project

ABIRISKAnti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance toMinimize the RiskSummary

A growing number of medicines are based on biological molecules such as proteins and monoclonal antibodies.These novel drugs have resulted in new, more effective treatments for a number of serious conditions. Yetsometimes these medicines trigger a response from the patients immune system, which can decrease theeffectiveness of the drug or cause severe side effects. The aim of the IMI-funded ABIRISK project is to shed newlight on the factors behind this immune response. The project, which represents the first concerted effort to solvethis problem, will aid in the creation of new, safer biopharmaceuticals and also generate tools to determine howindividual patients are likely to respond to them both in clinical trials and after release to the market.

Biopharmaceuticals are drugs that are biological in origin (i.e. are made of proteins or DNA for example) and aremanufactured using biotechnology. A number of biopharmaceuticals are already in use and have dramaticallyimproved quality of life for patients with serious, hard to treat conditions such as multiple sclerosis, Crohnsdisease, diabetes, rheumatoid arthritis, haemophilia A and some cancers. However, in some patients,biopharmaceuticals can trigger an immune reaction, a phenomenon known as immunogenicity. When this happens,the immune system produces antibodies (ADAs) that neutralise the drug, which can reduce the effectiveness of thebiopharmaceutical. In some patients, the immune response causes side effects such as a rash, chest pains, or afall in blood pressure. In the most severe cases, it can trigger anaphylactic shock and even prove fatal.

Immunogenicity the known unknowns Diverse factors appear to be involved in immunogenicity. On the drugside, both the compound and the route and duration of administration seem to play a role, while on the patient side,the type of disease, age, genetic background and interactions with other medicines may be risk factors. Thereforeit is extremely hard to predict which biopharmaceuticals will have immunogenicity problems; although many testsexist, these are not always accurate. Furthermore, knowing which patients are at greatest risk of mounting animmune response to a given biopharmaceutical is extremely difficult.

Reducing the risks Even though immunogenicity continues to pose a problem in the development of new drugs,until now there has been no major effort to solve the problem. Enter the ABIRISK project, which aims to givebiopharmaceuticals a much-needed boost and represents the first concerted effort to tackle the immunogenicityproblem by bringing together leading experts from hospitals, academia, industry and small companies. The projectwill set up laboratory tests to probe the immunogenicity of several biopharmaceuticals that are already used onpatients. The scientists will then match their test findings with the effect the drug actually has on patients. This willhelp the team to develop tools that are better at predicting immunogenicity during drug development.

Many pharmaceutical companies, academic institutions and patient registries have large amounts of data onbiopharmaceuticals and patients responses to them. In ABIRISK, these diverse databases will be assembled intoa single immunogenicity databank that will help researchers pinpoint the factors that influence a drugsimmunogenicity and patients risk of it. This will allow the researchers to generate tools that will accurately predictwhether a patient will mount an immune response to a biopharmaceutical and how that immune response will affectthe efficacy and safety of the drug.

Safer, more effective drugs for patients Immunogenicity means many patients today are denied the life-changingbenefits of biopharmaceuticals. ABIRISK will ultimately result in a new generation of biopharmaceuticals with lowerimmunogenicity that can be safely and effectively used by more patients. In addition, the project will allow cliniciansto determine which patients will respond best to which biopharmaceutical, thereby preventing patients fromsuffering the side effects of a drug that does not suit them.

For Europes pharmaceutical industry, better tests will help companies identify the safest, most effectivebiopharmaceuticals and weed out those that pose a high immunogenicity risk earlier in the drug development

Printed on: 26/04/2013

This project is funded by the Innovative Medicines Initiative, a public-private partnership betweenthe European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA)www.imi.europa.eu

process. This will save companies both time and money. Finally, by adding to our knowledge of the mechanismsbehind immunogenicity, the project will help to improve regulatory guidelines for the approval ofbiopharmaceuticals.

Participants

EFPIA

GlaxoSmithKline Research & Development Limited, Brentford, UKBayer Pharma AG, Berlin, GermanyIPSEN Innovation SAS, Paris, FranceMerck KGaA, Darmstadt, GermanyNovartis Pharma AG, Basel, SwitzerlandNovo Nordisk A/S, Bagsvrd, DenmarkPfizer Limited, Sandwich, UKSanofi-Aventis Research and Development, Paris, FranceUCB Pharma SA, Brussels, Belgium

Universities, research organisations, public bodies, non-profit groups

Institut National de la Sant et de la Recherche Mdicale (INSERM), Paris, FranceAcademisch Medisch Centrum, Amsterdam, the NetherlandsAcademisch Ziekenhuis Leiden Leids Universitair Medisch Centrum, Leiden, the NetherlandsCentre National de la Recherche Scientifique, Paris, FranceCommissariat a LEnergie Atomique et aux Energies Alternatives, Paris, FranceDRK-Blutspendedienst Baden-Wrttemberg Hessen gemeinntzige GmbH, Mannheim, GermanyFondazione per lIstituto di Ricerca in Biomedicina, Bellinzona, SwitzerlandFundaci Institut de Recerca de L'hospital Universitari Vall D'hebron, Barcelona, SpainGroupe dEtudes Therapeutiques des Affections Inflammatoires du Tube Digestif, Paris, FranceIstituto Giannina Gaslini, Genova, ItalyJohann Wolfgang Goethe Universitt, Klinikum und Fachbereich Medizin, Frankfurt, GermanyKarolinska Institutet, Stockholm, SwedenKlinikum rechts der Isar der Technischen Universitt Mnchen, Munich, GermanyMedizinische Universitt Innsbruck, Innsbruck, AustriaPaul-Ehrlich-Institut, Bundesinstitut fr Impfstoffe und biomedizinische Arzneimittel, Langen, GermanyQueen Mary and Westfield, University of London, London, UKRambam Medical Center, Haifa, IsraelRegion Hovedstaden, Hillerd, DenmarkUniversit di Firenze, Firenze, ItalyUniversittsklinikum Bonn, Bonn, GermanyUniversittsklinikum Dsseldorf, Dsseldorf, GermanyUniversity College London, London, UKUniversity Hospital Basel, Basel, SwitzerlandUniverzita Karlova v Praze, Prague, Czech Republic

SMEs

ALTA Ricerca e Sviluppo in Biotecnologie Srlu, Siena, ItalyBiomonitor A/S, Copenhagen, Denmark



Facts & Figures

Start Date 01/03/2012Duration 60 months

Contributions IMI funding 18 200 000EFPIA in kind 11 200 000Other 5 500 000Total cost 34 900 000

Links and Documents

Project website: www.abirisk.eu

IMI funding per project participant

Contact

Project Coordinator Daniel SikkemaGlaxoSmithKline USA

Tel: +1 610 270 6054 E-mail:dan.x.sikkema[AT]gsk.com

Managing Entity for EU funds MarcPallardy INSERM UMR 996 France Tel: +33 1 46 83 54 92 E-mail: marc.pallardy[AT]u-psud.fr



BioVacSafeBiomarkers for Enhanced Vaccine ImmunosafetySummary

Since their discovery, vaccines have protected millions of people worldwide from a broad range of infectiousdiseases, making them one of the most effective public health interventions out. New and better vaccines are stillurgently needed, yet their introduction is hampered by lengthy and expensive vaccine safety testing procedures.The aim of the IMI-funded BIOVACSAFE project is to develop cutting edge tools to speed up and improve thetesting and monitoring of vaccine safety, both before and after release to the market. By bringing togetherEuropes top industrial and academic teams for the first time, the project will ultimately usher in a new generationof safer, more effective vaccines.

Vaccines are widely acknowledged to be one of the cheapest and most efficient ways to combat infectiousdiseases in both developed and developing countries. With billions of doses of vaccines administered globallyevery year, vaccine safety is a top priority for pharmaceutical companies, regulators and the public alike. Theproblem is that testing and monitoring new vaccines for safety is a slow, cumbersome, and extremely expensiveprocess; the development of a new vaccine costs millions of euros, and less than 1 vaccine in 10 makes it throughclinical testing. As companies add new components to vaccines to make them more effective, testing them forsafety becomes even more challenging. And, while severe adverse reactions to vaccines are rare, predicting who isat risk of a severe reaction is extremely difficult; this problem will be further complicated by the ageing of thepopulation and the growing burden of chronic conditions and diseases of the immune system. A new approach tovaccine safety The BIOVACSAFE project will draw on the latest life science research findings to profile, in greatdetail, how individuals respond to the different components of vaccines at the cellular, genetic and molecular level.This will allow the project team to develop tools that can rapidly and accurately identify warning signs that apotential vaccine may be reactogenic. The tools could be employed early on in vaccine development, before vastamounts of time and money have been spent. Meanwhile, the team will develop new ways to identify, classify andrecord adverse reactions to vaccines; this should also boost researchers ability to pick up on problems early invaccine development. Finally, the team will probe how natural illnesses and infections, particularly diseases of theimmune system, interact with vaccines. By identifying these interactions, the team hopes to find ways of preventingthem occurring in the first place. Finally, the team will create databases that can be used to store information onand explore reactions to vaccines. Towards the next generation of vaccines By coming up with novel ways toidentify and better understand the causes of adverse reactions to vaccines at all stages of development,BIOVACSAFE will accelerate the development and introduction of a new generation of safer, more effectivevaccines to combat infectious diseases, cancer and chronic diseases. As well as speeding up vaccinedevelopment, the new, more accurate tools developed by BIOVACSAFE should help to boost public confidence invaccine safety. Furthermore, because the project includes studies of populations in both developed and developingcountries, its findings should be of global relevance. An injection of health for Europes vaccine developmentsector BIOVACSAFE brings together for the first time three of Europes leading vaccine development andmanufacture companies as well as top experts from academic institutions and small and medium-sized enterprises(SMEs). By sharing their expertise as well as access to data and patient groups, all project partners will see theirknowledge base and their competitiveness grow. Crucially, by pooling their expertise, the BIOVACSAFE partnershave a unique opportunity to make progress in this important area.

Participants

EFPIA

Novartis Vaccines and Diagnostics, Siena, ItalyGlaxoSmithKline Biologicals, Rixensart, BelgiumSanofi Pasteur, Lyon, France




University of Surrey, Guildford, UKChalmers University of Technology, Gothenburg, SwedenCharite? Universittsmedizin Berlin, Berlin, GermanyCommissariat a? l'e?nergie atomique et aux e?nergies alternatives, Paris, FranceGteborgs universitet, Gothenburg, SwedenHealth Protection Agency, London, UKImperial College London of Science, Technology and Medicine, London, UKLiverpool School of Tropical Medicine, Liverpool, UKMax-Planck-Gesellschaft zur Frderung der Wissenschaften, Berlin, GermanyStatens Serum Institut, Copenhagen, DenmarkUniversita? degli Studi di Siena, Siena, ItalyUniversiteit Gent, Ghent, BelgiumUniversiteit Utrecht, Utrecht, the Netherlands

SMEs

CDISC European Foundation, Woluwe-Saint Lambert, BelgiumImmunArrray, Rehovot, IsraelIslensk Erfdagreining ehf, Reykjavik, Iceland



Facts & Figures

Start date 01/03/2012Duration 60 months


Links and Documents

Project website: www.biovacsafe.eu IMI funding per participant

Publications

Contact

Project Coordinator Aldo TagliabueNovartis (Ext) Tel: +39 0577 243508 E-mail

Project Coordinator & ManagingEntity of EU funds David LewisUniversity of Surrey Tel: +44 1483689797 E-mail

Press Contact Mike FindlayUniversity of Surrey Tel: +44 1483686076 E-mail



BTCUREBe The CureSummary

New developments in our understanding of the pathology of Rheumatoid Arthritis (RA), a chronic disease affectingmany patients, show how disease-inducing immune and inflammatory reactions develop from an asymptomaticphase with autoimmune reactions into a phase of non-specific symptoms and then further into the full-blowndisease causing pain, joint destruction and functional deterioration.

The ultimate goal for therapeutic development is to identify the disease-causing molecular events early in thedisease and then influence immunity and inflammation so that functional deterioration is halted, immunity isre-regulated and the disease is cured.

The work from groups within the BTCure consortium (and others) has recently shown that very different genetic,environmental and thus molecular events are needed to trigger different subsets of the disease. Our aim is todevelop an understanding of the early process in arthritis subsets that will enable us to develop precise andeventually curative treatments to be used before irreversible destruction and loss of joint function and mobility haveoccurred in patients.

The BTCure project will develop new diagnostic methods to discover the early forms of RA and RA-like diseasesand new tools to differentiate the different forms of RA and RA-like diseases, where different molecularmechanisms are involved and where different therapies may be required.

To achieve these goals, samples from biobanks will be analysed in vitro and models will be aligned with differentvariants of human arthritis. In addition, new models will be established using similar molecular pathways as therelevant human arthritis subsets, leading to the understanding of the etiology and early pathology of the disease fora program aimed at early and curative treatment of RA and RA-like diseases. A major focus of these efforts will beto understand and subsequently alter the adaptive immune reactions in patients from a disease-inducing mode intoeither a protective mode against the disease or become asymptomatic. Advances made through initial researchinto the pathology of this group of diseases have been successful, given enough information available on thenature and regulation of disease-inducing and disease-protective immunity. With these tools at hand, we will beable to use new understanding of aetiology and early pathology of human disease for a program aimed at early andultimately curative treatment of human RA and RA-like diseases.

Participants

EFPIA

AstraZeneca AB, SwedenBoehringer Ingelheim International GMBH, GermanyBristol Myers Squibb EMEA sarl, USACENTOCOR B.V., NetherlandsF. Hoffmann-La Roche AG, SwitzerlandMerck, GermanyNovoNordisk A/S, DenmarkPfizer Limited, UKUCB Pharma, SA,Belgium

UNIVERSITIES, RESEARCH ORGANISATIONS, PUBLIC BODIES & NON-PROFIT

Alexander Fleming Biomedical Sciences Research Center, Greece



AMC/University of Amsterdam, NetherlandsCharit-University of Medicine, Berlin, GermanyDiakonhjemmet Hospital, NorwayFoundation for Research and Technology, GreeceGerman Rheuma Research Centre Berlin, GermanyHumanitas Foundation for Research, ItalyImperial College London, UKKarolinska Institute, SwedenKing's College London, UKNational Institute for Health and Medical Research (INSERM), FranceNational University of Ireland, DublinPhadia AB, SwedenRevmatologicky Institute, Czech RepublicSpanish National Research Council, SpainStichting Catholic University NetherlandsUniversity College Dublin, Ireland,University Hospital Centre, Montpellier, FranceUniversity Hospital Leiden (LUMC), NetherlandsUniversity of Erlangen, GermanyUniversity of Glasgow, UKUniversity of Leeds, UKUniversity of Manchester, UKUniversity of Zrich, Switzerland

SMEs

TcLand Expression, France



Facts & Figures


Contributions IMI funding 16 137 872EFPIA in-kind 14 172 302Other 7 807 923Total Cost 38 118 097

Links and Documents

Project website: www.btcure.eu

IMI Funding per project participant

Publications

Contact

PROJECT COORDINATOR UCBPharma SA Dr Neil GozzardPharmacology Alle de la Recherche,60 1070 Brussels Belgium Email:neil.gozzard[AT]ucb.com

MANAGING ENTITY OF IMIBENEFICIARIES Professor LarsKlareskog Karolinska Institute,Sweden Nobels vg, 5 17177Stockholm Sweden Email:lars.klareskog[AT]ki.se Tel: +46851774529



CHEM21Chemical manufacturing methods for the 21st century pharmaceutical industriesSummary

The CHEM21 project plans to generate a range of methods to make the drug development process moreenvironmentally friendly. Whats more, as well as being good for the planet, the methods developed by CHEM21will also help the pharmaceutical industry to cut costs, resulting in cheaper medicines for patients.

Towards more sustainability in drug manufacture

Today, drug manufacture often requires 100 kg of materials to produce just 1 kg of active ingredient. Thisinefficiency means that many products require long lead times and large facilities for their production and to dealwith any waste materials. This is not just bad for the environment; medicines produced in this way are expensive todevelop and produce.

Meanwhile, another emerging issue for the pharmaceutical sector is the scarcity of precious metals, like platinum,that are essential in the synthesis of many drugs but are being depleted at alarming rates.

Solving these problems will require a major revision in the way drugs are synthesised.

Smarter synthesis

CHEM21 will link leading academics in the field of green chemistry with scientists working in drug synthesis inindustry to tackle the challenges found in the commercial manufacture of drugs.

Specifically, the CHEM21 project aims to generate a range of technologies for medicines manufacture that aredemonstrably more sustainable that existing methods. Part of the project will be devoted to designing catalystsbased on common metals (such as copper, iron and nickel) instead of the rarer and more expensive preciousmetals used now. The team also aims to reduce the amount of solvent used and develop methods that favourstarting materials that result in less harmful waste. An additional aim of the team is to provide new tools formedicinal chemists which are greener and are robust for scaling up.

Elsewhere, the project plans to boost the use of enzymes as catalysts and to investigate what steps are needed toimplement synthetic biology for the sustainable production of more complex molecules.

In addition to promoting green and sustainable methodologies among current medicinal and process chemists,CHEM21 wants to make green drug production second nature for the next generation of scientists in this area.To this end, the project will develop and disseminate educational material, case studies, and reviews and trial themin selected universities and EFPIA companies.

Cheaper medicines for patients

Inefficient production processes and the use of rare precious metals raise the costs of drug production. By makingdrug production more efficient and swapping expensive materials for cheaper alternatives, CHEM 21 will help tolower the cost of medicines.

Participants

EFPIA

GlaxoSmithKline Research and Development Ltd, Brentford, UK



Bayer Pharma AG, Berlin, GermanyJanssen Pharmaceutica NV, Beerse, BelgiumOrion Corporation, Espoo, FinlandPfizer Limited, Sandwich, UKSanofi Chimie, Gentilly, France

Universities, Research Organisations, Public bodies & non-profit

University of Manchester, Manchester, UKLeibniz Institute for Catalysis, Rostock, GermanyStichting VU-VUMC, Amsterdam, NetherlandsTechnische Universitt Graz, Graz, AustriaUniversitt Graz, Graz, AustriaUniversitt Stuttgart, Stuttgart, GermanyUniversiteit Antwerpen, Antwerp, BelgiumUniversity of Durham, Durham, UKUniversity of Leeds, Leeds, UKUniversity of York, York, UK

SMEs

ACIB GmbH, Graz, AustriaCatScI Ltd, Wentloog, Cardiff, United KingdomCharnwood Technical Consulting Ltd, Quorn, UKEvolva Biotech A/S, Copenhagen, DenmarkReaxa Limited, Leeds, UK



Facts & Figures


Contributions IMI funding 9 800 000EFPIA in kind* 13 600 000Other 3 000 000Total Cost 26 400 000*includes non-EU contribution of0.3 million

Links and Documents

Project website: www.chem21.eu

Contact

Project Corodinator Philip Dell'orcoGlaxoSmithKline Research andDevelopment Ltd Tel: +1 610 2707316 E-mail:Philip.C.Dell'Orco[AT]@gsk.com

Managing Entity Nick TurnerUniversity of Manchester Tel: +44 161306 5100 E-mail:Nicholas.Turner[AT]manchester.ac.uk



COMBACTECombatting Bacterial Resistance in EuropeSummary

Antimicrobial resistance (AMR) is a growing problem worldwide, and with few new drugs making it to the market,there is an urgent need for new medicines to treat resistant infections. Enter the IMI-funded COMBACTE project,which aims to give antibiotic drug development a much-needed boost by pioneering new ways of designing andimplementing efficient clinical trials for novel antibiotics. COMBACTE forms part of the New Drugs for Bad Bugs(ND4BB) initiative, IMIs wider programme to tackle AMR.

The AMR arms race developing New Drugs for Bad Bugs AMR represents a serious and growing threat tohuman and animal health worldwide. According to the World Health Organization (WHO), antibiotic resistance isbecoming a public health emergency of yet unknown proportions. In the EU, AMR is responsible for some 25 000deaths every year, and the annual treatment and social costs have been estimated at some 1.5 billion.Meanwhile, new forms of resistance continue to arise and spread, leaving clinicians with few weapons to bringinfections under control. Yet despite the recognised need for new antibiotics, the reality is that only two newclasses of antibiotics have been brought to the market in the last three decades.

The reasons for this are manifold. On the scientific front, there is an urgent need for a greater understanding of howantibiotics work, how bacteria develop resistance to them, and what molecular mechanisms could be exploited toget round bacterial defence mechanisms. Running clinical trials on new antibiotics is also problematic due toregulatory requirements and the large numbers of patients required put simply, a lot of patients have to berecruited to the major studies of efficacy performed for each clinical indication sought in order to be sure of havingenough patients with the resistant bacteria under investigation and to demonstrate that the new antibiotic is notinferior to comparable antibacterial drugs. These issues mean that the costs of carrying out a clinical trial on a newantibiotic are extremely high.

At the same time, because some antibiotics will only be used on a very small number of patients, the costs ofdevelopment often exceed the potential return on investment. In other words, antibiotic development is simply nolonger a financially viable option for pharmaceutical companies, and just a handful of pharmaceutical companiesremain in the field.

If no action is taken to address these issues, we risk leaving society in a situation where doctors will have few, ifany, options to treat resistant bacterial infections. To avoid a public health emergency, the entire antibiotic researchcommunity, including researchers in universities, small and medium-sized enterprises (SMEs), and pharmaceuticalcompanies must work together to reinvigorate research into new antibiotics. As a public-private partnership (PPP),IMI is the ideal platform to launch such an initiative.

In its Action Plan against the rising threats from Antimicrobial Resistance of November 2011, the EuropeanCommission called for unprecedented collaborate research and development efforts to bring new antibiotics topatients by, among other things, launching an IMI programme for research on new antibiotics aimed at improvingthe efficiency of research and development of new antibiotics through unprecedented open sharing of knowledge.

The result is the New Drugs for Bad Bugs (ND4BB) programme, the first two topics of which were launched asIMIs 6th Call for proposals in May 2012. COMBACTE is the result of one of those topics. A third topic underND4BB was launched as part of IMIs 8th Call for proposals in December 2012.

Since the launch of ND4BB, the European Parliament has also weighed in on the issue. In December 2012 itadopted a resolution on the rising threat of AMR that highlights the important role of PPPs in reinvigoratingantimicrobial R&D.

COMBACTE improving clinical trials for antibiotics The COMBACTE project focuses on addressing the



barriers to clinical development. A key outcome of the project will be a high quality, pan-European clinical trialnetwork. Dubbed COMBACTE CLIN-Net, it will be capable of recruiting sufficient patients into multinational trials atall stages of development. Alongside this, the project will also establish a pan-European laboratory network(COMBACTE LAB-Net), which will deliver epidemiological information and data from microbial surveillance work toguide the selection of clinical trial sites.

Crucially, the COMBACTE team aims to generate innovative trial designs to facilitate the registration of novelantibacterial agents. It will also design and validate tests to support the diagnosis of patients, identify the mostappropriate treatments, and monitor the patients response.

A large part of the project will be devoted to the performance of clinical trials of drugs under development in thepharmaceutical companies involved in the project. The first antibiotic to undergo clinical trials under COMBACTE isGSK1322322, which inhibits the action of a bacterial enzyme called peptide deformylase (PDF) and appears to beeffective against multi-drug resistant respiratory and skin pathogens such as methicillin-resistant Staphylococcusaureus (MRSA). Most importantly, GSK1322322 represents a new class of antibiotics with a novel mode of action.

In COMBACTE, experts will run clinical trials to evaluate GSK1322322s efficacy at treating acute bacterial skinand skin structure infections and community-acquired bacterial pneumonia.

Looking to the future, trials of other drugs are planned. For example, IMIs 8th Call for proposals included asubtopic on the conduct of early clinical studies on MEDI4893, a new human immunoglobulin monoclocal antibodywhich targets S. aureus alpha toxin, which is behind much of the tissue and organ damage associated with S.aureus infection. The outcome of the 8th Call for proposals will be made public in the second half of 2013.

Hope for the future The challenge of antimicrobial development is so great that no organisation could take it onalone. By bringing together leading experts from universities, hospitals, and pharmaceutical companies who areskilled in microbiology, epidemiology, drug development, and clinical trial design, COMBACTE is set to giveantibiotic development in Europe a major boost.

Unique in its scale, ambition, and its potential benefits for patients, public health and pharmaceutical research inEurope, COMBACTE has the potential to become the powerhouse of antimicrobial drug development in Europethat could serve as a standard for other groups. Ultimately, the hope is that COMBACTE will provide a frameworkfor the rapid and efficient development of new treatments as well as diagnostic tests that can be speedilycommercialised for use on the patients that so urgently need them.

Participants

EFPIA companies

GlaxoSmithKline Research and Development Ltd, UKAstraZeneca AB, SwedenJanssen Infectious Diseases Diagnostics BVBA, Belgium


University Medical Center Utrecht, The NetherlandsCentre Hospitalier Rgional Universitaire de Besanon, FranceCentre Hospitalier Universitaire de Limoges, FranceCliniques Universitaires Saint Luc, BelgiumFundacio Centre de Recerca en Salut International de Barcelona, SpainHelmholtz-Zentrum fr Infektionsforschung GmbH, GermanyHospices Cantonaux CHUV, SwitzerlandInstitut National de la Sant et de la Recherche Mdicale, France



North Bristol National Health Service Trust, UKServicio Andaluz de Salud, SpainStichting Katholieke Universiteit / Radboud University Nijmegen Medical Centre, The NetherlandsUniversittsklinikum Freiburg, GermanyUniversittsklinikum Kln, AR (University Hospital of Cologne), GermanyUniversit de Genve, SwitzerlandUniversit Joseph Fourier, Centre de Recherche Inserm, FranceUniversity of Antwerp, Belgium

Small and medium-sized enterprises (SMEs)

Julius Clinical Research BV, The Netherlands



Facts & Figures

Start Date 01/01/2013Duration 84 monthsContribution IMI Funding 83 033 010EFPIA in kind 104 398 189Other 7 129 184

Total cost 194 560 383

Contact

Project coordinator Scott WhiteGlaxoSmithKline Research andDevelopment Ltd Tel.: +1 610 9177000 E-mail:scott.m.white[AT]gsk.com

Managing entity Marc J M BontenUniversity Medical Center Utrecht Tel.: +31 88 7557394 E-mail:mbonten[AT]umcutrecht.nl

Clinical trials lead Bruno FranoisCentre Hospitalier Universitaire deLimoges Tel.: +33 5 55 05 69 84 E-mail: b.francois[AT]unilim.fr andbruno.francois[AT]chu-limoges.fr



COMPACTCollaboration on the optimisation of macromolecular pharmaceutical access to cellulartargetsSummary

Many new medicines are based on biological molecules such as proteins, peptides or nucleic acids. The goal of theCOMPACT project is to shed new light on the obstacles these drugs (which are known as biopharmaceuticals)need to overcome to get to where they are needed in the body. The team will then use this information to developand validate biopharmaceutical formulations to deliver these novel drugs to their targets.

New drugs with a lot of potential

Biopharmaceuticals, medicines based on biological molecules such as proteins and nucleic acids, have alreadydelivered effective treatments for a number of serious, often hard to treat diseases, such as Crohns disease andmultiple sclerosis, dramatically improving patients quality of life.

The pharmaceutical industry is keen to expand its work on these novel drugs, but biopharmaceuticals still have anumber of drawbacks which are hampering their broader application. For example, because these molecules tendto be complex and delicate, most biopharmaceuticals have to be injected; if they were administered orally (a morepatient-friendly route), they would be destroyed by the harsh environment of the stomach. Furthermore, even oncebiopharmaceuticals are in the body, their large size means it is hard for them to get to their targets.

Overcoming obstacles

The overall aim of the COMPACT project is to overcome the delivery and targeting bottlenecks forbiopharmaceuticals. It will do this by tackling a number of key issues. Firstly, it will identify and characterise themain transport routes across biological barriers and through cell membranes that could be exploited for drugdelivery purposes. These include the intestinal barrier, skin barrier, and blood-brain barrier.

Secondly, the researchers will devise and characterise formulations to allow the delivery of peptide andprotein-based drugs via non-invasive routes (e.g. orally, via the airways, and via the skin). The team will also workto find ways to get these drugs across the blood-brain barrier.

Another goal involves transporting drugs based on nucleic acids (e.g. RNA) into and through the cell. Throughoutthe project, the team will use advanced imaging techniques to track the movement of biopharmaceuticals at the(sub) cellular, tissue, and whole body level.

Benefits for patients

Biopharmaceuticals have the potential to improve the lives of many patients with diseases and conditions that arecurrently hard or even impossible to treat. By finding more effective ways of administering these drugs, andimproving their ability to travel through the body to where they are needed, COMPACT will allow more patients tobenefit from biopharmaceuticals. Furthermore, designing less invasive administration routes and reducing the dose(and therefore the side effects) and frequency of administration will help to improve patient compliance withtreatments.

Participants

EFPIA

Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany



Abbott GmbH & CoKG, Wiesbaden-Delkenheim, GermanyBoehringer Ingelheim International GmbH, Ingelheim, GermanyGlaxoSmithKline Research and Development Ltd, Brentford, UKMerck KGaA, Darmstadt, GermanyNovo Nordisk A/S, Bagsvrd, DenmarkPfizer Limited, Sandwich, UK


Universiteit Utrecht, Utrecht, NetherlandsBioneer A/S, Hrsholm, DenmarkCardiff University, Cardiff, UKHelmholtz-Zentrum fr Infektionsforschung GmbH, Braunschweig, GermanyHelsingin Yliopisto, Helsinki, FinlandLudwig-Maximilians-Universitt Mnchen, Munich, GermanyNorges Teknisk-Naturvitenskapelige Universitet NTNU, Trondheim, NorwayStockholms Universitet, Stockholm, SwedenUniversitt Wien, Vienna, AustriaUniversitt Zurich, Zurich, SwitzerlandUniversiteit Gent, Ghent, BelgiumUniversiteit Leiden, Leiden, NetherlandsUniversity of Copenhagen, Copenhagen, DenmarkUniversity of Oxford, Oxford, UK

SMEs

Pharmacoidea Development and Service Ltd, Szeged, Hungary



Facts & Figures


Contributions IMI funding 10 200 000EFPIA in kind* 16 600 000Other 3 200 000Total Cost 30 000 000*includes non-EU contribution of1.6 million

Links and Documents

Project website:www.compact-research.org

Project Launch Press Release


Contact

Project Coordinator EkkehardLeberer Sanofi-Aventis DeutschlandGmbH Tel: +49 69 305 18998 E-mail:Ekkehard.Leberer[AT]sanofi.com

Managing Entity EnricoMastrobattista Universiteit Utrecht Tel: +31 6 22736567 E-mail:e.mastrobattista[AT]uu.nl



DDMoRe

Drug Disease Model Resources Summary

Model based-drug development (MBDD) is accepted as a vital approach in understanding patient risk/benefit andattrition. At the core of MBDD lies Modelling and Simulation (M&S), a technology providing the basis for informed,quantitative decision-making.

M&S facilitates the continuous integration of available information related to a drug or disease into constantlyevolving mathematical models capable of describing and predicting the behaviour of studied systems to addressthe questions researchers, regulators and public health care bodies face when bringing drugs to patients. The fulladoption of MBDD is perturbed by a lack of common tools, languages and ontologies for M&S, which often leads toinefficient reuse of data and duplication of effort by academic, industrial and regulatory stakeholders.

The Drug Disease Model Resources (DDMoRe) consortium strategy will have standards as its core: a newlydeveloped common definition language for data, models and workflows, along with an ontology-based standard forstorage and transfer of models and associated metadata.

A drug and disease model library will be developed as a public resource. Its flexibility and power will be showcasedby the addition of proof of concept drug and disease models from key therapeutic areas such as diabetes andoncology.

An open-source interoperability framework will be the backbone for the integration of M&S applications intoseamless standardized but flexible workflows. Initially, currently-used tools (e.g. NONMEM,WinBUGS, Matlab, R)will be integrated into the framework.

From the outset resources will also be dedicated to new application development which will be steered by identifiedgaps in the M&S software ecosystem. The DDMoRe projects standards and tools intended as the gold standardfor future collaborative drug and disease M&S - will be supported by comprehensive training and will be madepublicly accessible.

The DDMoRe consortium draws together its expert partners from across Europe including 5 SMEs and 9 academicpartners who will be working together to accomplish the aims of the project with 10 EFPIA companies.

Participants

EFPIA

AstraZeneca AB, SwedenEli Lilly & Co Ltd, UKF. Hoffmann-la Roche AG, SwitzerlandGlaxoSmithKline Research & Development Ltd, UKMerck KGaA, GermanyNovartis Pharma AGNovo Nordisk A/S, DenmarkPfizer Ltd, UKServier International Institute of Research, FranceUCB Pharma SA, Belgium

UNIVERSITIES, RESEARCH ORGANISATIONS,PUBLIC BODIES & NON-PROFIT



European Molecular Biology Laboratory, GermanyFreie Universitt Berlin, GermanyNational Institute of Research in ITTechnology (NRIA), FranceNational Research Council, ItalyUniversity of Leiden, NetherlandsUniversity of Navarra, SpainUniversity of Pavia, ItalyUniversity of Uppsala, SwedenUniversity Paris Diderot, France

SMES

Cyprotex Discovery Ltd, UKInterface Europe, BelgiumLixoft SAS, FranceMango Business Solutions Ltd, UKOptimata Ltd, Israel Simcyp Ltd, UK



Facts & Figures


Contributions IMI funding 9 615 058EFPIA in-kind 9 820 120Other 1 729 833Total Cost 21 165 061

Links and Documents

Project website: www.ddmore.eu


Publications

Contact

PROJECT COORDINATOR LutzHarnisch Pharmacometrics PfizerLtd UK Email:Lutz.O.Harnisch[AT]pfizer.com

MANAGING ENTITY OF IMIBENEFICIARIES Mats KarlssonUppsala University Sweden Email:Mats.Karlsson[AT]farmbio.uu.se



DIRECTDiabetes research on patient stratificationSummary

Diabetes treatment gets personal

Type 2 diabetes patients are a diverse group; in some, the disease progresses rapidly, while in others it takes aslower course. Similarly, a treatment that works well in one patient may prove less effective in another. This has ledresearchers to acknowledge that there are actually a number of different subtypes of type 2 diabetes. The goal ofthe IMI-funded DIRECT project is to identify these subtypes and determine most appropriate treatments for them.The project brings together Europes leading researchers from academia, healthcare, and the pharmaceuticalindustry.

Some 285 million people worldwide have type 2 diabetes, and that figure is set to rise to 439 million by 2030. Itarises when the body cannot make enough insulin (the hormone responsible for managing blood sugar levels), orwhen the body fails to respond to insulin. Although type 2 diabetes is a chronic, lifelong condition, it can bemanaged through a combination of medicines and lifestyle changes. If left unmanaged, patients blood sugarlevels become too high, triggering damage to the cardiovascular system, kidneys, eyes, and nerve endings.Although there are a number of risk factors for type 2 diabetes (such as obesity), it is not always clear why somepeople develop the condition while others do not. Furthermore, the course of the disease and the effectiveness ofdifferent medicines vary from one patient to another. In other words, there are a number of different kinds of type 2diabetes, and that is where the DIRECT project comes in. Variations on a theme The focus of the DIRECT projectis patient stratification, which involves identifying different subgroups of patients. The project will develop andvalidate tests to predict who will get diabetes, whose condition will deteriorate rapidly after diagnosis, and who willrespond well or badly to certain drugs. The tests will then allow the DIRECT project to determine which existingdrugs are effective for different varieties of type 2 diabetes. DIRECT will gather large amounts of data as well assamples from people at risk of diabetes, people with diabetes, and people undergoing diabetes treatment. This willenable the project team to identify biomarkers (biological markers such as the level of a certain molecule in theblood) associated with different subtypes of type 2 diabetes and different rates of disease progression. Thesebiomarkers will then be tested in prospective clinical trials, paving the way for their use as new diagnostic tests aswell as in the creation of personalised therapies. Getting the right treatments to the right patients. The testsdeveloped by DIRECT will ultimately usher in a new era of personalised medicine for diabetes patients. In practice,this means doctors will be able to diagnose their patients more accurately and tailor treatments to suit their ownparticular subtype of type 2 diabetes. In this way, patients will be able to manage their condition more effectivelyand hopefully avoid the complications associated with diabetes. Furthermore, patients who are at risk of diabetescould be identified and monitored. A boost for the drug development sector The work carried out under theDIRECT project will substantially boost industrys understanding of the underlying causes of type 2 diabetes,helping it to develop tailored treatments that can be targeted to the right patients. Pieces of a pharma puzzle Thework carried out in DIRECT complements the efforts of IMIs other diabetes projects. IMIDIA (Improving beta-cellfunction and identification of diagnostic biomarkers for treatment monitoring in diabetes) is studying the beta cellsof the pancreas, which are responsible for producing insulin, with a view to developing a cure for diabetes.Meanwhile SUMMIT (Surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetestools) is developing tools to identify the patients at greatest risk of developing complications relating to diabetes.

Achievements & News

IMI diabetes projects sign Memorandum of Understanding IMI currently has three projects working ondiabetes DIRECT, SUMMIT, and IMIDIA which have a combined budget ofjust over100 million. The projectstackle diabetes in different ways. For example, IMIDIA focuses on studying the pancreatic beta cells which areresponsible for producing insulin; it aims to use this knowledge develop treatments that can slow down theprogress of diabetes. Meanwhile, SUMMITs work addresses the urgent need for new treatments to tackle the



complications associated with diabetes, such as eye, kidney, and blood vessel problems. Finally, DIRECT takes apersonalised medicine approach to diabetes, as it works to identify different varieties of diabetes and effectivetreatments to tackle them. The projects already work together on an informal basis (as evidenced by their new jointleaflet produced with the support of the IMI Executive Office). However, IMIDIA and SUMMIT have now taken theircollaboration to a new level with the signature of a Memorandum of Understanding (MoU). The MoU covers thehandling of intellectual property, the transfer of knowledge and materials, and confidentiality. The projects believethat the MoU could serve as a template for collaboration between other IMI projects in the future. (November 2012)

Participants

EFPIA

Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, GermanyEli Lilly and Company Ltd, Hampshire, UKInstitut de Recherches Internationales Servier, Suresnes, FranceNovo Nordisk A/S, Bagsvrd, Denmark


University of Dundee, Dundee, UKCentre Hospitalier Regional et Universitaire de Lille, Lille, FranceCentre National de la Recherche Scientifique. Paris, FranceConsiglio Nazionale delle Ricerche, Rome, ItalyConsorci Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, SpainEberhard Karls Universitt Tbingen, Tbingen, GermanyHelmholtz Zentrum Mnchen Deutsches Forschungszentrum fr Gesundheit und Umwelt GmbH,Neuherberg, GermanyImperial College of Science, Technology and Medicine, London, UKKungliga Tekniska Hgskolan, Stockholm, SwedenLeiden University Medical Center, Leiden, the NetherlandsLunds Universitet, Lund, SwedenTechnical University of Denmark, Kgs. Lyngby, DenmarkUniversitt Ulm, Ulm/Donau, GermanyUniversit de Genve, Geneva, SwitzerlandUniversity of Bath, Bath, UKUniversity of Copenhagen, Copenhagen, DenmarkUniversity of Eastern Finland, Kuopio, FinlandUniversity of Exeter, Exeter, UKUniversity of Newcastle upon Tyne, Newcastle upon Tyne, UKUniversity of Oxford, Oxford, UKVereniging voor christelijk hoger onderwijs, wetenschappelijk onderzoek en patintenzorg, Amsterdam,Netherlands



Facts & Figures



Links and Documents

Project website: www.direct-diabetes.org


The IMI Diabetes Platform

Contact

Project Coordinator Hartmut RttenSanofi Tel: +49 69 305 13547 E-mail:hartmut.ruetten[AT]sanofi.com

Managing Entity Ewan PearsonUniversity of Dundee Tel: +44 1382740081 E-mail:e.z.pearson[AT]dundee.ac.uk

Press Contact Bernd JablonkaSanofi Tel: +49 69 305 5955 E-mail:bernd.jablonka[AT]sanofi.com



EHR4CRElectronic Health Records Systems for Clinical ResearchSummary

Current medical needs, the growth of targeted therapies and personalized medicines and escalating R&D costsresult in formidable cost pressures on healthcare systems and the pharmaceutical industry.Clinical research is alsogrowing in complexity, labour intensity and cost. There is a growing realization that the development and integrationof Electronic Health Record systems (EHRs) for medical research can:

enable substantial efficiency gainsmake Europe more attractive for R&D investmentprovide patients better access to innovative medicines and improved health outcomes.

EHRs can now be designed to seamlessly integrate with existing research platforms and healthcare networks tocreate opportunities for many stakeholders, including the pharmaceutical and bio-pharma industries.

However, key challenges are compliance with various ethical, legal and privacy requirements (and acceptance bythe general public, patients, and medical professionals), providing a platform that works across many EHR systemsand is sustainable within a scalable business model. A 4-year project, EHR4CR will involve a team of recognisedEuropean academic and industrial partners.

The project will build a platform to enable the use of EHR for more efficient medical research and run pilots (oninteroperability, security, data quality, data storage solutions, organisational issues,accreditation and certification,etc) to demonstrate the viability and scalability of an EHR4CR business model.

The EHR4CR project supports the IMI strategic agenda with an information gateway solution to enhance clinicalresearch efficiency and innovation. A key IMI aspect is the development of a knowledge management capabilitythat can, for example, provide information management support for other research on personalized medicines, nowan IMI 2010 call topic. EHR4CR also supports other IMI R&D projects by enabling the use (and reuse) of largeamounts of health data in an ethical and cost-effective way.

The EHR4CR project consortium draws its expert partners from academia, with 20 organisations and 4 SMEsworking with 10 EFPIA companies and is an example of the scale of collaboration made possible through IMI.

Achievements & News

Stakeholders in favour of using electronic health records for clinical research, EHR4CR project surveyshows An overwhelming majority (95%) of stakeholders are in favour of using electronic health records (EHR) inclinical research, according to the results of a recent survey run by IMI project EHR4CR (Electronic health recordsfor clinical research).The goal of the project is to come up with a platform and business model to enable there-use of data from EHRs for clinical research in Europe. The EHR4CR team set up the survey to identifyopportunities and challenges in this area. The survey gathered around 200 responses from researchers inacademia, the pharmaceutical industry, EHR system providers, patients organisations and others. Mosthighlighted complying with legislative, regulatory, ethical and privacy requirements as a top priority for thesuccessful use of EHR services for clinical research. The results of this survey confirm a high interest in re-usingEHR data for clinical research with the objective to optimise drug development efficiency and access to innovativemedicines in Europe, the project team states. This survey provides valuable information towards achieving thedevelopment and implementation of EHR4CR services and of a sustainable and scalable business model. Theteams findings will be published in a forthcoming issue of iHealth Connections. (November 2011)



Participants

EFPIA

Amgen NV, Belgium AstraZeneca AB, Sweden Bayer Schering Pharma AG, Germany Eli Lilly, UK F. Hoffmann-La Roche Ltd, Switzerland GlaxoSmithKline Research & Development, UK Janssen Pharmaceutica NV, Belgium Merck KGaA, Germany Novartis Pharma AG, Switzerland Sanofi-Aventis Research and Development, France

UNIVERSITIES, RESEARCH ORGANISATIONS, PUBLIC BODIES & NON-PROFIT

eClinical Forum Association, France European Association of Health Law, University of Edinburgh, UK European Institute for Health Records, France European Molecular Biology Laboratory, Germany European Platform for Patients Oganisations, Science and Industry, Belgium Friedrich-Alexander University, Erlangen-Nrnberg, Germany Heinrich-Heine University, Dsseldorf (representing ECRIN), Germany Kings College London, UK Medical University of Warsaw, Poland National and Kapodistrian University of Athens, Greece National Institute for Health & Medical Research (INSERM), France Public Service Hospitals of Paris, France Telematics Platform Medical Research Networks, Germany University College London, UK University Hospital of Geneva, Switzerland University of Dundee, UK University of Edinburgh, UK University of Glasgow, UK University of Manchester, UK University of Rennes 1, France Westflische Wilhelms University, Mnster, Germany

SMEs

Assero Limited (representing CDISC), UK Custodix NV, Belgium Data Mining International, Switzerland (sub-contracting partner) XClinical GmbH, Germany



Facts & Figures


Contributions

IMI funding 7 019 046EFPIA in-kind 7 042 616Other 1 989 852Total Cost 16 051 514

Links and Documents

Project website: www.ehr4cr.eu

IMI funding per project particpant

Publications

Contact

Project Coordinator Mats SundgrenGlobal Clinical DevelopmentAstraZeneca Sweden Email:Mats.Sundgren[AT]astrazeneca.com

Managing entity of IMI beneficiariesProf. Dr. Georges de Moor TheEuroRec Institute Belgium

Email: Georges.DeMoor[AT]UGent.be

For press inquiries:[email protected]



European Lead FactoryEuropean Lead FactorySummary

The European Lead Factory is a pan-European platform for drug discovery supported by the Innovative MedicinesInitiative (IMI) that is set to give a major boost to drug discovery in Europe. Comprising a collection of half a millioncompounds (derived from new public and existing private company collections) and a screening centre, theEuropean Lead Factory will offer researchers in academia, small and medium-sized enterprises (SMEs) and patientorganisations an unprecedented opportunity to advance medical research and develop new medicines.

A key tool in the earlier stages of drug development is a technique called High Throughput Screening (HTS), inwhich researchers screen large collections of chemical compounds in the hunt for molecules that could be potentialdrugs or be used in drug development in other ways. Although pharmaceutical companies have built up largelibraries of compounds over the years, access to these collections has been tightly restricted to in-house use by theowners.

Meanwhile, the academic community is becoming increasingly interested in HTS, but public compound collectionstend to be rather small and expertise in the area is scattered across many institutions. As a result, few public drugtargets have been screened against large, high-quality compound libraries. This has hampered efforts to generatepromising leads for the development of innovative drugs.

A unique resource

Enter the European Lead Factory, which will provide a select group of researchers in universities, small businessand patient organisations with access to an industry-like platform for the identification of hits. Hits are compoundsthat could potentially be developed into new medicines. The pharmaceutical companies in the consortium willcontribute a total of over 300 000 compounds to the project to create a joint compound collection.

To this will be added an estimated additional 200 000 novel compounds generated by public partner contributionsduring the project, resulting in a unique Joint European Compound Collection with some 500 000 compounds.Proposals for novel compounds from the public partners will be submitted to a transparent selection and validationprocess addressing several criteria such as novelty, diversity potential, innovative design and synthetic tractability.Once approved, the SMEs together with the academic institutions will seamlessly translate the most compellingideas into high quality compound libraries to be shipped to the consortiums HTS facilities.

The project will also establish a screening centre providing HTS services for projects for the selected publicprojects from academia and SMEs. It will also handle all logistics for the Joint European Compound Collection,acting as a neutral, honest broker in the transfer, handling and analysis of confidential data.

The project in practice

Once up and running, the European Lead Factory will provide the compounds and support for 48 HTS screens peryear. Of these, 24 will come from the industry partners, who will run their own screens. The other 24 HTS projectswill be selected from the public sector following competitive Calls for proposals.

Public programmes selected by the project will be further advanced by the European Lead Factory. It will provideguidance in the design of the experiments, support on medicinal chemistry, and help setting up partnerships withothers if needed. Once the HTS has been run, the target owner (i.e. the organisation that submitted the target forinclusion in the project) will receive a list of a maximum of 50 compounds that have been identified. The projecthopes to attract public screening proposals in a variety of therapeutic areas.

Strength in diversity



The European Lead Factory combines the power of the pharmaceutical industrys previously inaccessiblecompound libraries with the innovation of the academic communities in designing novel compounds and theexpertise of many SMEs in HTS and library generation. Importantly, it will provide a screening platform of industrialquality focused on value generation. Looking to the future, the European Lead Factory is set to become a centre ofexcellence in Europe for small molecule drug discovery programmes in the public sector. A key output of theproject is a comprehensive business plan that will ensure the viability of the initiative once the initial IMI project hasended.

Participants

EFPIA companies

Bayer Pharma AG, GermanyAstraZeneca AB, SwedenH. Lundbeck A/S, DenmarkJanssen Pharmaceutica NV, a Pharmaceutical Company of Johnson & Johnson, BelgiumMerck KGaA, GermanySanofi, FranceUCB Pharma SA, Belgium


Foundation Top Institute Pharma (Stichting Top Instituut Pharma), The NetherlandsLeiden University, The NetherlandsMax Planck Gesellschaft zur Frderung der Wissenschaften E.V., GermanyRadboud University Nijmegen, The NetherlandsStichting Het Nederlands Kanker Instituut, The NetherlandsTechnical University of Denmark, DenmarkUniversitt Duisburg-Essen, GermanyUniversity of Dundee, UKUniversity of Groningen, The NetherlandsUniversity of Leeds, UKUniversity of Nottingham, UKUniversity of Oxford, UKVU-University Amsterdam, The Netherlands

SMEs

BioCity Scotland Ltd, UKChemAxon, HungaryEdelris S.A.S, FranceGabo:Mi Gesellschaft fur Ablauforganisation:Milliarium Mbh & Co Kg, GermanyLead Discovery Center GmbH, GermanyMercachem B.V., The NetherlandsPivot Park Screening Centre B.V, The NetherlandsSygnature Discovery Limited, UKSyncom, The NetherlandsTaros Chemicals GmbH & Co KG, Germany



Facts & Figures

Start Date 01/01/2013Duration 60 monthsContributions IMI Funding 79 999 157EFPIA in kind 91 337 070Other 25 202 832

Total cost 196 539 059

Links and Documents


Contact

Project Coordinator Jrg HserBayer Tel: +49 202 36 3938 E-mail:joerg.hueser[AT]bayer.com HeadChemistry Consortium DimitriosTzalis Taros Chemicals Tel: +49 23197 427211 E-mail:dtzalis[AT]taros-chemicals.de HeadScreening Consortium TonRijnders TI Pharma Tel: +31 71 3322035 E-mail:ton.rijnders[AT]tipharma.com



EMIF

European Medical Information FrameworkSummary

The EMIF project aims to develop a common information framework of patient-level data that will link up andfacilitate access to diverse medical and research data sources, opening up new avenues of research for scientists.To provide a focus and guidance for the development of the framework, the project will focus initially on questionsrelating to obesity and Alzheimers disease.

Difficulties with data

Recent years have seen an explosion in the number of databases containing medical and research data, fromElectronic Health Records (EHRs), cohort studies (in which a group of individuals are followed for a number ofyears), disease-specific studies, and biobanks, to name a few. Because this data is scattered across diverseplatforms, it cannot be fully exploited. Linking up the data would allow scientists to significantly advance medicalresearch and drug development.

However, in practice, this is rather difficult. Not only is the data fragmented, differences in coding systems andlanguages, plus legal and ethical restraints, hamper efforts to combine these sources of data. Furthermore, thereare often information gaps.

There is therefore a need for a single system that allows researchers to link data on an immense scale, includingpatient health records, research data, survey and administrative data, imaging, social, environmental and economicdata. Such a system should also be able to bring together data from different populations; this would increasesample sizes and facilitate the study of rare or highly specific subgroups.

A common information framework

EMIF will develop a common information framework that will not only facilitate access to existing data sources, butease the creation of links between sources and, where needed, collect additional information. The work will requirethe team to address a number of issues, including data standards, semantic interoperability, ethics, data privacy,legal issues, and the development of an IT platform that allows access to multiple data sources.

To guide the development of the framework, the team will initially focus on two key research issues:

identifying the mechanisms that make some people more susceptible to dementias (such as Alzheimersdisease) than others;determining which individuals with obesity are most likely to develop complications such as diabetes.

Obesity and dementia are two of the greatest healthcare challenges of our time; EMIFs work will pave the way fornew diagnostic tools and treatments to help patients with these conditions. Looking to the future, additionalresearch areas may be added to the framework through future IMI Calls for proposals.

Participants

EFPIA

GlaxoSmithKline Research and Development Ltd, Brentford, UKAmgen NV, Brussels, BelgiumBoehringer Ingelheim International GmbH, Ingelheim, GermanyF. Hoffmann-La Roche AG, Basel, Switzerland



Institut de Recherches Internationales Servier, Suresnes, FranceJanssen Pharmaceutica NV, Beerse, BelgiumNovo Nordisk A/S, Bagsvrd, DenmarkPfizer Limited, Sandwich, UKUCB Pharma SA, Brussels, Belgium


Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, NetherlandsAarhus Universitetshospital, Aarhus Sygehus, Aarhus, DenmarkAgenzia Regionale di Sanita, Florence, ItalyAssistance Publique - Hpitaux de Paris , Paris, FranceBrighton Collaboration Foundation, Basel, SwitzerlandEaling Hospital NHS Trust, Southall, UKEuropean Institute for Health Records, Lille, FranceEuropean Molecular Biology Laboratory, Heidelberg, GermanyFondazione PENTA - for the Treatment and Care of Children with HIV-ONLUS, Padova, ItalyGteborgs Universitet, Gothenburg, SwedenHelsingin Yliopisto, Helsinki, FinlandInstitut fr Epidemiologie und Prventionsforschung GmbH, Bremen, GermanyInstitut National de la Sant et de la Recherche Mdicale, Paris, FranceIt-Suomen Yliopisto, Kuopio, FinlandKarolinska Institutet, Stockholm, SwedenKings College London, London, UKMaastricht University, Maastricht, NetherlandsMax-Planck-Gesellschaft zur Frderung der Wissenschaften, Munich, GermanyMedical Research Council UK, Swindon , UKProvincia Lombardo-Veneta - Ordine Ospedaliero di San Giovanni di Dio Fatebenefratelli, Milan, ItalyTartu Ulikool, Tartu, EstoniaTeknologian tutkimuskeskus VTT, Espoo, FinlandUniversidade de Aveiro, Aveiro, PortugalUniversit degli Studi di Pisa, Pisa, ItalyUniversitt Leipzig, Leipzig, GermanyUniversitat Pompeu Fabra, Barcelona, SpainUniversiteit Antwerpen, Antwerp, BelgiumUniversity College London, London, UKUniversity of Cambridge, Cambridge, UKUniversity of Copenhagen, Copenhagen, DenmarkUniversity of Glasgow, Glasgow, UKUniversity of Leicester, Leicester, UKUniversity of Manchester, Manchester, UKUniversity Pierre et Marie Curie, Paris, FranceVereniging Voor Christelijk Hoger Onderwijs Wetenschappelijk Onderzoek en Patintenzorg, Amsterdam,NetherlandsVIB, Zwijnaarde, Belgium

Patients organisations

Alzheimer Europe, Luxembourg, LuxembourgUniversittsklinikum Erlangen, Anstalt des ffentlichen Rechts, Erlangen, GermanyVestische Kinder- und Jugendklinik Datteln, Dattien, Germany

SMEs



Concentris Research Management GmbH, Frstenfeldbruck, GermanyCustodix NV, Sint-Martens-Latem, BelgiumElectrophoretics Ltd, Cobham, UKGENOMEDICS S.R.L., Florence, ItalyMAAT France, Archamps, FrancePharmo Cooperatie UA, Utrecht, Netherlands Synapse Research Management Partners S.L., Barcelona,SpainSocieta Servizi Telematici SRL, Padova, Italy Synapse Research Management Partners S.L., Barcelona,Spain



Facts & Figures



Links and Documents


Contact

Project Coordinator BartVannieuwenhuyse JanssenPharmaceutica NV Tel: +32 14600320 E-mail:BVANNIEU[AT]its.jnj.com

Co-coordinator Simon LovestoneKing's College London Tel: +44 207848 0239 E-mail:simon.lovestone[AT]kcl.ac.uk

Managing Entity Johan van der LeiErasmus Universitair MedischCentrum Rotterdam Tel: +31 10 70441 22 E-mail:j.vanderlei[AT]erasmusmc.nl



EMTRAIN

European Medicines Research Training Network Summary

The European Medicines Research Training Network (EMTRAIN) will establish a sustainable, pan-Europeanplatform for education and training (E&T) covering the whole life-cycle of medicines research, from basic sciencethrough clinical development to pharmacovigilance. This will be achieved by integrating the strengths andcompetencies of the ESFRI BMS Infrastructures, the EFPIA companies, the current and future IMI E&Tprogrammes as well as other scientific projects.

EMTRAIN will establish a pan-European platform for education and training, covering the entire life-cycle ofmedicines, from basic research, clinical tests and market authorisation to follow-up research of drugs already onthe market. The consortium will provide a mechanism to ensure that industry and academia cooperate on coursesthat can be rapidly designed and implemented, in order to enable a faster implementation of new scientific andtechnological developments in academic teaching. Through harmonisation and accreditation of Master level, PhDprogrammes and continuous education programmes, EMTRAIN aims to improve the mobility across disciplines andnational borders, as well as between academia, industry and regulatory authorities.

The EMTRAIN consortium will develop innovative concepts and methods in order to support the content for thetraining programmes, in close collaboration with three other IMI Education and Training projects, SafeSciMET,PharmaTrain and Eu2P. National implementation will be facilitated through contacts with university authorities,ministries of higher education and national liaison offices.

The consortium includes six established pan-European biomedical research infrastructures that cover a broadspectrum of competencies, from structural biology, bioinformatics, animal models, biobanks, translational researchand clinical research.

Achievements & News

Check out the IMI Education & Training projects video Four of IMIs Education & Training projects have puttogether a short video on their activities.In the six-minute clip, the coordinators of the EMTRAIN, SafeSciMET,Eu2P, and PharmaTrain projects present their courses and the benefits they offer for students and courseproviders alike. The film also features a presentation by IMI Executive Director Michel Goldman. (November 2012)

on-course launches video on-course has released a video explaining how different groups (especiallycurrent and potential students and course providers) can get the most out of on-course . Developed by IMIsEMTRAIN project, on-course is the most comprehensive and sustainable biomedical and medicines researchand development postgraduate course portal in Europe. Currently, the portal contains information on over 3 800courses, and more are being added all the time. While on-course is probably EMTRAINs most visible outcomeso far, the project is also making good progress on its other activities. The team sets out the projects highlights sofar in a recent press release and concludes: EMTRAIN has made considerable progress in the first 2.5 years ofthe project. We are now in the process of developing robust performance metrics to assess the impact of theproject, and we are exploring models of sustainability beyond the public funding period of the project. (July 2012)

Give your career a boost with on-course IMI Education & Training project EMTRAIN has launched on-course -Europes most comprehensive biomedical and medicines research and development postgraduate course portal.The portal gathers together information on over 3 000 courses taught in 20 languages in 39 countries and coveringover 60 scientific and therapeutic areas. Free and easy to use, on-course allows users to search for courses bytype (Masters, PhD, short course), schedule (full or part time, modular), learning type (distance, face-to-face,mixed), language, location, and scientific / therapeutic area. Users can also search for courses delivered by IMIsEducation & Training projects. For each course on the site, on-course provides a course description, list of



modules (if relevant), details of fees, contact information, and links to the course website. In addition, users cancompare courses quickly and easily. Finally, for people looking for courses while on the move, there is theon-course app , which can be downloaded to smartphones for free from Google Play (for Android phones) or theAppStore (for Apple products).

EMTRAIN holds first PhD workshop

Some 26 students involved public-private partnerships, including IMI projects, took part in the inaugural EMTRAINPhD workshop in Manchester, UK in February. The aim of the event was to create a forum for the students to shareexperiences and help them develop as industry-aware scientists. During the four-day workshop, experts fromacademia and industry provided an insight into the various aspects of industry-driven drug development, theopportunities for public-private partnership, and the relevant European initiatives and accessible Europeanresearch infrastructures. (March 2012)

OECD report spotlights IMI projects IMI projects EMTRAIN and EUPATI (European Patients' Academy onTherapeutic Innovation) are mentioned in a new report on facilitating international cooperation in non-commercialclinical trials.The report, by a working group of the OECD (Organisation for Economic Co-operation andDevelopment) Global Science Forum, sets out recommendations to overcome the main barriers facing theinternational clinical research community in setting up international clinical trials. Among other things, the reporthighlights the need to improve education and training support as well as the infrastructure framework in clinicalresearch, and to enhance the involvement of patients in trials. EMTRAIN is mentioned in the section oninfrastructure support, while EUPATI (which will start soon and is funded under IMIs 3rd Call for proposals) ishighlighted in the section on patient involvement. (January 2012)

IMI projects launch continuous professional development initiative IMIs Education & Training projects havesuccessfully launched an initiative to draw up a common framework for Continuous Professional Development(CPD) in the pharmaceutical sector.The first LifeTrain workshop, held in early October in the UK, gatheredrepresentatives of professional and scientific bodies from across Europe to start work on the development of acommon framework for CPD. Such a framework will help scientists working on all aspects of drug discovery anddevelopment to maintain their professional skills and knowledge and adapt to changes in the sector. The hope isthat this will ultimately help to make Europe more competitive. There was tremendous enthusiasm from allparticipants to combine forces for the good of research and development in Europe, commented AstraZenecasMike Hardman, who chaired the LifeTrain workshop steering committee. The workshop outputs exceeded ourexpectations and we are now working together on the next steps. More information on LifeTrain can be found onthe EMTRAIN website. (October 2011)

EMTRAIN joins group promoting quality in higher education EMTRAIN, on behalf of all of IMIs Education &Training (E&T) projects, has become an affiliate of the European Association for Quality Assurance in HigherEducation (ENQA), a pan-European body that aims to contribute to the maintenance and enhancement of thequality of European higher education. Joining the ENQA is an important move for the IMI E&T programmes, whichare jointly developing standards for the quality assessment of continuous professional development courses inbiomedical and medicines research. It is also important for the IMI life-long learning/continuous professionaldevelopment initiative LIFETRAIN, in which the IMI E&T programmes work together with professional and scientificbodies, course providers, and employers across Europe to encourage them to recognise these quality standards.Finally, ENQA affiliate status will enable the IMI E&T programmes to keep abreast of the latest developments,engage with experts, and share experiences with other ENQA members. (September 2011)

Participants

EFPIA

AstraZeneca AB, Sdertlje, Sweden (Project Coordinator)Genzyme Europe B.V., Naarden, The Netherlands



Novartis Pharma AG, Basel, SwitzerlandBayer Schering Pharma AG, Berlin, GermanyPfizer LTD, Sandwich, United KingdomF. Hoffmann-La Roche AG, Basel, SwitzerlandGlaxoSmithKline Research and Development LTD, Brentford, UKUCB Pharma SA, Brussels, BelgiumNovo Nordisk A/S, Bagsvaerd, DenmarkSanofi-Aventis Deutschland GMBH, Frankfurt/Main, GermanyBoehringer Ingelheim International GmbH, Ingelheim, GermanyJanssen Pharmaceutica NV, Beerse, BelgiumOrion Corporation, Espoo, FinlandLaboratorios Almirall S.A., Barcelona, SpainH. Lundbeck A/S, Valby, DenmarkLaboratorios del Dr Esteve SA, Barcelona, Spain

Universities, Research Organisations, Public Bodies & Non-Profit

Medizinische Universitt Wien, Wien, AustriaKarolinska Institutet, Stockholm, SwedenKarolinska Universitetssjukhuset, Stockholm, SwedenThe University of Manchester, Manchester, United KingdomInstitut National de la Sante et de la Recherche Medicale (Inserm), Paris, FranceEuropean Molecular Biology Laboratory, Heidelberg, GermanyHelmholtz-Zentrum fr Infektionsforschung Gmbh, Braunschweig, GermanyMedizinische Universitt Graz, Graz, AustriaCentre de Recherche en Biologie et Medecine, Illkirch, FranceHelmholtz Zentrum Mnchen Deutsches Forschungszentrum fr Gesundheit und Umwelt GMBH, MnchenNeuherberg, GermanyMinistry of Health, Social and Family Affairs, Medical Research Council , Budapest, Hungary



Facts & Figures


Contributions IMI funding 4 000 000EFPIA in kind 3 722 663Total cost 7 722 663

Links and Documents

Project website: www.emtrain.eu

Publications

IMI Education & Training Programmes


Contact

Project Coordinator MichaelHardman R&D Science PolicyAstraZeneca Macclesfield CheshireUK Tel: +44 (0)1625 519566 Email:Mike.hardman [AT] astrazeneca.com

Managing entity of IMI beneficiariesMichael Wolzt Department of ClinicalPharmacology MedizinischeUniversitt Wien Vienna Austria Tel:+431404002981 Email: michael.wolzt[AT] meduniwien.ac.at



eTOXIntegrating bioinformatics and chemoinformatics approaches for the development ofExpert systems allowing the in silico prediction of toxicities Summary

The eTOX project partners will develop innovative strategies and novel software tools to better predict the safetyand the side-effects of new candidate medicines for patients. Reliable prediction of side-effects in the initial phasesof drug development lowers the failure rate in later phases, significantly reduces the number of animal tests neededand accelerates the development of new drugs.

The eTOX scientists will use the complex relationships between the structure of a substance, its metabolism anddisposition, and its toxic effects in the body. The combination of this knowledge will enable them to create morereliable computer models to better predict potential side-effects that would otherwise only be discovered in a laterstage of the drug development or when the drug is already on the market.

Top experts in toxicology, knowledge management, bioinformatics, chemoinformatics, biostatistics and softwaredevelopment from industry and academia will join forces in the multidisciplinary consortium. To overcome the lackof publicly available toxicological data of 'drugable' chemicals which hampered progress so far, the multidisciplinaryteam will share and jointly exploit the archived results of more than 10.000 toxicological studies of the industrypartners. This data, which was previously only accessible to the owning pharmaceutical companies, will beintegrated with publicly available and new data, resulting in a unique database a treasure trove of toxicologicalinformation, which will be analysed using innovative approaches in data analysis.

Achievements & News

eTOX explains ontologies One of the goals of IMI project eTOX is to predict safety issues in silico (i.e. usingcomputer models) bylearning from companies existing preclinical data. The extraction of reports containing thisdata is now well advanced, raising the issue of standardisation. The question facing eTOX is: how can the projectmake sure that everybody uses the same term to describe the same thing? The answer lies in ontologies: thedescription of preferred terms and synonyms to be used in various places, as well as the relationships between theterms. Within eTOX, many ontologies are employed. Some of these are already available in the public domain inorder to increase interoperability, while others have been created by the consortium because nothing was availableyet. These new ontologies will be released into the public domain and discussed with interested partners (e.g.CDISC and IMI project OpenPhacts). The consortium will also release its annotation software, the first trulycollaborative interface dedicated to crowd sourcing of ontology annotations. (November 2012)

eTOX library goes public Since its launch in April 2010, IMI toxicology project eTOX has been compiling a vastlibrary ofinformation and data on the toxicology field. Now the project team has decided to make its eTOX Libraryavailable to the public, so that scientists outside eTOX can benefit from it. The library has three sections. UnderArticles, the project provides links to relevant journal articles; each reference has a list of keywords and a synopsishighlighting the articles relevance to eTOXs goals. The Journals section includes links to journals that covertoxicology issues, and the Links section includes links to public databases, computer modelling tools, projects, andmore. For their part, eTOX researchers are using the library to identify new data that can be integrated into theprojects databases, find out about new computational models, and identify potential drug targets and biologicalmarkers relevant to toxicity. The library is updated regularly. (October 2012)

eTOX makes progress on predictive toxicology IMI project eTOX is making progress towards its goal ofdeveloping a predictive toxicology system called eTOXsys, which is now at the proto