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Immediately following "The Impact of Genomics on Medicine," May 21-22, 2001, Bayerischer Hof, Munich, Germany
Corporate Sponsors
Corporate Support
Sponsoring Publications
Drug Discovery Today
Trends in Molecular Medicine
Pharmacogenomics
Trends in BiotechnologyPharmacogenomics is widely touted as the chief lady in waiting to the Human Genome Project. Clinical results are gathering to provide evidence that this is not just hype. Recently a biotech company discovered four genes whose haplotypes, when combined in a multigene model, resulted in a genetic profile of each drug's effectiveness. The ability to predict a drug response will have a substantial impact on drug marketing practices and may lead to a shakeup of the industry on a general scale. This leads us to question whether "Mass Customization" is a dream come true or a bitter pill for pharmaceutical companies to swallow. As a sidebar to this exciting moment, we should also note that North America came out ahead in the race to map our genes-but is Europe poised to take the lead with more direct biological implementation of disease etiology and protein function?
Session Chairs
Dr. Jörg Hoheisel, Deutsches Krebsforschungszentrum
Dr. Sebastian Meier-Ewert, GPC Biotech
Dr. Kevin Park, University of Liverpool
Dr. Frank Sistare, U.S. Food and Drug AdministrationAdditional Speakers
Dr. Jürgen Borlak, Fraunhofer Institut fuerToxikologie und Aerosolforschung
Dr. Gunnar Brink, Nanotype GmbH
Dr. Ulrich Brinkmann, Epidauros Biotechnologie, AG
Dr. Alan Chan, PamGene B.V.
Dr. Ann Daly, University of Newcastle
Dr. Huw Davies, Ciphergen Biosystems Ltd.
Dr. Fawad Faruqi, Molecular Staging Inc.
Dr. Mike Furness, Incyte Genomics Inc.
Dr. Patrick Hess, Quest Diagnostics, Nichols Institute
Dr. Gordon Holt, Oxford Glycosciences
Dr. Alan Houston, Variagenics Inc.
Dr. Francis Kalush, Celera Genomics
Dr. Ruth March, AstraZeneca
Dr. Michael Shi, Genometrix Inc.
Dr. Jason Simon, Schering-Plough Corporation
Dr. Collin Spraggs, GlaxoSmithKline Pharmaceuticals, Inc.
Dr. Sean Tavtigian, Myriad Genetics
Dr. Marie-Charlotte von Brevern, BASF-LYNX Bioscience AG
Dr. Klaus Wilgenbus, Boehringer Ingelheim R&D Austria
Dr. Alfred Zimmerlin, Novartis Pharmaceuticals Inc.SNPs and Genotyping
Find SNPs More Sensitively Along with False-Positive Binding Events
Less Biased Analysis Using PNA Arrays
The Human Reference SNP Database
RCA Technology for SNP Detection
Model Region for Pharmacogenomic Profiling
Genotyping for Clinical Trials and Post-market Monitoring of Drug Efficacy and ToxicityToxicology and Mode of Action
Discovery and Validation of Potential Diagnostic Biomarkers of Drug Toxicity
Type A and Type B Adverse Drug Reaction Prediction
Core Set of "Reference" Compounds of Known Efficacy and Toxicity
Database of Drug-Specific Fingerprints for Ranking Compounds
CYP2C9 SNP Predictive Analysis
Expression Analysis and Drug ActionTarget driven Pharmacogenomics
Genetic Variability of Drug Targets
Drug Transporter Polymorphisms
Target Prioritization
Pharmacogenomic Discovery, Characterization, and Delivery
In Silico DesignDrug Development
Drug Discovery and Development in the Era of Pharmacogenetics
Pharmacogenomics and the FDA
Lead Compounds Immune to Target-Related Pharmacogenetic Efficacy Issues
P450s and Integrated Risk Assessment
European Clinical Trial Design
Patient Identification and Patient Screening
Tuesday, May 22
18:00-20:00 Early Registration and Poster and Exhibit Set-up
Wednesday, May 23
7:00 Registration, Poster and Exhibit Viewing, and Light Continental Breakfast
SNPs and Genotyping
8:30 Chair's Opening Remarks
Dr. Jörg Hoheisel, Head, Functional Genome Analysis, Deutsches Krebsforschungszentrum8:35 Improved Readout of DNA- and Protein-Chips through High-Throughput Single Molecular (un)Binding-Force Detection
Dr. Gunnar Brink, Principal Scientist, Nanotype GmbHIn binding assays the equilibrium amount of bound molecules is detected and used to determine concentration or the presence of a molecule in the sample. Driving agent is the binding energy between two molecules, e.g., the protein-protein interaction energy or the nucleic acid base-pair binding energy. In contrast to all these equilibrium energy-based assays, nanotype's proprietary technology uses another aspect of the binding strength, the (un)binding forces. Since an independent parameter becomes accessible, molecular force assays can improve almost all existing assays or be the basis for completely new ones with additional information (e.g., determination of off-rates or of geometric effects). The presentation will introduce nanotype's parallel high-throughput technology and the design of chip-based assays formats and will show applications in genotyping and proteomics.
9:05 PNA-Arrays: Merging a Wide Range of Analyses
Dr. Jörg Hoheisel
PNA is a DNA derivative that exhibits various advantages compared to DNA because of its chemical composition. These features allow for superior, eventually less biased analyses across a wide range of chip applications—from genotyping to epigenetic measurements.9:35 Celera Human Reference SNP Map with 2.8 Million High-Quality Markers
Dr. Francis Kalush, Medical Affairs Department, Celera Genomics
This database is fully integrated with external public SNP databases that include Human Gene Mutation Database (HGMD) and dbSNP (with data from the SNP Consortium), providing the most comprehensive resource available for human variation studies. Redundancies across internal data and multiple external databases are resolved while the complementary information is extracted and maintained. Analysis of Celera SNP density shows that 95% of the contigs have a density range of 0.5 to 1.5 SNPs per KB. All internal and external SNPs are mapped to the Celera Reference Genome to a base pair resolution. A total of 31,406 cSNPs, including 12,000 markers from HGMD, are identified by mapping DNA variations to 9,627 RefSeq mRNA sequences. A total of 9,001 cSNPs, including 4,043 nonsynonymous cSNPs, are found in the Celera data. The human reference SNP database is the first product of Celera's pharmacogenomics module, and information related to polymorphisms—including allele frequency, population, quality classes, gene structure, protein changes, chromosomal locations, and disease associations—can be accessed via the web-based Celera Discovery System with its comprehensive queries and database search capabilities.10:05 Poster and Exhibit Viewing, Refreshment Break
10:45 RCA Technology for SNP Detection
11:15 HLA Genotyping on Microarrays as a Model for Pharmacogenomic Profiling
Dr. Fawad Faruqi, Senior Scientist, Molecular Staging Inc
We describe a solution-based, microplate method for SNP genotyping of human genomic DNA based upon padlock probes, RCA, and generic fluorescence resonance energy transfer (FRET) probes. This method was used to develop robust genotyping assays for 10 SNPs, and genotype 96 patient DNA samples for 10 SNPs with >90% accuracy. Given compatibility with homogeneous formats, and requirement for only 1ng of genomic DNA, padlock ligation / RCA appears to meet the exacting requirements of very high-throughput SNP scoring studies.
Dr. Alan Chan, Vice President, Application Development, PamGene B.V.
The human leukocyte antigen (HLA) genes on chromosome six represent the most polymorphic region of the entire human genome. Since HLA genotyping has already been established, with various molecular methods in place for matching donors to recipients during tissue transplantation, this hypervariable region serves as an ideal model for pharmacogenomic profiling in other gene regions. Data will be presented of a feasibility study that we have undertaken to extend the capabilities of HLA genotyping using our post-genomic flow-through microarray system for molecular typing of the DRB locus.11:45 Applying SNP Genotyping in Drug Development and Clinical Trials
Dr. Michael Shi, Senior Director, Applied Genomics, Genometrix Inc.Functional SNPs could be identified by analyzing patients' genotypes and drug response phenotypes. When applied to clinical trials, these data could help to explain if the trials are adequate and offer the potential for more efficacious and safer drug use in subpopulations of patients based on their genetic makeup. High-throughput SNP genotyping has been applied in drug development, assisting clinical trials, and post-market monitoring of drug efficacy and toxicity: (1) functional SNP identification and validation, (2) application of high-throughput genotyping in clinical trials, (3) clinical trial design based on SNP markers, (4) drug development decision making based on SNP information, and (5) clinical utility of SNPs for predicating drug efficacy and toxicity.
12:15 Panel Discussion
12:45 Lunch in the Exhibit Hall (sponsored by Cambridge Healthtech Institute)
Toxicology and Mode of Action
14:00 Chair's Remarks
Prof. Kevin Park, University of Liverpool14:05 ProteinChip® Technology in Preclinical Drug Safety Assessment
Dr. Huw Davies, UK Program Manager, Ciphergen Biosystems Ltd.
The ProteinChip® System from Ciphergen Biosystems uses patented SELDI™ (Surface Enhanced Laser Desoption/Ionization) ProteinChip technology to perform the separation, mass detection and analysis of proteins at the femtomole level directly from biological samples. The technology has been widely implemented by safety assessment groups of major pharmaceutical companies looking for novel protein biomarkers of drug toxicity. The speed of the technique means that a single user can screen literally hundreds of samples in a matter of days. Consequently, novel candidate biomarkers can be validated on the same platform by demonstrating a clear correlation between protein abundance and a biological or chemical perturbation. A number of applications of ProteinChip technology will be presented describing novel experimental approaches to investigate differential protein expression. Examples will include case studies showing the rapid discovery, validation, and identification of potential diagnostic biomarkers of drug toxicity. Methodologies for biomarker discovery using ProteinChip protein profiling and strategies for the identification of validated markers will be described.14:35 Toxicogenetics in Drug Development
Prof. Kevin Park
The major progress made in the understanding of the genetic basis of inter-individual variation in drug response, alongside the rapid advances in technology, provides major new opportunities to ensure the introduction of a new chemical entity into clinical practice. How such approaches can be used to predict type A and type B adverse drug reactions will be discussed.15:05 Analysis of Gene and Protein Expression for Drug Mode of Action and Mode of Toxicity
Dr. Mike Furness, Director, Pharmacogenomics, Incyte Genomics Inc.
The creation of an expression database containing both genomic and proteomic expression data will allow a much deeper analysis of toxicity and mode of action of drugs. By building a core set of "reference" compounds of known efficacy and toxicity, we are creating a reference data set that will identify key markers of drug action and/or toxicity to allow rapid screening of new drug candidates.15:35 Poster and Exhibit Viewing, Refreshment Break
16:15 Transcriptomics and Its Application in Predictive Toxicology
Dr. Marie-Charlotte von Brevern, BASF-LYNX Bioscience AG
We are performing an "in-depth" approach for predictive toxicology based on multidimensional sample material and complementary transcription profiling technologies (open and closed systems). Using the discovery technologies MPSS® and Megasort™ we identified novel marker genes that were subsequently used in hybridization experiments to classify sets of compounds including tumor promoters and hepatotoxicants. Our growing database of drug-specific fingerprints serves for ranking compounds.16:45 Relevance of CYP2C9 SNP Analysis to Prediction of Individual Anticoagulant Dose Requirement and Susceptibility to Adverse Drug Reaction
Dr. Ann Daly, Department of Pharmacological Sciences, University of Newcastle
General aspects of CYP2C9 polymorphisms including functional significance deal more specifically with the relationship between dose requirement for warfarin and other anticoagulants and CYP2C9 genotype. The general role of CYP2C9 genotype in determining susceptibility to other adverse drug reactions would also be discussed.17:15 Genomic Tools for Mode of Action Analysis in Drug Discovery
Dr. Sebastian Meier-Ewert, Vice President & Head of Research, GPC Biotech
Recently, the use of gene expression analysis has emerged as a powerful approach to associating drug or compound action with a measurable biological readout. The approach is to measure complex patterns of gene expression changes that are highly specific to the exact molecular action of a compound. Such complex expression patterns can be used for drug discovery in a number of ways including the assessment of drug specificity and mode of action analyses. In order to perform such analyses it has been necessary to (i) set up a robust work-flow-process with capacity of hybridization up to 100 arrays, each containing up to 13,000 genes, per day; (ii) introduce visualization tools for QC of data; (iii) implement data analysis algorithms for pattern recognition and gene-gene correlations. These developments will be presented together with data from a number of evaluations of this approach in both whole bacterial ORFs (H.pylori and B.subtilis) and mammalian cDNA (human, mouse and rat) systems.17:45 Panel Discussion
18:15 Martinsried Biotech Incubator Facility Tour hosted by Bavarian Ministry of Economic Affairs, Transport and Technology
Thursday, May 24
8:00 Poster and Exhibit Viewing and Light Continental Breakfast
Target Driven Pharmacogenomics
8:30 Chair's Remarks
Dr. Sebastian Meier-Ewert, GPC Biotech8:35 Pharmacogenomics in Early Drug Development: Characterizing SNPs and Haplotypes in Drug Target Genes
Dr. Alan Houston, Chief Medical Officer, Variagenics Inc.
Screening methods for identifying lead compounds do not currently take into account variability in the genes encoding drug targets. This may lead to the selection of compounds active against only one genetic form of the target. To avoid this, a thorough understanding of the genetic variability of drug target genes is essential. Since it is the haplotype, or combination of single-nucleotide polymorphisms (SNPs), that ultimately determines the properties of a drug target, the haplotypes found commonly in the population for a target must be defined. This is especially important in the lead optimization process, as characterization of drug target haplotypes allows assessment of lead compound activity against all of the versions of the drug target expected in the population. In the future, we predict that genetic variability data will be integrated into high-throughput screen design, to ensure development of only compounds active against the entire genetic spectrum of a drug target.9:05 Polymorphisms of the Drug Transporter MDR1 and Cyp3A Enzymes
Dr. Ulrich Brinkmann, Vice President, Pharmacogenetics, Epidauros Biotechnologie, AG
Blood levels and consequently effectivity and side effects of drugs are dependent on drug uptake and metabolism. Therefore, functional polymorphisms in genes encoding transporters and hepatic enzymes influence the blood levels and the activity of medications. This presentation describes the identification and characterization of functional polymorphisms in human drug transporter (MDR1) and drug metabolizing (Cyp3A) enzymes.9:35 Early Application of Pharmacogenomics for Target Prioritization
Dr. Klaus Wilgenbus, Boehringer Ingelheim R&D Austria
Summary unavailable at time of printing.10:05 Poster and Exhibit Viewing, Refreshment Break
10:45 Pharmacogenomic Discovery, Characterization, and Delivery
Dr. Susanne Wagner, Senior Scientist, Myriad Genetics, Inc.
We have identified four gene categories in which we are targeting our variant discovery efforts: (1) ADME, (2) Pharmacologic targets and the immediate biochemical pathways in which those targets function, (3) The panoply of hormone signalling pathways, and (4) Disease-specific pathways not covered in the preceeding 3 gene categories. Variants will be characterized through two complementary strategies: case-control association studies on disease specific sample sets we have built during our seven-years of positional cloning projects, and a massive Utah population-based study. We envision a series a genotyping based products. These will include products aimed at characterization and stratification of pharmaceutical company clinical trials, and consumer market products directed at both disease susceptibility prediction and drug efficacy prediction.11:15 Structural Pharmacogenomics: Designing New and Better Drugs against HIV-1 Protease
Dr. Patrick Hess, Director, Biotechnology Affairs, Quest Diagnostics, Nichols Institute
Recent developments in molecular modeling computational biology to become an integral part of drug discovery and development will be discussed. Utilizing a computational operating system capable of generating highly precise 3-D protein models solely from DNA sequence from anonymized patient viral genotypes, we have developed a database consisting of thousands of structurally variant HIV-1 protease and reverse transcriptase. This information is then used to determine the ability of clinically mutated forms of the proteins to bind antiviral drugs in silico. This is a structural pharmacogenomic approach to designing new, more efficacious drugs prior to long and expensive clinical trials.11:45 Genotyping in Clinical Trials.
Dr. Jürgen Borlak, Professor (visiting) and, Head of Center for Drug Research and Medical Biotechnology, Fraunhofer Institut fuer Toxikologie und Aerosolforschung
Certain genetic polymorphisms of drug metabolising enzymes greatly impact the pharmacokinetics of drugs and are responsible for significant variability in systemic drug levels. This change in drug pharmacokinetics is usually linked to an impaired drug clearance, although ultrarapid metabolism may also occur. Drug accumulation leads to adverse drug reactions (ADRs) and may happen very rapidly, particularly if the therapeutic window of a drug is narrow. ADRs rank between the 4th and 6th leading causes of death in the USA and single-nucleotide polymorphisms (SNPs) of drug-metabolizing enzymes (DME) are causally related to ADRs. Indeed, Lazarou et al. (1998) found that the incidence of serious and fatal adverse drug reactions in US hospitals were extremely high and as much as 2.216000 cases alone were reported for 1994 of with 106000 ADRs were fatal.12:15 Panel Discussion
12:45 Lunch in the Exhibit Hall (sponsored by Cambridge Healthtech Institute)
Drug Development
14:15 Chair's Remarks
Dr. Frank Sistare, Director, Division of Applied Pharmacology Research, U.S. Food and Drug Administration14:20 Drug Discovery and Development in the Era of Pharmacogenetics
Dr. Collin Spraggs,Therapeutic Advisor, Drug Development Genetics, GlaxoSmithKline Pharmaceuticals, Inc.
Medicines have significantly improved quality of life worldwide. However, not all patients respond to their prescribed drugs and some experience limiting side effects. Pharmacogenetics is the study of variability in drug response (efficacy and side effects) due to heredity factors in patient populations and offers novel opportunities to improve the benefit-risk ratio of medicines. This talk will illustrate opportunities both in drug discovery and development to achieve this and deliver the Right Medicine to the Right Patient.14:50 Pharmacogenomics and the FDA: New Initiatives and Strategies
Dr. Frank Sistare (tentative)
Summary unavailable at time of printing.15:20 Preclinical Pharmacogenomics for Optimized Lead Compound Identification
Dr. Jason Simon, Principal Investigator, Human Genomic Research, Schering-Plough Corporation
A preclinical program has been established to comprehensively screen Schering-Plough Research Institute drug target candidate genes for DNA sequence polymorphisms. The goal of this program is to identify common cSNPs in drug target genes prior to identification of lead compounds. This strategy will allow for the identification of lead compounds immune to target-related pharmacogenetic efficacy problems.15:50 Poster and Exhibit Viewing, Refreshment Break
16:30 Predictions from (in Vitro) P450 Screening Data for Product Decision Making
Dr. Alfred Zimmerlin, Novartis Pharmaceuticals Inc.
Developping "ideal" drugs supposes that the specific problems linked to the P450 enzymes and their high human variability are investigated early enough to make adequate decisions. A number of high throughput in vitro tools are available to screen for P450 polymorphism, clearance, inhibition and induction. To predict clinical relevance it is however crucial to validate and integrate these results. Finally, beyond the experimental, the key to success is an integrated risk assessment using a matrix of data including those from in vitro assays and pharmacogenomics.17:00 Pharmacogenetics within European Clinical Trials
Dr. Ruth March, Project Manager, R&D Genetics Department, AstraZeneca
At AstraZeneca, pharmacogenetics is used to understand why some patients respond better than others to certain medicines, and why a small number of patients experience serious side effects to certain medicines. Using pharmacogenetics to identify variations in genes that determine these individual responses will allow us to develop drugs that are suitable for the majority of patients and help to identify in advance those patients for whom a certain drug may not be the most appropriate. Our experience of current international standards of best practice for pharmacogenetics in European clinical trials will be presented.17:30 Proteomics - Applications to Molecular Medicine
Dr. Gordon Holt, Principal Scientist, Oxford Glycosciences
Proteomic analysis involves the systematic separation, identification, and characterization of proteins present in a biological or clinical sample. The relevance of proteomics to molecular medicine lies in (1) the fact that almost all successful drugs either target or are proteins, (2) proteins constitute the final form of gene expression, and (3) the function and 'dysfunction' of a protein and the pathways that it participates in are often dependent on post-translational modifications that are not directly encoded in the genome. For these reasons, proteomics is a core technology to translate genomic advances into a more detailed, coherent and pharmacologically useful understanding of proteins in disease. In this presentation, the impact of applying proteomics to a molecular dissection of disease processes in patients, improved lead compound selection and evaluation of pharmacology, and biomarker discovery to accelerate experimental medicine will be discussed.18:00 Panel Discussion
18:30 End of Conference
Corporate Sponsor Biographies 
Amersham Pharmacia Biotech(APBiotech), the life sciences business of Nycomed Amersham plc, is a leading provider of biotechnology systems, products and services for research into genes and proteins, for the discovery and development of drugs and for the manufacture of biopharmaceuticals. The customers for APBiotech's products and technology are pharmaceutical and biotechnology companies and leading research and academic institutions in North America, Europe, Latin America and Asia. For more information about APBiotech, please visit our web site at www.apbiotech.com
Incyte Genomics Inc. is a leading provider of an integrated platform of genomic technologies designed to aid in the understanding of the molecular basis of disease. Incyte develops and markets genomic databases, genomic data management software, microarray-based gene expression services, related reagents and services. These products and services assist pharmaceutical, biotechnology and academic researchers with all phases of drug discovery and development, including gene discovery, understanding disease pathways, identifying new disease targets and the discovery and correlation of gene sequence variation to disease.
QIAGEN Genomics Inc. is the foremost provider of commercial, high throughput genomic analysis services, including SNP genotyping using the highly multiplexable, robust and cost effective Masscode(tm) tagging system. The Masscode system uses only 1-3 ng of genomic DNA per sample, is precise and quantitative, and is proven and in use today for microbial, bacterial, viral, human, plant and animal applications. QIAGEN Genomics’ SNP genotyping services are performed in compliance with GLP standards, and the technology is available for license. QIAGEN Genomics also offers outsourcing to clients for their SNP validation, SNP discovery, DNA extraction and DNA sequencing solutions.
Please call the hotel directly to make your room reservation. Identify yourself as a Cambridge Healthtech Institute conference attendee to receive a reduced room rate. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.
Hotel Information
Hotel Bayerischer Hof
Promenadeplatz 2-6
80333 Munich
Germany
T: 49-89-21-20-0
F : 49-89-21-20-906
Cut-off Date: April 6, 2001Travel Information
Special Airline Discounts Available
You may call Great International and National Travel at 617-527-0800 and ask for Joyce Dunn or e-mail her at jdunn@greatintltravel.com.Poster Information
Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. Please fill out the registration form, with the poster title and primary author. To ensure inclusion in the conference binder, a one-page summary must be submitted and registration must be paid in full by April 13, 2001. POSTER INSTRUCTIONSExhibit Information
Exhibit space is available for companies interested in exhibiting equipment, instruments, reagents, software, information, or other products and services. Last year's meeting attracted highly targeted researchers and executives representing a large number of the leading commercial, academic, and government organizations active in Proteomics, Gene Expression, Functional Genomics, and related activity. Please contact Jim MacNeil of Cambridge Healthtech Institute at 617-630-1341 to obtain an exhibitor package or to inquire about offering a workshop during the meeting. Exhibit space is limited so call now to reserve a space at this event.
Phone: 617-630-1300, Fax: 617-630-1325
Email: chi@healthtech.com
