Track 3: Biomarker Assay 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

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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 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 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 Molecular Diagnostics 

Advanced Cell Diagnostics 

10:30-10:45 Advanced Molecular Diagnostics Based on Ultrasensitive RNA in situ Hybridization

Yuling Luo, Ph.D., Founder, President & CEO, Advanced Cell Diagnostics, Inc.

RNA biomarkers are traditionally analyzed by "grind-and-bind" assays such as RT-PCR, which loses critical cellular context for clinical interpretation. Recent advances in in situ RNA analysis capable of detecting single RNA molecules in routine clinical specimens may finally enable more advanced RNA-based diagnostics.

BioAgilytix Labs 

10:45-11:00 Lot Bridging Considerations for Single and Multiplex Immunoassay Kits in Biomarker Studies

Afshin Safavi, Ph.D., Founder & Vice President, BioAnalytical Operations, BioAgilytix Labs

Biomarker analysis has become a common practice by many pharmaceutical and biotechnology companies to help PK/PD modeling.  The reliability of outcomes is heavily influenced by the quality of the kits used to support the studies.  The goal of this presentation is to increase awareness of the bioanalytical considerations that are involved in bridging immunoassay assay kit lots.

11:00-12:00 Sponsored Presentations (Opportunities Available)

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

Luminex 

12:00-12:30 Utilization of One Platform from Discovery to the Clinic: A Multiplex Approach

Jeremy Bridge-Cook, Ph.D., Senior Vice President, Assay Group, Luminex Corporation

When formulating a biomarker strategy from discovery to commercialization, one ideally would utilize a flexible assay platform that could be applied to a broad array of biomarker types, could cover one or many biomarkers simultaneously, could be transitioned directly into clinical trials, regulatory submissions, and the clinic, and that is widely adopted in the diagnostics marketplace.  A platform which meets all these criteria will be presented, with examples from discovery to diagnostics.

12:30-2:00 Enjoy Lunch on Your Own

The Future of Laboratory-Developed Tests 

2:00-2:30 LDTs in the Context of CLIA: An NCI Experience

Daniel Edelman, Ph.D., Facility Head, Clinical Molecular Profiling Core, NIH/NCI/CCR/Genetics Branch

The mission of the Clinical Molecular Profiling Core (CMPC) of the National Cancer Institute (NCI) is to provide state-of-the-art genomic testing for specimens obtained from NCI clinical trials. The greatest impact is affected where test results have immediate clinical application for personalized cancer therapy for individual patients enrolled in these trials. To that end, the CMPC is CLIA compliant and provides a growing set of clinical test modalities. In this talk we'll present and discuss the challenges of meeting CLIA regulations for high-complexity tests that did not exist as diagnostic tests when the federal guidelines were written.

2:30-3:00 Laboratory-Developed Tests: Regulatory Requirements in the U.S.

Franklin R. Cockerill, III, M.D., Ann and Leo Markin Professor and Chair, Laboratory Medicine and Pathology, Mayo Clinic College of Medicine; President and CEO, Mayo Medical Laboratories

Testing performed in clinical laboratories in the United States is regulated by CLIA and FDA. Additionally, testing for New York State patients has additional requirements. Laboratory-Developed Tests (LDTs) are those tests developed and performed in laboratories which have not been approved or cleared by the FDA. Validation of clinical testing includes both analytical and clinical components. CLIA has traditionally regulated analytical validation and FDA/New York State, clinical validation.  Recently, validation of LDTs has come under increasing scrutiny by the FDA with an announcement that a guidance document is forthcoming. This lecture will review specific requirements by these agencies, identify redundancies, and provide potential solutions towards a consolidated approach for efficient value-driven regulation of clinical laboratory testing.

3:00-3:30 Talk Title to be Announced

Andrea Ferreira-Gonzalez, Ph.D., Professor and Chair, Division of Molecular Diagnostics; Director, Molecular Diagnostics Laboratory, Department of Pathology, Virginia Commonwealth University

3:30-4:00 Regulatory Considerations for Using a Laboratory-Developed Test (LDT) During a Pivotal Clinical Trial

Mya Thomae, CEO, Myraqa, Inc.

LDTs offer many advantages in the clinical trial setting including rapid development and service-oriented delivery. If an LDT will be used as a companion diagnostic, these benefits need to be carefully weighed against other considerations, including availability of appropriate documentation, level of regulatory sophistication and geographic limitations of the test itself. The presentation will explore best practices for risk mitigation to ensure that an LDT-based diagnostic does not hold up drug approval.

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

Biomarker Assay Development for Diagnostics 

5:00-5:30 Early Results of the NCI Clinical Assay Development Program

J. Milburn Jessup, M.D., Chief, Diagnostics Evaluation Branch, Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health

Academic investigators and small companies find it increasingly difficult to develop clinically useful diagnostics that are integral markers and essential for performance of clinical trials. The NCI initiated the Clinical Assay Development Program (CADP) to aid such development.  CADP has a network of 8 CLIA-certified laboratories (3 commercial and 5 academic laboratories) that develop assays selected after competitive review and give them back to the investigator for performance in a clinical trial. To date 16 applications have been reviewed in 3 rounds of funding with 3 projects under development that include assays to detect somatic mutations, 2-HG and validation of a gene expression assay. CADP offers advice for those assays that are not selected for development.

5:30-6:00 Building the Cancer Diagnostics Pipeline One Biomarker at a Time

John T. McDevitt, Ph.D., Brown-Wiess Professor, Bioengineering & Chemistry, Rice University

This presentation features creation of programmable nano-bio-chip sensors that are capable of sophisticated measurements of strategic biomarkers from bio-fluid samples like blood, urine and saliva. This universal detection modality is now on a fast track to FDA approval through the simultaneous completion of 6 clinical trials in the area of HIV immune function (number one global humanitarian issue), cardiac heart disease (largest killer globally) and three types of cancers (oral, ovarian, prostate).

• • •

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