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Thursday, March 27

8:25am Chairperson's Remarks
Sandor Szalma, Ph.D., Director, Discovery Informatics, Centocor R&D, Inc.

8:30 Diagnostics in Translation: A Challenge to Value 
Paul R. Billings, M.D., Ph.D., Senior Vice President, Strategic Planning and Corporate Development, Senior Geneticist, Center for Molecular Biology and Pathology, Laboratory Corporation of America

9:00 Conformational Amyloid Proteins as Biomarkers for Neurodegenerative Disease
Alan Rudolph, Ph.D., MBA, Chief Executive Officer, Adlyfe Inc.
Many amyloid diseases proceed with the accumulation and aggregation of proteins with specific conformational states that result in observed oligomeric, plaque and tangle neurotoxicity and pathology. These structural forms are characterized by beta sheet-rich secondary structure. We have developed a novel method of detecting and amplifying beta sheet rich species of amyloid proteins. This enables the creation of a biomarker panel that can be applied to clinical matrices for early diagnosis and progression of neurodegenerative disease. We have utilized short synthetic, fluorescently labeled peptides, sequence matched to targets of interest to detect and amplify clinically relevant species in both prion diseases (Transmissable Spongiform Encephelopathies) as well as those associated with a-beta amyloid protein (Alzheimer's). Clinical detection of disease has been demonstrated in both animal models of disease as well as human clinical samples including blood and cerebrospinal fluid. We are developing a simple clinical in vitro diagnostic assay for conformational amyloid protein in neurodegenerative disease. In addition, this approach has been shown to be useful in imaging amyloid aggregates as well as defining small molecule drug effects on conformational protein amyloid proteins.

9:30 RNA Amplification as an Essential Approach for Biomarker Discovery
Ena Wang, Ph.D., Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
Limited progress in biomarker discovery may be related to the lack of informative material that can be obtained at the appropriate time in relation to the natural history of disease or its response to therapy. We have focused our efforts to develop tools for the analysis in real-time of human samples applying serial sampling of the lesions, in our case those representing cancer tissue or chronically infected organs. Serial sampling allows a paired and, therefore, stringent comparison of the same biological entity at different time points, therefore, bypassing differences in phenotype that are related to the heterogeneity of human disease or the differences in the genetic background of individuals affected. This approach may be used to identify biomarkers predictive of the natural history of disease (prognostic biomarkers) or those that may be more directly predictive of the responsiveness to a given treatment (responsiveness biomarkers) that may bear practical usefulness in the context of tailored approaches to heath care delivery. Finally, serial sampling during therapy may inform about the mechanism of action of a given treatment (mechanist biomarkers) or it mechanisms of escape to treatment (resistance biomarkers). As previously discussed this strategy requires serial sampling of the same lesion/tissues and, therefore, it is more likely to be feasible if least invasive approaches are applied such as fine needle aspirates, through cut or punch biopsies. For this reason, we have developed and extensively validated an RNA amplification method that allows the utilization of minuscule clinical sample for global transcriptional profiling. Examples of the utility of this approach will be discussed.

10:15 Technology Spotlight (Sponsorship Available)

10:30 Poster Competition & Refreshment Break in the Exhibit Hall

1:30 Break

1:45 Chairperson's Remarks
Dominic Spinella, Ph.D., Global Translational Medicine Lead, Oncology, Pfizer Inc.

1:50 Challenges and Opportunities in Translational Oncology
Dominic Spinella, Ph.D.

2:20 Bidirectional Bedside Lab Bench Process as a Means to Optimize the Development of Innovative Immunotherapies in Cancer
Adrian Bot, Ph.D., Senior Director, Translational Medicine, MannKind Corporation
The emergence of many investigational molecular targeted therapies stimulated by an unprecedented progress in the genomics arena raised new challenges in drug development. In the era of molecular medicine, a major objective of modern translational research is to identify the target with the most optimal clinical opportunity and in turn, enhance the opportunity for every given target. This is most evident in case of �first in class�Einvestigational drugs without existing benchmark in terms of approved products. Using innovative cancer vaccines as a study case, we illustrate several key revisions of the drug development process aimed to expedite, direct and optimize the drug development. These proposed key modifications are (1) revising the role of preclinical models, (2) implementing biomarker guided processes during early exploration and (3) considering novel, adaptive trial designs to direct clinical development in a more optimal fashion.

2:50 Translating Mechanistic Understanding into Clinical Utility for HDAC Inhibitors
Sriram Balasubramanian, Ph.D., Director, Translational Research, Pharmacyclics, Inc. 
While the number of targeted therapeutics for treatment of cancer has grown dramatically in recent years, there are still relatively few clinical trials for small molecule therapeutics in which mechanism-based biomarkers are used to define dose or select patients for treatment. Often the problems include an incomplete understanding of the mechanism of action of the drug, or the inability to develop suitable biomarkers that can be rapidly and reliably evaluated in the clinic. We are currently developing novel broad-spectrum (PCI-24781) and isoform-selective (PCI-34051) inhibitors of histone deacetylase (HDAC) enzymes. We have combined extensive preclinical analysis with clinical data from Phase I trials to identify the best clinical indications, stratify patients and select an optimal dose schedule based upon a clear understanding of the pharmacology and mechanism of action. For example, we have recently shown that regulation of RAD51 by PCI-24781 is critical to its mechanism of action, both as a single agent and in synergy with radiation and DNA damaging agents. This talk will outline how we are utilizing this and other predictive mechanism-based biomarkers to advance the clinical testing of this compound. 

3:20 Plenary Keynote 

4:00 Ice Cream Refreshment Break in the Exhibit Hall with BEST OF SHOW AWARDS

4:45 Molecular Predictors for the Outcome of Bladder Cancer: A Multi-center Validation Study of 400 Patients
Torben Orntoft, Ph.D., Chairman, Clinical Biochemistry, Aarhus University Hospital
Our work has been carried out based on a very large biobank with >50,000 samples from bladder cancer patients. We have applied expression and SNP microarrays to detect systematic changes associated with clinical outcome of superficial tumors, and of patients receiving chemotherapy. A number of gene signatures for e.g. progression and CIS have been validated on large multi-center materials and shown independent predictive power in multivariate analyses. Some molecular predictors of outcome from chemotherapy have been transferred to IHC and shown independent predictive power on parrafin sections. These data are very promising and are now being tested in a prospective setting before final introduction into the clinic.

5:15 Antibody Program: From Discovery to Clinic 
Michael Perricone, Ph.D., Scientific Associate Director, Immunotherapy Research, Genzyme Corporation 

5:45 End of Day