Innovative Medicines Initiative

The European Union and the

pharmaceutical industry

have joined forces to make

drug R&D processes in Europe more

innovative and efficient,

enhance Europe’s competitiveness

& address key societal challenges

by forming

the biggest PPP in Life Science 2

Innovative Medicines Initiative:Joining forces in the healthcare sector

Pooling expertise, knowledge and resources

Developing incentives to address major unmet medical needs

Providing a neutral trusted platform to align public and private interests

Public-Private Partnerships: Why ?

IMI accelerates the development of new therapies for major yet unmet public health needs and

diseases where treatments are lacking

The Anti-Microbial Resistance Conundrum

- Anti-microbial resistance kills 25 000 European citizens every year

- Annual costs are estimated at €1.5 billion

- Only 2 new antibiotic classes developed over the last 30 years

- Low level of industry investments in antibiotic innovation

How IMI addresses infectious diseases

Invested €229 million in projects aiming at:

Solving scientific challenges

Fostering new models of industrial collaborations for antibiotics and diagnostics development

Developing networks for clinical trials

Revisiting regulatory environment

Providing necessary incentives for industry to reinvest in the area

COMBACTE CLIN-Network 280 members and Candidate members

Improved detection of infectious diseases

RAPP-ID is developing Point-of-Care Tests (POCTs) for rapid (hospital <2h, primary care <30min) detection of bacteria, mycobacteria, fungi and viruses

Developed conceptual POCTs platforms for community-acquired pneumonia, influenza, tuberculosis

Designed conceptual POCs for the detection of antibiotic resistance for Ventilator-Associated Pneumonia and tuberculosis

Developed a diagnostic device and protocol related to breath-born aerosol sampling - patent application filed

Concept RCA module chip

5 EFPIA companies; 10 Public organizations; 4 SMETotal Budget: 14.4 Mi €

The conundrum of brain disorders

Brain disorders affect 1 in 3 EuropeansAnd cost the economy € 798 billion / year

Developing new drugs to treat brain disorders takes longer, costs more than

for other diseases

There are few effective treatments in this area

IMI projects are tackling these issues

How IMI addresses brain disorders

Invested €148 million in projects aiming at:

Shedding new light on the underlying causes of autism (EU-AIMS)

Combining data to pave the way for new treatments for schizophrenia & depression (NEWMEDS)

Identifying new targets for drugs for chronic pain (Europain)

Developing models to predict the efficacy of drug candidates in Alzheimer’s patients (PHARMACOG)

Revisiting regulatory environment for drug development

Providing necessary incentives for industry to reinvest in brain disorders

Identified brain functional abnormalities that can be reversed in ASD patients by modulating brain 5HT - outcome predictor for clinical trials

Identified significant differences in cortico-cortical anatomical connectivity in ASD patients - outcome predictor for clinical trials

Identified significant differences in brain functional response to emotional sounds in infants at risk for autism - risk predictor

Published first study of EU wide prescribing in ASD

Advances in Autism6 EFPIA companies; 15 Public organizations; 3 SME1 patient org; Total Budget: 35.9 Mi €

2 Largest Clinical Trials for Early Detection and Monitoring of ASD Children

Identification of biomarkers that precede ASD onset− Prospective study of 300 high-risk infants (3 and 7 months) with

older siblings with ASD, and 100 low-risk

− Infant cognition, behavior, neuroimaging, neurophysiology

− Relation to symptoms/diagnosis of ASD at outcome

Accelerated longitudinal study for validation of ASD biomarkers in children and adults− 450 ASD patients and 300 controls

− magnetic resonance imaging, event-related potential, eye-tracking

Preclinical Alzheimer’s disease

Findings in preclinical Alzheimer’s disease:

common in cognitively normal elderly people

can be diagnosed by cerebrospinal fluid markers

associated with future cognitive decline and mortality – therapeutic target

9 EFPIA companies; 36 Public organizations; 7 SME3 patient org.; Total Budget*: 53.4 Mi €

* Total budget for the EMIF program that included EMIF AD, EMIF metabolomics and EMIF platform

Platelets: APP metabolites, 55 kD and 25 kD fragments - AlzProtect

Lymphocytes: ~ 150 RNA transcripts related to Abeta pathway, inflammatory pathway and to immune mechanism - Exonhit (now Diaxonhit)

Red blood cells: binding of Abeta1-42 on cellular membrane and change in PKC conformation in red blood cells - Innovative Health Diagnostics (IHD)

Red blood cells: panel of inflammatory markers- Innovative Concept in Drug Development (ICDD)

COMPLETED RECRUITMENT OF 150 MILD COGNITIVE IMPAIRED PATIENTS FOR BIOMARKER MATRIX CLINICAL TRIAL

Novel Disease Markers for Alzheimer’s Disease

12 EFPIA companies; 13 Public organizations; 5 SMETotal Budget: 27.7 Mi €

Advances in schizophrenia and depression research

Gained novel insights into the biology of schizophrenia

Standardised the cognitive models across several industrial partners

Developed novel tools for drug discovery - animal models, human imaging

Developed new web tools - image analysis, biomarker significance

Provided information for the design of more efficient clinical trials

10 EFPIA companies; 7 Public organizations; 3 SMETotal Budget: 23.2 Mi €

Achievements in chronic pain

Initiated international consensus meetings on conducting preclinical trials

Conducting clinical trials to improve patient stratification

Developing tools to predict which patients will respond to treatments

Studying the placebo effect to reduce clinical trial failures

Initiated EMA interactions to frame regulatory landscape

8 EFPIA companies; 12 Public organizations; 1 SMETotal Budget: 18.2 Mi €

DIABETES:Fighting the epidemic

through Public-Private Partnership

Major Public Health Need

Diabetes will affect 43 million Europeans in 2030

€89 million spent on 2011 on treating diabetes and its complications

Distrust in past-research

Cardiovascular complications of rosiglitazone and benfluorex

Hurdles to drug development

Patients’ heterogeneity

Lack of reliable markersfor disease activity and complications

How IMI facilitates the development of new diabetes therapies

Invested €125 million in 3 projects aiming at:

Solving scientific challenges

Developing reliable measures of diabetes activity and complications

Developing treatments tailored to the different needs of individual patients

Biomarkers ofDiabetic Complications

Generated the largest ever made database of GWAS samples in diabetic nephropathy (DN) from patients with T1D & T2D - discovery of potential biomarkers

Identified multiple biomarker candidates for diabetic related kidney damage, retina damage and coronary vascular disease

Developed an ultrasound/radiofrequency-based virtual histology for non-invasive assessment of plaque structure

3 patents in preparation

6 EFPIA companies; 18 Public organizations; 1 SMETotal Budget: 32.6 Mi €

Discovered a lipid signature in the serum of mice fed with high fat diet that correlates with physiological readouts – potential biomarker for diabetes

Generated the 1st human ß-cell line (EndoCBeta H1) and its beta cell phenotype maintenance has been confirmed by 3 pharma partners

Working on the 2nd generation human ß-cell lines with excisable immortality genes - more suitable for drug discovery purposes

Generated the world largest bio repository of human islets for diabetes research, with a bioinformatical analysis of the genome, transcriptome, lipidome and morphological and physiological characteristics - 138 islets

Advances in Diabetes8 EFPIA companies; 12 Public organizations; 1 SMETotal Budget: 25.9 Mi €

IMI DIABETES PLATFORMMemorandum of Understanding between IMIDIA, SUMMIT and DIRECT

for exchange of data and confidential information

IMI develops better tools to ensure the safety of existing and future medicines

Safer and Faster Evidence Based Translation

Evaluated 153 potential biomarker candidates for drug-induced

injury of the kidney, liver and vascular system

17 exploratory clinical studies started or completed

> 6500 retrospective samples collected

64 biomarker assays developed

Dialogue with Regulatory Agencies established

11 EFPIA companies; 5 Public organizations; 4 SMETotal Budget: 35.9 Mi €

Development of reliable toxicity predictive systems

5th release of the Vitic Nexus eTOX database

537 substances (165 confidential) linked to 1,703 study designs (Bayer, Boehringer, Esteve, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, Roche, Sanofi, Servier and UCB)

3rd release of the ChOX database

411 toxicology-linked targets; 162,287 distinct compounds and 701,181 activities

Version 1 of the integration system, eTOXsys, was released to all partners

7 out of 10 companies have already a running system.

90 predictive models developed

13 EFPIA companies; 8 Public organizations; 4 SMETotal Budget: 13.9 Mi €

Aims to strengthen the monitoring of benefit-risk of medicines in Europe by developing innovative methods

Works to enhance early detection and assessment of adverse drug reactions from different data sources (clinical trials, spontaneous reporting and observational studies)

Is developing methods to enable the integration and visual presentation of data on benefits and risks

Delivered PROTECT ADR database of adverse drug reactions (ADRs) – 45298 ADRs for 654 medicines

Delivered the inventory of Drug Consumption Databases in Europe – 17 countries

New Methodologies in Pharmacovigilance & Pharmacoepidemiology

12 EFPIA companies; 16 Public organizations; 2 SMETotal Budget: 29.8 Mi €

IMI provides a unique neutral platform for a continuous dialogue with patients, regulators,

academia and industry

Since 2009, 40 projects launched - total budget €1.2 billion

*: Estimate

*

Creation of unprecedented collective intelligence networksCollaborative publicationsamong IMI researchers -Call 1-3

Data & analysis: Thomson Reuters (Custom Analytics & IP Solutions)

Delivering high quality research

Pharmacology & Pharmacy

NeurosciencesMathematical & Computational

BiologyEndocrinology & Metabolism

Biology

Research & Experimental Medicine

Clinical Neurology

Psychiatry

Overall

0.0 1.0 2.0 3.0

EU average IMI Projects averageData & analysis: Thomson Reuters (Custom Analytics & IP Solutions)

Citation Impact by research area

Securing regulatory relevance of projects outputs via regulators’ involvement

Regulators represented in IMI projects as: Coordinator: EMA (1);

Participants: EMA (1) and other EU national Agencies (5); Advisory Board: EMA (>10) and FDA (5)

Informal interactions already established for a number of projects

EMA Qualification Advice procedures ongoing for 2 projects

IMI referred to the EMA Road Map to 2015 and more specifically highlighted in workprograms of some EMA Working Parties

Safety, Pharmacogenomics, Patients’ and Consumers’ Organisations

IMI/EFPIA held an information session for projects with EMA/FDA on the processes for Drug Development Tools advice and qualification (May 2013)

IMI actively involves patients

Aim: development of Patient Reported Outcomes that measure aspects of physical activity relevant to patients and are sensitive to changes due to treatment.

Development of tools to measure physicalactivity status in COPD

literature

patients2 questionnaires

6 activity meters 2 meters

initial validation(6 wks)

reductionintegration

230 patients

final validation:clinical &behavioural studies

2009-2011 2011-2012 2013-2014

re-assessment6+12 months for seasonal effects

8 EFPIA companies; 7 Public organizations; 1 SME3 patient org; Total Budget: 16.7 Mi €

Biomarkers for Predicting Severe Asthma Outcome

Established diagnostic criteria on severe asthma

Developed various “omics” platforms based on genetic, proteomic, metabolomic, breathomic biomarkers

Generated a preliminary phenotype ‘handprint’ by combining molecular, histological, clinical and patient-reported data

Patient cohort - 14 centres across Europe targeting 1025 subjects, to validate the handprints for their predictive efficacy in gold standard and experimental therapeutic intervention

An integrative system biology approach to understanding pulmonary diseases; Auffray et al., 2010

Diagnosis and definition of severe asthma: an international consensus; Bel et al., 2011

9 EFPIA companies; 21 Public organizations; 3 SME5 patient org; Total Budget: 20.1 Mi €

IMI contributes to the competitiveness of the European pharmaceutical sector

1. Establishment of robust validated models for drug development2. Identification of new drug targets3. Tools for predictive toxicology4. Advances in precision medicine5. Novel, clinically relevant biomarkers6. New patient reported outcomes (with regulatory guidance)7. New tools for ‘big data’ management, effective data interpretation, and

clinical decision support8. Streamlining of clinical trial design and regulatory frameworks9. Access and creation of clinical investigator networks 10. Resources for a successful translation - genes to animal models to patients11. Investment in reclassification of complex diseases

IMI improves pharmaceutical R&D productivity

Novel in vitro methods for cancer drug discovery

Developed cancer organoid cultures - 3D cultures that preserve cancer heterogeneity

Completed cancer drug screening 10 drugs on 5 patient derived cell lines each

Developed patient derived xenograft cancer models

Discovered potential biomarkers able to predict tumor sensitivity to Afatinib (105 BM)and to Regorafenib (69 BM) treatment

7 EFPIA companies; 7 Public organizations; 4 SMETotal Budget: 30.7 Mi €

Targeting Rheumatoid Arthritis

Identification and characteristics of cohorts and biobanks for different stages of RA (33 cohorts, more than 10.000 biosamples)

Identification of biomarkers for response to therapy

Standardization of existing and development of new animal models

Production of monoclonal human antibodies to autoantigenic targets in RA

Identification of new targets for therapy, including six potential miR targets that are translatable between mice and RA

Stittrich AB et al. Ann Rheum Disdoi: 2011 70: A4310.1136/ard.2010.148981.3, presented at the EWRR 2011

9 EFPIA companies; 24 Public organizations; 1 SMETotal Budget: 38.1 Mi €

Modeling and SimulationClinical Trial Simulator - Prototype v.2

Flexible study designs for PII clinical drug development:− parallel group studies− crossover studies− complex treatments

Simulation of patients sampled Simulating the exposure to the investigational drug Simulating types of drug effects related to drug exposure:

− Continuous effects− Time-to-event effects− Categorical effects− Count data as effects

Methods of evaluating the simulated trials− Optimal sampling times− Individual probabilities or risks− Trial success

Automatic reporting

10 EFPIA companies; 10 Public organizations; 5 SMETotal Budget: 21.2 Mi €

Efforts to Automate clinical research

Regulators

Clinical Trial Management

System (CTMS)

Trial Registry

Document Management System

Clinical DataManagement

System (CDMS)

1DESIGN

Feasibility Study

2EXECUTION

Patient Recruitment

3EXECUTION

Data Collection

XML XML

FDA-EMEASUBMISSIO

N

XML

XML

Protocol(CDISC PRM – SDM)

Case Report Form(CDISC ODM)

10 EFPIA companies; 21 Public organizations; 2 SMETotal Budget: 16 Mi €

€38.5 million invested in Education and Training programs

More than 1000 scientists have been trained so far

Many more scientists take advantage of industrial internships

Enhanced learning experience

IMI trains a new generation of industrial scientists and regulators, and reduces the cost of continuous

professional development for companies

Catalogued >5000 masters, PhD, CPD and short courses taught in 21 languages, from 39 countries, covering over 60 scientific, therapeutic and biomedical areas from about 1000 universities.

More than 320 students participated in various courses (50% from EFPIA companies) in 2012.Provided 20 new courses in drug safety sciences.

58 students are following the flexible and fully e-learning programme covering medicines risk identification and quantification, medicines and public health, medicine risk communication, assessing the benefits of medicines, and regulatory processes.

24 universities network + 16 universities affiliates.685 students have been following various courses (28% from EFPIA companies).

Europe’s first Patients’ Academy on Therapeutic Innovation aiming to provide scientifically reliable information on medicines and R&D, as well as an online public library that will empower patients to engage more effectively in the development and approval of new treatments and become true partners in pharmaceutical R&D.

IMI Education and Training programs> 1000 trainees so far

Draft available at http://bit.ly/1axI076

Comments and suggestions are welcome: SRAconsultation@efpia.eu

Strategic Research Agenda for IMI2:The right prevention and treatment for the right patient at the right time