In this podcast, Professor Ian Wilson, a globally recognised and leading expert in drug metabolism, with over 500 publications in the field, takes us on an engaging journey exploring the link between carboxylic acid containing drugs and their involvement in DILI. A special focus will be given to Ian’s latest paper: ‘Minimizing the DILI potential of carboxylic acid-containing drugs: a perspective’.

The episode explores the following:

• Are acyl glucuronides shouldering too much of the blame?
• Where else should we be looking?
• What are the possible risk mitigation strategies to reduce DILI with these chemotypes?

Speaker:

Ian Wilson – Professor, Department of Metabolism, Digestion and Reproduction at Imperial College
Ian Wilson trained as a biochemist at the University of Manchester Institute of Science and Technology UMIST) following this with a PhD in the Chemistry Dept. at Keele University on the gas chromatographic analysis of ecdysteroids (insect moulting hormones). Following a short period of postdoctoral research on HPLC-based methods for the analysis of penicillamine at University College in London he joined Pharma were he the embarked on a career in drug metabolism and bioanalysis is the pharmaceutical industry spanning over 30 years (beginning in 1979 at Hoechst, the ICI, Zeneca and AstraZeneca). On leaving AstraZeneca he joined Imperial College (London) in 2012 where he is currently a Visiting Professor of Drug Metabolism and Molecular Toxicology. More recently he has also been appointed as a visiting Prof at Liverpool University. As a biochemist turned analytical chemist, he tries to use advanced analytical methods, including those based on UHPLC and ion mobility separations to better characterize and understand biological systems. Currently these efforts are focused on high resolution, high throughput methods that can be applied to problems in metabolic phenotyping (metabonomics/metabolomics), drug metabolism/biochemical toxicology, systems biology and the microbiome. He is the author, or co-author, of over 600 papers, reviews or book chapters, and has received awards in separation and analytical science from the Royal Society of Chemistry and the Chromatographic Society amongst others.

Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!

In this podcast, Scott and John will discuss the LC-MS techniques that have been applied for the bioanalysis of biotherapeutics.

The episode explores the following:

• The impact that mass spectrometry is having in the biotherapeutics and biomarker space
• The rationale behind the use of LC-MS for certain biomarkers and how sensitive LC-MS assays can be developed (and the practical limits for lower limits of quantification that can be achieved)
• Developments in mass spectrometry that are expected to benefit the analysis of biomarkers and for biotherapeutics

Speaker:

John Mehl – Consultant

John Mehl is currently consulting and previously worked as a director at GSK, leading the Protein MS group within the Bioanalysis, Immunogenicity and Biomarkers (BIB) department, Collegeville, PA. The group developed LC-MS assays for quantitative & qualitative analysis of biopharmaceuticals, protein & small molecule biomarkers and for the determination of in vivo protein turnover kinetics to support preclinical and clinical studies. Prior to joining GSK, John worked for BMS where he was a Sr. Principal Scientist focused on biomarker & large molecule quantification and characterization using MS. John has a PhD degree in analytical chemistry from Vanderbilt University, postdoctoral training in protein MS from MIT and an MBA in business management from Temple University. Before joining BMS, John worked for Merck in different analytical research areas including proteomics, small molecule DMPK, large molecule immunoassay method development and vaccine and biologics protein characterization, spanning both discovery and regulated laboratories. He has published extensively on the use of hybrid LC-MS for both large and small molecule quantification.

Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!

This podcast format is inspired by the Charles Dicken’s novella “A Christmas Carol” whereby Phil Jeffrey (Bicycle Therapeutics), Beth Williamson (UCB) and Daniel Price (Nimbus) discuss DMPK Past, Present and Future with Scott. Key elements discussed include the evolution of DMPK as a predictive discipline that links helps the chemistry of drug design with the biology of drug disposition and effect.

The episode addresses the following questions:

• The founding names and principles of DMPK and the emergence of Discovery DMPK
• Today’s use of technologies and in silico modelling and DMPK’s role in the 3 pillars/5Rs and PK/PD
• The outlook for better prediction with advances in AI/ML

Speakers:
Phil Jeffrey - Senior Vice President of Preclinical Development at Bicycle Therapeutics

Phil Jeffrey is now semi-retired after contributing to DMPK for over 35 years in the pharmaceutical industry.  Most recently, Phil was Senior Vice President of Preclinical Development at Bicycle Therapeutics and previously has held positions at Pfizer, GlaxoSmithKline, SmithKline Beecham and The Upjohn Company.  Phil is a longstanding contributor the Society for Medicines Research and is an Honorary Professor at the William Harvey Research Institute, Queen Mary University of London.  Phil has a wide breadth of experience across DMPK from, Drug Discovery and early lead optimisation through to clinical proof of mechanism and proof of concept across a wide variety therapeutic areas and drug modalities and made significant contributions to the advancement of understanding the CNS penetration of drugs into the brain.

Beth Williamson - Head of ADME in the DMPK group at UCB

Beth graduated with a PhD in Pharmacology from the University of Liverpool and is now Head of ADME in the DMPK group at UCB where she also represents DMPK on projects throughout discovery and development. Beth’s work has focussed on in vitro and in vivo ADME assay optimisation and validation within drug discovery, particularly to address bespoke questions. Beth has worked in the fields of oncology, neurology and immunology. Her main research interests include drug-drug interactions, extrapolation of pre-clinical in vitro and in vivo data for the prediction of human pharmacokinetics and application of AI/ML approaches within DMPK. 

Daniel Price - Vice President of Computational Chemistry & Structural Biology at Nimbus Therapeutics

Dr. Daniel Price is Vice President of Computational Chemistry & Structural Biology at Nimbus Therapeutics, where he leads a team of internal and external scientists focused on delivering breakthrough medicines through structure-based design, leveraging both physics-based and knowledge-based predictive modeling. Before joining Nimbus, he spent 16 years at GlaxoSmithKline, where he led a team of computational chemists and data scientists across diverse areas of structure- and ligand-based drug design, high-content screening analytics, predictive ADME, predictive synthesis, and chemogenomics. He has led drug discovery programs, contributed to 4 clinical candidates, led the development of GSK’s first generation R&D data lake, and authored/co-authored 26 publications. Dr. Price received his undergraduate degree in chemical engineering from University of Colorado at Boulder followed by his Ph.D. in Molecular Biophysics & Biochemistry from Yale University with Prof. Bill Jorgensen. He completed an NIH postdoctoral fellowship with Prof. Charlie Brooks, III at The Scripps Research Institute prior to joining GSK.

Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!