MONDAY, 5 NOVEMBER 2007

08:00-08:30 Registration for Pre-Conference Tutorial

08:30-12:00 Pre-Conference Tutorial 
(Separate Registration Required)

FIT-FOR-PURPOSE BIOMARKER ASSAY 
DEVELOPMENT AND VALIDATION 

Instructors
John L. Allinson, FIBMS, Director, Veeda Clinical Research Ltd.
Viswanath Devanarayan, Ph.D., Director, Statistics, Biomarker Research, Abbott Laboratories
This tutorial will focus on the recommendations for the best practices in the development and validation of biomarker assay development, method validation and sample analysis, with special emphasis on assays where a reference standard material is available. First, an introduction to the concept of “Fit-for-Purpose” method validation, the different types of biomarker methods and data, and a broad roadmap to method development and validation will be provided. Second, the key ele-ments of fundamental validity to meet the objectives of exploratory biomarker studies will be discussed, including the basic requirements such as sample stability and collection integrity, validation and QC samples, calibration curve fitting methods, method optimization and method feasibility studies. The elements of more exten-sive assay validation (“advanced” validation) needed for the chosen biomarkers in pivotal studies will then be discussed. Finally, the recommendations for pre-study and in-study validation will be provided with case illustration.
Coverage Includes:

1. Introduction - Nomenclature, types of biomarker methods/assays, biomarker method development and validation roadmap, fundamental validity, similarity to PK assays and difference from diagnostic application 

2. Pre-analytical and Bioanalytical elements: Target range, standards, validation & QC samples, stability, matrix effect, and rela-tive selectivity

3. Calibration curve model selection and evaluation, method feasibility and optimization with precision profiles

4. Evaluation of some pre-study validation characteristics such as precision and sensitivity

5. Illustrations of pre-study validation and in-study validation (sample analysis)

6. Impact of analytical variability and acceptance criteria on clinical evaluations

12:00-13:00 Conference Registration

13:00-13:10 Welcoming Remarks from Conference Director
Julia Boguslavsky, Cambridge Healthtech Institute

BIOMARKERS IN PERSONALIZED MEDICINE

13:10-13:15 Chairperson’s Opening Remarks

13:15-13:45 Genome-Wide Pharmacogenetic Investigation of Adverse Events: A Case Study 
Ruth E. March, Ph.D., Senior Principal Scientist, R&D Genetics, AstraZeneca Pharmaceuticals
One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs) during drug treatment. To date, however, there have been only a few successful examples of this type of approach. In this presentation, I will describe a case study consisting of a case control pharma-cogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study involved a genome-wide scan using tagging single nucleotide polymorphisms (SNPs) and also a large-scale candidate gene SNP analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1*07 and DQA1*02 was discovered and subsequently replicated, suggesting a possible immune pathogenesis. Functional studies were consistent with this hypothesis, suggesting that ximelagatran may have the ability to stimulate an adaptive immune response.

13:45-14:15 Personalized Healthcare and Biomarker Strategies for Cancer Therapeutics
Stefan Scherer, M.D., Ph.D., Biomarker Program Leader, AVASTIN, F. Hoffmann-La Roche Ltd. 
Personalized healthcare (PHC) is built on the premise that laboratory tests can accurately predict the response of individual patients to a particular treatment. The recent stakeholder behaviors, from regulators to payers and patients, physicians and pharmaceutical and diagnostic industry, suggests that the pursuit of therapeutic stratification will become a standard in oncology drug development. Among the growing number of examples for individualization of cancer therapy, Avastin and Herceptin will be presented as a case study for translation of results form pre-clinical research into a successful, targeted therapy in a selected patient population and to demonstrate the associated challenges.

14:15-14:30 Mass Spectrometry Based Detection of Protein Biomarkers in Archival Formalin-Fixed Tissue
David Krizman,Ph.D., Chief Scientific Officer, Expression Pathology Inc.
Expression Pathology Inc. has developed tissue processing and microdissection technologies that enable protein biomarker discovery and validation in formalin fixed paraffin embedded (FFPE) tissue. Such tissue collections exist worldwide with patient outcome data such as disease progression, therapeutic response or toxicity. These collections offer great potential for discovery and analysis of protein biomarkers with high diagnostic and therapeutic value.

14:30-15:00 Discovery and Evaluation of Predictive Response Gene Expression Signatures
Hans Winkler, Ph.D., Senior Director, Functional Genomics, Johnson and Johnson Pharmaceutical R&D 
Target therapies in oncology have many advantages over chemotherapy regarding both safety and efficacy. However, due to the complex molecular make-up of tu-mors, the frequency of response and benefit is lower. Targeted therapies work very well but in a limited percentage of patients, usually below 20%. It is therefore criti-cal to be able to identify patients with high likelihood of benefit early during treatment and preferentially before treatment begins. We have identified a gene expres-sion signature with the potential to identify response to a multi-targeted kinase inhibitor before treatment. The challenges in identification and, specifically, valida-tion of such signatures will be discussed.

15:00-16:00 Refreshment Break with Poster and Exhibit Viewing

16:00-16:30 Quantifying the Additional Benefits of Proteomics in Patient Selection 
Chris Harbron, Technical Lead Statistician, Discovery Statistics, AstraZeneca Pharmaceuticals
Using LC/MS proteomics applied to a large-scale clinical trial, we illustrate some of the issues associated with generating robust and reliable data on this platform, how these may be addressed, and how the data may be explored and used in order to develop a patient selection biomarker. We then evaluate the true value of the proteo-mic technology in a clinical setting by calculating the additional predictive power of including proteomic data above making a clinical decision based solely on clinical endpoints.

16:30-17:00 Personalized Medicine and the Role of Pharmacogenetics in ADME: Understanding Potentials and Obstacles
Amin Rostami-Hodjegan, Ph.D., Reader in Clinical Pharmacokinetics & Drug Metabolism, Academic Unit of Clinical Pharmacology, School of Medicine, University of Sheffield
The talk will cover the current status and views by the FDA on the issue, disparities between existing drugs vs. those under development, biomarker dependent impor-tance of pharmacogenetics in pharmacokinetics, and modeling and simulation as a platform for integration of all available data and to make better decisions.

17:00-17:10 Opening Remarks
Overview of Caprion
Daniel Chelsky, Ph.D., Executive Vice President, Chief Scientific Officer, Caprion Proteomics
Caprion's leading proteomics discovery technology - CellCarta® - enables the discovery of novel targets for therapeutics development as well as the identification of protein biomarkers that can significantly reduce risk and enhance productivity and decision making in pharmaceutical research and clinical development. Caprion has established a long list of biomarker and target discovery collaborations with major pharmaceutical and biotechnology companies, including Pfizer, Johnson and Johnson, Abbott, Daiichi Sankyo, Biogen Idec and Vertex. The company works with both pre-clinical and clinical studies in a wide range of therapeutic areas.