2014 - ir - thematic seminar on new medicines

IR THEMATIC SEMINAR ON NEW MEDICINES

November 20, 2014

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Forward Looking Statements

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.

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Agenda

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Introductory Comments ● Serge Weinberg, Chairman of the Board of Directors - CEO

Advancing Late Stage R&D Portfolio ● Elias Zerhouni, MD, President, Global R&D

Cerdelga™ / Lemtrada® ● David Meeker, MD, CEO, Genzyme

Praluent™ (alirocumab) ● Jay Edelberg, MD, PhD, Vice President, Head of the PCSK9 Development & Launch Unit ● Harold Bays, MD, Medical Director, President of Louisville Metabolic & Atherosclerosis Research Center

● Victoria Carey, Vice President, Head of U.S. Alirocumab Commercial

Q&A Session Break

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Agenda (cont’d)

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Toujeo® / Afrezza® / LixiLan ● Riccardo Perfetti, MD, Senior Medical Officer, Diabetes ● Stewart B. Harris, MD, Professor of Medicine, Schulich School of Medicine, University of Western Ontario ● Andrew Purcell, Vice President, Commercial Business Unit Head U.S. Diabetes ● Pierre Chancel, Senior Vice President, Diabetes

Q&A Session Dengue vaccine

● Duane Gubler, ScD, MS, Professor, Emerging Infectious Diseases Program, Duke NUS, Singapore ● Nicholas Jackson, Associate Vice President R&D, Dengue Vaccine Company, Sanofi Pasteur ● Guillaume Leroy, Vice President, Dengue Vaccine Company, Sanofi Pasteur

Sarilumab / dupilumab ● Elias Zerhouni, MD, President, Global R&D

Conclusion ● Elias Zerhouni, MD, President, Global R&D

Q&A Session

IR Thematic Seminar Focus on Selected New Medicines and Vaccines

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Our main objectives for today are:

● Highlight the unmet medical needs addressed

by Sanofi’s key late stage assets

● Provide a high-level clinical profile of those products

● Share information on our strategy to seize their commercial potential

IR Thematic Seminar on New

Medicines

Help the Street to better evaluate near-term contribution from R&D

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Introductory Comments

Serge Weinberg

Chairman of the Board of Directors CEO

Introductory Comments ● Serge Weinberg, Chairman of the Board of Directors - CEO

Advancing Late Stage R&D Portfolio ● Elias Zerhouni, MD, President, Global R&D

Cerdelga™ / Lemtrada® ● David Meeker, MD, CEO, Genzyme

Praluent™ (alirocumab) ● Jay Edelberg, MD, PhD, Vice President, Head of the PCSK9 Development & Launch Unit ● Harold Bays, MD, Medical Director, President of Louisville Metabolic & Atherosclerosis Research Center

● Victoria Carey, Vice President, Head of U.S. Alirocumab Commercial

Q&A Session Break

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Agenda

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Sanofi – Opportunity for Sustainable Growth Driven by Platforms and Pipeline

Sanofi has transformed into a company positioned for sustainable growth through its growth platforms(1) and late-stage pipeline of new biologics

Growth platforms now account for 76% of sales(1)

47% of sales derived from biologics(2)

72% of R&D projects are biologics(3)

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(1) Growth Platforms include Emerging Markets, Diabetes Solutions, Vaccines, Consumer Healthcare, Animal Health, Genzyme & Other Innovative Products. In 9M 2014, sales from Growth Platforms accounted for 76.1% of Group sales or €18,801m

(2) Biologic sales in 9M 2014 were €11,625m and included insulins (Lantus®, Apidra®, Insuman®), Genzyme rare disease products, Lovenox®, Sanofi Pasteur vaccines, Merial vaccines, selected oncology products (Thymoglobulin®, Mozobil®, Zaltrap®), Lemtrada® and half of SPMSD sales (non-consolidated)

(3) R&D projects in clinical development: 33 NMEs and vaccines out of a total of 46 in Nov 2014

R&D Plays a Major Role in the Successful Execution of Sanofi’s Strategy

Deliver sustainable long-term growth

by improving patients' lives Seize value-enhancing growth

opportunities 3

Bring innovative products to market 2

Grow a global healthcare leader with synergistic platforms 1

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Adapt structure for future challenges and opportunities 4

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10 10

R&D Is Entering a New Era by Increasing its Expected Contribution to the Sustainable Growth of Sanofi

2007 - 2009 2010 - 2013 2014+

Low R&D Productivity

R&D Transformation

Strong R&D Pipeline Emerging

• Advanced high-value development projects

• Created efficient global R&D organization

• Shifted portfolio from small molecules to biologics

• Grew value of external R&D collaborations

• Launch new products • Maintain discipline in

portfolio prioritization • Accelerate early-stage

development • Expand open innovation

model

• Confronted multiple R&D setbacks

• Faced low returns despite growing R&D spend

• Cleaned up R&D pipeline

Over the Last 7 Years, Sanofi Launched Several New Drugs but Only One with Peak Sales Potential >$1bn

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®

(ex-U.S.)

(U.S.)

(ex-U.S.)

®

(U.S.)

10 Launches 2007-2013

Sanofi Expects to Launch High Potential New Medicines and Vaccines at an Accelerated Pace Beginning in 2014

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Up to 18 Launches 2014 - 2020

sarilumab

(U.S.)

Dengue Vaccine

patisiran Anti-CD38 mAb

PR5i Vaccine

Vaccine

Shan5

(U.S.)

insulin lispro

Praluent™ alirocumab

Rotavirus Vaccine

Praluent™ is the intended trade name for alirocumab. The trade name is currently pre-approved in the EU but not in other regions.

ILLUSTRATIVE

13 (1) At CER, 5 years for each product from and including the first full year of launch (2) Non-risk adjusted sales projections

Significantly Improving Returns from R&D

Up to 18 launches expected

10 launches achieved Potential cumulative

first 5 years sales

~€7.5bn(1,2)

2007 - 2013

2014 - 2020 Potential cumulative first 5 years sales

>€30bn(1,2)

10 Early Assets to Watch

1

2

3

4

5

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Vatelizumab(1) Multiple Sclerosis

IL4/IL13 bi-specific mAb Idiopathic Pulmonary Fibrosis

Anti-CD38 mAb Multiple Myeloma

Anti-GDF8 mAb Sarcopenia

Revusiran (TTRsc) Familial Amyloid Cardiomyopathy

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7

8

9

rhASM Niemann-Pick type B

Neo GAA Pompe Disease

C-MET kinase inhibitor Solid Tumors

Anti-CXCR5 mAb Systemic Lupus Erythematosus

GLP-1/GIP co-agonist Diabetes

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(1) Anti-VLA2 mAb

Sanofi Has Additional Potentially Transformative Drugs at Earlier Stages of Development

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Sanofi Has Established a Model of Productive R&D Collaborations

● Global strategic collaboration

● Secured access to highly productive therapeutic human antibody platform

● A platform to regularly bring new mAbs into clinical development

Example 1 Example 2

● World-class RNAi technology

● Focus on genetically defined diseases with a clear translational model for RNA interference

● A platform for sustained drug development for rare diseases for Genzyme

Strengthening the R&D Leadership Team with New Talent

Philip Just Larsen Diabetes - Head of Research & Early Development

Jay Edelberg VP, Head of Alirocumab Unit

Gary Nabel SVP, CSO Andrew Plump

SVP, Research and Translational Medicine

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Christian Antoni VP, Head Development Immunology & Inflammation

Victoria Richon Oncology - Head of Research & Early Development

Eckhard Leifke Diabetes - Head of Development

Mike Panzara VP, Multiple Sclerosis and Neurology, Genzyme

Fabian Kausche Head of Merial R&D

Anthony Muslin VP, Cardiovascular & Fibrosis Unit

Hilary Malone VP, Global Regulatory Affairs John Shiver

SVP, R&D, Sanofi Pasteur

Jorge Insuasty SVP, Development Maya Said

VP, Strategy External Innovation & Science Policy

Dominique Carouge VP, Administration & Management

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Agenda

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Genzyme ● David Meeker, MD, CEO, Genzyme

Cerdelga™ (eliglustat)

Lemtrada® (alemtuzumab)

Genzyme Understands Unmet Needs of Gaucher Patients

61% of Gaucher patients would like their treatment to be an oral formulation(1)

(1) PeopleMetrics survey in Gaucher patients (n= 238) What improvements would you like to see in treatments for Gaucher Disease? 18

GD-1: Gaucher Disease type 1 ERT: Enzyme Replacement Therapy (1) Cerdelga™ is a highly specific ceramide analogue inhibitor of GL-1 synthesis with broad tissue distribution (2) AEs generally mild to moderate, most common related to treatment being diarrhea (6%), headache (4%), arthralgia (3%),

flatulence (3%), abdominal pain (3%), fatigue (3%), nausea (3%). Less than 2% of people treated with Cerdelga™ discontinued treatment because of a side effect.

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● Novel substrate inhibitor(1)

● Largest ever development program in Gaucher

● Almost 400 adults in 29 countries

● Efficacy demonstrated in untreated patients (ENGAGE) and in patients switching from ERT (ENCORE)

● Majority of adverse reactions are mild and transient(2)

● Genotyping required before starting therapy to determine CYP2D6 phenotype

● U.S. FDA approval granted in Aug 2014

● EU CHMP opinion expected in Q4 2014

The Only First-Line Oral Therapy for Adults with Gaucher Disease Type 1

ENGAGE - Change in Primary and Secondary Endpoints at 9 Months(1)

Efficacy Demonstrated in Untreated Patients (ENGAGE)

Parameter Eliglustat Placebo Difference P Value

Spleen Volume -28% +2% 30% <0.0001

Hemoglobin Level +0.7 g/dL -0.5 g/dL 1.2 g/dL 0.0006

Liver Volume -5.2% +1.4% 6.6% 0.0072

Platelet Count +32% -9% 41% <0.0001

(1) Pastores et al. ACMG 2013 (poster) 20

Efficacy Demonstrated in Patients Switching From ERT (ENCORE)

(1) Baris Feldman EWGGD 2014 (presentation) (2) Non-Inferiority with respect to primary composite endpoint (i.e. lower bound of 95% CI of difference > -25% non-inferiority margin)

95% 93% 96% 96%

85%

100% 100% 100%94% 94%

0%

20%

40%

60%

80%

100%

StableHemoglobin

StablePlatelets

Stable SpleenVolume

Stable LiverVolume

Composite

Eliglustat Imiglucerase

ENCORE - % of Patients Who Met Stability at 12 Months(1,2)

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Potential to grow Gaucher market

and expand Genzyme Gaucher

franchise to

>€1bn(2)

Genzyme Leading Innovation in Treating Gaucher Disease with Cerezyme® and Now Cerdelga™

~38% ~42%

(1) 2013 Gaucher Treatment Tracker Survey, n = 241 physicians from15 countries - Q4 2013 / Q1 2014 (2) Genzyme Gaucher franchise includes Cerezyme® (imiglucerase) and Cerdelga™ (eliglustat)

% of Gaucher Patients in Whom Physicians Would Use Cerdelga™(1)

Existing patients Newly diagnosed patients

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Agenda

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Genzyme ● David Meeker, MD, CEO, Genzyme

Cerdelga™ (eliglustat)

Lemtrada® (alemtuzumab)

New MS Treatment Goals - Focus on Patient Outcomes

Symptom Alleviation Decrease MS activity and improve quality of life

Halt or reverse damage and disability

Promote repair, remyelination, durable disability improvement

Improve disease control Freedom from disease activity

Convenient treatment regimens to improve compliance

Dosing options, new routes of administration, less frequent dosing

Maximize patient outcomes Superior effectiveness and favorable benefit/risk vs. existing treatment

24 MS: Multiple Sclerosis

Unmet Needs in MS New Goals

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A Large and Growing Global MS Market

(1) National Multiple Sclerosis Society (2) http://msj.sagepub.com/content/18/5/628.full.pdf (3) Adapted from Evaluate Pharma July 2014; Reported sales of Copaxone®, Avonex®, Rebif®, Betaseron/Betaferon®, Extavia®,

Tysabri® and Gilenya® for 2013; 2007 sales converted using €/$ of 1.37, 2013 sales and 2020e sales converted using €/$ of 1.33

Multiple Sclerosis Market Global Sales(3)

2013

2020e

U.S. ROW

~€12bn

~€17bn

2007

~€5bn

~43% ~57%

~50% ~50%

Multiple Sclerosis

● Serious disease with significant unmet medical needs

● Symptoms include fatigue, weakness, walking and balance difficulties, vision problems

● A major impact on family, social and professional life

● ~2.1m patients worldwide(1)

● ~410,000 patients in the U.S.(1)

● ~630,000 patients in EU(2)

2013-20 growth driven by new therapies, satisfying the unmet needs of convenient administration and more efficacious therapy

DMT: Disease Modifying Treatment SAD: sustained accumulation of disability (1) Eva Havrdova, ACTRIMS-ECTRIMS 2014 (2) ln CARE-MS l, Lemtrada® was significantly more effective than interferon beta-1a at reducing annualized relapse rates;

the difference observed in slowing disability progression did not reach statistical significance. ln CARE-MS ll, Lemtrada® was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada® vs. interferon beta-1a.

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Sustained Reduction in Disability Through Year 4

Disease-Free Outcomes: 3-Year Follow-up of the CARE-MS Studies(1)

Parameter CARE-MS I CARE-MS II

% of Lemtrada® patients relapse-free 87% 82%

% of Lemtrada® patients 6-month SAD-free(2) 99% 96%

% of patients who did not receive alternative DMTs 99% 97%

% of Lemtrada® patients who did not receive retreatment in Year 3 82% 80%

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FDA Approval Is a Major Step Forward for People with Relapsing Forms of MS

(1) EU, Canada, Australia and other countries (2) The most common side effects of Lemtrada® are rash, headache, thyroid disorder, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia,

upper respiratory tract infection, herpes viral infection, urticaria, pruritus, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. Other serious side effects associated with Lemtrada® include autoimmune thyroid disease, autoimmune cytopenias, infections and pneumonitis.

(3) Label includes a boxed warning noting a risk of serious, sometimes fatal autoimmune conditions, serious and lifethreatening infusion reactions and noting Lemtrada® may cause an increased risk of malignancies including thyroid cancer, melanoma and lymphoproliferative disorders. Lemtrada® is contraindicated in patients with HlV infection.

(4) Genzyme holds the worldwide rights to alemtuzumab and has responsibility for its development and commercialízation in MS. Bayer Healthcare receives contingent payments based on global sales revenue.

● Regulatory approvals granted in >40 countries(1)

● FDA approval received on Nov 14, 2014 ● Because of its safety profile, the use of Lemtrada® should generally be reserved

for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS(2,3)

● Only available in the U.S. through a restricted distribution program: the Lemtrada® Risk Evaluation and Mitigation Strategy (REMS)

● New dedicated salesforce recruited for the U.S.(4) ● Targeted U.S. launch approach for the first 3 months

● Ensuring appropriate education and confidence to prescribe

● Full launch expected throughout 2015

With Aubagio® and Lemtrada®, Genzyme is well positioned to grow its MS franchise

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Agenda

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Praluent™ (alirocumab)

CV Disease Burden & ODYSSEY Program

● Jay Edelberg, MD, PhD Vice President, Head of the PCSK9 Development & Launch Unit

Clinical Perspective ● Harold Bays, MD, Medical Director and President of Louisville Metabolic and Atherosclerosis Research Center(1)

Evaluating the PCSK9 Opportunity

● Victoria Carey Vice President, Head of U.S. Alirocumab Commercial

Q&A Session

Praluent™ is the intended trade name for alirocumab. The trade name is currently pre-approved in the EU but not in other regions. (1) Harold Bays is an investigator of the ODYSSEY OPTIONS I and II clinical study

CV Disease Remains an Area of High Unmet Need

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(1) WHO. http://who.int/mediacentre/factsheets/fs317/en/ (EU, East. Mediterranean, The Americas, SE Asia, West Pacific, Africa) (2) NHLBI. http://www.nhlbi.nih.gov/about/documents/factbook/2012/chapter4.htm (3) WHO. http://www.who.int/whr/2002/en/whr02_en.pdf?ua=1 (4) U.S. NHANES, Market Scan, IMS and Sanofi estimates

LDL-C contributes to 60% of coronary heart disease and 40% of all ischemic stroke(3)

Cardiovascular disease causes 17.3m deaths per year(1)

Despite available treatment options, including statins, 24m high-risk patients fail to reach LDL-C goals(4)

The estimated economic cost of CVD is huge in the U.S.(2) ● $193bn in direct health expenditures ● $122bn in indirect cost of mortality

60%

17.3m

24m

$315bn

(1) Adapted from O’Keefe et al. J Am Coll Cardiol 2004;43:2142-6; LaRosa JC et al. N Engl J Med 2005;352:1425-35

LDL-C

25

20

15

10

5

0

CARE

TNT-80A TNT-10A

50 1.3

70 1.8

110 2.8

130 3.4

150 3.9

170 4.4

190 4.9

90 2.3

210 5.4

(mg/dL) (mmol/L)

CHD Events (%) Primary prevention trials

AFCAPS

WOSCOPS

ASCOT

AFCAPS

WOSCOPS

ASCOT

4S

CARE

LIPID

LIPID

Secondary prevention trials

Placebo

Placebo

4S

Active treatment

Active treatment

Lowering LDL-C with Statins Is Effective in Decreasing CV Risk

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Despite high efficacy of statin therapy, unmet needs persist in familial hypercholesterolemia, high CV risk and statin intolerance

LDL-C Prevention Trials(1)

Despite Current Therapy, a Significant Proportion of Hypercholesterolemic Patients Are at High CV Risk

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Diabetes(2)

10.1m

Secondary Prevention without Diabetes

10.3m

Statin Intolerant 2.9m

Heterozygous Familial Hypercholesterolemia

24m Patients With High CV Risk

(1) U.S. NHANES, Market Scan, IMS and Sanofi estimates (2) Diabetes with 2 Risk Factors with or w/o CV Event

Secondary Prevention

5.3m

Primary Prevention

4.8m

2016 Estimates for U.S., EU Top 5 and Japan (in million patients)(1)

1.2m

Sense of Urgency to Lower LDL-C to Reduce CV Risk Varies According to Patient Types

● Well defined but underdiagnosed population

● High engagement of patients

● Large proportion of uncontrolled patients with current therapies

HeFH

● High LDL-C levels comparable to HeFH

● Pragmatic approach used by physicians but no objective definition

● Low satisfaction level with existing treatment options

Statin Intolerant

● Large and diverse population with associated CV risks

● Large proportion of patients with previous CV event

● Strong awareness of risk, especially for recent events

● Significant overlap with diabetes population

High CV Risk

HeFH: heterozygous familial hypercholesterolemia 32

The Development of Alirocumab, an Anti-PCSK9 mAb, Is a Prime Example of Modern Translational Medicine

(1) Seidah NG. Proc Natl Acad Sci USA 003;100:928-33 (2) Abifadel M. Nat Genet 2003;34:154-6 (3) Maxwell KN. Proc Natl Acad Sci USA 2004;101:7100-5 (4) Rashid S. Proc Natl Acad Sci USA 2005;102:5374-79 (5) Cohen JC. N Engl J Med 2006;354:1264-72

The PCSK9 Discovery Decade

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PCSK9 discovery(1,2) PCSK9-targeted

mAb preclinical(8)

Gain-of-function mutations observed

2003 2004 2005 2006 2007 2008 2009 2010 2012 2013

Proof of principle in animals(3,4)

Human target validation(5,6,7)

2011

First subject treated with PCSK9 mAb

Phase II study results(9)

First Phase III study results

Loss-of-function mutations observed

(6) Zhao Z. Am J Hum Genet 2006;79:514-23 (7) Hooper AJ. Atherosclerosis 2007;193:445-8 (8) Chan JC. Proc Natl Acad Sci USA 2009;106:9820-5 (9) Lambert G et al. J Lipid Res 2012; 53(12): 2515-24

2014

U.S./EU regulatory submissions

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● Largest Phase III program

● 14 trials with >23,500 patients

● Primary endpoint evaluated at 24 weeks

● Double-blind design (6, 12, 18 and 24 months)

A Differentiated Clinical Development Program

● Evaluation of q2w and q4w dosing regimens and 75mg and 150mg doses

● Interim data on lower rate of adjudicated major CV events in LONG TERM trial

● ≥4,500 patient years exposure(4)

All studies: every two weeks (q2w) regimens (75/150mg with potential dose ↑ from 75 to 150 mg) except CHOICE I (300mg q4w) and II (150mg q4w) (1) Open-Label Extension open to HeFH patients included in other studies (2) ODYSSEY MONO included patients at moderate CV risk (3) ODYSSEY CHOICE II includes some patients on additional non-statin lipid-lowering therapy (4) ≥4,500 double-blind patient years at completion of pivotal studies in initial submission

HeFH High CV Risk

On top of max tolerated statin

On top of max tolerated statin

FH I (n=486)

COMBO II (n=720) FH II (n= 249)

HIGH FH (n=107)

OLE(1) (n≥1,000)

COMBO I (n=316) OPTIONS I (n=355)

OPTIONS II (n=305)

CHOICE I (n=700)

MONO(2) (n=103)

ALTERNATIVE (n=314)

CHOICE II(3) (n=200)

On top of regular statin doses

OUTCOMES (n=18,000)

LONG TERM (n=2,341)

Not receiving statin

Statin Intolerant

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Next Regulatory Milestones and Development Steps

(1) Rationale and design in Schwartz GG et al. Am Heart J 2014;0:1-8.e1.

Regulatory submissions in the U.S. and EU on track ● U.S. submission expected before year end 2014

6-month FDA priority review from filing date expected ● EU submission also targeted before year end 2014

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)(1)

● Assess the potential of alirocumab to demonstrate CV benefit

1

2

3

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Agenda

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Q&A Session

(1) Harold Bays is an investigator of the ODYSSEY OPTIONS I and II clinical study

Study Dosing q2w

Baseline LDL-C (mg/dL)

LDL-C Change from Baseline at 24 Weeks

Alirocumab Comparator

HeFH

HIGH FH 150 mg 198 ↓ 46% ↓ 7% placebo

On top of max statin doses

FH I 75/150 mg(1) 145 ↓ 49% ↑ 9% placebo

FH II 75/150 mg(1) 134 ↓ 49% ↑ 3% placebo

High CV Risk

LONG TERM 150 mg 122 ↓ 61% ↑ 1% placebo

COMBO I 75/150 mg(1) 102 ↓ 48% ↓ 2% placebo

COMBO II 75/150 mg(1) 108 ↓ 51% ↓ 21% ezetimibe

OPTION I 75/150 mg(1) 105 ↓ 44-54% ↓ 21-23% ezetimibe ↓ 5% statin x2 ↓ 21% statin switch

On top of regular statin

doses OPTION II 75/150 mg(1) 111 ↓ 36-51% ↓ 11-14% ezetimibe

↓ 16% statin switch

Statin Intolerant ALTERNATIVE 75/150 mg(1) 191 ↓ 45% ↓ 15% ezetimibe

Not receiving statins Moderate

CV Risk MONO 75/150 mg(1) 140 ↓ 48% ↓ 16% ezetimibe

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Significant and Consistent LDL-C Reduction across All 10 Reported Trials

Primary efficacy endpoint met in all 10 reported trials

(1) Per protocol dose increase to 150 mg possible based on pre-specified LDL-C levels

Achieved LDL-C Over Time(1) All Patients on Background of Maximally Tolerated Statin ± other LLT

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LONG TERM

Robust and Durable LDL-C Reduction Maintained over 52 Weeks

Mean (SE) LDL-C in mg/dL

0

20

40

60

80

100

120

140

Week

118.9 mg/dL (+0.8%)

48.3 mg/dL (−61.0%)

123.0 mg/dL (+4.4%)

53.1 mg/dL (−56.8%)

Difference −61.9%

0 4 8 12 16 24 36 52

Difference −61.3%

Placebo Alirocumab 150 mg q2w

LLT: Lipid lowering therapy Intent-to-treat analysis (1) LDL-C: Calculated LDL-C, least-squares (LS) means (SE standard error)

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Consistent LDL-C Reduction across a Range of Baseline LDL-C Values

Mean % Change in LDL-C from Baseline to Week 24 Placebo Alirocumab

-61.3% -62.0% -59.8% -59.5%

13.6% 0.5%

-5.2% -18.2%

-70-60-50-40-30-20-10

01020

100 to <130 mg/dL <100 mg/dL

130 to <160 mg/dL ≥160 mg/dL

Interaction p-value <0.0001

n=470 n=241 n=562 n=285 n=271 n=143 n=227 n=111

LDL-C Change from Baseline(1) All Patients on Background of Maximally Tolerated Statin ± Other LLT

LLT: Lipid lowering therapy Intent-to-treat analysis (1) LDL-C: Least-squares (LS) means

LONG TERM

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All patients on background of maximally tolerated statin ± other lipid-lowering therapy Safety Analysis (at least 52 weeks for all patients continuing treatment, including 607 patients overall who completed W78 visit) (1) 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 hospitalization, congestive heart failure requiring hospitalization, ischemia driven coronary revascularization procedure [PCI, CABG]

(2) Company MedDRA Queries (CMQ)

Alirocumab (n=1550)

Placebo (n=788)

General allergic reaction events 9.0 9.0

Treatment-emergent local injection site reactions 5.8 4.3

Myalgia 4.9 3.0

Neurological events(2) 4.2 3.9

All cardiovascular events(1) 4.0 4.4

Ophthalmological events(2) 2.5 1.9

Neurocognitive disorders(2) 1.2 0.5

ALT increase 1.1 0.5 CPK increase 0.5 0.5 AST increase 0.2 0

Safety Profile from Long Term Study LONG TERM

% of Patients with Treatment Emergent Adverse Events of Interest

41

Post-hoc Adjudicated Major Adverse Cardiovascular Events(1)

TEAEs: Treatment emergent adverse events (1) Primary endpoint for the ODYSSEY OUTCOMES trial: CHD death, Non-fatal MI, Fatal and non-fatal ischemic stroke, Unstable angina requiring

hospitalization. LLT, lipid-lowering therapy (2) ≥ 52 weeks for all patients continuing treatment, incl. 607 patients who completed W78 visit

Safety Analysis(2)

Placebo + max-tolerated statin ± other LLT Alirocumab + max-tolerated statin ± other LLT 150 mg q2w

788 1550

776 1534

731 1446

703 1393

682 1352

667 1335

321 642

127 252

84 72 60 48 36 24 12 0

0.06

0.05

0.03

0.02

0.01

0.00

0.04

Cum

ulat

ive

prob

abili

ty o

f eve

nt Cox model analysis:

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

Weeks No. at Risk Placebo Alirocumab

Mean treatment duration: 65 weeks

LONG TERM

Kaplan-Meier Estimates for Time to First Adjudicated Major CV Event

Patient at LDL-C Goal

42

ALTERNATIVE

Safety and Efficacy in Statin Intolerant Patients with Very High LDL-C (~190mg/dL)

Baseline LDL-C levels (ITT): 191.1 and 194.2 mg/dL in alirocumab and ezetimibe arms (1) Intent-to Treat analysis (2) Pre-defined category including myalgia, muscle spasms, muscular weakness, musculoskeletal stiffness, muscle fatigue (3) Cox model analysis (95% CI for alirocumab vs atorvastatin: 0.38 to 0.99 ; for alirocumab vs ezetimibe: 0.47 to 1.06) (4) 89.5% of randomized patients entered the Open-label Treatment Period (including 94% of those randomized to atorvastatin) and received alirocumab

Skeletal Muscle Adverse Events

Goals alirocumab ezetimibe

LDL-C <70 mg/dL or <100 mg/dL (depending on risk)

42% 4%

LDL-C <100 mg/dL 61% 10%

alirocumab vs.

atorvastatin

alirocumab vs.

ezetimibe

Hazard Ratio 0.61 0.71

Nominal P(3) 0.042 0.096

Only 0.7% myalgia leading to discontinuation with alirocumab in open-label treatment period(4)

∆: P<0.0001(1)

Significantly More SI Patients Achieved LDL-C Goals

with Alirocumab

Fewer Skeletal Muscle Adverse Events(2) with Alirocumab

than with Atorvastatin

Significant and sustained reductions in LDL-C over 1 year on top of existing therapies across different patient populations

Balanced safety and tolerability profile across patient groups with preliminary data on CV safety from long-term treatment trial

Flexible dosing providing options for physicians and patients

1mL dosage forms for subcutaneous self-injection at home

Alirocumab Has the Potential to Transform LDL-C Management

43

44 44

Agenda

44







Q&A Session

(1) Harold Bays is an investigator of the ODYSSEY OPTIONS I and II clinical study

Key Factors Impacting Uptake of PCSK9 mAbs in High CV Risk Patients

45

Physician awareness

Likelihood to prescribe

Efficacy attributes

Patient acceptance

Payor dynamics

1

2

3

4

5

1

62%

49%

36%

73%

54% 52%

Very High and Growing Awareness

46

(1) Aided and Unaided Awareness. Questions: ”Please name and describe all the potential treatments in development for hypercholesterolemia of which you are aware” and “Please indicate your familiarity with the following classes of therapy in development for hypercholesterolemia”

Source: Proprietary survey conducted in U.S., UK and Germany

~13,000 ~1,100 ~3,500

Percent of Specialists Aware of PCSK9 Inhibitor Class(1)

Q4 2013 Q2 2014

Estimated Number of Specialists Aware

High Likelihood to Prescribe

64%

49%

63% 71%

64% 71%

47

(1) Question: “Based on your experiences and anything you might have heard, how likely would you be to prescribe a PCSK9 Inhibitor for the treatment of hypercholesterolemia, if available in the future? (Answers based on own physician’s knowledge without being exposed to any product profile)

Source: Proprietary survey conducted in U.S., UK and Germany

2

Percent of Specialists Likely/Very Likely to Prescribe a PCSK9 Inhibitor(1)

Q4 2013 Q2 2014

Efficacy Attributes Are Most Important for Specialists

48

Substantial data in high CV risk patients like diabetes, CHD, stroke

Achieves significant reduction of LDL-C, particularly high CV risk patients

Achieves significant reduction of LDL-C for majority of patients

Good treatment option for statin intolerant patients

Demonstrates good tolerability profile resulting in minimal monitoring of AEs

Demonstrates significant decrease in CV morbidity / mortality

OOP: Out of pocket Source: Proprietary survey conducted in the U.S.

3

Covered, affordable for patients (reasonable level of OOP cost to patients)

Acts on atheroma plaque

Achieves significant increase of HDL-C

U.S. Specialists

67

78

95

116

146

163

211

232

247

Average score of importance = 100

High Patient Acceptance and Perception of Benefit

49

DM: Diabetes Mellitus CKD: Chronic Kidney Disease Source: Proprietary surveys conducted in the U.S/EU (2012/2013) The HeFH patient population was not part of the survey conducted in Europe

4

Share of Patients Likely / Very Likely to Accept and Fill PCSK9 Treatment Share of Patients Likely/Very Likely to Accept and Fill PCSK9 Treatment Prescription

70%

52% 52% 53%

HeFH Statin Intolerants

Primary Prevention (DM/CKD)


70% Managed by Endos

Statin Intolerants

Primary Prevention (DM/CKD)


65% 65% 65%

50

Satisfaction Rating ODYSSEY MONO(2)

(1) Some patients have been titrated up to 150mg; >70% of patients remained on 75 mg (2) 53 respondents out of 105 patients who completed the ODYSSEY MONO study Question: “How do you rate your overall experience in performing an injection on yourself with the study drug auto-injector pen?”; 98% respondents satisfied

Flexibility in Dose & Delivery Options Available Auto-Injector

75 mg(1)

150 mg

q2w

98%

Broad Experience of Home Self-Injection with Alirocumab 4

Payor Dynamics

51

5

Important Factors for the Alirocumab Payor Value Proposition

Payor price pressure on innovations

Large unmet medical need in a generic market

Importance of LDL-C as a primary risk factor for CV disease and of LDL-C lowering to reduce the risk

Sense of urgency to treat a condition with significant adverse outcomes and system costs

Recognition of PCSK9 inhibitors as effective tool in the treatment algorithm for appropriate patients

Definition of appropriate patients that can be targeted to ensure maximum allowable access to target populations

Engaging Significant Resources to Ensure Alirocumab Launch Success in the U.S.

52 Praluent™ is the intended trade name for alirocumab. The trade name is currently pre-approved in the EU but not in other regions.

Praluent™ alirocumab

Q&A

53

BREAK

54

Return in 15 Minutes

55 55

Agenda

55

Toujeo® / Afrezza® / LixiLan

Unmet Needs of Basal Insulin Management ● Riccardo Perfetti, MD, Senior Medical Officer, Diabetes

Clinical Evidence on Toujeo® ● Stewart B. Harris, MD, Professor of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada

Toujeo® - the Next Generation of Basal Insulin

● Andrew Purcell, Vice President, Commercial Business Unit Head U.S. Diabetes

Afrezza® ● Andrew Purcell, Vice President, Commercial Business Unit Head U.S. Diabetes

LixiLan ● Riccardo Perfetti, MD, Senior Medical Officer, Diabetes

Conclusion ● Pierre Chancel, Senior Vice President, Diabetes

Q&A Session

(1) Motivation and characterization of insulin patients, patient interviews (2) Highs = Hyperglycemia / Lows = Hypoglycemia

Frustration Imprisonment

Embarrassment

56

“I hate this so much. It’s like a constant thorn in my side that I can’t rip

out”

“When I experience a high(2), I go into a state of

euphoria and worry others notice”

At start, a challenge ● Frustration of poor

control

● Fear of hypoglycemia

At stay, a variable experience

● Satisfaction?

● Motivation?

There Is Need for an Improved Basal Insulin Experience to Get More Patients to Control(1)

Diabetes Patients in the U.S. (Random Sample)

Despite Treatment, Many Patients with Diabetes Are Still not at A1c Goal(1)

57

47% 47%

53% 53%

2013(437)

2013(2215)

Uncontrolled (>7%)

Controlled (<=7%)

T1D Patients T2D Patients

A1c: glycated haemoglobin (1) Adelphi Real World Diabetes Disease Specific Programme (DSP) X, 2013 Base: U.S. diabetic patients where doctor has stated most recent A1c (random sample) All patients are treated patients and must be on an OAD, GLP-1 or insulin

(1) Idea Exchange Report Toujeo® Titration Exploration (9.4.2014); Sanofi market research

>1 month

37%

<1 month

63%

58

Timing of Dose Increase after First Week on Basal Insulin

Patients wish for a quick titration

experience to achieve immediate control

but fear hypos

Most Patients Delay Increasing their Dose After Initiation of Therapy Despite Not Being at Goal(1)

(1) Data on file – Real-World Data on Hypos Following Basal Insulin Initiation (2) Peyrot M et al. Diabet Med 2012;29:682–689. (3) Leiter LA et al. Can J Diabetes 2005;29:186–192

modify their insulin dose after experiencing a severe hypoglycemia event(2) 6 in10

patients

59

4 in10 people experienced hypoglycemia within the first month(1)

of people who experienced hypoglycemia within 6 months of initiation had discontinued within 1 year(3) 77%

Patients Respond to Hypoglycemia by Modifying their Dose or Discontinuing Therapy

Inappropriate Diabetes Management Leads to Costly Consequences

60

Microvascular Complications

● Diabetic Retinopathy

● Diabetic Nephropathy

● Diabetic Neuropathy

(1) Endocrinol Metab Clin 1996;25:243 - 254 (DCC Trial) (2) Diabetes Care Publish Ahead of Print, published online March 6, 2013

Risk of Complications and A1c(1)

25% to 45% of diabetes-attributed medical expenditures spent treating complications of diabetes(2)

A1c (%)

Relative Risk in %

1

3

5

7

9

11

13

15

6 7 8 9 10 11 12

Retinopathy Nephropathy

Microalbuminuria Neuropathy

Macrovascular Complications

● Stroke

● Heart Disease

● Peripheral Vascular Disease

50% of basal insulin patients are

not at A1c goal

30% to 60% experience hypoglycemia

59% of new to Lantus® patients in the U.S. have

significant compliance gaps

(1) IMS Lifelink; U300 segmentation; Sanofi market research; expert interviews; Sanofi analysis 61

The launch of Toujeo® will offer opportunities to address unmet needs

Hypoglycemia Contributes to Poor Compliance and Affects Treatment Efficacy(1)

62 62

Agenda

62









Q&A Session

Patients Hate Hypoglycemia

Canadian Diabetes Association Clinical Practice Guidelines. Can J Diabetes. 2013;37(suppl 1):S1-212.

● Very unpleasant and disruptive symptoms (e.g. blurry vision, rapid heartbeat, sudden mood changes, headache, trouble concentrating)

● A medical emergency that can result in fainting, seizures, unconsciousness, coma and death

Mild to moderate

hypoglycemia

Severe hypoglycemia

Nocturnal hypoglycemia

● Imagine going to sleep each night needing to protect yourself against hypoglycemia while you sleep

● Imagine sleeping next to someone and worrying about whether their blood sugar is high enough

63

Toujeo®

A Smoother and Prolonged PK/PD Profile vs. Lantus®

Lantus®

Toujeo® Lantus®

64

Median insulin concentration, µU/mL

Glucose infusion rate, mg/kg/min

3

0

2

1

Lantus®

0 6 30 36 24 18 12

Toujeo®

Time, h

160

100

140

120

Lantus®

0 6 30 36 24 18 12

Toujeo®

Lantus® 10

20

0 6 30 36 24 18 12

Toujeo®

0

Blood glucose, mg/dL

64

Reduction of Volume by 2/3

Reduction of Depot Surface Area by 1/2

More Constant PK/PD Profile(1)

PK/PD Profile: Pharmacokinetic/Pharmacodynamic Profile (1) Steinstraesser A et al. Diabetes Obes Metab. 2014;16:873-6; Becker RHA et al. Diabetes Care. 2014 Aug 22.pii:DC_140006

Type 1 Diabetes - Continuous Glucose Monitoring Study(1)

Offering Greater Consistency Over the Course of the Day

Average 24-hour glucose profiles showed a more

constant glucose level with Toujeo®

vs Lantus®

65 (1) Bergenstal RM et al. Poster presentation at EASD 2014; data combining morning and evening injections

Time, h

Lantus®

Toujeo®

11

10

9

8

7 0 2 4 6 8 10 12 14 16 18 20 22 24

All Studies of EDITION Phase III Program Met their Primary Endpoint(1,2)

66

(1) Non inferiority on A1c (2) Riddle MC et al. Diabetes Care. 2014;37:2755-62; Yki-Järvinen H et al. Diabetes Care. 2014 Sep 5. pii: DC_140990; Bolli GB et al. Poster

presentation at EASD 2014; Abstract 947; Terauchi Y et al. Poster presentation at EASD 2014; Abstract 976; Home PD et al. Oral presentation at EASD 2014; Abstract 148; Matsuhisa M et al. Poster presentation at EASD 2014; Abstract 975

vs.

EDITION 1 EDITION 2

EDITION 3

EDITION JP1

EDITION 4

EDITION JP2

Primary Endpoint Non inferiority (Change in A1c) Population

T2DM on basal and mealtime insulin + OADs

T2DM on basal insulin + OADs

T2DM insulin-naïve + OADs

T1DM on basal and mealtime insulin

T1DM on basal and mealtime insulin

T2DM on basal insulin + OAD

0

10

20

30

40

50

-20%

-31%

% Participants with ≥1 Confirmed and/or Severe Hypoglycemia(2)

Baseline to week 8

Baseline to month 6

Week 9 to month 6

67

Nocturnal Hypoglycemia(1,3)

Pooled analysis of EDITION 1-2-3 Lantus®

Toujeo®

-25%

Benefit on Nocturnal Hypoglycemia

(1) Defined as 00:00–05:59h (2) ≤70 mg/dL (≤3.9 mmol/L) (3) Ritzel R et al. Poster presentation at EASD 2014; Abstract 963

RR 0.75 (0.68 to 0.83)

RR 0.69 (0.58 to 0.81)

RR 0.80 (0.71 to 0.91)

68

0

10

8

4

2

4 8 12 16 20 24 28

6

Time, weeks 0

0

3

Lantus®

Toujeo®

2

1

4 8 12 16 20 24 28 Time, weeks

0

Nocturnal(2) At any time(3)

(1) Confirmed events based on plasma glucose ≤3.9 mmol/L (≤70 mg/dL); Ritzel RA, et al. Poster presented at EASD 2014; Abstract 963. (2) 00:00–05:59h (3) 24 h

-31%

-14%

Confirmed or Severe Hypoglycemia per Patient per Year Significantly Lower

Cumulative Mean Number of Confirmed or Severe Hypoglycemia per Participant(1,3)

Pooled analysis of EDITION 1-2-3

p=0.0002

p=0.0116

Hypoglycemia Benefit Consistently Demonstrated

69

(1) Pooled analysis of Edition 1,2,& 3 - Type 2 Diabetic patients; Ritzel R et al. Poster presentation at EASD 2014; Abstract 963 (2) % Participants with ≥1 Confirmed (≤70 mg/dL [3.9 mmol/L]) and/or Severe Hypoglycemia baseline to month 6: -9% at any time and -25% nocturnal

(00:00–05:59h) / % Participants with ≥1 Confirmed (<54 mg/dL [3.0 mmol/L]) and/or Severe Hypoglycemia:-19% at any time and -27% nocturnal (00:00–05:59h)

(3) Lower rate of confirmed or severe hypoglycemia with Toujeo® during the night until 10 am (4) EDITION 1-1 year; Riddle MC et al. Poster presentation at EASD 2014; Abstract 980: % of participants reporting ≥1 event from baseline to month

12: -22% and annualized event rates from baseline to month 12: -26%

Benefit maintained regardless of hypoglycemia definition(1,2)

● ≤70 mg/dL [3.9 mmol/L] OR <54 mg/dL [3.0 mmol/L]

Consistent benefit on hypoglycemia independent of definition of night duration(1,3)

● Standard definition: 00:00–05:59h

● Lower rate up to 10:00h

Benefit in nocturnal hypoglycemia maintained over time either as % of Patients or Event Rate(4)

7,0

7,5

8,0

8,5

BL W12 M6 M12 M9

7,0

7,5

8,0

8,5

LS: Least Squares (1) Type 2 Diabetic patients uncontrolled with basal bolus (2) Type 2 Diabetic patients uncontrolled with Basal + OAD 70

EDITION 1(1)

EDITION 2(2)

Toujeo®

Lantus®

Toujeo®

Lantus®

LS Mean (95% CI) Difference in A1c Between Groups at Month 12

A1c (%) mean ± SE

Sustained Glycemic Control at 1 Year

8.5

8.0

7.5

7.0

8.5

8.0

7.5

7.0

−0.17% p=0.0074

0.06% p=0.4932

(1) Type 2 Diabetic patients; Ritzel R et al. Poster presentation at EASD 2014; Abstract 963

Weight Change Difference Maintained Over Time

71

LS mean difference: –0.28 kg p=0.039

1.5

1.0

0.5

0.0

-0.5 BAS Week

2 Week

4 Week

8 Week

12 Month

4 Month

6

Lantus®

Toujeo®

Mean Weight Change (kg ± SE)(1)

Pooled analysis of EDITION 1-2-3

0

10

20

30

40

50

60

70

Confirmed or severe at any time (≤70 mg/dL [3.9 mmol/L])

Confirmed or severe nocturnal (≤70 mg/dL [3.9 mmol/L])

Confirmed or severe at any time (≤70 mg/dL [3.9 mmol/L])

Confirmed or severe nocturnal (≤70 mg/dL [3.9 mmol/L])

Flexible dosing

Fixed dosing

(1) Riddle MC et al. Poster presentation at ADA 2014; Abstract 919-P 72

T2D Patients who Occasionally Adapted the Timing of their Once-Daily Injections of Toujeo® (24 ± 3 h) Did Not Impact Glycemic Control or Affect Frequency of Hypoglycemia(1)

72

EDITION 1 EDITION 2 Percentage of patients experiencing ≥1 event, %

Flexibility in Injection Time (24 hours ± 3 hours)

A Unique Clinical Profile

● Easy insulin initiation

Smoother glucose lowering and prolonged PK/PD profile

Less hypoglycemia during the initiation period when titration occurs

Less weight gain

● Long lasting benefit

Sustained glucose control at 1 year

Benefit in reduction of hypoglycemia maintained at 1 year

Flexibility in injection time, when occasionally patients need it

73 PK/PD Profile: Pharmacokinetic/Pharmacodynamic Profile

74 74

Agenda

74









Q&A Session

The Next Generation of Basal Insulin with a Smoother PK/PD Profile than Lantus®

TOUJEO • Smoother PK/PD

profile than Lantus®

• Full 24h coverage • Less hypos than

Lantus • Improved patient

experience

LANTUS

• Once daily • Less hypos

than NPH • Treat to target NPH

75 PK/PD Profile: Pharmacokinetic/Pharmacodynamic Profile

Total Addressable U.S. Basal Insulin Market for Toujeo® Is ~6m Patients(1)

(1) Sanofi market research, expert interviews

Million patients

● 14.3m insulin naïve drug-treated patients

● 1m new basal insulin starts every year

76

+ Levemir®

Existing Patients

5m

Million patients

Estimated Annual New Basal Insulin

Naïve Patients

1m/year

Total Addressable Market

~6m

A Compelling Value Proposition

(1) Jax T et al. Poster presented at EASD 2013; Abstract 1029. Available at http://www.easdvirtualmeeting.org/resources/6226 Accessed May 2014 (2) Ritzel R, et al. Diabetes 2014;63 (suppl 1A) (3) Riddle MC et al. Poster presentation at EASD 2014; Abstract 980 (4) ORIGIN Trial Investigators. N Engl J Med. 2012 Jul 26;367(4):319-28 77

77%

US EU Top 5

52%

US EU Top 5

Aided Awareness of Toujeo®(1)

Scientific Data Communication Created Strong Pre-launch Awareness and Willingness to Prescribe

78 (1) Sanofi Market Research – Awareness and Trial Tracking (August 2014)

50%

75%

% of Endocrinologist Willing to Prescribe

Willingness to Prescribe Toujeo®(1)

40%

60%

% of Endocrinologist Aware

Target Switch Segments Represent Almost 60% of Existing Basal Insulin Patients Pre-Launch(1)

(1) Toujeo® segmentation survey: Segmentation solutions and expert interviews (2) Target Patient Profile

Engaged and satisfied (Type 1 / Type 2 controlled)

Motivated but are falling short (Type 2 basal bolus, controlled w/ hypos)

Frustrated and challenged: Type 1 (Uncontrolled)

Frustrated and challenged: Type 2 (Uncontrolled)

More limited drivers for engaged and satisfied patients to switch from current treatment 43%

22%

6%

29%

Segment size % basal insulin pop

Receptive to Toujeo® TPP(2)

Concerned about hypos

Looking for better options

Natural switchers

Require convincing

79

May become unsatisfied over time

An Enhanced SoloStar® Device: Accurate, Precise and Easier to Use

80

● Smaller injection volume(1)

● Ergonomic design improvements

● No additional training needed(1)

● 50% more units per pen (450 IU)(1)

Toujeo® SoloStar®: Adapted for the Next-Generation Basal Insulin

(1) Compared to Lantus® SoloStar®

Regular touch points

Mix of face to face/ phone/ webinar

interactions

Adapted locally

Toujeo® and Customized Patient Support Program Intended to Ensure a Smoother Start and Better Stay

81

A Customized Patient Support Program to achieve personalized glycemic goals

● Support successful initiation of Toujeo® following prescription

● 31% of diabetes patients do not initiate prescription(1)

● Support patients to up-titrate quickly to target A1c

● 15% to 20% of patients discontinue insulin in first 3 months(2)

● Motivate patients to stay on therapy

(1) M Fischer et al., J Gen Intern. Med, 25(4):284-90, 2010 (2) Lantus® satisfaction study, Impact Rx, Dec 2012 (US/EU5 & JP)

Improved clarity and impact of Lantus® promotion messages Raised PCP preference for Lantus®

Increased sales force call productivity From 35% to 90% ≥ 8 calls/day

Increased sales force call targeting Significant improvement in % calls to priority customers

Raised perception of Sanofi on “best in meeting physician needs”

+4 pts over baseline

82

Ensuring U.S. Sales Force Readiness for Launch

Enhancement of U.S. commercial effectiveness to improve Lantus® performance and prepare for the Toujeo® launch

Toujeo® is a better insulin vs. Lantus® based

on the EDITION program

Achieving Payor Access is Necessary for Franchise Conversion

83 83

● Current Lantus® access and volume provides foundation for Toujeo®

● Price expected not to be a barrier to access

● Maintain top quality access over time with a strong documented value proposition

Preparing for Launch

July 2014: FDA acceptance of NDA review

● Expected regulatory decision: Q1 2015

May 2014: EMA acceptance of the marketing authorization application

● Expected regulatory decision: Q2 2015 July 2014: NDA submission to Japanese Health Authorities

● Expected regulatory decision: Q2 2015

84

Regulatory Timelines:

Ensure Toujeo® patients have an improved insulin experience

Convert basal insulin users, especially Lantus®, to Toujeo®

Become the preferred basal insulin

Our Diabetes Team is Focused on Improving Patient Outcomes

85

3

2

1 Ambition for

to generate a substantial

proportion of Sanofi’s glargine

volume in the U.S. within 3 years after launch

86 86

Agenda

86









Q&A Session

Patients on 2+ OADs Are Resistant to Starting Insulin Therapy

The Majority of Patients on 2+ OADs Resist Starting Insulin Therapy(1,2)

Resistant because of injections Resistant not because of injections Not Resistant to taking insulin

66%

% of Patients

39%

27%

66% Resistant to starting insulin

87

(1) Nielsen DD Quantitative Market Research (T2D patients on 2+OADs, n=77. Note that these data are patient reported captured in a market research setting and do not necessarily reflect actual future behavior.

(2) When physician recommends initiating insulin therapy

Indication

A New and Innovative Treatment Option for Diabetes

● Afrezza® is a rapid acting inhaled insulin indicated to improve glycemic control in adult patients with diabetes

● Not recommended for patients who smoke

Large 5-year safety study to assess potential risk of pulmonary malignancy to be conducted

● Acute bronchospasm has been observed in patients with asthma and COPD using Afrezza®

● Contraindicated in patients with chronic lung disease such as asthma or COPD

Afrezza® (insulin human) Product Label

Black Box Warnings & Precautions

88

● Most common adverse event is cough ● Should not be used in patients with

active lung cancer

Dosage & Administration

● Administered at the beginning of a meal ● Before initiating, perform a detailed

medical history, physical exam, and spirometry (FEV1) in all patients to identify lung disease

COPD: Chronic Obstructive Pulmonary Disease

Focus of Initial Commercial Strategy for Afrezza®(1,2,3)

~2.0m ~1.1m

Insulin Initiation Insulin Intensification

Uncontrolled patients(1) (A1c > 7%) Controlled patients (A1c < 7%)

Many Diabetes Patients Are Not at A1c Goals Due to Delayed Insulin Initiation and Intensification

(1) Adelphi Real World: Diabetes DSP 9 (2012), Data on File. US Data. (2) NHANES Data (2009-201), CDC, US Data, 16% of PWD are smokers; 19% are non-smokers w/ COPD (Chronic Obstructive Pulmonary Disease)

and/or Asthma; (3) Sanofi market research (4) Patients for whom Afrezza® is contraindicated

Patients on 2+ OADs or GLP1 ± OADs Patients on Basal Insulin or Basal ± GLP1 ± OAD

Smokers, patients with asthma & COPD(2,4)

89

~3.1m Diabetes Patients

Device is Unique and Innovative

90

● Small, discreet, easy-to-use inhaler

● No cleaning required

● No parts need to be replaced

● Breath powered

● Efficient delivery to the deep lung

● Minimal training needed

● Disposed after 15 days of use

91

Afrezza®

Higher bioavailability and faster clearance

Small device

Easy to use

Doses equivalent to insulin units

Less training required

No cleaning requirement

Exubera®

Lower bioavailability and slower clearance

Large device

Complicated titration system

Doses were in milligrams

Time consuming in-office training

Device required weekly cleaning

Afrezza® Delivers a Distinctly Different Patient Experience than the Previous Inhaled Insulin


Majority of Patients Surveyed Prefer Afrezza® over Insulin Pen Device or Injectable Mealtime Insulins(1)

Preference for Afrezza®

No preference Preference for insulin pen device

Preference for Adding Afrezza® vs. Injectable Mealtime Insulins

(% of basal patients)

57%

32%

11%

Preference for Afrezza® vs. Insulin Pen Device

(% of patients on 2+ OADs)

66%

60%

17% 23%

92

Preference for Afrezza®

No preference Preference for injectable mealtime insulin

(1) Nielsen DD Quantitative Market Research (T2D patients on 2+OADs, n=77; T2D patients taking basal insulin +/- OADs, n=79 ). Based on exposure to an Afrezza® product profile and a video demonstration (blinded as Product X). Note that these data are patient reported captured in a market research setting and do not necessarily reflect future behavior.


Physician Survey Indicates Afrezza® Would Be an Appealing Option for Insulin Initiation and Intensification(1)

56%

25% 19%

“The product will make it significantly easier to initiate insulin among my

uncontrolled oral patients” (% of physicians)

66%

62%

23% 15%

93

Agree

Neither agree nor disagree Disagree

“I would be comfortable using the product instead of injectable rapid acting insulin

for my basal bolus patients” (% of physicians)

(1) Nielsen DD Quantitative Market Research (n=583 physicians – PCPs, n=391; ENDOs, n=192. Based on exposure to a clinical Afrezza® product profile and a video demonstration (blinded as Product X). Note that these data are physician reported captured in a market research setting and do not necessarily reflect future behavior.

Agree

Neither agree nor disagree Disagree

Expansion Drivers

● Novel product delivery ● Early adopters ● Current label

94

2015 U.S. Launch

● Label enhancement studies

● Safety study completed

● Potential ex-U.S. launches

● Supply of Sanofi insulin

The Launch Will Occur in Two Phases

95 95

Agenda

95









Q&A Session

96

A Strong Drug Profile Emerging from PoC Study in Type 2 Diabetes

(1) Mean A1c change of 1.8% at Week 24 (n=161) (2) Mean change in body weight from baseline to Week 24 (n=161) (3) Documented symptomatic hypoglycemic events ≤70 mg/dL occured in 21.7% of patients (n=161)

Proof-of-Concept Study of Fixed-Ratio Once-Daily LixiLan in Type 2 DM on Metformin

84% of patients reached A1c goal <7%

68% reached this target with no documented hypoglycemia

56% reached it with no weight gain

46% with no weight gain and no documented hypoglycemia

● Robust A1c reduction from 8.1% to 6.3%

● Reduced body weight (-1 kg)

● Less frequent nausea and vomiting compared to what has been reported for the GLP-1 Rapid Acting class

● Low incidence of symptomatic hypoglycemia

(1) Proof of concept study (323 patients) - a 24-week randomized, open-label, trial comparing the efficacy and safety of insulin glargine/ lixisenatide fixed ratio combination versus insulin glargine, in type 2 diabetes inadequately controlled with metformin

(2) DUAL™ I Phase III study (around 1,600 people) – a 26-week, randomized, open-label trial comparing the efficacy and safety of IDegLira, insulin degludec and liraglutide, in people with type 2 diabetes inadequately controlled with metformin with or without pioglitazone

LixiLan(1) Data IDegLira(2) Liraglutide

8.06 Baseline A1c (%) 8.3 8.3

6.3 End point A1c (%) 6.4 7.0

-1.8 Change in A1c (Abs. %) -1.9 -1.3

-60 Change in FPG (mg/dL) -65 -32

84% % Achieving A1c <7% 81% 60%

7.5% Nausea (%) 8.8% 19.7%

2.5% Vomiting (%) 3.9% 8.5%

-1.0 Change in Body Weight (kg) -0.5 -3.0

High Proportion of Type 2 Diabetes Patients Reached A1c Target in PoC Study

97

Combining Insulin Glargine with Lixisenatide in a Single Daily Injection

98

● Phase III program initiated in Q1 2014 ● LixiLan-O study in patients insufficiently

controlled on OADs (1,125 patients)

● LixiLan-L study in patients not at goal on basal insulin (700 patients)

● Completion of both studies expected by Q3 2015

● Results of ELIXA CV outcome trial with lixisenatide expected in Q2 2015

● Targeted FDA submission of LixiLan as early as end of 2015

Patients Uncontrolled

with basal therapy

~4m patients

Patients Not at Target

on OAD ~5.5m

patients

Number of patients estimated for the U.S. (2017 projections based on internal model adapted from Adelphi)

1st injectable drug

Basal Intensification

U.S. Target Populations of T2D Patients for

99 99

Agenda

99









Q&A Session

Broadening our Portfolio to Sustain a Leadership Position in Diabetes

100

1 Establish next generation of basal insulins

2 Capture untapped patient needs by addressing their reluctance to start insulin

3 Innovate with a new combination of basal insulin and GLP-1

5 Drive better outcomes through integrated care solutions

4 Expand access to Lantus® in developing countries

http://www.google.com/url?url=http://www.innovativescience.net/fda-adcomm-blog/?Tag=afrezza&rct=j&frm=1&q=&esrc=s&sa=U&ei=AYAEVLHXCIWm0QWL04CQBg&ved=0CCQQ9QEwBw&usg=AFQjCNGHN8JtsZYsYkzq271hLGItKNO7HA

Q&A

101

102 102 102

Dengue Vaccine

Dengue – A Major Public Health Concern

● Duane Gubler, MS, ScD, Professor, Emerging Infectious Diseases Program, Duke NUS, Singapore

Dengue Vaccine – Clinical Development Program

● Nicholas Jackson, Associate Vice President R&D, Dengue Vaccine Company, Sanofi Pasteur

From Vaccine Development to Vaccination Programs

● Guillaume Leroy, Vice President, Dengue Vaccine Company, Sanofi Pasteur

Agenda

Aedes mosquito

Humans

Dengue: A Mosquito-Borne Disease

● Family Flaviviridae: Four serotypes ● Mosquito-borne virus

● Primary vector is Aedes aegypti ● Secondary vector is Aedes albopictus

● Female Aedes aegypti mosquito acquires virus while feeding on the blood of an infected person ● Highly domesticated ● Strongly anthropophilic

● Once infected, the virus is transmitted from the mosquito to other humans(2,3)

● The mosquito remains infective for the rest of its life(2)

103

Dengue Is the Most Important Vector-Borne Viral Disease of Humans(1)

(1) Gubler, 2010, Dengue, Trop Med Health (2) World Health Organization, 2009, Dengue guidelines for diagnosis, treatment, prevention and control (3) Whitehead, 2007, Nat Rev Microbiol.

● Urbanization ● Travel and globalization ● Vector control effectiveness and

sustainability ● Factors adding to the proliferation of

dengue(2,3)

● Seasonal trends

Spread of Dengue Follows Growing Trend of Urbanization

104

Important Determinants of the Dengue Disease Epidemiology(1)

(1) Kyle, 2008, Ann Rev Microbiol. (2) Higa, 2011, Trop Med Health (3) Descloux, 2012, PLoS Negl Trop Dis.

105

2.5 billion people(2)

live in dengue-endemic countries (over 40% of the world’s population)

50 to 100 million dengue infections(2)

occur worldwide each year

500,000 people with severe dengue(2)

require hospitalization each year

12,500(2,3)

people with severe dengue die

Estimates Based on 2013 Modeling(5)

WHO objective: estimate true

disease burden by 2015(4)

(1) World Health Organization, 2009, Dengue guidelines for diagnosis, treatment, prevention and control (2) World Health Organization, 2014, Dengue factsheet (3) ~12,500 people or 2.5% people with severe dengue die each year (4) WHO, 2012, Global Strategy for Dengue Prevention and Control (5) Bhatt, 2013, Nature

Four distinct serotypes with unpredictable distribution(5)

Dramatic Expansion of Dengue with a 30-Fold Increase in Dengue Incidence over the Last 50 Years(1)

WHO Estimates

96 million symptomatic infections per year

390 million infections per year

Contributes to a large reservoir

of infection that influences disease burden

Every Year, an Estimated 2 Million People with Dengue Require Hospitalization(1)

~2.5% of severe

dengue cases result in

death

106

Characteristics of Severe Dengue(2)

(1) Beatty 2009 (2) World Health Organization, 2009, Dengue guidelines for diagnosis, treatment, prevention and control

● Plasma leakage

● Severe gastrointestinal involvement

● Severe organ impairment

● Significant bleeding

● Altered level of consciousness

Dengue Has an Adverse Economic and Societal Impact in Endemic Regions

107

Dengue can affect anyone, regardless of age and socioeconomic status(4,8)

(5) Mavalankar, 2009, IIMA (6) Shepard, 2013, PLoS Negl Trop Dis. (7) Shepard, 2011, Am J Trop Med Hyg. (8) OK DoH website, 2013, Oklahoma Department of Health

(1) Shepard et al. 2014, poster ASTMH 2014 (2) Infectious Disease Cost Calculator, Accessed Nov 2014 (3) Gubler, 2002, Trends Microbiol. (4) Douglas, 2013, PLoS Negl Trop Dis.

Dengue Disease Is Estimated to Cost Between US$6.3bn(1) and US$12bn Each Year in Endemic Countries(2)

Lost productivity(3)

Fear of infection(4)

Dengue “phobia”(4)

Community disruption(4)

Economic cost(3,4,6,7)

Perceived government

failure(4) Decrease in

tourism(5)

Overcrowded healthcare facilities(3)

Sanofi Pasteur Dengue Vaccine Can Make the 2020 Objectives of WHO Achievable

108

WHO Objectives(1)

Technical elements

Diagnosis & case management

Future vaccine

implementation

*2010 is baseline year. Vaccination is a crucial element in achieving the WHO objectives

Sustainable vector control

Integrated surveillance &

outbreak preparedness

Basic operational & implementation

research

(1) WHO, 2012, Global Strategy for Dengue Prevention and Control

Reduce dengue

morbidity by ≥25% by 2020*

Reduce dengue

mortality by ≥50% by 2020*

Estimate true

burden of disease by 2015

Dengue Vaccine







109 109

Agenda

109

A Significant Technological Advance(1,2)

● 4 genetic constructs, 1 for each serotype

● Envelope and precursor membrane genes from each serotype combined with the genes encoding the capsid and non-structural proteins from the yellow fever (YFV 17D) vaccine strain

● 4 recombinant, live, attenuated dengue viruses combined into a single vaccine that is freeze-dried and contains no adjuvant or preservatives(3)

110

17D Yellow fever Dengue

Chimeric Virus

17D yellow fever Dengue

Recombinant virus

YFV 17D VIRUS DENV-1 DENV-2 DENV-3 DENV-4 RECOMBINANT DENV-1, -2, -3, and -4

C NS PrM E PrM E PrM E PrM E

(1) Vaccine referred to in the literature as Chimeric Yellow Fever 17D-Tetravalent Dengue Vaccine (CYD-TDV) (2) Guirakhoo, 2001, J Virol. (3) Guy, 2011, Vaccine

111

CYD14 Phase III Efficacy Study Asia Countries: Thailand, Indonesia, Malaysia, Viet Nam, Philippines

Sites : 11

Age group: 2–14 years

Sample size: 10,278

Phase III Evaluation Provides Complementary and Pivotal Data for Efficacy, Safety, and Immunogenicity of the Dengue Vaccine(2,3)

(1) Nearly 30,000 individuals across age groups have received the vaccine and approximately 12,000 individuals have received placebo or control vaccine Status as of October 25, 2013

(2) ClinicalTrials.gov, 2013, NCT01374516 (3) ClinicalTrials.gov, 2013, NCT01373281

CYD15 Phase III Efficacy Study in LatAm(2)

● Countries: Colombia, Mexico, Honduras, Puerto Rico and Brazil

● Sites: 22 ● Age group: 9 to 16 years ● Sample size: 20,875

CYD14 Phase III Efficacy Study in Asia(3) ● Countries: Thailand, Indonesia, Malaysia,

Vietnam and Philippines ● Sites: 11 ● Age group: 2 to 14 years ● Sample size: 10,278

More than 41,000 Individuals Included in Sanofi’s Dengue Vaccine Clinical Trial Program(1)

Inclusion Criteria

• Children 2–14 years (Asia) • Children 9–16 years (LatAm) • Good health • No plans to leave study area

Exclusion Criteria

• Febrile illness (until resolution)

• Receiving other vaccines (until 4 weeks after vaccination)

• Congenital or acquired immunodeficiency

RANDOMIZATION

0 6 12 13 18 25 Year 6 Months

Vaccination with Dengue Vaccine

Active Phase Active Surveillance/Detection of Dengue Cases

Hospital Phase Additional follow-up for safety of

hospitalized dengue cases for 4 years after the end of the active

phase

112

Vaccination with Placebo*

2:1

Phase III Studies Design: Randomized 2:1, Observer-Blind, Placebo-Controlled, Multicenter(1,2)

The vaccination follows a 3-dose schedule

*Participants who received placebo were designated as the control group (1) Capeding, 2014, Lancet (2) Villar, 2014, N Engl J Med.

● Per-protocol analysis: follow-up from month 13–25.

● Intent-to-treat analysis: follow-up from month 0–25.

Meta-Analysis Demonstrates Significant Reduction in Dengue across All Serotypes after 3 Doses Schedule(1,2)

113

STUDY (n cases) EFFICACY and 95% CI

DENV-1

ASIA / CYD14 (n=250)

DENV-2

DENV-3

DENV-4

LATAM / CYD15 (n=397) Any

Serotype


LATAM / CYD15 (n=132)

ASIA / CYD14 (n=67)


ASIA / CYD14 (n=33)


ASIA / CYD14 (n=51)


43.8 56.5 66.4

52.0 60.8 68.0

52.3 59.2 65.0

24.6 50.0 66.8

29.1 50.3 65.2

35.6 50.2 61.5

-9.2 35.0 61.0

14.0 42.3 61.1

18.7 39.6 55.2

52.9 78.4 90.8

61.9 74.0 82.4

65.1 74.9 82.0

54.5 87.0

60.2 77.7 88.0

65.0 76.6 84.4

-20 0 20 40 60 80 100

Pooled (n=647)

Pooled (n=233)

Pooled (n=175)

Pooled (n=158)

Pooled (n=109)

75.3

(1) Capeding, 2014, Lancet (2) Villar, 2014, N Engl J Med.

Overview of Efficacy Results Against Virologically Confirmed Dengue (Severe and Hospitalized)(1,2,3)

52.7 80.0 92.4

64.9 95.0 99.9

50.3 67.2 78.6

64.7 80.3 89.5

0 20 40 60 80 100

EFFICACY and 95% CI

ASIA / CYD14 (n=28)


Vaccine Efficacy on Dengue Hemorrhagic

Fever (DHF) cases (WHO 1997 definition)



Vaccine Efficacy(4) on hospitalized dengue cases

STUDY (n episodes)

(1) Capeding, 2014, Lancet (2) Villar and al., 2014, NEJM (3) Intent to Treat analysis (25m follow-up from months 0–25) (4) The relative risk (RR) of hospital admissions for virologically confirmed dengue was calculated as the ratio of annual incidence in the vaccine group

and control groups, and presented here as vaccine efficacy (i.e., 1−RR)

Higher Efficacy Demonstrated Against Severe Dengue, Including Reduction in Hospitalized Cases(1,2)

Results relevant in public health context (ie, vaccine could help reduce disease burden)(1,2)

114

Efficacy According to Dengue Serostatus at Baseline(2) in Asia & Latam(1,2)

EFFICACY and 95% CI

DENV + (n=52)

DENV – (n=41)

ASIA / CYD14

DENV + (n=31)

DENV – (n=18)

LATAM / CYD15

STUDY (n episodes)

Higher Efficacy Observed in Those Previously Exposed to Dengue, During the Active Phase

115

Age can be used as a surrogate of prior exposure to dengue

(1) Comparison made on ITT. RR=relative risk: incidence of VC dengue cases in CYD group vs control group. (2) Dengue +: baseline titer for at least 1 DENV serotype is ≥10 1/dil.

74.3

35.5

83.7

43.2

-80 -60 -40 -20 0 20 40 60 80 100

Favorable Safety Profile in Vaccinated Subjects during the Active Phase of Phase III Efficacy Studies

116

Safety analyses* showed similar reporting rates between the vaccine and control groups during the studies

(1) Capeding, 2014, Lancet (2) Villar and al., 2014, NEJM

CYD14 & CYD15 Safety Results (Active Phase)(1,2)

* solicited reactions, unsolicited events and Serious Adverse Events (SAEs)

SAEs were consistent with medical disorders in the age group: mainly infections, injuries and accidents

No safety issue and no evidence of sensitization over the 25-month follow-up period

Long term safety results analysis on-going for 60 months post-dose 3

Safety profile over the 25-month is favorable and

consistent with the favorable safety profile documented in

previous studies (Phase I, II, III)

Both Efficacy Studies in Asia and LatAm Consistently Demonstrate a Reduction in Dengue Disease

117

CYD 14, Asia(2) Key Study Results

CYD 15, LatAm(3)

*95% CI: 52.7-92.4 †95% CI: 64.9-99.9 ‡95% CI: 50.3-78.6 §95% CI: 64.7-89.5

56.5% Reduction in

symptomatic dengue(4)

60.8% Reduction in

symptomatic dengue(4)

Both Studies Met their Primary Efficacy Endpoints and Showed Consistent Safety Profile for the Observed Active Phase(2,3)

67.2%‡ Reduction in

hospitalized cases(6)

80%* Reduction in severe

disease(5)

80.3%§ Reduction in

hospitalized cases(6)

95%† Reduction in severe

disease(5)

(1) World Health Organization, 2014, Dengue factsheet (2) Capeding, 2014, Lancet (3) Villar and al., 2014, NEJM

2.5 billion people(1)

live in dengue-endemic countries (over 40% of the world’s population)

50-100 million dengue infections(1)

occur worldwide each year

500,000 people with severe dengue(1)

require hospitalization each year

2.5%(1) of people

with severe dengue die

(4) Post Dose 3 (5) DHF, WHO 1997 criteria, intent to treat (6) Intent To Treat

Dengue Vaccine







118 118

Agenda

118

119

No vaccination

Routine vaccination

at 10 y

Routine plus

catch-up 10–14 y

Routine plus

catch-up 10–18 y

Routine plus

catch-up 10–22 y

Routine plus

catch-up 10–26 y

40

35

30

25

20

15

10

5

0

19% 34%

53% 73%

81% Prevented

hospitalized cases (%)

Number of hospitalized

cases (per 10,000

dengue cases)

Hospitalized cases

A Broad Vaccination Program Has the Potential to Lead to a Significant Reduction in Hospitalizations

ILLUSTRATIVE

Modeling the Prevention of Hospitalized Dengue Cases by Adding Multiple Catch-up Cohorts to a Routine Vaccination Program in a Given Population(1)

(1) Sanofi internal analysis, based on Coudeville & Garnett [2010]; prevented cases in the first 10 years of vaccine introduction

From Vaccine Efficacy to Vaccination Impact(1-7)

120

(1) Chao, 2012, PLoS Negl Trop Dis. (2) Coudeville, 2012, PLoS One (3) Durham, 2013, Vaccine (4) Rodriguez-Barraquer, 2013, Vaccine

(5) Dasbach, 2006, Epidemiol Rev. (6) Farrington, 2003, Math Biosci. (7) McLean, 1998, Dev Biol Stand.

Vaccination Impact

Vaccination Coverage

# cohorts x coverage in each cohort

Vaccine Efficacy

Direct protection & indirect protection

% Population Protected by Vaccination

x

Disease Endemicity =

ƒ

A Successful Vaccination Program Defined by Several Factors

121

121

1

2

3

4

Age for routine vaccination

Define the optimal age range for routine vaccination population in an endemic country

Catch-up cohort size

Determine the optimal catch-up cohort size to maximize impact of vaccination (range of age)

Geographic breadth

Agree on the geographic breadth of the vaccination program with local government

Compliance Ensure highest impact through compliance with 3-dose schedule

Outbreaks Incorporate the outbreak nature of the disease into an integrated strategy 5

122 122

An Unprecedented Industrial Commitment to Ensure the Success of Large Scale Vaccination Programs

Manufacturing Site, Neuville-sur-Saone, France

122

● State-of-the-art facilities dedicated to the production of the dengue vaccine ● €300m investment

● Manufacturing capacity for 100m doses annually ● Initial inventory build-up underway

● Investment in additional manufacturing capacity in the U.S.

● Large scale filling and packing to start from 2015

● 1-dose and 5-dose vial presentations

Ready to Produce >1bn Doses over the Next 10 Years

The Global Roll-out of Sanofi’s Dengue Vaccine

123

Steady Uptake at Launch Due to Broad Coverage in Endemic Countries

● First launches in dengue most endemic countries

● Initial sales evolution expected to be driven by public markets

● Private markets to complement public programs and adding strong growth momentum

ILLUSTRATIVE 2015 2020

124 124 124

Dengue Vaccine Launch Expected to Start by End of 2015

Make Dengue

the Next Vaccine-Preventable

Disease

125 125

Agenda

125

● Elias Zerhouni, MD, President, Global R&D

Sarilumab

Dupilumab

Wrap-up and Q&A Session

Immunology & Inflammation Set to Become a New Growth Platform for Sanofi

126

Immuno-Modulation is at the core of

Sanofi’s R&D strategy

Rheumatoid Arthritis

Asthma Atopic Dermatitis

Multiple Sclerosis

Inflammatory Bowel Disease

Systemic Lupus

Erythematosus

Rheumatoid Arthritis Is a Chronic, Debilitating Autoimmune Disease and a Major Cause of Disability

Rheumatoid Arthritis (RA)

● Up to 70m people worldwide(1) estimated to be affected by RA

Joints become chronically inflamed, painful and swollen

Patients can become increasingly disabled as cartilage and bone is damaged(2)

127 (1) World Health Organisation. Chronic rheumatic conditions (2) Patient UK. Rheumatoid arthritis

https://www.google.com/url?q=http://solomonsseal.wordpress.com/&sa=U&ei=S9h2U-HOJ8mbqAbYooCIDg&ved=0CEQQ9QEwCzgU&usg=AFQjCNHyFD7Szara0hqM7HxcBzkBtWUokA

128

MTX/DMARDS 1st line treatment

Add Anti-TNF 1st line biologic

Switch to Other MOA’s (Add on to MTX)

RA Combination

Tx Market

~70%

RA Mono Tx Market

~30%

Current guidelines make no distinction between which biologic to start on

MTX/DMARDS 1st line treatment

T cell

IL-6R

JAK

CD 20

IL-6R

JAK

TNF

Current guidelines recommend using IL-6R

as a 1st choice monotherapy(1)

Incomplete Response or Intolerance Leads Patients to Cycle through Multiple Biologics

MTX: Methotrexate DMARD: Disease-Modifying Anti-Rheumatic Drugs Actemra® (tocilizumab) is marketed by Roche Humira® (adalimumab) is marketed by AbbVie Enbrel® (etanercept) is marketed by Amgen Remicade® (infliximab) is marketed by J&J Simponi® (golimumab) is marketed by J&J Cimzia® (certolizumab) is marketed by UCB Orencia® (abatacept) is marketed by BMS Xeljanz® (tofacitinib) is marketed by Pfizer Rituxan® (rituximab) is marketed by Roche (1) EULAR guidelines

http://www.enbrel.co.nz/

http://www.enbrel.co.nz/

129

Sarilumab: An Investigational IL-6R mAb for RA

● Fully human, high affinity, IL-6R mAb ● 2 effective doses: 150mg or 200mg ● Delivered subcutaneously every other week ● Evaluated for use with ergonomic pre-filled syringe or autoinjector

● Efficacy demonstrated across three co-primary endpoints in first Phase III trial(1)

● Additional Phase III data expected in 2015

● Regulatory submission expected in late 2015 in the U.S. and late 2016 in EU and Japan

IL-6R – Interleukin-6 receptor Sarilumab is developed in collaboration with Regeneron (1) SARIL-RA-MOBILITY in MTX IR moderate-to-severe RA - Clinically relevant and statistically significant improvements in

both sarilumab groups compared to placebo in all three co-primary endpoints: ACR 20 at 24 weeks, improvement of physical function at 16 weeks and inhibition of progression of structural damage at 52 weeks

sarilumab

A Broad Clinical Development Program Aiming for a Robust Label at Launch

130

~2,500 RA patients targeted in SARIL-RA program

Study Design n Objectives Status sarilumab + MTX MTX IR patients 1,197

● Evaluation of use as 1st & 2nd line biologic therapy

● Assessment of long term safety up to 5 years

● Safety calibration

● Duration of inhibition of structural damage

Completed

sarilumab + DMARD Anti-TNFα IR patients 546 2015

sarilumab + MTX Anti-TNFα IR patients Safety calibrator vs. Actemra®

200 2015

sarilumab + DMARD Long-term extension study 2,000 Ongoing

sarilumab monotherapy (open-label) DMARD-IR patients 120

● Evaluation of use with or without DMARD (MTX)

2015

sarilumab monotherapy vs. Humira® MTX-IR, intolerant and inappropriate patients 340 2016

sarilumab + MTX Auto-injector real-life use 200 ● Assessment of pre-filled

syringe vs. autoinjector 2015

MOBILITY

EASY

MONARCH

ONE

EXTEND

ASCERTAIN

TARGET

MTX: Methotrexate DMARD-IR: Disease-Modifying Anti-Rheumatic Drugs Inadequate Responders Actemra® (tocilizumab) is marketed by Roche Humira® (adalimumab) is marketed by AbbVie

Significant Improvements in Signs and Symptoms of RA with Sarilumab(1)

SARIL-RA-MOBILITY - ACR Scores (% of Patients)

33

17 7

32

18*

9

58*

37*

20*

54*

40*

25*

66*

46*

25*

59* 53*

28*

ACR 20 ACR 50 ACR 70 ACR 20 ACR 50 ACR 70

Placebo + MTX Sarilumab 150mg + MTX Sarilumab 200mg + MTX

ACR Response at Week 24 ACR Response at Week 52

* p<0.0001 vs. placebo ** Co-primary endpoint (n=398) (n=400) (n=399)

**

ACR – American College Of Rheumatology (ACR) Scoring System (1) Clinically relevant and statistically significant improvements in both sarilumab groups compared to placebo in all three

co-primary endpoints: ACR 20, improvement of physical function and inhibition of progression of structural damage 131

SARIL-RA-MOBILITY - Change from Baseline in mTSS

* p<0.0001 vs Placebo Week

*

*

mTSS: modified

Total Sharp Score

Sarilumab: van der Heijde

modified Total Sharp Score

(0-448)

Inhibiting Progression of Structural Damage in RA with Sarilumab

70% 90%

132

3

2.5

2

1.5

1

0.5

0

0 13 26 36 52

Placebo + MTX

Sarilumab 150 mg + MTX

Sarilumab 200 mg + MTX

SARIL-RA-MOBILITY - Safety Data

Safety Findings Consistent with Prior Investigational Studies with Sarilumab

133

● Higher incidence of TEAEs leading to withdrawal

● Higher incidence of infections, the most frequently reported adverse events(1) ● Dose-dependent decrease in mean

neutrophil counts

● Serious infections not associated with grades 3 and 4 neutropenia in this study

● Increases in mean LDL-C and transaminases observed

TEAEs – Treatment Emergent Adverse Events (1) Sarilumab and placebo, both in combination with MTX

Placebo +MTX

2.3%

31.1%

Sarilumab 200mg +MTX

39.6%

2.6% 4.0%


40.1%

Infections of which serious infections

Placebo +MTX

4.7%


13.9%

Sarilumab 150mg + MTX

12.5% TEAEs leading to withdrawal

Rheumatoid Arthritis - Worldwide Sales of Biologics(1)

~$18bn

● Share of IL-6R inhibitors projected to increase four-fold to nearly 20% of the RA market by 2021 driven by expanded use and new entrants

● Blockbuster status reached with ~5% share

IL-6R 5%

IL-6R 19%

Further Establish the IL-6R Class in an $18bn Rheumatoid Arthritis Biologic Market

134

~$21bn

2013 2021

Anti-TNFα

Other(2)

IL-6R

(1) Decision Resources - Internal estimates (2) Other includes: JAK inhibitors, B Cell, Co-stimulation, IL-17, IL-1

Develop sarilumab to become the preferred IL-6R mAb

135 135

Agenda

135


Sarilumab

Dupilumab


PULMONOLOGY

Moderate-to-Severe Asthma

DERMATOLOGY

Moderate-to-Severe Atopic Dermatitis

OTOLARYNGOLOGY

Chronic Sinusitis with Nasal Polyps

Dupilumab is a fully human monoclonal antibody targeting IL-4Rα blocking intracellular signaling of both IL-4 and IL-13

Dupilumab Offers Potential to Change Management of Multiple Th2-Mediated Allergic Inflammatory Diseases

Dupilumab is developed in collaboration with Regeneron Th2: T-helper 2 cells, involved in “humoral-mediated” immunity 136

IL-4

IL-4Rα γc

Type I Receptor

Type II Receptor

IL-13

IL-4Rα IL-13Rα1

or

1

2

3

IL-4/IL-13 pathway may be a fundamental driver in allergic diseases

● >5m people in the U.S. and EU(1)

estimated to be affected by moderate-to-severe atopic dermatitis

● Characterized by eczematous dermatitis with intractable pruritus

● Current therapies often inadequate and associated with unwanted side effects ● 40% of moderate-to-severe patients

uncontrolled with topicals

137

Atopic Dermatitis (AD)

Atopic Dermatitis Is a Serious, Chronic, Inflammatory Skin Condition

137 (1) Adapted from White Book on Allergy published in 2011, http://www.worldallergy.org/UserFiles/file/WAO-White-Book-on-Allergy_web.pdf

Negative impact on QoL Similar or higher than

in psoriasis Determined by degree

of skin involvement, severity and localization

3

2

1

The Negative Impact of Atopic Dermatitis on Quality of Life Is Largely Underestimated

(1) Journal of Psychomatic Research 57 (2004) 195-200 (2) Acta Derm Venereol 2004;84(3):205-12 (3) Suicide Life Threat Behav 2006 2006 Feb;36(1):120-4 (4) J Allergy Clin Immunol 2006 Jul;118(1):226-32 138

Sleep disturbance and fatigue(4)

Greater risk for psychological distress • Mood disorders, such as anxiety and depression(1)

• Suicidal ideation(2,3)

Low self-esteem • Impact on social life

Dose-Dependent Efficacy in Adults with Moderate-to-Severe Atopic Dermatitis Uncontrolled by Topicals

139

Phase IIb Study in AD - Mean Percent Change in EASI

At Week 16 Over 16 Weeks

EASI=Eczema Area Severity Index IL-4Rα – Interleukin-4 receptor sub-unit α

-90

-80

-70

-60

-50

-40

-30

-20

-10

0Placebo

100 mgq4w

300 mgq4w

200 mgq2w

300 mgq2w

300 mgqw

p < 0.0001 vs placebo -90

-80

-70

-60

-50

-40

-30

-20

-10

00 2 4 6 8 10 12 14 16

Placebo

100mg q4w

300mg q4w 200mg q2w 300mg q2w 300mg qw p<0.0001 vs placebo at Week 16

All other time points p<0.05 vs placebo

Phase IIb Study in AD - Change in Efficacy Endpoints at 16 Weeks(1-5)

Parameter Placebo 300mg q2w 300mg qw

EASI Score 18% 68.2% 73.7% 50/75/90 EASI Improvement 29.5%/11.5%/3.3% 78.1%/53.1%/29.7% 82.5%/60.3%/36.5%

IGA Response 1.6% 29.7% 33.3%

Pruritus NRS 11.4% 52.9% 59.7% 5-D Pruritus

Score 8.2% 35.4% 43.6%

(1) Mean percent change in EASI (Eczema Area Severity Index) (2) Proportion of patients achieving EASI-50/70/90 (3) Proportion of patients achieving IGA ≤ 1 (Investigator’s Global Assessment score of 0 “clear” or 1 “almost clear”) (4) Mean percent change in pruritus NRS (Numeric Rating Scale) weekly averaged (5) Mean percent change 5-D Pruritus Score

Dupilumab Significantly Improved Signs and Symptoms in Moderate-to-Severe AD Patients Uncontrolled by Topicals

300mg qw and 300mg q2w dose regimens selected for Phase III program

140

p<0.0001 vs placebo for all parameters

Phase IIb Study in Moderate-to-Severe Atopic Dermatitis - Safety Data

Safety Findings in Moderate-to-Severe Atopic Dermatitis

141

21%

Placebo Dupilumab

23%

18.5%

Nasopharyngitis

8%

Placebo Dupilumab

15%

12%

Headache

3%

Dupilumab Placebo

9.5%

5%

Injection site reactions

● Nasopharyngitis, the most common adverse event, balanced across dupilumab treatment groups vs. placebo

● Headache and injection site reactions more frequent with dupilumab

Ongoing follow-up period of 16 weeks after treatment

LIBERTY - Phase III Clinical Program of Dupilumab in Moderate-to-Severe AD

Dupilumab Leads Development of Biologics in AD with Recent Start of Phase III Program

CHRONOS Combination with

topical corticosteroids in adults(1)

142

(1) CHRONOS study will assess efficacy of dupilumab in combination with topical corticosteroids through 16 weeks and long-term safety and efficacy of dupilumab up to 52 weeks, using 2 dosing regimens of dupilumab or placebo in 700 adult patients

(2) SOLO 1 and 2 studies will assess efficacy and safety of dupilumab as monotherapy in adults through 16 weeks using 2 dosing regimens of dupilumab and matching placebo in 600 adult patients each

(3) The Open-Label Extension (OLE) study will assess long-term safety and efficacy of repeat doses of dupilumab in adults who have previously participated in controlled studies of dupilumab

SOLO 1 SOLO 2 Monotherapy

in adults(2)

OLE Open-label

extension study in adults(3)

● 235-300m people worldwide estimated to be affected by asthma(1)

● ~25m people in the U.S. alone ● 10 to 20% of patients uncontrolled despite

existing therapies

● Chronic inflammatory disease leading to acute and chronic narrowing of the airway and increased mucus production

● Patients with asthma experience wheezing, shortness of breath, cough and chest tightness

143

Moderate-to-Severe Asthma

Moderate-to-Severe Asthma Negatively Impacts the Lives of Patients and Is Associated with High Burden to Society

143 (1) WHO, http://www.who.int/mediacentre/factsheets/fs307/en/

Dupilumab Shows Improvement in Lung Function in Phase IIb in Moderate-to-Severe Asthma

144

Phase IIb - Mean Improvement in FEV1 (mL and % Change from Baseline)

FEV1=forced expiratory volume over one second During the treatment period, patients continue their stable medium- or high-dose inhaled corticosteroid and long-acting beta agonist (ICS/LABA) combination product This result was based on a pre-specified interim analysis, which occurred when all patients had reached Week 12 of the 24-week treatment period

0

100

200

300

400

500

High Eosinophils Population Overall population

Placebo200mg Q2W300mg Q2W

10.4%

25.9%(1)

25.8%(2)

mL

18.0%(1) 17.7%(1)

6.2%

(1) p<0.001 vs placebo


Phase IIb: Annualized Rate of Severe Exacerbation Events

145

Dupilumab Shows a 64-75% Reduction in Exacerbations in Phase IIb in Moderate-to-Severe Asthma

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

High Eosinophils Population Overall population

Placebo200mg Q2W300mg Q2W

During the treatment period, patients continue their stable medium- or high-dose inhaled corticosteroid and long-acting beta agonist (ICS/LABA) combination product This result was based on a pre-specified interim analysis, which occurred when all patients had reached Week 12 of the 24-week treatment period

-75%(1)

-64%(1) -67%(2)

-67%(3)




0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

146

Safety Profile in Moderate-to-Severe Asthma

Phase III start in moderate-to-severe uncontrolled asthma expected in 2015

Phase IIb Study in Moderate-to-Severe Asthma - Safety Data

46%

Placebo Dupilumab

45% 42%

Infections

5%

Placebo Dupilumab

7%

3%

Severe AEs

12%

Dupilumab Placebo

25%

13%

Injection site reactions

● Injection site reaction was the most common adverse event and was more frequent with dupilumab ● Other common adverse events in the study included upper respiratory tract infection, headache,

nasopharyngitis and bronchitis ● Incidence of infections of serious adverse events was balanced across treatment groups

● CSwNP causes mucosal inflammation and polyps in the nasal cavity and sinuses ● Long-term symptoms of nasal obstruction and congestion

● Reduction in or loss of sense of smell

● Facial pain

● Many patients do not respond to intranasal corticosteroids

● In the U.S. alone, approximately 200,000 CSwNP patients have sinus surgery(2)

147

Chronic Sinusitis with Nasal Polyps (CSwNP)

Prevalence of Chronic Sinusitis with Nasal Polyps Is Estimated at 3% to 5% in EU and the U.S.(1)

147 (1) Adapted from White Book on Allergy published in 2011: http://www.worldallergy.org/definingthespecialty/white_book.php (2) Bhattacharyya 2010 otolaryngology head and neck surgery (2010) 143,147-151

http://www.google.fr/url?url=http://rhinitis.hawkelibrary.com/album12/143_G&rct=j&frm=1&q=&esrc=s&sa=U&ei=w81cVKS8AozzauKzgEA&ved=0CC4Q9QEwDDgo&usg=AFQjCNHrdqpcQ0yjM4Q218TQ624KXm-bDA

http://www.google.fr/url?url=http://rhinitis.hawkelibrary.com/album12/142_G&rct=j&frm=1&q=&esrc=s&sa=U&ei=ic9cVJPWKdLgaI6WguAP&ved=0CDwQ9QEwEzg8&usg=AFQjCNGxATQeShX5NU01Z-ybjABGbwYSFg

http://www.sinussurgeryprocedure.com/wp-content/uploads/2014/01/Nasal-polyp00.jpg

Dupilumab Delivers Positive Results in PoC Study in Patients with Nasal Polyposis and Chronic Symptoms of Sinusitis

148

Chronic Sinusitis

with Nasal Polyps(3)

(1) From baseline to week 16 / p<0.0001 (2) Sense of smell, congestion, postnasal drip, runny nose and sleep disturbance (3) Who do not respond to intra-nasal corticosteroids

● Strong efficacy of dupilumab 300mg qw vs. placebo, on top of Nasonex®

● Rapid, clinically and significant reduction size of nasal polyposis(1)

● Consistent improvement in measures of sinusitis by CT scan, nasal air flow and patient-reported symptoms(2)

● Most common AEs were injection site reactions, nasopharyngitis, oropharyngeal pain, epistaxis, headache and dizziness

Nasal Polyp Score (NPS)

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

Week Baseline 4 8 12 16

Placebo

Dupilumab

Mean change +/- SE

149

Dupilumab Has the Potential to Change Management of Patients Severely Affected by Various Allergic Diseases(1)

● Execute Phase III program in Atopic Dermatitis as first-in-class biologic

● Design Phase III program in Asthma to potentially position as best-in-class biologic

● Accelerate development in Chronic Sinusitis with Nasal Polyps

● Expand development program with new indications

1

2

3

4

(1) Atopic Dermatitis, Asthma, Nasal Polyposis

150 150

Agenda

150


Sarilumab

Dupilumab


New R&D Strategy Expected to Continue to Lead to Innovative New Medicines and Vaccines Reaching Market

151

Multiple new product launches underway or imminent

High potential late stage projects

Promising early stage development pipeline

Q&A

152

APPENDICES R&D Pipeline

153

154

Late Stage Pipeline – Pharma & Vaccines

LixiLan lixisenatide + insulin glargine Fixed-Ratio / Type 2 diabetes

alirocumab Anti-PCSK-9 mAb

Hypercholesterolemia

Dengue Mild-to-severe

dengue fever vaccine

Toujeo® (U300) Insulin glargine

Type 1+2 diabetes, U.S., EU

Lyxumia® (lixisenatide) GLP-1 agonist

Type 2 diabetes, U.S.

Kynamro® (mipomersen) Apolipoprotein B-100 antisense

Severe HeFH, U.S.

Clostridium difficile Toxoid vaccine

Lemtrada® (alemtuzumab) Anti-CD52 mAb

Multiple sclerosis, U.S.

sarilumab Anti-IL-6R mAb

Rheumatoid arthritis

Jevtana® (cabazitaxel) Metastatic prostate cancer (1L)

Rotavirus Live attenuated tetravalent

Rotavirus oral vaccine

Cerdelga™ (eliglustat tartrate) Glucosylceramide synthetase inhibitor

Gaucher disease, EU

dupilumab Anti-IL4Rα mAb Atopic dermatitis

SYNVISC-ONE®

Medical device Pain in hip OA

VaxiGrip® QIV IM Quadrivalent inactivated

influenza vaccine

PR5i DTP-HepB-Polio-Hib

Pediatric hexavalent vaccine, U.S.

patisiran mRNA inhibitor

Familial amyloid polyneuropathy

Fluzone® QIV ID Quadrivalent inactivated

influenza vaccine intradermal

Quadracel® Diphtheria, tetanus, pertussis & polio vaccine; 4-6 y of age

N

154

N

N

N

N New Molecular Entity Immune Mediated Diseases

Rare Diseases

Oncology Diabetes Solutions

Vaccines Infectious Diseases Cardiovascular / Renal Diseases

Age Related Degenerative Diseases

Ophthalmology

Biosurgery

N

Phase III Registration

N

N

Early Stage Pipeline – Pharma & Vaccines

dupilumab Anti-IL4Rα mAb

Asthma; Nasal polyposis

SAR391786 Anti-GDF8 mAb

Sarcopenia

Rabies VRVg Purified vero rabies vaccine

vatelizumab Anti-VLA 2 mAb Multiple sclerosis

SAR650984 Anti-CD38 naked mAb

Multiple myeloma

Meningitis ACYW conj. 2nd generation meningococcal

conjugate infant vaccine

SAR156597 IL4/IL13 Bi-specific mAb

Idiopathic pulmonary fibrosis

SAR3419 Maytansin-loaded anti-CD19 mAb

B-cell refractory/relapsed malignancies

Tuberculosis Recombinant subunit vaccine

SAR438714 (ALN-TTRsc) RNAi

Familial amyloid cardiomyopathy

Combination SAR245409 (XL765) / MSC1936369B Oral dual inhibitor of PI3K & mTOR / pimasertib

Ovarian cancer

sarilumab Anti-IL-6R mAb

Uveitis

Combination ferroquine / OZ439

Antimalarial Malaria

fresolimumab TGFβ antagonist

Focal segmental glomerulosclerosis

Phase II

N

N

N

N

N

155

N

155

N


Rare Diseases




Ophthalmology

Biosurgery

N

N

Early Stage Pipeline – Pharma & Vaccines

SAR405838 (MI-773) HDM2 / p53 antagonist

Solid tumors

SAR408701 Anti-CEACAM5 ADC

Solid tumors

GZ402663 (sFLT-01) Gene therapy

Age-related macular degeneration (AMD)

Streptococcus pneumonia Meningitis & pneumonia vaccine

SAR566658 Maytansin-loaded anti-CA6 mAb

Solid tumors

SAR113244 Anti-CXCR5 mAb

Systemic lupus erythematosus

StarGen® Gene therapy

Stargardt disease

Herpes Simplex Virus Type 2 HSV-2 vaccine

SAR125844 C-MET kinase inhibitor

Solid tumors

SAR252067 Anti-LIGHT mAb Crohn’s disease

UshStat® Gene therapy

Usher syndrome 1B

SAR260301 PI3K β selective inhibitor PTEN – Deficient tumors

SAR228810 Anti-protofibrillar AB mAb

Alzheimer’s disease

GZ402665 (rhASM)

Niemann-Pick type B

SAR307746 Anti-ANG2 mAb

Solid tumors

SAR425899 GLP-1 / GCGR agonist

Diabetes

GZ402671 Oral GCS Inhibitor

Fabry Disease

SAR245408 (XL147) Oral PI3K inhibitor

Solid tumors

SAR342434 Insulin Lispro

Diabetes

GZ402666 neo GAA

Pompe Disease

Combination SAR405838 / MSC1936369B

Solid tumors

SAR438584 (REGN2222) anti-RSV-F protein mAb

Respiratory syncytial virus

Phase I N

N

N

N

N

N

N

N

N N

N N

156 156

N

N


Rare Diseases




Ophthalmology

Biosurgery

N

N

N

N

157

Phase I Phase II Phase III Registration TOTAL

Oncology 7 3 0 0 10

Diabetes Solutions 1 0 1 1 3

Cardiovascular / Renal Diseases 0 1 1 0 2

Immune Mediated Diseases 2 2 2 0 6

Infectious Diseases 1 1 0 0 2

Ophthalmology 3 0 0 0 3

Rare Diseases 3 1 1 1 6

Age Related Degenerative Diseases 1 1 0 0 2

Vaccines 2 3 4 3 12

TOTAL 20 12 9 5

R&D Pipeline Summary Table(1)

32 14 NMEs & Vaccines

46

157

34

(1) Excluding life cycle management programs

158

Expected R&D Milestones

158

Product Event Timing New Insulin Lispro (SAR342434) Expected start of Phase III trial in Diabetes Q4 2014

Praluent™ (alirocumab) Expected U.S. and EU regulatory submissions in Hypercholesterolemia Q4 2014

Fluzone® QIV ID Expected U.S. regulatory decision Q4 2014

Fluzone® High Dose Expected U.S. label upgrade Q4 2014

Cerdelga™ (eliglustat tartrate) Expected EU regulatory decision in Gaucher disease Q1 2015

PR5i (DTP-HepB-Polio-Hib) Expected EU regulatory submission Q1 2015

Quadracel® Expected U.S. regulatory decision Q1 2015

Toujeo® (U300) Expected U.S. regulatory decision in Diabetes Q1 2015

Dengue vaccine Expected regulatory submission in endemic countries H1 2015

Toujeo® (U300) Expected EU regulatory decision in Diabetes Q2 2015

Lyxumia® (lixisenatide) Expected ELIXA CV outcome trial top-line results Q2 2015

Dupilumab Expected start of Phase III trial in Asthma Q2 2015

159

Expected R&D Milestones (cont’d)

159

Product Event Timing Praluent™ (alirocumab) Expected U.S. regulatory decision in Hypercholesterolemia Q3 2015

PR5i (DTP-HepB-Polio-Hib) Expected U.S. regulatory decision Q3 2015

LixiLan Expected Phase III top line results in Diabetes Q3 2015

Lyxumia® (lixisenatide) Expected U.S. regulatory submission in Diabetes Q3 2015

Sarilumab Expected Phase III top line results in Rheumatoid Arthritis H2 2015

Dengue vaccine Expected regulatory decision in endemic countries Q4 2015

LixiLan Expected U.S. and EU regulatory submissions in Diabetes Q4 2015

Sarilumab Expected U.S. regulatory submission in Rheumatoid Arthritis Q4 2015

APPENDICES Regeneron Agreement Financial Terms

160

Antibodies Collaboration Agreement with Regeneron

● In November 2007, Sanofi and Regeneron entered into a global collaboration to discover, develop and commercialize fully human monoclonal antibodies.

● The collaboration is governed by a Discovery and Preclinical Development Agreement and a License and Collaboration Agreement (each as amended in November 2009).

● In January 2014, Sanofi and Regeneron agreed to amend and restate the original investor agreement. The Amended Investor Agreement was amended to, among other things, provide Sanofi with the right to nominate a single independent director to the Regeneron Board of Directors upon reaching 20% ownership of Regeneron's outstanding Share Capital and to extend the term of the lock-up obligations.

161

Discovery and Development Activities with Regeneron

● Regeneron leads the antibody discovery activities to identify and validate potential drug discovery targets and develop fully human monoclonal antibodies against these targets.

● In return, Sanofi funded $120 million per year for 2007 through 2009 and will fund up to $160 million per year of Regeneron’s antibody discovery activities from 2010 through 2017

● Sanofi has an option to extend certain antibody development and preclinical activities for up to an additional three years after 2017.

162

Discovery activities

Development activities

● For each drug candidate identified through discovery research under the discovery agreement which advances to an IND filing, Sanofi has the option to license rights to the candidate under the license agreement. If Sanofi elects to do so, Sanofi co-develops the drug candidate with Regeneron through product approval.

● Development costs for the drug candidate are generally funded up front by Sanofi, except that following receipt of the first positive Phase III trial results for a co-developed drug candidate, subsequent Phase III trial-related costs for that drug candidate are funded 80% by Sanofi and 20% by Regeneron.

● Regeneron is responsible for reimbursing Sanofi for half of the total development costs for all collaboration antibody products from their share of profits from commercialization of collaboration products; limited to 10% of their share of profits from commercialization of collaboration products in any calendar quarter.

● The discovery fees as well as the total development costs for all collaboration antibody products are booked under the “Research and development expenses” P&L line.

● The reimbursement to be received from Regeneron for half of the total development costs for all collaboration antibody products will be booked under the “Research and development expenses” P&L line.

Accounting treatment in Sanofi’s income statements

Commercial Activities with Regeneron

163

● Sanofi leads commercialization activities for products developed under the license agreement, subject to Regeneron’s right to copromote such products.

● In the event that Regeneron desires to copromote in a particular country, Regeneron’s copromotion effort shall be between 25% and 50% of the anticipated total effort.

● Sanofi and Regeneron share profits and losses from sales. ● Within the United States, Sanofi and Regeneron share equally profits and

losses. ● Outside the United States, Sanofi and Regeneron share profits on a sliding

scale based on sales starting at 65% (Sanofi) / 35% (Regeneron) and ending at 55% (Sanofi) / 45% (Regeneron), and share losses at 55% (Sanofi) / 45% (Regeneron).

● In addition to profit sharing, Sanofi is required to pay to Regeneron up to $250 million in sales milestone payments, with milestone payments commencing after aggregate annual sales outside the United States exceed $1.0 billion on a rolling 12-month basis.

● If Sanofi does not exercise its licensing option for an antibody under development, Sanofi would be entitled to receive a royalty once the antibody begins to be marketed.

Commercial activities

● The sales will be booked by Sanofi solely and the commercial costs incurred by Sanofi are booked under the “Selling and general expenses” P&L line.

● Regeneron share of net profit or loss is recognized under the “Other operating income and expenses” P&L line.


Record of Sanofi Holding in Regeneron

164

● Pursuant to the Amended and Restated Investor Agreement, Sanofi has purchased additional shares of Common Stock to increase its beneficial ownership to approximately 22% of the Common Stock outstanding.

● Sanofi has recorded under the “Share of profits from associates” P&L line its holding in Regeneron (approximately 22%) accounted for using the equity method since beginning of April as follows ● Segment operating result (BOI) includes the share of Regeneron net profit (IFRS restated) before

• acquisition-related effects (workdown of acquired inventories and intangible assets remeasured at fair value at the acquisition date) and dilution impact due to stock option exercises

● Net income additionally includes:

• Workdown inventory step-up, after tax

• Amortization intangible step-up, after tax

• Dilution impact due to stock option exercises


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