Joining Private and Public Forces to Boost

Innovation in Healthcare - The IMI Model

Magda Gunn, PhD

Scientific Project Manager

Open Info Day, Lisbon, 19 November 2012

“Non-competitive” collaborative

research for EFPIA companies

Competitive calls to select partners of

Key Concepts

Open collaboration in public-private consortia (data

sharing, wide dissemination of results)

Competitive calls to select partners of

EFPIA companies (IMI beneficiaries)

Innovative Medicines Initiative:Joining Forces in the Healthcare Sector

Private

Investment

in kind

(€ 1 billion)

EFPIA

Pharma 1

Pharma 2

Pharma 3

Pharma 4

Pharma 5

Pharma 6

A Typical IMI Consortium

EU Public

Funding

cash

(€ 1 billion)

ACADEMIA

HOSPITALS

PATIENTS’

ORGANISATIONS

SMALL AND

MEDIUM-SIZED

ENTERPRISES

REGULATORS

IMI JU and EFPIA commitmentsas of September 2012

• 7 Calls launched so far

(42 projects)

Mil

lio

n E

uro

(42 projects)

Mil

lio

n E

uro

Key Hurdles in Pharma R&D

• Disease heterogeneity

• Lack of predictive biomarkers

for drug efficacy/ safety

• Insufficient pharmacovigilance tools• Insufficient pharmacovigilance tools

• Unadapted clinical designs

• Societal bottlenecks

• Lack of incentive for industry

Projects Address Hurdles in R&D

7regulators

22 patient

91 SMEs

514 Academic & research

teams

347 EFPIAteams

€ 603 mln IMI JU

cash contribution

€600 mln

EFPIA ‘n kind

contribution

Key Figures of 37 on-going Projects

patient

org

R&D Productivity Improvements

~ 3500 researchers

> 240 publications

40

50

60

70

Number of Web of Science publications

Bibliometric Output so Far – Calls 1-3

By August 2012

eTOX

82% published in top quartile journals

11% of publications are

“highly cited

0

10

20

30

40

2009 2010 2011 2012

Call 1 Call 2 Call 3

EU-AIMScontributionto autism

eTOXcontribution tocardiotoxicity

Mapping Collaborative Networks - Call 1

2048 distinct co-authorship activities – 40% cross sector

Value Chain Coverage - Calls

Alzheimer’s Disease

translatable sleep deprivation model developed

characterized multiple Tg mice models

Chronic Pain sleep deprivation model validation on-going

menthol model validation on-going

UVB irradiation model validation on-going

Schizophrenia Depression

new animal models developed, multiple models evaluated

Establishment of robust validated models for drug development

Improving R&D productivity (1)

Depressiontranslatable imaging methodology develop

Autism developed animal model that mimics nonsyndromathic autism

Diabetes developed new animal models that mimic T1 and T2 diabetes, multiple models evaluated

Tg mice developed

developed human B cell line

Asthma 2 new animal models developed FCA/HDM and CT & MRI imaging of chronic HDM model

evaluated and harmonized multiple animal models

ScienceOctober 5th 2012

The consortium has developed an animal model replicating a nonsyndromic autism

and demonstrated that the condition can be reversed with specific therapy

This new development is be of great

importance for clinical development of new

treatments for autism

Alzheimer’s Disease novel biomarkers that follow disease progression in Tg mice

Chronic Paintranslatable imaging biomarkers of brain activation related to chronic pain

Schizophrenia Depression

clinical imaging biomarkers

clinical and molecular biomarker candidates for antidepressant response

Development of novel biomarkers for drug development

Improving R&D productivity (2)

Depression clinical and molecular biomarker candidates for antidepressant response

surrogate proteomic biomarkers for efficacy prediction

Diabetes candidate lipodomic and metabolomic biomarkers

novel genetic markers identified

Asthmagenetic, proteomic, metabolomic, breathomic biomarker candidates – validation on-going

Safetynovel early non genotoxic carcinogen biomarkers identified

potential biomarkers of drug induced injury of liver, kidney and vascular system

Development of liver injury alert algorithm for real time patient assessment and comparison with the

efficacy of the routine examination efficacy of the routine examination

The new strategy was much more efficient in identifying potential liver injury incidents, 12x more cases

were identified than with the standard strategy

The cases identified with the centralized strategy were much milder allowing for timely intervention

This new approach presents a significant improvement in timely identification of DILI cases

and will allow faster intervention to prevent from more serious events such as liver failure

Schizophrenia Depression

combined data analysis of 23,401 schizophrenia patients

Data from 45 randomized controlled studies of antidepressants on 11,000 patients – de novo analysis pending

combined genetic data analysis on 2146 DNA samples

Autism sequenced 78 Icelandic parent–offspring trios, a total of 219 distinct individuals (44 autistic, 21 schizophrenic offspring) and identified 4933 de novo mutations

Joining forces to make a difference – data pooling

Improving R&D productivity (3)

Chronic Pain pooled data from 43 past trials to understand the pain medicines mechanism of action and factors important in placebo response

Safety building a toxicology information database utilising toxicology legacy reports to develop better in silico tools for toxicology prediction of new chemical entities (1274 reports extracted so far, 2092 were cleared, 3564 are planned in total)

exploited EFPIA in vivo mouse and rat toxicology studies, tissue archives and molecular profiling data for >30 reference compounds to study NGC, genotoxic carcinogens and non-hepatocarcinogen controls

NEWMEDS - schizophrenia trials results

Proposed ways to reduce required numbers of patients needed for antipsychotic trials while preserving 90% power (p<.05)

Based on resampling of data from 34 such trials (n=11,670 patients) data from Astra Zeneca, Janssen, Lilly, Lundbeck, Pfizer

Samples can be reduced from 79 to 46 patients per arm by targeting trials

In addition the trial duration can be reduced from 6 to 4 weeks

Current mix =70% female; 20% early episode; 40% enriched

Average cost savings € 2,8 million

Enriched=prominent positive and negative symptoms

Early episode=under 3 with 4 or more years of illness

Note: Per patient cost 6wk study $70,000-$100,000

Asthmadiagnostic criteria on severe asthma

Schizophrenia Depression

clinical biomarker meaningfulness calculator for predicting biomarker candidate utility in predicting antidepressant response

identified phenotypes associated with schizophrenia CNVs

Agreeing development and regulatory submission of

key standards for drug development

Improving R&D productivity (4)

identified phenotypes associated with schizophrenia CNVs

Diabetes developed non-invasive carotid histology for diabetic macroangiopathy

generated phenotype definitions for diabetic complications

COPDderived a conceptual model for physical activity

developed patient reported outcome tools – validation on-going

Safetyestablished generic qualification strategy for translational biomarkers

building ontology for preclinical pathology, 3917 terms and 2535 synonyms have been mapped

Activity

monitor(s)

selection

Development of

Patient Reported Outcome tools

Discussion Guide

Focus GroupsWP2B

Initial Item Pool

Cognitive debriefingWP2B

Selection of Activity monitors

Validation

(Validity and usability)WP2D

Sources

LiteratureWP2A

ExpertsWP2C

PatientsWP2BWP2B

Reduced Item Pool Chosen Activity monitor

Initial PROs

Initial

Validation Study

in patientsWP4

Clinical Validation studiesWP6 A-C

Draft PROs

Final PROs validated

Integration in

Electronic platformWP3

WP2B

Work

Package

Deliverable

Milestone

Schizophrenia Depression

proposed reduction in duration of schizophrenia trials

proposed reduction in number of patients required

developing new approach of combining medication with therapy

Alzheimer’s Disease

new clinical study designs

Chronic Pain optimizing clinical trial design to reduce placebo response

Optimizing clinical trials

Improving R&D productivity (5)

Antibiotics Autism

creation of pan-European clinical investigator networks

Asthma COPD

involving patients in clinical trials and beyond

established network of excellence in in bronchoscopy in severe asthma

generated central registry of patients with severe asthma

Tuberculosis aims to improve the development of new more effective treatment combinations for TB

Knowledge Management

identification of clinical sites through EHR

IMI Projects’ ImpactPATIENTS

New, more effective and

safer medicines faster

Personalized treatment

approaches

Faster adverse effects

detection and interventionINDUSTRY

Faster and cheaper trials

Reduce late phase attrition

Facilitating regulatory

ACADEMIA

Reduced time to patient

Building collaborative

networks

Access to industry expertise

Access to data and samples

SOCIETY

Decreased societal burden

Reduced use of ineffective

drugs

Reduced cost due to drug

adverse effects cases

More productive economies

Decreased use of animals

Facilitating regulatory

approval

Better informed go/no-go

decisions

Reshaping regulatory

landscape

Reduced cost Access to data and samples

Focus on applied research

Building an IMI Project (1/2)

Submission of

Expressions of Interest

First Peer review Competition

between

By applicants’ consortia

(academics, SMEs, Patient org….)

Independ. experts + EFPIA coordin.

Independ. experts

assessment

ranking

22

First ranked consortium

Invitation to submit

Full Project Proposal

between

applicants’

consortia(potential IMI beneficiaries)

Independ. experts

Approved by IMI Governing Board

to first ranked applicants’ consortium

+ EFPIA consortium

ranking

Submission of

Full Project Proposal

Second Peer review

Joint Preparation

of

By full project consortium

(first ranked applicants’ consortium

+ EFPIA consortium)

Independent experts

Building an IMI Project (2/2)

23

Second Peer review

(including ethics)

Approval of Full Project

Proposal

of

Full Project

Proposal

Independent experts

by IMI Governing Board

Developing a framework for rapid assessment of vaccination benefit/risk in Europe

Incorporating relative effectiveness research into development strategies

The Pipeline

Developing an etiology-based taxonomy for human diseases

(Rheumatoid arthritis, Lupus, COPD, Parkinson’s…)

Building a European bank to hold and supply iPS cells

Call 7 Call 8 Future Calls

Building a European bank to hold and supply iPS cells

Additional projects to tackle anti-microbial resistance

− ND4BB Topic 3: Discovery and development of new drugs combatting Gram-negative

infections

− ND4BB Topic 1C (Innovative trial design & clinical drug development

Developing combination therapies

Leveraging emerging technology for pharmacovigilance

Developing an aetiology based

taxonomy of human disease

Systemic Lupus

Erythematosus (SLE) &

related connective

tissue disorders &

Rheumatoid Arthritis

(RA)

Neurogenerative

disorders focus on

Alzheimer’s disease and

Parkinson’s disease

Chronic Obstructive

Polmonary Disorders

(COPD)

Taxonomy Platform TOPICS

(RA)

Coordinated by UCB

+

3 separate grant agreements

New calls for next disease areas

In-kind commitment

€25 million

+

IMI JU up to

€25 million

European Induced Pluripotent Stem

Cell Bank

Scientific

• Generation of a full complement of geno- &

phenotypic data for key patient cohorts

• Research and implementation of current gold

standard practises for the generation and

differentiation of iPS cells

Operational

• Set-up of a sustainable, not-for-profit, specialist

production, storage and distribution centre for

iPS cells across Europe

• Provide patient derived iPS cells to a defined

quality and within a defined time from placing

an order• Development of automatable processes for iPS

cell culture and banking

• Application of best practise in cryopreservation

& biobanking to develop a ‘commercial

standard’ state of the art iPS facility

• Provision of quality protocols and training in iPS

cell growth & development

an order

• Supply an iPS differentiation service during the

latter half of the call

• Provide searchable anonymized geno-,

phenotypic & clinical data associated with each

iPSC line

Budget €30 million in-kind commitment + € 40-45 million IMI JU

ND4BB Topic 3: Discovery and development of new

drugs combatting Gram-negative infections

• Focuses on Gram-negative infections only

• Invites public and private partners with Hits and Leads with a

novel mechanism of action

• Invites experts and professionals in medicinal chemistry,

microbiology, biochemistry, pharmacokinetics microbiology, biochemistry, pharmacokinetics

• Aims to combine expertise and knowledge to create a “European

Drug Discovery Centre of Excellence for antibiotic resistance”.

• Goal is the delivery of novel Leads and Development Candidates

• Successful Development Candidates can move forward up

through Phase 1 clinical trial

ND4BB Topic 3: Discovery and development of new

drugs combatting Gram-negative infections

European Drug

Discovery Centre

of Excellence for

antibiotic

resistance

Hit-to-Lead

programs novel

mechanism of

actionfrom public and

private partners

medicinal chemistry,

microbiology,

biochemistry,

pharmacokinetics,

etc. from academia, SME and

EFPIAEFPIA

Qualified Leads

Qualified Candidates

Phase-1 ready

Phase 1 clinical trial

GSK/Sanofi

collaboration

Portfolio

Management

Committee (50:50 EFPIA:Public)

In-kind

commitment

€26 million

IMI JU

€ 58.9 million

ND4BB 1C : Innovative trial Design & Clinical Drug

Development against MRSA.

WP6 of Topic 1: Conduct clinical trials supporting the development of

MEDI4893, a monoclonal antibody targeting S. Aureus alpha toxin

In-kind

• WP6A: Epidemiologic Surveillance of Surgical Site Infections in the EU

• WP6B: Prospective observational study

SSI: surgical site Infections; VAP: ventilator associated pneumonia

In-kind

commitment

€25.4 million

IMI JU

€26.4 million

• WP6C: Phase 1b/2 study with MEDI4893 for ventilator associated

pneumonia (VAP)

• WP6D: Phase 1b/2 study with MEDI4893 for prevention of surgical

site infections by Staphylococcus aureus

WP7: Conduct of clinical trials supporting the development of AZ9773.

• Looking for additional funding

• Interested in patient-centric biomedical/pharmaceutical research

Why apply ?

• Interested in collaborating with large pharmaceutical companies

IMI Executive Office as a Neutral

Third-Party

• Ensures that projects are carried out in the

common interest of all stakeholders

• Guarantees fair conditions for knowledge • Guarantees fair conditions for knowledge

exploitation and dissemination

• Facilitates the dialog between industry, patients’

organizations and regulatory agencies

Find project partners

• IMI Partner Search Tool: www.imi.europa.eu/content/partner-search

• IMI States Representatives Group (SRG) member: IMI States Representatives Group (SRG) member: www.imi.europa.eu/content/states-representatives-groups

• Health National Contact Point (NCP): cordis.europa.eu/fp7/health/ncp_en.html

Keep up to date

• Visit www.imi.europa.eu

• Sign up to the IMI Newsletter

• Follow us on Twitter: @IMI_JU• Follow us on Twitter: @IMI_JU

• Join the IMI group on LinkedIn

• Questions? E-mail us: infodesk@imi.europa.eu

EXPLORING NEW SCIENTIFIC

OPPORTUNITIESOPPORTUNITIES

Objectives (1/2)

• To carry out new activities demonstrating significantadded value to on-going IMI projects following• promising results• major changes in the field after the start of the project• new needs generated by the activities of the project• new needs generated by the activities of the project

• To create synergies or complementarities with otherIMI projects, which provide significant added valuebeyond the initial project objectives

35

Objectives (2/2)

• To build on IMI projects’ results (Foreground) that offer apotential interest for further investigations going beyondthe initial project objectives

• To explore ways to ensure the sustainability of IMI• To explore ways to ensure the sustainability of IMIprojects’ achievements

• To obtain extra funding to involve new partner(s) capableof major contributions to IMI projects

36

RDG Endorsement Procedure

Project Coordinators should inform the EFPIA secretariat and the RDG project sponsor well in advance of deadline.

Coordinators then fill in the RDG endorsement form with details of extra in-kind contribution.

Both the RDG form and the ENSO application form are forwarded to the RDG by the RDG sponsor for review.

If the application is supported by the RDG, the Project Coordinator shall submit the application to the IMI.

Timelines and Budgets

• 15th December 2012 €5,378,249• End Q2 and Q4 2013 ~€6 – €7 million equally divided

between dates + carry-over

• Evaluation outcomes: within 2 months following cut-off-datedate

• Successful consortia finalize the scientific/financial details(“negotiation phase”)

• Amendment to on-going grant agreement for successfulrequest(s)

THANK THANK YOU !YOU !THANK THANK YOU !YOU !

www.imi.europa.eu