OVERVIEW

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OVERVIEW
GOMEZ Emmanuel SQUEDIN Thomas LETURGEZ
Thibaut DELEPIERRE Alban
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Institut Mérieux
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• Silliker, headquartered in Chicago
• Institut Mérieux has a 89 holding in the
  company
• Within the Nutrition / Health division of
  Institut Mérieux, Sillikers mission is both to
  improve nutrition and enhance the quality and
  safety of food products.

4

• Transgene, based in Strasbourg
• Biopharmaceutical company dedicated to treating
  infectious diseases and cancer.
• Institut Mérieux has a 55 holding in the
  company
• It develops therapeutic vaccines and innovative
  immunotherapy products based on exclusive
  technologies for stimulating patient immune
  systems by using vectors for the expression of
  tumoral or infectious antigens in target cells.

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BioMérieux Presentation

• A world leader in the field of in vitro
  diagnostics for over 45 years.

• Designs, develops, manufactures and markets
  Reagents,
• Automated instruments.

• For medical analysis and quality control of
  products of agro-food, cosmetics and
  pharmaceuticals.

• Contribute to the improvement of public health
  worldwide

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History
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Global presence

• BioMérieux a part of the Institut Mérieux group

BioMérieux is present in 150 countries.
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Global presence

• It has 17 production sitesDistributed in
  France, the Netherlands, the United Kingdom,
  Italy, the United States, Brazil, Japan and
  Australia
• A European logistics center located in France.

• Based in Marcy-l'Etoile, France

• Employs 6000 people worldwide, 880 people are
  dedicated in bioMérieux, research, divided in 13
  research centers in the United States, Brazil and
  Europe (Lyon - France, Florence - Italy, Boxtel -
  Country Netherlands).

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BioMérieux Some results in 2008

• 8th Global Society in diagnostic biological

• AC 1 111 million Euros
• Realizes over 81 of its international business

• Anonymous Society, capital 12.029.370
• Sales growth 9,8
• Cash flow 19

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Status

• Anonymous society (AS) is a corporation so named
  because his name does not reveal the names of
  shareholders it may not even know the identity
  when the company is on the stock exchange.
• Conventional Structure
• A GD
• A Board of Directors (11)
• General meetings.

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Corporate Governance

• Board of Directors, Chairman Alain Mérieux.
• Management Committee 11

Alexandre Mérieux
Alain Mérieux
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CAPITAL
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Stock-Market

• Stock exchange data
• Number of shares 39 453 740
• Capitalization of stock-market 3 223.77 MEUR
• Activity sector Medical equipment

• Share characteristics
• Market NYSE Euronext Paris
• Stock symbol BIM

• Average daily trading volume in 2008
  approximately 34,700 shares gt for a value of 2.3
  million euros.

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SHARE PRICE PERFORMANCE IN 2009
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Acquisitions
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2006 Sales by technology
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Economic model

• ?Very different business model from the
  pharmaceutical industry.
• Highly diversified product portfolio ? less risk
• In sales no blockbuster
• In the development pipeline
• Shorter development cycles
• No risk from generics
• Lower product liability risk In vitro vs In
  vivo

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A promising market
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The sentence
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Strategy

• From a strategy focused on the laboratory
• ?Infectious diseases, oncology and cardiology
• ?Industrial applications

• To a strategy focused on pathologies and
  clinicians needs
• ?Infectious agents clinical and industrial
  applications
• ?Tests delivering high medical value
• Oncology
• Cardiology
• Point-of-care tests
• Theragnostics therapeutics and diagnostics

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Strategy Domain
Technologies Bacteriology Molecular Biology Immunoassay Clinical Chemistry Hematology Hemostasis
2300 1800 8700 9100 1200 1200
Growth 3 - 4 10 - 12 3 - 4 4 -5 3 - 4 3 - 4
Low Medium High High Medium Medium
Pathologies
Industrial applications
Infectious diseases
Cancers
Cardio-vascular diseases
Diabet
Clinical chemistry
Endocrin Tests
Blood analysis
Auto-immun diseases
TDM/DOA tests
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Clinical applications
?become a major reference for doctors and
biologists on key pathologies
?Partnerships with pharmaceutical / biotech
companies specialized in these pathologies. ?Cross
-functional approach by pathologies - One lead
manager for each pathology
Bacteriology Molecular biology Immunoassays
Infectious diseases
?Sepsis Bact/Alert GeneXpert VIDAS PCT
?Nosocomial infectious PPM, VITEK 2 Diversilab VIDAS CDA2
?Tuberculosis Bact/Alert Gen-Probe
?VIH/Hepatitis easyMAG/EasyQ VIDAS HIV
Cancers VIDAS PSA
Cardio-vascular diseases VIDAS D-dimers
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Commercializing network
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Commercializing on the quality of commercial
network
2007 2012 Growth rate
5-6

• Internal RD pipeline
• Sales network optimization

1
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Optimization of commercial network

• Geographical priorities United states and Japan
• Sustained creation of new subsidiaries
• Algeria 2007, South Africa 2007,
• Singapore 2008, Dubai - 2008

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Etablishment of a global department

• Creating a world business management

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Commercializing on the quality of commercial
network

• Pipeline after internal RD
• Optimization of commercial network

5-6
1

• Business Development
• Distribution agreement
• Acquisitions
•  Product companies

1-2
Total
7 - 9
Compound annual growth rate
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Industry Control
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Industry Control
?leader sector consolidation
Aim 2012 ? a market share of 30
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Industry - Strategy
?Became the leader in industry consolidation

• Undisputed Leadership
• Capitalizing on the clinical commercial network

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Partnerships

• Copan 2007
• Exclusive worldwide distribution agreement
  authorizing bioMérieux to market, for the
  pharmaceutical industry, an innovative sample
  collection system based on technology developed
  by Copan.
• This patented product marks a major breakthrough
  because it is the first swab on market that can
  be used to perform a quantitative environmental
  control.
• ?The unique texture of the Nylon flocked swab
  picks up more microorganism than conventional
  swabs. It is specifically designed for aseptic
  manufacturing facilities control.

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Acquisition for Industry
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BTF

• Provides the world's most precise quantitative
  reference standards for microbiological testing .
• Use to verify the performance of control methods.
• Target customers in the industrial microbiology
  market, specifically testing water, food and
  pharmaceutical products
• ?BTFs range of products and expertise are a key
  addition to portfolio of solutions for
  microbiological control

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• Infectious diseases expertise

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Infectious diseases Clinical diagnostic and
industrial microbiology.

• Independence and expertise field
• International scope
• 45 years of experience and know-how
• Scientific and technological innovation
• 13 of the sales in RD
• 3 main technologies
• Bacteriology
• Immunoassays
• Molecular biology

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Strategic plan 2007/2012

• Bacteriology be an incontrovertible leader
• Accelerate the complete automation of analysis
  processes
• Focus on chromogenic media
• Molecular biology become the key leader in
  sepsis and HAI
• Be the leader of molecular diagnostic automation
  of HIV and hepatitis
• Biochips launch of a multi-target genetic test
  PLC (ADNA project)
• Immunoassays increase the number of
  high-medical-value tests and reinforce the Point
  of Care activity
• VIDAS/VIDIA extend the product range
• Patients Point of Care
• Based on the expertise in infectious diseases,
  technical mastery and on a large number of
  products already on the market.
• Positioning Full automation Point of care in
  clinical market

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Areas of Expertise

• Healthcare Associated Infections ?
• HIV ?
• Sepsis ?
• Tuberculosis ?
• CNS infections
• Gastro-intestinal infections
• Hepatitis
• Mother-to-child transmission
• Urinary tract infections
• Respiratory infections
• Sexually transmitted infections

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Products and strategy

• Improve the clinical presence (Superbugs,
  Theranostic )
• Transverse approach regarding pathologies
• One manager for each pathology
• One sponsor for each pathology in the executive
  committee
• ?Partnerships with pharmaceuticals
  industries/biotechs working on those diseases.

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Healthcare Associated Infections

• Among the 10 leading causes of mortality in
  industrialized countries.
• Impact on the length of hospitalization and
  related healthcare expenses.
• 5 billion annually in U.S. (WHO figures, 2005)
• Affect around 10 of hospitalized patients, 1.4
  million worldwide each day
• Often characterized by resistance to antibiotics
• bioMérieux research
• New strains of drug-resistant bacteria adding to
  collection of over 30,000 bacterial stains,
  Centers for Disease Control (CDC)
• Automation Full Microbiology Lab Automation,
  futher reducing time to result for bacterial
  identification.
• Chromogenic media direct, reliable and rapid
  isolation of bacteria
• Prevention and surveillance screening of
  patients, hospital environmental controls,
  epidemiological surveillance.
• Intervention identification, antibiotic
  susceptibility testing, genotype
  characterization, identify the source of
  infection and prevent epidemics.

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Sepsis

• Sepsis is the leading cause of death in
  non-coronary intensive care units.
• Mortality from severe sepsis 32 to 54
• In developed countries estimation of 3,000
  people die of severe sepsis a day.
• In US, total cost of 16.7 billion dollars a year
• Due to the aging of the population, invasive
  diagnostic techniques and increasing bacterial
  resistance to antibiotics, the number of patients
  with sepsis is rising steadily worldwide.
• bioMérieux research a race against the clock
• Tests easier to use, at the patient points of
  care
• Reduced time for the analysis of blood samples
  from several days to just 2hours
• Diagnostic
• Procalcitonin (PTC), introduced in VIDAS system.
• 20min to have early indications so the patient
  can be given adequate treatment
• Same technology for monitoring antibiotic therapy
  and patients response to treatment
• Bacterial identification and antibiotic
  susceptibility testing VITEK 2 system, Etest
  (MIC)
• Automated blood culture BacT/ALERT 3D, rapid
  growth and detection.

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FMLA Full Microbiology Lab Automation TM

• To face challenges, automation
• Standardization
• Speed
• Controlling healthcare costs
• Added value

• - Inoculation of Petridishes PREVI Isola
• - Automated staining of sample slides PREVI
  Color Gram
• - Urinary screening (detection of bacteria and
  particles) UF-1000i 
• - Blood culture BacT/ALERT
• Identification of bacteria and automated
  antibiogram VITEK 2
• - Genotyping of microbialstrains DiversiLab
• - VIDAS
• - NucliSENSEasyQ
• - NucliSENS easyMAG

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A strategic partnership with Hitachi
High-Technologies Corporation focused on
microbiology and molecular diagnostics
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Patients Point of Care

• Test performed and interpreted near the patient,
  by a physician or a nurse.
• An estimatedmarket of 4b
• U.S. 65 of the market
• Averagegrowth rate 10 a year
• bioMérieux POC strategy
• Manualrapid tests
• QuickVue tests distribution agreement
  withQuidel (2008)
• Meikang Biotechrapid tests following acquisition
  (2010)
• Handheld diagnostic solution Partnership with
  Philips (2013)

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Results - Q4 2009

• Clinical field 7,4 sales increase
• Extraction reagents (NucliSENS easyMAG) H1N1
  influenza
• Interest in FMLA (audit asked) especially PREVI
  Isola and PREVI Color Gram
• Immunoassays VIDAS, microplate screening, rapid
  testing

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2009 Product Launches

• bioMérieux expanded its line of automated
  screening tests for Methicillin Resistant
  Staphylococcus aureus (MRSA), one of the leading
  causes of healthcare-associated infections
• In the US, chromID MRSA, chromogenic media that
  enables visual identification of MRSA colonies in
  patient sample
• In Europe, NucliSENSEasyQ MRSA, molecular
  diagnostic MRSA test on the EasyQ automated
  platform
• For both emergency and routine patient situations
• 17 new productswerebrought to marketduring the
  year
• NucliSENSEasyQ HIV-1 v2.0, help FU of HIV
  positive patients
• VIDAS EBV, detection of EBV, 80 of infectious
  mononucleosis cases
• VILINKTM, a secure network connection for VITEK2
  installations
• VITEK2 PC 4.02, software application compatible
  with European antimicrobial susceptibility
  standards (EUCAST)

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Bacteriology - strategy
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Bacteriology - Strategy

• ?Become the undisputed leader

• More than 40 years of experience
• More than 50 of the market in automated
  bacteriology

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Partnerships

• Cepheid - 2007
• The product menu comprises both bacterial and
  fungal identification assays as well a series of
  genetic markers for antibiotic resistance.
• Cepheid is in charge of manufacturing
• bioMérieux distributes the sepsis assays
• LabTech Systems - 2007
• signed an exclusive worldwide license agreement
  for LabTech Systems automated pre-poured media
  (PPM) ? MicroStreak.
• Eiken Chemical Co., Ltd. (Japan) - 2007
• Production of PPM for Biomérieux by Eiken
  Chemical Co.
• Sysmex (Japan) - 2008
• UF-1000i is highly standardized and automated
  solution for urinary screening methods.
• Quidel (USA) 2008
• Exclusive distributor of Rapid diagnosis test for
  Quidel. (Except USA, Japan and Scandinavia)

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Acquisitions for bacteriology
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Acquisition of PML microbiological

• In vitro diagnostics company that provides
  culture media and microbiological products for
  both clinical and industrial applications.
• ?With this acquisition, bioMérieux is now

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Molecular biology
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Molecular biology - Strategy

• ?Become the leader in sepsis and
  hospital-acquired infections

• Expertise across the chain
• ? extraction, amplification, detection
• Ability to capitalize on know-how in infections

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Partnerships

• NuGEN Technologies Announce Cross-License and
  Supply Agreement. (USA) - 2007
• NuGEN's exclusive WT-Ovation RNA Amplification
  System.
• enhances Biomérieux amplification capabilities
  for clinical use.
• AdvanDx (USA) - 2007
• To provide rapid results for Bloodstream results.
• identification of bacteria and yeast from
  positive blood cultures in less than three hours.
• Hitachi High-Technologies (Japan) 2008
• RD partnerships Focus on Microbiology and
  Molecular Diagnostics

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Immunoassays
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Immunoassays - Strategy
?Extend the high medical-value test menu and
strengthen the point of care business

• Installed base of more than 20,000 instruments
• Expertise in antibodies

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Partnerships and Acquisitions
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China Strategy
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bioMérieux in China today

• A long-standing presence
• Since 1978
• 1992 Hong Kong
• 2005 HQ moved to Shanghai
• 5 offices and more than 100 FTE
• A large distributor network
• A strategic foot hold in China
• A large site and a strong team (mid-2010)
• China becomes bioMérieux 3rd corporate pillar
• Research team in Fudan University Cancer Hospital
  (Shanghai)
• Joint-venture with Shanghai Kehua Bio-engineering
  (microplates)
• POC strategy Manual rapid testsPhilips
  partnership
• Meikang Biotech acquisition  this adds up 

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MeikangBiotechActivites synergy

• A well-establishedc ompany, Dr Chang - 1992
• 150 employees, 100 contractors
• Sales about 5M
• A wideproduct range rapid tests
• Infectious diseases
• Carido-vascular and oncology
• Drugs of abuse
• Pregnancy and hormone testing
• A fully-owned manufacturing site in Shanghai
• 9,000m2 on 2 hectares of land
• 30 million tests per year
• Certifications GMP, ISO 9001, ISO 13485,
  Manufacturing license class III (Shanghai FDA)

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MeikangBiotechHigher ambitions for the Group

• Support business growth in China
• Rapid tests ideally complementing bioMérieuxs
  product offering, mainly for infectious diseases
• In the coming years additional production
  capacities
• Optimize cost structure of products for
  developing countries
• Leverage RD expertise and develop innovative
  products
• Additional immunoassay RD capabilities for new
  rapid tests
• A beachhead for the rapid diagnostics and POC
  markets

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Theranostics
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Theranostic

• The good drug for the good patient at the good
  time
• A theranostic is a diagnostic test that helps
  clinicians make the right therapeutic decision
  for the right patients, enabling a more
  personalized approach to medicine.

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Theranostic
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•  Le theragnostic devrait déboucher sur un fort
  développement commercial après 2012 

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The Scientific need

• The overall five-year survival rate is still only
  66. Causes for this high mortality rate include
  
• late diagnosis
• challenging tumor identification and
  classification
• inappropriate treatment, all of which lead to
  poorer patient outcomes

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Partnerships - Cancer

• Leading Biotech for discovery and validation of
  molecular biomarkers and proteomics,
• particularly for early detection and prediction
  of treatment efficacy
• ExonHit (France) breast, colon and prostate
• ProteoSys (Germany) prostate cancer
• Other partners contribute their expertise
• French Atomic Energy Commission (CEA)
• the French National Scientific Research Center
  (CNRS)
• the Lyon University Hospitals (HCL)
• ST Microelectronics (ST)
• Claude Bernard University in Lyon (UCBL).

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Biomarkers Development
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Plan 2007 -gt 2012
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Sept. 17, 2007. Patership in theragnostic
development

• Co-funded The development of a companion test for
  BN83495 intended for both
• Clinical development of the compound
• Diagnostic test  potentially for future
  commercialization
• The test will be developed on NucliSENS EasyQ
  molecular diagnostics platform. NASBA
  amplification technology.(CLIA certified
  laboratory)
• Tumour marker tests
• determining the molecular signature of tumours
• guiding a rational choice of treatment for
  defined patient groups.

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The Target

• Novel breast cancer therapy
• designed to block the steroid sulfatase enzyme
  (STS).
• sulfated steroid precursors estrogens
• STS
• during pregnancy
• Found in hormone-dependent breast cancer in
  postmenopausal women, but not BMI.

Role of steroid sulfatase in local formation of
estrogen in post-menopausal breast cancer
patients.Nakata T, Takashima S, Shiotsu Y,
Murakata C, Ishida H, Akinaga S, Li PK, Sasano H,
Suzuki T, Saeki T.Pharmaceuticals Research and
Development Division Kyowa Hakko Kogyo, Tokyo,
Japan. taisuke.nakata_at_kyowa.co.jp
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BN 83495 Phase I
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Tyverb, lapatinib

• Lapatinib is an oral small-molecule
• inhibitor of the ErbB2/ ErbB1 TK receptor.

Trastuzumab Lapatinib
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Tyverb, lapatinib

• Develop in breast cancer
• Over expression of these receptors has been
  reported in a variety of human tumors.(squamous
  cell/gastric cancer)
• Associated with poor prognosis and reduced
  overall survival.(agresive form of advanced
  breast cancer)
• Limits
• Not in Monotherapy
• Poso 5 tablets/ day, every days
• 2 x 70 tablets 2537,74
• Adverse reactions, at least 10 of patients
  (Gastro-intestinal, dermatologic, fatigue)

2174 / month
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Approval and fundedLapatinib received approval
in june 2008

• FDA - EMEA
• 1st indication In combination with Xeloda
  (growth inhibitor) for a particular type of
  aggresive breast cancer ErbB2. After treatment
  with standard chemotherapy regimes including
  intravenous trastuzumab
• 2nd indication in combination with letrozole
  (aromatase inhibitor) for the first-line
  treatment of HER2-positive metastatic breast
  cancer in postmenopausal women.
• FDA
• 3thr indication in combination with letrozole
  (aromatase inhibitor) for the first-line
  treatment of HER2-positive metastatic breast
  cancer .
• Refusal to pay for lapatinib as a 1st-line and
  2nd-line treatment for HER2-positive breast
  cancer (EGF 30008)
• gtfinding it was not cost-effective.

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Cost-effectiveness

• Analysis lapatinib capecitabine vs capecitabine
  monotherapy
• the QALY gain was 0.171 at an incremental cost of
  13,873
• Incremental cost-effectiveness ratio (ICER) of
  81,251 per QALY gained. Max 35,000
• the cost effectiveness of lapatinib was
  particularly influenced by the extent of
  trastuzumab use post progression and the
  progression free patients receiving trastuzumab.

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COMMISSION DE LA TRANSPARENCEAvis 16 juillet 2008

• LEMEA a attribué à TYVERB une AMM
  conditionnelle, en labsence
• - de données robustes sur lefficacité de TYVERB
  sur lincidence des métastases cérébrales
• - et de démonstration sur la survie globale.
• Le rapport bénéfice/risque sera réévalué
  annuellement. La firme sest engagée auprès de
  lEMEA
• - données de survie étude EGF 100 151
• - phase III comparative vs HERCEPTIN
• Evaluer leffet de TYVERB sur lincidence des
  métastases cérébrales site de rechute (Le
  rapport final soumis en mai 2013).

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November 17, 2009

• Development of a predictive test gt treatment
  best suited to different populations suffering
  from breast cancer.
• This test will be developed from new biomarkers.
  After approval by regulatory agencies, it can be
  used for both cancer receiving adjuvant therapy
  and metastatic cancer
• Test ErbB2 / ErbB1 ???
• GSK did not reveal the specific breast cancer
  drugs that the predictive test would accompany.

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Oncology pipeline
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• GSK's decision to work with BioMerieux capacity
  to scale up the development and marketing of the
  test. (not only a biotech)
• GSK Opportunity for label integration and
  co-marketing

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AviaraDx acquisition

• En septembre 2008
• le Groupe a acquis la société AviaraDx, Inc.
  spécialisée en diagnostic moléculaire des tissus
  tumoraux à partir de biopsies.

Accrédité par un CAP
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THEROS Breast Cancer IndexSMBreast cancer
recurrence

• Breast cancer patients are typically classified
  by 3 factors
• 40 to 50 percent of breast cancer patients are
  inaccurately classified as intermediate risk
  according to St. Gallens risk
  assessment guidelines.
• under-treatedgt overall survival
• over-treatedgt cost, side effect
• Better classification means better treatment
  selection
• Test is a combination of 2 independent tests
• ER and PR , endocrine therapy.
• Tumors ,be sensitive or resistant to
  chemotherapy.

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THEROS technology

• THEROS Breast Cancer ? and THEROS CancerTYPE ID
• objective diagnostic tool
• quantifiable
• Practical
• clinically impactful.
• faster,
• effective
• avoid expensive
• real time RT-PCR based assays compatible with
  many form of samples.
• extraction of RNA
• reverse transcription to cDNA
• quantitative measurement using real time PCR

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THEROS CancerTYPE ID

• 1.4 million new cases ofcancer in the US, 3 to 5
  of new cancer are  cancer
• of unknown primary  Diagnotisis
• -lengthy
• -expensive 18,000
• Diagnostic tools used studying cells and tumors
  with microscopes, laboratory cell stains ,
  imaging
• often fall short of identifying where a cancer
  started and what type it is.
• Molecular diagnostics provides important
  information for cancer type identification
• The price of a Cancer type test is 3600
• Recognize over 75 of solid tumors. activity
  levels of 92 genes
• distinguish up to 39 different tumor types and 64
  subtypes

Schapira DV, Jarrett AR. The need to consider
survival, outcome, and expense when evaluating
and treating patients with unknown primary
carcinoma. Arch Inter Med.1552050-2054, 1995.
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• SAN DIEGO Breast Cancer Symposium
• December 12, 2009
• three studies using the companys breast cancer
  molecular test (leader dopinions)

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• http//www.biotheranostics.com/wp-content/uploads/
  Test-Requisition-Form-website.pdf
• a two-year agreement with Lab21 to commercialize
  the bioTheranostics THEROS CancerTYPE ID

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• Conclusion

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Clear objectives

• a strategy focused on patients and pathologies
• Infectious agents clinical and industrial
  applications
• high medical-value tests oncology, cardiology,
  point of care and theragnostics
• Strategy that leverages their strenghs
• Bacteriology leadership
• Industry lead sector consolidation
• Molecular biology become the leader on sepsis
  and hospital-acquired infections
• Immunoassays extend the high medical-value test
  menu and strengthen the point of care business
• Theranostics become a preferred partner for
  pharmaceutical and biotech compagnies

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Good financial results for the third quarter
Sysmex Biomerieux become Sysmexs global
partner for distributing UF-1000i
Acquisition of BTF
Institut Mérieux sells Laboratoire Marcel Mérieux
shares its CEO
AviaraDx acquisition Bad financial results in
USA1
Flu threat
Cepheid Relationship in the development and
commercialization of an innovative line of sepsis
test products
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SWOT
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Future Acquisitions ?

• Biomonitor ?
• Danish biotechnology company leader in thenostics
  and combine development of innovative and
  proprietary clinical bioassays.
• Products iLite ? Products based upon the
   gene reporter  technology.
• Exonhit ?
• A world leader in the exploitation of alternative
  RNA splicing.
• Is ability to identify genes whose splice
  variants produce abnormal proteins can be used to
  develop tests for diagnosing diseases at an early
  stage.

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Conclusion
Conclusion
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Who wants to work at bioMérieux
Name Opinion
Alban
Emmanuel
Thibaut
Thomas