Ortho biotech 04 aug-081

www.eurofinsmedinet.com11/03/13 confidential

Eurofins Medinet

Ortho Biotech Oncology R&D

August 4, 2008

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Content

Eurofins Scientific S.A.

Eurofins – Medinet overview

Central Laboratory Services

Bioanalysis Structure

Biomarkers

Summary

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Eurofins Scientific SA

Food

Environment Pharmaceuticals

A leading international life sciences company providing an unparalleled range of analytical testing and advisory services

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Major player in Europe and several laboratories in USA

No. 1 worldwide in dioxin testing

No. 1 in Europe

No. 1 or No. 2 in several segments/countries in Europe & USA

Among top USA, Europe & rest of world players in Central Laboratory, Anti-Infective Services, and Genomic Information services

Food Testing

< No. 1 worldwide >

Environmental Testing

< In top 3 worldwide >

Pharmaceutical/BiotechnologyTesting

< In top 10 worldwide >

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Laboratories

Food

Environment

Pharma

Sales office

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Eurofins Pharma Services

Full Spectrum of Global Laboratory Services supporting pharmaceutical and biotech drug development

Safety and efficacy testing

Anti-infective services

Bioanalysis

Method development and validation

Biomarkers and therapeutic drug monitoring

Pharmacogenomics

HIV – drug resistance testing

Phase I clinical and laboratory services

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Eurofins Medinet CLS

Own Laboratory Facility Standardized Partner

Breda

Paris

Singapore

Denver

Washington DC

India

South Africa

Brazil

Israel

Argentina

Japan

Australia

Shanghai

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Eurofins Medinet Locations

Eurofins Medinet Breda Bergschot 71

4817 PA BredaThe Netherlands

Eurofins Medinet Herndon13665 Dulles Technology Drive

Herndon, VA 20171USA

Eurofins Medinet Paris48-52 Rue de la Gare78370 Paris France

Eurofins Medinet DenverBioscience Park Center12635 E. Montview Blvd.

Denver, Co 80045USA

Eurofins Medinet Singapore# 01-16 the Synergy

1 International Business Park Singapore

Eurofins Medinet ShanghaiEurofins Technology Service Co., Ltd.

No. 10B1 Longshan Road SNDSuzhou, Jiangsu Province P.R.

China

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Eurofins Medinet Services


Safety Testing and Biomarkers

Project and Data Management

Established Logistical Support

Standardized Global Data

Bioanalysis

Method Development and GLP Validation

PK/PD Analysis and Toxicology

Therapeutic Drug Monitoring

Microbiology to support Clinical Trials

Comprehensive range of Genomic Services

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Eurofins Medinet Breda

Total Laboratory space: 1200 sq. meters

Clinical Laboratory (25 analysts)

Safety testing

Routine analysis

Biochemical analysis and immunoassays

Bioanalytical Laboratory (27 analysts)

Pharmacokinetic analysis

Drug determination in plasma and serum

Immunoassays

LC-MS/MS and HPLC

GLP accreditation

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Safety

Global reference ranges

Same analyser platforms

Same lot numbers of QC & Calibrators

Biweekly comparison of results of proficiency testing (EQA)

Ongoing monitoring of QC results

Internal exchange of samples for correlation checking

Global SOPs

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Bioanalysis Structure

B i o a n a l y t i c a l L a b o r a t o r yD e n v e r

S c i e n t i f i c A d v i s o rO . L a g a t i e ( 1 )

S t u d y A s s i s t a n tM . N i e u w e n h u i z e n

S e n i o r S t u d y D i r e c t o rR . W o r t e l b o e r

S t u d y D i r e c t o rF . d e J o n g

S t u d y D i r e c t o rL . J a c o b s

A s s . S t u d y D i r e c t o rP . t e n H a c k e n

A s s . S t u d y D i r e c t o rV a c a n c y

A s s . S t u d y D i r e c t o rR . L a g e w a a r d

B i o a n a l y t i c a l S t u d y M a n a g e m e n tM a n a g e r B i o a n a l y t i c a l S t u d i e s

G . W o u t e r s

A n a l y s tB . v a n D o r s t

A n a l y s tW . D e k k e r

A n a l y s tJ . V r o l i j k

A n a l y s tW . d e G r o o t

A n a l y s tC . V a n w e s e n b e e c k

A n a l y s tL . K o e v o e t s

S t a g i a r e

T e a m AA n a l y s t

T e a m L e a d e rT h . d e J o n g

A n a l y s tA . H u y s k e n s

A n a l y s tA . O u l d e l H a d j

A n a l y s tM . v a n B i j s t e r v e l d t

A n a l y s tY . A d r i c h e m

A n a l y s tV a c a n c y

T e a m BA n a l y s t

T e a m L e a d e rJ . v a n d e n E l s h o u t

A n a l y s tR . V e r m u n t

A n a l y s tM . D u r a n

A n a l y s tD . v a n d e n B u i j s

A n a l y s tR . v a n L e e u w e n

A n a l y s tM . L a n s l o t s

A n a l y s tD . v a n D i e s t

A n a l y s tA . A l s a a d y

A n a l y s tM . V i s s e r s

A n a l y s tJ . D i e l e m a n s

( A n a l y s t )( V a c a n c y )

T e a m T D MA n a l y s t

T e a m L e a d e rT . d e M o o i j

B i o a n a l y t i c a l L a b o r a t o r yM a n a g e r B i o a n a l y t i c a l L a b o r a t o r y

R . v a n d e r W e g e n

S t u d y D i r e c t o rR . M a r t e n s

S t u d y D i r e c t o rH . V e r d o n k

( S t u d y D i r e c t o r )( V a c a n c y )

A s s . S t u d y D i r e c t o rP l a n n i n g O f f i c e r

E . H o v i n g

A s s . S t u d y D i r e c t o rR . H u l i k u n t a

S t u d y M a n a g e m e n tS p e c i a l i z e d B i o m a r k e r s

S t u d y D i r e c t o rM . v a n d e r L i n d e n / J . P . B o o n

A n a l y s tB . J a n s e n

A n a l y s tF . K o n i n g s

A n a l y s tM . K o r n e e f

A n a l y s tS . V o e r m a n s

A n a l y s tV a c a n c y

S t a g i a i r e

S p e c i a l i z e d B i o m a r k e r s L a b o r a t o r yL a b o r a t o r i u m M a n a g e r

M . v . d . L i n d e n a . i . / J . P . B o o n a . i .

I n t . A c c o u n t M a n a g e rW . S m i t s

D i r e c t o r B u s i n e s sD e v e l o p m e n t

M . O ' B r i e n

B u s i n e s s D e v e l o p m e n tM a n a g e rV a c a n c y

I n t . A c c o u n t M a n a g e rV a c a n c y

S a l e s M a n a g e m e n t B i o a n a l y s i s

L a b o r a t o r y O p e r a t i o n s B i o a n a l y s i sG l o b a l H e a d / V P B i o a n a l y s i s

H e a d o f T e s t F a c i l i t yJ . D a n k e r s

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Study Director Group

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LC-MS/MS

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HPLC

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Chromatographic instrumentation

LC-MS/MS: 7 systems (Sciex, API 3000 (3x), API 4000 (4x))

HPLC: 9 systems (Waters, PE)

GC-MS (Agilent)

ICP-AES

Tecan Genesis RSP 100

Tecan Genesis RSP 150

Hamilton Starlet

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Biomarkers

Clinical SafetyAssays

(NCCLS/CLIA)

Drug PK Assays

(FDA/GLP)Biomarker

Assays

Routine Biomarkers

Novel Biomarkers

Pre- / early clinical phase

Efficacy parameter or not

Safety or PK

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Biomarkers

Sensitivity

Linearity

Accuracy

Precision

Matrix effect

Dedicated Biomarker Group: A dedicated Study Director for your study

Determine level of validation required for your study

Full GLP validation

NCCLS/CLIA validated analysis

Sponsor specific requirements

Select appropriate method considering

Meet your requirements on reporting times

Advise on sample handling and storage conditions

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Biomarker Group

Combine the best of both

Biomarkers need advanced validation

“Fit for Purpose”

Biomarkers have a need for a dedicated project leader (study director)

Biomarkers need a batch approach

Sometimes GLP is required for biomarker analysis

Provide a scientific partnership

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Biomarker Group

What expertise do we offer

Biomarker analysis

PK analysis of biological drugs (using immunoassays)

Immunogenicity testing

• Screening

• Confirmation

• Titration

Cell-based assays (under development)

Custom ELISA development

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Validation Criterion:

Quantitative Relative Quantitative

Quasi-Quantitative

Qualitative

Accuracy

Precision

Sensitivity LLOQ) (LLOQ)

Specificity (LLOQ) (LLOQ)

Dilutional Linearity

Assay Working range

(LLOQ, ULOQ)

(LLOQ, ULOQ)

Standard stability

Matrix Effects

Reagent Stability

Defined BiomarkersDefined Biomarkers

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Biomarker assay validation

Discussion about level of validation with Sponsor

Evaluation plan for ELISA assays

Assay Optimization

Assay Validation

CLIA ----> Exploratory ----> Advanced

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Equipment

Immunoassay equipment:

4 x BEP2000

2 x Advia Centaur

Elecsys 2010

Immulite 1000 and 2000

Luminex

MSD SECTOR Imager 2400

Tecan Freedom EVOlyzer (in process)

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Equipment

Other clinical equipment:

2 x Modular system (Roche Diagnostics)

FACSCalibur (B&D)

Advia 120 (Bayer Corporation)

ABI prism 6100 and 7000 real time PCR

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Equipment

Spectrophotometric equipment: Spectramax M5

Absorbance (Visible, UV, IR)

Fluorescence

Luminescence

Time Resolved Fluorescence

Fluorescence Polarization

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Equipment

Automation equipment:

Tecan Genesis RSP100 (4-needle)

Tecan Genesis RSP150 (8-needle)

Tecan Freedom EVOlyzer

Hamilton system

4 x BEP2000

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Available Methods Available Methods 1/51/5

Steroids specie matrix method LOQ unit

11-Desoxycortisol human plasma ria 1 nmol/L6-Hydroxycortisol human plasma eia 0.05 ng/mLACTH human serum cia 5 ng/LAldosterone human plasma cia 0.03 nmol/LAndrosteendione(D4) human plasma ria 0.35 nmol/LCortisol human plasma gc-ms 20 nmol/LCortisol human urine gc-ms 10 nmol/LCortisol humam plasma cia 30 nmol/LCortisol humam urine cia 30 nmol/LCortisol humam urine ria 30 nmol/LCortisol dog plasma lc-ms/ms 5 nmol/LCortisol/ 6-hydroxycortisol human plasma lc-ms/ms 20 nmol/LCortisol/ 6-hydroxycortisol human urine lc-ms/ms 10 nmol/LDHEA human serum eia 0.1 nmol/LDihydro-testosterone human serum ria 0.01 ng/mLEstradiol human serum ria 10 pmol/LEstrone human leucocytes lc-ms/ms 0.5 nmol/LEstrone sulphate human serum ria 0.05 ug/LFSH human serum cia 0.1 IU/LGrowth Hormone human serum cia 0.1 ug/LProgesterone human serum cia 0.3 nmol/LTestosterone total human serum cia 2 nmol/LTestosterone free human serum ria 2 pmol/L

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Bone markers specie matrix method LOQ unit

Bone Spec.Alk.Phos. human serum eia 1 U/LCTx human serum eiaNTx human urine eiaOsteocalcin human serum ciaDesoxypyriridinoline human urine hplc 2 nmol/LDesoxypyriridinoline human urine cia 20 nmol/LPyridinoline human urine hplc 5 nmol/L

CardiovasularAngiotensin Conv Enz human serum enzANP human serum riaApo A1 human serum turbApo B human serum turbAsymmetric Dimethyl Arginine (ADMA) human plasma hplc 0.2 umol/LBNP human serum ciaCKMB human serum meiaLDL-Cholesterol human serum directLH human serum ciaTroponin I human serum ciaVLDL human plasma ultracentrVLDL human plasma hplcLDL human plasma hplcHDL human plasma hplc

InflammatoryRheumatoid factor human serum turb

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Catecholamines specie matrix method LOQ unit

Adrenalin human plasma hplc 0.1 nmol/LAdrenalin human urine hplc 0.01 umol/LDopamin human plasma hplc 0.2 nmol/LDopamin human urine hplc 0.02 umol/LNoradrenalin human plasma hplc 0.1 nmol/LNoradrenalin human urine hplc 0.01 umol/L

Glycoproteine1,5-Anhydro-D-Glucitol human plasmaAmylin human plasma eiaGlucose human plasma enzymHbA1C (NGSP level I) human blood hplcInsulin human serum ciaInsulin C-peptid human serum ciaPro Insulin human serum ria

Vitamins25-OH Vitamin D3Beta-carotene human serum hplc 0.15 umol/LVitamin A human serum hplc 0.35 umol/LVitamin B1 human blood hplc 30 nmol/LVitamin B6 human blood hplc 10 nmol/LVitamin C human blood hplc 5 umol/LVitamin E human serum hplc 12 umol/L

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Infection diseases specie matrix method LOQ unit

A1-Globulin human serum electroforesisA2-Globulin human serum electroforesisAnti HLA-Ab human serum flowcytometricBeta-Globulin human serum electroforesisCMV-IgG Ab human serum ciaCMV-IgM Ab human serum ciaGamma-Globulin human serum electroforesisH.pylori IgG Ab human serum ciaHBc IgM human serum meiaHBeAb human serum meiaHBeAg human serum meiaHBeAg human serum meiaHBsAb (anti-HBs) human serum meiaHBsAG human serum meiaHBsAg human serum meiaHepatitis C Ab human serum meiaHIV human serum meiaHSV-IgG human serum ciaIgA human serum turbIgE human serum ciaIGF-1 human serum ciaIGFBP1 human serum eiaIGFBP3 human serum ciaIgG human serum turbIgM human serum turb

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Tumor markers code specie matrix method LOQ unit Pathologies

Alpha-fetoprotein (AFP) human meia Liver, ovary, testicle. Beta-2-microglobulin (ß2-m) human cia Haematopoietic system. Cancer antigen 125 (CA 125) human cia OvaryCancer antigen 15-3 (CA15-3) human cia BreastCancer antigen 72-4 (CA72-4) human cia StomachCarbohydrate antigen 19-9 (CA19-9) human cia Colorectal cancer, pancreas, stomach, bile duct. Carcinoembryonic antigen (CEA) human cia Colorectal, pancreas, lung, breast, stomachChorionic gonadotropin (hCG) human meia Testicle, ovary, liver, stomach, pancreaComplexed Prostate-specific antigen (cPSA) human cia ProstateFree Prostate-specific antigen (fPSA) human cia ProstateHuman Cytokeratin 18 (TPS) human cia Breast, ovarian, lung,prostate, bladder, GINeuron specific endolase (NSE) human ria Lung: small cells cancers ("SCLC"); pancreasNucleair matrix protein (NMP22) human cia BladderThyreoglobulin (THY) human cia ThyroidTotal Prostate-specific antigen (tPSA) human cia ProstateVasopressin human serum ria 1 pmol/LVasopressin human urine ria 1 pmol/L

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Biomarker support

Prof. P. Braquet (Eurofins Medinet Paris, France)

• Published hundreds of papers in biomarker field

Prof. U. Christians (University of Colorado, Denver, USA)

• Specialist in development of new biomarkers

• Proteomics and metabolomics

Dr. O. Lagatie

• Cell Biology specialist providing a scientific discussion partner for our customers

Longstanding experience in the bioanalytical and clinical laboratory

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Data Management

MedLIMS(Watson®)

final report

EDT

analysis

results

authorization

reference mat

pipette data

analyzer

supportive data

temp logging

21 CFR part 11

electronic signature

& archive

Validated LIMS – Environment

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Quality Assurance

GLP

ISO 15189

ISO 17025

ISO 9001

CAP

CLIA

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Why Eurofins Medinet?

High Quality Standards

Dedicated Study Director/Project Leader

Custom development of your assays

Attention to validation of the assays

Personalized approach communication

Established business between EM and Ortho Biotech (DORIINI2002 study)

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Questions

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The end

Ortho biotech 04 aug-081

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