TUESDAY, JANUARY 27
8:00-8:30 Sponsored Presentation (Opportunity Available) or Morning Coffee
Contact Ilana Schwartz, Manager, Business Development, 781-972-5457 or ischwartz@healthtech.com.
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 Sponsored Presentation
Speaker to be announced, MesoScale
Sponsored by
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9:30-10:10 Multiplexed Biomarker Assay Development
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.
Sponsored by
3:00-3:15 Drug-Induced Nephrotoxicity – Multiplex Detection of Key Kidney Damage Biomarkers in Rat Urine
Scott Hayes, PhD., R&D Director, Assays, EMD Chemicals
In 2008 the Predictive Safety Testing Consortium (PSTC), a public-private consortium led by the Critical Path Institute (C-Path) submitted a list of urinary biomarkers indicative of drug-induced kidney damage to the FDA and EMEA regulatory authorities. The FDA and EMEA have issued new guidelines on the submission of the biomarkers as indicators of kidney damage in pre-clinical studies. Rules Based Medicine worked with the members of the PSTC to develop the assays used in the kidney toxicity study, and made the assays available in the Rat Kidney MAP testing service. EMD and Rules Based Medicine have collaborated to develop these assays as commercially available kits, exclusively for the Luminex® xMAP® Technology platform, to support preclinical rat nephrotoxicity studies. This presentation will describe the assessment of temporal and dose-dependent changes in biomarker levels in response to known kidney damaging agents.
3:15-3:30 Millipore, the Experienced Leader in ‘Fit-for-Purpose’ Biomarker Solutions Sponsored by
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Ronald R. Bowsher, Ph.D., Chief Scientist Biopharma Services, Millipore Corporation
Biomarkers are viewed widely within pharma/biotech as a key strategy for improving the success rate and cost-effectiveness of rational drug development. To help companies streamline drug development, Millipore has combined its expertise in ‘research diagnostic’ biomarker assays (single and multiplex) and bioanalytical services to provide sponsors with customized biomarker solutions to meet their individualized needs across the drug development continuum from Discovery through Registration phase and beyond. When combined with our superior LBA bioanalytical services, we are capable of providing sponsors with ‘one-stop’ shopping for generation, analysis, reporting and interpretation of PK/PD data.
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 – Practical Considerations
Bing Kuang, Ph.D., Principal Scientist, Translational Research, Department of Pharmacokinetics, Dynamics & Metabolism, Pfizer, Inc.
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. The knowledge on what the analytical assay measures, is important for quantitative understanding of the pharmacology of biotherapeutic agents. This presentation will provide perspectives on the requirement for measuring different forms of biotherapeutics and the analytical assessment challenges. Theoretical consideration for ligand binding assay and practical consideration for pharmacokinetic assays supporting development of biotherapeutic agents will be discussed. Aspects of “free” assay measuring unbound biotherapeutic agent in biological matrices will be addressed. Examples will be given to demonstrate the challenges of developing “free” ligand binding assay for soluble circulating target and the practical utility for antigen-specific capture assay in the development of antibody therapeutics.
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 Title to be Announced
Miro Venturi, Ph.D., Senior Biomarker & Experimental Medicine Leader, Roche Pharma Development, Roche Diagnostics GmbH
To be Announced.
6:00-7:00 Roundtable Discussions
Topics include:
• Multiplexed biomarker assays
• Total vs. free analyte quantification
• Assays for “omic” biomarkers
• Novel detection technologies
• In-house vs. outsourcing
7:00 Close of Day