Emerging Safety Science: Workshop Summary (2008)

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Appendix B Speaker Biographies June S. Almenoff, MD, PhD, received her bachelor’s degree with honors from Smith College. She graduated from the MD–PhD program at the Mount Sinai School of Medicine. She did her residency training in inter- nal medicine, followed by an infectious diseases fellowship at Stanford University School of Medicine. Following this, she completed a fellow- ship in molecular pathogenesis at the Howard Hughes Medical Institute at Stanford. In 1993, she joined the faculty at Duke University Medical Center, where she directed a research program in molecular pharmacol- ogy. In 1997, she joined the clinical safety group at GlaxoSmithKline (GSK) (formerly GlaxoWellcome). Dr. Almenoff is currently Vice President of Safety Evaluation and Risk Management at GSK, where she manages a therapeutic portfolio. She also leads the GSK team that has developed two pioneering, award-winning systems for detecting safety issues in pharma- ceutical products. These systems (Web VDME and Online Signal Manage- ment), which were developed to enhance the protection of public safety, have since been implemented at regulatory agencies such as the U.S. Food and Drug Administration and the UK Medicines Healthcare Regulatory Agency, as well as numerous pharmaceutical companies. Dr. Almenoff is a fellow of the American College of Physicians and is an associate faculty member at Duke Medical School. She has authored 40 publications and served on the editorial board of the Drug Information Association Journal. She currently co-chairs the collaborative PhRMA–FDA working group for safety signal detection, and was lead author of its benchmark publication on quantitative signal detection. Dr. Almenoff is also a member of the 125 

126 EMERGING SAFETY SCIENCE Council for International Organizations of Medical Sciences (CIOMS) VIII Working Group on Safety Signal Detection. Eric Blomme, DVM, PhD, is currently leader of the cellular and molecular toxicology group at Abbott Laboratories. Eugene C. Butcher, MD, is a professor in the Department of Pathology at Stanford University and a staff physician in the Veterans Affairs Palo Alto Health Care System. He received a BS in chemistry from the Massachu- setts Institute of Technology and an MD from the Washington University School of Medicine, St. Louis, Missouri. His work has focused on the cel- lular and molecular mechanisms of leukocyte trafficking in immunity and inflammation, and on systems-level insights into mechanisms of cell–cell recognition and function. He has been elected to the Association of Ameri- can Physicians and has been awarded the Warner Lambert/Parke Davis Award by the American Association of Pathologists, the AAI-Huang Foun- dation Meritorious Career Award by the American Association of Immu- nologists, and an Outstanding Inventor Award from Stanford University. He received the Crafoord Prize from the Swedish Academy of Sciences in 2004 for the scientific discovery of mechanisms of leukocyte trafficking contributing to the treatment of arthritis and inflammatory diseases. Dr. Butcher has been active in biotechnology, most recently cofounding and serving as chair of the Scientific Advisory Board of Bioseek, Inc. He previ- ously helped found Leukosite, Inc., and has served on the scientific advi- sory boards of Millennium, Medimmune, and Thios Pharmaceuticals. Mark I. Cockett, PhD, joined Bristol-Myers Squibb (BMS) in January 2000, and is responsible for functional genomics and bioinformatics applied to preclinical research and development. His group manages and supports key strategic alliances with Lexicon, Artemis, Xenogen, Athersys, Pharmagene/Asterand, Exelixis, Iconix, and the Broad Institute, and is a centralized resource supporting all therapeutic areas at BMS. Before joining BMS, Dr. Cockett worked for 7 years in the neuroscience group at Wyeth, ultimately as Director, Molecular and Cell Biology, and for 10 years in the biotechnology industry for Celltech PLC, where he worked on mammalian gene expression technology and in oncology. While at Celltech, he obtained his PhD in collaboration with the Strange- way Research Laboratory, Cambridge, United Kingdom, working on the involvement of matrix metalloproteinases in tumor cell invasion. Dr. Cockett has published more than 40 peer-reviewed articles in the fields of recombinant gene expression in mammalian cells; the biochemistry and function of several matrix metalloproteinase enzymes and their role 

APPENDIX B 127 in disease; and, more recently, heterotrimeric G protein signaling, and genomics in the pharmaceutical industry. William DuMouchel, PhD, is currently Chief Statistical Scientist at Lin- coln Technologies. From 1996 to 2004, he served as a Senior Scientist at AT&T Labs and was Professor of Biostatistics and Medical Informatics at Columbia University from 1994 to 1996. His professional interests include Bayesian statistics, data mining, pharmacovigilance, clinical data analy- sis, and meta-analysis. Dr. DuMouchel served as chair of the Section on Statistical Graphics for the American Statistical Association from 1996 to 1997 and as chair of the Societal Institute of the Mathematical Sciences from 1999 to 2001. He has received awards for the Best Application Paper, KDD-2001, and the Best Application Paper, KDD-2003. He was elected as a fellow of the American Statistical Association in 1981 and as a fellow of the Institute of Mathematical Statistics in 1986. Dr. DuMouchel received his PhD in statistics from Yale University in 1971. Kendall Frazier, DVM, PhD, is Director of Cellular and Molecular Patho- logy for Safety Assessment at GlaxoSmithKline (GSK) in King of Prussia, Pennsylvania. He received his DVM degree from Kansas State University in 1987 and a PhD in molecular biology from the University of Miami School of Medicine. He completed a residency and National Institutes of Health–funded fellowship in comparative pathology at the University of Miami Jackson Memorial Hospital in 1996 and served on the faculty of the University of Georgia College of Veterinary Medicine as assistant and associate professor of pathology prior to joining GSK. He has coauthored more than 80 peer-reviewed scientific articles and abstracts. Felix Frueh, PhD, holds the position of Associate Director for Genomics in the Office of Clinical Pharmacology in the Center for Drug Evalua- tion and Research (CDER) at the U.S. Food and Drug Administration (FDA) and also chairs the FDA-wide Interdisciplinary Pharmacogenom- ics Review Group. Prior to his appointment at the FDA, Dr. Frueh was Managing Partner at Stepoutside Consulting, LLC, and served as a spe- cial government employee to the FDA and as a consultant to the Centers for Disease Control and Prevention’s (CDC) National Health and Nutri- tion Examination Survey (NHANES) project. He held the position of Research Director for Pharmacogenetics at Transgenomic, Inc., managing the expansion of the business into new program areas for the diagnosis of genetic disorders. Previously, Dr. Frueh was Assistant Director for B ­ iology at Protogene Laboratories, Inc., responsible for application devel- opment based on novel, in situ synthesized DNA microarray technology. He held an appointment as Assistant Professor at Georgetown University, 

128 EMERGING SAFETY SCIENCE W ­ ashington, DC, in the Departments of Pharmacology and Medicine, and was a postdoctoral fellow at Stanford University and at the Biocenter of the University of Basel, Switzerland. Steven K. Galson, MD, MPH (Drug Forum Member), was named Director of the FDA’s Center for Drug Evaluation and Research (CDER) in July 2005. He provides leadership for the center’s broad national and inter- national programs in pharmaceutical regulation. Dr. Galson began his public health service (PHS) career as an epidemiological investigator at the Centers for Disease Control after completing a residency in internal medicine at the Hospitals of the Medical College of Pennsylvania. He has held senior-level positions at the Environmental Protection Agency (EPA); the Department of Energy, where he was Chief Medical Officer; and the Department of Health and Human Services. Prior to his arrival at the FDA, Dr. Galson was Director of the Office of Science Coordination and Policy, Office of Prevention, Pesticides and Toxic Substances, at the EPA. He joined the FDA in April 2001 as CDER Deputy Director. Dr. Galson is the recipient of numerous PHS awards, including the Outstanding Service Medal for his leadership and management of CDER while serving as Act- ing Center Director from November 2001 to February 2002. He is also the recipient of three Secretary of Energy Gold Awards. Dr. Galson is a board member of the National Board of Medical Examiners and a regular peer reviewer for medical journals. He holds a BS from the State University of New York at Stony Brook, an MD from Mt. Sinai School of Medicine, and an MPH from the Harvard School of Public Health. He is board certified in preventive medicine and public health and occupational medicine. Donald N. Halbert, PhD, joined Iconix Biosciences in March 2005 as Executive Vice President of Research and Development. Iconix works with a wide range of pharmaceutical clients to apply gene expression profiling as well as biomarker discovery and validation to understand- ing mechanisms of drug toxicity and improving preclinical drug safety. Dr. Halbert came to Iconix from Abbott Laboratories, where he was most recently Director of Genomics, Proteomics and Bioinformatics in the Global Pharmaceutical Research and Development Group. Beginning in 1991 at Abbott, Dr. Halbert was responsible for the development and integration of molecular biology and bioinformatics in the Pharmaceutical Division. In 1997 he established Genomics within the Advanced Technol- ogy Group, with responsibility for the application of human genomics, genetics, proteomics, and bioinformatics across all therapeutic areas. In 2001 he assumed additional responsibility for the Cell and Molecular Toxicology Group and was instrumental in establishing Abbott as a rec- ognized industry leader in the application of gene expression analysis to 

APPENDIX B 129 the understanding and prediction of compound toxicity. In his 13-year tenure at Abbott, Dr. Halbert served on and chaired numerous biotech- nology scientific collaboration committees and was head of the Abbott Corporate Genomics Task Force. Prior to joining Abbott, he held scientific and management positions at Becton Dickinson in molecular biology and diagnostics, and was a cofounder of the molecular diagnostics company Gene-Trak Systems in Framingham, Massachusetts. Dr. Halbert has pub- lished extensively and holds five patents related to his work. He earned a bachelor’s degree in biology from the State University of New York at Buffalo, and a doctoral degree in molecular virology from Washing- ton University in St. Louis. He completed his postdoctoral fellowship in molecular virology with Dr. Thomas Shenk at the State University of New York at Stony Brook. Edward W. Holmes, MD (Drug Forum Co-Chair and Workshop Chair), was appointed a Howard Hughes Medical Investigator at Duke University School of Medicine in 1974 and later became James B. Wyngaarden Pro- fessor of Medicine. He was recruited to the University of Pennsylvania School of Medicine in 1991 as Chair of the Department of Medicine and Frank Wister Thomas Professor of Medicine and Genetics. In 1997 he became Joseph Grant Professor in the School of Medicine, Senior Associ- ate Dean for Research, Vice President of Translational Medicine and Clini- cal Research, and Special Counsel to the President of the University on Biomedical Research at Stanford University. In January 1999, Dr. Holmes returned to Duke University as Dean of the School of Medicine and Walter Kempner Professor in Medicine and Genetics. He was appointed Vice Chancellor for Health Sciences and Dean of the School of Medicine at the University of California, San Diego, in fall 2000 and served in this role until October 2006. He is currently a Distinguished Professor of Medicine at the University of California, San Diego, and Vice Chancellor/Dean of Health Sciences, Emeritus, at the University of California, San Diego. Dr. Holmes became Executive Deputy Chairman of the Biomedical Research Council and Executive Chairman of the National Medical Research Coun- cil in Singapore in October 2006, and he also holds an appointment as Lien Ying Chow Professor of Medicine at the Yong Loo Lin School of Medicine, National University of Singapore. He has engaged in basic biomedical and clinical research throughout his academic career, and his laboratory work has focused on the molecular bases of human disease. Dr. Holmes has served on the Council of Advisors for the National Institute for Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health, and he currently serves as Chair of the Research Advisory Board of GlaxoSmithKline. He has received Distinguished Alumnus Awards from the University of Pennsylvania and Duke University. He has been 

130 EMERGING SAFETY SCIENCE elected to membership in the American Society for Clinical Investigation and the Association of American Physicians, is a fellow of the American Association for the Advancement of Science, and is a member of the Insti- tute of Medicine of the National Academy of Sciences. Ronald L. Krall, MD (Drug Forum Member), is Senior Vice President and Chief Medical Officer for GlaxoSmithKline (GSK). He is responsible for all matters of human safety for all GSK compounds in development and medicinal and vaccine products, and for pharmaceutical regulatory affairs and GxP compliance. Dr. Krall joined GSK in 2003. Previously, he held positions at AstraZeneca Pharmaceuticals, Abbott Laboratories, and Lorex Pharmaceuticals. He earned a bachelor’s degree in mathematics from Swarthmore College and an MD from the University of Pittsburgh, trained as a staff associate at the National Institutes of Health Epilepsy Branch, and completed his training in neurology and clinical pharmacol- ogy at the University of Rochester. He is board certified in neurology, and is a former member of the board of directors of the National Sleep Foundation, a member of the Board of Directors of the Delaware Valley Science Fairs, a member of the University of Pennsylvania Center for Bioethics Advisory Board, and a past trustee of the American Academy of Pharmaceutical Physicians. Eric Lai, PhD, is Vice President of Pharmacogenetics (PGx) Experimen- tal Project Coordination and Analysis at GlaxoSmithKline (GSK). The research activities in this unit include PGx experimental design, planning and coordination; sample management and storage; genotyping; and genetics data analysis. From 2003 to 2006, Dr. Lai was Vice President, Discovery and Pipeline Genetics Division. From 2000 to 2003 he was Vice President, SNP Capability, Discovery Genetics Division, and project leader of the experimental team formed to study genetic factors associ- ated with abacavir hypersensitivity reactions. Dr. Lai also played a major role in the planning and creation of The SNP Consortium (TSC) and was co-leader of the TSC scientific management team. He received his BSc (Hon) from the University of Waterloo and his PhD in pharmacology from Columbia University College of Physicians and Surgeons in 1989 under the guidance of Dr. Elvin Kabat. He did his postdoctoral training at the California Institute of Technology under the supervision of Dr. Leroy Hood. His postdoctoral accomplishments include the development of pulsed field gel electrophoresis and the cloning and mapping of human and mouse T-cell receptor loci. Prior to joining GlaxoWellcome in 1995, Dr. Lai was an assistant professor at the University of North Carolina at Chapel Hill. His previous works include cloning and mapping of human chromosome 2 using bacterial artificial chromosomes and extrachromo- 

APPENDIX B 131 somal mini-chromosomes. Dr. Lai and other GSK scientists are leading the way in single nucleotide polymorphism (SNP) discovery, genotyping technology, and the use of SNP maps in the search for susceptibility genes and in pharmacogenetics. Philip MacLaughlin, MD, PhD, has been designing software and content for data modeling over the last 9 years. He spent 3 years with SciVision and the last 6 with Elsevier MDL, and is now with Elsevier Pharmaceuti- cal Development Group. He serves as Principal Investigator for Elsevier MDL on an existing cooperative research and development project with the FDA’s Center for Drug Evaluation and Research that involves mod- eling toxicity and adverse events by assembling data sets and creating quantitative structure-activity relationships (QSAR) models. The latest efforts in this area include the release of a new, widely used product on drug safety, PharmaPendium. Michael Milburn, PhD, has served as Chief Scientific Officer for Metabo- lon, Inc., since 2005. Previously, he was most recently Senior Vice Presi- dent of Research and Corporate Development at Sirtris Pharmaceuticals. At Sirtris, he led the preclinical/clinical development of projects in the areas of metabolic disease and neurodegeneration. Prior to his work at Sirtris, Dr. Milburn was Senior Vice President of Research at Plexxikon, where he was responsible for the development of the company’s pro- prietary high-throughput cocrystallography drug discovery platform. He has also held positions at Structural Genomix and GlaxoSmithKline. Dr. Milburn received his PhD in structural chemistry at the University of California, Berkeley, and was a research fellow at Harvard Medical School for his postdoctoral work. Richard Platt, MD, MSc, is Professor and Chair of the Department of Ambulatory Care and Prevention, Harvard Medical School. He is an inter- nist trained in infectious diseases and epidemiology. He is a member of the Association of American Medical Colleges Advisory Panel on Research and the Institute of Medicine’s Roundtable on Evidence Based Medicine, and he currently chairs the FDA’s Drug Safety and Risk Management Advisory Committee. He chaired the Executive Committee of the HMO Research Network, was co-chair of the Board of Scientific Counselors of the Centers for Disease Control and Prevention’s (CDC’s) Center for Infec- tious Diseases, chaired the National Institutes of Health’s study section Epidemiology and Disease Control 2, and chaired CDC’s Office of Health Care Partnerships Steering Committee. His research focuses on develop- ing multi-institution automated record linkage systems for use in phar- macoepidemiology and in population-based surveillance, reporting, and 

132 EMERGING SAFETY SCIENCE control of both hospital- and community-acquired infections, including bioterrorism events. He is Principal Investigator of the CDC-sponsored Center of Excellence in Public Health Informatics (www.phiconnect.org) and the Agency for Healthcare Research and Quality (AHRQ)–sponsored HMO Research Network Center for Education and Research in Thera- peutics (CERT [www.certs.hhs.gov]), and co–Principal Investigator of the Modeling Infectious Disease Agent Study (MIDAS [http://www.nigms. nih.gov/Initiatives/MIDAS]) and the CDC-sponsored Eastern Massachu- setts Prevention Epicenter. Brian B. Spear, PhD, is Research Director within Abbott Laboratories’ Global Pharmaceutical Research and Development Division, with respon- sibility for genomics, pharmacogenetics, cell and molecular toxicology, and bioinformatics. Previously, he was Director of Technology Assess- ment and Acquisition in the Abbott Diagnostics Division, and he has held R&D management positions in diagnostics, agricultural products, and corporate molecular biology. Dr. Spear graduated from Amherst Col- lege with honors and received his PhD from Yale University. He has held positions at the University of Colorado and Northwestern University and carried out research in chromosome structure and genome organization. Dr. Spear’s recent publications have addressed applications of pharma- cogenomics in drug development and patient management, and ethical and regulatory issues relating to pharmacogenetics. Jacky Vonderscher, PhD, obtained an engineering degree in biological chemistry from the National Institute of Applied Sciences (INSA, Lyon, France). He joined the Biopharmaceutical Department of Sandoz as a research fellow investigating new drug delivery systems and in 1986 was awarded a PhD in biochemistry from the University of Geneva. Continu- ing at Sandoz, he and his group dealt with all biopharmaceutical aspects of various drug administration routes (oral, parenteral, dermal, nasal, and pulmonary), with techniques ranging from cell culture to healthy human subject trials. After the creation of Novartis, he became Head of the Drug Metabolism and Pharmacokinetics Department in Europe. In 2002, he was named Global Head of a new function called Integrative Compound and Product Profiling, working at the R&D interface to improve the value of the drug pipeline by making optimal use of pharmacogenomics, bio- markers, and in silico and in vitro profiling assays. In October 2002, he was nominated as Head of Drug Development for Novartis Institutes in Cambridge, Massachusetts, in addition to his global duties in preclini- cal safety. He is a member of the extended Development Management Board of Novartis Pharma, Ltd., and of the Discovery Board at Novartis Institutes. Dr. Vonderscher is co-author of more than 50 publications and 

APPENDIX B 133 presentations, and co-inventor on several formulation and drug substance patents. In 1995, he shared the Golden Sandoz Triangle award for the development of Sandimmune Neoral, the new microemulsion formula- tion of cyclosporine. He is also a co-inventor of the recently developed immunosuppressant Myfortic. Klaus M. Weinberger, PhD, is a biomedical scientist with particular exper- tise in metabolomics, infectious diseases, public health, and immunology, and serves as Chief Scientific Officer and member of the management board for BIOCRATES Life Sciences. Before joining BIOCRATES in January 2003, he led a research group specializing in clinical virology, infection immunol- ogy, and molecular epidemiology at the Institute for Medical Microbiol- ogy and Hygiene at the University of Regensburg, Germany. His personal research focus was on hepatitis viruses and on the implementation of inno- vative technologies (e.g., quartz crystal biosensor analyses) and bioinfor- matics tools in biomedical research and routine diagnostics. Dr. Weinberger holds an MSc in biophysics, biochemistry, and microbiology and a PhD in medical microbiology from the University of Regensburg. He serves as a referee for scientific journals and for organizations of public science funding. He is a member of several scientific societies and was awarded a 5-year-scholarship by the Bavarian Ministry of Education (Munich, 1989– 1994). He holds memberships in the World Health Organization’s (WHO) Collaborating Centre for Virus Associated Cancer (Regensburg, 1994) and the WHO Reference Centre for Viral Hepatitis (Regensburg, 1996), and has received the triennial Saul Krugman Award for substantial contributions to molecular and clinical hepatitis virology (Atlanta, 2000). John K. Westwick, PhD, has worked in the field of cell signaling for more than 23 years, and he has been responsible for research and development at Odyssey Thera since 2002. He was previously Associate Director of Cell Signaling and Target Discovery at Celgene Corp. Prior to his work with Celgene, he was Group Leader and Project Team Leader of multiple projects at Signal Pharmaceuticals. Dr. Westwick holds a BA in biology from the University of California at San Diego and a PhD in molecular pathology from the University of California at San Diego School of Medi- cine. He performed postdoctoral studies in medicine and pharmacology at the University of North Carolina, Chapel Hill, School of Medicine, and was subsequently named Lineberger Cancer Center Fellow at that institution. Dr. Westwick’s work is focused on signal transduction, the cellular mechanisms of cancer, inflammatory and metabolic disease, and the development of novel technologies for translating this knowledge into improved therapeutics. He has authored or co-authored more than 60 scientific articles and patents. 

134 EMERGING SAFETY SCIENCE Janet Woodcock, MD (Drug Forum Member), is Deputy Commissioner for Operations and Chief Operating Officer, FDA. She is responsible for overseeing agency operations and cross-cutting regulatory and scientific processes. Dr. Woodcock served as Director of the FDA’s Center for Drug Evaluation and Research from 1994 to 2005. She previously served in other positions at the agency, including Director, Office of Therapeutics Research and Review, and Acting Deputy Director, Center for Biologics Evaluation and Research. Dr. Woodcock received her MD from North- western Medical School, and completed further training and held teach- ing appointments at the Pennsylvania State University and the University of California at San Francisco. She joined the FDA in 1986.