Conference Documentation: Advances in Target Validation

Published by: SMI Publishing, Ltd

Published: Apr. 29, 2002

Table of Contents

Day 1

8.30 Registration & Coffee

9.00 Chairperson's Opening Remarks

Dr Juergen Hammer, Global Head of Bioinformatics, Genetics Genomics, F. Hoffmann-La Roche.

9.10 Introduction

Overview of target validation

Aims of target validation

Target validation as a primary requirement for drug development

Increasing efficacy and profitability during drug discovery

Interaction between target validation and target identification

Impact of Human Genome Project

New target validation technology

Validating new drug discovery paradigms

Dr Mark Lindsay, Project Leader, AstraZeneca.

9.40 Target Validation

Past, present and future

Developments in target validation

Where the industry lies now

Emerging markets and new opportunities

Profile of key players in the field

Challenges faced the industry

What lies ahead for the industry?

10.20 New Tools For Target Validation

Controlling gene expression

Challenges for target validation

High-throughput methods

Engineered transcription factors

Transgenic animals

Gene delivery

Dr Casey Case, Vice President, Research, Sangamo.

11.00 Morning Coffee

11.20 Identification Of Novel Targets Using Subtractive Hybridization Library Screening

A functional genomics approach

We generate and fully sequence large numbers of subtractive libraries from different pain and nerve injury models

Using custom arrays to perform transcriptional profiling

Using transgenic and viral approaches target validation is then performed

Professor David Wynick, Chief Scientific Officer, Bristol University.

12.00 Evaluation Of Target Validation Strategies

Learning from experience

Target validation- the challenge

From gene to (drug) target

The power of genetic validation

Advances in antibody technology helps in the validation of extracellular targets

HTS and target validation

Dr Martin Perry, Head, NCE Biology, UCB-Celltech.

12.40 Lunch

1.40 Industrial-scale, In Organismo™ Target Validation

High- throughput gene fuctionalisation using morpholino antisense technology in zebrafish

Use of in organismo™ bioassays and morpholino antisense technology

Genome-wide gene functionation screen

New, functionally validated targets in vascular biology, hematopoiesis, and regenerative medicine

New in organismo™ disease models for validation of targets and compounds

Discovery and development of small molecules, antibodies, and proteins

Mr Alexander Crawford, President, Mermaid Pharmaceuticals GmbH.

2.20 COPAS Flow Sorting of Small Animal Model Organisms & Beads: Seamless integration of target validation, assay development and HTS.

COPAS applications for target validation include:

Automated genetic/enhancer/suppressor screens

Bulk animal sorting for biochemical/microarray experiments

Dispensing of sorted organisms in multi-well plates for drug screening

Automated re-sampling of 'in well' animal populations

Statistical multi-parametric analysis of drug effects

3.00 Identifying And Validating Drug Targets

Protein-directed target validation

Nearly all validated drug target are proteins

Proteins are predominant executors of biological function and can have multiple functions (moonlighting proteins)

Validation at the protein level vs. validation at the RNA or DNA levels

Protein drug target validation using chromophore-assisted laser inactivation (XCALIbur)

Target-driven or hypothesis-driven protein target validation

Disease-directed protein target validation

Dr Vic Ilag, Chief Technology Officer, Xerion Pharmaceuticals.

3.40 Afternoon Tea

4.00 Models For Target Validation

In vivo techniques

C. elegans models of human diseases

High-throughput target validation in vivo

Functional validation of protein interactions

Exploration of pathways associated with validated targets

Dr Michael Saunders, Head of Metobolic Diseases, Devgen NV.

4.40 Animal Models In Target Validation

Using the right tool for the job

Benefits of using an animal model for target validation

Potential pitfalls

Applying knowledge of animal models to human disease

Alternative models: how do they compare?

A look to the future

Dr Lori Friedman, Program Leader, Oncology, Exelixis.

5.20 Chairman’s Closing Remarks and Close of Day One

Day 2

8.30 Re-registration & Coffee

9.00 Chairperson's Opening Remarks

Professor David Wynick, Chief Scientific Officer, Bristol University.

9.10 Application of process biology in target validation

Can tools in economics and decision modelling be applied to biomedical research?

‘Process biology’ and the drug discovery process

Genomics and bioinformatics-based target ID process

High-throughput in vitro validation process

Tissue index: integration of clinical and microarray data

The vaccinome approach

Dr Juergen Hammer, Global Head of Bioinformatics, Genetics Genomics, F. Hoffmann-La Roche.

9.40 Functional Genomics Applications Of Antisense

Applications

Recent developments in antisense technology

High-through put target validation in animal models

Rapid gene function analysis

Dr Nicholas Dean, Vice President, Functional Genomics, ISIS Pharmaceuticals.

10.20 Chemical Genomics

Bridging the gap between genomics and drug discovery

Opportunities and challenges for drug discovery in the post-genomic era

Chemical genomics: a strategy for post-genomic drug discovery

The NeoGenesis chemical genomics technology platform

Selected Neogenesis project synopses

NeoGenesis chemical genomics programs

Dr Huw Nash, Vice President, External Collaborations, NeoGenesis Pharmaceuticals.

11.00 Morning Coffee

11.20 Target Validation Using HSV Vector-Based Gene Delivery

From gene to validated drug target

HSV biology

Vector technology overview

Gene delivery/target validation applications in neurons

Gene delivery/target validation in other cell types

Dr Robert Coffin, Chief Scientific Officer, Biovex.

12.00 Intrabodies - A Valuable Tool For Target Validation

Dr Kirsten Mundt, Business Development, ESBA Tech AG.

12.40 Lunch

1.40 Validating Cancer Targets

Developments and application

Genomics derived anti-cancer drug developments

Use of patient-derived anti-cancer drug developments

Use of biological assays to aid genomic mining

Determination of target prevalence

Assessment of target-based therapeutics

Dr Bruce Roberts, Vice President, Applied Genomics, Genzyme Gentics.

2.20 Strategies Of Target Validation

Cardiac disease

The development of new therapeutic agents for heart failure requires extremely high hurdles as several classes of therapeutics are already available

Selection of new targets for treatment of heart failure will require clear validation of substantial additional benefits over current combination therapy

The use of genomics, functional genomics, proteomics and related technologies are critical in identification of qualified new targets for heart failure

Selection of clinically relevant ‘end-points’ will be critical in seamless translational medicine in heart failure

Dr Giora Feuerstein, Executive Director, Cardiovascular Biology, Bristol Myers Squibb.

3.00 Validating Mitotic Targets

Drug discovery and development

Mitosis and cancer chemotherapeutics

High-throughput target identification in model organisms

Phenotypic correlation between drosphilia cells and human cells

Rapid confirmation of compound mode-of-action

Pursuit of multiple pathways as a risk reduction strategy in drug discovery

Dr Simon Green, Programme Manager, Polgen, Cyclacel Limited.

3.40 Afternoon Tea

4.00 Prioritising The Proteome

Identifying pharmaceutically relevant targets by linking sequence to function through 3D structure

Focussing on the application of protein 3-D structural data to the identification of distantly related homologs of pharmaceutically important gene families

Combined bioinformatics and chemoinformatics platform that significantly improves the yield and quality of functional annotation

Correlating annotation with an estimation of druggability

Specific examples of the application of this technology to the target discovery process

Mr Kevin Bottomley, Director of Alliances, Inpharmatica.

4.40 Target and compound validation using a functional proteomics approach

Utility of phosphorylation

Impact of protein phosphorylation on cell function

Examining function of protein kinases by tracking protein phosphorylation

Requirement for enrichment strategies

Antibody profiling and mass spectrometry applications

Phosphoprotein fingerprinting as a tool for compound specificity determination

Monitoring function of targets in signalling pathways

Dr Jasbinder Sanghera, Chief Scientific Officer, Kinetek Pharmaceuticals.

5.20 Chairman's Closing Remarks and Close of Conference

Abstract

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