTUM, IPSOS SI, EU: NHANES, Decision Resources, Cegedim, IPSOS SI 10

Lipid-Lowering Market Sales Are ~$30 Billion Lipid-Lowering Agents (1) Worldwide Sales 2013 $30 Billion 60% 8% 16% 15% Statins remain the primary treatment option for high LDL-C Many hypercholesterolemic patients not at LDL-C goal with statins Patients with LDL-C too high at maximally tolerated statin dose Patients unable to tolerate a recommended statin dose Patients completely statin intolerant Statins Fibrates Ezetimibe (mono/fdc) Others (2) Approximately 8 million patients worldwide receive ezetimibe (1) (mono/fdc) (1) Worldwide MAT sales in bn of dyslipidemia market, IMS MIDAS (2) Niacin, omega-3 therapies FDC = fixed dose combination 11

Economic Burden From CV Disease Remains Substantial Cost Estimation of Cardiovascular Disease Events in The US (1) Attributable Costs Per Patient Over 36 Months Following Event $73,300 $71,600 $36,000 Non-Fatal MI Hospitalizations for Angina Non-Fatal Hemorrhagic Stroke (1) O Sullivan AK et al. Pharmacoeconomics 2011; 29(8): 693-704 12

Alirocumab: Potential Novel Treatment For Patients at High CV Risk With Unmet Needs Fully human monoclonal antibody against PCSK9 Binds PCSK9 with high affinity Up to 70% LDL-C reduction observed in Phase 2 trial Being investigated in a broad Phase 3 program to lower LDL-C and to reduce the risk for CV disease Dosing flexibility in terms of dose, titration, and interval Patient friendly pen being evaluated in Phase 3 13

High Awareness of PCSK9 Class Among Cardiologists, Endocrinologists, And Subset of PCPs Percent of Physicians Aware of PCSK9 Inhibitor Class And Perceiving New Class as Very or Extremely Innovative 11% 11% Awareness 66% 57% 35% 37% Innovation of Class 84% 89% 82% 80% 88% 86% Primary Care Physicians (PCP) Cardiologists Endocrinologists Source: Proprietary survey conducted in U.S. (CARDS=150; ENDOS=152, PCPs=306 and in EU5 (CARDS=379, ENDOS=376, PCPs=379), measured in November-December 2013 Q1: Please name and describe all the potential treatments in development for hypercholesterolemia of which you are aware Q2: In your opinion, how innovative are the following classes of medication (PCSK9 inhibitors, CETP inhibitors and statins) 14

High Likelihood to Prescribe a Self Injectable Treatment or a Monoclonal Antibody Treatment Percent of Physicians Likely or Very Likely to Prescribe For Treating Hypercholesterolemia 29% 31% Self Injectable Treatment 53% 52% 48% 50% Monoclonal Antibody Treatment 27% 51% 52% 29% 41% 40% Primary Care Physicians (PCP) Cardiologists Endocrinologists Source: Proprietary survey conducted in U.S. (CARDS=150; ENDOS=152, PCPs=306 and in EU5 (CARDS=379, ENDOS=376, PCPs=379), measured in November-December 2013 Q1: Based on your experiences and anything you might have heard, how likely would you be to prescribe a self-injected subcutaneous treatment for hypercholesterolemia, if available in the future? Q2: Based on your experiences and anything you might have heard, how likely would you be to prescribe a monoclonal antibody for the treatment of hypercholesterolemia, if available in the future? 15

Market Development Activities Underway: Unbranded Education And Awareness Campaigns Looming Threat of Unmet Need PCSK9 Role in LDL-C Metabolism 16

ALIROCUMAB CLINICAL DEVELOPMENT Jay Edelberg, M.D., Ph.D. Vice President, Head of the PCSK9 Development & Launch Unit Sanofi 17

Blocking PCSK9 Lowers LDL-C Levels Sources: (1) Tibolla G et al. Nutr Metab Cardiovasc Dis 2011;21:835-43. (2) Akram ON et al. Arterioscler Thromb Vasc Biol 2010;30:1279-81. (3) Duff CJ et al. Expert Opin Ther Targets 2011;15:157-68. (4) Horton JD et al. J Lipid Res 2009;50 Suppl:S172-7. (5) Cariou B et al. Atherosclerosis 2011;216:258-65. 18

Key Differentiating Features of The Phase 3 Alirocumab ODYSSEY Program 14 studies with primary endpoint evaluated at 24 weeks Double-blind for 6, 12, 18, and 24 months Solid long-term double-blind exposure ( 5,000 patient years) at completion of studies This will allow for a robust characterization of safety and efficacy prior to the data of ODYSSEY OUTCOMES Phase 3 Program Dosing flexibility Q2W and Q4W dosing regimens 75mg and 150mg doses Up-titration treat to target approach provides physicians the ability to tailor therapy to suit individual patient needs Several key patient populations studied Patients with HeFH (largest cohort of such patients) Hypercholesterolemic patients at high CV risk and poorly controlled LDL-C despite standard of care treatment First PCSK9 Phase 3 trial in statin intolerant patients with a re-challenge arm (1) Q2W = Every two weeks dosing (2) Q4W = Every four weeks dosing 19

ODYSSEY Phase 3 Clinical Trial Program: 14 Studies Including More Than 23,500 Patients High CV Risk MI, Stroke, T2D, CKD LONG TERM (1) (n=2,100) High CV Risk Recent CV Event COMBO I (n=306) COMBO II (n=660) OPTIONS I (n=350) OPTIONS II (n=300) CHOICE I (n=700, 300mg Q4W) HeFH Patients receiving statins FH I (n=471) FH II (n= 250) HIGH FH (n=105) OUTCOMES (n=18,000) OLE (Open-Label Extension, n 1,000) Patients not receiving statins Monotherapy MONO (n=100) Statin Intolerant ALTERNATIVE (n=250) CHOICE II (2) (n=200, 150mg Q4W) Except CHOICE I & II, all studies are investigating Q2W regimens: a dose titration scheme (75mg up-titrated to 150mg, based on LDL-C levels at Week 12) or a continuous treatment with 150mg for patients with LDL-C >160mg/dL (HIGH FH) n = Target enrollment (except for ODYSSEY MONO for which results are already reported). Chronic Kidney Disease (CKD) (1) LONG TERM includes a subset of FH patients (2) CHOICE II includes some patients on additional non-statin lipid-lowering therapy 20

Lipid-Lowering Trials: Double-Blind for 6, 12, 18, and 24 Months (1) Double-Blinded Efficacy and Safety Evaluation Primary Endpoint Evaluation at Week 24 MONO (n=100) OPTIONS I (n=350) OPTIONS II (n=300) CHOICE II (n=200) 24 Weeks COMBO I (n=306) CHOICE I (n=700) 52 Weeks FH I (n=471) FH II (n= 250) HIGH FH (n=105) ALTERNATIVE (n=250) LONG TERM (n=2,100) 78 Weeks COMBO II (n=660) 104 Weeks Solid long-term double-blind exposure data ( 5,000 patient years) at completion of studies (1) Does not include ODYSSEY OUTCOMES (event-driven) and ODYSSEY OLE (open label safety study; up to 120 weeks), ODYSSEY ALTERNATIVE will have an indefinite open label extension 21

ODYSSEY Program Evaluates Multiple Options to Personalize Dosing Regimen Dosing Regimens Evaluated in Phase 3 Looking to Flexible Dosing Based on Patient Needs Q2W dosing 75mg Q2W as the starting dose Possibility to titrate up to 150mg Q2W if needed Alternatively, 150mg Q2W as a starting dose for patients with high baseline LDL-C Q4W dosing 150mg Q4W for patients not receiving statins 300mg Q4W for patients receiving statins Patient Preference Baseline LDL-C Values Flexible Model Background Lipid- Lowering Therapy Patient CV Risk Profile 22

ODYSSEY MONO (1) : ~50% LDL-C Reduction Achieved With 75mg Q2W at 12 Weeks; Sustained Over 24 Weeks LDL-C % Change From Baseline 0-10 -20-30 -40-50 -60-70 Week 0 4 8 12 16 20 24 Ezetimibe 10mg QD 20.4% Alirocumab 75/150mg Q2W 86% of patients stayed on 75mg from W12 to W24 17.2% 53.2% 54.1% Up-titration if needed Difference vs. ezetimibe: -36.9%. P<0.0001 Percent of patients reporting TEAEs 78.4% with ezetimibe 69.2% with alirocumab Most common class of AEs Infections (39.2% with ezetimibe vs. 42.3% with alirocumab), included nasopharyngitis, influenza, and upper respiratory tract infection Injection-site reactions in <2% of patients in both groups Muscle-related adverse events (3.9% patients treated with ezetimibe vs. 3.8% with alirocumab) (1) Roth et al. 2014 ACC Abstract #1183/125 TEAEs = Treatment-emergent adverse events 23

Clinical Study Supports 150mg Q4W Dosing in Patients Not on Statins ~48% LDL-C Reduction Maintained Over 28-Day Dosing Interval (1) LDL-C % Change from D-29 Baseline 10 0-10 -20-30 -40-50 -60 Run-in (2) Alirocumab 150mg Q4W - Alirocumab + placebo (N=24) - Alirocumab + ezetimibe (N=24) - Alirocumab + fenofibrate (N=24) Follow-up (2) 4 W 4 W 4 W -70-29 -1 8 15 22 29 57 64 71 78 85 99 120 Study Day Alirocumab sc (1) Rey et al. 2014 ACC Abstract #1183/131 (2) Patients received placebo, ezetimibe or fenofibrate alone (w/o alirocumab) 24

Delivery Options Evaluated in ODYSSEY Program Option 1 Patient-friendly single-use, disposable pen being evaluated Small injection volume of 1ml (75 or 150mg) Allows quick injection Interchangeably injected in the abdomen, upper arm, or thigh (1) >90% compliance in Phase 2 open label extension (2) Option 2 Ready-to-use pre-filled syringe Small injection volume of 1ml (75 or 150mg) Self-injection at home in clinical studies Both options have been included in studies intended for registration (1) Lunven et al. 2014 ACC Abstract #1183/132 (2) Stein et al. 2014 ACC Abstract #1183/126 25

Alirocumab Generally Well Tolerated in Completed Studies (1) Most Frequent TEAEs From Pooled Phase 2 Studies ODYSSEY Program Overseen by Two Data Monitoring Committees (DMC) Injection site reactions Diarrhea Fatigue Headache All above events were of mild intensity DMC for the lipid program and DMC for the CV outcome trial DMCs meet every 3 months to review unblinded data Safety assessment includes Injection site reactions Immunogenicity Hypersensitivity reactions Neurocognitive disorders DMC review of Phase 3 and CVOT data (March 2014) detected no signal for neurocognitive adverse events (1) Three Phase 2 studies ( Stein EA et al. Lancet 2012;380:29-36; McKenneyJM et al. J Am Coll Cardiol 2012;59:2344-53; Roth EM, N Engl J Med 2012;367:1891-900) and ODYSSEY MONO (Roth et al. 2014 ACC Abstract #1183/125) 26

ODYSSEY OUTCOMES: Large CV Outcomes Trial Initiated in November 2012 Patients with recent ACS >40 years of age Run-in period Randomization must be 4-52 weeks after index event Double-blind treatment period (minimum of 2 years) R N=9,000 N=9,000 Continued high dose statin Alirocumab 75mg SC Q2W Up-titration at Week 12 if needed + Diet (NCEP ATP III TLC or equivalent diet) Placebo SC Q2W Primary Endpoint (3) A composite of major CV endpoints Screening visit: Initiate high dose statin therapy (1) Qualifying visit: LDL-C must be >70mg/dl (2) 49 countries/ 1,110 sites expected to participate (1) High intensity statin therapy include atorvastatin 40/80mg or rosuvastatin 20/40mg (2) Patients can also qualify with apob>80mg/dl or non-hdl-c > 100 mg/dl (3) Primary endpoint is a composite endpoint of coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), fatal and non-fatal ischemic stroke, and unstable angina requiring hospitalization 27

Q&A 28