Tuesday, May 22
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.
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
Stafford O'Kelly, M.B.A., President, 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
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.
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
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
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
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
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.
9:00-9:30 Analytical-Grade Multiplexed Assays:
Requirements from the Biomarker Community
Pankaj Oberoi, Ph.D., Director, Scientific Services and
Research & Development, 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.
12:00-1:30 Enjoy Lunch on Your Own
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 Utilization of Biomarkers in Development of
Treatments for Heterogeneous Immunologic Diseases
Carrie Brodmerkel, Ph.D., Director, Immunology Biomarkers,
Centocor Research & Development
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 dysregulated pathways. These
results offer insight into the patient subpopulations most likely to benefit
from therapy.
3:00 Close of Conference