Pharma IQ presents Europe’s dedicated forum for fast, effective & integrated lead discovery Save up to £200 by booking early (see back page) HIT-HIT-TOTO-LEAD-LEAD Enhancing lead generation to accelerate quality compounds into lead optimisation Conference: 18th & 19th July 2005 • Masterclass: 20th July 2005 Detailed case studies will be Café Royal, London, UK presented by: Discover the hit-to-lead successes and failures experienced by Pfizer leading pharma companies to understand how you can improve Roche decision-making and generate better quality leads faster. Wyeth ➨ Explore proven and creative hit-to-lead strategies and key criteria to increase the speed and efficiency of your drug discovery processes AstraZeneca ➨ Enhance the quality of validated hits to improve the prioritisation and Bayer Healthcare selection of hit and lead series Merck KGaA ➨ Analyse DMPK data effectively to optimise properties at an early stage and to drive and prioritise hit-to-lead projects University of Sheffield ➨ Optimise ligand-based and structure-based approaches to virtual Sanofi-Aventis screening to aid lead identification and assessment ➨ Apply chemogenomics to enhance all stages of early drug discovery Tripos ➨ Improve the design and quality of hit-to-lead libraries to speed the University of generation and optimisation of lead series Heidelberg ➨ Ensure research efforts are focussed only on the most promising compounds to increase the number of successful candidates in your Novartis development pipeline Inpharmatica Don’t miss the interactive masterclass on 20th July GPC-Biotech Chemogenomics in Drug Discovery Led by Professor Hugo Kubinyi IMIM Media Partners “Excellent networking opportunities, Johnson & Johnson very interesting presentations.” Vincent Mikol, Sanofi-Aventis Array Biopharma +44 (0)20 7368 9300 +44 (0)20 7368 9301 www.iqpc-pharma.com/2484a UK Freephone: 0800 652 2363 [email protected] to-lead. It will discuss how high quality materials are provided to improve the DAY ONE: 18th July 2005 speed and quality of the process, and in particular will discuss: • Optimising hit finding and generation 08:30 Coffee and registration • Exploring the best approaches and technologies for screening • Providing excellent starting points for hit-to-lead 09:00 Pharma IQ welcome Martin Klumpp, Lab Head, Assay Development & Screening, Novartis 09:10 Opening remarks and presentation from the Chair: 15:00 Enhancing hit quality and diversity from HTS through evolving Search for new leads - from serendipity to design hit selection schemes The pharmaceutical industry is short of new drugs. As only a few lead structures The HTS process at Wyeth is currently undergoing considerable change, and the can be optimised to clinical candidates and many such projects fail in the process by which project teams select from the hits generated by HTS is clinics, there is an urgent need for new leads. This presentation will discuss and evolving to keep pace. The consistent focus has been on enhancing the quality explore the following lead sources and strategies: (in terms of 'lead-likeness') and diversity (in terms of chemical scaffolds, • Plant and microbial natural products fingerprints, etc) of the selected hits. After secondary screening and further • Serendipitous and rational approaches filtering, this approach aims to provide the team with the best possible • Chiral and metabolic switch selection of candidates for the lead optimisation phase of the project. The • Combinatorial chemistry various methods of hit selection and filtering that have been employed and the • Virtual screening evolution of the process will be presented, exemplified by results from several • Structure-based, computer-aided and fragment-based design recent and representative projects at Wyeth. Hugo Kubinyi, Professor of Pharmaceutical Chemistry, Iain McFadyen, Senior Research Scientist II, Chemistry and Screening Sciences, University of Heidelberg, and formerly BASF Wyeth 10:00 The hit-to-lead process at Bayer Healthcare 15:45 Coffee In the hit selection process, the understanding of compound liabilities needs to be ensured as early as possible in order to identify leads with the minimum 16:15 Application and benefits of knowledge-driven chemistry number of liabilities. This presentation will explore the key requirements and Tripos Discovery Research employs knowledge-driven informatics processes to features of Bayer’s hit-to-lead process, and will discuss two case studies in computationally assess every compound it makes for biological relevance and Cancer and Thrombosis. The session will consider: synthetic feasibility. These proven technologies have enabled Tripos to reduce its • In silico parameters customers' lead identification and optimisation timelines by up to 30%. Case • In vitro high throughput screening data studies will be presented that support this approach to lead identification and • Physicochemical and ADMET data the development of follow-up compound libraries. Berthold Hinzen, Director of Medicinal Chemistry, Dr. Mark Allen, Senior Vice President, Discovery Research and Managing Bayer Healthcare Director, Tripos Discovery Research, Ltd. 10:45 Coffee 17:00 Lead discovery at Roche Palo Alto This presentation will focus on the development approaches that are being 11:15 Hit identification and validation to speed hit-to-lead implemented in Roche to enhance the cross-functional process of lead High throughput screening and other hit generation techniques usually result in discovery. Multiple approaches for novel lead finding and tools to assess the huge numbers of actives being identified. Over the last couple of years, Merck hits identified will be described. Examples of the application of these tools will KGaA has implemented various processes and tools that allow a better also be discussed. characterisation of HTS hits by experimental and calculated data. Tools were Michael Dillon, Director, Medicinal Chemistry, also developed that help display those characteristics in a convenient fashion. Roche Palo Alto This session will discuss: • Improvements that have been implemented in high throughput screening 17:45 Chair’s summary and close of day one • What data is being used for the characterisation of hits • How the data is provided to help prioritisation of hit and lead series Michael Arlt, Department Manager, Global Medicinal Chemistry Lead Finding, Merck KGaA DAY TWO: 19th July 2005 12:00 Optimising DMPK properties in hit-to-lead – an AstraZeneca 08:30 Coffee and registration perspective DMPK properties are being assessed much earlier in drug discovery now to 09:00 Chair’s welcome avoid complications in lead optimisation. In this session, AstraZeneca will Iain McFadyen, Senior Research Scientist II, Chemistry and Screening Sciences, review their approach and show how early DMPK analysis has influenced Wyeth projects downstream. • Optimising compounds using experimental and computational tools 09:15 Optimising ligand-based approaches to virtual screening • Using DMPK data to drive hit-to-lead projects Given an initial hit, similarity searching provides a simple way of prioritising • Safety considerations: reactive metabolites etc compounds in a corporate or public database for biological testing, and thus of Richard Weaver, Team Leader, DMPK Research, Physical and Metabolic Sciences, identifying potential new leads. This session will describe recent work that AstraZeneca provides effective tools for fingerprint-based virtual screening. • Conventional approaches to similarity-based virtual screening 12:45 Enhancing profiling strategies: Compound prioritisation and • Use of nearest neighbour information to increase search effectiveness optimisation • Combination of similarity searches when several hits are available Inpharmatica has developed an interactive and visually engaging interface, Peter Willett, Head, Department of Information Studies, Admensa InteractiveTM, which allows scientists to select compounds with the University of Sheffield best overall balance of properties and potential for success. The interface also includes a predictive ADME modelling suite, the results of which can be 10:00 Identifying and assessing potential leads through structure- incorporated with any in vitro and in vivo measurements (such as potency and based virtual screening selectivity) in a unique prioritisation suite. This presentation will give a brief Structure-based virtual screening has become an important tool in the hit-to- overview of Admensa InteractiveTM and will share a number of case studies lead process. This session will explore how this technique can be applied in demonstrating its applicability in the hit-to-lead stages of drug discovery. order to aid lead generation and assessment. Joelle Gola, Computational Chemist, ADME modelling, • Generating plausible hypotheses for molecular recognition (pose prediction) Inpharmatica • Rank-ordering potential lead series (affinity prediction) • Generating and assessing potential leads (fragment screening) 13:15 Networking lunch Romano Kroemer, Head of Drug Design, Sanofi-Aventis 14:15 Generating high quality candidates for effective hit-to-lead This presentation will explore how Novartis uses HTS to effectively support hit- 10:45 Coffee +44 (0)20 7368 9300 +44 (0)20 7368 9301 www.iqpc-pharma.com/2484a UK Freephone: 0800 652 2363 [email protected] 11:15 Lead-hopping via structure-based drug design 16:15 2nd generation kinase inhibitors In order to increase the chances of success against a given target, it is a great • Small