Innovative Medicines Initiative

Innovative Medicines Initiative

Innovative Medicines Initiative: Joining forces in the healthcare sector 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

Public-Private Partnerships: Why? Pooling expertise, knowledge and resources Developing incentives to address major unmet medical needs Providing a neutral trusted platform to align public and private interests

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 5 EFPIA companies; 10 Public organizations; 4 SME Total Budget: 14.4 Mi 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

The conundrum of brain disorders Brain disorders affect 1 in 3 Europeans And 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

Advances in Autism 6 EFPIA companies; 15 Public organizations; 3 SME 1 patient org; Total Budget: 35.9 Mi 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

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, eyetracking

Preclinical Alzheimer s disease 9 EFPIA companies; 36 Public organizations; 7 SME 3 patient org.; Total Budget*: 53.4 Mi 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 * Total budget for the EMIF program that included EMIF AD, EMIF metabolomics and EMIF platform

Novel Disease Markers for Alzheimer s Disease 12 EFPIA companies; 13 Public organizations; 5 SME Total Budget: 27.7 Mi 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

Advances in schizophrenia and depression research 10 EFPIA companies; 7 Public organizations; 3 SME Total Budget: 23.2 Mi 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

Achievements in chronic pain 8 EFPIA companies; 12 Public organizations; 1 SME Total Budget: 18.2 Mi 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

DIABETES: Fighting the epidemic through Public-Private Partnership Major Public Health Need Distrust in past-research Hurdles to drug development Diabetes will affect 43 million Europeans in 2030 89 million spent on 2011 on treating diabetes and its complications Cardiovascular complications of rosiglitazone and benfluorex Patients heterogeneity Lack of reliable markers for 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 of Diabetic Complications 6 EFPIA companies; 18 Public organizations; 1 SME Total Budget: 32.6 Mi 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 noninvasive assessment of plaque structure 3 patents in preparation

Advances in Diabetes 8 EFPIA companies; 12 Public organizations; 1 SME Total Budget: 25.9 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 1 st human ß-cell line (EndoCBeta H1) and its beta cell phenotype maintenance has been confirmed by 3 pharma partners Working on the 2 nd 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

IMI DIABETES PLATFORM Memorandum 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 11 EFPIA companies; 5 Public organizations; 4 SME Total Budget: 35.9 Mi 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

5 th release of the Vitic Nexus etox database Development of reliable toxicity predictive systems 537 substances (165 confidential) linked to 1,703 study designs (Bayer, Boehringer, Esteve, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, Roche, Sanofi, Servier and UCB) 3 rd 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 SME Total Budget: 13.9 Mi

New Methodologies in Pharmacovigilance & Pharmacoepidemiology 12 EFPIA companies; 16 Public organizations; 2 SME Total Budget: 29.8 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

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 networks Collaborative publications among IMI researchers -Call 1-3 Data & analysis: Thomson Reuters (Custom Analytics & IP Solutions)

Delivering high quality research Citation Impact by research area 0,0 1,0 2,0 3,0 Pharmacology & Pharmacy Neurosciences Mathematical & Computational Endocrinology & Metabolism Biology Research & Experimental Medicine Clinical Neurology Psychiatry Overall Data & analysis: Thomson Reuters (Custom Analytics & IP Solutions) IMI Projects average EU average

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

Development of tools to measure physical activity status in COPD 8 EFPIA companies; 7 Public organizations; 1 SME 3 patient org; Total Budget: 16.7 Mi Aim: development of Patient Reported Outcomes that measure aspects of physical activity relevant to patients and are sensitive to changes due to treatment. literature 2 questionnaires patients 6 activity meters 2 meters initial validation (6 wks) reduction integration 230 patients re-assessment 6+12 months for seasonal effects final validation: clinical & behavioural studies 2009-2011 2011-2012 2013-2014

Biomarkers for Predicting Severe Asthma Outcome 9 EFPIA companies; 21 Public organizations; 3 SME 5 patient org; Total Budget: 20.1 Mi 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 Diagnosis and definition of severe asthma: an international consensus; Bel et al., 2011 An integrative system biology approach to understanding pulmonary diseases; Auffray et al., 2010

IMI contributes to the competitiveness of the European pharmaceutical sector

IMI improves pharmaceutical R&D productivity 1. Establishment of robust validated models for drug development 2. Identification of new drug targets 3. Tools for predictive toxicology 4. Advances in precision medicine 5. Novel, clinically relevant biomarkers 6. New patient reported outcomes (with regulatory guidance) 7. New tools for big data management, effective data interpretation, and clinical decision support 8. Streamlining of clinical trial design and regulatory frameworks 9. Access and creation of clinical investigator networks 10. Resources for a successful translation - genes to animal models to patients 11. Investment in reclassification of complex diseases

Novel in vitro methods for cancer drug discovery 7 EFPIA companies; 7 Public organizations; 4 SME Total Budget: 30.7 Mi 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

Targeting Rheumatoid Arthritis 9 EFPIA companies; 24 Public organizations; 1 SME Total Budget: 38.1 Mi 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: A43 10.1136/ard.2010.148981.3, presented at the EWRR 2011

Modeling and Simulation Clinical 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 SME Total Budget: 21.2 Mi

1 DESIGN Feasibility Study Efforts to Automate clinical research Protocol (CDISC PRM SDM) 2 EXECUTION Patient Recruitment 10 EFPIA companies; 21 Public organizations; 2 SME Total Budget: 16 Mi 3 EXECUTION Data Collection Case Report Form (CDISC ODM) FDA-EMEA SUBMISSIO N Regulator s XML XML XML Trial Registry Document Manageme nt System Clinical Trial Management System (CTMS) Clinical Data Management System (CDMS) XML

IMI trains a new generation of industrial scientists and regulators, and reduces the cost of continuous professional development for companies 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 Education and Training programs > 1000 trainees so far 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.

Strategic Research Agenda for IMI2: The right prevention and treatment for the right patient at the right time Draft available at http://bit.ly/1axi076 Comments and suggestions are welcome: SRAconsultation@efpia.eu