www.eu-openscreen.euwww.eu-openscreen.eu

Initiative for a Initiative for a European Research Infrastructure of OpenEuropean Research Infrastructure of OpenScreening Platforms for Chemical BiologyScreening Platforms for Chemical Biology

Partners of preparatory phase project

• NOR-OPENSCREEN• Swedish Chemical Biology Consortium• Drug Discovery and Chemical Biology

network Finnland• Danish Chemical Biology Initiative• Dutch Chemical Library Program• ChemBioNet Germany• POL-OPENSCREEN• CZ-OPENSCREEN and Czech ChemGen• Austrian PLACEBO• Spanish ChemBioBank• French Chimiothèque Nationale, Réseau

Nationale de Criblage, FR-OPENSCREEN• Romanian Chemical Biology Net• Flemish Network on Chemical Biology• Collezione Nazionale dei Composti Chimici e

Centro Screening

Current partners Associated members

Coordination Centre at FMP Berlin

EU-OPENSCREEN builds on national networks in 14 European countries.

Investigation of biological systems using chemical tools

Chemical Biology

IQPC Drug Discovery Partnerships February 2013Page 318/04/23 3

Infrastructures for the European Research Area

Physics

AstronomyInformationTechnology

Biological & Medical SciencesUnderstanding the principles of life

Social Sciences“Modern research in all scientific fields requires expensive instruments and resources, and is characterised by a

continuous interplay between new scientific challenges and our technical responses to

them.“ (ESFRI report)

Infrastructures for the European Research Area

European Strategy Forum on Research Infrastructures (ESFRI)Set up in 2002 by the Competitiveness Council.

Meeting of Senior Representatives for informal consultations on strategic issues related to research infrastructures (RI).

Independent from the European Commission.

2004: Mandate to develop a European Strategic Roadmap for Research Infrastructures - to describe the needs for the next 10 to 20 years - to identify vital new European research infrastructures.

Infrastructures for the European Research Area

ESFRI Roadmap

Published in October 2006, updated in 2008 and 2010.

Will be used to facilitate decision-making by member

states and EC.

Will not prioritise or decide on funding and locations.

Four areas: Physical Sciences and Engineering (PSE),

Biological and Medical Sciences (BMS), Social Sciences

and Humanities (SSH), Environment (ENV).

Total: 48 ESFRI infrastructures.

18/04/23 7

ESFRI BMS – Fields of Activity

Biological Sciences

Biological Resources & Production Systems

Medical Sciences

Bio Banking & Molecular Resources

Functional Genomics in the Mouse

Systems Biology

High Security Laboratories

Clinical Research

Translational Medicine

Structural BiologyMarine Biology

Ecosystems

Chemical Biology (EU-OPENSCREEN)

Bioinformatics

Imaging

Microbial Resources

ESFRI BMS – Fields of Activity

Towards supporting aninnovation chain without gaps

MIRRI

ANAEE ISBE

The EU-OPENSCREEN database will be linked to other biological databases through ELIXIR: BioMedBridges

Compounds with potential as drug candidates can be further developed through EATRIS and ECRIN

Cell-lines and animal models for bioprofiling of compounds are available through BBMRI and INFRAFRONTIER (BMS-RI) support

Natural products from MIRRI and EMBRC.

A pan-European infrastructure to...

accelerate the discovery of biologically active substances in all areas of the life sciences

facilitate transnational access to the most advanced technologies, chemical and biological resources, knowledge and expertise

advance the elucidation of the molecular mechanisms of complex biological processes

increase knowledge on the bio-activities of chemical substances, as well as the responses of biological systems to these substances

promote the availability of safe and efficacious chemical products for unmet needs in medicine, nutrition, agriculture, environment

EU-OPENSCREEN’s Mission

THE PREPARATORY PHASE PROJECT

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WP12Chem&

BioInformatics

WP6Governance

structure

WP7Financial plan

WP3Training and

education

WP5Strategy

WP2Standardisation

WP11TechnologyResources

WP9Chemical

Resources

WP10Biology

Resources

WP4Disseminationand outreach

WP8IPR issues

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Advisory Board

Prof. Dr. Dr. Ernst Rietschel, former president of the Leibniz Association of

Research centres (WGL), now acatech - National Academy of Science and Engineering (technology advisor for the German federal government)

Prof. Dr. Ferran Sanz, Director of GRIB (Research Group in Biomedical Informatics) at IMIM (Municipal Institute for Medical Research) in Barcelona. He is also a member of the Scientific Advisory Board for the Innovative Medicines Initiative (IMI).

Prof Dr. Serge Braun, scientific director of the Association Francaise contre les Myopathies (AFM)

Dr. Steve Rees, VP of Screening Sciences, AstraZeneca (AZ)

Expert Groups

Chemical Diversity Group (WP9) chaired by Dr. Michael Foley, Broad Institute, USA

Innovative Target & Assay Group (WP10) chaired by Sir Philip Cohen, UK

Industrial Advisory Group (WP5) chaired by Dr. Philip Gribbon, European ScreeningPort; members: J. Everett (f. Pfizer), J. Kihlberg (Univ. Uppsala, former AZ), T. Langer (Prestwick), H-U. Stilz (SA)

EU-OPENSCREEN Strategy Group (WP5) chaired by Dr. James Inglese, Chemical Genomics Centre, NIH, USA

OBJECTIVES

EU-OPENSCREEN´s objective is the development of novel research ‘tool’ compounds for all fields of the Life Sciences. Tool compounds enable researchers to investigate molecular mechanisms of physiological

and pathological processes, many of which can only be studied with these chemical ‘tools’

Chemical tools complement methods of molecular biology, such as mutagenesis or RNA interference

All generated tools and data are made publically available to the scientific community

Chemical compounds, such as this small molecule, can bind to cellular structures (e.g. proteins) and modulate their functions.

Chemical keys for life’s locks

A Chemical Biology InfrastructureServing research in all Life Sciences

No Life Without Chemistry

Service Portfolio

EU-OPENSCREEN will provide services to support the development of tool compounds at all stages

LAYOUT OF RI

ChemistryCompounds

BiologyAssays & Targetsmeets

Partner SitesScreening Technology

Compound Profiling

Chemistry Services

Compound Management

EU-OPENSCREEN-ERICCompound Collection

Project Management

Database

Training & Education

User User

Activityprofiles

Toolcompounds

EU-OPENSCREEN integrates Europe´s expert resources and facilities into its unique concept of a knowledge-creating Chemical Biology Centre and supports all stages of tool development projects in an RI ‘open’ for external researchers.

Service contracts

The European Chemical Biology Library ECBL will - be designed and built on the expert knowledge of European chemists

- cover unbiased chemical diversity with an expected size of 200k to 300k compounds

- be driven by the prospect of bioactivity, intellectual curiosity, uniqueness, and the goal of generating knowledge (not necessarily new chemical entities, NCEs)

- be composed to optimally serve the community and its needs; will contain selections from academic chemistry labs, commercial collections, known drugs, natural products, environmentals, etc.

- be quality controlled by approved standard method (LC-MS)

- be fully profiled with a set of basic properties (biophysical, cellular cytotoxicity, antimicrobial)

- be systematically profiled against hundreds of assays conducted by the network of screening centres.

UNIQUE ERIC ELEMENTS

UNIQUE EUROPEAN ASSETS

The European Chemical Biology Database (ECBD) will be a web portal with powerful search and analysis capabilities:• contains validated output from screening centres in a public as well as pre-

release environment.

• supports curation, annotation and organization of data + metadata.

• data deposition with flexible privacy model for rapid and safe dissemination and exploitation. Optional hold period of 18 months for data publication.

• The broadest possible use of data through public accessibility and dissemination. Public data also freely available for complete download, redistribution.

• High standards of security and traceability of IP (citable indexing of data points (EUOS, DOI or URL). Links to originator labs for primary raw unprocessed data.

• Links to SAR (e.g. ChEMBL), Chemical Structure (e.g. PubChem), and Target (e.g. UniProt) resources. Links established with new NIH-funded BARD resource.

Project Selection

TOOL COMPOUND

Projects are evaluated by external reviewers and implemented according to milestones along a defined timeline.

Validated chemical structure

Extensive basic Bio-profile

Bioactivity data from hundreds of assays

BUDGET (LIMITED CAPACITY)

The required minimum budget for EU-OPENSCREEN is modest and shared between member countries.

Upgrade 1

Upgrade 2

Upgrade 3

Upgrade 4

Upgrade 5

45 m€ already invested

Service site upgrades

National funding

Office

ECBL

ECBD

Training

Central costs(6 years)

Shared funding~ 27 m €

(e.g. GDP-share)

Project costs(6 years)

Shared funding~ 30 m €

(e.g. GDP-share,cost ceiling)

Shared funding ofMember countries

BUDGET (FULL CAPACITY)

The required minimum budget for EU-OPENSCREEN is modest and shared between member countries.

Upgrade 1

Upgrade 2

Upgrade 3

Upgrade 4

Upgrade 5

45 m€ already invested

Service site upgrades

National funding

Office

ECBL

ECBD

Training

Central costs(6 years)

Shared funding~ 27 M €

(e.g. GDP-share)

Project costs(6 years)

Shared funding ofMember countries

EU-funding to EU-OPENSCREEN

Users(research grants, in addition to EU-grants)

EU-funding to users (research grants)

Diversefundingsources~ 60 m€

ADDED VALUE

Without EU-OPENSCREEN:Limited chance of finding a hit against a

target from local or national compound collections

FR

UK

DE

ES

IT

x

Compounds

Tar

gets

With EU-OPENSCREEN:European Scale Advantage: Exponential

increase of the likelihood of finding a hit against a target from a national compound collection

Tar

gets

FR

UK

DE

ES

IT

x

CompoundsHit

French compound

Sp

an

ish

ta

rge

t

EU-OPENSCREEN´s ‘open’ character: large pool of external biologists and chemists provide wide range of expertise, assays and diverse

compounds.

ADDED VALUE

Without EU-OPENSCREEN:Limited chance of finding a hit against a

target from local or national compound collections

FRUK

DEES

ITx

Compounds

Tar

gets

With EU-OPENSCREEN:European Scale Advantage: Exponential

increase of the likelihood of finding a hit against a target from a national compound collection

Tar

gets

FR

UK

DE

ES

IT

x

CompoundsHit

French compound

Sp

an

ish

ta

rge

t

EU-OPENSCREEN´s ‘open’ character: large pool of external biologists and chemists provide wide range of expertise, assays and diverse

compounds.

Human Genome Organisation

Structural Genomics Consortium

EU-OPENSCREEN

OutputSequence data of human genomes

Human protein structures

Novel tool compounds for LifeSciences

Model Not-for-profit Not-for-profit Not-for-profit

Data policy Open-access Open-access Open-access

Impact

Advancing our understanding of biological processes.

New approaches to disease treatment, diagnosis,

prevention

Advancing our understanding of biological processes.

New approaches to disease treatment

Advancing our understanding of biological processes.

New druggable targets for disease treatment

In the Life Sciences, large-scale open-access research consortia have already proven fundamental to breakthroughs in their fields.

Weigelt (2009): “The case for open-access chemical biology. A strategy for pre-competitive medicinal chemistry to promote drug discovery.” EMBO Rep. 10: 941–945

IMPACT ON SCIENCE

Stevens, A.J. et al., 2011, N ENGL J MED 364:535-541.

IMPACT ON DRUG DISCOVERY

Public Sector Research Institutions (PSRI) contribute particularly to new NCEs and new indications .

TIMELINE

• ESFRI Roadmap: ESFRI considers EU-OPENSCREEN as vital to the excellence of research and innovation in Europe and included it on the “European Roadmap of Research Infrastructures”.

• Preparatory Phase (3 years): Preparation of a business plan describing in detail the mode of construction and operation. MoU signed. EU funding: 3.7 M€.

• Interim Phase (1-1.5 years): ERIC application and approval. Institutional funding.

• Construction Phase (1 year): Construction of infrastructure (existing and new sites). National funding.

• Operation Phase: Active infrastructure with access for researchers. Diverse funding sources.

Roadmap Interim Construction OperationPreparation

Now in the 3rd year of its Preparatory Phase, EU-OPENSCREEN will initiate construction and operation in 2014-2015.

• EU-OPENSCREEN in 3rd year of Preparatory Phase: Challenge before Construction and Operation Phases is the securing of (financial) commitment of member countries

• Timelines of member countries vary: Transition Committee for the time between the end of the Preparatory Phase and the start of the Construction and Operation Phases will be formed

• EU-OPENSCREEN included on several nationalRoadmaps

• MoU document , financial plan, funding strategy, draft ERIC statutes and draft Business Plan

already available

CURRENT STATUSAND NEXT STEPS

EU-OPENSCREEN was included on several national roadmaps and is now initiating negotiations with governments and funding organisations.

EU-OPENSCREEN – Executive Summary August 2013Page 27

On national Roadmap start negotiations

Decision expected in 2013

18/04/23 28

Tuesday, 19 Nov – Project Meeting 09:00-13:00 General Assembly meeting (project participants) 14:30-18:00 EU-OPENSCREEN outreach and synergies (invited guests) Interactions with representatives of other ESFRI infrastructures, JPI's and IMI´s European Lead Factory 19:30 EU-OPENSCREEN networking dinner

Wednesday, 20 Nov – Stakeholder Meeting 09:30-16:00 EU-OPENSCREEN Science Day (open)

- 3 presentations from EU-OPENSCREEN- 6 reports on flagship projects

13:00-16:00 Transition Committee Meeting (closed)

Next Project & Stakeholder Meeting

OsloNorway

Thank you for your attention

THE TEAM

www.eu-openscreen.eu