Next-Generation Non-Invasive Molecular Diagnostics
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Wednesday, September 19
» Opening Plenary Session
2:00-3:00 Main Conference Registration
3:00-3:10 Welcoming Remarks from Conference Director
Julia Boguslavsky, Executive Director, Conferences, Cambridge Healthtech Institute
3:10-3:15 Chairperson's Opening Remarks
3:15-3:45 Rules, Tools and Data Pools: The Critical Path's Recipe for Speeding Drug Development
Carolyn Compton, M.D., Ph.D., President & CEO, Critical Path Institute
Both regulatory agencies and the medical products industry recognize the need for new biomarkers and methods to speed the development and delivery of effective, safe medicines to patients. However, developing consensus on the utility of new biomarkers and establishing a process for putting them into routine practice in medical product development and regulatory decision making is a complex undertaking. In 2009 and 2010, respectively, the European Medicines Agency and the FDA released guidance that describes a voluntary pathway for "qualification" of novel drug development tools or methods. Determining the relative advantages/disadvantages and evidentiary standards required for regulatory "qualification," applying a novel biomarker on a specific drug development program, or submitting an application for a diagnostic device are challenging tasks. The Critical Path Institute (C-Path) acts as a trusted third party to lead six pre-competitive global consortia that, with the cooperation of the FDA, develop and qualify molecular and imaging biomarkers as well as patient-reported outcomes instruments for specific contexts of use in medical product development. Several C-Path consortia use Clinical Data Interchange Standards Consortium disease area data standards in constructing clinical trial databases from which disease progression models and virtual clinical trial simulations are developed. Specific examples from these consortia will be utilized to illustrate the power of pre-competitive collaboration in the generation and qualification of drug development tools.
3:45-4:15 Technology Transformation at FDA: Driving Efficiency and Unleashing Innovation
Eric D. Perakslis, Ph.D., Chief Information Officer and Chief Scientist, Informatics, U.S. Food and Drug Administration
The U.S. Food and Drug Administration has recently taken significant steps to modernize and improve its information technology and informatics capabilities. The resulting infrastructure, architecture, innovation pathways and data sharing initiatives are intended to ease regulatory burden on innovators while maintaining the highest quality standards. In this talk, Eric Perakslis, Ph.D., the Chief Information Officer and Chief Scientist for Informatics at FDA, will discuss these initiatives in detail and will provide success examples, recent progress and future directions.
4:15-4:45 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 risk 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 development of drugs and diagnostics today and in the future.
4:45-5:15 Strategies to De-Risk Drug Development Utilizing Biomarkers in Early Clinical Trials
Scott Kennedy, Ph.D., Global Head, Biomarker Development, Novartis Institutes for BioMedical Research, Inc.
Other than recent examples in oncology, the emerging field of personalized medicine has yet to live up to its promise of enabling more rapid, efficient drug development and providing customized therapies to patients. This presentation will exemplify and discuss how leveraging biomarkers which inform a biological understanding of targeted and disease pathways can increase the success of early clinical development. These biologically relevant markers can also enable the identification and treatment of parallel disease populations and serve as stratification or response markers for later stage development. This presentation will also discuss several of the challenges that this paradigm presents.
5:15-5:45 Implementing a Personalized Medicine Strategy: Is There Light at the End of the Tunnel?
Jeremy Barton, M.D., Vice President, Head of Oncology Clinical Research, Pfizer
Personalized medicine, the practice of tailoring treatment to individual characteristics of the patient, has emerged as a major force in oncology in the last decade with the expectation of significant improvement in safety and efficacy of therapeutics. The ultimate success of this paradigm is dependent on a variety of factors. The choice of drug target, selection of patients by companion diagnostic, regulatory authority acceptance of novel trial designs which best serve this strategy, improved health care information technology, insurance coverage and reimbursement are just a few of the important variables in the equation. This presentation will provide an overview of the current situation and discuss factors which will impact future progress in the field.
5:45-6:45 Welcome Reception in the Exhibit Hall with Poster Viewing
Thursday, September 20
7:30-8:15 am Morning Coffee or Sponsored Breakfast Presentation (Opportunity Available)
Contact Ilana Quigley at email@example.com or 781-972-5457
8:30-8:55 Exosomes as Biomarkers for Translational Medicine
Holly Hilton, Ph.D., Head, Disease and Translational Genomics, F. Hoffmann-La Roche
The need for new, relevant biomarkers for translational drug discovery research is critical. Exosomes are small microvesicles secreted by a wide range of mammalian cell types under normal and pathological conditions. The unique signature of exosomal membrane and cytoplasmic proteins as well as mRNAs and miRNAs can reveal the cell of origin and the condition of those cells. Isolation and profiling of exosomes from accessible patient biofluids, such as urine, blood, BALF and CSF, make them ideal candidates as biomarkers. Examples of their utility as disease biomarkers of chronic kidney disease and Alzheimer’s as well as possible applications of patient stratification will be discussed. The current state of challenges to the widespread use of fluid-based biomarkers will be explored.
8:55-9:20 Genetic Insights into Brain Tumors Using Extracellular Vesicles in Biofluids
Xandra Breakefield, Ph.D., Professor, Neurology, Harvard Medical School; Geneticist, Molecular Neurogenetics, Massachusetts General Hospital
Glioma tumor cells release a variety of extracellular vesicles containing proteins, lipids and nucleic acids, which are representative of the tumor cells. These vesicles provide a means for the tumor to eliminate unwanted substances and also to communicate with cells in their environment. In the case of brain tumors some of these microvesicles are released into the cerebrospinal fluid (CSF) and blood. Our group has used RNA in CSF and serum microvesicles from brain tumor patients to detect mutations in EGFR and IDH1 by RT-PCR, BEAMing and deep sequencing. These serve as robust and non-invasive biomarkers for tumor status.
9:20-9:45 Clinical Utility of Exosomes as Diagnostic and Prognostic Markers in Cancer
Rachel E. Raab, M.D., Assistant Professor of Medicine, Division of Hematology/Oncology, East Carolina University Brody School of Medicine
Tumor-derived exosomes are membrane-bound, endosome-derived vesicles between 50-100 nm that bear protein signatures related to their cell of origin and contain mRNAs and microRNAs. Most cell types, including tumor cells, secrete them. Exosomes play a role in cell-cell communication and affect target cells by stimulating them directly or by transferring molecules between cells. Tumor-derived exosome analysis may be a novel diagnostic and prognostic biosignature in many solid tumors including breast cancer, ovarian cancer, colon cancer, lung cancer and prostate cancer.
9:45-10:45 Coffee Break in the Exhibit Hall with Poster Viewing
10:45-11:10 Exploring Exosomes as a Surrogate Marker for Neuroscience Clinical Research
Reyna Favis, Ph.D., Scientific Director and Head, Neuroscience Biomarkers Laboratory, Janssen Pharmaceutical Companies of Johnson & Johnson
Neurological and neuropsychiatric disease research has been hampered by the inability to perform molecular assessments of the CNS in living patients. While analyses of postmortem brain tissue and lymphocytes from living donors have been exploited in an attempt to obtain insight, both tissue types suffer from numerous caveats. Exosomes are a recognized mechanism for intercellular communication. By tapping into this cellular communication modality, we reason that it will be possible to gain insight into the activities of inaccessible tissue of the central nervous system.
11:10-11:40 Predictive Biomarkers that Reflect Cellular Decision Making: Exosomal Transcription Factors and microRNA
Peter S. T. Yuen, Ph.D., Staff Scientist, Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Proximal fluid biomarkers can add a dimension of organ specificity to complement circulating biomarkers. Exosomes represent a minor subfraction of urine that promises unique insights into kidney function, because their biogenesis preserves information content from the cytoplasm and plasma membrane from all types of epithelial cells that line the nephron. We demonstrated that exosomal transcription factors Wilms Tumor-1 (WT-1) and Activating Transcription Factor 3 (ATF3) are diagnostic biomarkers for chronic acute and kidney diseases, respectively. Further, exosomal microRNAs are diagnostic biomarkers. However, we demonstrate that these complementary biomarkers have great potential to predict the extent of injury in outbred mice with a wide range of severity.
11:40 am-12:05 pm The Majority of microRNAs Detectable in Serum and Saliva Are Concentrated in Exosomes
Alessia Gallo, Ph.D., Fellow, Molecular Physiology and Therapeutics Branch, NIDCR, National Institutes of Health
12:05-1:30 Enjoy Lunch on Your Own
1:30-1:35 Chairperson’s Opening Remarks
1:35-2:00 Early Adopters in Pharmaceutical Applications of Imaging: Pre-Clinical and Clinical Case Studies
Paul J. McCracken, Ph.D., Director of Imaging, Biomarkers and Personalized Medicine CFU, Eisai, Inc.
Novel therapeutic drugs may require imaging biomarkers that are at the leading edge of imaging technology or tracer discovery. Imaging biomarkers may be used to inform decision making at many key milestones in the discovery and development pipeline, but the value depends on many factors. Early use of imaging in the pre-clinical and translational space requires a significant understanding of the information provided by animal models and the applicability or challenges faced with clinical translation. Brief case studies will be reviewed including pharmacologic MRI (phMRI), novel PET tracer chemistry, oncology markers including biodistribution, and Alzheimer’s disease methods.
2:00-2:25 Homemade or Store Bought? Bringing Molecular Imaging to Cancer Clinical Trials
Peter Choyke, M.D., F.A.C.R., Chief, Molecular Imaging Program, National Cancer Institute, National Institutes of Health
Conceptually, Molecular Imaging (MI) is useful in patient selection and therapy monitoring. The realities of MI in a clinical trial are daunting. There is a limited menu of available MI PET/SPECT probes. Nonetheless, because of their availability, these agents are more relevant post-approval. Highly specific imaging probes require a “homemade” approach. Thus, there is a long lead time for the agent to become available. In this talk, examples of both “store-bought and homemade” MI probes are presented. The decision to use existing probes or develop them rests on the kind of information that is sought and speed with which it is needed.
2:25-2:50 Overcoming Regulatory Hurdles in Investigational Molecular Imaging
Paula M. Jacobs, Ph.D., Associate Director, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health
Molecular imaging agents have great promise for investigating biology and for assisting in the development of new therapeutic drugs. However, it can be difficult to obtain the regulatory approvals to investigate them in the clinical trial setting, particularly when pairing an investigational molecular imaging probe with an investigational therapeutic drug. This presentation will discuss the NCI’s experience with non-proprietary investigational molecular probes in both imaging only and imaging-therapy trial settings as well as a variety of regulatory strategies.
2:50-3:15 Presentation to be Announced
3:15-4:15 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15-4:20 Chairperson’s Opening Remarks 4:20-4:45 Contribution of Proteomics to Blood-Based Cancer Diagnostics
Samir Hanash, M.D., Ph.D., Program Head, Molecular Diagnostics, Fred Hutchinson Cancer Research Center
A major contribution of proteomics to personalized medicine is the development of blood-based tests for early detection, disease classification and predicting and monitoring response to treatment. Application of proteomics to lung cancer has resulted in panels of markers that complement other molecular profiling approaches. Advances in proteomics and their applications to cancer diagnostics will be presented.
4:45-5:10 Antibody-Based Assays for the Identification of Circulating Protein Biomarkers in the Clinic: Technological and Methodological Challenges
Corinne Solier, Ph.D., Group Head, Clinical Protein Biomarkers, F. Hoffmann-La Roche
Monoparametric and multiparametric immunoassay methods have been commonly used in biomarker research. Proper method development and validation are however required prior to assessing the biological relevance of the intended biomarkers in the clinic. Here we provide recommendations for the validation of immunoassays for clinical applications. We also provide a viewpoint on the concept of “fit-for-purpose” assay validation in light of the intent of generated biomarker results. We illustrate the main technical features of popular and breakthrough immunoassay platforms; we highlight the main technical caveats of multiplexed immunoassay methods; and illustrate the need for the development of tailored validation guidelines applicable to these methods.
5:10-5:35 Use of Protein Multiplex Arrays to Identify Blood-Based Biomarkers for Anti-Angiogenic Therapies
Andrew B. Nixon, Ph.D., M.B.A., Assistant Professor, Medicine and Medical Oncology; Co-Director, Phase I Biomarker Laboratory, Duke University Medical Center
We have recently optimized a multiplex ELISA approach for use in cancer patient plasma. The application of multiplex ELISA approaches in clinical samples is rapidly evolving and has recently shown positive results. The design of our multiplex panel to interrogate diverse biologies related to angiogenesis is novel, and many of the analytes within our array have been developed specifically for our use. In our role as a Molecular Reference Laboratory for the Alliance cooperative group, multiplex profiles can be easily compared across studies, helping to optimize future profiling approaches and provide the disease-specific context needed for clinically meaningful companion diagnostics.
5:35-6:00 Next-Generation Sequencing for Identification of microRNAs as Biomarkers for Lung Cancer
Feng Jiang, M.D., Ph.D., Associate Professor, Pathology, University of Maryland School of Medicine
We proposed to develop miRNAs as sensitive and specific noninvasive biomarkers for the early detection of lung cancer. From bronchial washing specimens of 26 lung cancer and 26 healthy controls, using NGS, we identified 12 miRNAs that displayed different expressions between cancer and healthy subjects. The different expression levels of the miRNAs were confirmed in the same set of the specimens by uring qRT-PCR assay. On bronchial washing samples of 36 cancer patients and 36 healthy individuals, a panel of miRNAs was optimized that had a higher diagnostic power compared to a single one used alone. Validation of the marker panel in an independent set of cases and controls confirmed the sensitivity and specificity of the panel of biomarkers, which demonstrated the potential of translation to laboratory settings for improving the early detection of lung cancer.
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