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 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
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
10:30-11:00 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.
11:00-12:30 Sponsored Presentations (Opportunities Available)
Contact Ilana Quigley at iquigley@healthtech.com or 781-972-5457
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.
2:00-2:30 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.
2:30-3:00 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.
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 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.
4:00-5:00 Refreshment Break in the Exhibit Hall with Poster
Viewing
5:00-5:30 Oncology Biomarkers from Proof of Principle to
Proof-of-Concept and Beyond
Hans Winkler, Ph.D., Senior Director and Global Head, Oncology
Biomarkers, Johnson & Johnson
The application of biomarkers in clinical trials can add
significantly to the successful conduct of a clinical development program. In
the very early stages, pharmacodynamic markers can be applied to assess and
demonstrate a compound’s pharmacological effect on the target at least in a
surrogate tissue. By the end of Phase I, through best application of
preclinical PK PD modeling data it should be possible to determine if a specific
compound should be able to shrink sensitive tumors at a safe dose. Furthermore,
predictive biomarkers can be applied to identify sensitive patient populations.
For rapid proof-of-concept, i.e., the demonstration that a certain compound is
able to achieve a beneficial clinical effect at a safe dose, predictive
biomarkers can be decisive in the success or failure of a program. If sensitive
patient populations are small, a companion diagnostic development is necessary
to identify patients eligible for a treatment in medical practice.
5:30-6:00 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.
• • •
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 R&D
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