1. 1 EFPIA EHR Integration Workshop Topic: The Innovative Medicines Initiative Brussels 10-03-2007 Marc Peeters Ir. Leopoldstraat 18 2300 Turnhout Belgium marc_dvf_Peeters@hotmail.com

2. 2 What is IMI (1) Preparatory Phase From ETP to JTI Active Phase IMI Joint Undertaking 20-12 Council approval 04-02 Publication 03-03 1st Board Meeting < 1st May 1st Call published From European Technology Platform (ETP) to Joint Technology Initiative (JTI) –ETP: Create Strategic Research Agenda (SRA) + Initiate pilot project (InnoMed) –JTI: Create Statutes and Regulations (Structure, R+R, procedures, processes) –Prepare hand-over: 1st IMI call / call topics documents -EC DG RTD: Irene Norstedt -EFPIA: RDG & Ian Ragan -Stakeholder workshops -IMI Governance Board -IMI Executive Office & Scientific Committee -IMI Member States Group & Stakeholder Forum IMI JU autonomous 10-10 IMI JTI approval 15-09-06 SRA approved

3. 3 What is IMI (2) IMI is a legal entity, a Commission Body, that will call for-, review-, approve-, fund- and oversee Research Projects implementing the IMI Research Agenda. It results from new and innovative approaches to Community R&D introduced with FP7 (Research Council, Joint Technology Initiatives) and as such is part of FP7 and funded by FP7 budget. JTIs are based on industry led R&D topics. It is a EU JTI embodied in a joint undertaking between the European Commission and the Pharmaceutical Industry represented by EFPIA. Is funded by the European Commission (cash, 1Billion Euro, public sector and SMEs) and the BioPharmaceutical Industry (in kind, 1Billion Euro). This covers the operations of the Executive Office (4% max) and the IMI Research Projects. Preparatory Phase From ETP to JTI Active Phase IMI Joint Undertaking 20-12 Council approval 04-02 Publication 03-03 1st Board Meeting < 1st May 1st Call published -EC DG RTD: Irene Norstedt -EFPIA: RDG & Ian Ragan -Stakeholder workshops -IMI Governance Board -IMI Executive Office & Scientific Committee -IMI Member States Group (MSG) & Stakeholder Forum IMI JU autonomous 10-10 IMI JTI approval 15-09-06 SRA approved

4. 4 The drivers for action The need to enhance European’s competitiveness –Academic – industrial platform for bio-medical research –Network of SMEs with expertise in various niche areas –Capabilities development The potential for increased cooperation between stakeholders –The convergence of disciplines creates the necessity for multidisciplinary research –The scale of the landslide change is such that a collaborative effort is required Wealth of novel opportunities from genomics –New undestanding leads to a continuous development of new subdisciplines –Biomolecular findings become tools for the further exploration of biomolecular mechanisms with an acceleration of new findings and potential industrial application as a consequence Timelines and cost of drug development –Attrition rates and their associated costs become an unacceptable burden. –New science based Pre-dictive tools understood by scientists and by regulators.

5. 5 EFPIA Research Directors Group (RDG)....Others In line with the ETP concept of industry led R&D the Biopharma industry took responsibility for the creation of the Strategic Research Agenda (SRA) under the direction of the EFPIA RDG. Multiple workshops with representatives from all the stakeholders (Academia, University hospitals, Patient organisations, SMEs, Regulators, non-Pharma- and Pharma industry, EU Commission) shaped the SRA.

6. 6 Efficacy Safety Predictive pharmacology Predictive toxicology Identification of biomarkers Validation of biomarkers Benefit/Risk assessment with regulatory authorities Patient recruitment Preclinical research Discovery development Translational medicine Clinical develop. Pharmaco vigilance The Strategic Research Agenda (1) Is an umbrella programme that describes the kind of advanced pre-competitive research needed to broaden throughout the EU Union, the academic and industrial know-how and skills required to successfully discover and develop novel medicinal products at acceptable cost. It is based on the the identification of the current drug development bottlenecks and suggests the drug development tools and processes that need further R&D to overcome these bottlenecks. Developing drugs is not within the scope. It emphasizes close collaboration with the regulators to promote the acceptance and use of these new methods and tools.

7. 7 Identifies pre-competitive bottlenecks in the R&D process Proposes recommendations to address these bottlenecks –Safety –Efficacy (Cancer, Brain Disorders, Metabolic diseases, Infectious diseases, Inflammatory diseases) –Knowledge Management (KM) –Education and Training (E&T) Proposes a new model of Public-Private collaborations to implement these recommendations http://www.imi-europe.org under “Publications” tabhttp://www.imi-europe.org The Strategic Research Agenda (2)

8. 8 EC + EFPIA initiative ETP >>> JTI >>> IMI Joint Undertaking Strategic Research Agenda (SRA) –IMI is about R&D processes including regulatoy approval –IMI is about tools and understanding of diseases, not about medicinal products –IMI is about public and private sector collaboration in pre-competive biopharmaceutical research Predictivice Safety and –Efficacy tools, methods and expertise –that can lead to treatments that affect disease progression and ultimately to the cure of diseases. 4 Pillars:SafetyEfficacyKME&T Pre-clinicalPharmaco 5 DiseaseTransIntegrated VigilanceAreaslationData al KMExploration Platform Implementation based on calls (call topics). Project funding stems in equal amounts from EC funding and EFPIA company contributions in kind. I.e. In a typical Research Project half of the costs are covered by in kind contributions from the participating BioPharma and other industry companies and the other half by IMI cash contributions to the participatns from SMEs and the Public sector. Synopsis

9. 9 InnoMed is a FP6 project It is a pilot demonstrating successful pre-competitive collaboration between 16 BioPharmaceutical companies, 14 Universities and 8 SMEs. Two targets: Toxicogenomics and Alzheimer disease. The Pilot Project ‘InnoMed’ PredTox www.innomed-PredTox.com For a number of compounds from each of the participating Pharma companies create a database of toxicity profiles. Integrating the traditional endpoints with new data from transcriptomics, metabonomics and proteomics. In search of new hepatitic toxicity biomarkers. AddNeuroMed www.innomed-QAddNeuroMed.com In search of diagnostic markers markers of progression markers of response / non-response in Alzheimer disease involving animal studies/models and clinical trials.

10. 10 IMI Process - Pre-Call Annual Implementation Plan Executive Office Governance Board Scientific Committee IMI Research Agenda 1st Call: Industry Scientific Priorities Survey + Preparatory team Call Topics RDG MSG Call Topic Documents Call = Call Topic Documents Call Guidance Documents RDG Pharma Companies Executive Office Workshops

11. 11 Heading Topic Title Project Description (Background, Scope, Approach, Requirements, Project Plan,..) Key Deliverables of the project (Packages, lists,...) EFPIA participants in the project (Company, Contact person(s)) Role of EFPIA participants in the project Indicative Duration of the project Indicate total in kind contribution from the EFPIA companies Indicative Expectations from the ‘Public Consortium’ (i.e. SMEs, Academia, Patient Organisations, Regulators and non-EFPIA companies) From 6 to 10 pages. Call Topic ToC

12. 12 IMI Process - Post-Call Expression of Interest Executive Office Phase 1 Call Published Invitation to submission Full Project Proposal Call = Call Topic Documents Call Guidance Documents Phase 2 Finalization Project Agreement Grant Agreement Submit

13. 13 SRA recommendations pre-Clinical Safety 1Establish the framework for Biomarker development and validation with human relevance and regulatory utility in mind Define datapackage needed to support acceptance of Biomarkers 2Establish a pre-Clinical Safety data warehouse, cross species and supportive of multi-scale modelling 3Enhance the relevance for predictive toxicology/pre-clinical, of in- vivo, in-vitro and in-silico models determine the relevance of rodent non-genotoxic carcinogenicity: mechanistic studies to understand mechanisms of receptor-mediated carcinogenicity develop widely applicable in-silico models of toxicity to improve the predictivity of endpoints understand intractable toxicity….develop new animal models, cellular models, stem cells, human tissues, imaging, ….. Knowledge Management is often embedded in the Safety and Efficacy pillar recommendations. It is a matter of emphasis.

14. 14 SRA recommendations Clinical Efficacy - Mechanism of Action based 1 Tools for the rational selection of molecular targets Tools for assays that demonstrate real pharmacological action and predict efficacy in human disease Diagnostic tests capable of early detection Need for Understanding of the disease mechanism of action 2 In order to use methods and endpoints that most closely reflect those that could can be used in clinical trials Need for In-silico models of disease pathology; i.e. ‘disease lifecycle models’ that directly link the rationale in pre-clinical modeling to the treatment of clinical disease. Systems Biology 3 For improved ‘confidence in the rationale’ pre-clinical experiments must carry higher relevance in relation to the clinical experience Need for In-vitro & in-vivo models predictive of clinical efficacy

15. 15 SRA recommendatios Clinical Efficacy – Integrated Healthcare 7In order to speed-up the recruitment process and to recruit the right patient We need Integrated patient selection networks that involve patient organisations and access first class electronic patient records (EHR) linked with Biobanks 8Baseline data for a number of observations derived from pooling EMEA and National agency data EU Drug risk/benefits database compiled from patient EMR Healtheconomics data Are all part of Innovative Clinical trial Designs and analysis 9Intelligent Clinical Trial Environment EHR – CRF integration Patient database of he future The EFPIA EHR Integration Taskforce objectives and recommendation - Eligibility broker (CRFQ framework), EHR information broker, CRF-EHR core data sets - closely align with these expressed needs in the IMI umbrella research programme

16. 16 SRA recommendations Pharmacovigilance 1Optimise data resources and EU datawarehouse 2Develop lifecycle approach to pharmacovigilance 3Develop novel methods of risk prediction and benefit-risk assessment 4Establish EU academic network of pharmacoepidemiology

17. 17 SRA recommendations Knowledge Management (KM) Special attention for collaboration and reuse with DG INFSO ICT for Health. Open offer to present the ICT for Health programme and projects and results to IMI Governance Board and IMI staff. 1 Systematically integrate / embed KM in the Safety and Efficacy projects through the Translational KM approach 2 Develop and maintain IMI Data Exploration Platform supporting the needs of safety and efficacy researchers across projects and disease areas. –Develop enhanced knowledge representation models and data exchange standards for complex systems –Design standards for and build an expert tool to allow the federation of local databases in a secured environment –Build a core reference database of validated experimental data –Integrate mechanistic multi-scale modeling and simulation tools that operate on top of the reference database

18. 18 EFPIAEuropean Commission Brian Ager EFPIAFranco BiscontinDG RTD Andreas BuschBayerDaniel JacobDG RTD Jackie HunterGSKGeorge LalisDG ENTR Carlo IncentiGenzymeAndrzej Jan RysDG SANCO Jonathan KnowlesRocheZoran StancicDG RTD IMI Governance Board IMI JU MSG STAKE HOLDERS FORUM EU COMMI SSION SCIENTIFIC COMMITTEE EXECUTIVE OFFICE BOARD EFPIARDG SAFETY EFFICACY KM E&T

19. 19 IMI Web site www.imi-europe.org Go to ‘Contact’ link Open ‘Contact Us’ form Write the message, provide personal data and submit Messages are handled by Question and Answer software at the IMI offices. IMI staff checks open questions on a daily basis and will respond asap. IMI Contact