Programme for ERS Live on understanding the 2008 IMI calls

1. Introduction The COPD call The Severe Asthma Call Summary and questions from participants Programme for ERS Live on understanding the 2008 IMI calls Leo Fabbri, ERS Ingela Wiklund, GSK Tim Higenbottam, Chiesi Chris Compton and Leo Fabbri, EFPIA and ERS

2. The 2008 Respiratory Calls: COPD PRO Ingela Wiklund

3. 2008 COPD Patient Reported Outcomes (PRO) call: Background Explanation of the need: • Efficacy evaluation of new therapies has relied on demonstration of reduction of airflow obstruction. • European Regulatory guidelines recommend the use of symptom endpoints, in addition to lung function measurements • A PRO is any report coming directly from patients about how they function or feel in relation to a health condition and its therapy : • Without interpretation by physicians or others • PRO Measurement tools should be generated with adequate patient input. • The areas that should be developed: • Symptoms: A patient with COPD experiences a variety of symptoms including dyspnoea (shortness of breath). • Restricts patients’ ability to exercise and perform daily activities • Results in psychological consequences • Significant impairments to overall health status. • Exacerbations: Acute worsening of symptoms that often require a change in treatment or could result in hospitalization. There is a need for scientifically developed and validated PRO measures that capture symptoms, exacerbations and their impact on patients

4. COPD call: What is it about? • Objectives • Understanding of the patients’ experience of COPD to inform the strategy to measure outcomes that are relevant to patients for assessing treatment benefit • Selection and/or Development of measures with good measurement properties that capture the COPD patients’ experience of the disease and effects of treatment. Eg PRO focussed on exacerbation: • To inform the definition of exacerbation • Understand day-to-day experience of symptoms characterizing an exacerbation • Evaluate the impact of these symptoms • Scope • Build consensus on the measurement strategy, especially PRO tools, by working with the key consumers of the information on treatment benefit: • Clinicians, academic clinical & health outcomes researchers, patients and payers

5. COPD call: Deliverables A measurement strategy that includes specific PRO tools: • Developed using robust psychometric methods • With input from and review by the major customer groups • Validated for use in treatment evaluations across Europe that can link to global efforts • Using appropriate prospective studies • Developed or adapted for capturing data using electronic data capture (EDC) devices for daily recording at home

6. COPD call: What are we expecting and going to do? • A Consortium or ‘Centre of Excellence’ • To develop a measurement strategy to evaluate the benefits of COPD treatment from a patients’ point of view • With contributions from the key customers and ‘Subject Matter Experts’. For example… • University • Clinical centres • SME researchers • Patient groups • EMEA • Payers • Health Technology Assessment agencies • Agencies that make decisions about reimbursement Project plan outline • Planned in two phases : • Phase A: Develop a framework to understand the Patients experience of COPD, especially in a broad European context, to inform strategies to measure outcomes meaningful to patients in global clinical trials • Phase B: Develop/select and validate PRO measurement tools, to use in clinical trials evaluating treatments for the disease • It is important to link to and build on existing International ‘Initiatives for the measurement of PROs in COPD’ to avoid redundancies

7. The 2008 Respiratory Calls: Understanding Severe Asthma Tim Higenbottam

8. Challenges to Drug Development in Severe Asthma • Heterogeneous disease (the “asthmas”) • Lack of standard definition of severe • Lung function • Medication requirements • Exacerbation frequency • Symptom burden • What are the phenotypes of a severe asthmatic? • Is there a genotype(s) of severe asthma? • Effect and detection of non-compliance • Lack of regulatory path in severe asthma • Lack of patient availability for clinical trials • Big gaps in care: • There is high unmet need for more effective, convenient and safe therapies, particularly for patients with moderately severe and severe disease. • 10% of asthmatics with the most severe disease account for up to 50% of the total costs of asthma care.

9. Challenges to Drug Development in Severe Asthma • What should we measure in severe asthma and with what instruments? Are they validated? • What are appropriate study designs and inclusion criteria in severe asthma? • Are there biomarkers to identify patient phenotypes and/or follow therapy • Identification of key targets and mediators of severe asthma • Understanding molecular pathways of steroid resistance • Role of imaging and/or other modalities for early decision making in development programs • Understanding mucosal immune function in severe asthma • Big gaps in care: • There is high unmet need for more effective, convenient and safe therapies, particularly for patients with moderately severe and severe disease. • 10% of asthmatics with the most severe disease account for up to 50% of the total costs of asthma care.

10. Longitudinal study of a severe asthma Patient Cohort Define disease Innovative Clinical measurements New model development Recruit cohort Longitudinal study Optimal dosing ideal PK/PD and high therapeutic index Optimal clinical measures of efficacy Newly defined cohort New clinical study design

11. The deliverables for severe asthma over 5 years First part of call deliverables: EU and Globally agreed Diagnostic criteria for severe asthma that are aligned to EMEA requirements A longitudinal cohort of severe asthma patients with relevant phenotype and genotype ~ recruited with a standardised protocol, data collection, and database with flexibility for novel measures to be added in during the project Identification as well as validation of novel targets for pharmacological therapy and biomarkers to assess response and predict effects on clinical outcomes Second part of the call: Translating the cohort into a new therapeutic paradigm Identification of targets relevant to specific phenotypes or genotypes of severe asthma. Understanding of aetiology and pathogenesis ofasthma exacerbations as mechanism to identify newtargets and therapeutic approaches especially withregard to delaying time to exacerbation and reducingseverity of exacerbation, which ultimately will deliversignificant pharmaco-economic benefits. Accurate targeting of an intervention to a particular,well-defined patient sub-population. Capability to develop translational models forappropriate prediction of clinical relevance throughpreclinical modelling. Access to defined patients which will facilitate enrolment and study of patients for clinical trials byacademic and pharmaceutical research.

12. What is needed in expression of interest in severe asthma • A CRO or SME partner to provide management and operational processes to the patient cohort • A multi-disciplinary scientific management board that includes clinical expertise, patients interest groups and laboratory scientists • An accepted definition ~ including the means for achieving one and engagement that enables alignment with the EMEA [FDA] requirements • Measurements to phenotype patients and to have agreed inclusion criteria for a database of patients • A standardised patient recruitment process across Europe • A standardised patient management using conventional therapy and adequate instruments/tests to determine compliance

13. Strategic Research Agenda (SRA): COPD, Asthma, Rhinitis • SRA identified one priority respiratory disease based on medical need: Asthma ~ severe or refractory was seen as the most important be the EFPIA resp group • As with each disease key bottlenecks fall into three main areas: • Disease understanding: Epidemiology, diagnosis, assessment of severity, phenotyping, biochemical and genomic markers • Translational models: Identification and validation of new preclinical and clinical models to facilitate translational research • Measurable outcomes: QOL measures that are sensitive to pharmacological interventions and can predict pharmacoeconomic benefit • Objective is to build a European Network or “Centre of Excellence” for asthma through the life of IMI, starting with 2008 calls • 2008 calls will be focussed to disease understanding for Asthma and outcomes for COPD

14. Full Consortium “ ” EFPIA + Public Consortium Joint working between the Industry, SMEs and Academia as Consortia:IMI is different from other Framework Initiatives New way of working * Shared research agenda • Joint preparation of the final proposal • Establish the process for managing the proposal • Establish timelines for deliverables • Select the partners and manner of working Focus on disease and patient need Tightly Managed Investment *Consortium includes EFPIA colleagues as active contributors not passive donors of money

15. 1Billion Euro 1Billion Euro The IMI is an independent company founded by EU Commission and EFPIA Funding is 2 billion Euros over 8 years In-Kind Contribution A non-monetary contribution to the consortium eg personnel, equipment, consumables etc 2 Billion EURO In kind + Cash In kind

16. Severe Asthma Project management Clinical FTE for protocol and CRF technical input and development and clinical monitoring of the project in the field Technical input and resources related to assays, imaging and application of other technologies Database and informatics support Statistics expertise Facilities and management of biobank for tissue samples Coordinate input from key stakeholders where relevant e.g. ERS/ ATS, EMEA, patient organisations COPD Project management Outcome Research Scientists and clinical scientists to contribute to both phase A and phase B, including relevant framework and protocol development and monitoring of validation studies Statistics and database expertise Hardware for home monitoring and electronic data capture Application and data management/ reporting of the questionnaire/instrument in phase II and III studies Coordinate input from key stakeholders where relevant e.g. ERS/ ATS, EMEA, patient organisations Potential in-kind contributions

17. Research Agenda Annual Implementation Plan Call definition Call Topics Call Expression of Interest 1st Peer Review ≈ 5 months • Stage 1: Scientific excellence • “Public” consortia (academia, SME, patient organisations) only. No EFPIA Invitation to Submit Full Proposal Full Project Proposal ≈ 3 months • Stage 2: Feasibility and scientific excellence. EFPIA join successful consortium from stage 1 2nd Peer Review 1. Project Agreement 2. Grant Agreement Contract Execution The Call & Evaluation Process

18. Evaluation Process for Successful EoI at Stage 1:EFPIA plus EC appointed independent experts Note EoI only eligible if submitted through web-based system • Scientific and/ or technological excellence • Quality of the approach • Likelihood to meet key project objectives • Complementarities with EFPIA consortium • Innovation, progress beyond state-of-art, impact • Partnership case • Quality and relevant experience of individual participants • Appropriateness of role/ input of each applicant • Quality of the applicant consortium as a whole • Unique features, balance • Quality and soundness of the workplan • Timelines, budget

19. Call 2008: Planned timelines • Publication of calls Apr 30th • Deadline for Expressions of Interest Jul 15th • Evaluation Stage 1 completes Jul 16th - Sep 30th • Submission period for full proposals Oct 1st - Nov 30th • Evaluation Stage 2 Dec 1st – Dec 3st • Negotiation, signature of Grant Jan 1st – Feb 28th Agreements, first payments

20. The IMI IPR Policy Must Align with the Objectives of IMI • IMI aims to remove the bottlenecks in R&D by conducting pre-competitive collaborative research utilising public and pharmaceutical industry resources IMI findings must be widely and readily available for research into the discovery and development of medicines IMI findings (Foreground IPR) must be widely and readily available for research into the discovery and development of medicines Information that Participants bring into a Project (Background IPR) that is necessary for the research use of IMI findings (Foreground IPR) must be widely and readily available for research into the discoveryand development of medicines

21. Note: The IMI IPR Policy Does Not Affect Commercialisation of IPR “Participants may use, exploit, sublicense or otherwise commercialise their intellectual property rights as they see fit beyond the Research Use rights described in this IPR Policy.” Total control for owner of Foreground andBackground IPR for non-research use

22. IMI Helpdesk can be accessed through IMI Website • Includes call documentation, submission tool and FAQ • Includes Helpdesk form for specific questions • http://www.imi-europe.org/Pages/IMI_Call_2008_1.aspx

23. Thank you very much for your attention! http://www.imi-europe.org IMI is public-private partnership between the European Commission and the European Pharmaceutical industry to promote biomedical innovation in Europe and to address the bottlenecks in the R&D process.