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2012 - JP Morgan Multiple Sclerosis Event
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J.P. Morgan Cazenove Therapeutic SeminarDavid Meeker - CEO, Genzyme
June 25, 2012
Jannan, MS
2
Forward Looking Statements
This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of1995, as amended. Forward-looking statements are statements that are not historical facts. These statementsinclude projections and estimates and their underlying assumptions, statements regarding plans, objectives,intentions and expectations with respect to future financial results, events, operations, services, productdevelopment and potential, and statements regarding future performance. Forward-looking statements aregenerally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similarexpressions. Although Sanofi’s management believes that the expectations reflected in such forward-lookingstatements are reasonable, investors are cautioned that forward-looking information and statements are subjectto 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 orprojected by, the forward-looking information and statements. These risks and uncertainties include among otherthings, the uncertainties inherent in research and development, future clinical data and analysis, including postmarketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when toapprove any drug, device or biological application that may be filed for any such product candidates as well astheir decisions regarding labelling and other matters that could affect the availability or commercial potential ofsuch product candidates, the absence of guarantee that the product candidates if approved will be commerciallysuccessful, the future approval and commercial success of therapeutic alternatives, the Group’s ability to benefitfrom external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of costcontainment policies and subsequent changes thereto, the average number of shares outstanding as well asthose discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listedunder “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annualreport on Form 20-F for the year ended December 31, 2011. Other than as required by applicable law, Sanofidoes not undertake any obligation to update or revise any forward-looking information or statements.
3
1. Key Highlights on MS Market & Genzyme
2. The Aubagio™ Opportunity
3. The Lemtrada™ Opportunity
4. Summary
Agenda
Aubagio™ is the trademark submitted to health authorities for the investigational agent teriflumomideLemtrada™ is the trademark submitted to health authorities for the investigational agent alemtuzumab
KEY HIGHLIGHTSON MULTIPLE SCLEROSIS MARKET& GENZYME
4
5
Global MS Market - Significant and Expected to Grow
Key Facts about MS
● ~2.1m patients worldwide(1)
● Prevalent in young women (~2.1 female/male ratio)
● Life expectancy 5-10 years lower than unaffected people
● A major impact on family, social and professional life
● Symptoms include fatigue, weakness, walking and balance difficulties, vision problems
Multiple Sclerosis
(1) National Multiple Sclerosis Society(2) 2011: Reported sales of Copaxone®, Avonex®, Rebif®, Betaseron/Betaferon®, Extavia®, Tysabri®, and Gilenya®
(3) 2016e: Adapted from Evaluate Pharma report - December 2011
Multiple Sclerosis Market Global Sales(2,3)
CAGR >6%
2011 2016e
U.S.
ROW
56%
54%
44%46%
$12.5bn
$17.8bn
Key Facts about MSMS Therapies
Global MS Market - Still Dominated by ABCRE Products
6
(1) ABCRE stands for Avonex®, Betaseron®/Betaferon®, Copaxone®, Rebif® and Extavia® . Avonex® is a registered trademark of Biogen Idec; Betaseron® is a registered trademarks of Bayer Healthcare; Copaxone® is a registered trademark of Teva Pharmaceuticals Inc; Gilenya® is a registered trademark of Novartis; Rebif® is a registered trademark of EMD Serono, Inc.; Tysabri® is a registered trademark of Biogen Idec.
(2) Reported sales of ABCRE products plus Tysabri®, and Gilenya® in 2011
● “ABCRE” products(1) represented 84% of the global MS market in value in 2011
● Moderate efficacy and patients continue to relapse on therapy
● Require frequent injections
● Latest entrants represent treatment alternatives
● Drives the benefit vs. risk discussion
$3,884m31%
$2,686m21%
$1,553m12%
$494m4%
$2,350m19%
$1,511m12%
2011 Sales and Market Share in Value(2)
$154m1%
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Lemtrada™
Aubagio®Rebif®
Lemtrada™
Aubagio™
(1) CIS – Clinically Isolated Syndrome, TOPIC Phase III study presently ongoing (2) RRMS – Relapse Remitting Multiple Sclerosis(3) RMS – Relapsing Multiple Sclerosis 7
Emergence of a Franchise Addressing Individual Needs for People Living with MS
Unmet need 3
Efficacy with manageable safety
Unmet need 2
Convenience, efficacy & safety
Early MS/CIS(1) RRMS(2) and early active MS
RMS(3) severe/ highly active
Unmet need 1
Convenience& safety
- Key Milestones Complete
● CARE-MS I Data Presentation
● CARE-MS II Data Presentation
● FDA & EMA Regulatory Submissions
● TEMSO Data Presentations
● TENERE/TOWER Headline Results
● FDA & EMA Regulatory Submissions
8
The Aubagio™ Opportunity
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10(1) Adjusted for Expanded Disability Status Scale score strata and region at baseline and takes duration of treatment into account
Once-Daily Oral Therapy Solid Reduction of Relapse Rates
TEMSO STUDY TOWER STUDYAnnualized Relapse Rate(1)
Placebo
- 31.5%p=0.0005
Aubagio™
14mg
n=370
Placebo Aubagio™
14mg
0.539
0.3190.369
0.501
n=363 n=359 n=388
Annualized Relapse Rate(1)
- 36.3%p=0.0001
11(1) At Week 108(2) Derived using Cox proportional hazard model with treatment, EDSS strata at baseline and region as covariates(3) Derived from log-rank test with stratification of EDSS strata at baseline and region
First Oral Therapy to Show Positive Results in Two Phase III Trials
TEMSO STUDY TOWER STUDYReduction in Progression of
Disability(1)
Placebo
-29.8%(2)p=0.0279(3)
Aubagio™
14mgPlacebo Aubagio™
14mg
0.273
0.1580.202 0.197
-31.5%(2)p=0.0442(3)
Reduction in Progression of Disability(1)
12(1) Adjusted for Expanded Disability Status Scale score strata and region at baseline and takes duration of treatment into account
“Interferon-like” Efficacy Observed in TENERE Study
TENERE STUDY
Rebif®
p=ns
Aubagio™
14mg
n=104
0.2590.216
n=109
Annualized Relapse Rate(1)
● No statistically significant difference in adjusted ARR between teriflunomide 14 mg and IFNβ-1a● 26% with T. 14 mg
● 22% with IFNβ-1a
13
Safety and Tolerability Summary
● Manageable safety profile across Phase III trials:● Headache● ALT elevations● Hair thinning/decreased hair density● Diarrhea● Nausea● Neutropenia
14Aubagio data on file, Genzyme Corporation
● “Interferon-like” efficacy on relapse rate reduction
● First oral to show significance on disability in two Phase III studies
● Solid safety profile
● Convenient once-daily oral dosing
An Exciting Potential New Oral Treatment for Multiple Sclerosis
The Lemtrada™ Opportunity
15
16
CARE - Comprehensive Study Program
CARE-MS I CARE-MS II
Randomized Patients 581 840
Study Duration 2 years 2 years
PatientPopulation
Treatmentnaïve
Relapsed on prior treatment
TreatmentArms
Alemtuzumabvs. Rebif®
Alemtuzumabvs. Rebif®
CARE-MS Phase III program enrolled patients with relapsing-remitting multiple sclerosis
17
Rebif®
- 55%p<0.0001
n=426
0.39
0.26
0.18
0.52
n=187 n=376 n=202
Lemtrada™Rebif® Lemtrada™
- 49%p<0.0001
CARE-MS I CARE-MS IIAnnualized Relapse Rate Annualized Relapse Rate
Significant Comparative Efficacy Results with Unique Annual Dosing Regimen
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CARE-MS I - Strong Effect on Relapse
Proportion of Relapse-Free Patients at Year 2
59%
78%
Lemtrada™ 12 mg/day Rebif®
HR 0.45 P<0.001
Coles AJ ECTRIMS 2011; platform presentation
HR: Hazard RatioSAD: Sustained Accumulation of DisabilityCohen J AAN 2012: platform presentation
Time to SAD
19
21.1%
12.7%
Rebif®Lemtrada™ 12 mg/dayHR 0.58
Treatment effect 42%p=0.0084
CARE-MS II - Slowing Accumulation of Disability
CARE-MS II - Reversing Disability in Some Patients
20
Mean EDSS Change from Baseline
p<0.0001
0.24p=0.0064
‒0.17 p=0.0044
Rebif®Lemtrada™ 12 mg/day
EDSS: Expanded Disability Status ScoreCohen J AAN 2012; platform presentation
Slowing Accumulation of Disability Sustained for 6 months vs. Active Comparator
3 month
Active Comparators
Placebo
6 monthEDSS
HigherHurdle
21
(1) Based on CARE-MS II
HigherHurdle
(1)
For Illustrative Purposes
Typical Threshold for Approval
CARE-MS - Substantial Treatment Effect vs. Rebif®
22
● Substantial treatment effect on relapse rate
● Meeting co-primary endpoint vs. active comparator in CARE-MS I & II
● Statistically significant difference in Time to 6-month SAD in CARE-MS II
● No statistically significant difference in CARE-MS I due to unexpected low rate
of sustained disability in comparator arm
● Patients treated with Lemtrada™ in CARE-MS II were more than twice
likely to experience disability improvement over Rebif®
● Statistically significant effect on other efficacy endpoints
in both CARE-MS I & II
SAD: Sustained Accumulation of Disability
CARE-MS Overview of Adverse Events (AE)
CARE-MS data on file, Genzyme Corporation(1) This death was due to a motorcycle accident(2) One death was due to a pedestrian accident and the other was due to an incident of aspiration pneumonia following a severe MS relapse
CARE-MS I CARE-MS IIRebif®
SC INFB-1aLemtrada™
12 mg/dayRebif®
SC INFB-1aLemtrada™
12 mg/day
(%) (%) (%) (%)
Adverse EventsPatients with events
InfectionsThyroid DisordersImmune Thrombocytopenia
AEs leading to treatment withdrawalAEs leading to study discontinuation
92.045.56.40.55.92.7
96.067.318.10.81.30
94.666.35.00
8.93.0
98.476.815.90.93.20.2
Serious Adverse EventsPatients with serious events
Serious Infections14.41.1
18.41.9
21.81.5
19.53.7
Deaths 0 0.3(1) 0 0.5(2)
23
CARE-MS - Well Characterized Safety Profile
● Infusion-associated reactions very common● Premedication reduced/alleviated symptoms
● Infections common in both groups
● Predominantly mild to moderate, some serious
● Autoimmune events included thyroid disorders and immune thrombocytopenia● Detected via routine monitoring and generally managed using
conventional therapies
24
25CARE-MS data on file, Genzyme Corporation
● Ground-breaking efficacy results
● Treatment effects across multiple endpoints
● Manageable and consistent safety profile
● Monitoring program successful at early detection of AEs
● Favorable benefit/risk
● Convenient annual dosing
- A Transformative Approach to MS Treatment
26
- A Strong Commitment to MS
● Experience in developing innovative treatments for chronic disease
● Promising Multiple Sclerosis clinical development program
● Extensive global relationships with physicians, payers and patient advocacy groups
Changing the treatment paradigm
across the MS spectrum of
disease
Q&A SESSION
27
APPENDIX
28
- Novel PK & PD Profile
● Humanized monoclonal antibody
● IV infusions administered in two courses: ● 12 mg daily on 5 consecutive days
in the first year ● 12 mg daily on 3 consecutive days
12 months later
● Serum concentrations of Lemtrada™ are low or undetectable within ~30 days following treatment
● Leads to immunomodulation through depletion and repopulation
29(1) CARE-MS I data on file, Genzyme Corporation
–500
1500
4500
2500
3500
500
0
0 1 3 6 9 12 2415 18 21
Con
cent
ratio
n (n
g/m
L)
13
Months on Study
Serum concentrations(1)
- Selectively Targets Lymphocytes
● Selectively targets CD52 protein, depleting B and T cells responsible for MS inflammatory process
● B and T cell repopulation begins within weeks and continues over time(1)
● Other white blood cells are minimally or transiently affected(2,3)
● Protective serum antibodies are unaffected(4)
30
White Blood Counts in MS patients(5)
5.0
Neutrophils
MonocytesEosinophilsBasophils
Lymphocytes
0.0
0.5
1.0
1.5
2.0
4.0
4.5
0 1 2 3 4 5 6 7 8 9 10 11 12
Cel
l Cou
nts
(109 /L
)
Months after Alemtuzumab
(1) Coles AJ et al. AAN 2010; poster P06.172(2) Hu Y et al. Immunology 2009;128:260-270, Turner MJ, et al. ECTRIMS 2011; poster 791(3) Coles AJ et al, AAN 2012; platform S01.006(4) Coles AJ et al. Lancet 1999;354:1691-5, McCarthy CL, et al. ECTRIMS 2011; poster 781(5) CARE-MS I data on file, Genzyme Corporation
- Rebalancing the Immune System
● A distinctive pattern of lymphocyte repopulation occurs over time(1)
● May reduce inflammatory processes in MS and have disease modifying effects
● Supported by up to three years durable efficacy after two short treatment courses(2)
Increased % of T Cells with T-Regulatory Phenotype(1)
Perc
enta
ge o
f CD
4+T
Cel
ls C
D25
high
0
20
30
HealthyControl
1 3 6 9 12
Time in months
10
*p<0.01
Pre-treatment
*
*
*
31(1) Cox AL et al. Eur J Immunol 2005;35:3332-42., Hu Y et al. Immunology 2009;128:260-70, Havari E et al. ECTRIMS 2010; poster 424, Jones JL et al.
Brain 2010;133:2232-47(2) Coles AJ et al. NEJM 2008;1786-1801
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