TUESDAY, JANUARY 27

7:30-8:15 Sponsored Presentation (Opportunity Available) or Morning Coffee

Incorporating Assay Development into Overall Biomarker Strategy

8:30-9:00 Opportunities and Challenges of Biomarker Assays in Drug Development
Francois Legay, Ph.D., Head, Marker and Assay Development, Novartis Pharma
The development of new drugs requires the understanding of the relationship between the dose, the exposure, the efficacy and the toxicity of the compound. In addition, it requires following the pathway from the interaction to the drug target until the clinical/therapeutic effect. For all these steps the development of specific, sensitive and validated assays for soluble, cellular or tissue biomarkers are key. The measurement soluble biomarker in blood, plasma or other biological fluids is going in the direction of more sensitivity (cracking the pg/mL is often a must) more specificity (we need to evaluate protein processing or post translational processing) and more multiplexing. The measurement and characterization of cells in blood is going in the direction of rare events or intracellular protein expression and protein phosphorylation. Antibody-free technology (mass spectrometry) is now allowing us to evaluate pharmacological drug activity very early in development. This presentation will review the different areas where these technologies can play a key role and what will be the future challenges.

9:00-9:30 Moving Beyond Fit-for-Purpose: Use of Lean Practices to Accelerate Biomarker Assay Development
Russell S. Weiner, Ph.D., Group Director, Biomarker and Bioanalytical Sciences, Bristol-Myers Squibb Co.
Recently, there has been a significant increase in the number of clinical protocols that include biomarker measurements. Unfortunately, while the number of biomarkers has increased, there remains a gap in the resources needed to meet the clinical team’s growing appetite for biomarker data. Often, attempts are made to develop assays as if they were supporting regulated pharmacokinetic analysis. Rarely is this a requirement of the clinical team, but more of an historical practice. To address this resource gap many labs have implemented a fit-for-purpose approach where assays are developed to meet the specific needs of the clinical team. While this practice has helped reduce the resource gap in assay development, there still remains a significant problem with the delivery of the large volume of assay results. This session will focus on increasing bioanalytical capacity by using Lean thinking, where results are provided when needed (just in time delivery) versus as soon as possible.

9:30-10:10 Multiplexed Biomarker Assay Development  Sponsored by 
Michael Pisano, Ph.D., President and Chief Executive Officer, NextGen Sciences
Biomarkerexpress™ is a suite of mass spectrometry-based biomarker services that utilize proprietary methods to significantly decrease timelines and increase the success rates traditionally associated with biomarker development.   The services include discovery of protein biomarkers, development of protein biomarker assays, and testing biological samples utilizing the assays to determine levels of protein biomarkers. Case studies will include: discovery and assay development for putative biomarkers of lung cancer progression and assay development for a panel of 30 biomarkers for Alzheimer’s disease.

10:10-11:00 Coffee Break with Exhibit and Poster Viewing

Multiplex Biomarker Assays

11:00-11:30 Application of Intra-Assay Calibration Curves to Quantitate Clinical Biomarker Immunoassays
Paul Rhyne, Ph.D., Associate Director, Bioanalytical Sciences, Research and Development, Bristol-Myers Squibb Co.
The measurement of biomarkers in clinical samples using immunoassays is typically accomplished using calibration curves generated from known concentrations of standards or calibrators.  These standards usually consist of purified protein standards diluted in assay buffer and are run in separate wells.  We have developed a different approach using the multiplexing capabilities of the Luminex bead-based xMAP technology, where the calibration standards are incorporated into each well along with a clinical sample.  This allows for the first time, reference standard information to be generated simultaneously with the measurement of the biomarker in the same well.  The benefits of this approach include increased number of clinical samples run on as assay plate, higher replicates of the calibration curve points, and the elimination of buffers dedicated to dilution of reference standards.  The principles of this biomarker assay design will be discussed and examples of its application will be shown.   Additionally, the benefits and risks of using intra-assay calibration based assays will be discussed.

11:30-12:00 Automated Platforms for Biomarker Analysis:  Multiplexing Assays and Case Histories
John Allinson, FIBMS, Laboratory Director, Veeda Clinical Research
This presentation will cover structuring and developing a biomarker laboratory service; options for analytical platforms and multiplexing; capitalizing on benefits for the laboratory; new technologies and how they fit in, and present case studies of assay validations on different platforms.

12:00-12:30 Statistical Issues in the Evaluation of Single and Multi-Plex Biomarker Assays
Viswanath Devanarayan, Ph.D., Director, Global Exploratory Statistics, Abbott Laboratories
This presentation will provide a brief overview of important considerations such as multi-factorial approach to assay optimization, evaluation of calibration curves, analytical precision and assay sensitivity. This will be followed by an illustration of the impact of analytical and biological variability on the evaluation of novel biomarkers, on clinical study design, sample evaluations and on method comparisons.

12:30-2:00 Lunch on your own

Biomarker Assay Development for Diagnostics

2:00-2:30 Pre-Analytical and Analytical Considerations for Assay Development
Gerard J. Davis, Ph.D., Research Scientist and Project Manager, Cancer Diagnostics Research and Development, Abbott Laboratories
Pre-analytical and analytical variation often can influence the specimen results that are determined in biomarker studies and in clinical laboratories. Pre-analytical considerations relate to the changes to analytes of interest that can occur between the time of veni-puncture to collect the specimen and time of result generation in the laboratory, including factors such as tube type, processing parameters, and storage conditions. Analytical considerations relate to the performance of the method to measure the analyte concentration, including factors such as sensitivity, accuracy, precision, robustness to cross reactants or interferences, and longterm reproducibility of the test across sites, instruments, technicians, lots of reagents, etc. Some of our own work will be shown to demonstrate the importance of these parameters, as well as a review of some key illustrative data from the literature.

2:30-3:00 Biomarker and Companion Diagnostics Assay Development: An IVD Perspective
Thomas Li, Ph.D., Senior Director, Technology Management, Roche, Inc.
This presentation will focus on current issues in biomarker assay and platform development. Updates on blood-based and tissue-based oncology diagnostics, multiplexed platforms, real time quantitative PCR and protein biomarker panel testing will be provided. Assay and platform commercialization strategy from an in vitro diagnostics (IVD) perspective will also be discussed.

3:00-3:30 Sponsored Presentations
(Opportunities Available)

3:30-4:30 Refreshment Break with Exhibit and Poster Viewing

Total vs. Free Analyte Quantification

4:30-5:00 Assessment of Free-and Total- Drug Concentration in the Development of Biotherapeutic Agents - Analytical and Biological Considerations
Scott Fountain, Ph.D., Senior Director, Translational Research, Department of Pharmacokinetics, Dynamics & Metabolism, Pfizer Global Research and Development
Full characterization of exposure/response kinetics of antibody therapeutics, such as PKPD and PBPK modeling, often requires assessment of both the “free” and “total” concentration of the biotherapeutic in circulating and target bound forms.  This presentation will provide perspectives on both the analytical and biological considerations of these in vivo assessments.  Analytical approaches to fully characterize these biological systems, including alternatives to ligand-binding assay formats such as mass spectrometry and flow cytometry, will be discussed in this presentation.  Considerations and applications of “free” and “total” concentration in biologics systems, focusing on the therapeutic agents themselves, will be discussed and framed to complement the following discussion on target protein biomarkers.

5:00-5:30 Quantification of “Total” and/or “Free” Target Protein Biomarker: Approaches and Applications
Jean Lee, Ph.D., Scientific Director, PKDM, Amgen
Many protein therapeutics actions are through target mediation of receptors. The protein drug would bind to a tissue membrane receptor and its soluble form(s) in circulation, which often is the target biomarker analyzed. In general, the soluble protein biomarker is present at low abundance as compare to the membrane-bound target in the tissue. Most protein drugs are given at a high molar ratio relative to the soluble target. Measuring the free soluble target after dosing would be extremely difficult. For ligand binding assays choice of specific or nonspecific binding reagents and pretreatment steps can be designed to measure either the free or total analyte. Information of free and total target biomarker and the therapeutic would provide valuable information on binding constants and PK/PD exposure/effect over time. This presentation will discuss the challenges, approaches of ligand binding assays and applications of “free” or “total” target biomarker quantifications.

5:30-6:00 Target-Related Pharmacodynamic Analysis to Guide Successful Development of Biological Therapies: Novel Biomarker Concepts and Analytical Strategies
Miro Venturi, Ph.D., Head, PK/PD Assay Development Group, Novartis Biologics
Knowing the pharmacokinetics (PK) and pharmacodynamics (PD) of a drug candidate and the response of a patient to therapeutic intervention is crucial to the design and effectiveness of clinical testing. Specifically, in the rapidly expanding field of biological therapies (i.e. monoclonal antibodies) it is becoming of paramount importance to understand their mode of action and precise dosing and regimen of administration as early as possible in the drug development process, so as to best assess both safety and efficacy in pivotal clinical trials. Commonly, monoclonal antibodies targeting soluble circulating targets (namely cytokines) would bind to their specific antigen and produce an increase in its half-life, depending on diverse factors such as the production rate of the targeted analyte, the disease staging and etiology, the elimination rate of the drug itself. Since the level of free (non-antibody bound) cytokine drives clinical response and may constitute a powerful biomarker, there is a need to determine the suppression of free cytokine levels to validate the ability of the mAb to find and bind its target. However, free cytokine levels are often in the attomolar range even in most disease states. When the drug is added, free cytokine levels then decrease further, providing an even greater bioanalytical challenge. Most commonly used methods for mAb drug and cytokine measurements are ligand-binding assays. In this talk, we will address the bioanalytical challenges posed by analyzing not the free cytokine, but the total (i.e. the complex of target antigen with its mAb drug) using descriptive case studies, which have then permitted calculation of the free target levels by computational PK/PD modeling approaches.

6:00-7:00  Roundtable Discussions

Topics include:

7:00 Close of Day