1. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 “My Genes, My Health” Shaping the Scenario for Personalised Health Management Chris De Bruijn, PhD, MBA Director Science & Technology European Institute of Molecular Medicine EURIMM Düsseldorf, Germany

2. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Significant changes are ahead in the way healthcare will be provided and financed in the industrialised world, due to Empowered Health Clients ICT / Web-based e-Health Management Health Genomics “My Genes, My Health” Shaping the Scenario for Personalised Health Management

3. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Empowered Patients will be Demanding and Impatient Patients The healthcare system, including doctors, hospitals and insurers, is viewed as not being up to par with socio-economic, scientific and technological developments Healthcare´s traditional purchasers (national healthcare systems, insurers) will shift more costs to individual patients Having become healthcare consumers, paying clients will want more personalised cure and care Healthcare clients will prefer brands of well-marketed, cost-effective services and products, leading to healthcare “trade marks” “My Genes, My Health” Shaping the Scenario for Personalised Health Management

4. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Web-Based e-Health Adaptability will be Key for Survival in the Healthcare Sector Transactions: communication with suppliers, payers, regulators and health clients Information: trustworthy, dynamic, searchable, easy-to-use web-sites that can engage the health client Interaction: two-way communication between care provider and client; “personal health manager” expert systems Organisation: small companies will be first movers, since they adapt faster than the existing large bureaucracies “My Genes, My Health” Shaping the Scenario for Personalised Health Management

5. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Health Genomics: “Live up to Your Genes” From Cure to Prevention Analysis of individual genetic predisposition (genotyping) will lead to more emphasis on prevention: "knowing your genetic profile is a great motivator" Genotyping and phenotyping (= how genes are actually working in an individual situation) will lead to more effective "personalised molecular medicine", especially with respect to chronic diseases Genotyping and phenotyping will pave the way to "personalised health management", providing a rational basis for preventive anti-aging and personalised wellness strategies “My Genes, My Health” Shaping the Scenario for Personalised Health Management

6. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Foreseeable Consequences of the Emerging Personalised Molecular Medicine Health insurance financing will create levels of privatisation and defined contribution programs Curative and preventive health processes will be standardised, but on a personalised level (web-based expert systems) Technology will push more diagnostic and therapeutic activities into outpatient and home settings: healthcare professionals will need to change and adapt accordingly The aging population in the industrialised societies, the new technological possibilities (gene transfer, stem cells) and the attitude of empowered health clients will put unheard pressure on policy makers to make difficult choices “My Genes, My Health” Shaping the Scenario for Personalised Health Management

7. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Implications for the Next Decade (1) Consumer friendly healthcare organisations will be winners Successful organisations will distinguish themselves through branding (“trade mark”) Service and speed will be keys to consumer satisfaction “My Genes, My Health” Shaping the Scenario for Personalised Health Management

8. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Implications for the Next Decade (2) Healthcare professionals will need to give up the traditional frameworks they are working in and create transparent service systems for health clients Payers will put more emphasis on prevention because disease diagnosis and disease intervention increase costs Health clients will want more, but they will not be willing to pay significantly more “My Genes, My Health” Shaping the Scenario for Personalised Health Management

9. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Introduction 1) All human diseases are caused by the interaction between genetic predisposition and modifiable environmental factors 2) Slight variations in genetic make-up, called single nucleotide polymorphisms (SNP´s), are associated with almost all diseases 3) The genetic variations (SNP´s) identified with the MedPlus Predictive Genomics Panels do not cause disease by themselves. Rather, they influence the individual susceptibility to specific environmental factors that increase disease risk and/or to the efficacy of pharmaceutical drugs 4) The MedPlus Predictive Genomics Panels provide a clinical foundation for designing comprehensive, personalised prevention and treatment plans that optimise health and reduce disease risk in patients “My Genes, My Health” Predictive Genomics Panels (1)

10. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Requirements for SNP´s to be Included 1) Relevance: the SNP exerts direct influence over specific individual biochemical characteristics that may lead to disease symptoms and/or to an individual´ s reaction to a specific therapeutic drug 2) Prevalence: the SNP is relatively common among the general population 3) Modifiable: the expression of the SNP is modifiable by environmental factors, such as nutrition, diet, toxic exposure, lifestyle and adaptation of drug administration 4) Measurable: the impact of clinical interventions to modify the expression of the SNP can be monitored by using specialised functional assessments (phenotypic analysis) “My Genes, My Health” Predictive Genomics Panels (2)

11. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Predictive genomic testing can provide improved healthcare for all patients, but especially for 1) Proactive Risk Assessment to provide earlier and more precise preventive interaction for proactive individuals: "personalised anti-aging and wellness management" 2) Family History to identify inherited risks for chronic diseases within families that can be modified by environment 3) Personalised Pharmacotherapy: pharmacogenomic analysis allows the development of more effective treatment options based on genetic individuality “My Genes, My Health” Predictive Genomics Panels (3)

12. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 Risk Determination / Predictive Pharmacogenomics CYP1A1: detoxifies cancer-causing polycyclic aromatic hydrocarbons, present in nutrition and environment (e.g. smoke, charbroiled foods etc.; relevant for cigarette-induced lung cancer); it also metabolises anti-cancer drugs CYP1A2: is significantly induced by cigarette smoking, leading to more rapid metabolism of pharmaceutical drugs handled by this enzyme; certain polymorphisms lead to decreased inducibility CYP3A4: detoxifies over 50% of all prescription drugs and most steroid hormones; polymorphism associated with prostate cancer susceptibility “My Genes, My Health” Predictive Genomics Panels: Oncology (11 SNP´s) Examples

13. © EURIMM European Institute of Molecular Medicine The Scientific Institute of MedPlus Europe S.A. Club of Amsterdam, 28 May 2003 NAT 1: mainly active outside the liver; detoxifies environmental toxins including tobacco smoke and exhaust fumes; linked with susceptibility for developing lung, colon, bladder (most clearly established) or head & neck cancer; both slower and faster detoxification polymorphisms increase risks GSTM1: detoxifies environmental toxins including herbicides, fungicides, oxidised fats and heavy metals; SNP with decreased activity can contribute to oxidative stress and development of various cancers throughout the body (e.g. lung, bladder, estrogen-associated breast cancer) GSTP1: similar function; polymorphism associated with early onset prostate cancer “My Genes, My Health” Predictive Genomics Panels: Oncology (11 SNP´s) Examples (continued)