Advances in Target Based Drug Design - GPCRs

part of 60+ Speakers - 10+ Hours of Networking Pharma / Biopharm Prices from 799* Academic Prices- Flat Rate 499* CONFERENCE Advances in Target Based Drug Design - GPCRs 18-19 March 2014 Hotel Palace Berlin, Berlin, Germany Utilise the latest discoveries in GPCR science and technology to develop new drug candidates Conference Highlights Ligand Development Graeme Milligan, University of Glasgow Allosteric Modulators Sylvain Celenire, Addex Therapeutics Structural and Biophysical Studies Ali Jazayeri, Heptares Therapeutics Limited Application of Biosensors Stephan Schann, Domain Therapeutics Conference Highlights for 2014 Advancing GPCR Drug Discovery Using Biochemical and Structural Data - Heptares, Sanofi Aventis and FMP discuss the application of GPCR crystal structure information to understand biological functions and enhance drug design Understanding The Impact of Biased Signalling and Signalling Pathways on Drug Discovery Understand the biological relevance of biased signalling and signalling pathways and how to translate knowledge into drug products Drug Discovery Case Histories: Recent Highlights in the Discovery and Development of Novel GPCR Drug Products Benefit from 6 industry case studies on lead optimisation strategies and the development from initial screening results into later stage drug products for GPCRs, allosteric modulators and multi-target products Application of Novel Screening Technologies and Assay Development for GPCRs Discuss the latest developments in multi-pathway screening technologies and the use of more physiologically relevant cell types for GPCR targets in our interactive round table discussion Part of Drug Discovery Innovations 1 Exhibition 3 Conference Streams 1 Location Unlocking GPCRs with Antibodies Stefanie Urlinger, MorphoSys AG Impact of Biased Signalling on Drug Discovery Xavier Leroy, Actelion Pharmaceuticals Ltd Application of Structural Data in Drug Design Gerhard Hessler, Sanofi-Aventis Deutschland CONFERENCE CONFERENCE CONFERENCE Cell Based Assay Developments, Phenotypic Screening and Pioneering Technologies Advances in Target Based Drug Discovery- GPCRs and Epigenetics Novel Approaches to Drug Design and Lead Optimisation Event Partners: To register: +44 (0) 20 7017 7481 registrations@informa-ls.com

Agenda at a Glance PRE-CONFERENCE SYMPOSIUMS: 17 March 2014 Symposium A Practical Strategies for Developing 3D Cell Culture Assays and 3D Tissue Models for Use in Drug Discovery DAY ONE: 18 March 2014 KEY For attendees with a particular interest in the following areas please follow the highlighted streams below RED: GPCRs ORANGE: Epigenetics Symposium B Exploring New Chemical Space and Unlocking Non Druggable Targets Cell Based Assays, Phenotypic Screening and Pioneering Technologies Designing More Physiologically Relevant Cellular Assays for Complex Pathways and Implementation in HTS Programmes Designing More Physiologically Relevant Cellular Assays for Complex Pathways and Implementation in HTS Programmes Designing More Physiologically Relevant Cellular Assays for Complex Pathways and Implementation in HTS Programmes Obtaining Sources of Physiologically Relevant Cells in High Volume Converting Data Into Knowledge: Extracting Meaning from Complex Data Advances in Target Based Drug Discovery GPCRs and Epigenetics Evaluating and Selecting Targets for Drug Discovery Morning Coffee and Exhibition Viewing Understanding the Function and Mechanism of Action of Targets Networking Lunch and Exhibition Viewing Impact of Biased Signalling and Signalling Pathways on Drug Discovery Afternoon Tea and Speed Partnering Impact of Biased Signalling and Signalling Pathways on Drug Discovery End of Day One: Networking Drinks Reception Novel Approaches to Drug Design and Lead Optimisation Advancing Drug Discovery Using Biochemical and Structural Data Advancing Drug Discovery Using Biochemical and Structural Data Fragment Based Screening Novel Concepts in Lead Optimisation and Drug Design Evening Seminar, Discussion and Dinner: 18 March 2014 Establishing and Evaluating the Success of Collaboration Models and Open Innovation in Accelerating Early Stage Drug Discovery DAY TWO: 19 March 2014 Cell Based Assays, Phenotypic Screening and Pioneering Technologies Target De-Convolution: De-Convoluting the Target and Mechanism of Action from Phenotypic Screening Results Advances in Target Based Drug Discovery GPCRs and Epigenetics Application of Novel Screening Technologies and Assay Development for Target Classes Novel Approaches to Drug Design and Lead Optimisation Understanding and Utilising Receptor Binding Kinetics in Drug Design Increasing Throughput and Improving Cell Analysis Using Flow Cytometry Cell Based Assay Developments and Pioneering Technologies to Enhance Lead Identification, Cell Analysis and Validation Cell Based Assay Developments and Pioneering Technologies to Enhance Lead Identification, Cell Analysis and Validation Techniques to Improve In Vitro Target Validation Morning Coffee and Exhibition Viewing Application of Novel Screening Technologies and Assay Development for Target Classes Networking Lunch and Exhibition Viewing POST-CONFERENCE SYMPOSIUMS: 20 March 2014 Symposium C Natural Products- Application and Development in Drug Discovery Drug Discovery Innovations Key Logos: Employing New Techniques to Unlock Classical / Challenging Membrane Targets and Modulating Protein-Protein Interactions Afternoon Tea and Poster Competition Employing New Techniques to Unlock Classical / Challenging Membrane Targets and Modulating Protein-Protein Interactions End of Day Two Drug Discovery Case Histories: Recent Highlights in Discovery and Development of Novel Drug Products Applying the Knowledge of Epigenetic Pathways and Mechanisms of Action into Effective Drugs Translating the Results from Phenotypic Screens into Drug Products Symposium D Allosteric Modulators in Drug Discovery Keynote Presentation Interactive Roundtable Discussion Strategic Discussion Panel Collaborative Project Case Study 2 t: +44 (0) 20 7017 7481 f: +44 (0) 20 7017 7823 w:

DAY ONE: 18 March 2014 Advances in Target Based Drug Discovery GPCRs 08:20 Registration 08:55 Chairperson s Opening Remarks and Welcome Address DESIGNING NEW LIGANDS AND ADVANCING DRUG DISCOVERY USING BIOCHEMICAL AND STRUCTURAL DATA 09:00 Enabling GPCR Drug Discovery with Structural and Biophysical Studies For further details of this presentation please refer to the event website at Ali Jazayeri, Heptares Therapeutics Limited, UK 09:35 Towards a Better Description of Protein Ligand Interactions Current computer-based drug design allows the prediction of biological activity for the target of interest to a certain degree of accuracy. A key factor for successful application of computer-aided drug design is a meaningful description of the underlying physics of protein-ligand interactions. Scientific results of academic collaborations will be presented, which develop novel descriptions of proteins and ligands to improve the predictive capabilities of computational methods. Gerhard Hessler, Head of Computational Structural Drug Design, LGCR, Structure, Design & Informatics, Sanofi-Aventis Deutschland GmbH, Germany 10:10 GPCR Homology Modelling Resource to Determine Structure-Function Constraints The rapidly growing number of GPCR crystal structures demonstrates that apart from their close homology also distinct structural differences exist. We assigned these differing structural features to their underlying fingerprint motifs. In our updated multi-template approach for GPCR homology modelling, template selection is based on a fingerprint scoring strategy for each helix separately to reveal an optimal template for a given GPCR. Our database including the more accurate pre-calculation of 20500 GPCR models will be extremely helpful supporting analyses on ligand binding, receptor activation and G-protein- or beta-arrestin interactions. Gerd Krause, Head Structural Bioinformatics and Protein Design, Leibniz Institut für Molekulare Pharmakologie (FMP), Germany 10:45 Morning Coffee and Exhibition / Poster Viewing Time UNDERSTANDING THE FUNCTION AND MECHANISM OF ACTION OF TARGETS 11:15 Cell Surface Receptor Biosensors for Structural Dynamics Studies and High-Throughput Screening Cell surface receptors represent the vast majority of drug targets. Efforts have been conducted to develop biosensors reporting their conformational changes in living cells for pharmacological and functional analysis. Fluorescence resonance energy transfer (FRET) appeared as an ideal approach for such biosensors, but its use is limited by the very low signal to noise ratio. Here we report a toolbox composed of a combination of labelling technologies, specific fluorophores compatible with time-resolved FRET, and a new method to quantify signals that allows the development of receptor biosensors with large signal to noise ratio. We illustrate the usefulness of this toolbox through the development of GPCR biosensors, including all mglu, GABAB, LH, TSH, relaxin and PTH receptors, as well as RTK biosensors, including EGFR and InsulinR. Not only these biosensors can be used for high throughput screening but they also revealed new important information on the activation process of these receptor complexes in their cellular environment. Jean-Philippe Pin, CNRS Director of Research, Director of the Institute of Functional Genomics, France 11:50 Utility of Chemical Probes in Drug Discovery A major challenge in the development of novel therapeutics is to properly characterise the disease state of an individual animal at a given point in time in an ongoing pharmacological study and to assess efficacy of the examined therapeutic regimen in vivo. In this presentation exemplary approaches toward non-invasive monitoring of different disease states in will be discussed. Oliver Plettenburg, Head of Biosensors & Chemical Probes, Research & Translational Medicine, BD Diabetes, Sanofi, Germany UNDERSTANDING THE IMPACT OF BIASED SIGNALLING AND SIGNALLING PATHWAYS ON DRUG DISCOVERY 12:25 Spotlight Presentation Spotlight presentations are hosted by leading companies within the GPCR and Epigenetics field. These sessions offer an opportunity to learn about the latest developments and technologies within industry. For more information about hosting a spotlight session please contact: Linda Cole, Tel: +44 (0)20 7017 6631, Email: linda.cole@informa.com 13:00 Lunch and Exhibition / Poster Viewing Time 14:15 Biased Agonism of the AT1 Receptor: Perspectives in Drug Discovery? The Angiotensin II type 1 Receptor (AT1R) belongs to the family of seven trans-membrane (7TM) receptors, also referred to as G Protein Coupled Receptors. The AT1R is the primary effector of the renin-angiotensin system, and serves as a key regulator of cardiovascular physiology. The importance of the receptor is clearly illustrated by the frequent use of AT1R blockers and ACE inhibitors in cardiovascular medicine. Upon binding of Ang II the AT1R is signals through both G protein dependent and independent pathways. The G protein dependent pathways are well established and studied in detail whereas we know less about G protein independent pathways. Pharmacological targeted activation and blocking of the signalling cascades provides novel tools to increase the understanding of how these receptors exert their cellular functions and importantly it present a new clinical potential. This so-called biased agonism (or functional selectivity) has been studied extensively for the last decade and the focus is still increasing. In this talk I will introduce the concept of AT1R mediated biased agonism, discuss the underlying complexity of the AT1R signalling transduction networks and gene regulation and present the clinical potential of AT1R biased agonists. Jakob Lerche Hansen, Principal Scientist Diabetes Biology, Novo Nordisk A/S, Denmark 14:50 Detailed Analysis of GPCR Signal Transduction by Protein- Protein Interaction Studies For further details of this presentation please refer to the event website at Xavier Leroy, Project Promoter & Leader, Associate Director, Drug Discovery Dept., Actelion Pharmaceuticals Ltd, Switzerland 15:25 Afternoon Tea and Speed Partnering 16:05 BRET-based Biosensor Platform to Explore GPCR Signalling Complexity and Identify Biased Ligands GPCR Biased Ligands (BLs) consist in a family of molecules that can recruit, in a restricted way, specific signaling pathway(s). They represent a promising alternative approach for the development of safer GPCR drugs with reduced side effects. A novel platform of BRET-based biosensor assays was assembled enabling rapid BL s identification and characterisation. Stephan Schann, Head of Research, Domain Therapeutics, France 16:40 camp Measurements in GPCR Research Using Biosensors and Time-Resolved FRET camp is a major second messenger of G protein-coupled and thus important to measure in pharmacological experiments. In the talk, two novel high throughput camp assays will be presented, which both are based on Förster Resonance Energy Transfer (FRET). One is an endpoint assay based on timeresolved FRET and the other is a genetically encoded real-time assay based on Epac fused with two fluorescent proteins. Hans Bräuner-Osborne, Professor, University of Copenhagen, Denmark 17:15 Interactive Round Table Discussion: Delegates will split into groups and the following topics will be discussed amongst the group in this interactive practical session. Table One: GPCRs Understanding and Applying Knowledge of GPCR Functional Properties and Signalling Pathways in Drug Discovery Table Two: Epigenetics Techniques for Measuring Inhibition of Epigenetic Targets with Small Molecules 17:50 End of Day One followed by Drinks Reception in the Exhibition Hall t: +44 (0) 20 7017 7481 f: +44 (0) 20 7017 7823 w: 3

DAY TWO: 19 March 2014 Advances in Target Based Drug Discovery GPCRs 08:55 Chairperson s Opening Remarks 09:00 Development of Ligands at GPR40 and GPR120: Where Does this lie in Relation to Translation into Animal Models of Glucose Homeostasis and Diabetes For further details of this presentation please refer to the event website at Graeme Milligan, Professor of Molecular Pharmacology, University of Glasgow, UK 09:35 Discovery of Selective Ligands for the Trace Amine- Associated Receptor TAAR1 The Trace Amine-Associated Receptors are a discrete family of GPCRs, the subtype TAAR1 being involved in the modulation of biogenic amine activity in the brain. The structural similarity of TAAR1 to other aminergic receptors such as the adrenergic receptor superfamily has presented a challenge - but also an opportunity - in the discovery of novel, selective, drug-like TAAR1 ligands. Guido Galley, Principal Scientist, Pharma Research and Early Development, F. Hoffmann-La Roche AG, Switzerland APPLICATION OF NOVEL SCREENING TECHNOLOGIES AND ASSAY DEVELOPMENT FOR GPCRS 10:10 Interactive Round Table Discussion: Delegates will split into groups and the following topics will be discussed amongst the group in this interactive practical session. Table One: GPCRs: Use of more physiologically relevant cells type in assay developments for GPCR targets Application of label free technologies to target biological function, receptor activation and signalling pathways Multi-pathway screening technologies: Developing HTS multiplex assays to detect or exclude ligand biased signalling Designing screening assays to monitor biological pathways Studying dimerisation and beta arrestin pathways Relationships between signalling pathways and screening assays 10:45 Morning Coffee and Exhibition / Poster Viewing Time DRUG DISCOVERY CASE HISTORIES: RECENT HIGHLIGHTS IN THE DISCOVERY AND DEVELOPMENT OF NOVEL GPCR DRUG PRODUCTS 11:15 Novel Approaches to Target the FGF-FGFR-Heparan Sulphate Complex: Identification of Allosteric Antagonists and Oligosaccharides Agonists as Potential Novel Therapeutics The fibroblast growth factors (FGF s) / fibroblast growth factor receptors (FGFR s) signalling network plays an important role in cell growth, survival, differentiation and angiogenesis. FGFR s activation requires the presence of heparan sulphate chains functioning as a template to favor dimerisation and ultimately signalling when ligand binding. In the search of antagonists of FGFR s signalling, we have identified SSR128129E (SSR), which binds to the extracellular domain (ECD) of these receptors. SSR does not compete with FGF s for binding to FGFR s but inhibits some, but not all, FGF s-induced signalling pathways linked to FGFR s internalisation through an allosteric mode of action (MOA) as indicated by several biophysical techniques, molecular dynamics simulations, structure-activity relationship (SAR) analysis and FGFR s mutagenesis studies. This represents the first reported small molecule allosteric inhibitors of FGF s/fgfr s signalling, with potential advantages, that will be described, compared to inhibitors of their tyrosine kinase (TK) domains. Conversely, in the search of agonists of these ternary complexes, we have investigated fragments of heparan sulphate. Through rational design, we have identified a series of oligosaccharides optimised in terms of lengths, O-sulfation pattern, N-substitutions and variations of the aglycone. The first biological characterisations of these optimised heparan sulphate mimetics will be presented. Gilbert Lassalle, Section Leader, Medicinal Chemistry, Early to Candidate DPU, Sanofi R&D, Toulouse, France 11:50 Recent Advance of Class C GPCR Allosteric Modulators: From Hit to Clinical Candidates and Perspectives in Translational Science Allosteric modulator is an important class of drugs targeting major CNS and non CNS disorders, as well as orphan diseases with high unmet medical needs. Translational science is playing a major role in the drug discovery and development process of novel therapeutics. Recent progress in the field of glutamate receptor-based modulators will be presented, from HTS screen to clinical candidate selection phase for the treatment of neurodegenerative, autoimmune and psychiatric disorders. Sylvain Celanire, CNS R&D Professional, former Associate Director Medicinal Chemistry, Addex Therapeutics, Switzerland 12:25 Spotlight Presentation Spotlight presentations are hosted by leading companies within the GPCR and Epigenetics field. These sessions offer an opportunity to learn about the latest developments and technologies within industry. For more information about hosting a spotlight session please contact: Linda Cole, Tel: +44 (0)20 7017 6631, Email: linda.cole@informa.com 13:00 Lunch and Exhibition / Poster Viewing Time EMPLOYING NEW TECHNIQUES TO UNLOCK CLASSICAL / CHALLENGING MEMBRANE TARGETS AND MODULATING PROTEIN PROTEIN INTERACTIONS 14:15 Antibodies against Challenging Targets: How to Tackle G- Protein Coupled Receptors GPCRs comprise a huge class of proteins, many of which are considered relevant targets for drug discovery. Due to their membrane embedded structure only 25-30% of the protein is accessible for antibodies, making GPCRs notoriously difficult targets. We have generated fully human antibodies against GPCRs of therapeutic interest using phage display in combination with sophisticated antibody libraries, a broad range of selection methods and various antigen variants. Different strategies for successful antibody generation will be presented. Stefanie Urlinger, Director Discovery Alliances Technologies, MorphoSys AG, Germany 14:50 High-Throughput Discovery of Small Molecules Targeting Orphan GPCRs We have established a high-throughput technology that identifies small molecule agonists, antagonists and allosteric modulators for orphan GPCRs. Using this approach, we have discovered small molecules for 46 Class A orphan GPCRs. The small molecules we have identified are selective, chemically tractable and modulate receptor signalling and activity. Alexander Gragerov, Senior Director of Research, Omeros Corporation, USA 15:25 Afternoon Tea and Exhibition / Poster Competition 15:55 A Multifaceted Approach to Tackle High Value Intractables : The Reality of Modulating Protein-Protein Interactions Given the multitude of approaches and technologies that start to show promising results in identifying PPI modulators, targets will require holistic strategies to effectively deliver a range of starting points worth considering for lead generation. This will be exemplified by showing a multifaceted approach including fragment-based screening, encoded library technologies as well as cyclic peptides for delivering promising starting points. Stefan Geschwindner, Principal Scientist, Discovery Sciences, AstraZeneca R&D Mölndal, Sweden 16:30 Antibody-Guided Discovery of Small Molecule Protein- Protein-Interaction Inhibitors Protein-protein interactions can be readily modulated by antibodies but remain challenging targets for small molecules. Antibodies can constrain target proteins in biologically relevant conformations which enables initial binding of low affinity small-molecule fragments. Binding of optimised hits will eventually become independent of antibody constraint. Examples of structure-constrained proteins will be used to introduce the strategy of antibody-stabilised fragment screening at UCB. Wolfgang Fecke, Group Leader, Primary Pharmacology Department, UCB Pharma, UK 17:05 Closing Remarks from the Chair and End of Conference 4 t: +44 (0) 20 7017 7481 f: +44 (0) 20 7017 7823 w:

PRE-CONFERENCE SYMPOSIUMS: 17 March 2014 Registration: 10:00. Start: 10:30. End 16:30. Lunch, Morning and Afternoon Refreshments will be included. SYMPOSIUM A: Practical Strategies for Developing 3D Cell Culture Assays and 3D Tissue Models for Use in Drug Discovery For drug discovery, cell-based assays are getting increasingly complex in order to mimic more realistic biological processes and their diversifications in diseases. Multi-cellular co-cultures embedded in 3D matrices have been explored to more closely approximate the physiology of the human microenvironment. This multispeaker symposium will focus on overcoming the practical challenges of designing and screening with complex 3D cell culture assays in high throughput and high content screening platforms. Culture technologies and techniques for mimicking the culture in a well will be discussed as will the application of these technologies in drug discovery. The design of 3D tissue modelling systems will also be discussed as strategies for improving target identification and validation. How to mimic the disease state feasibly? - Setting up effective functional screens using 3D cell cultures - Assay design: How to adapt and develop 3D assays for HTS and HCS Evaluation of 3D matrix materials and reagents for establishing 3D cell cultures - Dealing with variations in matrix materials - Protocols for handing 3D matrix media in automated systems - Costs Transitioning from 2D to 3D assays - Integrating 3D cultures with traditional screening platforms Developing 3D tissue cultures - Strategies to grow 3D tumour-like spheroids and tissues in screening well Application of 3D assays to identify the target from phenotypic screening Benefits of 3D assays in drug discovery - Comparison between 2D and 3D assays and transfer to in vivo development - Are the results from 3D screens better than 2D results for in vitro screening? Case studies on the application of 3D cell culture assays drug discovery Symposium Leaders: Patrick Steigemann, Scientist, Bayer Pharma AG, Germany Laure Bouchez, Research Investigator II, Novartis, Switzerland Anthony Davies, Director, Irish National Center for High-Content Screening and Analysis (INCHA), Ireland Mike Atkinson, Director of Institute of Radiation Biology, Helmholtz Zentrum München and Chair of Radiation Biology, Technical University Munich, Germany For more information of this symposium please see the event website SYMPOSIUM B: Exploring New Chemical Space and Unlocking Non- Druggable Targets The ability to explore new chemical space is essential to establish new ways to prevent and treat disease and advance drug discovery. With the advancement in new technologies the potential to access previously non-druggable targets has been made possible. This multi-speaker symposium will focus on overcoming the practical challenges of exploring new chemical space, discuss the best ways to search for new small molecules and provide an overview on the development of tools and technologies to unlock previously non-druggable targets. Expanding the druggable genome Efficient sampling of chemical space Tools and technologies to identify novel target space Technologies to explore new chemical space and unlock and address difficult targets Use of historical biological assay data to efficiently sample bioactive chemical space New chemistries for non-drugable targets Chemical probes for target validation and pathway analysis Lead identification techniques for difficult to address targets Drug design strategies for less defined binding pockets Symposium Leaders: Anne Mai Wassermann, Presidential Postdoctoral Fellow, Novartis Institutes for Biomedical Research, USA For more information of this symposium please see the event website A state of the art overview with practical hints and discussion on the pros and cons of technologies and models University of Santiago de Compostela, Symposium Attendee 2013 EVENING SEMINAR, DISCUSSION AND DINNER: 18 March 2014 Registration: 18:35. Start: 18:45. End 20:30 A Networking Dinner will follow for all seminar attendees. Free to Attend with a 4 Day Pass Establishing and Evaluating the Success of Collaboration Models and Open Innovation in Accelerating Early Stage Drug Discovery This highly interactive evening seminar will address and provide real-life practical experience on the implementation of different collaboration models to advance early stage drug discovery. Perspectives from large / small pharma and academia will be presented in short 20 minute case study presentations with a key emphasis being placed on: How companies are tackling the major bottlenecks observed Evaluating the success of collaboration results from each approach Lessons learnt from experiences Case study presentations will be followed by an interactive discussion with the audience allowing the opportunity to share experiences of the impact of collaboration models on end results, strategies for translating drug discovery externalised projects to the next level and evaluating the impact and management of an ever changing R&D landscape on present and future collaborations. Establishing effective models for collaborations in early stage drug discovery Which models are best suited to different stages of drug discovery? Applicability of model to run alongside other models Minimising IP risks in collaborative research Can models be used to validate new targets and drug candidates? Do these models deliver? Open innovation: Are new targets and compounds being identified using these methods? EU-OPENSCREEN as a novel collaboration model Management: Establishing effective collaborations between pharma and academia - How to best work together to both benefit from collaboration - Meeting expectations and translating research into commercial products - External and internal alignment for successful collaborations Lessons learnt: Evaluating what s working and what s not working Adding value to pipelines: Translating project results and ideas into products - How and what will be taken forward into future alliances and translating into future medicines Seminar Leaders: Ulrich Betz, Director Department Head Innovation & Entrepreneurship Incubator, Global Business Development & Strategy, Merck Serono, Germany Stefan Jaroch, Head, External Innovation Technologies, Bayer, Germany Ronald Frank, Coordinator of EU-OPENSCREEN, Leibniz-Institut für Molekulare Pharmakologie (FMP), Germany Bert Klebl, CEO & CSO, Lead Discovery Center GmbH, Germany t: +44 (0) 20 7017 7481 f: +44 (0) 20 7017 7823 w: 5

POST-CONFERENCE SYMPOSIUMS: 20 March 2014 Registration: 08:30. Start: 09:00. End 15:00. Lunch, Morning and Afternoon Refreshments will be included. SYMPOSIUM C: Natural Products Application and Development in Drug Discovery Over the years, natural products have proved be to an important source of lead compounds and therapeutic agents for drug discovery; however the development of these leads into medicines has previously been hampered by the complex molecular architecture of natural products which impacts chemical tractability. Recent technological advancements have allowed the bioactive of natural products to be evaluated successfully re-establishing natural products as a major easy-to-use source in drug discovery programmes. This multi-speaker symposium will focus on the identification and development of natural product leads into drug discovery products. Natural product screening, target identification and assay development - Application of natural product libraries to identify new targets and chemical compounds for drug discovery - Overcoming the challenges in selecting new drugs from natural product libraries - Combining natural product collections with advanced cell based assays to identify new leads - Novel technologies in the discovery of natural products Understanding biological function with natural products - De-convoluting the target mechanism of action from natural product library screens - Probing biology with natural product fragments - Technologies to associate biological function with results - Translating chemical biology into human biology Natural products and synthetic biology - How can recent advances in synthetic biology help drive natural product research to facilitate drug discovery? Natural product lead optimisation and drug product development - Understanding chemistries and lead optimisation of natural products - Case studies on recent highlights in the discovery and development of natural drug products Symposium Leaders: Tim Schuhmann, Investigator III, Novartis Pharma AG, Switzerland Karl Gademann, Department of Chemistry, University of Basel, Switzerland Andrea Alimonti, ERC Investigator, Head Molecular Oncology, Institute of Oncology Research (IOR), Switzerland Armin Bauer, Head of Medicinal Chemistry II, R&D LGCR / Chemistry FF, Sanofi-Aventis Deutschland GmbH, Germany For more information of this symposium please see the event website SYMPOSIUM D: Allosteric Modulators in Drug Discovery For a receptor to illicit a response, the ligand does not have to bind to the ligand binding site. By certain factors binding to other sites on the receptor, this can cause a change in the downstream signalling of the receptor. By identifying these allosteric ligands it is possible to exploit them as a potential leads in drug discovery. However the identification and characterisation of allosteric modulators using standard assays and the translation into the clinic has proven challenging in drug discovery. This multi-speaker symposium will focus on novel tools to identify, validate and understand allosteric modulators and present latest developments on their translation into later stage drug discovery. Tools to identify and understand allosterism - Technologies and methodologies to identify, characterise allosteric modulators and understand allosterism - Characterising mechanisms of action and functionality of allosteric modulators - Adapting screening strategies to novel GPCR modulation paradigms Allosteric modulators lead optimisation and drug product development - Lead optimisation of allosteric modulators - Understanding chemistries - Novel approaches for allosteric modulators - Case studies on recent highlights in the discovery and development of allosteric drug products Overcoming the challenges in translating allosteric modulators into later stage drug development Proof of concept, in vivo effects of allosteric modulators Translating allosteric modulators into clinical trials Targeting allosteric modulators in drug discovery Translating knowledge from allosteric modulators for GPCRs to other target classes Symposium Leaders: Sylvain Celanire, PhD, CNS R&D Professional, former Associate Director Medicinal Chemistry, Addex Therapeutics, Switzerland Stephan Schann, Head, Research, Domain Therapeutics SA, France For more information of this symposium please see the event website Drug Discovery Innovations is doubtless a must-event! Director and Owner, Atheris Laboratories, 2013 Present a Poster at the Event or Submit a Paper to Win $500* Best Paper Award: Sponsored and judged by In recognition of the significant educational impact and value papers provide our attendees, the publishers at Computational and Structural Biotechnology Journal have created the 2014 Drug Discovery Innovations Best Paper Award. Computational and Structural Biotechnology Journal will be the forum for the publication of selected papers from the Drug Discovery Innovations Conference 2014. Participants presenting and attendees at DDI 2014 are encouraged to submit their work as full length manuscripts to Computational and Structural Biotechnology Journal. CSBJ will devote a special volume comprised of articles from the speakers/oral and poster presenters of the Drug Discovery Innovations Conference 2014. Among the paper submissions CSBJ will receive, the Editorial team will review and select an article from the full length manuscripts submitted to CSBJ by the participants/attendees of DDI 2014 for the Best Paper Award of $500* with the winning paper announced at the conference. To apply for the CSBJ Best Paper Award please see the event website for full details Present a Poster at the Event Posters submitted by academics, biopharmaceutical and pharmaceutical organisations will not be charged a fee Posters submitted by service providers/vendors are welcome and will be subject to evaluation by the scientific advisory board. Upon approval a fee of 399 + VAT will apply Last date for poster submission is Friday 21 February 2014 *See event website for full terms and conditions for paper submissions for CSBJ Best Paper Award 6 t: +44 (0) 20 7017 7481 f: +44 (0) 20 7017 7823 w:

18-19 March 2014 Hotel Palace Berlin, Berlin, Germany Drug Discovery Innovations 2014 - Sponsorship and Exhibition Opportunities WHY JOIN DRUG DISCOVERY INNOVATIONS 2014? Save time and money: Meet all your prospects in one location 3 conference streams delivering real data and facilitating the exchange of knowledge and ideas: Cell Based Assay Developments, Phenotypic Screening and Pioneering Technologies Advances in Target Based Drug Discovery Novel Approaches to Drug Design and Lead Optimisation Present your latest scientific developments or launch new technology products on the conference programme to the sectors most important decision-makers Build brand awareness amongst industry s best through an exhibition stand and extensive marketing opportunities that guarantee you achieve high visibility NEW for 2014: DDI Innovation Hub Contact us for more information on the flexible packages we can tailor-make for new clients and smaller organisations VITAL STATISTICS 130+ attendees 60+ industry speakers 100+ companies represented 10+ hours of dedicated networking 1 Exhibition 3 Conference Streams 1 Location For more information on the opportunities available please contact Linda Cole, Email: linda.cole@informa.com Tel: +44 (0) 20 7017 6631 A clear focus on enabling top scientific and industry leaders to connect and learn in an environment that fostered meaningful interactions. For my money, this is one of the best meetings of its kind VP Sales at Horizon Discovery 2014 Event Partners: 2013 AUDIENCE ANALYSIS 14% VP & C-Level 40% Heads & Managers 27% Senior Scientists & Researchers 19% Academia Attendee Job Title Breakdown Directors, Managers, Heads of Departments, Team Leaders, Investigators and Principal / Senior / Research Scientists from: Assay Development Chemical Biology Computational Chemistry Discovery Chemistry Drug Design Drug Discovery Epigenetics GPCRs In-Vitro Pharmacology Department Lead Identification / Discovery / Generation Lead Optimisation Medicinal Chemistry Molecular and Cellular Pharmacology Molecular Biology Oncology R&D Screening and Compound Profiling Structure Based Drug Design Target Identification and Validation The meeting was not only perfectly organised, it was also attended by a broad audience of high level decision makers, most of whom I had not met before. Drug Discovery Innovations" is a must-attend event! Director and Owner, Atheris Laboratories WAYS TO MEET PEOPLE - Utilise our networking and interactive activities to improve your conference experience Speed Partnering Joint Exhibitor and Delegate Lunch Sessions Drinks Reception Scientific Poster Session Exhibition Hall Round Table Discussions For more information on the opportunities available please contact Linda Cole Email: linda.cole@informa.com Tel: +44 (0)20 7017 6631 t: +44 (0) 20 7017 7481 f: +44 (0) 20 7017 7823 w: 7

INVESTMENT OPTIONS 5 EASY WAYS TO REGISTER +44 (0)20 7017 7481 +44 (0)20 7017 7823 Pre and Post-Conference Symposiums & Evening Seminar Monday 17 March - Pre- Conference Symposiums Application and Practical Strategies for Developing 3D Cell Culture Assays and 3D Tissue Models for Use in Drug Discovery A Exploring New Chemical Space and Unlocking Non Druggable Targets B 18-19 March 2014 Hotel Palace Berlin, Berlin, Germany registrations@informa-ls.com #DrugDiscovery @DDI2014 The Bookings Department Informa UK Ltd PO Box 406 Byfleet KT14 6WL Tuesday 18 March - Evening Seminar, Discussion and Dinner Establishing and Evaluating the Success of Collaboration Models and Open Innovation in Accelerating Early Stage Drug Discovery S CQ2260C Group Bookings: To take advantage of group bookings, please contact Natalie Crow on +44 (0) 20 33 77 3285 or email natalie.crow@informa.com Thursday 20 March - Post - Conference Symposiums Natural Products- Application and Development in Drug Discovery C Allosteric Modulators in Drug Discovery D STANDARD INDUSTRY RATES* Pass 2 Day Pass: Conference Only 2 Day Pass: Conference + Evening Seminar 3 Day Pass: Conference + Pre or Post Conf Workshop 3 Day Pass: Conference + Pre or Post Conf Workshop AND Evening Seminar FULL Pass: Conference + Pre AND Post Conf Workshop + FREE Evening Seminar Book BEFORE Dec 13th 2013 799 +19%VAT = 950.81 998 +19%VAT = 1187.62 1198 +19%VAT = 1425.62 1397 +19%VAT = 1662.43 1399+19%VAT = 1664.81 SAVE 500 Book BEFORE Feb 14th 2014 999 +19%VAT = 1188.81 1198 +19%VAT = 1425.62 1398 +19%VAT = 1663.62 1597 +19%VAT = 1900.43 1599+19%VAT = 1902.81 SAVE 200 200 200 200 400 Book AFTER Feb 14th 2014 1199 +19%VAT = 1426.81 1398 +19%VAT = 1663.62 1598 +19%VAT = 1901.62 1797 +19%VAT = 2138.43 1799+19%VAT = 2140.81 SAVE 100 100 100 100 SUPPLIER/ VENDOR RATES Book BEFORE Dec 13th 2013 1799 +19%VAT = 2140.81 1998 +19%VAT = 2377.62 2198 +19%VAT = 2615.62 2397 +19%VAT = 2852.43 2399+19%VAT = 2854.81 Book AFTER Dec 13th 2013 1899 +19%VAT = 2259.81 2098 +19%VAT = 2496.62 2298 +19%VAT = 2734.62 2497 +19%VAT = 2971.43 2499+19%VAT = 2973.81 NOTE: The VAT rate is subject to change and may differ from the advertised rate. The amount you are charged will be determined when your invoice is raised. *T&CS DISCOUNT PROMOTION: 1. Only applicable for the 2 main conference days and not available on add-on days. 2. Not applicable to supplier/vendor companies. Only available for biopharm and pharmaceutical companies. Informa Life Sciences will verify whether you are a vendor/supplier when your registration is processed. (Mr/Mrs/Ms/Miss/Dr) Family Name E-mail Tel Head of Department: E-mail Tel Booking Contact: E-mail Tel Name of Company/Department Fax Fax Fax 4. SME/Industry start ups only available to biopharm and pharmaceutical companies. 5. Discounts cannot be accumulated. SUBMIT A POSTER: FREE for Standard Industry, Academic, Start-Up and SME Delegates Supplier/Vendor 399 + VAT @ 20% DELEGATE DETAILS Please photocopy form for multiple bookings! To assist us with future correspondence, please supply the following details: Forename Job Title Any special requirements? Address Postcode To make payment by credit card: to ensure we provide the highest level of security for your credit card details we are unable to accept such payments via email or fax which ensures that these details are never stored on our network. To make payment by credit card on-line, please enter your credit card details in our secure payments website that you will use when making your booking via the event website (the event web address is near the top of the booking form). Alternatively call our customer service team on +44 (0) 20 7017 7481. Due to unforeseen circumstances, the programme may change and Informa reserves the right to alter the venue and/or speakers. Copyright Informa BV, 2013/2014 Terms and Conditions FEE: This includes all technical sessions, refreshments, lunch and access to speaker presentations that we have permission to make available. CANCELLATIONS: Cancellations received in writing before and on Monday 3rd March 2014 will be subject to a service charge of 99. The full conference fees remain payable after Monday 3rd March 2014. Substitutions are welcome at any time. It may be necessary for reasons beyond the control of the organiser to alter the content and timing of the programme or the identity of the speakers. In the unfortunate event that an event is cancelled Informa are not liable for any costs incurred by delegates in connection with their attendance. This contract is subject to English Law. ARE YOU REGISTERED?: You will always receive an acknowledgement of your booking. If you do not receive anything please call +44 (0)20 7017 7481 to make sure we have registered your booking. ANY SPECIAL REQUIREMENTS?: Please inform us if you have any special requirements by calling +44 (0)20 7017 7481 Tel DATA PROTECTION: The personal information shown on this form, and/or provided by you, will be held on a database and may be shared with other companies in the Informa Group in the UK and internationally. If you do not wish your details to be available to companies in the Informa Group please contact the Database Manager at Maple House, 149 Tottenham Court Road, London, W1T 7AD, Tel : +44 (0)20 7017 7077, Fax: +44 (0)20 7017 7828 or email: integrity@informa.com. Occasionally your details may be obtained from, or made available to, external companies who wish to communicate with you offers related to your business activities. If you do not wish to receive these offers, please tick the box. INCORRECT MAILING: If you are receiving multiple mailings or you would like us to change any details or remove your name from our database, please contact the Database Manager at the above address, Tel +44 (0)20 7017 7077, Fax +44 (0)20 7017 7828 or email: integrity@informa.com - quoting the reference number printed on the mailing label. City Country Fax Investment options for 2014: Academic Prices -Flat Rate 499* + VAT SME/industry Start ups - 50%* off the current price tier + VAT Customer VAT Number Nature of Company Business No. of employees on your site: 1) 0-49 2) 50-249 3) 250-499 4) 500-999 5) 1000+ VENUE DETAILS: Hotel Palace Berlin, Budapester Str. 45 10787 Berlin Tel.: +49 30 2502-0 Fax: +49 30 2502-1119 www.palace.de hotel@palace.de REDUCED RATE ACCOMMODATION: The cost of accommodation is not included in the conference fee. Please visit the event website, Accommodation tab for information on how to book reduced rate accommodation. Please book early to avoid disappointment. CONFERENCE DOCUMENTATION: CANNOT ATTEND? For those busy executives who cannot take full advantage of this event, the CD gives you a useful record of the presentations made at the event. The set of speakers papers and/or slides in CD format from the conference is available after the event for 499 + 20% VAT. UK VAT: The VAT rate is subject to change and may differ from the advertised rate. The amount you are charged will be determined when your invoice is raised. Contact Customer Services on tel: +44 (0) 20 7017 7481, fax +44 (0) 20 7017 7823 or e-mail: registrations@informa-ls.com