Monday, October 16

1:00 Chairperson’s Opening Comments
Louis A. Tartaglia, Ph.D., Senior Vice President and General Manager, Drug Repositioning & Selection, Gene Logic Inc.

1:10 Keynote Presentation Frank L. Douglas, Ph.D., M.D., Executive Director, MIT Center for Biomedical Innovation (CBI), Massachusetts Institute of Technology, former Executive Vice President of Aventis  • Challenging the business models and organization structure • Exploiting off-label uses; serendipity vs. strategy • Learn about biology from how drugs work in vivo • Developing new methodologies for indications discovery

 

	1:45 Finding New Applications for Canceled Development Candidates  Marcel van Duin, Ph.D., Executive Director and Head, Department of Pharmacology, NV Organon  Taking advantage of serendipitous findings and obser vations is, at least in part, an important element behind innovation in the pharmaceutical industry. Continued research efforts with development candidates (DC's) are the motor behind this process. Given that these DC's are only the tip of the iceberg in terms of the number of compounds synthesised by Pharma, but that failed somewhere in the process, it is indeed appealing to address the question of what could be discovered if also compounds that did not make it to the market would be subjected to the three R concept (Reprofiling, Repositioning and Repurposing). Strategies and efforts along these lines will be discussed.
	2:15 New Leads from Old Drugs: The SOSA Approach Prof. Camille Georges Wermuth, Faculty of Pharmacy, Louis Pasteur University, Strasbourg, and President and Chief Scientific Officer, Medicinal Chemistry, Prestwick Chemical  Selective optimization of side activities of drug molecules (the SOSA approach) is an intelligent and potentially more efficient strategy than HTS for the generation of new biological activities. Only a limited number of highly diverse drug molecules are screened, for which bioavailability and toxicity studies have already been performed and efficacy in humans has been confirmed. Once the screening has generated a hit it will be used as the starting point for a drug discovery program. Using traditional medicinal chemistry as well as parallel synthesis, the initial “side activity” is transformed into the "main activity" and, conversely, the initial "main activity" is significantly reduced or abolished. This strategy has a high probability of yielding safe, bioavailable, original, and patentable analogues.
2:45 Refreshment Break
	3:15 Casting Nets to Catch Hypotheses: Building an Infrastructure for Indications Discovery  Andrew L. Hopkins, Ph.D., Associate Research Fellow, Knowledge Discovery, Pfizer Global R&D  Drug discovery and development is commonly mod- eled as a linear pathway from idea to approval. Analysis of the source of ideas in drug discovery, however, shows the source of new drugs often comes from a network of ideas rather than a single inspiration. Serendipity plays a far larger role in drug discovery than acknowledged by the linear school of portfolio management. Therefore, it is a strategic question to ask, how can we engineer organisations to encourage serendipity? In this talk we will explore a range of experimental and informatics approaches that can be employed to engineer serendipity. The merits of methods from text mining for hypothesis generation to the in vivo screening of chemical tools will be discussed.
	3:45 Epistemic Drug Discovery: A New Way to Improve R&D Productivity Josep Prous, Jr., Ph.D., Executive Vice President, Prous Institute for Biomedical Research  Over the past decade, and despite major advances in new technologies, the pharmaceutical sector has witnessed  how the number of new drugs introduced in the market every year has stayed level or decreased while the cost of drug discovery and development has doubled. The safety of drugs used in clinical practice is under constant scrutiny and the withdrawal of several compounds in recent years confirms the serious productivity challenges faced by modern biomedical research. A knowledge-based project was initiated to overcome these productivity bottlenecks and to contribute to the faster discovery of new and safer drugs, as well as the finding of new uses for known molecules. In-house developed datamining algorithms have led to a model thatcharacterizes 300 different molecular mechanisms of action simultaneously. Millions of molecules are being used to develop the project. Models have been built that discriminate between active and inactive compounds for specific pharmacological activities, and to differentiate drug from non-drug compounds. Quantitative models for experimental pharmacology parameter determination have also been developed. Importantly, ADMET properties can be traced with the system with a high degree of accuracy. The development and application in explaining antipsychotic therapy-induced diabetes and the finding of new therapeutic applications for angiotensin AT1 antagonists will be presented.
	4:15 Repositioning in the Public Sector Dr. Bryan Roth , Professor, Department of Pharmacology, University of North Carolina, Chapel Hill  With the annotation of the human genome approaching completion, public-sector researchers - spurred in part by various National Institutes of Health Roadmap Initiatives - have become increasingly engaged in drug discovery and development efforts. Although large and diverse chemical libraries of 'drug-like' compounds can be readily screened to yield chemically novel scaffolds, transforming these 'chemical probes' into drugs is a daunting endeavour. A more efficient approach involves screening libraries of approved and off-patent medications; both phenotypic- and molecular target-based screening of 'old drugs' can readily yield compounds that could be immediately used in clinical trials. Using case studies, we describe how this approach has rapidly identified candidate medications suitable for clinical trials in disorders such as progressive multifocal leukoencephalopathy and amyotrophic lateral sclerosis. This approach has also led to the discovery of the molecular targets responsible for serious drug side effects, thereby allowing efficient 'counter-screening' to avoid these side effects.

4:45 Discussion with Speakers: Focusing on Failure • How to manage risk and turn failures into success stories • How you can best take advantage of techniques available • Which approach or combination of approaches or technologies is best? Moderator: Malorye Branca, Editor in Chief & VP Pharmaceutical Discovery, Pharmaceutical Discovery, Cambridge Healthtech Institute

5:15 Reception Sponsored by

6:30 Close of Day One