Dr Robert Copeland
Accent Therapeutics, United States of America
Talk title: Evolution of the Drug-Target Residence Time Model in Drug Discovery
Robert A. Copeland, Ph.D. founded Accent Therapeutics, Inc. in September2017 and serves as its President and Chief Scientific Officer. He is also President of the independent consulting firm, Ki Consultant, LLC. He was formerly President of Research andChief Scientific Officer of Epizyme, Inc. and before that, Vice President of Cancer Biology, Oncology Center of Excellence in Drug Discovery, GlaxoSmithKline. Dr. Copeland serves on a number of advisory boards within industry, academia, professional societies and professional journals. Hereceived his B.S. in chemistry from Seton Hall University, his doctorate in chemistry from Princeton University and did postdoctoral studies as the Chaim Weizmann Fellow at the California Institute of Technology. His research interest is in elucidating the determinants of drug recognition by their biological targets and the use of this information in the discovery and design of new medicines. He has contributed to drug discovery and development efforts leading to 19 investigational new drugs entering human clinical trials. These include the cancer drugs Tazverik™(tazemetostat), Tafinlar™(dabrafenib) and Mekinist™(trametinib), the anemia drug Duvroq™(daprodustat) and the antibiotic Altabax™(retapamulin). Dr. Copeland has contributed more than 200 publications to the scientific literature, holds 14 issued U.S. patents and has authored 5 books in the areas of protein science and enzymology.In 2016 he waselected a Fellow of the American Association for the Advancement of Science (AAAS) and in 2020 he was elected a Fellow of the Royal Society of Chemistry.
Dr Adriaan Ijzerman
Leiden University, Netherlands
Talk title: Target binding kinetics and G protein-coupled receptors
Ad IJzerman is emeritus professor of medicinal chemistry at the Leiden Academic Centre for Drug Research of Leiden University. He is an expert on drug targets, in particular G protein-coupled receptors (GPCRs). His team focuses on concepts in GPCR drug discovery and pharmacology, such as partial agonism, inverse agonism and constitutive activity, allosteric modulation and target binding kinetics. As he sees it, the challenge is to link these pharmacological principles with structural biology, i.e. to unravel the molecular features of ligand and receptor that govern these paradigms. He has been involved in the structure elucidation of a number of GPCRs, including one of the first, i.e. the adenosine A2A receptor, which has become a citation classic (Science, 2008). Later his team was part of a collaborative effort to successfully determine the structure of the chemokine CCR2 receptor (Nature, 2016), providing evidence for the presence of two antagonists at the same time in the receptor architecture. He has been nominated Highly Cited Researcher over the past few years. In terms of leadership Ad has contributed significantly to the field of medicinal chemistry. He led a number of European research consortia, including on adenosine receptors, inverse agonism and target binding kinetics, where industry and academic partners share the privilege of advancing novel concepts in drug discovery.
Dr Elizabeth de Lange
Leiden University, Netherlands
Talk title: On in vivo binding kinetic modelling approaches
Elizabeth de Lange, PhD, is Professor of Predictive Pharmacology at the Division of Systems Pharmacology and Pharmacy of the Leiden Academic Centre for Drug Research (LACDR) at Leiden University in the Netherlands. She combines advanced multi-level experiments and analytical techniques to produce smart data, and mathematical modelling, as a unique approach to build robust mathematical models for the prediction of drug effects in human, which is the ultimate aim of her research.
In the development of mathematical models that predict pharmacokinetic (PK)- pharmacodynamic (PD) relationships in human, in health and disease, she involves identification and characterization of key factors as well as their interdependencies. Particular emphasis lies on investigations on target tissues protected by special barriers, like the central nervous system (CNS).
This research has a comparative and integrative design to elucidate conditional influences of individual factors to the whole (Mastermind research Approach). This is a crucial basis for translation between species and conditions. A recent success is the development of a physiologically-based CNS PK model that is able to adequately predict drug distribution into and within multiple compartments of the rat and human CNS. Another highlight is the contribution to understanding the in vivo context of drug target residence time to predict the effects of drugs.
She has published >145 papers, has provided >150 invited lectures, and has (co-)organized > 85 scientific meetings. In 2013, she received the AAPS Fellow Award. In 2020, she received an Honorary doctorate from Uppsala University. Also in 2020 she received the Lewis Sheiner lecture award from the International Society of Pharmacometrics for her life time achievements in modelling and simulation.
Dr Piet van der Graaf
Leiden University, Netherlands
Talk title: Translating binding kinetics from in vitro pharmacological property to therapeutic benefit using mechanistic PKPD modelling
Piet van der Graaf is Senior Vice President Quantitative Systems Pharmacology at Certara (UK) and Professor of Systems Pharmacology at Leiden University (The Netherlands). From 2013-2016 he was the CSO of the Leiden Academic Centre for Drug Research. From 1999-2013 he held various leadership positions at Pfizer in Sandwich (UK) in Discovery Biology, Pharmacokinetics and Drug Metabolism and Clinical Pharmacology. He was the founding Editor-in-Chief of CPT: Pharmacometrics & Systems Pharmacology from 2012-2018 before becoming Editor-in-Chief of Clinical Pharmacology & Therapeutics. Piet received his doctorate training in clinical medicine with Nobel laureate Sir James Black at King's College London and was the recipient of the 2021 Leadership Award from the International Society of Pharmacometrics (ISoP). He is a Fellow of the British Pharmacological Society.
Dr Peter Tonge
Stony Brook University, United States of America
Talk title: Widening the Therapeutic Window: Kinetic Selectivity and Target Vulnerability
Dr. Tonge is a Distinguished Professor of Chemistry and of Radiology (by courtesy) at Stony Brook University, where he is the Chair of the Department of Chemistry, and Director of the Center for Advanced Study of Drug Action. He is also an Associate Editor for ACS Infectious Diseases. Dr. Tonge earned his B.Sc. and Ph.D. degrees in Biochemistry from Birmingham University, UK, and was a SERC/NATO post-doctoral fellow in the Division of Biological Sciences at the National Research Council of Canada (NRCC). After positions as a Research Associate and Research Officer at NRCC, he was a Staff Investigator at the Picower Medical Research Institute before joining Stony Brook University. His awards include an Alfred P. Sloan Research Fellowship in 2000, and a Fellowship from the Pharmaceutical Research and Manufacturers of America (PhRMA) in 2017 which funded a sabbatical at Genentech.
Dr Daniel Thomas
Arctoris, United Kingdom
Talk title: Digitised Drug Discovery and the future of kinetics
Dr Daniel Thomas is an experienced drug discovery professional with over 20 years in early stage R&D across pharma and biotech. He has extensive theoretical and practical knowledge of assay development, molecular profiling and enzyme kinetics and is an accomplished leader with a track record of developing trans-national matrix research teams. As Head of Discovery Biology, he is responsible for the development and implementation of a comprehensive scientific strategy designed to deliver the best in data quality. Combining a world-class team of engineers and drug discovery experts, Arctoris has developed the world’s first fully automated drug discovery platform, Ulysses. Together with pharma, biotech and AI drug discovery companies, Arctoris deploys this platform generating research data at unprecedented quality and speed, building unique data resources for machine learning applications around the globe. Combining the latest laboratory techniques with advanced robotics and AI, Arctoris brings drug discovery into the digital age.
Professor Steven Charlton
OMass Therapeutics and University of Nottingham, UK
Talk title: How the kinetics of target binding and rebinding influences drug efficacy
Steven Charlton is Vice President, Pharmacology at OMass Therapeutics, a company utilising high-resolution native mass spectrometry to drive drug discovery. Prior to that he was co-founder and CSO at Excellerate Bioscience, a CRO providing specialist molecular pharmacology support to the pharmaceutical industry. Steven has over 20 years drug discovery experience, with previous roles at both SmithKline Beecham and Novartis. At Novartis he was Director of the Molecular Pharmacology Unit in Respiratory Diseases, responsible for compound profiling across a broad range of drug targets. He also served on development teams covering late clinical development through post-launch. In 2007 Steven was awarded Novartis Leading Scientist in recognition of his contribution to the field of quantitative pharmacology and to the Novartis pipeline. Steven is currently also Professor of Molecular Pharmacology and Drug Discovery in the School of Life Sciences at Nottingham University, and a Fellow of the British Pharmacological Society. He is interested in all aspects of the quantitative assessment of ligand-receptor interactions, with a particular interest in the kinetics of ligand binding and signalling.
Dr Rachel Grimley
Cancer Research Horizons, Cancer Research UK
Talk title: Mechanistic Insight in Drug Discovery: “Elephant” or “Unicorn”?
Rachel is Senior Vice President of Drug Discovery for Cancer Research Horizons, Cancer Research UK. Rachel has over 20 years’ experience in pre-clinical drug discovery, incorporating target identification through to drug candidate nomination, across a number of companies. She has contributed to the discovery and characterisation of numerous drug candidates, and 3 marketed medicines, across a diverse range of disease areas including oncology, neuroscience, respiratory, cardiovascular and anti-infectives.
Rachel is also an Expert-in-Residence at the University of Oxford.
Prior to joining Cancer Research Horizons in 2021, Rachel was Executive Director and Head of Mechanistic Biology & Profiling at AstraZeneca, with global responsibility for in vitro mechanism of action studies, SAR biology profiling, Wave1 DMPK and pre-clinical safety screening across the UK, US and Sweden. Previously, Rachel held roles of increasing responsibility at Pfizer in Sandwich, GlaxoSmithKline in Stevenage and Pfizer Neusentis in Cambridge.
Rachel gained her PhD in Mechanistic Enzymology from the University of Birmingham and completed post-doctoral studies at the University of Oxford.
Dr Margaret Porter Scott
Vice President, Genentech, UK
Talk title: Impact of drug binding kinetics across large and small molecules at Genentech
Dr. Margaret Porter Scott is Vice President of Biochemical and Cellular Pharmacology at Genentech. She and her team bring expertise in quantitative in vitro assays and the mechanistic study of molecules to all of Genentech’s research programs across all therapeutic areas and all modalities. Previous to joining Genentech, Margaret was the first employee of Epizyme rising to Senior Director of Lead Discovery and was instrumental in delivering several first-in-human inhibitors including the approved drug Tazemetostat for the treatment of epithelioid sarcoma. Prior to Epizyme, Margaret had over a decade of training in drug discovery through her scientific positions at Millennium, Neogenesis, Vertex and Pfizer. Margaret received her BA from Oberlin College and her PhD from SUNY Stony Brook.
Professor Steve Hill
University of Nottingham, UK
Talk title: Kinetic analysis of fluorescent ligand binding to investigate conformational changes and allosterism in living cells
Professor Steve Hill is Professor of Molecular Pharmacology in the School of Life Sciences, University of Nottingham. He was the inaugural Co-Director of University of Birmingham and University of Nottingham Centre of Membrane Proteins and Receptors (COMPARE) from 2016-2021 and was President of the British Pharmacological Society from 2018-2019. Steve obtained his first degree in pharmacology at the University of Bristol and his PhD (pharmacology) at the University of Cambridge. His research has concentrated mainly on the molecular pharmacology of cell surface receptors (particularly G protein-coupled receptors [GPCRs] but more recently receptor tyrosine kinases and cytokine receptors). Currently, the emphasis of his work is on the study of kinetics of ligand-receptor interactions in single living cells using a variety of fluorescent imaging techniques including fluorescence correlation spectroscopy, confocal imaging, CRISPR/Cas9 genome editing and resonance energy transfer techniques. In particular, he is interested in the cooperative interactions (positive and negative) between the protomers of receptor dimers, the influence of small molecule allosteric regulators on orthosteric ligand binding and signalling and the potential for protein-protein interactions between receptors and associated co-receptors and signalling proteins. He joined the University of Nottingham in 1981 and was subsequently promoted to Reader (1989) and Professor of Molecular Pharmacology (1995). In 1997, he became Director of the Institute of Cell Signalling and in 2008 Head of the School of Biomedical Sciences (until 2013). He was a founding director of the University of Nottingham spin-out company CellAura Technologies Ltd that provided fluorescent ligands to the scientific community until it was acquired by HelloBio in 2014. Steve is also a previous Chair of the MRC Molecular and Cellular Medicine Board. His work is currently funded by MRC and the EU ITN ONCORNET2.0. Steve was awarded the 2018 Vice Chancellor’s Medal from the University of Nottingham and the 2019 Ariens Award from the Dutch Pharmacological Society for outstanding contributions to pharmacology.
