ISSX 2021 North American Meeting: Friday, September 17, 2021

Symposium 9: New Approaches to Improve the ADME Kinetics of Biologics
Co-chairs: Joseph Balthasar, University at Buffalo, Buffalo, New York, USA and Greg Thurber, University of Michigan, Ann Arbor, Michigan, USA

Biological agents such as siRNA, mRNA, peptides, and proteins often exhibit poor in vivo absorption, distribution, and elimination kinetics. This symposium highlights recent advances in the development of optimization strategies for the ADME of biologics, including approaches to enable improved oral and subcutaneous bioavailability, new methods to extend persistence / half-life, and strategies to improve tissue selectivity / targeting and within-tissue distribution. Speakers will review ADME challenges and discuss optimization methods, with in-depth discussion of solutions that have been recently advanced within their laboratory.

Symposium 10: Non-invasive Approaches for Drug Disposition Prediction: Biomarkers, Liquid Biopsies and PBPK Modeling
Co-chairs: Bhagwat Prasad, Washington State University, Spokane, Washington, USA and A. David Rodrigues, Pfizer Inc., Groton, Connecticut, US

Characterization of variability in drug disposition is important for clinical study design and for individualized drug treatment. Because variability in drug disposition cannot be completely described by genetics, characterization of phenotypic variability is ideal. The use of non-invasive exosomes (i.e., isolated from biofluids) and endogenous biomarkers are emerging tools for prediction of drug metabolism and transport. Integration of metabolomics and proteomics data from tissue, blood, urine or exosomes into PBPK modeling provides a translational tool for better prediction of drug disposition. This symposium will provide an update on various non-invasive and in silico approaches of in vivo drug disposition prediction.

Plenary Session: Predicting the Unpredictable – Idiosyncratic Drug Toxicity
Co-chairs: Amit S. Kalgutkar, Pfizer Inc., Cambridge, Massachusetts, USA and Kaushik Mitra, Janssen Pharmaceutica

Cumulative research over several decades has implicated the involvement of bioactivation (formation of electrophilic reactive species) in idiosyncratic drug toxicity. Consequently, “avoidance” strategies have been inserted into drug discovery paradigms, which include the exclusion of structural alerts and possible termination of reactive metabolite-positive compounds. The symposium will focus on the recent progress on the limitations of the structural alert avoidance strategy and novel strategies to assess idiosyncratic toxicity in preclinical/clinical drug discovery paradigm.