ISSX 2021 North American Meeting: Wednesday, September 15, 2021

Plenary Lecture 1: The Economics of the Pharmaceutical Industry
Joseph DiMasi, Tufts Center for the Study of Drug Development, Boston, Massachusetts, USA

The new drug development process is highly costly, very lengthy, and fraught with risk.  This presentation will show data on the trends in drug development and regulatory approval cycle times, transition probabilities for clinical phases, approval success rates for clinical development, and pharmaceutical R&D costs.  Drug development metrics vary by therapeutic area and for classes within therapeutic areas, and this will be demonstrated through a number of analyses, including for drugs to treat infectious diseases and cancer.  The extent to which firms compete in development of therapies within therapeutic classes will also be examined through empirical analysis.

Symposium 5: Driving Innovation in Qualitative and Quantitative Bioanalysis
Co-chairs: Lucinda Hittle, Merck & Co., Inc., Rahway, New Jersey, USA and Valerie Kramlinger, Novartis, Cambridge, Massachusetts, USA

As a partnership between the ISSX Bioanalysis in ADME Science and Biotransformation Mechanisms and Pathways Focus Groups, this session will present various aspects of quantitative and qualitative analysis. Topics include novel informatics, instrumentation and imaging; approaches will be presented with an emphasis on application to both small and large molecules. The objective of this session is to highlight state-of-the-art methodologies that are being applied to continuously improve bioanalytical and biotransformation capabilities for xenobiotics.

Symposium 6: Beyond Rule of 5
Co-chairs: Per Artursson, Uppsala University, Uppsala, Sweden and Dehua Pei, The Ohio State University, Columbus, Ohio, USA

The drug space beyond rule of five (bRo5) is populated with drug molecules that are substantially larger than traditional drugs. These include macrocycles, cyclic and stapled peptides as well as PROTACs (degraders). bRo5 drugs can interact with promising intracellular targets that are “difficult-to-drug” using traditional membrane permeable molecules. For instance, bRo5, but not traditionally sized molecules can target protein-protein interactions, which typically have large, featureless, flat or groove-shaped interfaces. While bRo5 drugs offers the opportunity to expand the number of “druggable” intracellular targets, they have well known drawbacks, including poor membrane permeability and oral bioavailability. This has stimulated the search for solutions that improve intracellular uptake and transcellular permeability, respectively. In this session, factors that influence the uptake and permeability of bRo5 compounds will be presented. Innovative approaches that increase intracellular target access will be covered and case stories from ADME and DMPK optimization of cyclic peptides and degraders in the pharmaceutical industry will be reviewed.