2010 - ir - diabetes and oncology
DESCRIPTION
Diabetes and Oncology IR Thematic SeminarTRANSCRIPT
1
Diabetes
and Oncology IR Thematic
Seminar
September
30, 2010
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-aventis’
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-aventis, 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 products candidates, the absence of guarantee that the products 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 as well as those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under “Risk Factors”
and “Cautionary Statement Regarding Forward-Looking Statements”
in sanofi-aventis’
annual report on Form 20-F for the year ended December 31, 2009.Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.
2
3
Introduction
Christopher A. ViehbacherChief Executive Officer
4
Agenda
Overview of Oncology Business Division and Next
Wave
of Oncology
DrugsDebasish Roychowdhury, Senior Vice President - Oncology Division
Update on BiPar
and IniparibAtul Dhir, CEO - BiPar Sciences
Beyond Iniparib: Additional Phase III Candidates and Early Clinical Stage Pipeline
Tal Zaks, Vice President, Head of Development - Oncology Division
Concluding RemarksDebasish Roychowdhury, Senior Vice President - Oncology Division
Q&A Session
Sanofi-aventis Poised for Growth in Diabetes
Pierre Chancel, Senior Vice President - Diabetes Division
Building up on a Strong Commercial Presence
Christoph Heinemann, Vice President, Strategy & Operations - Diabetes Division
Today’s Commitments for the Treatments of Tomorrow
Jochen Maas, Vice President, Research & Development - Diabetes Division
Concluding RemarksPierre Chancel, Senior Vice President - Diabetes Division
Q&A Session
Oncology Diabetes
5
Oncology IR Thematic
Seminar
September
30, 2010
6
Overview of Oncology Business Division and Next
Wave
of
Oncology
Drugs
Debasish
RoychowdhurySenior Vice President – Oncology Division
7
Oncology – A Strategic Priority
Unmet
Medical
Need
Impact on Society
Innovative
Science
Strong
Heritage
Cancer is a leading cause of death globally(1) requiring new treatment options
(
1
)
Source: World Health Organization; cancer accounted for 7.9 million deaths in 2007(
2
)
Source: The American Cancer Society and Livestrong
report “The Global Economic Cost of Cancer”
Cancer is the #1 reason for economic loss among the top causes of death(2)
Sanofi-aventis is
poised
to maximize
the opportunity
and potential
in oncology
Taxotere®
and Eloxatin®
are the foundation
of chemotherapy
Tumors
now
characterized
at
the molecular
level, treatments
more personalized
8
Our Strategy
in Oncology
is
Based
on Five Core
Beliefs
Innovative
treatments
-
Proven
substantial
benefits
are necessary
Personalization
-
Biomarkers, patient stratification tools, and targeted
therapies
Environment
shaping
-
Facilitating
patient access
to medicine
Creation
of more synergies
-
Integrate
business functions
into
the Division
External
partnering
-
Embrace
external
innovation to leverage
internal
capabilities
Vitry, France headquartersCambridge, MA headquarters
9
A New Approach to Developing Cancer Therapies
Innovative targets
From To
Our Oncology
Division is
flexible in adapting
to a fast
changing
environment
Known
targets
Small molecules
Best in class, differentiation classical
Common cancers, all comers
Monotherapy, add-on
Minimal biomarkers, diagnostics, imaging
Internal discovery
U.S. and EU centric
Small molecules, biopharmaceuticals, nanodelivery
technologies, etc.
First in class, best in class, differentiated by superior efficacy and unmet need
Genetically stratified, smaller populations
Combination therapies, factorial designs
Translational medicine embedded trials
Externalization
Increased focus on Asia
10
Redefining
our
Oncology
Presence
Creating
an empowered
and agile Oncology
Division
More than 100 new hires
to the oncology division in 2010 Many key hires have academia and biotech backgrounds Oncology Division will also be based in Cambridge
to benefit from networking with a leading scientific community
R&D centers reduced from 11 to 3
Jevtana®
NDA filed in about
4 months
of pivotal results versus the industry average of 6 to 8 monthsImproved target selection and the use of translational medicine to reduce development costs
Creation of a new Oncology Review Board to optimize and prioritize
oncology investmentsGlobal Protocol Review Committee established to facilitate accelerated filing timelinesEmpowerment
of teams
Streamlining GovernanceRecruiting
Talent
11
Maximizing
Value Through
the Integration
of R&D and Commercial Activities
Fully integrated in 9 key countries
Sales & Marketing, R&D, Market Access, Medical affairsImproves speed to marketFacilitates collaborative decision makingRest of world managed through regional offices
Creation of a biotech center of excellence in ChinaResearch and development centers
Cambridge, MAVitry, FranceSan Francisco, CA (BiPar)
Oncology
Division Direct countries in
Oncology
Divisionfacilities
U.S.
Russia
ChinaJapan
France
Germany
Italy
Spain
UK
12
New Leadership Team Broad, Diverse and In-Depth Expertise
Alain Curaudeau
VP, Head of Strategy & Portfolio Management, Oncology
•
SVP, Project Planning & Management at
QTL•
Head of Project Management, Aventis
Christoph
Lengauer
VP & Head of Oncology Drug Discovery & Preclinical Research
•
Exec Dir & Sr
Unit Head Oncology Discovery, Novartis Institute for Biomedical Research
•
Adjunct
Associate
Professor of
Oncology, Johns
Hopkins
University
Tal Zaks
VP, Head of Development, Oncology
•
Genetic Research Group, Head Oncology Clinical Research Team, Cephalon
•
Adjunct Associate Professor of Medicine, University of Pennsylvania
Tamas Suto
VP & Head of Medical Affairs, Oncology
•
Therapeutic
Head for Haematology/Oncology
& Head of International Medical
Affairs, Amgen
Debasish
Roychowdhury
SVP & Head of Oncology Division
•
Drug development
and clinical
development
in oncology
& hematology
at
GSK and Lilly
•
Oncologist, hematologist
John Harrington
VP & Chief Commercial Officer, Oncology
•
VP & Head US Oncology
Division, sanofi-aventis
•
VP Metabolism
Business Unit, sanofi-aventis US
•
VP Primary
Care Sales, Aventis US
Atul
Dhir
CEO, BiPar Sciences
•
President, Cancer Research
Group, US Oncology
•
VP Healthcare, Monsanto •
Consultant, McKinsey
13
BiPar
internal
project
externalized
project
External projects to have the choice of using sanofi-aventis platforms or working directly with external partners
Overall objective is to have at least 50% of projects externalized
Bring in learnings
and transform internal process
Competitive funding process for internal and external projects
PI3K
Internal
and External
Expertise as well
as Networks to be
Maximized
14
A Partner of Choice
in Oncology
Demonstrating
our
ability
to add
valueCutting-edge
technical
expertiseInvestigating
novel-novel
combinationsGlobal execution
and distribution, especially
in Emerging
MarketsProviding
access
to a broad
industrial platform
and control over supply
chain
Allowing
partner
to develop
and prosperEnabling
partner
to lead
key
activitiesCollaborating
while
partner
develops and expands
expertiseFlexible deal structure
Regeneron
-
-
Exclusive option of co-development-
Opportunity
for partner
to lead
clinical
development-
Acquisition but with
significant
autonomy
15
Emerging
Markets
–
Executing
a Local Approach
CHINA ESTIMATED CANCER INCIDENCE: BOTH SEXES, ALL AGES
185
221
259
402
464
522
0 100 200 300 400 500
Breast
Colorectum
Oesophagus
Liver
Stomach
Lung
Thousands
Addressing regional differences in cancer epidemiology and biology
Eloxatin®: Development of liver cancer indication for the Asia-Pacific regionJevtana®: Asia-Pacific region to lead development in gastric cancer
Creating basic research
alliances regionally, especially North East Asia Specific development
plans for
these regions -
executed in parallelSynchronized submission
timelines
Providing access through multi-tiered pricing
strategies or
risk sharing models
Differences
in incidence require
regional
approach
to each
indication
China Estimated
Cancer Incidence(1)
Number
of new patients (2008)
(1) Source: GLOBOCAN 2008, IARC -
12.6.2010
16
Maximizing
the Emerging
Markets
Opportunity
(
1
)
Pricing
comparisons
are adjusted
to a baseline
of 100.(
2
)
HRPC: Hormone Resistant
Prostate Cancer
Sustainable
global sales post EU/U.S. patent expiries
expected
to be
around
€500m
New indications in ChinaHRPC(2) in 2010Advanced gastric
cancer in 2012Head and neck cancer in 2014
Expand
the gastric
cancer indication in other
Emerging
MarketsPursue
breast
and prostate cancer
indications in India, Russia, and Brazil
0
50
100
150
200
EU5 China Russia Brazil
Taxotere®
Relative Pricing(1)
17
Leveraging
Brand Equity
Settlement of U.S. patent litigation Inventory workdown
is progressingReimbursement for Eloxatin®
expected to return
to
levels
seen prior
to generic entry in early 2011
Planned growth drivers in China:Advanced HCC(1)
in 2011Liquid solution launch in 2012Advanced Gastric cancer in 2014Adjuvant Gastric cancer in 2015
Sustainable
global sales post EU/U.S. patent expiries
expected
to be
around
€300m
Generic
oxaliplatin
Branded
Eloxatin
U.S. Eloxatin® Demand (MGs in 000s)(2)
-
300
600
900
1,200
1,500
Jan-10 Feb-10 Mar-10 Apr-10 May-10 Jun-10 Jul-10
(
1
)
HCC: Hepatocellular
cancer(2)
Source: IMS
U.S. Eloxatin®
Demand (MGs
in 000s)(2)
18
Pipeline Rebuild
Underway…February
2009 Before Portfolio Review
Aflibercept
Phase I Phase II Phase III Marketed
larotaxel
Taxane
–
Tubulin
inhibitor
Pancreatic, Bladder cancer
xaliproden
Neurotrophic
peripheral sensory neuropathies
AVE 1642 IGF1R mAb
Breast Cancer
alvocidib
Cyclin-dependent kinase
inhibitor
CLL
ombrabulin
Vascular disrupting agent
Sarcoma
Jevtana®
Taxane
-
Tubulin
inhibitor
Prostate cancer
aflibercept
1L mProstate; 2L NSCLC;
2L mCRC;
Oforta®
fludarabine
phosphate
Elitek®
rasburicase
Eloxatin®
oxaliplatin
Taxotere®
docetaxel
Project terminated
(Feb
2009 to Sept 2010)
SAR3419 Maytansin-loaded anti-CD19 mAb
non-Hodgkin’s lymphoma
SSR97225 Antimitotic
agent
TroVax
(SAR109659)
Renal Cancer
aflibercept
1st line mPancreatic
cancer
19
Pipeline Rebuild
Underway…September
2010 Rich and Strong Portfolio
iniparib
PARP inhibition
mTNBC; NSCLC
SAR3419*
Maytansin-loaded anti-CD19 mAb
non-Hodgkin’s lymphoma
SAR245408 (XL147)
Oral PI3K inhibitor
Endometrial
& breast
cancer
Aflibercept
Taxotere®
docetaxel
SAR650984* Anti-CD38 naked mAb
Hematological malignancies
SAR103168
Multikinase
inhibitor
AML
Elitek®
rasburicase
Oforta®
Fludarabine
phosphate
ombrabulin
Vascular disrupting agent
Sarcoma
SAR256212 (MM121)
anti-ErbB3 mAb
Breast cancer
SAR302503 JAK2 inhibitor Myelofibrosis
SAR153192* Anti-DLL4 mAb
Solid tumors
iniparib
PARP inhibition
Ovarian
cancer
aflibercept* VEGF-Trap
1st
line colorectal cancer
Phase I Phase II Phase III Marketed
SAR566658*
DS6 Antibody-Drug Conjugate
DS6 Positive Solid
Tumors
aflibercept* 1st line mProstate;
2nd line NSCLC; 2nd line mCRC
Jevtana®
cabazitaxel
Eloxatin®
oxaliplatin
SAR245409
(XL765)
Oral dual inhibitor
of PI3K/mTOR
Cancer
New clinical
project
since
February
2009
* Biologic
product
20
Our Next
Wave
of Oncology
Drugs Maximizing
Late
Stage Opportunities
Iniparib
Aflibercept Ombrabulin
21
New semi-synthetic taxaneSelected to overcome the emergence of taxane
resistance(1)
Mechanism of actionMicrotubule stabilizer(2)
Estimated new cases of prostate cancer in U.S. in 2009 =192,000;
Deaths 27,360
575,000 new cases of Prostate Cancer diagnosed in Europe and U.S. yearly(3)
mHRPC
accounts for 15% of patients
Taxotere®
chemotherapy is the current standard of care in mHRPC
After Taxotere®
failure, Jevtana®
is the only approved drug -
supportive care, unapproved agents, or hospice are other treatment options
No improvement in overall survival demonstrated with current therapies
A New Cytotoxic
Agent
Prostate cancer
The molecule
(
1
)
Attard
G, Greystoke
A, Kaye S, De Bono J. Pathol
Biol
(Paris). 2006;54(2):72-84.(
2
)
Pivot X, Koralewski, P, Hidalho
JL, et al. Ann Oncol. 2008;19(9):1547-1552.(3) Ferley
J et al. Eur
J Cancer 2010 –
American Cancer Society, Facts & Figures, 2009
22
0
20
40
80
60
100
0 month 6 months 12 months 18 months 24 months 30 months
cabazitaxel+prednisone
(CBZP)
mitoxantrone+prednisone
(MP)
mitoxantrone
+ prednisone 377 300 188 67 11 1
cabazitaxel
+ prednisone 378 321 231 90 28 4
Number
at
risk
Proportion
of Overall
Survival
(%)MP CBZP
Median
OS (months) 12.7 15.1
Hazard
Ratio 0.70
95% CI 0.59–0.83
P-value <.0001
Source: TROPIC data per the Jevtana
product insert
Overall
Survival
(ITT Analysis) from
TROPIC
23
MP (n=371) CBZP (n=371)
All grades (%) Grade ≥3 (%) All grades (%) Grade ≥3 (%)
Any
adverse event 88.4 39.4 95.7 57.4
Febrile
neutropenia 1.3 1.3 7.5 7.5
Diarrhea 10.5 0.3 46.6 6.2
Fatigue 27.5 3 36.7 4.9
Asthenia 12.4 2.4 20.5 4.6
Back pain 12.1 3 16.2 3.8
Nausea 22.9 0.3 34.2 1.9
Vomiting 10.2 0 22.6 1.9
Hematuria 3.8 0.5 16.7 1.9
Abdominal pain 3.5 0 11.6 1.9
Most Frequent
Treatment-Emergent AEs in ≥2% of Patients (Grade ≥3)(1): Safety
Population
(1) Sorted
by decreasing
frequency
of events
grade ≥3 in the CBZP arm.2010 Genitourinary
Cancers SymposiumProgress in Multidisciplinary
Management
24
Jevtana Abraxane Afinitor Ixempra Sprycel Tasigna
Launch
Exceeding
Expectations
Launch
Analogs
(Sales: 2-months
post launch)(4)
(1) Factors
in analog
selection
include
2L or 3L indication in smaller
metastatic
patient populations with
unmet
medical
need(2) National Comprehensive
Cancer Network(3) EUA: European
Urology
Association(4) Source: IMS NSP
Sales tracking ahead of other analogs(1)
at a similar time post-launchFY 2010 sales expected to be around €60m
Reimbursement:80% of Medicare carriers have made coverage decisionsMinimal formulary restrictions by the vast majority of payorsMajority of plan decisions are expected by early 2011
Adopted into the NCCN(2)
and EUA(3)
guidelinesSafety profile since launch has been consistent with the TROPIC trial
® ® ® ® ®
25
Global Rollout
Beginning
in 2011
EuropeCHMP opinion expected
in H1 2011380,000 new cases of prostate cancer annually12% mortality
rateAbout 25,000 to 30,000 cases are treated
with
chemotherapy
Emerging
Markets2011: Brazil, South Korea
planned
launches2012: Turkey, South Africa
planned
launchesRussia
filing
submitted
in Q3 2010
2010 2011 2012
Planned
launch
schedule*
* non exhaustive
26
New Indications to Drive Future Growth
Probability
of Success
Fast
erLa
unch
Tim
ing
Weaker
Slow
er
Stronger
Asymptomatic
prostate cancer
2L mHRPC
2L SCLCGastric
1L mHRPC
Size of circle represents relative patient population size Based on total U.S. incidence of cancer type (not specific patient segment)(1) Cabazitaxel
doses of 25 mg/m²
or 20 mg/m²
will be studied
Phase III study in first line prostate cancer to begin enrolling Q1 2011
Study to include about 1,100 mHRPC
patients
Primary endpoint: superiority of cabazitaxel(1)
vs. docetaxel
in OS
Phase II second line small cell lung cancer study to begin H2 2011
Early clinical work in asymptomatic prostate cancer to begin in 2011
Phase I bridging study in Japan to begin Q4 2010
Jevtana®
global peak sales in 2L mHRPC
expected to be in the range of €300m to €500m
Jevtana®
Development
Opportunities
BiPar is a wholly owned subsidiary of sanofi-aventis 27
Update on BiPar
& Iniparib*
Atul
Dhir, CEO –
BiPar
Sciences
*Iniparib
is
the United States Adopted
Name (USAN) for the investigational
PARP1 inhibitor, BSI-201
BiPar is a wholly owned subsidiary of sanofi-aventis 28
The BiPar
Model: A New Model for Drug Development
Large Pharma
Global Scale Technical expertise / Depth
Process Discipline
BiPar
Model
Building an innovative
platform
within
sanofi-aventis to improve
speed and efficiency
in drug
development
Biotech
Entrepreneurial Flexible / Nimble
Outsourced
partners
BiPar is a wholly owned subsidiary of sanofi-aventis 29
Iniparib: A novel
anticancer
agent
PARP: Poly ADP-Ribose Polymerase(1)
Phase 1b ASCO ’08 poster presentation
(2) Phase 1 ASCO ’08 poster presentation (3) Phase 2 mTNBC
SABCS ’09 oral presentation(4) ASCO 2010 online abstract: Pharmacokinetics of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in cerebrospinal fluid (CSF) of a breast cancer patient with
carcinomatous
meningitis. Michael Castro, Lingyun
Li, and Todd Stallings
• Small molecule: penetrates blood
brain
barrier(4)
• Novel
agent for treating tumors
with
DNA repair
defects
• Expected
to be
combined safely
with
multiple
chemotherapy
agents(1)
• Clinical
evidence
for efficacy in advanced
breast
cancer
• No significant
side
effects
at recommended
dosing(1,2,3)
Chemotherapy
Plus Iniparib
DNA Not
Repaired
Chemotherapy
Chemotherapy
Alone
PARP1 Facilitates
DNA Repair DNA Repair
PARP1 Activity
InhibitedIniparib
Hypothesized
Anti-Tumor
Activity
Tumor
DNA Damage
BiPar is a wholly owned subsidiary of sanofi-aventis 30
Iniparib
in mTNBC: Phase II Trial Interim Data (Overall Survival)
O'Shaughnessy
J, et al. SABCS 2009. Abstract 3122. Months
OS,
%
BiPar is a wholly owned subsidiary of sanofi-aventis 31
Rapid Progress in Development of iniparib
in mTNBC
• Phase II study in mTNBC• Overall Survival advantage without added toxicity• Final results in ESMO (October 2010)
• Phase III in mTNBC• Completed enrollment in February 2010• Regulatory submission planned for Q1 2011 in U.S.
and Q2 2011 in EU• Clinical development in mTNBC
started in Japan
• New trials to explore new combinations, schedules, etc. started in mTNBC
• Neoadjuvant
trials initiated in the U.S. and EU and to lay the groundwork for adjuvant therapy in early TNBC
TNBC: 15%
Breast
Cancer
U.S. ~14,000EU: ~ 17,000First, second & third line(4)
References:(1) Carey L et al. JAMA. 2006;295:2492-2502.
(2) Swain S. ASCO Annual Meeting. June 3, 2008.
(3) Public epidemiology sources and company models (4) Public epidemiology sources and company models
mTNBC
Population
BiPar is a wholly owned subsidiary of sanofi-aventis 32
Lifecycle
Plan for iniparib
Broad development
plan in multiple cancer indications
First WaveLead
Indication
Bladder
CancerPancreatic
CancerColorectal Cancer
Small Cell
Lung Cancer Head and Neck Cancer
Glioblastoma
Multiforme
Second Wave
Squamous
NSCLC
Recurrent Ovarian Cancer
Early-Stage TNBC
HER2-/HR+ Metastatic Breast Cancer
Metastatic Triple Negative Breast Cancer (mTNBC)
BiPar is a wholly owned subsidiary of sanofi-aventis 33
The Squamous
Non-Small Cell Lung Cancer Opportunity
• Squamous
NSCLC biologically an attractive target
• PARP1 upregulation(1)
• Associated with basal-like phenotype, similar to TNBC(2,3)
• Evidence of DNA repair impairment of BRCA pathway
• High frequency of microsatellite instability
• High unmet patient need
• Gemcitabine
+ Carboplatin
commonly used in NSCLC
(1) Ossovskaya
et al. Genes and Cancer, in pressDakir
et al. Carcinogenesis 2008;29:2377
(2) Dakir
et al. Carcinogenesis 2008:29:2377(3) Chu et al. Histopathology 2001;39:9
(3) Reis-Filho
et al. Virchows
Arch 2003;443:122(4) GLOBOCAN 2008 (http://globocan.iarc.fr/)
(5) American Cancer Society: Cancer Facts and Figures 2010. Atlanta, Ga: American Cancer Society, 2010.
NSCLC: 80%
Lung cancer
Squamous
cell: 25-30%
Lung cancer deaths
in the U.S.: 222,520 in 2010(4,5)
BiPar is a wholly owned subsidiary of sanofi-aventis 34
The Development of Iniparib
in Lung Cancer
Phase 3 Squamous
Lung Cancer Study
(International)
Phase 2 Non-Small Cell
Lung Cancer Trial (EU only)
STAGE IV
Squamous
Cell
Lung Cancer
n=825
STAGE IV
Squamous
Cell
Lung Cancer
n=825
GemcitabineCarboplatinGemcitabineCarboplatin
GemcitabineCarboplatin
iniparib
GemcitabineCarboplatin
iniparib
STAGE IV
Non-Small Cell
Lung Cancer
n=105
STAGE IV
Non-Small Cell
Lung Cancer
n=105
GemcitabineCisplatin
GemcitabineCisplatin
GemcitabineCisplatininiparib
GemcitabineCisplatininiparib
2:1
Status
• Initiated
in US in March 2010
• EU and ROW sites opening in Q4 2010
• Primary
analysis: H2 2012
• Initiated
in EU in May 2010
• Close to half
of patients accrued
• Primary
analysis: H2 2011
1:1
BiPar is a wholly owned subsidiary of sanofi-aventis 35
Iniparib
Development
in Recurrent
Ovarian
Cancer
High unmet
need• Leading
cause of death
from
gynecologic malignancy
• Poor
prognosis
in advanced-stage disease
Rationale
and opportunity
for iniparib• Preclinical
activity
of iniparib
in ovarian cancer models(2)
• Sporadic
cancers associated
with BRCA1/2 dysfunction
• PARP1 is
upregulated
in ovarian
cancers(3)
• Gemcitabine/carboplatin
is
established regimen
in recurrent
ovarian
cancer
(1) Jemal
et al. CA Cancer J Clin 2009;59:225.(2) Ossovskaya
et al. AACR 2008(3) Ossovskaya
et al. AACR 2007
Platinum- Sensitive: ~65%
Ovarian cancer
~22K new diagnoses and ~15K deaths
in the U.S. in 20091
BiPar is a wholly owned subsidiary of sanofi-aventis 36
Ongoing
Phase 2 Studies
in Recurrent
Ovarian
Cancer
Phase 2 Platinum-Sensitive Ovarian
Cancer (U.S.)
Platinum-Sensitive Recurrent Ovarian
Cancer
Gem/Carbo
+ iniparib
n=41
Platinum-Sensitive Recurrent Ovarian
Cancer
Gem/Carbo
+ iniparib
n=41
Stage 1(n=17)
Stage 1(n=17)
Status• Initiated
in Dec
2009• Minimum 8 responses
to proceed
to Stage 2• Stage 1 response
threshold
reached• Interim
analysis: H1 2011
Stage 2(n=24)
Stage 2(n=24)
Phase 2 Platinum-Resistant
Ovarian
Cancer (U.S.)
Platinum-Resistant Recurrent Ovarian
Cancer
Gem/Carbo
+ iniparib
n=48
Platinum-Resistant Recurrent Ovarian
Cancer
Gem/Carbo
+ iniparib
n=48
Stage 1(n=23)
Stage 1(n=23)
Stage 2(n=25)
Stage 2(n=25)
• Initiated
in Dec
2009• Minimum 4 responses
to proceed
to Stage 2• Stage 1 response
threshold
reached• Interim
analysis: H1 2011
BiPar is a wholly owned subsidiary of sanofi-aventis 37
Conclusions
• Iniparib
is a leading anti-cancer agent with PARP inhibitory activity with a survival advantage in mTNBC
and an excellent safety profile
• Iniparib
regulatory
submissions
in the U.S. and EU on track
for 2011
• Major progress
has been made in developing
iniparib
in breast, lung
and ovarian
cancer
• Iniparib
has tremendous
potential
across
multiple cancers both clinically
and commercially
38
Beyond iniparib: Additional Phase III Candidates
Early Clinical Stage PipelineTal ZaksVice President, Head of Development
39
Aflibercept and Ombrabulin A Commitment
to Targeting
Tumor
Vasculature
Antiangiogenic
approach:
Prevention of new vessel growthChronic inhibition
of neovascularization
Vascular-disrupting approach:
Tumorinitiation
Late
stageDissemination
Vascularizedtumor
Angiogenicswitch
Avascularphase
Disruption of microvessels
Acute blood flow shutdown, extensive tumor necrosis
aflibercept ombrabulin
40
Aflibercept –
Novel Anti-VEGF Candidate Differentiated from Bevacizumab
Partnered with worldwideVEGF Trap: a fusion protein blocking VEGF, a well-validated anti-angiogenic
approach
Structure of VEGF Trap
Humanized MAb~160,000 MWKd
= 400-1000pMOnly blocks primate VEGF-AForms Immune Complex with VEGF-A
All human amino acid sequences~110,000 MWKd
= 0.5pM (tighter than natural receptors)Blocks all mammalian VEGF-A, as well as VEGF-
B & PIGFBinds VEGF-A as monomer without Immune Complex formation
Bevacizumab Aflibercept
41
Aflibercept –
Development
Program
Three
Phase III studies
fully
enrolledVELOUR study
continues based
on recommendation
by IDMC(1)
(
1
)
IDMC: Independent Data Monitoring Committee. Recommendation
of IDMC was
announced
in September
2010
XL147(PI3K)
Phase III VELOUR
Indication Design # of patientsPhase / Study
Phase III VITAL
Phase III VENICE
2nd
line metastatic non-small cell lung cancer +
Taxotere®
2nd
line metastaticcolorectal cancer
+ FOLFIRI (folinic
acid / 5-FU / irinotecan)
1200
900
1240
Data Expected
Final analysis
H2 2011
Interim
analysis
H1 2011/
Final analysis
H1 2012
Final analysis
H1 2011
1st
line metastatichormone resistantprostate cancer +
Taxotere®
prednisone
Phase II AFFIRM 230 Final Analysis
H2 20111st line metastaticcolorectal cancer
42
Ombrabulin – Most Advanced Vascular Disrupting Agent
Good safety profile and encouraging signs of activity in Phase I/II(3)
No QT prolongation(1)
observed and very limited hematotoxicityAntitumor activity observed in combination with chemotherapy
Complete Response observed in triple-negative breast cancer patient
Antivascular
effect demonstrated using DCE-US(2)
No potential for “VEGF-rebound”
effect
Promising
earlyPhase II data atASCO & ITC 2010
2 classes of Vascular
Disrupting
Agents with
different
molecular
targets
Unidentified target:Vadimezan
(ASA404): Phase III NSCLC 1st
line trial failed
Tubulin-binders:OmbrabulinFosbretabulinPlinabulin
(
1
)
Toxic
effect
on ECG observed
with
some
agents in the class(
2
)
Digital Contrast
Enhanced
Ultrasound(
3
)
Presented
at
ASCO 2010
43
Ombrabulin Development Program
Mechanism
of action and preclinical
data support development
in most
solid tumors
High unmet
medical
need
in soft-tissue sarcoma
after
failure
of standard therapyOrphan
Drug
status
expectedAround
30,000 patients in the U.S. and EU with
soft-tissue sarcoma
Pivotal
Phase III
study
is
more than
85% enrolledOn track
for U.S. and EU filing
in 2011Two
Phase II
proof of concept trials in preparation
1st
line NSCLC
to start
20112nd
line ovarian
cancer
to start
2011
Baseline
After
cisplatin/ombrabulin
Shut Down of Tumor Blood Flow(1)
(1) DCE-Ultrasound
images of an ovarian
cancer patient treated
in a combination
Phase I trial; the red
contour outlines
the tumor
mass.
44
Early
Clinical
Stage Pipeline: Our Oncology Discovery Approach
Discovering
drugs
against common
cancer pathways
Focus on antibody
drug conjugates
Leverage
external complementary
innovation
DrugCancer Target
Pathogenesis1
2
3
45
Biological
Importance of
PI3K Pathway
in Cancer
C2
Tumor Fraction mutatedColon Brain Gastric Breast
1/24 (4%)
74/234 (32%) 4/15 (27%)
3/12 (25%) 1/12 (8%)
Lung
8% 47% 33%
E545K H1047R
(
1
)
Parsons et al., Nature 436 (2005)Diagram
Source: Samuels
et al., Science 304 (2004) , Samuels
et al., Cancer Cell
561 (2005)
PI3K pathway:Mutations that
activate
this
pathway
occur
frequently
in human
tumors
and promote
tumor
cell
growth
and survival(1)
Activation of the pathway
is
associated
with
resistance
to cancer therapiesTwo
drugs
targeting
this
pathway
in clinical
development: XL147, XL765Preclinical
cancer research
projects
against
PI3K alpha and PI3K beta
Tumor Fraction Mutated
Colon
Brain
Gastric
Breast
Lung
32%
27%
25%
8%
4%
Locations of Activating Mutations in the PI3K Gene
46
XL147 -
Potentially
First in Class
As a single-agentStrong inhibition of the PI3K/AKT
pathwayModerate inhibition of the ERK/MAPK pathway(1)
Preliminary anti-tumor activity in NSCLC, adenocarcinoma, vaginal carcinomaPhase II program started
Evaluating combinations with standard of care and novel agents
No apparent additive toxicity or PK interaction Upregulation
of ERBB3 is seen in a cell line model treated with XL147(2)
Maximum tolerated
dose is
600mg(1) Demonstrated
in all tumor
samples
at
the maximum tolerated
dose(2) Hanker, Translational
Cancer Medicine
Meeting, 2010
PI3K
AKT
mTOR
Growth
Survival
Resistance
Genetic
Alterations
XL147
Rapalogs
47
XL147 -
Clinical
Activity
Observed
Baseline Cycle 8 –
200 mg XL147Vaginal Carcinoma
(1) Surgical resection, pelvic and periaortic
radiation, cisplatin
weekly, paclitaxel/carboplatin, and investigational therapies
54 year-old patient with vaginal cancerSequential CT scans of the abdomen
32% interval reduction of a left para-aortic soft tissue mass in Cycle 814% overall tumor reduction in Cycle 6; 21% reduction in Cycle 8
Multiple prior treatments(1)
48
XL147 –
Development
Program
Three
Phase II studies
enrolling
patientsExtensive biomarker
work
being
performed
XL147(PI3K)
Phase I
Indication Combination
AgentPhase
Ph Ib/II
Ph Ib/II
Phase II
Phase II
MTD with
expansion in NSCLCLymphoma
in MTD expansion
Endometrial, ovarian,
NSCL cancer
2nd
line endometrial
cancer
Refractory
HER2+ metastatic
Breast
cancer
Single agent
Erlotinib
Carboplatin
and paclitaxel
Single agent
Trastuzumab
orTrastuzumab/paclitaxel
Number
of Patients
125
74
35
80
74
62LetrozolePhase IIRefractory
ER/PR+ metastatic
Breast
cancer
MTD: Maximum Tolerated
Dose
NSCLC in MTD expansion
49
XL765 -
PI3K and mTOR
inhibition
Compelling mechanism of action that blocks two different enzymatic
activities along the same pathwayAs a single agent:
Strong impact on PI3K and
mTOR pathway
Effect on ERK/MAPK
pathwayDose limiting toxicity: transaminase
elevationIn combination:
Combination with temozolomide
in glioblastoma
and with erlotinib
in lung cancerDose escalation ongoing
Maximum Tolerated
Dose is
50 mg BID and 90mg QD
PI3K
AKT
mTOR
Growth
Survival
Resistance
Genetic
Alterations
XL147 XL765
Rapalogs
50
XL765 -
Demonstrates
Robust
PI3K Pathway
Inhibition
(
1
)
pEBP1T70, pPRAS40T246
and pS6S240/S244
also evaluated –
post-dose decreases of 68%, 52% and 84%, respectively; TUNEL staining
increased on average 1.6 fold. Note: This table summarizes results from all patients assessed for tumor pharmacodynamic
response. Data on file. ASCO 2010 presentation. N = 9 patients.
0
20
40
60
80
100
% In
hibi
tion
(+s.
d.)
pAKTT308 pAKTS473 pERKT202/Y204 Ki67
XL765: Average
of Percent Pathway
Inhibition(1)
“Proof of mechanism"
obtained
by demonstrating
inhibition of the PI3K pathway
in tumor
biopsies from
treated
patients
Inhibition of ERK pathway
demonstrated
51
XL765 - Development
Program
Phase I
Indication Combination
AgentPhase
Ph Ib/II
Solid
tumors
Lymphoma
in
MTD expansion
Glioblastoma
NSCLC in MTD expansion
Single agent
temozolomide
erlotinib
Number
of Patients
120
110
110
Phase II study
in ER/PR+ breast
cancer enrolling
patientsExtensive biomarker
work
being
performed
XL765 + letrozole
in refractory
ER/PR+(1)
Breast cancerletrozole 62Phase II
Ph Ib/II
(
1
)
Estrogen
Receptor
/ Progesterone
Receptor
positive
52
MM-121 -
A Novel
ERBB3 Antagonist
Importance of the ERBB3
receptorCentral signaling node in maintaining growth of tumor cellsKey regulator of AKT driven pro-
survival signals Implicated in the development of resistance to targeted and chemotherapeutic agents
Key modes of actionBlocks HEREGULIN binding to and subsequent phosphorylation
of ERBB3Inhibition of the cross talk between ERBB3 and ERBB1 or ERBB2 and consequent downstream activation of AKT
Sensitivity
Analysis
of Ligand-Induced
ERBB3 Pathway
Activation(1)
(1) Science Signaling, Therapeutically Targeting ErbB3: A Key Node in Ligand-Induced Activation of the ErbB
Receptor–PI3K Axis by Birgit Schoeberl, et al, 30 June 2009
53
MM-121 Development
Program
Translational
medicine
program to identify
biomarkers
integrated
into
clinical
trialsPhase II proof of concept program launched
in July 2010Several
other
phase II studies
to be
initiated
in the near
future
XL147(PI3K)
Phase I
Indication Combination
AgentPhase
Ph Ib/II
Phase Ib
Phase II
Solid
Tumors
NSCLC
Gynecological
tumors,
Ovarian
cancer
ER/PR+ Metastatic
breast
Single agent
Erlotinib
paclitaxel
Exemestane
Number
of Patients
55
Phase Ib: 24
Phase Ib: 24
Phase II: 240
130
54
Targeting
Key Signaling
Pathways
PI3K and HER3
Source: Drug discovery approaches targeting the PI3K/Akt pathway in cancer C
Garcia-Echeverria and W R
Sellers, Oncogene
27: 5511–5526. (1) Science Signaling, Therapeutically Targeting ErbB3: A Key Node in Ligand-Induced Activation of the ErbB
Receptor–PI3K Axis by Birgit Schoeberl, et al, 30 June 2009
ERBB family receptor tyrosine kinases, such as EGFR and HER2/neu, can be activated by mutationsERBB3 activates the PI3K pathway in response to HEREGULIN growth
factors(1)
Plans to conduct combination trials: MM-121
and XL147;
MM-121
and XL765
55
TG 101348 / SAR302503 Highly
Potent
and Selective
JAK-2 Inhibitor
Molecular characteristicsOrally available
Highly potent against wild-type and mutant JAK2 kinase
JAK2 selectivity reduces potential for off-target side effects
Myelofibrosis
disease burdenU.S. prevalence is about 14,000
Median survival is about 5 years
AML(1)
transformation is 5% to 20%
Clinical signs: enlarged spleen, bruising, bleeding, fatigue, shortness of breath, anemia
SB 1518
INCB 18424
SAR302503
CYT 387
JAK1 JAK2 JAK3 TYK2
3
2.8
22
1811
528
155
3.3
1276
428
405
Not reported
19
JAK Selectivity
Profile (2,3)
17
1002105
(1) AML: Acute Myelogenous
Leukemia(2) Measured by IC50, nM(3) Sources: SAR302503 –
Cancer Cell. 2008 April; 13:311-320; INCB 18424 -
Blood. 2010 Apr 15;115(15):3109-17; SB 1518 -
Blood 2009 November; 114: 3905; CYT 387 -
Blood. 2010 June; 115(25):5232-40
56
SAR302503 - Potentially “Best in Class”
for Myelofibrosis
Potential for “best in class”
and for myelofibrosis
disease transformationMajor spleen reduction and improvement in constitutional B symptoms(1)
Lack of spleen and cytokine rebound after missed dose or discontinuation
Signs of potential for reversal of fibrosis
Reduction in JAK2 mutant allelic burden (V617F)
Pre-treatment After
36 weeks
of SAR302503Significant Spleen Size Reduction
(1) Fever greater
than
38°
C, drenching
sweats, unintentional
weight
loss
of >10% of normal body weight
over a period
of 6 months
or less
57
SAR302503 -
Development
Program
0
10
20
30
40
50
60
70
80
Perc
enta
ge o
f Sub
ject
sCycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6
>/=50% 100%
Decrease
in Palpable Spleen Size(1)
Phase I
dose escalation
study
in MFGenerally
well
tolerated
with manageable
gastrointestinal effects, primarily
at
high
dosesManageable
anemia
observedOnce-daily
dosingIn the expansion cohort, 36/43 patients continued
on active treatment
for at
least 12 months
Phase II
in MF to start
Q1 2011
(1) ASH 2009: A Phase I Evaluation of TG101348, A Selective JAK2 Inhibitor in Myelofibrosis
–
Clinical Response is Accompanied by a Significant Reduction In JAK2V617F Allele Burden
Refractory Polycythemia
Vera
(PV)PV is driven by JAK2 mutationsPhase II
dose ranging to start 2011
58
SAR3419 –
Antibody
Drug (DM4) Conjugate
CD19 Target
Phase I -
Two dose-ranging studies in patients with refractory/relapsed B-cell lymphoma (NHL)
TED6828 (U.S.) completed; once every 3-weeks
x 6 cyclesTED6829 (France) underway; weekly
for 8 weeks
SAR3419 was
created under a research collaboration with ImmunoGen, Inc.(1) Except Multiple Myeloma
Specifically expressed on B lymphocytes
Except plasma cellsIncluding early B cell progenitors (unlike CD20)
CD19 expressed in nearly all B-cell malignancies(1)
Potentially increased cytotoxic
effect against lymphoid tumors but with lower toxicity
Drug ~
Drug ~
~ Drug
~ Drug
Monoclonal
antibody
that
binds
specifically
to an antigen
target
found
on a cancer
cell
Linker that
keeps
the
cytotoxic
agent
attached
to the
antibody
until
inside
a cancer
cell, where
it
becomes
activated
Highly
potent cytotoxic
molecule
59
Our Early
Stage Development
Portfolio: Exciting, Novel
and Embracing External Innovation
BiTE®
antibodies combine targeting cancer with activating immune cells
Potential for treating both solid and hematological cancers
Combining
targeting
capability
of a mAb
with
cytotoxic
“warhead”
Early
signs
of clinical
activity
in lymphoid
malignancies
with
SAR3419
Blocking of ErbB-family signaling through the node of highest pathway sensitivity
Anticipated favorable safety profile to facilitate combinations
XL147 is
potentially
a first-in-class PI3K inhibitor
XL765 is
first in class with
a unique mechanism
of action combining
PI3K and mTOR
inhibition
Activity with long-term tolerability in patients with myelofibrosis
Potential for best-in-class based on biochemical profile and emerging clinical data
Discovering
activators
of p53 to restore tumor
cell
sensitivity
to treatment
Novel
approach
of inhibiting
protein-
protein
interactions
60
Concluding Remarks
Debasish
Roychowdhury, MDSenior Vice President, Global Oncology Division
61
Established
a nimble
organization
Solid
portfolio after
rigorous
pipeline review
Leveraged
internal
expertise and embraced
external
innovation
Created
networks with
scientific
community
Strong
Commitment
to Success
Implementing
a new approach
to the development
of late
stage and early
stage cancer treatments
Altering
governance
structures to support innovative
work
environment
Changing
attitude
Two fast track designations
Approval and launch of Jevtana®
Improved life cycle management
Realized synergies and new efficiencies across the entire oncology division
Drawing top talent with diverse background from industry and biotech, academia
Translating research findings from academia to developing cancer drugs
Creating new models for biotech alliances
Built Delivered
Transforming Attracting
62
Q&A Session
63
Diabetes IR Thematic
Seminar
September
30, 2010
64
Sanofi-aventis Poised
for Growth in Diabetes
Pierre ChancelSenior Vice President - Diabetes Division
65
A Strong
and Experienced
Team Presenting
Today
Christoph
Heinemann
Vice President Strategy & Operations, Diabetes Division•
Director Marketing & Access, sanofi-aventis Germany
•
Director
Metabolism
Business
Units, sanofi-aventis Germany
•
Director Strategy & Business Development, sanofi-aventis Germany
Jochen
MaasVice President Research & Development, Diabetes Division• Vice President
, R&D Europe•
General Manager, R&D sanofi-aventis Deutschland GmbH
•
Professor at Gießen-Friedberg University of Applied Sciences
Pierre ChancelSenior Vice President Diabetes Division•
Senior VP Global Marketing & Access, sanofi-aventis
• Managing
Director, Aventis UK & Ireland• VP Metabolism
Worldwide, Aventis
66
Diabetes
Burden
Expected
to Increase
Dramatically
Emerging
global epidemic of diabetes
More than
285m
people worldwide
are living with diabetes
Each
year
another
7m people develop
diabetes
Diabetes
causes about 5% of all deaths
globally
each
yearDiabetes
deaths
are likely
to increase
by more than 50%
in the next
10 years
Source: WHO, Multiple sources and internal
estimates
Diabetes
Prevalence (in million patients)
201020152020
BRIC-M U.S. EUTop 5
Japan
+48%
+30% +26%+8%
260
240
220
200
160
40
20
180
% Growth
over 2010-2020
67Harris MI. Clin
Invest Med 1995;18:231–239; Nelson RG et al. Adv Nephrol
Necker Hosp 1995;24:145–156; World Health Organization 2002;Fact Sheet N°
138.
Microvascular
Complications Macrovascular
Complications
Diabetic
RetinopathyLeading
cause of blindness
in working-age
adults
Diabetic
NephropathyLeading
cause of end-stage renal
disease
Heart
DiseaseLeading
cause of mortality
in patients with
Type 2 diabetes
PeripheralVascular
DiseaseLeading
cause of non-
traumatic
lower-extremity
amputations
Diabetic
NeuropathyLeading
cause of diabetic
foot syndrome and non-traumatic
lower-extremity
amputations
Stroke25% of all ischemic
strokes
are due to diabetes
alone
or with
hypertension
Diabetes is Associated with Multiple Micro and Macrovascular
Complications
Endocrinol
Metab
Clin 1996;25:243 -
254 (DCC Trial)
Risk of complications and HbA1c
HbA1c (%)
Relative risk
in %
1
3
5
7
9
11
13
15
6 7 8 9 10 11 12
RetinopathyNephropathy
MicroalbuminuriaNeuropathy
68
Significant
Unmet
Needs
in Diabetes
U.S. and EU Countries “Treat
to Target”(1)
HbA1c –
Glycated
hemoglobin(1) Adelphi Disease Specific Program (DSP) III and VII (sample of over 10,000 diabetic patient records) (2) Multiple sources and internal estimates
BRIC-M Countries Diagnosis(2)
42
37
13
4 40
5
10
15
20
25
30
35
40
45
50
<7% 7-8% 8-9% 9-10% >10%
165
71
Diabetes Patients DiagnosedPatients
(in million patients)% of patients Recommended
HbA1c Target
(43%)
58% above
target67%
undiagnosed
69
A Rapidly
Changing
Market
1990-2000 2000-2010 2010-2020
Therapies
Treatmentapproaches
Geographies
Business models
•
Metformin
/ Sulfonylurea
•
Insulin
•
Metformin
/ Sulfonylurea
•
TZDs, GLP-1s, DPP-IVs
•
Insulin analogues / Lantus®
•
Numerous
novel
drugs
& regimens
•
New insulin
forms, low-cost
insulin
analogs
•
Disease
modifying
& regenerative
medicine
•
1 to 2 OADs
•
Late insulinization
•
Premixed insulins
•
Insulin: Specialists
•
OADs: Primary Care Physicians
•
U.S. / Europe
•
Earlier insulinization
•
More drugs in treatment algorithms
•
Disposable pens
•
Broader
role
of PCPs
•
Higher
regulatory
hurdles
•
Greater
market
access
challenges
•
Holistic
approach
to diabetes
care
•
Identification of patient subpopulations
•
Advances
in insulin
pump
therapy
•
Disease
management program offerings
to payers
•
Cost-value relationship
key
to decision
•
Growing
role
of new players
(e.g. telecom, digital media, nutrition)
•
China the future largest
diabetes
market
in the world
TZDs
–
Thiazolidinediones
GLP-1s –
Glucagon-like peptide 1 agonists DPP-IVs –
Dipeptidyl
peptidase-4 inhibitors OADS –
Oral antidiabetic
agents
•
Skyrocketing
prevalence
in Asia, Latin America
and the Middle-East
70
Diabetes
Remains
One of the Largest
Growth Opportunities
in the Healthcare
Space
One of the fastest growing marketsOutgrew pharma
market by 5 pp between 2004 and 2010 A €33bn
market projected to reach close to €50bn
by 2015
Multiple drivers for growth> 300m clinically obese people globally(3)
Aging population Sedentary lifestyleUnhealthy dietImproved screening and earlier diagnosis
(1) IMS MIDAS Q2 2010, internal
analysis
(2) Multiple sources, internal
estimates
(3) WHO, “Global Infobase”
2010 and International Obesity Task Force (IOTF)
Devices
0
10
20
30
40
50
2004 2010e * 2015e *
Global Diabetes
Market(1,2)
Insulins
& injectables
OADs
+16%
+7%
20
33
+5%
48
+11%
+4%
+7%
CAGR+9%
CAGR+8%
€bn
71
FY 2009sanofi-aventis diabetes
sales€3,764m+19.4%
Western EuropeDiabetes
sales in 2009: €858m, +6.6%Diabetes
market
share
19.4%Rank #2
22.8%
Rest
of WorldDiabetes
sales in 2009: €313m, +24.0%Diabetes
market
share
13.6%Rank #3
8.3%
Emerging
MarketsDiabetes
sales in 2009: €621m, +25.0%Diabetes
market
share
13.9%Rank #2 16.5%
Sanofi-aventis Has a Well
Established
Global Presence in Diabetes
Net sales growth is at constant exchange rate
Market share in Diabetes market: IMS MIDAS MAT June 2010W. Europe: France, Germany, UK, Italy, Spain, Greece, Cyprus, Malta, Belgium, Luxembourg, Portugal, Netherlands, Austria, Switzerland, Sweden, Ireland, Finland, Norway, Iceland, DenmarkEmerging markets: World less North America (USA, Canada), Western Europe, Japan, Australia and New ZealandRoW: Japan, Canada, Australia and New Zealand
U.S.Diabetes
sales in 2009: €1,972m, +23.8%Diabetes
market
share
17.1%Rank #2 52.4%
72
0
1
2
3
4
5
2005 2006 2007 2008 2009 H1 2010
Lantus Apidra Insuman Amaryl
: Strong
Backbone
for Sanofi-aventis
A solid
heritage
: Still
an opportunity
for entry in volume markets
: Remains
a reference
in emerging
markets
and Japan
A success
story based
on innovation
: Our flagship
brand# 1 insulin
brand worldwide
# 1 anti-diabetic
drug
worldwide(1)
: Add-on to Lantus®
in basal-bolus
regimen
Two
award-winning
pen
devices
(1) IMS MAT June
2010
Sanofi-aventis Sales in Diabetes
CAGR 16.3%
€bn
® ® ® ®
73
0
2
4
6
2007 2008 2009 2010 2011 2012 2013
Lantus Apidra Insuman Amaryl
On Track
to Deliver
on our
Ambition
x2
® ® ® ®
€bnGlobal Diabetes
Sales
74
Our Growth
Drivers over 2010-2015
BG StarTM
i-BG Star®
LixisenatideFamily
EmergingMarkets
Potential
further
change to the treatment
paradigm
of type 2 diabetes
Significant
value added
offering
beyond
glucose measurement
Competitive profile now emerging for lixisenatide
within the growing GLP-1 segment Lixisenatide/Lantus®
combination expected to offer good fasting and post-prandial
glucose control
Positioned
to offer
a full set of solutions to a fast
growing
diabetes
patient population
PipelineIn-Licensing
Covering
the full treatment
options to adress
unmet
needs
in diabetes
75
Becoming
the 360°
Partner Delivering Best-in-Class and Integrated
Diabetes
Solutions
Disease
management
Patient education
Nutrition
Oral therapies(Amaryl®, Amaryl M®)
Insulin & other injectables
(Lantus®, Apidra®, lixisenatide)
Regenerativemedicines
Disposable
(SoloSTAR®)
Reusable (ClikSTAR®)
Pump
Blood Glucose Monitoring
(BGStar®, iBGStar
TM)
76
One Global Diabetes
Division: Delivering
on Sanofi-aventis’
Ambition in Diabetes
A global organization
focused
on diabetes
leadership and innovation
Objective to become
the first global diabetes
care company
Integrated
structure
comprising
all key
functions
working
on diabetes
R&D, Device
Development, Medical
Affairs, Commercial Operations and Business DevelopmentDirect responsibility
for 12 markets
(U.S., France, Germany, UK, Italy, Spain, Brazil, Mexico, China, Russia, India
and Japan)
Headquartered
in Frankfurt
77
World-class integrated insulin- dedicated site in Frankfurt
Active ingredient production, vials and cartridges filling, pen assembly & packaging Demonstrated ability to build innovative and competitive device solutions
Fast track industrial projects in emerging markets
Local insulin manufacturer acquired in Orel, Russia in 2009Plant to manufacture Lantus®
SoloSTAR®
in Beijing, China, in 2012
Strong
In-House Manufacturing
Capabilities
78
Diabetes
R&D Pipeline Continues to Build
New human peptide for islet neogenesis
New powerful
weapon
to lowering
LDL cholesterol
and CV risk
Potential
first-in-class GPR119 receptor
agonist
acting on both
insulin
secretion
and GLP-1 release
Lixisenatide
novel once-daily GLP-1 agonist
in late phase IIICompetitive profile vs. other once-daily GLP-1 productsPromising combination with Lantus®
Devices
to become strategic priority across the portfolioBlood glucose monitoring: Partnership with
Pipeline expanding into novel classes
via external innovation
79
Building on a Strong
Commercial Presence
Christoph HeinemannVice President, Strategy & Operations - Diabetes Division
0
5
10
15
20
25
2010e * 2015e *
€bn
CAGR+11%
Sanofi-aventis Well Positioned to Sustain Growth in the Fastest Growing Diabetes Market Segment
(1) Source: IMS Data
(2) MS MIDAS Q2 2010, internal analysis
Strong Historical Performance in the Injectable
Market(1)
Share of Sales
12
21
Global Injectables
Sales Expected to Grow Double-Digit(2)
Insulins GLP-1s
0%
10%
20%
30%
40%
50%
2001 2002 2003 2004 2005 2006 2007 2008 2009
Sanofi-aventis Novo Nordisk Eli Lilly
80
81
A Portfolio of Four Marketed Brands Supporting Growth
0
1
2
3
4
2005 2006 2007 2008 20090
50
100
150
200
2005 2006 2007 2008 2009
0
50
100
150
200
2005 2006 2007 2008 2009
Net
Sal
es (€
bn)
Net
Sal
es (€
m)
Net
Sal
es (€
m)
Net
Sal
es (€
m)
0
100
200
300
400
500
600
700
2005 2006 2007 2008 2009
82
Strong
Sales Evolution across
all Geographies
Lantus®
Apidra®
Insuman®
Amaryl®
0
0,5
1
1,5
2
2005 2006 2007 2008 20090
200
400
600
800
1000
2005 2006 2007 2008 2009
0
100
200
300
400
2005 2006 2007 2008 2009
Net
Sal
es (€
bn)
Net
Sal
es (€
m)
Net
Sal
es (€
m)
Net
Sal
es (€
m)
Western Europe
Emerging
Markets Rest
of World
U.S.
0
200
400
600
800
2005 2006 2007 2008 2009
83
0
1
2
3
4
#1 Diabetes
Brand Worldwide
Worldwide Rank of Leading Diabetes Brands
MAT June 2010 (€bn)
* Includes meters and strip test products sales
Source: IMS Data and Boston Biomedical consultants
Worldwide MAT June 2010 Diabetes Products Quarterly Review (data
converted to €
using 1.3$/€)
Actos® Avandia®Novomix®Januvia®/ Janumet®
Levemir®Humalog®Novorapid®Lantus® Accu-chek®* One Touch®*
#1
84
33%33%
23%
30%
44%
37%
0%
10%
20%
30%
40%
50%
2005 2006 2007 2008 2009
Short Acting Premix Basal
Leading
the Treatment
Paradigm
Shift towards
Basal Insulin
(1) IMS Data
Global Insulin Market Share by Class(1)
66%
54%
17%
3%
17%
41%
0%
10%
20%
30%
40%
50%
60%
70%
2005 2006 2007 2008 2009
Lantus Levemir NPH
Lantus®
Owns 2/3 of the Global Basal Market(1)
®®
Market share by type of basal insulin
85
China: Strong
Growth
due to
Diabetes center of excellenceAddressing need for medical educationTrain 10,000 healthcare providers within 3 years
Significant clinical developmentORIGIN study: >450 patients from ChinaLantus®
and Amaryl®
Phase IV trialsLixisenatide: participation in GetGoal
program
Partnerships with Chinese Diabetes Society
0%
10%
20%
30%
40%
Novo N
ordisk
Bayer
sanofi
-aven
tisEli L
illy BMS
Hangzh
ou Huad
ong
Servier GSK
0%
10%
20%
30%
40%
50%
60%55%
Diabetes
Market
Share
(%) MAT Growth
vs. last year
Top 8 Companies in Diabetes(1)
(1) IMS CHPA MAT June 2010
and
86
Brazil: Diabetes Leadership for Several Years
Highly
skilled
sales force at
specialist
and GP levels
Long-term
commitments to medical
education
Full portfolio offer including
Lantus®
and Amaryl®
High level
of service to health-care system (nurses, web, point-of-care)
(1) IMS MAT June
2010
0
10
20
30
40
50
60
70
2007 2008 2009 2010
Sanofi-aventisNovo NordiskEli Lilly
Sales (€m)
Sales in the Brazilian Retail Market(1)
(1) Schreiber SA, et al. Diabetes Obes
Metab
2007;9(1):31-38
(2) Schreiber SA, et al. Diabetes Technol
Ther
2008;10(2):121-127 (3) Pfohl
M, et al. ISPOR 2008 (4) Riddle M, et al. Diabetes Care 2003:26(11):3080-3086(5) Reviewed in:Eskesen
S, et al. Fam. Pract. 2006 Nov;55(11):1001-1003
(6) Arnolds S, et al. Diabetes Care July 2010 33:1509-1515 (7) Buse
J, ADA 2010 (8) Bergenstal
RM, EASD 2010
Lantus Cornerstone in Treatment Guidelines
Adapted from D.M. Nathan et al. Diabetes Care (2009) 32 (1):193-203ADA –
American Diabetes Association EASD –
European Association for the Study of Diabetes
At diagnosis
Lifestyle+
MET
Lifestyle + MET+
Lifestyle + MET+
SU
Lifestyle intervention
+ Intensive insulinBasal Insulin
Tier 1: Well-Validated Core Therapies
Well-Established in ADA and EASD Consensus Statement
Tier 2: Less Well-Validated Core Therapies
Partner Approved
indication Studies Note
Metformin (1) –
(5)
Sulfonylurea (1) –
(5)
Glitazones Pioglitazone(5)
DPP-IVs Sitagliptin(6,7)
GLP-1sExenatide(7,8)
other studies running
--
Well-Established to Partner with Other Agents
87
88
Lantus Use Has Led to Earlier Insulinization
0%
10%
20%
30%
40%
50%
60%
1-2 years 3-4 years 5-6 years 7-8 years 9-10years
>10years
2000 2010
0%
10%
20%
30%
40%
50%
60%
1-2 years 3-4 years 5-6 years 7-8 years 9-10years
>10years
2000 2010
Type 2 diabetes
and specialists
only
Source: Adelphi
DSP
Time from
Diagnosis Time from
Diagnosis
EU U.S.Patientson insulin
Patientson insulin
89
The ORIGIN Study
Has the Potential
to Change the Landscape
of Type 2 Diabetes
Treatment
Intermediate
Hyperglycemia
an important predictor
of diabetes
and CV risk2-fold
increased
risk
of diabetes
when
both
IFG and IGT are present(1)
IGT a marker for both
increased
risk
for diabetes
and CV disease(1)
More than
4 m people with
early
diabetes
in the U.S. and top 5 EU countries(2)
Other agents for glycemic
control
Endpoints:CV morbidity/mortality
All-cause mortality
Risk of diabetic microvascular
outcomes
Rate of progression of IFG or IGT to type 2 diabetes
+/-
ω-3 PUFA
+/-
ω-3 PUFA
Patients at
high
CV riskand IFG, IGT or newly
detected
diabetes
or established
diabetes(on 0 or 1 oral agent)
(1) Metabolic Disorders Study, Decision Resources, 2010 (2) GfK
2008 & Roper Global Diabetes Report. (Early diabetes: Type 2 diabetes patients with CV risk and on diet & exercise or 1 OADORIGIN: Rationale, design, and baseline characteristics in Gerstein HC, et al. Am Heart J 2008;155:26–32PUFA –
Polyunsaturated fatty acids IFG–
Impaired fasting glucose IGT–
Impaired glucose tolerance
90
Strong
and Sustainable
Platform for the Future
Insulin analogues are biological productsBiotechnology-derived proteins
Lantus®
covered by compound patent in key countries until November 2014
6-month pediatric exclusivity granted in the U.S. until February 2015 (pediatric study underway in EU)
No specific regulatory pathway currently established
U.S.: Under considerationEU: Guidance only for biosimilar
human soluble insulin since June 2006
Production capacity to meet market demand an important factor
Continuous COGS improvementLife-cycle management
Patient Support
Lantus®
to Become
Part of an Integrated
offer
MedicalEducation
91
Blood Glucose Monitoring Market is a Highly Attractive Market
Strip usage%
65%
23%
11%
1%
Strip Usage Pyramid
PumpUsers
IntensiveInsulin Users
OAD Users ± GLP-1
Diet & Exercise (No drugs)
Conventional Insulin + Basal
More Than 80% of Strips are Used by Insulin Patients(1)
(1) Proprietary Market Research(2) Source: Sanofi-aventis analysis using data from Boston Biomedical consultantsWorldwide Q1:10 Diabetes Products Quarterly ReviewSales 2010-2015=$69,248bn data converted to € using 1.3€/$
6.66.8
5.75.04.7
10.8
7.4
0
2
4
6
8
10
12
2005
2006
2007
2008
2009
2010
E20
11E
2012
E20
13E
2014
E20
15E
BGM Market Sales Forecasts
€bnCAGR (2005-2015e):
8 %
Market Offers Sustainable Growth(2)
No Generics
92
Co-Development
of innovative Devices
& Strips
Supply
viaCommercialization
through
sanofi-aventis
Strong
Partnership
with
Co-exclusive access to patented Dynamic ElectrochemistryTM
New levels of accuracy translating into higher patient safetyNo-coding, fully compliant with FDA requirements (no GDH-PQQ )
GDH-PQQ –
Gglucose
dehydrogenase
pyrroloquinoline
quinoneSource: AgaMatrix
(1) Parkes, J.L., et al Diabetes Care; 23:1143-1148, 2000.
Consenus
Error Grid
00 600500400300200100
600
500
400
300
200
100
iBGStarTM
Meter (mg/dL)
100% iBGStarTM in highest accuracy area(1)
Reference: YSI 2300 (mg/dL)
93
Leading
Innovation Towards Mobile Diabetes
Management
• First meter to connect to iPhone
and iPod touch
• Easy-to-use, no-coding
• Discreet design
• Applications to support Disease Management
CE mark and 510 k submission planned in Q4 2010 for iBGStarTM
94
Smartphone Platform Providing Superior Applications for Patient Self-management
Distribution of Smartphone Users Among
Diabetes
Population (U.S. estimates)
Smart phone usage of diabetic
patients increasing
from
17% today
to 46% in 2014
•
Electronic logbook for blood glucose, insulin dose and carbohydrates
•
Color-coding for hypo-hyperglycaemia
•
Seamless data exchange & communication
CE mark and 510 k submission planned in Q4 2010 for iBGStarTM
4.13.32.61.91.3
6.55.3
4.13.1
2.1
3.1
2.6
2.0
1.51.1
0
2
4
6
8
10
12
14
2010 2011 2012 2013 2014
65+45-6420-44
million
Sources: AdMob
Mobile Metrics Highlights May 2010, Gartner Mobile Trends 2010,
International Diabetes Federation website
95
Meal-time tagging
for glucose patterns
Positive feedback
Meal-time tagging
for glucose patterns
Positive feedback
Patented
Dynamic
Electrochemistry®
for assured
accuracy
Integrated Support Services 24h / 7d for Insulins, SoloSTAR®
/ ClikSTAR®
and iBGStarTM
Mini-USB for data transfer
to PC
Mini-USB for data transfer
to PC
Easy-to-use meterNo coding
Large, backlit
display
Easy-to-use meterNo coding
Large, backlit
display
Designed
by Listening
to Patients
96
Advanced technology:
Expertise with pen devices
Strong commercial presencePhysicians, nurses, pharmacies
Business model leveraging synergiesDiabetes sales forces for HCPsDTC for patientsDistribution: Wholesalers, pharmacy and mail-orderCustomer service integrating Lantus®
Revenues on sales of stripsPositive halo effect expected on Lantus®
and other products
All Elements
in Place for Successful
BGM Market
Entry
Launches
in U.S., Germany and France early
Q1 2011
Further
roll-out across
Europe in 2011Asia
and Latin America
launches
planned
for 2012
CE mark and 510K obtained for BGStar®
CE mark and 510 k submission planned in Q4 2010 for iBGStarTM
97
BGStar®
and iBGStarTM: Introductory video
98
Today’s
Commitments for the Treatments
of Tomorrow
Jochen
MaasVice President, Research & Development - Diabetes Division
99
Holistic
Approach
to Innovation in Diabetes
Diabetes
Pre-Diabetes
and Diabetes
are the “entry”
into
multiple diseases
Innovative Improvement of the Classical Paradigm• New drug combinations• New modes of action• New insulins
+ Risk
Factors• Lipid
disorders• Obesity• Metabolic
syndrome
+ Late Manifestations• Microvascular
complications• Macrovascular
complications
+ Diagnosis
and Devices• Monitoring• Delivery
(pen
devices, pumps)
100
Diversity
of Targets
to Address
Unmet
Needs
in Diabetes
–
Five Main Pillars
for R&D
Short-Mid
Term
Win
Improve
on classical
paradigm
•
Extended drug action•
Combinations•
Improved devices•
Safer compounds•
Disruptive device
technology
•
New superior insulins•
Cost-effective solutions
Long-Term
Win
Address
-celldefect
Protectend-organs
•
Protect/improve
-
cell
function•
Preserve/increase
-
cell
mass•
Replace -cell
pool via regeneration,
cell
or gene
therapy
•
Microvascular
complications:
NephropathyNeuropathyLimb ischemiaRetinopathyWound healing•
Macrovascular
complications:
CAD / MIStroke
Less
Morbidity, Better
Quality
of Life, “More Value for Money”
Towards
artificialpancreas
Development of closed-loop system•Continuous glucose sensors•Insulin pumps, IT and control algorithm•Short-acting insulins
and glucagon analogues
Correct metabolic
dysfunction
•
Mimic caloric restriction
•
Target mitochondria dysfunction
•
Address lipid dysfunction (lipid toxicity, dyslipidemia, NAFLD/NASH)
•
Address vascular and cardiomuscular
metabolism dysfunction
Clinicians Patients PayersHealth
Care Providers
NAFLD –
Non-Alcoholic Fatty Liver Disease
NASH –
Non-Alcoholic Steato
Hepatitis
101
Worldwide
Connected
Network of Selected
Partners
EUROPE
Corporate Partners•
Genfit, France•
Zealand Pharma, Denmark
Academia/Consortia•
AVIESAN (Alliance Nationale
pour les Sciences de la Vie et de la Santé), France
•
IMI (Innovative Medicines Initiative) / IMIDIA (Innovative Medicines Initiative Diabetes project), EU
•
Institut
de la Vision, France•
Charité
-
Universitätsmedizin
Berlin, Germany•
Juvenile Diabetes Research Foundation (JDRF), WW
Academia•
California
Institute of Technology•
Salk
Institute for Biological
Studies•
Burnham Institute
Corporate Partners•
AgaMatrix•
CureDM•
Regeneron•
Wellstat•
Metabolex
U.S. ASIA
Corporate Partners•
Huya, China
Academia•
SIBS (Shanghai Institutes for Biological
Sciences), China
102
Lantus®
Insulin glargine
Reduction in CV morbidity & mortality
SAR236553 (REGN727)
Anti-PCSK9 mAb
Hypercholesterolemia
SAR260093 (MBX-2982)
GPR-119 agonist
Type 2 Diabetes
lixisenatide
+ Lantus®
GLP-1 agonist + insulin glargine
Type 2 diabetes
SAR176975 (PN2034)
Insulin
sensitizer
Type 2 diabetes
lixisenatide
(AVE0010)
GLP-1 agonist
Type 2 diabetes
Phase I
Phase II
Phase III
Pipeline Products
in Development
Already
a Significant
Expansion of the Diabetes R&D Portfolio
Status
Update
Phase IIa
study results expected in Q4 2010
Planned
submissions
for EU and Japan
in H2 2011 and for the U.S. in H2 2012
Investigated
as “free combination”
in Phase III
Evaluating
preclinical
observations and performing
additional
preclinical
work
ORIGIN study
results
expected
in 2012
Initiation of Phase II expected
in H1 2011
Partners: Lixisenatide
(AVE0010)/Zealand Pharma
–
SAR176975 (PN2034)/Wellstat Therapeutics –
SAR260093 (MBX-2982 )/Metabolex
–
SAR236553 (REGN727)/Regeneron
103
Lixisenatide: A New GLP-1 to Overcome
Limitations of Standard Type 2 Diabetes
Treatments
Current
Therapy
Limitations•
Risk
of hypoglycemia
•
Inadequate
PPG control•
Weight
gain
•
Specific
adverse events•
Progressive ß-cell
failure
GLP-1 Actions•
Low
risk
of hypoglycemia
•
Pronounced
effect
on PPG•
Weight
loss
•
Good safety
profile•
ß-cell
preservation
effect
(animal models)
Lixisenatide•
Modified
exendin-4 molecule
•
SIP®
technology•
Half
life ideal
for once daily
dosing
PPG –
Post-Prandial
Plasma Glucose
104
Lixisenatide: Promising Profile in Phase IIb
Good effect on HbA1c, postprandial glucose levels and weight loss
Favorable gastrointestinal tolerability profile (nausea, vomiting or diarrhea)
Convenient once-daily subcutaneous injection
Clear dose-effect relationship 20 μg
once-daily selected for
phase III
Ratner
R, Poster 433P, ADA 2008 13-week, multicenter, randomized, placebo-controlled, parallel-group study in metformin-treated patients (52-56 patients/group) –
Results of 5, 10, 20, 30μg BID not given in above charts
HbA1c (%)
-0.8
-0.6
-0.4
-0.2
0
AVE0010 QD Dose
Cha
nge
in H
bA1c
at
Wee
k13
5
μg placebo
10μg
20
μg
30μg
(Baseline mean
HbA1c: 7.55%)
Mean
Body Weight
(kg)
-4
-3
-2
-1
0
AVE0010 QD DoseCha
nge
in W
eigh
tat
Wee
k13
placebo5
μg
10μg
20
μg
30μg
(Baseline mean
weight: 89kg)
105
Phase III Program Covers Multiple Treatment
Paradigms
Study Objective # of Patients
GETGOAL-MONOMonotherapy
360
GETGOAL-MDose flexibility
680
GETGOAL-F1Titration
regimen
(1 or 2-step
titration) 450
GETGOAL-SEfficacy
on top of SU (+
MET)855
GETGOAL-PEfficacy on top of pioglitazone
(+
MET)450
GETGOAL-X Head-to head vs. exenatide
(+
MET) 600
GETGOAL-LEfficacy
on top of basal insulin(+
MET)450
GETGOAL-L
Asia
Efficacy
on top of basal insulin(+
SU)300
GETGOAL-MONO Japan
Monotherapy 66
GETGOAL-M-AsChina
Efficacy
on top of MET (+
SU) 380
Program fully enrolled(1)
All studies expected to be completed and analyzed in 2010 or 2011 Lixisenatide
given 20 µg
once-daily for 24 weeks(2)
Long-term study extensions includedFirst results available for
GETGOAL-MONOGETGOAL-L Asia
Phase II/IIIb
studies initiatedVs. liraglutideVs. sitagliptin
(1) Except GETGOAL-M-As which started mid-2010 (2) Except in GETGOAL-MONO (12 weeks) SU –
Sulfonylurea MET –
Metformin
106
GETGOAL-MONO: Encouraging
Initial Phase III Data
Statistically significant improvement in all blood glucose parameters
Pronounced effect on PPG
More patients reached HbA1c targets in lixisenatide
groups
Mean decrease in body weight (-2 kg) observed in all study groupsGood safety and tolerability
Gastro-intestinal adverse eventsNausea: 22.2% (lixi.) vs. 4.1% (placebo)
Vomiting: 7.1% vs. 0%
Diarrhoea: 2.9% vs. 2.5%
FPG -
Fasting Plasma Glucose PPG –
Post-Prandial
Plasma GlucoseGETGOAL-MONO: 12-week study in patients with type 2 diabetes not treated with antidiabetic
agents (361 patients randomized)Baseline overall mean HbA1c 8.04 % Baseline overall mean body weight 87.2 kg
Efficacy Parameters
Two-Step Titration
One-Step Titration
Change in HbA1c (%) vs. placebo
-0.54 -0.66
Change in FPG (mmol/L) vs. placebo
-0.87 -1.08
Change in 2-hour PPG (mmol/L) vs. placebo
-3.86 -4.82
% of patients with HbA1c 6.5%
31.9 25.4
(12.5% in placebo group)
% of patients with HbA1c <7%
52.5 46.5
(26.8% in placebo group)
GETGOAL-L Asia Shows First Results of Lixisenatide Used on Top of Basal Insulins
Lixisenatide
given as add-on treatment to basal insulin ±
SU
60% of patients on Lantus®
Study met HbA1c
primary endpointNo specific safety concernFull data presentation expected in 2011 at ADASimilar GETGOAL-L trial in U.S., EU & other countries
GETGOAL-L Asia: 24-week study in patients with Type 2 diabetes previously treated with basal insulin ± sulfonylurea (311 patients randomized)Baseline mean HbA1c: lixisenatide
8.54% Placebo 8.52%
Mean Change in HbA1c Baseline to Endpoint
0.11
-0,77
LS Mean Change vs. Placebo -0.88-1
-0,8
-0,6
-0,4
-0,2
0
0,2
Plac
ebo
N=1
54
Lixi
sena
tide
N=1
46
p<0.0001
107
108
Lixisenatide, Emerging Competitive Profile in the GLP-1 Arena
Current trial results bode well for the success in demonstrating an excellent profile The right candidate after OAD failure or as an add-on to basal insulinsPen device planned for market entryCardiovascular investigational plan aiming at making lixisenatide
the first GLP-1 with a cardio-safety “claim”
at launch (U.S.)
Cardiovascular outcome study initiated mid-2010
6,000 patients with Type 2 Diabetes who experienced an Acute Coronary Syndrome event
Full Range of Delivery Systems Considered
109
Lixisenatide: the 1st
Step to a Unique Combination with Lantus®
Elements in favor of a GLP-1 acting on PPG vs. short-acting or premix insulins
Better weight managementLower risk of hypoglycemiaLimited number of daily injections
Strong rationale for combination with Lantus®
Lantus®
the only true 24h basal insulinMixability
of compoundsLixisenatide
successfully tested on top of Lantus®
in GETGOAL-L AsiaComplete Phase III development plan being finalized following interactions with FDA / EMA
Expected Benefits on Fasting and Post-Prandial
Glucose
Blood glucose
PPG –
Post-Prandial
Plasma Glucose
Breakfast Lunch Dinner
Blood glucose
110
Different Patient Populations Likely to Benefit from lixisenatide
and Lantus®
Combined Use
Patients who have failed on OADsEarly stage patients failing 1 or 2 OADs
(HbA1c>8.0%) and overweight or obese (BMI>30)
GLP-1 optimizationPatients already
treated
with
a GLP-1 and still
uncontrolled
(HbA1c>7.5%)
Lantus®
optimizationPatients already on Lantus®
who could benefit from a GLP-1 induced additional post-prandial
effectCurrently investigated in clinical trial(2)
~5m patients
~1.8m patients
~2.2m patients
Estimated
Target Population(1)
(U.S. and top 5 EU countries)
(1) Adelphi
estimates
(2) Study
EFC10781
111
: Continuous
Commitment
to Safety
Any
new observational
study
on the associations between
insulin
and cancer risk
needs
to be
of the highest
standards
Consensus on Best Practices published
in December
2009(1)
Ambitious
epidemiological
investigational
plan ongoing:
Two
retrospective
cohort
studiesPrescription databases
in Nordic
countriesU.S. diabetes
registriesData presentation
expected
in 2012
One case-control study
The International Study on Insulin and Cancer (ISAC)A case-control study
of recent
breast
cancer occurring
in patients with
diabetes
selected
from
general
practiceFrance, UK and CanadaData presentation
expected
in 2013
(
1
)
P Boyle, ecancer, 174, 11/12/2009
112
Targeting
Slowdown
of Diabetes
Progression with
a Novel
GPR Agonist
SAR260093: A potent selective orally active GPR119 agonist
Unique dual mechanism of action (insulin secretion and GLP-1 release)
Phase IIa
results expected in Q4 2010
GPR –
G-protein-coupled
receptors
Figure sourced from Overton, HA et al.; Br. J. Pharmacol. 2008, 153, S76-S81.
113
LDL levels
Corrections of Metabolic
Dysfunctions Lower
PCKS9 Leads
to Lower
LDL and CV Risk(1)
PCSK9
LDLR degradation
LDL
LDLR
(1) Cohen J, et al. N Engl
J Med 2006; 354:1264-1272c
Inhibition of the PCSK9 enzyme
# of Low
Density Lipoprotein
Receptors
(LDLR)
114
Encouraging Early Phase I Data: Read Out with our Anti-PCSK9 mAb
> 60% LDL reduction following single iv doseSimilar LDL reduction with single dose delivered scDuration of effect with sc dosing suggests at least q2week dosing, if not moreNo serious adverse events to datePreliminary data suggest similar magnitude of LDL reduction when added to statins
in Familial
Hypercholesterolemia (FH) and non-FH subjectsInitiation of Phase II program expected in H1 2011
-70%
-60%
-50%
-40%
-30%
-20%
-10%
0%0 1 3 7 10 14
Days
% C
hang
e in
LD
L fro
m B
asel
ine
Dose G Dose H Dose I
SAR236553
Single Dose sc
Effect
on LDL
SC–
Sub-cutaneous
115
One of the First Regenerative
Approaches
Entering
into Clinical
Trials
Pancreatic islet neogenesis, one of the potential curative approaches to restore patients own pancreatic functionSAR288233, the Human proIslet
Peptide (HIP)(1)
14-amino acid bioactive peptideImproved glycemic
control and significant increased islet number observed in mice(2)
Could apply to both type 1 and type 2 patients Ready to enter Phase I in 2011
Light green: Adult
pancreatic
isletcontaining
ß-cells
which
still
proliferate
(1) Partnership with CureDM(2) Levetan
C et al. Endocr
Pract. 2008;14(No. 9);1075-1083
116
Early
Projects
Directly
Addressing
Complications of Diabetes
Cardiovascular complicationsStrong effectiveness evidenced with Cathepsin
A inhibitor SAR164653 in pharmacological models of heart
failureInnovative first-in-class approach
Very favorable ADME and safety profile demonstrated in preclinical studies
Phase I expected to start in 2011
Diabetic nephropathy
SAR101099,
a long lasting
Urotensin
II antagonistPhase I initiated in Q3 2010
Intensive cooperation with internal partners (e.g. Fovea, Fibrosis Unit)
(1) AHA heart
disease
statistics
2010
(2) http://schoolwalk.diabetes.org
Increased
Risk
of Serious Complications in
Diabetes(1,2)
2-fold
increase
in the risk
of death
within
one year
post-MI
Diabetes, the leading
cause of kidney
failure
Diabetic
retinopathy, a leading
cause of blindness
117
Concluding
Remarks
Pierre ChancelSenior Vice President - Diabetes Division
118
Sanofi-aventis –
Poised
for Growth
in Diabetes
Diabetes presents healthcare and economic challenges in terms of prevention and control
Diabetes is one of the largest business opportunities in the healthcare space and a growth platform for sanofi-aventis
Sanofi-aventis is well positioned with concrete steps forward fulfilling our vision to deliver tailored and integrated solutions to people living with diabetes and healthcare providers
Lantus®
poised for future growth despite a more complex environmentLixisenatide
and [lixisenatide
+ Lantus®] opportunity to open new avenues in the management of diabetesR&D and business development fully committed to adress
unmet needs Towards an integrated offer with new devices
119
Q&A Session
120
Conclusion
Hanspeter
SpekPresident, Global Operations