Wednesday, August 9th 2023
More than 50 bispecific antibodies are in oncology clinical development with a large diversity in formats, directed at a range of immune and tumor targets. Bispecifics have demonstrated the potential for enhanced efficacy and reduced systemic toxicity. However, they are complex modalities with challenges to overcome in early clinical trials, including selection of relevant starting doses and dose escalation strategy due to non-intuitive exposure-response relationships. In this context, prediction and management of cytokine-release syndrome (CRS) is important.
Multiple factors can contribute to between-patient variability, including tumor type, avidity, receptor expression, effector-to-target-cell ratio, and presence of soluble target. Mechanistic, quantitative systems pharmacology (QSP) models are increasingly being used in the design of bispecifics and to guide translation research, clinical trial design, dose regimen optimization, and patient selection.
Our Speakers:
Piet van der Graaf Ph.D. PharmD is Senior Vice President and Head of Quantitative Systems Pharmacology at Certara 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 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. He was the recipient of the 2021 Leadership Award from the International Society of Pharmacometrics (ISoP) and is an elected Fellow of the British Pharmacological Society. Piet has published >200 peer-reviewed papers and is ranked in the top 2% of most cited authors in the Pharmacology & Pharmacy discipline worldwide.
Alison Betts Ph.D. is Vice President and Head of Global DMPK & Modelling at Takeda. She has 29 years of experience in the industry, as DMPK, PK/PD and QSP modeling and simulation leader. Alison started her career at Pfizer in the UK in 1994 in the department of Drug Metabolism. Across her 25-year tenure at Pfizer Alison worked across 3 different sites (Sandwich UK, Groton, CT, and Cambridge MA) supporting the discovery and development of many different drug modalities across therapeutic areas. In the last 10 years she led the modeling and simulation group supporting the Oncology research unit. Notable highlights included support of the relaunch of Mylotarg, the approval of Inotuzumab and the discovery of the BCMA-CD3 bispecific mAb.
After 25 years at Pfizer, Alison started a new role as Vice President of Scientific Collaborations at Applied BioMath in 2019. During her time at ABM she was also recipient and Principal Investigator of an NIH SBIR Grant to build a platform QSP model for ADCs (ADC Workbench) capable of predicting efficacy and toxicity with the aim of reducing TI.
In her diverse and extensive modeling and simulation career, Alison has published 31 manuscripts and has given 40 invited presentations at conferences. Alison holds a Ph.D. in Systems Pharmacology from the University of Leiden, the Netherlands, and a B.Sc. in Biochemistry from the University of St Andrews, UK.
