Immediately following CHI's Sixth Annual Impact of Genomics on Medicine

Corporate Sponsor:
Corporate Support:
Sponsoring Publications:
Genome Letters Genomics & Proteomics Pharmacogenomics American Journal of Pharmacogenomics PharmaGenomics Scientific Computing World

Coding variation directly impacts how the body handles drugs. What is significant is the extent to which this information can be sought out and used in rational drug design and delivery. As the jury deliberates, evidence accumulates to show that the market will be the final arbiter. North America came out ahead in the race to map the human genome, but can Europe take the lead by implementing this information faster to elucidate disease etiology and protein function, and to improve the drug discovery development process?

Session Chairs
Dr. Lan R. Bandara, Oxford Glycosciences (UK) Ltd
Dr. Jürgen Borlak, Fraunhofer Institut für Toxikologie und Aerosolforschung
Dr. Roger B Derbyshire, Orchid BioSciences Europe Ltd
Dr. Wolfgang Sadee, Ohio State University

Genotyping and the Clinic
Dr. Anthony J. Brookes, Karolinska Institute
Dr. Roger B Derbyshire, Orchid BioSciences Europe Ltd
Dr. Francis Kalush, Celera Genomics
Dr. Søren Møller, Exiqon A/S
Dr. Carl Risinger, Sequenom AB
Mr. Tim Tiemann, Motorola Life Sciences

Biomarkers
Dr. Lan R. Bandara, Oxford Glycosciences (UK) Ltd
Dr. Laurent Bracco, Exonhit Therapuetics SA
Dr. Steve Gardner, Viaken Systems, Inc.
Dr. Erik Jongedijk, Phase-1 Bioresearch N.V.
Dr. Peter R. Jungblut, Max Planck Institute for Infectionbiology
Dr. Jean-Daniel Tissot, Unité de Médecine Transfusionnelle

Pharmacokinetics and Toxicology
Dr. Jürgen Borlak, Fraunhofer Institut für Toxikologie und Aerosolforschung
Dr. Ulrich Brinkmann, Epidauros Biotechnologie AG
Dr. David M. Iovannisci, Children's Hospital Oakland Research Institute
Dr. Mark Porter, Gene Logic, Inc.
Dr. Andreas P. Russ, Ingenium Pharmaceuticals AG

Applications in Drug Development
Dr. Michael Furness, Iconix Pharmaceuticals, Inc.
Dr. Karen Jones, Oxagen, Ltd.
Dr. Ruth March, AstraZeneca
Dr. Jim Lillie, Millennium Pharmaceuticals, Inc.
Dr. Wolfgang Sadee, Ohio State University
Dr. Gerald F. Vovis, Genaissance Pharmaceuticals, Inc.

 

Tuesday, May 14

16:00-18:00 Early Registration, Poster and Exhibit Set-up

Wednesday, May 15

7:30 Registration, Poster and Exhibit Viewing, and Light Continental Breakfast

 

Genotyping and the Clinic

8:30 Chairperson's Opening Remarks
Dr. Roger B Derbyshire, Associate Director, Genotyping Operations, Orchid BioSciences Europe Ltd

8:40 Celera Human Reference SNP Map
Dr. Francis Kalush, Scientist, Medical Affairs, Celera Genomics
(Summary unavailable at time of printing.)

9:10 eSensor™ Electronic Detection Technology: The New Paradigm for Clinical Trials Genotyping
Mr. Tim Tiemann, Director, Clinical Diagnostics Business Development, Motorola Life Sciences
Though pharmacogenomics holds tremendous potential for improving the practice of medicine, the speed and scope with which this future is realized depend upon costs, practicality, and the value of testing. This talk will focus on economic, technical, and intellectual property drivers of the new DNA diagnostics opportunity. Using eSensor™ DNA Detection Technology as an example, we will explore the links between technology features and market acceptance and between commercial and clinical success.

9:40 Enabling the Power of SNP Genotyping across a Broad Range of Research and Pharmacogenetics Studies
Dr. Roger B Derbyshire, Associate Director, Genotyping Operations, Orchid BioSciences Europe Ltd
To fully exploit the power of single-nucleotide polymorphism (SNP) genotyping in areas from basic research to applied clinical pharmacogenetics, a genotyping technology is needed that enables an array of projects ranging from mapping studies, designed to analyze thousands of SNPs across the genome to identify those with biological relevance, to clinical studies, where thousands of patient samples are screened against panels of SNPs with known function. Orchid's SNP-IT™ genotyping technology, implemented on Orchid's novel array-based platforms, SNPcode™, SNPstream® UHT, and SNPstream MT, allows the completion of SNP genotyping projects covering the full spectrum of sample and SNP panel sizes. Representative studies using these platforms and SNP-IT will include allele frequency determination in different ethnic populations using SNPs from the SNP Consortium database and approaches to whole chromosome mapping using SNPs.

10:10 Poster and Exhibit Viewing, Refreshment Break

11:00 Genomewide SNP Analysis for Pharmacogenetics and Personalized Medicine
Dr. Carl Risinger, Sequenom AB
By implementing genomewide SNP association studies in well-characterized clinical trial patient samples, causative genetic markers that are associated with differential drug responses can be rapidly identified and characterized without any prior knowledge of the genes. Sequenom has validated over 200,000 single-nucleotide polymorphisms (SNPs) with confirmed allele frequencies across the human genome using MALDI-TOF (MassARRAY™) technology. This enabling tool is well positioned to bring personalized medicine into reality.

11:30 Locked Nucleic Acid (LNA) Microarrays: A New Tool for SNP Genotyping
Dr. Søren Møller, Manager, Department of SNP Microarrays, Euray, Exiqon A/S
Exiqon has developed a microarray technology based on Locked Nucleic Acids (LNA) and a polymer microarray platform. LNA is a DNA derivative with unprecedented high-binding affinity and selectivity, and the polymer microarray slide has furthermore been adapted as a microfluidics chip for low-volume hybridizations. Development of a multiplex SNP genotyping array focusing on CYP450 will be demonstrated.

12:00 Next generation SNP Genotyping by DASH: One Million Genotypes for One Thousand Dollars (USD)
Dr. Anthony J. Brookes, Vice Chairman and Clinical Genomics Unit Coordinator, Center for Genomics and Bioinformatics, Karolinska Institute
A system has been prototyped for achieving 1,000,000 individual SNPgenotypes per week per assay device, at << 1c per call (i.e., total cost of around 1,000 USD). The system is a '2nd generation' implementation of DASH (Dynamic Allele Specific Hybridization). DASH involves dynamically tracking DNA denaturation as a (PCR amplified) target and (oligonucleotide) probe duplex is steadily heated - providing an accuracy of >99.9% and a reproducibility of 100%. Throughput enhancements in the 2nd generation system have been achieved by devising i) a means to instantly create high-density macro-arrays by centrifugation, and ii) an improved form of FRET signal generation (called iFRET) that yields ~40x stronger signals than the norm. Three levels of multiplexing are intrinsic to the method (parallel plate/membrane processing, spectrally distinct sets of iFRET probes, serial probing), together enabling unprecedented genotyping throughput at absolutely minimal cost. Importantly, the final system is extremely flexible both in terms of the target SNPs interrogated and in the scale of application, making it an attractive platform for many research and diagnostic applications.

12:30 Panel Discussion

13:00 Lunch (on your own)

 

Biomarkers

14:15 Chairperson's Remarks
Dr. Lan R. Bandara, Pharmacoproteomics Manager, Oxford Glycosciences (UK) Ltd

14:20 RNA Splicing Deregulations as a Source of Pharmacogenomics Markers
Dr. Laurent Bracco, Executive Vice President of Research, Exonhit Therapuetics SA
ExonHit is focusing on systematic identification of RNA splicing alterations that can occur between normal and tumoral tissues or upon the pharmacological or toxicological effects of drugs. Such RNA splicing expression markers form the basis of two lines of products. The first one focuses on the clinical validation of splicing arrays to identify responders and nonresponders in cancer patients. The second one is a genotyping assay based upon selecting genes identified to be deregulated by splicing in toxic settings.

14:50 Identification of Small Sets of Predictive Biomarker Genes for Kidney and Liver Toxicity
Dr. Erik Jongedijk, Director of Business Development, Phase-1 Bioresearch N.V.
This presentation will describe the identification of genetic markers for kidney and liver damage in the rat and their possible use as a screening tool. Gene expression profiling using the Phase-1 Rat CT microarrays was performed on kidney/liver samples obtained from male rats treated with a variety of nephrotoxic and hepatotoxic compounds. Overall perturbation of the tissues, as evidenced by the number of up- or downregulated genes, correlated with histopathology. Determination of correlation between individual gene expression and histopathology indicated a number of genes whose induction or repression in the kidney or liver specifically correlated with, respectively, kidney acute tubular necrosis and liver necrosis. Correlating genes at earlier times tended to be more reflective of damage and compound-specific while genes correlating at the later time point tended to be responsive to all compounds. These patterns are consistent with sequential transition from active damage processes to repair processes. The use of subsets of correlating genes in a correlation matrix analysis enhanced discrimination between compounds that did and those that did not produce kidney and liver histopathology. Sets of predictive biomarkers associated with nephrotoxicity and hepatotoxicity that predict the occurrence of toxicity issues with an overall accuracy of about 90% at the individual sample level and about 95% at the compound level were identified and validated.

15:20 Using High-Throughput Proteomics to Discover Surrogate Markers of Drug Toxicity
Dr. Lan R. Bandara
Selection of drug candidates based on evaluation of their toxicity profiles as early as possible during development represents a major cost-saving opportunity. Proteomics can identify preclinical and clinical safety markers that will help this selection process. Examples of treatment-induced toxicity will be presented, including doxorubicin-induced cardiotoxicity studies done in collaboration with the U.S. Food and Drug Administration.

15:50 Poster and Exhibit Viewing, Refreshment Break

16:30 Applied Proteomics
Dr. Jean-Daniel Tissot, Professor, Unité de Médecine Transfusionnelle; and President, Swiss Proteomics Society
Several examples of proteomic applications will be highlighted in this presentation. Using proteomic tools, different populations of lymphocytes isolated from human blood can be separated according to their protein expression, and the discriminating proteins can be identified. Proteomic tools also allow analysis of the modifications of protein production of many proteins during cell culture, as illustrated by the study of fetal skin. Finally, the study of "old and well-characterized molecules" such as immunoglobulins may reveal unexpected secrets.

17:00 Proteomics Reveal Open Reading Frames in Mycobacterium tuberculosis H37Rv not Predicted by Genomics
Dr. Peter R. Jungblut, Leader, Central Core Facility of Protein Analysis, Max Planck Institute for Infectionbiology
Genomics revealed the sequence of 3924 genes of the H37Rv strain of Mycobacterium tuberculosis. Proteomics complements genomics in showing which genes are really expressed, and here we show the expression of six genes not predicted by genomics, as proved by two-dimensional electrophoresis and matrix-assisted laser desorption ionization and nano-electrospray mass spectrometry.

17:30 Integrating Expression and Marker Data into the Drug Discovery and Development Process
Dr. Steve Gardner, Chief Technology Officer, Viaken Systems, Inc.
Effective application of gene and protein expression information in discovery and development requires a strong supporting informatics infrastructure. For example, a gene expression data set may be compared with other gene or protein expression arrays, or even small molecule data. To enable these comparative studies, semantic content of the original experimental data must be understood, and an appropriate framework for its integration with other data must be created. The key challenge for life science informatics staff is to make these information systems function together seamlessly in an integrated enterprise-scale informatics infrastructure. This challenge is being addressed by bringing together cutting-edge informatics technologies, coupled with a strong understanding of the scientific domain and R&D process. This approach combines sophisticated data mapping, mining, data visualization, workflow mapping, automation, and textual retrieval and analysis tools with an optimized and integrated ontology-based data schema containing data public and private sources from the life science R&D domain. This presentation will show how these technologies and methodologies have been integrated, deployed, and used in various drug discovery related projects over the last year. It will also show a unique approach to implementing these technologies to ensure their wide deployment and effective adoption.

18:00 Panel Discussion

18:30 Reception (sponsored by Cambridge Healthtech Institute)

19:45 Close of Day One

 

Thursday, May 16

8:00 Poster and Exhibit Viewing and Light Continental Breakfast

 

Pharmacokinetics and Toxicology

8:30 Chairperson's Remarks
Dr. Jürgen Borlak, Head, Center for Drug Research and Medical Biotechnology, Fraunhofer Institut für Toxikologie und Aerosolforschung 

8:35 Title and abstract to be announced.
Dr. Andreas P. Russ, Vice President Research, Ingenium Pharmaceuticals AG

9:05 Drug Metabolizing Genes, Cigarette Smoking, and Orofacial Clefting
Dr. David M. Iovannisci, Assistant Staff Scientist, Children's Hospital Oakland Research Institute
That genetic variation of drug metabolizing genes can result in interindividual differences in the ability to metabolize pharmaceutical agents and carcinogenic compounds has been well established. However, much less is known about the role of these genes during fetal development. We have observed that 24% of pregnant California women report smoking cigarettes during pregnancy, and we have identified a small increased risk of orofacial clefting if the mother smokes cigarettes while pregnant. To better understand the increased risk of oral cleft malformations, we genotyped fetal-derived DNA samples for known polymorphisms affecting the activity of several xenobiotic metabolizing genes and interviewed the mothers concerning cigarette-smoking behavior. We now report the identification of several variants of drug metabolizing genes that increase the risk for cleft lip/cleft palate formation when the mother smokes cigarettes during pregnancy. Increased risk is observed only when the developing fetus has these pharmacogenomic variants and the mother smokes, but not with either factor alone.

9:35 Polymorphisms in Human Drug Transporters and Drug Metabolizing Enzymes
Dr. Ulrich Brinkmann, Chief Scientific Officer, Epidauros Biotechnologie AG
Blood and tissue concentrations, and hence the activity of many drugs, are influenced by factors that are subject to interindividual variation. Variables that influence blood levels are metabolizing enzymes and transporters. The latter control drug uptake, distribution, and elimination. Transport by ATP-driven efflux pumps such as MDR1-encoded P-glycoprotein (PGP) or by MRPs can influence the bioavailability of drugs. Knowing the transporter "status" may allow compensation of differences in drug uptake, e.g., by dose adjustment, which is important for drugs with narrow therapeutic windows. Intestinal as well as renal and lymphocytic expression and function of P-glycoprotein correlate with defined polymorphisms in drug transporters, which influences the uptake as well as tissue distribution and excretion of drugs and thereby directly affects the therapeutic efficacy of drugs.

10:05 Poster and Exhibit Viewing, Refreshment Break

10:35 Genotyping in Clinical Trials: Towards an Improved Drug Safety
Dr. Jürgen Borlak
The presentation will focus on nucleotide polymorphisms of drug-metabolizing enzymes and the use of pharmacogenetics to better understand the pharmacokinetics of drugs and subsequent adverse drug reactions. An overview of human enzymes that code for phase I and phase II functions, e.g., modification of functional groups by oxidation or conjugation with endogenous substituents, will be provided, and examples of clinical relevant genetic polymorphisms will be given. Also included will be a detailed discussion on severe and potentially fatal toxicity that can occur when patients with genetic polymorphisms are treated with standard doses of certain drugs.

11:05 Predictive Toxicology Using Gene Expression Profiles of Multiple Compounds
Dr. Mark Porter, Associate Director, Toxicology Bioinformatics, Gene Logic, Inc.
Gene Logic's ToxExpress program utilizes gene expression data resulting from the administration of multiple toxicants to in vivo and in vitro systems in order to construct predictive models of toxicity. These models contain highly invariable genes capable of predicting the potential toxic response of unknown compounds. These models and the methods on which they are based will be discussed.

11:35 Panel Discussion

12:05 Luncheon (Sponsored by Cambridge Healthtech)

 

Applications in Drug Development

1:30 Chairperson's Remarks
Dr. Wolfgang Sadee, S.&L. Felts Mercer Professor of Medicine and Pharmacology; Chair, Department of Pharmacology; and Director, Pharmacogenomics Program; College of Medicine and Public Health, Ohio State University

1:35 DrugMatrix: Expansion of Expression Data to Integrate Pharmacology and Chemistry Data
Dr. Michael Furness, Scientist, Iconix Pharmaceuticals, Inc.
DrugMatrix is a database and predictive system being constructed at Iconix that integrates biology and chemistry built on gene expression data, pharmacological assays, and chemical structures and properties for 2,000 compounds, including all marketed drugs and a large number of paradigm compounds and toxins. The goal of the database is to provide a more comprehensive analysis of the mechanism of action of new drugs by comparing them to this data set and drug signatures identified by Iconix within these data sets. This will enable rapid removal of compounds with adverse effects, provide a mechanistic understanding of how new compounds work, and identify new applications for known drugs.

14:05 Title to be Announced
Dr. Stephen Miller, European Manager, GMP Companies

14:35 Drug marketing in the Pharmacogenomic Era: Issues and Opportunities
Dr. Gerald F. Vovis, Executive Vice President, Genaissance Pharmaceuticals, Inc.
Biochemical researchers are rapidly adopting pharmacogenomic technologies for drug discovery and development. Using genetically defined criteria to prescribe medication creates a new series of new issues and opportunities for the marketing professional. This presentation will discuss the transition that pharmacogenomics is making from research tool to marketing tool: how to use target populations to gain stronger claims and improved product differentiation, potential reimbursement advantages, and enhanced customer relationships.

15:05 Poster and Exhibit Viewing, Refreshment Break

15:30 Personalized Medicine: Revolutionizing Drug Discovery and Patient Care
Dr. Jim Lillie, Senior Director Pharmacogenomics, Millennium Pharmaceuticals, Inc.
Personalized medicine, the use of marker-assisted diagnosis, and targeted therapies derived from an individual's molecular profile will impact the way drugs are developed and medicine is practiced. Knowledge of the molecular basis of disease will lead to novel target identification, toxicogenomic markers to screen compounds, and improved selection of clinical trial patients, which will fundamentally change the pharmaceutical industry. An integrated, heuristic approach to drug discovery will replace the traditional linear process. Patient care will be revolutionized through novel molecular predisposition, screening, and diagnostic, prognostic, pharmacogenic, and monitoring markers. Although numerous challenges will need to be overcome, personalized medicine will replace the traditional trial-and-error practice of medicine.

16:00 Pharmacogenomics: Impact on Drug Discovery and Therapy
Dr. Wolfgang Sadee
Recognizing genetic variability holds promise for novel drug discovery and optimized therapy, but it also limits efficacy throughout diverse patient populations. Moreover, severe adverse effects can occur even though the drug is administered appropriately-also a possible result of genetic differences among patients. We need to determine where pharmacogenomics can have the greatest impact on therapy.

16:30 The Potential of Genetic Information to Improve the Drug Discovery and Development Process
Dr. Karen Jones, Business Development Director, Oxagen Ltd
Knowledge of genetic diversity, combined with the appropriate clinical resources, has the potential to deliver new drug targets that are linked to critical disease processes. A genetic filter can also be applied to select promising targets emerging from genomic studies and other approaches. Knowledge of genetic risk factors will improve the diagnosis of disease and is the essential basis for future pharmacogenomic studies. Biological insights provided by genetics can be used to select the most promising indications for new drugs and to extend the utility of existing drugs.

17:00 Impact of Pharmacogenetics within the Pharmaceutical Industry
Dr. Ruth March, Head, Development Genetics Group, Research and Development Genetics, AstraZeneca
Recent years have seen an explosion in the use of genetics in the drug discovery and development process. This presentation will describe how recent advances in genetics technologies are being used within the pharmaceutical industry to develop medicines suitable for the majority of patients while maximizing safety and efficacy in each treatment group. The current impact of these advances will be assessed and the potential for future development outlined.

16:30 Panel Discussion

17:00 Close of Conference

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Hotel Accommodations
Hilton Munich Park
Am Tucherpark 7
D-80538 Munich, Germany
T: 49-89-3845-0
F: 49-89-3845-2588
Room Rates: DM 420/S, 480/D
Cut-off Date: April 25, 2002
Please call the hotel directly to make your room reservation. Identify yourself as a Cambridge Healthtech Institute conference attendee to receive the 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.

Call for Sponsorship and Exhibit Opportunities
Certainly, the importance of relating genomic data to the drug discovery and development process is immeasurable. This conference will take particular interest in using case studies to help estimate the actual benefit of integrating genomic data into drug research and clinical practices. We strongly encourage any company with services or products related to target validation, chemical genomics, animal models, lab chips, proteomics, structural genomics, disease research, to consider sponsoring or exhibiting at this event. Sponsorship is the best way to prominently elevate your company's presence and influence at this conference. Although exhibit space can be purchased separately, many sponsorship packages also include a booth. 

For more information on sponsorship opportunities, please contact Angela Parsons at 781-972-5467 or aparsons@healthtech.com.

To reserve a booth, please contact Pam Crane at 781-972-5431 or pcrane@healthtech.com.

Impact of Genomics on Medicine exhibitors
The following companies are registered to exhibit as of 5/13/02:

1. Bavarian Ministry for Economics Affairs
2. DxS Ltd.
3. Gene Logic Inc.
4. Golden Helix, Inc.
5. Incyte Genomics
6. LION bioscience AG
7. Oxagen Ltd.
8. Third Wave Technologies, Inc.
9. Variom Biotechnology AG

Pharmacogenomics/Pharmacoproteomics Europe Exhibitors
The following companies are registered to exhibit as of 5/13/02:

1. DxS Ltd.
2. GeneScan Europe AG
3. Golden Helix, Inc.
4. Incyte Genomics
5. Orchid BioSciences, Inc.
6. Oxagen Ltd.
7. PerkinElmer Life Sciences Inc.
8. Sequenom GmbH
9. Variom Biotechnology AG

Call for Posters
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 5, 2002.  Click here for poster instructions