Translational Approaches To T1DM

Report
From IMI to IMI2
Hugh Laverty
Senior Scientific Project Manager
Vilnius, 11th September 2014
The way in which pharmaceutical companies
develop new medicines is changing
Regulators
Rising
R&D cost
EU Pricing
Pharma
Patent cliff
Generics
Declining R&D
productivity
HC Reform
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.”
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
•
Large pharmaceutical industry,
represented by EFPIA, contributes in-kind
All EU funds go to SMEs, academia, patient
organisations and regulatory agencies
How it works
SMEs
Academic
research teams
Step 1
Topic
Definition
& Launch
Hospitals
Step 2
EFPIA
EoI
Submission
Step 3
Applicant
Consortia
IMI
Regulatory
authorities
18 weeks
Step 5
Governing
Board
approval
IMI
Signatures
& project
kick-off
Patients’
organisations
GB approval of
1st ranked FPP
negotiations
start
1st ranked
EoI
Selection
Call
Launch
Full Project
Proposal
Submission
Step 4
1st
ranked
EoI +
EFPA
9 weeks
Signatures
& project
kick-off
6 weeks
The
Consortium
The IMI community
46 projects
Calls 1-8
> 6000 researchers
410
EFPIA teams
714
academic &
research
teams
61% of projects
reported some form of
PATIENT
INVOLVEMENT
23
patient
org.
135
SMEs
14
regulators
REGULATORS ON BOARD OF
50% of projects have
12
REGULATORY AUTHORITIES
PROJECTS
representatives in Scientific
Advisory Boards
The IMI portfolio
Calls 1-8 participations per country
IMI projects
IMI scientific output
708
3709
2.04
19%
PUBLICATIONS
CITATIONS
CITATION IMPACT
HIGHLY CITED
Number of publications per year
350
300
250
200
150
100
50
0
2009
2010
2011
2012
2013
Making a difference
Implementation of project results inside industry
Project
IMIDIA
Results description
Area
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
eTRIKS
knowledge
management
Adoption of the eTRIKS results, TransMART system deployments in 5
further developed inside the industry.
pharmaceutical companies.
Preclinical model of spontaneous pain in rodents has been developed,
standardized, validated, and is already used for internal decision
EUROPAIN
Chronic pain
making in the drug development process.
The ultraviolet B (UVB) pain model has also started to be used for in
house R&D.
Impact on regulatory framework
Project
Area
PROactive
COPD
EU-AIMS
autism
Results description
Qualification Advice completed at the EMA
Started EMA formal scientific advice procedure for qualification of 5
biomarkers in ASD
Provided an update on the eTOX database and the prediction system to the CHMP
eTOX
drug safety
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
DDMORE
drug safety
Developed and now progressed towards an aligned EMA/FDA qualification
a set of novel safety biomarkers for drug-induced kidney, liver, and vascular injury.
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.
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
% SME
15%
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.”
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
For patient-centric R&D
more trained patients are needed
Competent
authorities
Public
Trial protocol design,
informed consent, ethical
review, marketing
authorization, value
assessment, health policy
Policy makers
Driving force
Co-researcher
Reviewer
Advisor
Info provider
Research subject
Research Ethics
Committees
HTA agencies
& committees
Clinical
Research
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
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.
The measures of success
SUCCESS
New models
developed &
published
Setting new
standards
In house
implementation
by industry
Better Science = Better Decisions
Impact on
regulatory
guidelines
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
European Lead Factory
Target
screening
www.europeanleadfactory.eu
Hit-to-lead
Lead-tocandidate
Preclinical
Phase I
Phase II
Phase III
ND4BB Drug Discovery Platform
Lead
nd4bb-enable.eu
Clinical
Candidate
ENABLE Focus: to move promising hits
into early clinical development
Phase 1ready
ENABLE Budget:
€26.0m EFPIA in-kind
€58.9m IMI JU
Towards IMI2
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
Basic research
Idea generation and non-clinical
testing
Primary focus of
early IMI calls
2007 SRA
Regulatory
Human testing
Approval
HTA and
Pharmacovigilance
Shift to also addressing challenges in
in society and healthcare
2011 SRA
Daily
Medical
practice
IMI 2
includes real life
medical practice
2013 SRA
The Vision for IMI2 – The right prevention and
treatment for the right patient at the right time
effective
A
effective
Dx
Test
not
effective
Biologically
heterogeneous
patient population
Adverse
events
Trial and Error
e.g.
biomarker
vs
not
effective
adverse
events
B
C
Information based
treatment decisions
Graphic adapted from C. Carini, C. Fratazzi, Eur. Pharm. Rev. 2008, 2, 39-45
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
24
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.
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, …
1.3.
Building on the strengths of Europe......
1.4.
Learning from the Innovative Medicines
2.Establishing the Research Priorities for IMI2 ........
2.1.
Challenges facing the healthcare ecosys
2.2.
The role of Research & Development in
2.3.
Regulatory, health technology assessme
3.Research Objectives of IMI2 ................................
3.1.
Four major axes of research ..................
3.1.1. Axis 1: Target validation and biomarker
3.1.2. Axis 2: Adoption of innovative clinical tr
3.1.3. Axis 3: Innovative Medicines .................
3.1.4. Axis 4 : Patient tailored adherence prog
4.Enabling Technologies ........................................
4.1.
Excellence in Data Management ...........
5.Implementation strategies ..................................
5.1.
Education
andinTraining
required to imp
Therapeutic
Areas
IMI2 SRA
Excellence in clinical trial implementatio
(no5.2.
priority order)
6.European Health Priorities to be addressed by IM
Europe
Antimicrobial resistance ........................
World 6.1.
6.2.
Osteoarthritis ........................................
6.3.
Cardiovascular diseases .........................
6.4.
Diabetes .................................................
6.5.
Neurodegenerative diseases .................
6.6.
Psychiatric diseases ...............................
6.7.
Respiratory diseases ..............................
6.8.
Autoimmune diseases ...........................
6.9.
Ageing-associated diseases ...................
6.10. Oncology ................................................
6.11. Rare/Orphan Diseases ...........................
6.12. Vaccines .................................................
7.Translating research to tangible benefits for Euro
2013: WHO report on priority medicines for Europe and the World:
societal challenge reflected in the IMI2 SRA
WHO report: Percentage of DALYs for top 20
high burden diseases and conditions
12
10
8
6
4
Tuberculosis
Malaria
Birth asphyxia and birth trauma
Prematurity and low birth weight
Breast cancer
Colon and rectum cancer
Cirrhosis of the liver
Osteoarthritis
Trachea, bronchus, lung cancer
Alzheimer and other dementias
Lower respiratory infections
Alcohol use disorders
HIV/AIDS
COPD
Hearing loss
Diabetes mellitus
Unipolar depression
Cerebrovascular
Ischaemic heart disease
0
Neonatal infections and other…
2
IMI2: Major Axes of Research
Biomarker identification/validation
(precision medicine)
Innovative methodologies to
evaluate treatment effect
Reclassification of disease
by molecular means
Target Identification and
validation(human biology)
Target &
Biomarker
Identification
(safety &
efficacy)
Determinants of drug /vaccine
Safety and efficacy
Innovative drug delivery
methodologies
Innovative
clinical trial
paradigms
European
Health
Priorities
Innovative
Medicines
Manufacturing for personalised
medicines
Discovery and Development
of novel preventative and
therapeutic agents
Adoption of innovative clinical
trial designs
Benefit/Risk Assessment
Patient
tailored
adherence
programmes
Healthcare delivery: focus on the
treatment programmes not just
the medicine
Innovative adherence
programmes
Drive change in delivery of medical practice
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
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)
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.
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)
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
IMI2: The First Call
Two topics:
Translational approaches to disease modifying therapy of
type 1 diabetes mellitus (T1DM)
[email protected]
Discovery and validation of novel endpoints in dry agerelated macular degeneration and diabetic retinopathy
[email protected]
Submission date: 12 November 2014
Translational approaches to disease
modifying therapy of type 1
diabetes mellitus (T1DM)
Vilnius, 11th September 2014
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.
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.
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.
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.
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
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
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
Discovery and validation of novel endpoints
in dry age-related macular degeneration
and diabetic retinopathy
Vilnius 11th September 2014
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
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
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
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
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
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
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
Questions?
[email protected]
www.imi.europa.eu

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