2012/06 - ir - diabetes

IR Thematic Conference Call on Diabetes

June 12th, 2012

2

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 labelling 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, 2011. Other than as required by applicable law, Sanofi

does not undertake any obligation to update or revise any forward-looking information or statements.

3

Agenda

3

ORIGIN – A Landmark Study

● Matthew C. Riddle, Professor of Medicine - Oregon Health & Science University

ORIGIN Steering Committee Member

Retrospective Cohort Studies on Insulin and Cancer Risk

● Peter Boyle, DSc FRCP FRCPS FMedSci - International Prevention Research Institute, Lyon

Principal Investigator, Northern European Database Study

Lyxumia® (lixisenatide) – An Ideal Profile in Combination with Basal Insulin

● Riccardo Perfetti, MD - Vice President Global Medical Affairs, Sanofi Diabetes

Sanofi – A Long-term Commitment to Fighting Diabetes

● Pierre Chancel - Senior Vice President, Sanofi Diabetes

Q&A Session

ORIGIN – A Landmark Study

Matthew C. Riddle, Professor of Medicine

Oregon Health & Science University

ORIGIN Steering Committee Member

4

Summary of Findings

Compared to standard glycemic care of people

with early diabetes, IGT and/or IFG … using once

daily basal insulin glargine to target a FPG < 95

mg/dl (5.3 mmol/l) for a median of 6.2 years ...

• Maintains near-normal glycemic control

• Has a neutral effect on CV outcomes and on cancers

• Slows progression of dysglycemia

• Modestly increases hypoglycemia

• Modestly increases weight

5

Baseline Glycemia (N=12,537)

N %

Prior Diabetes (for ~ 5.4 y) 10321 82

New Diabetes 760 6

IFG and/or IGT 1452 12

No G Drug 5052 40

Metformin 3435 27

Sulfonylurea 3711 30

Other G Drug 351 3

Median FPG 125 mg/dl 6.9 mM

Median A1C 6.4% 6

Glycemic Levels Over 7 Years: A1c

7

Summary of Findings

• 1st CV Composite: HR = 1.02 (0.94, 1.11)

• 2nd CV Composite: HR = 1.04 (0.97, 1.11)

• Microvascular Composite: HR = 0.97 (0.90, 1.05)

• Death: HR = 0.98 (0.90, 1.08)

• Cancer: HR = 1.00 (0.88, 1.13)

• Conversion IFG/IGT to DM: HR = 0.72 (0.58, 0.91) P=0.006

8

Implications of Findings

• Supplementing endogenous insulin with basal insulin

injections slows progression of dysglycemia

• Although later benefits or harms cannot be ruled out

exogenous basal insulin’s main effect over 6-7 years

is to flexibly lower glucose

• Despite lower glucose levels, routine early use of basal

insulin glargine is not better than guideline-based

standard care in limiting serious health outcomes

• Basal insulin glargine is now the best-studied glucose-

lowering drug available and no new safety concerns

limit early use when needed

9

Retrospective Cohort Studies

on Insulin and Cancer Risk

Peter Boyle, DSc FRCP FRCPS FMedSci

International Prevention Research Institute, Lyon

Principal Investigator, Northern European

Database Study

10 © iPRI – International Prevention Research Institute www.i-pri.org

Northern European Database Study of Insulin and

Cancer Risk

A total of 17,800 cancers of all forms, excluding non-melanoma skin cancer, were detected in 447,821 users of insulin since glargine was introduced into the individual countries

The study generated over 1.5 million person-years of exposure to insulin. There was an average of 3.1 years of follow-up for patients using glargine

While the study size, and hence the statistical power and the quality of the individual registries are impressive, this study shares important limitations in common with other studies of this type

Notable among these is the lack of information as to why specific treatments were prescribed for individual patients and why treatments were changed

11

© iPRI – International Prevention Research Institute www.i-pri.org

Three Primary Hypotheses were identified by the

CHMP: to compare the risk of

(1) breast cancer in women

(2) prostate cancer in men

(3) colorectal cancer in men and women, who

were prescribed insulin glargine versus those

prescribed human insulin and in all users of

insulin combined

This study found no evidence of an increased risk

of any of these forms of cancer in all users of

insulin glargine or among users of human insulin

Northern European Study: Summary and

Conclusions – Glargine and Cancer Risk


Secondary objectives focused on comparing the

risk of all forms of cancer combined (excluding

non-melanoma skin cancer but including

haematological malignancies) in adults

prescribed insulin glargine versus those

prescribed human insulin and in all users of

insulin combined

There was no evidence of an increased risk of

cancer of all forms found in this study when

users of insulin glargine were compared to other

insulins




A number of Exploratory Objectives included

comparing the risk of lung cancer and pancreatic

cancer between adults prescribed insulin glargine

and other insulins

The study found no indication of a risk increase of

these forms of cancer with use of glargine

In addition,

no difference was found between the effects of insulin glargine

on cancer risk and those of other long-acting insulins

no effect of metformin associated with the risk of the forms of

cancer considered in this study

no effect of adjusting for confounders including Body Mass

Index (BMI) and tobacco smoking




Summary and Conclusions

The Northern European Study of Insulin and

Cancer is the largest study of its type and was

based on methodology correcting for flaws

seen in previous studies

There has been no causal association

demonstrated between glargine use and

increased cancer risk in the Northern European

Database Study of Insulin and Cancer

© iPRI – International Prevention Research Institute www.i-pri.org

15

Studies of Glargine and Malignancy

21 Independent Estimates

1 million patients with diabetes

3 million person-years of observation


Glargine and Cancer Risk

Previous

Meta-analysis

Northern

European

Update

Meta-analysis

All Cancers 0.88 (0.79, 0.97) 0.98 (0.94, 1.03) 0.91 (0.84, 0.99)

Breast 1.16 (0.97, 1.39) 1.12 (0.99, 1.27) 1.11 (1.00, 1.24)

Breast-new user 0.87 (0.27, 2.80) 1.29 (1.01, 1.63) 1.22 (1.00, 1.48)

Colorectal 0.73 (0.59, 0.91) 0.86 (0.76, 0.98) 0.83 (0.74, 0.94)

Prostate 1.22 (0.99, 1.50) 1.11 (1.00, 1.24) 1.14 (0.93, 1.39)

Lung 0.97 (0.85, 1.11) 0.97 (0.85, 1.11)

Pancreas 0.99 (0.82, 1.20) 0.99 (0.82, 1.20)


Summary and Conclusions

Based on findings from 21 independent

studies involving one million patients and 3

million person-years of exposure, it has not

been possible to identify any increased risk

in any form of cancer among glargine users

compared to those patients who use other

insulins


Lyxumia® (lixisenatide)

An Ideal Profile in Combination

with Basal Insulin

Riccardo Perfetti, MD

Vice President Global Medical Affairs, Sanofi Diabetes

19

A GLP-1 Agonist for A1c Control with a Unique Biological Profile

Lyxumia® is the intended trademark for lixisenatide. Lixisenatide is currently not approved or licensed anywhere in the world.

Lixisenatide was in-licensed from Zealand Pharma A/S.

(1) Except for the device intended for Japan (2 steps to maintenance dose with one pen) 20

Pronounced effect on postprandial glucose (PPG) levels

Favorable safety profile with low risk of hypoglycemic events

Once-daily injection, simple 1 step to maintenance dose, 1 pen per dose(1)

A Unique Profile:

®

Fasting and Prandial Glycemia Contribute to A1c

21

Time of day

Glu

co

se

(m

mo

l/L

)

22.2

16.6

11.1

5.5

0

06:00 06:00 hrs 10:00 14:00 18:00 22:00 02:00

Diabetic

T2

Diabetic

T2

Meals

Jay Skyler, adapted from Polonsky et al, N Engl J Med 1988

T2D

Not Treated

T2D on Basal Excursion of Blood

Glucose Still Not

Fully Covered

Normal Subjects

T2D Patients Treated

with Basal Insulin(1) (worldwide)

On basal insulin On basal insulin

with controlled fasting

glucose control

but A1c >7%

4 million on other

basal insulins(2)

4 million on Lantus®

4 million

T2D – Type 2 Diabetes A1C – HbA1c or Glycated hemoglobin

(1) Adapted from IMS data (2) Includes all types of basal insulins

Clinical Development Designed to Support Use in Combination with Basal Insulin

®

22

Mono

Mono Japan Monotherapy

Placebo-controlled

in OAD failure M (metformin)

F1 (metformin)

M Asia (metformin)

S (sulfonylurea)

P (pioglitazone)

X vs. exenatide Active-controlled

L Asia

L Placebo-controlled

on top of

basal insulin Duo 1

Phase III Program

GetGoal-L & -L Asia: Primary Objective of A1c Change Met

with Lixisenatide on top of Basal Insulin +/- Orals

23

-5 0 5 10 15 20 25

8.6

8.4

8.2

8.0

7.8

7.6

7.4

7.2

7.0

- 8

- 6

- 4

- 2

0

Placebo

(n=123))

-1.72

Lixisenatide

(n=235)

-5.54

2-hour PPG

LS

mean c

hange (

mm

ol/L)

Mean A

1c (

%)

Week

(1) Lixisenatide on top of basal insulin (Lantus® 50.1% of pts) +/- metformin

Duration of T2DM at screening Lixisenatide (L) 12.5 years / Placebo (P) 12.4 years

BMI (kg/m2) at baseline L 31.9/ P 32.6 – Lantus® dose at baseline L 54.0U / P 57.6U

MC Riddle, ADA 2012 (abstract 983-P)

Mean A1c (%) by visit

Lixisenatide

(n=304)

Placebo (n=158)

Week

Mean A

1c (

%)

- 8

- 6

- 4

- 2

0

-7.96

Placebo

(n=142))

-0.14

Lixisenatide

(n=131)

2-hour PPG

(2) Lixisenatide on top of basal insulin (Lantus® 60% of pts) +/- sulfonylurea

Duration of T2DM at screening L 13.7 years / P 14.1 years

BMI (kg/m2 ) at baseline L 25.4 / P 25.2 – Lantus® dose at baseline L 24.9U / P 24.1U

Y Seino, et al. Diabetes, Obesity and Metabolism online, May 30, 2012

LS

mean c

hange (

mm

ol/L)

GetGoal-L(1) GetGoal-L Asia(2)


LS mean difference lixisenatide vs placebo =

-0.36% (95% CI -0.550, -0.174 ; p=0.0002)

P<0.0001 vs

Placebo

-0.38%

-0.74%

+0.11%

-0.77%

LS mean difference lixisenatide vs placebo =

-0.88% (95% CI -1.116, -0,650 ; p<0.0001)

P<0.0001 vs

Placebo

-5 0 5 10 15 20 25

8.4

8.6

8.2

8.0

7.8

7.6

7.4

7.2

7.0

Lixisenatide

(n=146)

Placebo (n=154)

c

GetGoal Duo 1: Significant A1c & PPG Reduction Achieved with

Lixisenatide on top of Lantus® in T2D Uncontrolled with Orals

24

Lantus ®

+ Metfomin (+/- TZDs)

Lantus ® + Metformin (+/- TZDs)

+ Lixisenatide OR Placebo

-1.0

-2.0

-3.0

Placebo

(n=204)

0.08

Lixisenatide

(n=194)

-3.09

0.0

2-hour PPG

LS mean change in 2-hour postprandial plasma

glucose (mmol/L) from baseline to Week 24

LS

mean c

hange (

mm

ol/L)

Mean A

1c (

%)

Week


p<0.0001 vs

placebo

7.30%

6.96%

Screen

Duration of T2D at screening: Lixisenatide (L) 9,6 years / Placebo (P) 8,7 years – BMI (kg/m2) at baseline: L 32.0 / P 31.7 – Lantus® dose at baseline L 43.4U / P 44.2U

LS mean difference L vs P in body weight (kg) change from baseline to endpoint: -0,89 (95%CI: -1.42 to -0.35 ; p=0.0012)

LS mean difference L vs P in Lantus® dose from baseline to endpoint: -2.24U (95%CI: -4.26 to -0.22 ; p=0.03) J. Rosenstock, ADA 2012 (abstract 62-OR)

(n=221) (n=215)

16 8 Baseline -12 24

8.6

7.4

7.0

6.6

8.2

7.8

Lixisenatide Placebo

- 30

0

30

60

90

3.5 2.5 2.0 1.5 1.0 0.45 0.5 4.5

Postprandial glucose excursion after a standardized breakfast test in patients with type 2 diabetes

inadequately controlled with metformin (n=143) – Adapted from Kapitza C., IDF 2011 (Poster D-0740)

(1) ClinicalTrials.gov identifier: NCT01596504

Optimal Complementary Pharmacological Profile with Basal Insulins

25

More Pronounced Effect on Postprandial Glucose

With Lixisenatide vs. Liraglutide

Mean C

hange f

rom

Pre

meal

Pla

sm

a G

lucose (

mg/d

L)

Time after Study Drug Administration GLP-1

Agonist

Meal

Lixisenatide

Liraglutide

Day -1

(full lines)

Day 28

(dotted lines)

®

c Lixisenatide OR liraglutide

on top of Lantus® after a

standardized breakfast

Target randomization: 140 patients

New study ongoing in

patients on basal insulin(1)

Expected EU regulatory decision in Q4 2012(1)

Recent submission in Japan on June 11th, 2012

CV outcomes study ongoing(2)

● 6,000 T2D patients with a recent ACS event

● Event driven completion

● On track to deliver necessary data to support U.S. filing

U.S. submission planned in Q4 2012

Regulatory Submission on Track

(1) Submitted in EU in October 2011 (EMA acknowledged receipt of the MAA filing in November 2011)

(2) ClinicalTrials.gov identifier: NCT01147250 26

®

Next steps

Fix-Flex Device Has Been Developed for Joint

Administration of Lantus® and Lyxumia®

● Convenience of a single injection

per day coupled with possibility

to adjust Lantus® dose

● Entering phases for

industrialization, validation,

usability and manufacturing

● Device expected to be available

mid-2013 for Phase III initiation

+ ®

Lyxumia® is the intended trademark for lixisenatide. Lixisenatide is currently not approved or licensed anywhere in the world. 27

Sanofi – A Long Term Commitment

to Fighting Diabetes

Pierre Chancel

Senior Vice President - Sanofi Diabetes

28

Diabetes Remains One of the Largest Opportunities

in the Healthcare Space

Adults with diabetes worldwide(1) 350m

% of patients not achieving glycemic control target values in the U.S. and EU(2) >50%

Patients remaining undiagnosed in BRIC countries(3) ~2/3

Expected size of global diabetes market in 2015(4) $43-48bn

Expected CAGR growth of global diabetes market between 2011 and 2015(4) 4-7%

29

(1) G. Danaei, Lancet 2011; 378: 31-40

(2) Adelphi Disease Specific Program (DSP) III and VII (sample of over 10,000 diabetic patient records)

(3) Internal estimates based on multiple sources

(4) The Global Use of Medicines: Outlook through 2015, IMS Institute for Healthcare Informatics, May 2011

Lantus® is the Leading Insulin in the Leading Segment

NovoRapid® Humalog®

Family

NovoMix® Levemir®

Apidra®

(1) Sales reported by originator companies in their FY2011 reports and converted into EURO using USD/EURO of 1,3917 and DKK/EUR of 7,4507

€3.9bn

€1.7bn €1.7bn

€1.1bn €1.0bn

€190m

Basal

Fast Acting

Premix

30

48%+17%

38%+17%

14%+9%

46%+6%

35%+3%

19%-4%

43%+24%

19%+14%

38% +15%

38%+11%

32%+6%

30%-3%

Basal Insulins Constitute the Leading and Fastest

Growing Insulin Segment

Basal

Premix

Short Acting

31

2011 Insulin Market Breakdown by Insulin Type (Value) Market Share (%)

Growth vs. prior year (%)

Western Europe: France, Germany, UK, Italy, Spain, Greece, Cyprus, Malta, Belgium, Luxembourg, Portugal, Netherlands, Austria, Switzerland,

Sweden, Ireland, Finland, Norway, Iceland, Denmark

Emerging Markets: World less the U.S. and Canada, Western Europe, Japan, Australia and New Zealand

Others: Japan, Canada, Australia and New Zealand Source: IMS Q_Global 12/2011

U.S. Western

Europe

Emerging

Markets

Japan/Can

Aus/NZ

37%+14%

37%+16%

26%+19%

Sanofi Holds a Strong Position Among Insulin Players

2011 Insulin Market Share by Insulin Player (Value) Market Share (%)

Growth vs. prior year (%)

Novo

Sanofi

46%+1%

33%+7%

15%+5%

6%-8%

47%+16%

25%+22%

19%+14%

9%+28%

56% -1%25%

+24%

19%+3%

32

Lilly

Others

Western Europe: France, Germany, UK, Italy, Spain, Greece, Cyprus, Malta, Belgium, Luxembourg, Portugal, Netherlands, Austria, Switzerland,

Sweden, Ireland, Finland, Norway, Iceland, Denmark

Emerging Markets: World less the U.S. and Canada, Western Europe, Japan, Australia and New Zealand

Others: Japan, Canada, Australia and New Zealand Source: IMS Q_Global 12/2011

U.S. Western

Europe

Emerging

Markets

Japan/Can

Aus/NZ

From Lantus® Brand to Lantus®-based Solutions

33

● Encouraging launches

in most EU countries

● Q1 2012 sales of €6m

● Launched in the U.S.

in May 2012

/

● Majority of U.S. patients on

Lantus® expected to use

SoloSTAR® by 2015

● Accounted for >50% of U.S. sales in Q1 2012

New Glargine Formulation with Unique Pharmacokinetics

● New glargine formulation: ● Unique flat PK/PD profile

● Lower injection volume

● Phase III trials ongoing in T2D

high-dose insulin users(1)

● Targeting ~1,600 patients

● Second set of studies expected to start in H2 2012

EDITION I

T2D Patients

Basal Bolus

EDITION II

T2D Patients

Basal + OAD

PK/PD – Pharmacokinetic/Pharmacodynamic OAD – Oral anti-diabetic drugs

(1) ClinicalTrials.gov Identifier: NCT1499082 & NCT01499095

New Insulin Glargine Formulation Depot formation after subcutaneous injection

Schematic illustration

Lantus® New Glargine

Formulation

34

Sanofi – A Long-term Commitment to Fighting Diabetes

ORIGIN - Lantus®: neutral effect on CV outcomes, delayed progression

from pre-diabetes to type 2 diabetes, targeted long-term glycemic control

achieved, no association between insulin glargine use and increased risk

of any cancer

Large-scale epidemiological studies: safety profile of Lantus® further

reinforced

Lyxumia®: a new tool for A1c control with a unique biological effect

Multiple initiatives to further develop Lantus® family (e.g. new formulation,

GLP-1 combination) and offer patient centric solutions (e.g. pen devices,

BGM systems)

1

2

3

4

35

Q&A Session

36

2012/06 - ir - diabetes

Documents

forwardlooking statements

forwardlooking information

endogenous insulin

basal insulininjections

g drug

control of sanofi

cancer riskpeter boyle

cancer risk peter boyle