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
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)
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
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
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: [email protected]
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)