Wednesday, May 6
11:00 am Conference Registration
12:15 pm Luncheon Presentation: Ultrasensitive Multiplexed Cytokine Measurements
Mark Roskey, Ph.D., Vice President & General Manager,
Applications and Reagents, Quanterix Corporation
The normal healthy range for many cytokines is very close to the limit of detection of conventional immunoassay measurement techniques. Ultra-sensitive Simoa technology measures biomarkers in blood at extremely low levels of detection, allowing researchers to measure both healthy and sick subjects with confidence. Multiplex cytokine panels allow users to achieve similar sensitivity with each marker in a multiplex panel as they would if they were to test individual assays.
1:30 Chairperson’s Opening Remarks
Michael E. (Ransom) Burczynski, Ph.D., Executive Director, Biomarker Technologies, Exploratory Clinical and Translational Research, Bristol-Myers Squibb
1:35 Enabling Robust Biomarker-Driven Decision-Making in Drug Development: Key Factors and Considerations
Michael E. (Ransom) Burczynski, Ph.D., Executive Director, Biomarker Technologies, Exploratory Clinical and Translational Research, Bristol-Myers Squibb
Prospective biomarker testing strategies in the clinic benefit from multiple perspectives including those of discovery biologists, translational scientists, biomarker technologists, physicians, statisticians, bioinformaticians and operational personnel. Studies designed from these perspectives enable teams to combine biomarker data across platforms from sufficiently powered, feasible-to-execute clinical studies that can potentially 1) elucidate disease pathophysiology, 2) confirm mechanism of action, 3) demonstrate target engagement, 4) confirm dose-dependent pharmacodynamic effects and even 5) determine if efficacy/safety profiles are enhanced in certain molecularly defined subsets of patients. In addition, judicious sampling in those same studies for future exploratory research can ultimately yield a biorepository of great value for identifying new disease indications, drug targets, biomarkers and other value-added information to the R&D organization in the future. Early definition of the biomarker strategy, coupled with a system that permits flexible re-evaluation of the strategy in light of new information, provides an optimal scenario for executing biomarker studies in the clinic. Finally, committing to objectively assessing each biomarker study’s success and impact in the overall decision-making around a candidate drug’s development permits a return-on-investment (ROI) calculation that can help refine future biomarker strategies to ensure only the most highly informative biomarker approaches and methodologies are employed. The present talk will review the basic tenets of a robust biomarker evaluation process and illustrate several biomarker study approaches in this paradigm that have led to rapid data generation, analysis and interpretation to support key decisions during the early clinical development of candidate therapies.
2:00 Who Owns Biomarker Qualification and Surrogate Endpoints?
John A. Wagner, M.D., Ph.D., Senior Vice President & Head, Global Clinical and Translational Sciences, Takeda Pharmaceuticals
2:25 Talk Title to be Announced
Ian McCaffery, Ph.D., Head, Companion Diagnostic Development, Genentech
2:50 Ultrasensitive Measurement of IL-17 in Psoriasis Patients
Cathy Soderstrom, Senior Scientist, Regulated Biomarkers Group, Pfizer Groton
Interleukin 17 A (IL-17A) plays a central role in psoriasis pathogenesis. Pfizer is pursuing the development of drugs for the treatment of psoriasis, with projects in various stages of clinical and preclinical development. To better understand the role of IL-17A and IL17A/F in response to psoriasis therapies, we used the Singulex Erenna to analyze serum samples (n=328) from a previous Pfizer clinical study comparing two therapies in patients with moderate to severe psoriasis. Results from placebo, treatment responders and treatment non-responders were closely compared. Additionally, a pilot method study was done to compare skin biopsies and serum samples from psoriasis patients.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 Chairperson’s Remarks
Johan Luthman, D.D.S., Ph.D., Vice President, Clinical Neuroscience, Eisai
4:30 Current Status for AD Biomarkers: From Mice to Men to Trials and Clinical Practice
Johan Luthman, D.D.S., Ph.D., Vice President, Clinical Neuroscience, Eisai
Alzheimer’s disease (AD) is a clear illustration of the introduction of biomarkers that has entirely changed the way drug R&D is executed, but also shows the challenges of addressing remaining hurdles. In AD research, biomarkers are now applied to translate animal data to early clinical studies, as well as to both identify and stage the disease in clinical trials. For example, biomarkers have become critical for diagnosis of AD pre-dementia. Moreover, demonstration of the presence of AD pathology using biomarkers has become central for drug trial stratification and enrichment strategies. Several modalities of AD biomarkers, imaging (e.g. MRI and PET), bio-fluid (e.g. CSF measures) and functional, are available for which there are different, but also commonly overlapping applications. At the same time, for many AD biomarkers considerable work remains in obtaining sufficient data on assay performance, clinical qualification for the intended context of use, standardization of use and regulatory approval before one can fully implement them in clinical trials and practice. In addition, it is also important to note the possibilities for operational implementation as well as the general acceptance and commercial potential of various AD biomarker modalities varies considerably. Commonly there are also differing opinions between academic and industrial scientists and regulators of what constitutes satisfactory validation and qualification for use of AD biomarkers as stand-alone or companion diagnostics, or as supportive outcome measures in clinical trials.
4:55 Approaches to Biomarkers that can “Translate the Stubbornness of Fortune”
William B. Mattes, Ph.D., DABT, Director, Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration
The terms “biomarker” and “translational” are all too often abused buzzwords; to have practical meaning for public health a certain rigor must be applied to their use. Per the Working Group definition a “biomarker” should be “a characteristic that is objectively measured” and to that end the assay used to measure it should be robust and validated for performance characteristics. Research in many laboratories, including ours, focuses on potential biomarkers, but that distinction should not be forgotten. Furthermore, the biomarker should be “an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention”; the implication is that the context of use need be explicitly defined. This is the process of qualification, to be distinguished from analytical validation. To be truly “translational” a biomarker needs to satisfy the above criteria and be qualified in at least two experimental settings, such as measuring liver injury in rodents and in humans. Of course, that means the assay must be validated for performance in the biological media obtained from the different settings. More difficult for the translational qualification is the reality that experimental designs in non-clinical and clinical investigations are too often vastly different. Approaches to address these challenges and examples will be discussed.
5:20 Understanding IMiDs: Mechanism, Differentiation and Biomarkers
Patrick R. Hagner, Ph.D., Scientist, Translational Development, Celgene
Thursday, May 7
7:30 am Breakfast Presentation: Next Generation in Situ Hybridization (ISH) and Immunohistochemistry (IHC)
Sven Müller, Ph.D., Manager, R&D, ISH pharmDx, Dako - an Agilent Technology company
The need for solid tumor biomarkers to be confirmed in context of tissue morphology calls for routine involvement of slide based techniques like IHC and ISH. The major drawbacks of these methods relates to a qualitative readout and a slow turn-around time, respectively. Based on Dako, an Agilent Technologies Company's long term IHC and ISH expertise we are bringing these technologies to the next level, enabling us to continue being a One Stop Shop in IHC and ISH solutions for pharma partners - from early development to IVD class III kits. The symposium focuses on game changing improvements of the ISH and IHC technologies.
8:25 Chairperson’s Remarks
Ken Chang, Ph.D., Clinical Assay Development & Outsourcing Lead, Merck
8:30 Development and Validation of a Clinical Biomarker Assay to Quantitate Thymic Stromal Lymphopoietin in Human Plasma at Sub-pg/mL level
Xuemei Zhao, Ph.D., Principal Scientist, Molecular Biomarkers and Diagnostics Laboratory, Merck
TSLP is an attractive therapeutic target for the treatment of allergic diseases, and plasma TSLP is a potential biomarker in the development of therapeutic agents. We developed and validated an ultra-sensitive electrochemiluminescence assay for measurement of TSLP in plasma with a lower limit of quantitation of 0.12 pg/mL, which allowed the quantitation of TSLP in approximately 90% of human plasma samples tested. The assay demonstrated excellent performance characteristics. The validated TSLP assay enables assessment of circulating TSLP as a patient selection marker in the development of therapeutics to treat atopic diseases.
8:55 Fit-For-Purpose in situ Analytical Validation of NGS Mutation Profiling in FFPE Tissue
Ken Chang, Ph.D., Clinical Assay Development & Outsourcing Lead, Merck
We have developed a “Concordance Calculator” to quantify reproducibility of multi-variant calls among Next-Generation Sequencing (NGS) replicates (same gDNA with different library preparations). This novel approach also allowed us to eliminate many different technical artifacts including Post Tissue Collection Modifications (PTCM) such as deamination and oxidation artifacts. We then developed a “Fit-for-Purpose in situ analytical validation” strategy using RainDance ThunderBolts Cancer Panel to include part of the analytical validation directly on each and every clinical sample. This strategy also involves using a set of normal FFPE tissue samples to eliminate panel/library prep/pipeline specific artifacts. The detail of this novel analytical validation approach will be discussed in detail.
9:20 SOMAmer® Reagents and the SOMAscanTM Assay, Tools for Real-Time Biology
Andy Keys, Associate Director, Sales, North America, SomaLogic
SomaLogic’s proteomic tools have found broad success in R&D applications including: biomarker discovery and diagnostics development, target validation in pre-clinical and clinical research; pharmacology in cells, tissues, and clinical samples; and custom assay development. We offer tools from broad biomarker discovery to developing single detection reagents.
9:35 The Impact of Preanalytical Variables on Biomarker Research
David Craft, Ph.D., Senior Manager Sciences, Preanalytical Systems, Becton Dickson & Company
The use of biomarkers can potentially improve the efficiency of the drug development process. The preanalytical phase has great potential for errors. This presentation will focus on the potential impact of sample handling on RNA, proteins, cells within blood / tissue and how this variability can be controlled.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Discover Genomic Biomarkers for Assisting Vaccine Research and Development
I-Ming Wang, Ph.D., Principal Scientist, Genetics and Pharmacogenomics, Merck Research Labs
This presentation describes our integrated analysis of immune response to infection and vaccination by a genome-wide blood gene expression approach. Our main goal is to determine prediction rules governing the immune system’s behavior under different conditions. Proof-of-concept human and non-human primate genomic studies were conducted to identify potential accessible biomarkers for predicting vaccine response/safety and disease susceptibility to infection. Harvesting results from these efforts and applying them in the clinical setting should significantly enhance our capacity for future vaccine development.
11:10 Drug Target Validation in Concert with Clinical Development
Liling Warren, Ph.D., Senior Scientific Investigator, GlaxoSmithKline
11:35 Novel Biomarker Approaches for Pathologic Angiogenesis in Human Cancers
Aejaz Nasir, M.D., MPhil, Fellow, College of American Pathologists; Senior Medical Advisor & Surgical Pathology Lead, Molecular Solid Tumor & Anatomic Pathologist, Tailored Therapeutics, Diagnostic & Experimental Pathology, Eli Lilly and Company
12:00 pm Luncheon Presentation: Reagent Qualification and Platform Selection Considerations for Single and Multiplex Biomarker Analysis in Support of Clinical Studies
Afshin Safavi, Ph.D., Founder and CSO, BioAgilytix Labs
Biomarker analysis has become a common practice by many pharmaceutical companies to support PK/PD modeling. The reliability of outcomes is heavily influenced by the quality of the reagents and commercial kits as well as the selection of bioanalytical platform. Case studies will be presented to highlight the key bioanalytical considerations involved in running successful biomarker analyses in support of clinical studies with consideration to platform selection and critical reagents as well as kit selection.
1:30 Chairperson’s Opening Remarks
George A. Green IV, Ph.D., Group Director, Pharmacodiagnostic Center of Excellence, Bristol-Myers Squibb
1:35 Creating and Managing the Multiple Interfaces of Drug/Diagnostic Co-Development
George A. Green IV, Ph.D., Group Director, Pharmacodiagnostic Center of Excellence, Bristol-Myers Squibb
Andrea H. Lauber, Ph.D., Executive Director, Business Development, Clinical Biomarkers and Pharmacodiagnostics, Bristol-Myers Squibb
Many pharmaceutical companies are using an external partnering model to pursue co-development of drugs and diagnostic products. This approach provides access to diverse biomarkers, technology and platforms, as well as diagnostic manufacturing and commercialization expertise, thus maximizing diagnostic development capabilities. External partnering creates multiple interfaces of functions both within and between the drug and diagnostic companies. We will explore some of the challenges that accompany these interfaces, their management and implications, along with ideas for optimizing the “virtual diagnostic company” model for the Rx/Dx co-development environment.
2:25 Innovative Strategies and Progress in Translational Biomarkers in Clinical Oncology through Public-Private Partnerships
Paula Eason, Ph.D., Scientific Program Manager, Cancer Division of Research Partnerships, Foundation for the National Institutes of Health
The continual need for development of biomarkers with robust clinical utility is an ongoing challenge for all cancer types. Incorporation of prognostic and predictive biomarkers into clinical trial strategies and therapeutic decision-making is essential to disentangle the complexities of the pathogenic process, drug pharmacodynamics, and tumor heterogeneity. Success will require strategic partnerships and alliances between public and private sectors to share resources, risks, experience and expertise, and to align multiple stakeholder incentives to support and accelerate sustainable innovation.
2:50 Close of Conference