Track 1: Biomarkers In Drug Development 

Archived Content

Monday, May 21

1:00-2:00 Main Conference Registration

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

Julia Boguslavsky, Executive Director, Conferences, Cambridge Healthtech Institute

Biomarkers as Decision-Making Tools 

2:10-2:15 Chairperson's Opening Remarks

2:15-2:45 Turning an Active Compound into a Personalized Medicine: Do Biomarkers Help or Hinder?

Geert Kolvenbag, M.D., Ph.D., Global Product Vice President, AstraZeneca

The co-development of drug and biomarker has several inherent risks and challenges. In addition, the expectations and demands of the oncology community have increased over the last years. These challenges will be illustrated by a case study of a very active compound destined for a fast development program as a personalized medicine, but running into scientific, diagnostic and development challenges. This experience creates questions for the development of drugs and diagnostics today and in the future.

2:45-3:15 Evaluation of Biomarker Performance in the Real World: Comparative and Cost-Effectiveness Considerations

Felix W. Frueh, Ph.D., President, Medco Research Institute, Medco Health Solutions, Inc.

The difference between the potential to achieve an outcome and actually achieving it for a biomarker-guided intervention can be measured as the performance of a biomarker under controlled (optimized) conditions and its actual performance in the real-world.  Similar to post-approval safety and efficacy evaluations of drug therapies that differ from data found in pre-market assessments, the impact on clinical outcomes using biomarker-guided interventions are often not fully understood until these interventions are performed and analyzed in the heterogeneous environment of real-world clinical practice.  Following the two most critical factors, clinical outcomes and cost associated with reaching these outcomes, the Medco Research Institute has been conducting a series of real-world assessments of the performance of biomarkers to determine whether or not they should be integrated into everyday clinical practice.

3:15-3:45 Biomarkers: Finding the Balance between Driving Decision Making and Value or Distraction from Developing Drugs

Duncan McHale, Ph.D., Vice President, Global Exploratory Development, UCB Pharma

The past 5 years have seen an increasing focus on the identification and qualification of biomarkers. We now have tools which can generate proteomic or nucleotide data on hundreds of thousands of markers in single experiments and whole departments whose aim is to identify and qualify biomarkers. There are now 2 ICH guidances (E15 and E16) on genomic biomarkers and new regulatory processes developed specifically for qualifying biomarkers for use in regulatory decision making. This talk provides examples of where real value has been obtained using biomarkers as well as other areas where it has not. It will ask whether we have the balance right and how much should we invest in biomarkers and when.

3:45-4:15 Predicting Benefit to Therapy: Biomarkers and Molecular Profiles in Oncology Drug Development

Nicholas C. Dracopoli, Ph.D., Head, Oncology Biomarkers, Janssen R&D

The main goals of biomarker research in the pharmaceutical industry are to increase efficiency of the drug development process by improving understanding of the mechanism of action, deeper exploration of PK-PD interactions and predicting response to novel therapies in clinical development. However, predictive biomarkers are still only included in the labels of a minority of the oncology drugs approved in the U.S. since Herceptin in 1998. The development of novel biomarkers has enormous potential to impact drug development and improve patient outcomes. However, no complex molecular or protein profiles have been approved by the FDA to drive therapeutic use of any drug. This presentation will show how the small numbers of patients enrolled in clinical trials and the lack of long-term outcome data have limited the discovery of complex molecular profiles with strong predictive values (both negative and positive), and show how simple biomarkers measuring the status of the drug target or pathway (BRAF mutation, ALK-EML4 translocation, etc.) have been much more successful in the identification of highly predictive biomarkers which have been developed as companion diagnostics to drive therapeutic use of novel oncology drugs.

4:15-5:15 Welcome Reception in the Exhibit Hall with Poster Viewing

• • •

Tuesday, May 22

Myriad-RBM 

7:30-8:15 am Breakfast Presentation

Identification of Fluid Biomarkers of Treatment Response in Schizophrenia CSF and Plasma Samples

Eric Schaeffer, Ph.D., Director, Neuroscience Clinical Biomarkers, Bristol-Myers Squibb

Schizophrenia is a heterogeneous disease of complex and poorly understood etiology. Patients are often prescribed one of several approved medications based on their symptoms, but there is a high rate of switching among medications during a period of trial and error, while physicians seek to identify a drug(s) which will result in stabilization of symptoms. Given the variability in treatment response, there would be considerable value in the identification of a biomarker(s) which could provide an indication of whether a patient is responding to a particular medication early in the treatment regimen. This talk will discuss a biomarker identification and validation strategy focusing on highly multiplexed immunoassay panels offered by Myriad RBM.

CASE STUDIES IN Rx/Dx CO-DEVELOPMENT 

8:25-8:30 Chairperson’s Opening Remarks

8:30-9:00 Zelboraf: The Co-Development of Zelboraf and Its Companion Diagnostic

Walter H. Koch, Ph.D., Vice President and Head of Global Research, Roche Molecular Diagnostics

Cancers can be categorized based on their molecular etiology, including oncogenic driver mutations that are present. The development of targeted therapies alongside companion diagnostics that will identify patients most likely to receive benefit provides the opportunity to increase the success rate for oncology drugs and to decrease development time and associated costs. This presentation will detail the co-development of Zelboraf and the cobas 4800 BRAF V600 mutation test from the diagnostics perspective. This integrated process resulted in approval of the first personalized medicine for the treatment of metastatic melanoma within 6 years of the drug’s discovery, a remarkably short time.

9:00-9:30 Crizotinib: The Xalkori, ALK CDx Partnership

Karen S. Long, Ph.D., Vice President, Medical, Regulatory and Clinical Affairs, Abbott Molecular

Pharmaceutical companies are increasingly engaging diagnostic companies to develop companion diagnostics to help select patients for their therapeutics. There are a number of factors that guide the pharmaceutical company’s choice of diagnostic partner including IP considerations, diagnostic platform requirements and commercialization capabilities. However, in view of the relative size and importance of the U.S. market, the ability of the diagnostic company to navigate through the sometimes ambiguous regulatory process in the U.S. becomes a critical consideration, as this is vital to achieve product launch timing objectives and overall success of the therapeutic. There have been some recent examples of rapid co-development and approval of therapeutic/diagnostic product combinations in the U.S. including the recent Xalkori/ALK CDx approval. This session explores the factors that were most important in the successful co-development effort, approval and subsequent commercialization of the diagnostic.

9:30-10:30 Coffee Break in the Exhibit Hall with Poster Viewing

TECHNOLOGY SHOWCASE: Biomarkers in Drug Development 

Caprion 

10:30-11:00 Successful Mass Spectrometry Strategies for Biomarker Discovery and Verification

Daniel Chelsky, Ph.D., CSO, Caprion Proteomics

Two mass spectrometry methods have been applied for the rapid discovery of biomarker and diagnostic candidates. In the first approach, a non-hypothesis driven strategy was applied to compare multiple disease cohorts in TB. Hundreds of proteins were identified, of which 90 were found to be differentially expressed, based on relative peptide signal intensity. The candidate proteins were then specifically targeted with a multiplexed “MRM” mass spectrometry assay and analyzed in different populations, resulting in verification of many of the disease markers.  In a second discovery approach, the non-hypothesis based strategy was bypassed in favor of focusing on the known biology. Hundreds of proteins associated with immune response were specifically targeted in an MRM assay to identify a subset associated with vaccine efficacy.

Huntingdon Life Sciences11:00-11:30 Translational Biomarkers in Drug Development

Mark Fidock, Ph.D., Global Head, Biomarkers & Translational Sciences, Huntingdon Life Sciences
The Pharmaceutical Industry faces many challenges in the development of new medicines.  As part of risk management, the strategic development and use of Biomarkers will ensure that the projects hypothesis is confidently tested in the clinic.  To exemplify these principles, a case study form the area of inflammation will describe how Biomarker data was employed for key decision making during the TLR7 drug development programme.


11:30-12:30 Sponsored Presentations (Opportunities Available)

Contact Ilana Quigley at iquigley@healthtech.com or 781-972-5457

BioScale 

12:30-2:00 Luncheon Presentation

Activity State Quantification of Kinase Pathways Using AMMP Single Plate Technology

W. Matthew Dickerson, Ph.D., Senior Scientist, Assay Development, BioScale, Inc.

Gathering data on the activation-state of MAP and PI3 kinases from tumor samples could accelerate drug development. Non-optical, AMMP technology is used to quantitate the activity state of multiple kinases including EGFR, MEK/ERK dimer, AKT, p38 and JNK. Unstimulated tumor lysates were compared with those stimulated by ligands to well-known surface receptors for changes in their phosphorylation states. The data show AMMP assays can monitor the MAP/K pathway activation from EGF stimulation through ERK phosphorylation.

Biomarkers to Predict Clinical Outcome 

2:00-2:30 Utilization of Biomarkers in Development of Treatments for Heterogeneous Immunologic Diseases

Carrie Brodmerkel, Ph.D., Director, Immunology Biomarkers, Janssen

Ulcerative colitis (UC) and Crohn's disease (CD) are heterogeneous diseases that impact the gastrointestinal system. While anti-TNF therapy is effective in both diseases, there remains a significant population that does not derive benefit. Understanding the molecular signature of response to anti-TNF treatment can identify the core pathway modulation required to achieve clinical response while understanding the non-response signature can aid in identifying novel pathways which may be driving disease in anti-TNF non-responders. Here we present molecular cross-comparison of UC and CD as well as the effects of biologic therapies on the dystregulated pathways. These results offer insight into the patient subpopulations most likely to benefit from therapy.

2:30-3:00 Biomarkers in Discovery and in Clinical Trials

Suso Platero, Ph.D., Director, Oncology Biomarkers, Janssen Research & Development

Biomarkers are the tools that can bring personalized therapy to fruition. They have the ability to become companion diagnostics if there is a good correlation between the readout of the biomarker and response to a specific therapy, such as the recent case of ALK translocation and Crizotinib. Early studies in development of compounds are required if one expects to have biomarkers ready at the same time the drug is approved. The discovery of several predictive and pharmacodynamic biomarkers will be described using both in vitro and in vivo methods together with their applications in clinical trials

3:00-3:30 Hodgkin’s Lymphoma Biomarkers to Predict Clinical Outcome

K. Stephen Suh, Ph.D., Director, Genomics and Biomarkers Program, Cancer Center, Hackensack University Medical Center

Hodgkin’s lymphoma (HL) represents 12% of all lymphoma cases and up to 16% of HL patients are either refractory or undergo multiple relapses. To investigate whether circulating HL cells are associated with poor clinical outcome, PBL of HL patient samples were analyzed for the presence of CD30+/CD15+ cells in the PBL buffy coat. Our data showed that circulating HL cells were only found in the bad outcome group and these cells overexpress SDC1 and FGF2. A subpopulation of HL tissues tested include CD30+ HL cells that co-overexpress SDC1, FGF2 and metastatic markers TGF-beta and MMP9. Together, these data suggest that aggressive HL cells may shed from the tumor microenvironment to enter systemic circulation and metastasize to distant organs.

3:30-4:00 Case Study: Identifying a Predictive Biomarker of Response to Imetelstat, a Telomerase Inhibitor

Katia Bassett, Ph.D., Scientist II, Translational Oncology, Geron Corporation

Imetelstat is a specific inhibitor of telomerase, currently in Phase II clinical trials. Differential sensitivity to Imetelstat has been observed in vitro. Diseases with short telomeres are highly susceptible to Imetelstat in vitro. Telomere length is a candidate predictive biomarker for Imetelstat responsiveness, being developed to increase probability of success of Imetelstat in the clinic

4:00-5:00 Refreshment Break in the Exhibit Hall with Poster Viewing

Use of Biomarkers in Proof-of-Concept 

5:00-5:30 Using Predictive Diagnostics to Enable Therapeutic Proof-of-Concept in Cancer Subpopulations

Garret Hampton, Ph.D., Senior Director, Oncology Biomarker Development, Development Sciences, Genentech

Clinical development of new medicines in cancers has typically taken an all-comers approach, assessing drugs on the basis of anatomic origin. This approach has led to generally high clinical failure rates, increasing the overall cost of bringing new drugs to patients, and creating an unsustainable development paradigm. Here, we discuss how reasonably formulated diagnostic hypotheses, coupled with appropriate clinical trial design and clinical operations, enable therapeutic proof-of-concept in cancer sub-populations. We discuss how these studies further our understanding of disease and enable the co-development of companion diagnostics to make informed treatment decisions.

5:30-6:00 Toward Personalized Medicine in Metabolic Disease

Alain van Gool, Ph.D., Professor, Molecular Profiling, Radboud University, Netherlands; Coordinator, Netherlands Organization for Applied Sciences Research; Head, Radboud Proteomics Centre

The field of oncology has paved the way in the use of biomarkers in translational and personalized medicine, enabling the selection of the most responsive patients for specific treatments. The most successful examples are those where disease can be linked to a single genetic driver and drugs are used to shut down an overactivated pathway. A challenge appears, however, when these lessons learned are to be applied to complex chronic diseases as metabolic syndrome. The progression from a healthy state to obesity, diabetes and ultimately to diabetes complications, including cardiovascular events, nephropathy and brain disorders to name a few, is based on a gradual disturbance of multiple equilibria. Influencing one equilibrium using specific nutrition or drugs affects other pathways in this complex system, resulting in seemingly positive effects on short-term but deleterious effects in seemingly non-related diseases on long term. Key to successful treatment in metabolic disease is the use of system biology, not only to elucidate key disease mechanisms and identify key biomarkers, but also to use panels of such biomarkers to monitor the effect of interventions on the human system as a whole, and timely adjust when needed. Opportunities to implement such an approach in health care through public/private partnerships will be discussed.

• • •

Wednesday, May 23

7:30-8:15 am Breakfast Presentation (Opportunity Available)

Contact Ilana Quigley at iquigley@healthtech.com or 781-972-5457

Biomarker Assays to Support Drug Development 

8:25-8:30 Chairperson’s Opening Remarks

8:30-9:00 Automated Platforms in Biomarker Analysis Past, Present and Future: Case Studies, Comparisons and Review of Assay Validation Data

John L. Allinson, FIBMS, Vice President, Biomarker Laboratory Services, ICON Development Solutions

Presentation will cover a variety of analytical platforms used to measure biomarkers in support of drug development. It will look at the evolution and development of the platforms, and give case-study data generated on some of them. It will also give a personal insight into possible developments in the future as the use of biomarkers for patient stratification and companion diagnostics increases; and discuss the challenges in developing and transferring methods for new biomarkers on to these platforms—including point-of-care-type equipment.

Meso Scale Discovery 

9:00-9:30 Analytical-Grade Multiplexed Assays: Requirements from the Biomarker Community

Robert Umek, Ph.D., Director, External Scientific Affairs, Meso Scale Discovery

Scientists and clinicians appreciate the importance of protein biomarkers in drug development and therapeutic management. We will explore the challenges associated with an increasing demand for reliable, meaningful biomarker panels and how these demands can be met using MSD’s multiplexed quantitative immunoassays. This talk focuses on protein biomarkers from a practical perspective, exploring the complex roles played by corporations, regulatory agencies, and independent researchers, and the challenges they face meeting the demand for biomarker panels that support their research and clinical objectives.

9:30-10:00 Leveraging Enabling Technologies for Biomarker Discovery and Validation

Bonnie J. Howell, Ph.D., Head, Molecular Biomarkers, Merck West Point

10:00-11:00 Coffee Break in the Exhibit Hall with Poster Viewing

11:00-11:30 Bioanalytical Challenges to Quantify Soluble “Free” Target Biomarkers in Antibody Therapeutics

Jenny Wang, Ph.D., Principal Scientist, Pharmacokinetics, Dynamics, and Metabolism, Pfizer

Many therapeutic antibodies act through neutralization of soluble targets in circulation. The free target concentration is an important biomarker for understanding the dynamic relationship of the drug and the target for determining therapeutic efficacy and assisting the model-based determination of optimal dose selection and regimen. The association and dissociation of the immune complexes, dynamic ratios of the drug and the target over time after dosing, and multiple sources of disturbance of the drug/target equilibrium during bioanalysis and sample handling pose a tremendous challenge for accurate quantification of free target concentrations in biological samples. In this presentation, a therapeutic antibody against a soluble peptide is used as a case study to illustrate major factors that affect the accuracy of free target measurement. Immune complex separation techniques and critical reagent selection will be discussed.

11:30-12:00 Integrating Proteomics and Genomics into Next-Gen Systems Pathology

Michael H. A. Roehrl, M.D., Ph.D., Assistant Professor and Director of BioBanking, Department of Pathology and Laboratory Medicine, Boston Medical Center

We will discuss proteomic and metabolomic cancer biomarker discovery, cancer exome sequencing, and joint computational data interpretation of next-gen sequencing with proteomics. We will discuss specific applications from our institution of comprehensive omic profiling of solid tumors from patients and the application of cutting-edge technology development in mass spectrometry and next-gen sequencing to drive and innovate personalized molecular medicine. We will demonstrate that ultra-rapid tissue biobanking is critically important for faithful physiome preservation to enable biomarker discovery and next-gen molecular diagnostics.

Singulex12:00-1:30 Luncheon Presentation
Advanced Single Molecule Detection: Accelerating Biomarker Development through Ultrasensitive Immunoassay Technology
Lynn Zieske, Ph.D., Vice President, Commercial Solutions, Singulex, Inc.Biomarker verification and validation programs are in need of sensitive detection technologies to provide precise biomarker measurements in clinically relevant samples. To address this critical need, the patented Erenna® Immunoassay system from Singulex offers sub-picogram per mL resolution at an improvement of 1-3 fold over standard ELISAs. Here we present case studies demonstrating how the use of the Erenna Immunoassay System has provided critical insights toward improving the clinical utility of biomarkers.
 

Pharmacogenomic Biomarkers to Predict Benefit from Therapy 

1:30-2:00 Discovery of Pharmacogenomic Biomarkers in Cardiovascular and CNS Disorders through Expression Genomics

Wolfgang Sadee, Dr.rer.nat., Professor and Chair, Pharmacology; Director, Program in Pharmacogenomics, The Ohio State University

Genetic biomarkers have potential clinical utility for predicting disease risk and outcomes, including response to therapy. Pharmacogenomic biomarkers are rapidly gaining acceptance in drug discovery, development and therapy; however, a substantial portion of the responsible genetic factors is still uncertain (“missing heritability”). Available evidence suggests that genetic variants affecting expression regulation and RNA processing/translation may account for a large portion of genetically-determined phenotypic variability. We have developed comprehensive assays to detect regulatory variants, recently including the use of second-generation sequencing. Results have revealed the existence of frequent genetic variants with strong influence on clinical phenotypes, including drug response, even in important pharmaco-genes that had been under intense study for some time (e.g., CYP3A4, DRD2, DAT, HTR2A, CETP, ACE, NAT1). Several of these variants have promise as biomarkers for drug therapy, possibly as companion diagnostics in specific cases.

2:00-2:30 Improving Efficacy and Reliability for Personalized Medicine: The Role of Companion Diagnostics in Drug Development

Amelia Warner, Ph.D., Director, Clinical Pharmacogenomics, Merck

Identification of subpopulations of patients who either have subclinical response or toxicity to a drug in clinical development is a challenge. Historically, identification of patients who have less than optimal response to drugs has occurred late in large global clinical trial review. However, the pharmaceutical industry is working to optimize preclinical models, known genetic variation across populations, and earlier inclusion of surrogate biomarkers in early development programs to allow for early identification of populations that will benefit from alternate dosing or alternate therapies. Adapting development strategies to include companion diagnostics remains a challenge, but pharmaceutical companies are developing clear working models to enable development of personalized therapies.

2:30-3:00 Applying Pharmacogenomics Effectively in Psychiatry and How to Overcome the Hurdles

Nadine Cohen, Ph.D., Senior Director, Head of Pharmacogenomics and Biomarker Execution Leader, Neuroscience Biomarkers, Janssen Pharmaceuticals Companies of Johnson & Johnson

An overview of pharmacogenomics applications at Janssen Neurosciences in Psychiatry will be discussed. Learn about using genomics to redefine mental disorders, managing complexity in psychiatric diseases with heterogeneity in disease biology and treatment response, and identifying genetic markers of clinical utility associated with treatment response for psychiatric drugs

3:00 Close of Conference