Quantitative Systems Pharmacology: Progress Towards Integration into Drug Discovery and Development

Speakers

Organizers

Joshua Apgar, PhD

Applied BioMath

Mercedes Beyna, MS

Pfizer, Inc.

John Burke, PhD

Applied BioMath

John M. Burke, PhD, is President, CEO and Co-founder of Applied BioMath, a Systems Biology and Pharmacology company. Dr. Burke’s BS and MS are in Applied Mathematics, University of Massachusetts, Lowell. His PhD degree is in Applied Mathematics, Arizona State University, where he studied dynamical systems, singular perturbation theory, and control of signal transduction networks and protein expression. Prior to Applied BioMath, Dr. Burke joined Boehringer Ingelheim (BI), as Global Head of Systems Biology, where he started, developed and managed the Systems Biology and Pharmacology group, portfolio, strategy and tactics. At BI, his group supported over 100 projects and over 11 transitions into Development or Clinical Trials in five years. Prior to BI, he was a Sr. Fellow in Douglas A. Lauffenburger’s lab, Biological Engineering Department, MIT; Co-Scientific Director of the Cell Decision Processes Center, Systems Biology Department, Harvard Medical School; then Merrimack Pharmaceuticals. He provided systems consulting support for drug discovery companies, including AstraZeneca, Pfizer, and Momenta, while at MIT and HMS. He presently serves on advisory boards for the MIT “Human Physiome on a Chip” MIT-DARPA Program and the Mathematics Department at the University of Massachusetts, Lowell, and is Adjunct Faculty at UMass, Lowell.

Nahor Haddish-Berhane, PhD

Johnson & Johnson

Cynthia Musante, PhD

Pfizer, Inc.

Sonya Dougal, PhD

The New York Academy of Sciences

Speakers

Richard Allen, PhD

Pfizer, Inc.

Richard is a Principal Scientist within Pfizer’s Cardiovascular and Metabolic Research Unit. At Pfizer, he applies quantitative approaches, such as mathematical modeling, to address crucial questions in drug discovery and development. Prior to joining Pfizer Richard was a postdoctoral researcher at Department of Pharmacology, UNC, where he used modeling and image analysis to probe the mechanisms that control cell migration. Richard got his Ph.D. in mathematical biology from University College London.

John Burke, PhD

Applied BioMath

John M. Burke, PhD, is President, CEO and Co-founder of Applied BioMath, a Systems Biology and Pharmacology company. Dr. Burke’s BS and MS are in Applied Mathematics, University of Massachusetts, Lowell. His PhD degree is in Applied Mathematics, Arizona State University, where he studied dynamical systems, singular perturbation theory, and control of signal transduction networks and protein expression. Prior to Applied BioMath, Dr. Burke joined Boehringer Ingelheim (BI), as Global Head of Systems Biology, where he started, developed and managed the Systems Biology and Pharmacology group, portfolio, strategy and tactics. At BI, his group supported over 100 projects and over 11 transitions into Development or Clinical Trials in five years. Prior to BI, he was a Sr. Fellow in Douglas A. Lauffenburger’s lab, Biological Engineering Department, MIT; Co-Scientific Director of the Cell Decision Processes Center, Systems Biology Department, Harvard Medical School; then Merrimack Pharmaceuticals. He provided systems consulting support for drug discovery companies, including AstraZeneca, Pfizer, and Momenta, while at MIT and HMS. He presently serves on advisory boards for the MIT “Human Physiome on a Chip” MIT-DARPA Program and the Mathematics Department at the University of Massachusetts, Lowell, and is Adjunct Faculty at UMass, Lowell.

Nitin Mehrotra, PhD

US Food and Drug Administration (FDA)

Dr. Nitin Mehrotra is a Team Leader in Division of Pharmacometrics, Office of Clinical Pharmacology at the US FDA. He joined FDA in 2007. Prior to joining FDA, Dr. Mehrotra obtained his Ph.D. degree from Birla Institute of Technology and Sciences, India. Following which, he worked as a post-doctoral fellow at the UTHSC where he focused on the utilization of Pharmacometrics in (1) developing dosing guidelines for pediatrics and (2) development of a multifactorial index to predict mortality subjects with obstructive airway disease. In his current role at the FDA, Dr. Mehrotra works in the areas of Oncology, Metabolic and Endocrinology, gastroenterology and inborn error products. His job profile includes applying pharmacometrics for regulatory decisions such as dose selection, evidence of effectiveness, trial design, etc. Dr. Mehrotra is a strong proponent of the concept of ‘rationale dose selection’ and believes it to be pivotal for success of any drug development program. He has published several articles in the area of pharmacometrics and has been invited to national and international conferences to present on topics pertaining to application of pharmacometrics in drug development and regulatory decisions.

Sian Ratcliffe, BSc, PhD

Pfizer Inc.

Dr. Sian Ratcliffe is Global Head of Safety Pharmacology CoE in Drug Safety R&D at Pfizer, Groton, Connecticut, US

Dr. Ratcliffe's Safety Pharmacology group spans preclinical safety disciplines of In Vitro profiling, Electrophysiology, Cardiovascular, Neuropharmacology and Physiology.

In her 15 year tenure at Pfizer, Sian has also held other senior leadership roles in Clinical, Safety Risk Management and Regulatory Affairs, managing projects throughout development stages from research to post-approval in the Neurology, Psychiatry, Pain, Women’s Health and Respiratory therapeutic areas. Sian has a keen interest in translational and predictive safety analyses, systems pharmacology and data mining approaches. Sian is an active member of the internal Neuropsychiatric and Abuse Potential Advisory Council, with a particular focus on detection of treatment emergent suicidal ideation and behavior as well as Human Abuse Liability study methodology and the use of novel data mining and statistical techniques to assess abuse potential. Prior to joining Pfizer, Sian worked for Elsevier as an editor for a number of the Trends journals. Sian has a PhD in Pharmacology from the University of Cambridge (1996) where she also held post-doctoral research and academic posts.

Tim Rolph, PhD

Pfizer, Inc.

Tim Rolph is Vice President, Program Value Enhancement, at Pfizer. Formerly Chief Scientific Officer of Pfizer’s Cardiovascular & Metabolic Disease Research Unit, he established it in Cambridge, Massachusetts. During his leadership, ertuglifozin was discovered and progressed to Ph3 in partnership with Merck as a fixed-dose combination with JanuviaTM.

He received a BSc in Biochemistry from University of London (UK), and D.Phil from University of Oxford (UK). His pre-and post-doctoral training was at the Nuffield Institute for Medical Research, studying metabolic adaptations of skeletal & cardiac muscle during development. Subsequently, he joined Glaxo’s veterinary R&D, initially studying modulation of growth for food production, then research for anti-parasitic vaccines against protozoan (anti-coccidial for poultry, ParacoxTM) and metazoan species (gastrointestinal helminths).

Beginning in a similar role at Pfizer, he became leader of human anti-infective research at Sandwich (UK), during which the prototypical CCR5 antagonist, Maraviroc (CelzentryTM), was discovered and launched as a novel antiretroviral for HIV. He then became Head of Research at Pfizer’s Sandwich laboratory and more recently at Groton, CT.  Through his career, he has led groups who have taken many different therapeutic mechanisms into Ph2, covering HIV, diabetes, inflammatory and renal diseases.

Matthew Rizk, PhD

Merck & Co., Inc.

Matt Rizk is a scientist in the Quantitative Pharmacology and Pharmacometrics group within the department of PK, PD and Drug Metabolism at Merck, where he serves as the therapeutic area lead for activities in HCV and antibacterial drug development. Matt obtained his PhD from UCLA in Chemical Engineering, with research focused in the area of synthetic biology. Since obtaining his doctorate, he has been at Merck and served on interdisciplinary drug development teams whose work impacted all areas of drug discovery and development ranging from target identification through all phases of development and post-licensure activities, with contributions primarily in the areas of clinical pharmacology and the modeling and simulation strategy and execution. Matt has had numerous publications and given many presentations, particularly in the areas of antibacterials and HIV.

Vikram Sinha, PhD

US Food and Drug Administration (FDA)

Vikram Sinha, PhD, is the Director, Division of Pharmacometric at the USFDA. In his current role, Vikram leads the Pharmacometrics Division. The Division plays a critical role in understanding the impact of variability in response to drugs and relates it to assessing benefit and risk. He leads a multidisciplinary team of quantitative clinical pharmacologists, statisticians, engineers, and data management experts. Within CDER, pharmacometric work is conducted with the intent to aid the decision to approve and label the drug product. There is particular attention on providing a consulting function on drug dosing for patients and advice on trial design decisions by sponsors. Previously, Vikram was at Eli Lilly, where he was scientific lead for global pharmacokinetics/pharmacodynamics and pharmacometrics. At Lilly, he was accountable for developing quantitative translational strategies, clinical plans, and regulatory strategies in the area of clinical pharmacology. He has 16 years of experience in the pharmaceutical industry. He has made notable contributions to the general scientific community through teaching, publications, and engagement with industry/government consortia dedicated to advancing innovation in the area of drug discovery and development. Vikram earned a bachelor’s degree in pharmacy and a doctorate degree in pharmaceutical sciences from the University of Arizona. He completed post-doctoral training at the University of Nebraska Medical Center.

Peter Sorger, PhD

Harvard Medical School

Peter Sorger, PhD, is a Professor of Systems Biology at Harvard Medical School whose research focuses the systems biology of signal transduction with an emphasis on apoptotic and oncogenic networks in normal and tumor cells. Peter serves as Head of the Harvard Program in Therapeutic Sciences (HiTS) and Director of its Laboratory of Systems Pharmacology. In these roles he leads a university-wide effort to advance basic and translational science used to develop new medicines, evaluate drugs through clinical trials and identify patients most likely to benefit from specific therapies. Peter’s laboratory applies diverse computational and experimental approaches to cancer and inflammatory diseases in human cells and genetically engineered mice. His group also develops open-source software for assembling computable knowledge about signal transduction and for using this knowledge to understand and predict the responses of cells and tissues to therapeutic drugs applied individually and in combination. Sorger was cofounder of Merrimack Pharmaceuticals and Glencoe Software and is an advisor to multiple public and private companies and to research institutes in Europe and Japan.

Paul Watkins, MD

Hamner-UNC Institute for Drug Safety Sciences

Dr. Paul B. Watkins is director of the Hamner-University of North Carolina Institute for Drug Safety Sciences. He is also Professor of Medicine, Pharmacy and Public Health at the University of North Carolina, Chapel Hill. Dr. Watkins is a trained clinical hepatologist and also an accomplished basic and translational investigator in the fields of drug metabolism and hepatotoxicity. He serves as the chair of both the Steering and Genetics Committees for the U.S. Drug-Induced Liver Injury Network (DILIN) (U01DK065201). He is one of the most frequently cited authors in the field of pharmacology according to www.ISIhighlycited.com. He is the recipient of numerous honors and awards including the Therapeutic Frontiers Award from the American College of Pharmacy election to the Association of American Physicians (AAP), the 2013 Agilent Therapeutic Frontiers Award, and he will receive the Rawls-Palmer Award for Progress in Medicine at the 2015 annual meeting of the American Society for Clinical Pharmacology and Therapeutics.