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

2. Declining R&D productivity
The way in which pharmaceutical companies
develop new medicines is changing
Pharma
Regulators
EU Pricing
Generics
HC Reform
Rising R&D cost
Declining R&D productivity
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 more innovative and efficient
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 18 weeks 9 weeks 6 weeks SMEs Academic research teams
EFPIA
IMI
Topic Definition
& Launch
Applicant Consortia
EoI Submission
1st ranked EoI + EFPA
Full Project Proposal Submission
Governing Board approval
Signatures & project kick-off
How it works
SMEs
Academic research teams
Hospitals
Step 1
Step 2
Step 3
Step 4
Step 5
The
Consortium
Regulatory authorities
Patients’ organisations
Call Launch
1st ranked EoI Selection
GB approval of 1st ranked FPP
negotiations start
Signatures & project kick-off
18 weeks
9 weeks
6 weeks

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

7. The IMI portfolio

8. Calls 1-8 participations per country

9. IMI projects

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

11. Implementation of project results inside industry
Making a difference
Implementation of project results inside industry
Project
Area
Results description
IMIDIA
diabetes
The human beta cell line EndoC BetaH1 has been validated by Endocells and 3 pharma partners confirming their initial insulin secretion capacity. These cells have been successfully transferred as a research tool for drug discovery to industrial partners.
DDMORE
knowledge
management
Several drug/disease models identified by DDMORE are adopted or further developed inside the industry.
eTRIKS
Adoption of the eTRIKS results, TransMART system deployments in 5 pharmaceutical companies.
EUROPAIN
Chronic pain
Preclinical model of spontaneous pain in rodents has been developed, standardized, validated, and is already used for internal decision making in the drug development process.
The ultraviolet B (UVB) pain model has also started to be used for in house R&D.

12. Impact on regulatory framework
Project
Area
Results description
PROactive
COPD
Qualification Advice completed at the EMA
EU-AIMS
autism
Started EMA formal scientific advice procedure for qualification of 5 biomarkers in ASD
eTOX
drug safety
Provided an update on the eTOX database and the prediction system to the CHMP Safety Working Party (SWP) at EMA. Scientific Advice Procedure was initiated.
MARCAR
cancer
Has developed new biomarkers, technologies, and alternative test systems that help explain or predict animal and/or human carcinogenic pathways and mechanisms for non-genotoxic carcinogenesis. This will provide enhanced scientific rationale for Carcinogenicity Assessment Document (CAD) submissions, with potential impact for ICH S1 carcinogenicity testing guideline revisions.
Safe-T
Developed and now progressed towards an aligned EMA/FDA qualification a set of novel safety biomarkers for drug-induced kidney, liver, and vascular injury.
DDMORE
knowledge
management
In May 2012 an advisory meeting with EMA and FDA representatives was held. Through a Modelling Review Group , DDMoRe is in regular contact with both the EMA and FDA regarding the qualification of the content of the project’s Model Library.

13. 18.4% 15% SME participation in IMI projects (up to 8th Call)
Total IMI commitment
€ 723 million
Total received by SMEs
€ 133 million
% SME
18.4%
Total IMI participations
886
Total SME participations
135
15%

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 in PharmaCog project
“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&D more trained patients are needed
Competent authorities
Policy makers
Trial protocol design, informed consent, ethical review, marketing authorization, value assessment, health policy
Public
Research subject
Info provider
Advisor
Reviewer
Co-researcher
Driving force
Clinical Research
Research Ethics Committees
HTA agencies & committees

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 Will build competencies & expert capacity among patients & public Will facilitate patient involvement in R&D to collaborate in academic research, industry research, authorities and ethics committees

18. Key collaborative activity areas:
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. Better Science = Better Decisions
The measures of success
SUCCESS
New models developed & published
Setting new standards
In house implementation by industry
Impact on regulatory guidelines
Better Science = Better Decisions

20. www.europeanleadfactory.eu nd4bb-enable.eu
IMI’s drug discovery platforms
Target
screening
Hit-to-lead
Lead-to-candidate
Preclinical
Phase I
Phase II
Phase III
European Lead Factory Focus:
identification of new hits
ELF Budget:
€92.0m EFPIA in-kind
€80.0m IMI JU
‘Qualified’
hit
European Lead Factory
ND4BB Drug Discovery Platform
Lead
Clinical
Candidate
Phase 1-
ready
Insert web addresses for applicants
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
Originally designed as a technology platform to resolve scientific bottlenecks in drug discovery and development to reduce attrition rate, the research agenda of IMI evolved to also address main challenges for society.
IMI agenda was broadened to include all stages of medicines development to translate more effectively invention into innovation.
As a consequence, IMI directly addresses a number of European and national priorities/policies:
Active and Healthy Ageing
Antimicrobial Resistance and infectious diseases (diagnostics and treatment)
Pharmacovigilance
Personalised Medicines
Impact of chronic diseases
Mental health
Beyond resolving scientific bottlenecks and contributing to resolve significant healthcare challenges, the endavour of IMI2 is to translate scientific results into standards of care to have a real beneficial impact on patients.
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. The Vision for IMI2 – The right prevention and treatment for the right patient at the right time
effective
effective
not effective
Adverse events
Trial and Error Dx
Test B
not effective
Biologically heterogeneous patient population C
adverse events
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
“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.”

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 Areas in IMI2 SRA
(no priority order)

28. Drive change in delivery of medical practice
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
Discovery and Development
of novel preventative and
therapeutic agents
Innovative adherence
programmes
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

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. Submission date: 12 November 2014
IMI2: The First Call
Two topics:
Translational approaches to disease modifying therapy of type 1 diabetes mellitus (T1DM)
Discovery and validation of novel endpoints in dry age-related macular degeneration and diabetic retinopathy
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 / / 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
IMI2 JU: EUR
Total: EUR

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 % 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
IMI2 JU: EUR
Total: EUR

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

51. Questions?