September 2nd, 2014

IR Thematic Call on Alirocumab

Sanofi Forward Looking Statements

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This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group's ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2013. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements.

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, such as alirocumab, including the potential of alirocumab to demonstrate any cardiovascular benefit; 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, such as the ODYSSEY global trial program evaluating alirocumab; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron’s late-stage product candidates, such as alirocumab, including the impact (if any) of the planned use of the U.S. Food and Drug Administration’s Rare Pediatric Disease Priority Review Voucher in connection with the contemplated Biologics License Application submission for alirocumab; 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; uncertainty of market acceptance and commercial success of Regeneron’s products and product candidates; 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 LLC, to be cancelled or terminated without any further product success; and risks associated with intellectual property of other parties and pending or future litigation relating thereto. A more complete description of these and other material risks can be found in the Company’s filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2013 and its Form 10-Q for the quarter ended June 30, 2014. The reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

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Agenda

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Introduction ● Pascale Witz, Executive VP, Global Divisions & Strategic Development, Sanofi

Cardiovascular Disease Burden

● Bill Sasiela, VP, Program Direction, Regeneron

ODYSSEY Program Overview ● Jay Edelberg, M.D., Ph.D. VP, Head of the PCSK9 Development & Launch Unit, Sanofi

ODYSSEY LONG TERM, FH I, FH II, and COMBO II Data ● Jennifer Robinson, M.D., MPH, University of Iowa

Next Steps ● Robert Terifay, Senior VP, Commercial, Regeneron

Q&A Session

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INTRODUCTION

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Pascale Witz

Executive Vice President, Global Divisions & Strategic Development

6

Alirocumab Illustrates Sanofi’s Focus on Gearing Up to Successful Launches of Biologics

7

PCSK9 Inhibitors Have the Potential to Revolutionize LDL-C Management of High Cardiovascular (CV) Risk Patients

● High LDL-C and CV diseases remain an area of high unmet medical need

● Large and comprehensive Phase 3 ODYSSEY clinical program designed to assess the safety and efficacy of alirocumab in patients with hypercholesterolemia at high CV risk

● Detailed positive safety and efficacy results of four pivotal alirocumab studies(1) recently highlighted at a hotline session at ESC

● Submission planned in the U.S. and EU by end of 2014

(1) ODYSSEY LONG TERM, FH I & II, and COMBO II studies.

CARDIOVASCULAR DISEASE BURDEN

8

Bill Sasiela

VP, Program Direction, Regeneron

Cardiovascular Disease Remains an Area of High Unmet Need

9

Aggressive LDL-C goals for high-risk patients

Despite best available treatment, including statins, many high-risk patients fail to reach LDL-C goals

● 21M very high-risk patients with elevated LDL-C in the US and EU5

CVD: High Morbidity, Mortality, and Cost

Cardiovascular disease (CVD) is the leading cause of death globally, accounting for ~30% of all deaths(1)

● By 2030, almost 24.3M people/year globally will die from CVD(2)

Limited Treatment Options

Beyond statins, existing agents provide only modest LDL-C reduction

● None shown to improve CV clinical outcomes on top of statins

High LDL-C =

High CV Risk

Cholesterol is the most well-established risk factor for CVD ● Continuous, positive relationship between cardiovascular risk and serum

total cholesterol concentrations(2)

(1) WHO Top 10 Causes of Death. http://www.who.int/mediacentre/factsheets/fs310/en/index2.htmlAccessed August 2014 (2) Mathers CD, Loncar D. PLoS Med. 2006; 3(11):e442. doi:10. 1371/journal.pmed.0030442. LDL-C= Low density lipoprotein-cholesterol

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Many Patients With High CV Risk Are Not Achieving Optimal LDL-C Levels

● Statins +/- ezetimibe are the standard of care for LDL-C management

● However, many patients are not reaching LDLC goals with standard-of-care therapy due to suboptimal reductions in LDL-C(1-3)

High risk patients(1) HeFH patients(2,3)

23% not at goal

76% not at goal ~80% not at goal

LDL-C Goal <100 mg/dL LDL-C Goal <70 mg/dL LDL-C Goal <100 mg/dL

(1) Jones PH, et al. J Am Heart Assoc. 2012;1:e001800. doi: 10.1161/JAHA.112.001800. (2) Stein EA, et al. Am J Cardiol. 2003;92:1287-1293. (3) Pijlman AH, et al. Atherosclerosis.2010;209:189-194.

Despite Current Therapies, There Exists a Significant Population of Patients at High Cardiovascular Risk

21M High Risk

2.7M 0.9M 9M 8.9M 11M

SI SI High Risk

FH Secondary Prevention

w/o Diabetes

Diabetes 2 risk factors

with or w/o event

Diabetes 0/1 risk factor

1 M recent CV events

3.1M

1M recent CV events

SI: Statin intolerant - FH: Familial hypercholesterolemia Source: US NHANES, Market Scan – US+EU5 inputs Recent CV event: EU5 volume extrapolated from US incidence rate 11

36M Eligible Population (US+EU5 in 2016)

ODYSSEY PROGRAM OVERVIEW

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Jay Edelberg, M.D., Ph.D.

VP, Head of the PCSK9 Development & Launch Unit, Sanofi

Key Features of The Phase 3 Alirocumab ODYSSEY Program

13 (1) Q2W = Every two weeks dosing (2) Q4W = Every four weeks dosing

● HeFH patients (largest cohort of such patients)

● Hypercholesterolemic patients at high CV risk and poorly controlled LDL-C despite standard of care treatment, including statin intolerants

● Patient friendly single use, 1 mL, disposable pen device

● Ready to use, 1 mL, pre-filled syringe

● 14 studies with primary endpoint evaluated at 24 weeks

Double-blind for 6, 12, 18, 24 months

● Solid long-term double-blind exposure (≥5,000 patient years) at completion of studies Robust characterization of safety and efficacy

prior to data from ODYSSEY OUTCOMES

● 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

Dosing flexibility

State-of-the-art drug delivery systems Several patient populations studied

Comprehensive clinical development

Key Efficacy Findings From Alirocumab Phase 3 ODYSSEY Program(1)

(1) Based on data presented to date in top line press release and data presentations at ESC (2) Pre-specified LDL-C goal: either 70 mg/dL or 100 mg/dL depending on patients’ baseline CV risk (3) In the FHI, FH II and COMBO II studies, patients receiving the low, 75mg dose every two weeks, could be up titrated to receive 150 mg if they did not achieve individual treatment goals 14

EFFICACY

● Primary efficacy endpoint achieved in all ten reported Phase 3 ODYSSEY trials

● 62% LDL-C reduction compared to placebo in 2,341 high CV risk patients treated with alirocumab 150mg Q2W in ODYSSEY LONG TERM ● 81% reaching LDL-C goal at Week 24(2)

● Majority of patients treated in up-titration trials reached LDL-C goals on 75 mg Q2W dose(3)

● Approximately 50% reduction in LDL-C in patients using an up-titration approach and/or in monotherapy

● Efficacy consistent across trials testing alirocumab as monotherapy or in combination with statins and/or other lipid-lowering therapies vs. placebo or active comparator

Key Safety Findings From Alirocumab Phase 3 ODYSSEY Program(1)

(1) Based on data presented to date in top line press release and data presentations at ESC 15

SAFETY

● Alirocumab was generally well-tolerated ● Most common adverse events were nasopharyngitis and upper

respiratory tract infections, which were generally balanced between treatment groups

● Safety well balanced across trials ● Injection site reactions were infrequent and occurred more often in the

alirocumab group compared to placebo ● Key adverse events including deaths, musculoskeletal, neurocognitive

and liver-related events were balanced between treatment groups

● From a pre-specified safety interim analysis of ODYSSEY LONG TERM, a post-hoc assessment showed fewer adjudicated major cardiovascular events* (cardiac death, myocardial infarction, stroke and hospitalization for unstable angina) in the alirocumab arm compared to placebo (1.4% vs. 3%, nominal p<0.01)

* Same endpoint as ODYSSEY OUTCOMES. A pre-specified interim safety analysis was performed when all patients reached one year and approximately 25% of patients reached 18 months of treatment.

ODYSSEY Phase 3 Clinical Trial Program: 14 Studies Including More Than 23,500 Patients

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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

Statin Intolerant

High CV Risk Recent CV Event

Patients receiving statins

Patients not receiving statins

HeFH FH I (n=486) FH II (n= 249) HIGH FH (n=107)

OLE (Open-Label Extension, n≥1,000)

High CV Risk MI, Stroke, T2D, CKD

COMBO I (n=316) COMBO II (n=720)

OPTIONS I (n=355) OPTIONS II (n=305)

CHOICE I (n=700, 300mg Q4W) LONG TERM(1) (n=2,341)

OUTCOMES (n=18,000)

Monotherapy

CHOICE II(2) (n=200, 150mg Q4W)

MONO (n=103)

ALTERNATIVE (n=314)

Schema of ODYSSEY FH I, FH II, COMBO II And LONG-TERM Studies

FH I N=486

FH II N=249

COMBO II N=720

LONG TERM N=2,341

Patient Population HeFH patients on max tolerated statin +/- other lipid-lowering therapy

High CV risk patients on high intensity

statins

HeFH or high CV risk patients on max

tolerated statin +/- other lipid-lowering therapy

Baseline Characteristics

• 100% patients on statins • Over 80% of patients on high dose statins • 60% patients on ezetimibe

• 90% of patients had history of CHD

• 67% on high intensity statins

• 100% on statins • 68% had a prior CHD • 36% had Type 2

diabetes

Dose Regimen Alirocumab 75 mg to 150 mg SC Q2W (1)

Alirocumab 150 mg SC Q2W

Comparator Arm Placebo Placebo Ezetimibe Placebo

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High intensity statin defined as atorvastatin 40 to 80 mg daily, rosuvastatin 20 to 40 mg daily, or simvastatin 80 mg SC= sub-cutaneous Q2W= every two weeks CHD= Coronary Heart Disease (1) FH I, FH II and COMBO II studies utilized a dose titration scheme: alirocumab-treated patients received an initial dose

of alirocumab 75 mg every two weeks, increasing to 150 mg at Week 12 if needed to reach pre-specified LDL-C levels

ODYSSEY LONG-TERM, FH I & II, AND COMBO II

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Jennifer Robinson, M.D., MPH

Professor, Departments of Epidemiology & Medicine (Division of Cardiology) Director of the Prevention Intervention Center University of Iowa

Long-term safety, tolerability and efficacy of alirocumab versus placebo in high

cardiovascular risk patients: first results from the ODYSSEY LONG TERM study in 2,341 patients

Jennifer G. Robinson,1 Michel Farnier,2 Michel Krempf,3 Jean Bergeron,4 Gérald Luc,5 Maurizio Averna,6 Erik Stroes,7 Gisle Langslet,8 Frederick J. Raal,9 Mahfouz El Shahawy,10 Michael J. Koren,11 Norman Lepor,12 Christelle Lorenzato,13 Robert Pordy,14 Umesh Chaudhari,15 John J.P. Kastelein7

1University of Iowa, Iowa City, IA, USA; 2Point Médical, Dijon, France; 3CHU de Nantes - Hôpital Nord Laennec, Saint-Herblain, France; 4Clinique des Maladies Lipidiques de Quebec Inc., Quebec, Canada; 5University Hospital of Lille, Lille, France; 6Università di Palermo – Policlinico “P.Giaccone”, Palermo, Italy; 7Department of Vascular Medicine, Academic

Medical Center, Amsterdam, The Netherlands; 8Lipid Clinic, Oslo University Hospital, Oslo, Norway; 9University of Witwatersrand, Johannesburg, South Africa; 10Cardiovascular Center of Sarasota, Sarasota, FL, USA; 11Jacksonville Center

For Clinical Research, Jacksonville, FL, USA; 12Westside Medical Associates of Los Angeles, Beverly Hills, CA, USA; 13Sanofi, Chilly-Mazarin, France; 14Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 15Sanofi, Bridgewater, NJ, USA

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All patients on background of max-tolerated statin ± other lipid-lowering therapy

Alirocumab (n=1553)

Placebo (n=788)

Age, years, mean (SD) 60.4 (10.4) 60.6 (10.4)

Male, % (n) 63.3% (983) 60.2% (474)

Race, White 92.8% (1441) 92.6% (730)

BMI, kg/m2, mean (SD) 30.2 (5.7) 30.5 (5.5)

HeFH, % (n) 17.8% (276) 17.6% (139)

CHD history, % (n) 67.9% (1055) 70.1% (552)

Type 2 diabetes, % (n) 34.9% (542) 33.9% (267)

Any statin†, % (n) 99.9% (1552) 99.9% (787)

High-intensity statin‡, % (n) 44.4% (690) 43.4% (342)

Any LLT other than statins, % (n) 28.1% (437) 27.9% (220)

Ezetimibe, % (n) 13.9% (216) 15.0% (118)

LDL-C, calculated mean (SD), mmol/L [mg/dL]

3.2 (1.1) [122.7 (42.6)]

3.2 (1.1) [121.9 (41.4)]

Baseline Characteristics

†Patients should receive either rosuvastatin 20-40 mg, atorvastatin 40-80 mg daily, or simvastatin 80 mg daily unless not tolerated and/or appropriate other dose given according to the judgement of the investigator

‡High-intensity statin: atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily. 20

-61,0

0,8

-70

-60

-50

-40

-30

-20

-10

0

10LS

mea

n (S

E)

% c

hang

e fr

om b

asel

ine

to W

eek

24

LS mean difference (SE) versus placebo: −61.9% (1.3); P<0.0001

Placebo

Alirocumab N=1530 N=780

Primary Endpoint: Percent Change from Baseline to Week 24 in LDL-C All patients on background of maximally-tolerated statin ± other lipid-lowering therapy

Alirocumab Significantly Reduced LDL-C from Baseline to Week 24 versus Placebo

Intent-to-treat (ITT) analysis 21

Alirocumab Maintained Consistent LDL-C Reductions over 52 Weeks

39

53

67

81

95

109

123

137

151

1

1,5

2

2,5

3

3,5

4

0 4 8 12 16 20 24 28 32 36 40 44 48 52Week

3.1 mmol/L 118.9 mg/dL

1.3 mmol/L 48.3 mg/dL

3.2 mmol/L 123.0 mg/dL

1.4 mmol/L 53.1 mg/dL

mg/

dL

Placebo Alirocumab

LDL-

C, L

S m

ean

(SE)

, mm

ol/L

Achieved LDL-C Over Time All patients on background of maximally-tolerated statin ±other lipid-lowering therapy

Intent-to-treat (ITT) analysis 22

81% 79%

9% 8%

0

10

20

30

40

50

60

70

80

90 P<0.0001

% p

atie

nts

Very high-risk: LDL-C <1.8 mmol/L (70 mg/dL) High-risk: <2.6 mmol/L (100 mg/dL)

<1.8 mmol/L (70 mg/dL) regardless of risk

P<0.0001

Most Patients Receiving Alirocumab on Background Statin ± Other LLT Achieved LDL-C Goals

Placebo

Alirocumab

Proportion of patients reaching LDL-C goal at Week 24

Intent-to-treat (ITT) analysis; LLT = lipid-lowering therapy 23

Significant Reductions in Secondary Lipid Parameters at Week 24

-60

-50

-40

-30

-20

-10

0

10Apo B

−52% P<0.0001

Non-HDL-C

LS m

ean

(SE)

% c

hang

e fr

om

base

line

to W

eek

24

Adjusted mean (SE) shown for Lp(a).

Lp(a)

LS mean difference versus placebo:

−54% P<0.0001

−26% P<0.0001

Placebo

Alirocumab All patients on background of maximally-tolerated statin ± other lipid-lowering therapy

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Treatment-Emergent Adverse Events Safety Analysis (at least 52 weeks for all patients continuing treatment, including 607

patients who completed W78 visit)

% (n) of patients All patients on background of max-tolerated statin ± other lipid-lowering therapy

Alirocumab (n=1550)

Placebo (n=788)

TEAEs 78.6% (1218) 80.6% (635)

Treatment-emergent SAEs 16.5% (255) 17.6% (139)

TEAE leading to death 0.5% (7) 1.0% (8)

TEAEs leading to treatment discontinuation 6.2% (96) 5.5% (43)

Mean treatment duration: 65 weeks (both treatment arms)

26.1% (405/1553 alirocumab) and 25.6% (202/788 placebo) completed 78 weeks

Statistical analyses have not been performed. 25

Adverse Events of Special Interest Safety Analysis (at least 52 weeks for all patients continuing treatment, including 607

patients who completed W78 visit)

% (n) of patients All patients on background of max tolerated statin ± other lipid-lowering therapy

Alirocumab (n=1550)

Placebo (n=788)

Treatment-emergent local injection site reactions 5.8% (90) 4.3% (34)

General allergic reaction events 9.0% (140) 9.0% (71)

All cardiovascular events† 4.0% (62) 4.4% (35)

Neurological events‡ 4.2% (65) 3.9% (31)

Neurocognitive disorders‡ 1.2% (18) 0.5% (4)

Ophthalmological events‡ 2.5% (38) 1.9% (15)

Haemolytic anaemia 0 0

† Confirmed by adjudication. Adjudicated CV events include all CV AEs positively adjudicated. The adjudication categories are the following: CHD death, non-fatal MI, fatal and non-fatal ischemic stroke, unstable angina requiring hospitalisation, congestive heart failure requiring hospitalisation, ischemia driven coronary revascularisation procedure [PCI, CABG]. ‡Company MedDRA Queries (CMQ). Statistical analyses have not been performed. 26

Post-hoc Adjudicated Cardiovascular TEAEs† Safety Analysis (at least 52 weeks for all patients in ongoing study)

% (n) of patients All patients on background of max tolerated statin ± other lipid-lowering therapy

Alirocumab (n=1550)

Placebo (n=788)

CV events confirmed by adjudication 1.4% (22) 3.0% (24)

CHD death 0.2% (3) 0.8% (6)

Non-fatal MI 0.7% (11) 2.2% (17)

Fatal + non-fatal ischaemic stroke 0.5% (8) 0.3% (2)

Unstable angina requiring hospitalisation 0 0.1% (1)

Patients are censored at the end of TEAE period (last injection of study treatment + 70 days).

†Primary endpoint for the ODYSSEY OUTCOMES trial: CHD death, Non-fatal MI, Fatal and non-fatal ischemic stroke, Unstable angina requiring hospitalisation. “Unstable angina requiring hospitalisation” is limited to the UA events with definite evidence of progression of the ischemic condition (strict criteria).

Safety Analysis (at least 52 weeks for all patients continuing treatment, including 607 patients who completed W78 visit)

27

No. at Risk Placebo Alirocumab

Weeks

Mean treatment duration: 65 weeks

Placebo + max-tolerated statin ± other LLT

Cum

ulat

ive

prob

abili

ty o

f eve

nt

Alirocumab + max-tolerated statin ± other LLT

Cox model analysis: HR=0.46 (95% CI: 0.26 to 0.82) Nominal p-value = <0.01

†Primary endpoint for the ODYSSEY OUTCOMES trial: CHD death, Non-fatal MI, Fatal and non-fatal ischemic stroke, Unstable angina requiring hospitalisation. LLT, lipid-lowering therapy

Kaplan-Meier Estimates for Time to First Adjudicated Major CV Event Safety Analysis (at least 52 weeks for all patients continuing treatment, including 607 patients

who completed W78 visit)

84 72 60 48 36 24 12 0

0.06

0.05

0.04

0.02

0.01

0.00

0.03

788 1550

776 1534

731 1446

703 1393

682 1352

667 1335

321 642

127 252

Post-hoc Adjudicated Cardiovascular TEAEs† Safety Analysis (at least 52 weeks for all patients in ongoing study)

28

Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolaemia

(heFH) not adequately controlled with current lipid-lowering therapy:

Results of ODYSSEY FH I and FH II studies

John J.P. Kastelein,1 Henry N. Ginsberg,2 Gisle Langslet,3 G. Kees Hovingh,1 Richard Ceska,4 Robert Dufour,5 Dirk Blom,6

Fernando Civeira,7 Michel Krempf,8 Michel Farnier9

1Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 2Columbia University, New York, NY, USA; 3Lipid Clinic, Oslo University Hospital,

Oslo, Norway; 4Center of Preventive Cardiology, 1st School of Medicine and University Hospital, Charles University, Prague, Czech Republic; 5Institut de Recherches Cliniques de Montréal, Montreal,

Canada; 6Division of Lipidology, Department of Medicine, University of Cape Town and MRC Cape Heart Group, Cape Town, South Africa; 7Lipid Unit, Hospital Universitario Miguel Servet, Zaragoza,

Spain; 8CHU de Nantes - Hȏpital Nord Laennec, Saint-Herblain, France; 9Point Médical, Dijon, France

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All patients on background of max-tolerated statin ± other lipid-lowering therapy

FH I FH II

Alirocumab (N=323)

Placebo (N=163)

Alirocumab (N=167)

Placebo (N=82)

Diagnosis of heFH†, % (n) Genotyping Clinical criteria

39.9% (129) 59.8% (193)‡

38.0% (62) 62.0% (101)

70.1% (117) 29.9% (50)

81.7% (67) 18.3% (15)

Age, years, mean (SD) 52.1 (12.9) 51.7 (12.3) 53.2 (12.9) 53.2 (12.5)

Male, % (n) 55.7% (180) 57.7% (94) 51.5% (86) 54.9% (45)

Race, white, % (n) 92.9% (300) 88.3% (144) 98.2% (164) 97.6% (80)

BMI, kg/m2, mean (SD) 29.0 (4.6) 30.0 (5.4) 28.6 (4.6) 27.7 (4.7)

CHD history, % (n) 45.5% (147) 47.9% (78) 34.1% (57) 37.8% (31)

Current smoker, % (n) 12.1% (39) 18.4% (30) 21.6% (36) 15.9% (13)

Hypertension, % (n) 43.0% (139) 43.6% (71) 34.1% (57) 29.3% (24)

Type 2 diabetes, % (n) 9.6% (31) 15.3% (25) 4.2% (7) 3.7% (3) †Diagnosis of heFH must be made either by genotyping or by clinical criteria. For those patients not genotyped, the clinical diagnosis may be based on either the Simon Broome criteria for definite FH or the WHO/Dutch Lipid Network criteria with a score of >8 points. ‡In FH I, one patient was categorised as “probable” FH by clinical criteria – genotyping results for this patient are pending.

Baseline Characteristics

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Any statin†, % (n) 100% 100% 100% 100%

High-intensity statin‡, % (n) 80.8% (261) 82.8% (135) 86.2% (144) 87.8% (72)

Ezetimibe, % (n) 55.7% (180) 59.5% (97) 67.1% (112) 64.6% (53)

LDL-C, mean (SD), mmol/L [mg/dL]

3.7 (1.3) [144.7 (51.2)]

3.7 (1.2) [144.4 (46.8)]

3.5 (1.1) [134.6 (41.3)]

3.5 (1.1) [134.0 (41.6)]

All patients on background of max-tolerated statin ± other lipid-lowering therapy

FH I FH II

Alirocumab (N=323)

Placebo (N=163)

Alirocumab (N=167)

Placebo (N=82)

†Patients should receive either rosuvastatin 20-40 mg, atorvastatin 40-80 mg daily, or simvastatin 80 mg daily unless not tolerated and/or appropriate other dose given according to the judgement of the investigator. ‡High-intensity statin: atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily.

Lipid Medication and LDL-C at Baseline

31

Alirocumab Significantly Reduced LDL-C from Baseline to Week 24 versus Placebo

-48.8% -48.7%

9.1% 2.8%

-60

-50

-40

-30

-20

-10

0

10

20

LS m

ean

(SE)

% c

hang

e fr

om b

asel

ine

to W

eek

24

LS mean difference (SE)

vs. placebo:

N=163

Alirocumab

N=322

−57.9% (2.7) P<0.0001

N=81 N=166

−51.4% (3.4) P<0.0001

FH I Placebo

FH II

43.4% had dose

increase at W12

38.6% had dose

increase at W12

Primary Endpoint: Percent Change from Baseline to Week 24 in LDL-C All patients on background max-tolerated statin ±other lipid-lowering therapy

Intent-to-treat (ITT) Analysis 32

LDL-

C, L

S m

ean

(SE)

, mm

ol/L

39

58

77

97

116

135

155

174

1

1,5

2

2,5

3

3,5

4

4,5

0 4 8 12 16 20 24 28 32 36 40 44 48 52

3.5 mmol/L

1.8 mmol/L

3.7 mmol/L

1.9 mmol/L mg/

dL

1.8 mmol/L 1.7 mmol/L

4.0 mmol/L 4.0 mmol/L

Alirocumab Maintained Consistent LDL-C Reductions Over 52 Weeks

Achieved LDL-C Over Time on Background of Maximally-Tolerated Statin ±Other LLT

Placebo: FH I FH II

Alirocumab: FH I FH II

Week Intent-to-treat (ITT) Analysis LLT = lipid-lowering therapy

Dose ↑ if LDL-C >70 mg/dL at W8 33

Safety Analysis (Pooled Data from FH I and FH II) All Data Collected Until Last Patient Visit at Week 52

% (n) of patients All patients on background of max tolerated statin ± other lipid-lowering therapy

Alirocumab (N=489)

Placebo (N=244)

TEAEs 74.8% (366) 75.4% (184)

Treatment-emergent SAEs 10.0% (49) 9.0% (22)

TEAEs leading to death 0.8% (4) 0 TEAEs leading to discontinuation 3.1% (15) 3.7% (9)

Adverse Events of Interest Adjudicated CV events† 1.6% (8) 1.2% (3)

Injection-site reactions 11.5% (56) 9.0% (22)

Neurocognitive disorders 0.2% (1) 1.2% (3)

ALT >3 x ULN 2.1% (10/488) 1.2% (3/244)

Creatine kinase >3 x ULN 3.5% (17/483) 6.2% (15/243)

4 TEAE-related deaths were all in alirocumab arm, 2 due to metastatic cancer (non-small cell lung and pancreatic), 2 due to MI (1 acute, 1 sudden cardiac death)

†Adjudicated CV events include all CV AEs positively adjudicated. The adjudication categories are the following: CHD death, non-fatal MI, fatal and non-fatal ischaemic stroke, unstable angina requiring hospitalisation, congestive heart failure requiring hospitalisation, ischaemia-driven revascularisation procedure (PCI, CABG). Statistical analyses have not been performed. 34

Efficacy and safety of alirocumab in high cardiovascular risk patients with

inadequately controlled hypercholesterolaemia on maximally tolerated daily statin: results from the

ODYSSEY COMBO II study

Christopher P. Cannon,1 Bertrand Cariou,2 Dirk Blom,3 James M. McKenney,4 Christelle Lorenzato,5 Robert Pordy,6

Umesh Chaudhari,7 Helen M. Colhoun8

1Harvard Clinical Research Institute, Boston, MA, USA; 2L’Institut du Thorax, CHU de Nantes, Nantes, France; 3Division of Lipidology, Department of Medicine, University of

Cape Town and MRC Cape Heart Group, Cape Town, South Africa; 4Virginia Commonwealth University and National Clinical Research, Inc., Richmond, VA, USA;

5Sanofi, Paris, France; 6Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 7Sanofi, Bridgewater, NJ, USA; 8University of Dundee, Dundee, Scotland, UK

35

All patients on background max tolerated statin

Alirocumab (n=479)

Ezetimibe (n=241)

Age, years, mean (SD) 61.7 (9.4) 61.3 (9.2)

Male, % (n) 75.2% (360) 70.5% (170)

Race, White, % (n) 84.3% (404) 85.5% (206)

BMI, kg/m2, mean (SD) 30.0 (5.4) 30.3 (5.1)

CHD history, % (n) 91.2% (437) 88.0% (212)

Hypertension, % (n) 79.7% (382) 82.2% (198)

Type 2 diabetes, % (n) 30.3% (145) 31.5% (76)

Any statin†,% (n) 99.8% (478) 100% (241)

High-intensity statin‡, % (n) 66.8% (320) 66.4% (160)

LDL-C, calculated mean (SD), mmol/L [mg/dL]

2.8 (0.9) [109 (37)]

2.7 (0.9) [105 (34)]

Baseline Characteristics

†Patients should receive either rosuvastatin 20-40 mg, atorvastatin 40-80 mg daily, or simvastatin 80 mg daily unless not tolerated and/or appropriate other dose given according to the judgement of the investigator. ‡High-intensity statin: atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily. 36

Alirocumab Significantly Reduced LDL-C from Baseline to Week 24 versus Ezetimibe

-50.6%

-20.7%

-60

-50

-40

-30

-20

-10

0

LS m

ean

(SE)

% c

hang

e fr

om

base

line

to W

eek

24

LS mean difference (SE) vs. ezetimibe: −29.8% (2.3); P<0.0001

n=467 n=240

Primary Endpoint: Percent Change from Baseline to Week 24 in LDL-C All patients on background of maximally-tolerated statin

Ezetimibe

Alirocumab

Intent-to-treat (ITT) analysis

18.4% had

dose increase

at W12

37

Safety Analysis (Baseline-W102) Including All Data Collected Until Last Patient Visit at Week 52

% (n) of patients All patients on background max tolerated statin

Alirocumab (n=479)

Ezetimibe (n=241)

TEAEs 71.2% (341) 67.2% (162)

Treatment-emergent SAEs 18.8% (90) 17.8% (43)

TEAE leading to death† 0.4% (2) 1.7% (4)

TEAEs leading to discontinuation 7.5% (36) 5.4% (13)

Adverse Events of Interest Adjudicated CV events‡ 4.8% (23) 3.7% (9)

Injection-site reactions 2.5% (12) 0.8% (2)

Neurocognitive disorders 0.8% (4) 1.2% (3)

ALT >3 x ULN 1.7% (8/470) 0.4% (1/240)

Creatine kinase >3 x ULN 2.8% (13/467) 2.5% (6/236) †Both deaths in the alirocumab arm were due to CV events (cardiac arrest and sudden cardiac death). Of the four deaths in the ezetimibe arm, two were due to CV events (malignant lung neoplasm, suicide, defect conduction intraventricular, sudden cardiac death and sudden death – one patient was counted in two categories) ‡Adjudicated CV events include all CV AEs positively adjudicated. The adjudication categories are the following: CHD death, non-fatal MI, fatal and non-fatal ischemic stroke, unstable angina requiring hospitalisation, congestive heart failure requiring hospitalisation, ischemia driven coronary revascularisation procedure [PCI, CABG]. Statistical analyses have not been performed. 38

CLINICAL PERSPECTIVE ON ODYSSEY LONG-TERM, FH I & II, AND COMBO II

39

Jennifer Robinson, M.D., MPH

Professor, Departments of Epidemiology & Medicine (Division of Cardiology) Director of the Prevention Intervention Center University of Iowa

NEXT STEPS

40

Robert Terifay

Senior VP, Commercial, Regeneron

Phase 3 Clinical Trial Program: 10 Trials Form Core of Initial Regulatory Submission

41

Double-Blinded Efficacy and Safety Evaluation

MONO (n=103) OPTIONS I (n=355) OPTIONS II (n=305) ALTERNATIVE (n=314)

24 Weeks

COMBO I (n=316) 52 Weeks

COMBO II (n=720) 104 Weeks

FH I (n=486) FH II (n= 249) HIGH FH (n=107) LONG TERM (n=2,341)

78 Weeks

Primary Endpoint Evaluation at Week 24

(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

≥5,000 double-blind patient years at completion

of studies

42

Next Steps

ACS: Acute Coronary Syndrome (1) American Heart Association, Chicago, Nov 15-19, 2014 http://www.abstractsonline.com/pp8/#!/3547/session/5166 (2) http://www.sciencedirect.com/science/article/pii/S0002870314004943#

● Additional Phase 3 data to be presented at AHA, November 2014(1)

● ODYSSEY OPTIONS I, OPTIONS II, HIGH FH, COMBO I and ALTERNATIVE

● Regulatory submissions planned in the U.S. and EU by end of 2014

● Companies plan to use Priority Review Voucher for BLA submission in the U.S.

● ODYSSEY CHOICE I & II and Open Label Extension (OLE) ongoing ● CHOICE I & II explore monthly dosing of alirocumab ● Expect to report primary endpoints in 2015 and beyond

● ODYSSEY OUTCOMES ongoing (n=18,000)

● Tests the hypothesis that alirocumab improves CV outcomes after ACS(2) ● Study completion event-driven(2)

1

2

3

4

Summary

43

Alirocumab well placed to address significant unmet medical need in the management of high cardiovascular risk patients

Significant and sustained reductions in LDL-C over one year on top of existing therapies across different patient populations Balanced safety and tolerability profile across patient groups Flexible dosing provides options for physicians and patients Convenient 1-mL dosage forms

Q&A SESSION

44