From IMI to IMI2 Hugh Laverty Senior Scientific Project Manager

1. From IMI to IMI2 Hugh Laverty Senior Scientific Project Manager Vilnius, 11th September 2014

2. The way in which pharmaceutical companies develop new medicines is changing Regulators EU Pricing Pharma Rising R&D cost HC Reform Declining R&D productivity Generics Patent cliff

3. New approaches needed “Deciphering the complexity of human diseases and finding safe, cost-effective solutions that help people live healthier lives requires collaboration across scientific and medical communities throughout the health care ecosystem. Indeed, we must acknowledge that no single institution, company, university, country, or government has a monopoly on innovation.”

4. Innovative Medicines Initiative:Joining forces in the healthcare sector • The biggest public/private partnership in Life Science aiming to: • Make drug R&D processes in Europe moreinnovative andefficient • Enhance Europe’s competitiveness • Address key societal challenges • Features: • 1:1 funding, joint decision making • All EU funds go to SMEs, academia, patient organisations and regulatory agencies • Large pharmaceutical industry, represented by EFPIA, contributes in-kind

5. How it works SMEs Academic research teams Hospitals Step 2 Step 3 Step 4 Step 5 Step 1 • The • Consortium • Signatures & project kick-off • Call Launch • 1st ranked EoI Selection • GB approval of 1st ranked FPP • negotiations start Regulatory authorities Patients’ organisations 18 weeks 9 weeks 6 weeks

6. The IMI community • 46 projects • Calls 1-8 • > 6000 researchers 23 patient org. 135 SMEs 50%of projects have regulatory authorities representatives in Scientific Advisory Boards regulators on board of 12 projects 714 academic & research teams 61%of projects reported some form of PATIENT involvement 14 regulators 410 EFPIA teams

7. The IMI portfolio

8. Calls 1-8 participations per country

9. IMI projects

10. IMI scientific output 3709 citations 708 publications 19%Highly cited 2.04citation impact

11. Making a difference

12. Impact on regulatory framework

13. SME participation in IMI projects (up to 8th Call)

14. SME success stories SME involved in SAFE-T project “Thanks to IMI our company went from 6 to 50 employees. Now we are ready to go to further expand.” SME involved in IMIDIA project – “1st product released to the market in 2013 – IMI was instrumental in validation of the first cell line product, 2nd product release planned this year, 3rd diagnostic product in development. In preparation: a new patent filing to protect technologies for the creation of third generation human beta cell lines. SME involved inPharmaCogproject “We are developing a blood panel for AD for diagnosis, stratification and companion diagnostics in AD. The Panel was tested on 300 patients in IMI project” SME involved in eTOX project “We have developed in silico models for predicting toxicity, which were validated by pharmas in eTOX. Now we have signed a contract with one of the companies to use our models in house.”

15. Promoting patient involvement • IMI makes efforts to enhance patient centric approach • Patient dedicated workshops • Involving patients at all levels • Providing forum for discussion • IMI best practice examples: EUPATI U-BIOPRED PROactive

16. For patient-centric R&Dmore trained patients are needed Competent authorities Policy makers • Trial protocol design, informed consent, ethical review, marketing authorization, value assessment, health policy Public Drivingforce Co-researcher Reviewer Advisor Clinical Research Info provider Research Ethics Committees HTA agencies& committees Research subject

17. Paradigm shift in empowering patients on medicines R&D Key European initiative to provide objective, credible, correct and up-to-date public knowledge about medical research Willbuild competencies & expert capacity among patients & public Willfacilitate patient involvement in R&D to collaborate in academic research, industry research, authorities and ethics committees

18. Collaboration Key collaborative activity areas: Diabetes, CNS disorders, Tuberculosis, Patient Reported Outcomes, Cancer, Preclinical Safety and Education & Training. IMI signed horizontal agreements with: Critical Path, Juvenile Diabetes Research Foundation as well as with Clinical Data Interchange Standards Consortium.

19. The measures of success New models developed & published In house implementation by industry Setting new standards Impact on regulatory guidelines Better Science = Better Decisions

20. IMI’s drug discovery platforms European Lead Factory Focus: identification of new hits ELF Budget: €92.0m EFPIA in-kind €80.0m IMI JU ‘Qualified’ hit www.europeanleadfactory.eu European Lead Factory ND4BB Drug Discovery Platform Phase 1- ready Clinical Candidate Lead nd4bb-enable.eu ENABLE Budget: €26.0m EFPIA in-kind €58.9m IMI JU ENABLE Focus: to move promising hits into early clinical development

21. Towards IMI2

22. The Evolution of IMI: From bottlenecks in industry – to bottlenecks in Industry and Society • Make Drug R&D processes in Europe more efficient and effective • and enhance Europe’s competitiveness in the Pharma sector Idea generation Basic research and non-clinical testing Human testing Regulatory Approval HTA and Pharmacovigi- lance Daily Medical practice Primary focus of early IMI calls 2007 SRA Shift to also addressing challenges in in society and healthcare 2011 SRA IMI 2 includes real life medical practice 2013 SRA

23. effective noteffective Adverseevents Trial and Error The Vision for IMI2 – The right prevention and treatment for the right patient at the right time A effective B Dx Test noteffective Biologically heterogeneous patient population C adverseevents e.g. biomarker Information based treatment decisions vs Graphic adapted from C. Carini, C. Fratazzi, Eur. Pharm. Rev. 2008, 2, 39-45

24. Science is driving advances in diagnosis: breast cancer is actually 10 different diseases Thursday April 19 2012 “A landmark study has reclassified the country’s most common cancer in breakthrough research that could revolutionise the way we treat breast tumours… scientists found breast cancer could be classified into 10 different broad types according to their common genetic features.” http://www.nhs.uk/news/2012/04april/Pages/breast-cancer-genetic-diversity-mapped.aspx

25. Objectives of IMI2 – what the Regulation says • increase the success rate in clinical trials  • where possible, reduce the time to reach clinical proof of concept in medicine development • develop new therapies for diseases for which there is a high unmet need and limited market incentives • develop diagnostic and treatment biomarkers for diseases clearly linked to clinical relevance and approved by regulators; • reduce the failure rate of vaccine candidates in phase III clinical trials through new biomarkers for initial efficacy and safety checks; • provide support for the development of tools, standards and approaches to assess efficacy, safety and quality of regulated health products.

26. The premises • Alignment with Horizon 2020 objectives of the Health challenge • Addressing healthcare priorities identified by the WHO 2013 report on priority medicines for Europe and the world  • Strategic Research Agenda aimed at progressing the vision of personalised medicines, for both prevention and treatment • Collaboration across sectors to harness all knowledge and technologies which can contribute to IMI2 vision - diagnostics, imaging, IT, medical devices, … 

27. 2013: WHO report on priority medicines for Europe and the World:societal challenge reflected in the IMI2 SRA Therapeutic Areasin IMI2 SRA (no priority order)

28. IMI2: Major Axes of Research Biomarker identification/validation (precision medicine) Innovative methodologies to evaluate treatment effect Reclassification of disease by molecular means Innovative clinical trial paradigms Target & Biomarker Identification (safety & efficacy) Adoption of innovative clinical trial designs Target Identification and validation(human biology) European Health Priorities Benefit/Risk Assessment Determinants of drug /vaccine Safety and efficacy Innovative Medicines Patient tailored adherence programmes Healthcare delivery: focus on the treatment programmes not just the medicine Innovative drug delivery methodologies Manufacturing for personalised medicines Innovative adherence programmes Discovery and Development of novel preventative and therapeutic agents Drive change in delivery of medical practice

29. Strategic Research Agenda Comprehensive framework for a 10-year programme Prepared with input from 80+ organisations (internet and targeted) Project ideas from industry and third parties will be screened against it http://goo.gl/jqMP9g

30. IMI2 -Broad participation to be able to set ambitious goals IMI is evolving, with a stronger focus on the needs of patients and society and with simpler rules and procedures Evolution in scientific focus • Stronger focus on needs of patients and society, including unmet needs • Increased emphasis on improving patient access to innovative medicines (in addition to medicines development) • Focus on personalised medicine (the right treatment for the right patient at the right time)

31. IMI2 - Broad Participation to achieve ambitious goals: Bigger budget: 3,45 Billion Euro, equally shared by EU and industry • Not limited to EFPIA members: open for other industries / companies, which can contribute to the PPP goals (Healthcare IT, medical devices,…) giving them the opportunity to establish their own projects • The principle of large companies providing an inkind contribution matched by IMI funding for public beneficiaries will be retained.

32. IMI2 - Broad Participation to achieve ambitious goals: Specified Budget: 225 million Euros reserved for non-EFPIA led projects (to be matched by inkind contributions) • Objectives, deliverables and timelines determined by the company(ies) proposing the project • Inkind contribution determined by the company(ies) • Once approved by IMI’s Governing Board the Programme Office will launch a call for proposals to identify public partners for the project • The call process and review of submitted proposals will be independent of the company(ies)

33. The Role Of The Programme Office A neutral broker: • To implement programmes and activities in the common interest of all stakeholders • To monitor the use of public funds and industry investment • To guarantee fair and reasonable conditions for optimal knowledge exploitation and dissemination • To facilitate the interaction between stakeholders, including Intellectual Property agreements • To actively communicate and promote IMI and its activities

34. IMI2: The First Call Two topics: Translational approaches to disease modifying therapy of type 1 diabetes mellitus (T1DM) Magda.Gunn@imi.europa.eu Discovery and validation of novel endpoints in dry age-related macular degeneration and diabetic retinopathy Nathalie.Seigneuret@imi.europa.eu Submission date: 12 November 2014

35. Translational approaches to disease modifying therapy of type 1 diabetes mellitus (T1DM) Vilnius, 11th September 2014

36. Translational Approaches To T1DM:Background • A chronic disease affecting worldwide around 17 Million people and with highest incidence rate in Europe ( ~ 22 / 100.000/ year), with major regional differences. • The incidence of childhood T1DM is reported to be rising rapidly worldwide, especially in the under 5 year old age group. • T1DM is generally seen today as an autoimmune disease, but its cause is unknown (genetic susceptibility, diabetogenic trigger(s) and/or exposure to a driving antigen). • The disease is currently not preventable and no cure is available. The only available pharmacotherapy for T1DM patients is the lifelong injection of insulin.

37. Translational Approaches To T1DM:Aims and Objectives Better Disease Biology and Translational Medicine (Target & Biomarker Identification) • Generation of a high quality and comprehensive European network of clinical and translational research centres(providing a prospective clinical trials database for T1DM) including at risk and early T1DM patients. • Establishment of systematic large-data repository enabling extensive cross functional data mining and integrated data analysis • Phenotypical characterization (in silico based on medical records as well as active through experimental medical studies) • Systematic prospective and retrospective launch of broad “–omics” characterization of human biological samples • Development and characterization of the most appropriate preclinical T1DM model(s) for discovery of novel clinical therapies.

38. Translational Approaches To T1DM:Aims & Objectives Innovative clinical trial paradigms for preventative and disease modification trials in T1DM. • Development of standardized entry criteria and endpoints for T1DM trials (both metabolic and immune profiles) with participation of patient advocacy groups, and regulatory authorities. • Implementation of the use of electronic data capture devices to collect an array of “real world data” • Testing and development of novel bio-statistical methodologies applicable to new compositions of relevant end points for T1DM clinical trials. • Evaluation of novel mono- and combination approaches (i.e. combining multiple immune modulatory approaches, immune cell migration modification, immune tolerance inducers, β-cell enhancing therapeutics) in people with T1DM.

39. Translational Approaches To T1DM:Key Deliverables • An improved understanding of the immunological and beta cell biology aspects of T1DM to disentangle its heterogeneity both in at risk and early diagnosed patients and for staging participants in future T1DM clinical trials. • The development of novel and relevant endpoints & readouts for T1DM clinical trial based on clinical & standardised molecular “real world data” obtained from T1DM patients, and on the application of novel bio-statistical methodologies. • Pre-clinical T1DM models with improved translational value. • Improved understanding of the human T1DM disease biology and optimised clinical trial setting to allow testing novel mono- and combination approaches in T1DM.

40. Translational Approaches To T1DM: EFPIA PARTICIPANTS AND ASSOCIATED PARTNERS Sanofi (coordinator), Juvenile Diabetes Research Foundation (JDRF) (co-coordinator), Novo Nordisk, Eli Lilly, GSK, Helmsley Charitable Trust. DURATION OF THE PROJECT The indicative duration of the project is 84 month (7 years). BUDGET EFPIA and associated partners: EUR 17 630 000 IMI2 JU: EUR 17 630 000 Total: EUR 35 260 000

41. Translational Approaches To T1DM: APPLICANT CONSORTIUM • Academic endocrine clinics and associated supporting departments • Basic, translational, and clinical researchers from the fields of T1DM autoimmunity and β-cell biology • Drug discovery and medical staff in Pharmaceutical Industry and Small and Medium size Enterprises • Hands-on data base specialists and big data managers • Patient organizations/representatives • Experts in regulatory science and health technology assessment preferably representing European health authorities. The project will be expected to establish a T1DM Patient Advisory Committee

42. Translational Approaches To T1DM:Suggested Work Plan • A plan for interactions with Regulatory Agencies/Health Technology Assessment bodies with relevant milestones and appropriate resource allocation should be included • Synergies with other EU and global initiatives, including IMI projects

43. Discovery and validation of novel endpoints in dry age-related macular degeneration and diabetic retinopathy Vilnius 11th September 2014

44. Novel Endpoints For Retinal Diseases • Retinal diseases among leading causes of blindness worldwide • Age-related macular degeneration (AMD):  Early form reported to occur in 30% of the population of 75 years and above (over 50% by age 80);   late form in 4 - 8% of the population over 70 years  • Approximately 93 million affected by diabetic retinopathy (DR) in 2010 • Limited treatment options for dry form of AMD or DR • Major development hurdles: lack of suitable endpoints for early exploratory and pivotal clinical trials, lack of predictive markers and models

45. Novel Endpoints For Retinal Diseases: Aims & Objectives To evaluate novel endpoint candidates for dry AMD and DR: • technical, medical and health economic appropriateness • bridging preclinical and clinical studies. Methods in scope: • Visual function testing beyond Best Corrected Visual Acuity (BCVA) • Electrophysiology • Imaging methods to assess retinal structure • Soluble and genetics biomarkers • Patient reported outcome tools and Quality of Life-related endpoints • A combination of these methods

46. Novel Endpoints For Retinal Diseases: Key Deliverables Generation of robust data resulting from retrospective and/or prospective studies as basis for discussion of regulatory acceptability of the endpoints for future clinical programmes. It is expected that the proposed research program delivers data on:  • Technical evaluation of methods (validity, repeatability, reliability, interpretability, translatability and acceptability by patients) • Development of novel methods and tools • Clinical validation of methods/tools in patient studies for dry AMD & DR • Collection of biomarkers for selection of high risk populations • Synergies between dry AMD and DR vs condition-specific aspects

47. Novel Endpoints For Retinal Diseases: EFPIA PHARMA PARTICIPANTS AND OTHER PARTNERS Bayer HealthCare (coordinator), Sanofi, Novo Nordisk, Zeiss DURATION OF THE PROJECT The indicative duration of the project is 60 month (5 years). BUDGET EFPIA and associated partners: EUR 7 000 000 IMI2 JU: EUR 7 000 000 Total: EUR 14 000 000

48. Novel Endpoints For Retinal Diseases: Setting-up & running of studies required to meet topic’s objectives Multidisciplinary applicant consortium with a track record of • Clinical expertise in ophthalmology • Clinical research experience • Access to patients and databases • Public health expertise • Health economic expertise • Understanding of pre-clinical models in ophthalmology • Biomarkers • Data management • Regulatory, ethics, patients and project management

49. Novel Endpoints For Retinal Diseases: Suggested Work Plan • Architecture for the full proposal to be suggested by the Applicant consortium • Intention to set-up of an Advisory panel to the Consortium comprising payers, regulatory agencies and other relevant expert advisors • Plan for interactions with Regulatory Agencies/Health Technology Assessment bodies expected • Synergies with other EU and global initiatives, including IMI projects

50. IMI2 Info Day • Crowne Plaza Hotel, Brussels, Tuesday 30 September 2014 • Workshops and presentations of topics by the topic writers • Overview of IMI 2 funding and intellectual property (IP) rules • Tips on applying for funding under IMI 2 • Networking opportunities • IMI staff on hand to answer questions • We warmly encourages small and medium-sized enterprises, mid-cap businesses, patient organisations, regulatory authorities, academic teams, industry, hospitals and other organisations 50