Monday, January 25, 2010

MAIN CONFERENCE

12:00-2:00 pm Main Conference Registration

2:00-2:10 Welcoming Remarks from Conference Director

Julia Boguslavsky, Cambridge Healthtech Institute

Analytical and Biological Validation
of Biomarkers

2:10-2:15 Chairperson’s Remarks

2:15-2:45 Patient Characterization and Clinical Assay Development Centers: Programs to Support Biomarker Development in NCI-Supported Clinical Trials

J. Milburn Jessup, M.D., Chief, Diagnostics Evaluation Branch, Cancer Diagnosis Program, DCTD/National Cancer Institute, National Institutes of Health

Prognostic and predictive biomarkers will become increasingly important for assuring that patients receive the right therapy at the right time. This requires that the analytical performance of the assays for these biomarkers is clinically robust and useful within the context of their intended use. With the American Recovery and Reinvestment Act (ARRA) funding the NCI will initiate a Molecular Characterization Center that will include a Patient Characterization Center (PCC) and a Clinical Assay Development Center (CADC). The PCC will test whether total genomic analysis on clinical samples from the National Community Cancer Centers Program including gene expression, microRNA, SNP, gene methylation and gene sequencing analysis can be performed in a CLIA-certified laboratory with appropriate data integration. The intent is to build a large, continually clinically annotated database which over time will be a resource for personalized medicine. The CADC will serve to assure the analytical performance of assays in first late-phase and then earlier-phase NCI clinical trials as the program develops. The intent of this program will be presented and is to benefit both academia and industry in the development of clinically useful assays.

2:45-3:15 Challenges and Considerations for the Development and Validation of Intracellular Biomarkers

Naveen Dakappagari, Ph.D., Scientist II, Clinical Sciences and Technology, Biogen Idec, Inc.

The talk would describe case studies to illustrate the challenges involved in the collection of clinical samples for assessment of intracellular biomarkers, evaluation of sample stability, assessment of longitudinal variation, determination of cut-off values, development of appropriate internal quality controls and validation of a companion protein estimation assay to support early stage clinical trials. An example will be presented to illustrate the key differences and challenges in the validation of an intracellular versus serum biomarker encoded by the same gene.

3:15-3:30 Isotopic Mass Tags for the Facilitated Development of 
Multiplex SRM Mass Spectrometric Assays for Protein and
Peptide Biomarkers

Malcolm Ward, Ph.D., Head of Research UK, Proteome Sciences plc, UK
In order to verify those biomarkers that have most utility and value, the biomarker development pipeline requires rapid progression from candidate discovery to biomarker qualification using fit-for-purpose assays. Mass spectrometric methods, such as Selected Reaction Monitoring (SRM), are increasingly used for the quantitation of peptides and proteins. One drawback of the typical approach is the expense and delay associated with the production of the heavy isotope-doped versions of the target peptide(s) to serve as standards. For many biomarker candidates synthesis of the required standard(s) may also be challenging or impossible, due to post-translational modifications. To overcome these limitations Proteome Sciences has developed isotopic versions of its proprietary tandem mass tag (TMT) reagents to differently label sample and standard. The TMT-SRM method therefore allows the use of either synthetic or natural reference standards and thus provides a quick and economical way to establish assays for any peptide or protein in a given sample material. Furthermore, because isotopic TMT’s are identical in structure to isobaric TMT’s used for biomarker discovery there is minimal set up time or costs when moving from candidate discovery to assay qualification and validation. Proteome Sciences is the only company to offer this unique method as part of their PS Biomarker Services to the pharmaceutical and biotech sector and the presentation will include examples to illustrate the provision of multiplex TMT-SRM mass spectrometry assays for candidate biomarkers of Alzheimer’s disease and demonstrate the exceptional performance criteria than can be achieved.

3:30-4:00 Networking Refreshment Break

4:00-4:30 Challenges in IHC Assay Validations

Iman Jilani, M.S., CLS, MT (ASCP), Biomarker Assay Specialist, Manager, Clinical Assay Group, Pfizer, Inc.

4:30-5:00 Validation of Biomarkers for Antiangiogenic Drug Development

Cindy Chau, Ph.D., Pharmacist, National Cancer Institute, National Institutes of Health

As biomarkers become integrated into drug development and clinical trials, assay validation becomes essential with the need to establish standardized guidelines for analytical methods used in biomarker measurements. While there are currently no validated biomarkers of response to antiangiogenic therapy, a number of candidate biomarkers are emerging that need to be prospectively validated. Potential pharmacodynamic biomarkers of antiangiogenic therapy will be presented followed by a discussion of the current challenges in angiogenesis biomarker assay development and a perspective on the future validation of biomarkers for antiangiogenic drug development.

5:00-6:00 Opening Reception in the Exhibit Hall