Rob Geraerdts

1. Gepersonaliseerde gezondheidszorgVan utopie tot realiteitPersonalised HealthcareHype or reality? Rob Geraerdts

2. Personalised Healthcare (PHC)Is it more than a media reality – hype – or will it truly develop ? Personalised medicine may be our future approachTargeted drugs: The race is onTargeted cancer drugs gain backersPersonalised drugs draw biotech dollarsPersonalised approach to cancerPersonalised medicine: New approach to staying well‘Targeted‘ drugs prove powerful against forms of cancerFDA acts to foster ‘personalised drugs`

3. The Challenge of Personalised HealthcareWhat the public came to expect of PHC are truly individualised therapies – something science and industry may not be able to deliver for some time Source: JAMA. 2006;296:1453-1454.

4. Why a new approach to staying well is required ? What's the challenge and promise of Personalised Healthcare? ...different effects Variability of disease Drug metabolism Drug-drug interactions Non-compliance Same symptoms Same findings Same disease Same Drug...

5. Development towards A More Personalised HealthcareUsing clinical differentiators to achieve optimal pharmaceutical efficacy and safety for the purpose of creating sustainable clinical benefits Increasingly,treatmentwill be tailored to patient groups defined by their genetic disease pattern Still today, almost all patients are treated in a few similar ways Therapeutic stratification

6. Personalised HealthcareNot a totally new concept but an evolution Today Diagnosis and treatment expanded with rapidly growing insights into molecular processes and variations in our genes For more than 10, 000 years Diagnosis and treatment based on what could be seen, smelled, tasted, palpated or intuited The last 100 years Diagnosis and treatment expanded with knowledge about biochemistry and cellular processes

7. Challenges for the Healthcare system Technological development and evolution in Diagnostics Potential future role for the General Practioner

8. Empowered people withincreased health consciousnessand demands to the system Cost pressure Aging population Payers controlling providers and redistributing costs to people Borderless world Providers forced by people and payers to change the way they perform medical practice IT revolution Medical innovation Involvement of all players in the creation of health networks that form strong health care brands. Health Economic Value of Medical Devices The outside world is changing Payers Cost control Best medicalpractice Qualityof Life People Providers

9. Challenges for the Healthcare system Technological development and evolution in Diagnostics Potential future role for the General Practioner

10. Personalised Healthcare: hype or reality?Evolution in literature of definitions for In Vitro Diagnostics In Vitro Diagnostics are Medical Devices which enable analysis of bodily fluids and tissues for determining disease conditions In Vitro Diagnostics are enabling technologies to structure tomorrow's health care processes based on medical evidence In Vitro diagnostics are a valuable tool for preventing illness, for early diagnosis and for optimising therapy through patient monitoring and/or stratification

11. Result Standardisation ImprovedInformation Novel Content Tomorrow: Personalised Healthcare: hype or reality?The need for health information as basis for medical decisions Today: • Tests with blood, liquid and tissue • Health information • „the right information in the right place at the right time“ • individual patient treatment (i.e. test result, risk profile, treatment recommendation) • transition of today's IVD products into specific biomarkers

12. Personalised Healthcare: hype or reality?How did technological development in IVD testing contribute to creating value in the laboratory ? Re-engineeringMedical Processes with IVD - DRG’s - Indication management - Personalised Health Care Productivity Total IVD infrastructure( Lab Network / IT ) - IT solutions -Hospital solution Laboratroy Organisation - Increase laboratory productivity Systems - System portfolio- Professional System Service Reagents - Reagent harmonization- Robustness improvement - Result standardisation investments

13. Personalised Healthcare: hype or reality? Populating the laboratory health value chain with tools and content to create personalised healthcare Predisposition screening Targeted monitoring Preventive measures Diagnosis Therapy decision Therapy monitoring toring Tools Instruments and Reagents Portable Sensor Platform Instruments and Reagents Instruments and Reagents TOOLS Decision Algorithms Decision Algorithms Decision Algorithms Risk profile analysis CONTENT Riskalerts Risk Stratification Algorithms Databases Data Management Systems Current Offering + Personalised Health Information Supporting and Integrative Services

14. Personalised Healthcare: hype or reality?More fundamental knowledge of the "system biology" increases our understanding for underlying causes for diseases

15. mRNA (transcript) protein transcriptome proteome genome transcriptomics proteomics genomics Personalised Healthcare: hype or reality?To unveil the secrets of the "system biology" novel technologies are to be developed – used for diagnostic purposes DNA (gene) Bioinformatics

16. Personalised Healthcare: hype or reality?To understand "system biology", convergence of novel technologies will provide the full potential to understanding disease patterns Ascher Shmulewitz et al, Nature Biotechnology – March 2006

17. Personalised Healthcare: hype or reality? "Systems biology" transparency in disease processes

18. Creating PHC from an industrial perspectiveDiagnostics input is key - from discovery to market of pharmaceuticals Research Develop Commercialise Target Selection LeadGeneration/Optimisation Market Phase 0 Phase I Phase II Phase III Filing Phase IV DiscoveryPhase PoC Confirmatory Phase Exploratory Phase      Biomarker development Dx launch/ Post-launch assessment Companion diagnosticfeasibility & attractiveness Target identification Tailored prescribing & monitoring Patient selection Research assay Technically validated assay Clinically validated IVD assay

19. Personalised healthcare: hype or reality?Understanding of disease "genetic" pattern will drive usage of new technologies in DiagnosticsExamples Parameters (eg, Genes, Mutations) 1 10 100 1000 PCR Linear Arrays Microarrays Point Mutations; Simple Gene Analysis Complex Gene Analysis Resequencing Genotyping Examples: • AmpliChip CYP450Test (CE-IVD) • CF Linear Array (US) • AmpliChip p53* • CYP450 2C9 • Factor II/V Expression Examples: Single parameter “Expression”: Complex Expression: • Leukemia* • Breast Cancer • Cardiovascular Disease • Taqman HIV Monitor • Taqman HCV Monitor * under development

20. Personalised Healthcare in the market todayCurrent examples in oncology • Implementing biomarker strategyfor all pipeline drugs • Distribution of K-RAS and EGFR Cancer Mutation Tests • Tests identify genetic mutations that can affect patient response to certain cancer drugs • Identifying patients who have an improved response to launched drugs • e.g. Tarceva in 1st line maintenance NSCLC / SATURN trial • Assessing opportunities for companion diagnostics • Pertuzumab/HER dimerization inhibitors: Expression of HER 2 • MDM2: Active only in p53 wild-type patients • PLX4032: Presence of BRAF V600E gene mutation

21. Personalised Healthcare today in the marketCurrent examples in virology • Detecting Hepatitis C virus subtype and monitoring viral load/ Pegasys response • Determine length of treatment by strain of virus • Monitor viral load to determine likelihood of response and aid in compliance • Determining genotype 16 and 18 of Human Papilloma Virus • Reduce risk of cervical cancer by closer monitoring • Support Roche Pharma studies on therapeutic vaccines

22. Oncology Virology/Infectious Diseases CNS Phenytoin Venlafaxine Modafinil Resperidone Atomoxetine Thioridazine Levodopa Tasmar Aripiprazole CYP2C9 CYP2D6 CYP2D6 CYP2D6 CYP2D6 CYP2D6 COMT COMT CYP2D6 Tamoxifen Tamoxifen Tamoxifen Tamoxifen Chemotherapy Arimidex Herceptin Xeloda 6-Mercaptopurine Gleevec (CML) Gleevec (GIST) Dasatinib Iressa Tarceva Irinotecan Erbitux Retinoic acid MabThera Tykerb ER/PR Status BRCA1 BRCA2 CYP2D6 Oncotype Dx ER/PR status HER2 assay Enzyme activity TPMT BCR-ABL C-Kit BCR-ABL EGFR Status EGFR/HER1 UGT1A1 EGFR status PML/RAR gene CD20 EGFR status Pegasys/Copegus HIV Prot. Inh. (1st to mkt)1 HIV Prot. Inh. (2nd to mkt)2 HIV Prot. Inh. (1st to mkt)1 HIV Prot. Inh. (2nd to mkt)2 Isoniazid Tamiflu PegintronA Roferon HCV Genotyping Viral Load Viral Load Viral Genotyping Viral Genotyping NAT Influenza A/B test HCV EVL HCV EVL Personalised Healthcare in the market todayIAT-Beispielliste Respiratory Metabolic and Vascular Disease Fosamax Somatropin Insulin Simvastatin Prolastin Theophylline PiZZ, PiZ Pi CYP2D6 P1NP Chr 15 HbA1c Lipid profiles GIT Omeprazole Proton pump inh. and Antibiotics CYP2C19 H Pylori Haematology Warfarin Warfarin Heparin EPO CYP2C9 VKORC1 APTT CBC Autoimmune and Transplant Cardiovascular Cellcept Azathioprine Neoral (Cyclosporine) Prograf (Tacrolimus) Rapamune (Sirolimus) Mabthera IA TPMT IA’s for CsA IA IA RA profiles Ethnicity NAT NAT Troponin Troponin BiDiL Hydralazine Procainamide GPIIb/IIIa Streptokinase Anaesthesia Succinylcholine Pseudochol- Inesterase levels 1. Invirase; 2. Crixivan

23. Challenges for the Healthcare system Technological development and evolution in Diagnostics Potential future role for the General Practioner

24. Personalised Healthcare: hype or realityThe proven promise of personalised health care is to further improve effectiveness of treatment • Effectiveness of treatment can be improved… • 20-75% of patients do not receive effective treatment1 • >100.000 deaths/yr from adverse drug reactions in US2 …by tailoring treatments to selected patient groups defined by biomarkers 1 Spears et al., Trends Mol Med, 20012 Lazarou et al., JAMA, 1998

25. Today Today diagnostics often addresses end stages of diseases. Here (e.g. late cancer phase) treatment is expensive and may not cure the patient. New markers for the disease onset change this picture dramatically. Health care cost go down and treatment success improves. This is were marker identification programs like proteomics and genomics come in. lower Genomics Proteomics Likelihood of treatment success for the individual patient lower Future Cost Effectiveness higher higher Patient Status asymptomatic symptomatic New testing algorithms – A new paradigm shift in "how to treat" patients Earlier, better diagnosis allowing for better and cost effective treatment – Early patient stratification

26. Asymptomatic disease Chronic disease Cured Healthy Symptomatic disease Personalised healthcare: hype or reality Role of the treating physician across the healthcare value chain Risk Assessment Screening/ Diagnosis Prognostic Predictive Monitoring Predisposition for developing disease Early detection Predict probable disease course Predict likely response to a drug Monitor efficacy/ recurrence Patient Stratification / Therapy Selection Therapy adaptation

27. Patients Best treatment Regulators & Policy Makers Physicians & Providers Increased efficacy & safety Reduced healthcare costs Maximum benefit,minimum toxicity Payers & Reimbursers Efficient use of healthcarebudgets Personalised Healthcare: hype or reality? Benefits for patients and healthcare system