Biologics: Rational Molecular and Process Design Enabled by Computational Modeling

Join the UH Drug Discovery Institute for this hybrid event. A Zoom link will be emailed to registered attendees.

About the Event

Design of a new compound or molecular entity is a continuum that is complex and challenging, focused on definition of Structure Activity Relationship (SAR) in Discovery combined with an assessment of manufacturing and development feasibility or Computational Developability. The types and extent of the challenges evolve, shift, and grow over the course of development through commercial manufacturing. SAR has historically been deployed in small molecule space and has been recently extended to large molecule biologics. SAR is a broad inquiry that often focuses on target engagement for a specific receptor which ironically is the most straightforward to define and is most relevant to compound discovery. However, the most challenging aspect, and often overlooked, is the SAR component related to off‐target interactions (ex. host cell protein/product interactions, alternate target engagement including ligand/product interactions and/or self‐association). These off‐target interactions become more important later in the molecule’s lifecycle, e.g. process development. There is an opportunity that now exists, enabled by various aspects of modeling, Machine Learning (ML) and Artificial Intelligence (AI) to pursue a more elegant approach that encompasses all the elements required for successful development of a new compound (ex. process, formulation, stability). These modeling efforts are still enabled by experimental high throughput screening that generates sufficient training or calibration data sets (as necessary). Specific examples that illustrate these concepts will be reviewed during the seminar.

About the Speaker

Dr. David Roush is a Distinguished Scientist in Biologics Process Research and Development at Merck Research Labs. He received his B.S. in Chemical Engineering from Rice University, worked at BASF, and then completed his Ph.D. at UH under the guidance of Dr. Richard Willson, where he researched the thermodynamics of protein adsorption on ion-exchange surfaces through experiments and computational electrostatics modeling. He joined Merck Research Labs in 1994 and has co-authored over 130 publications on the purification of biologics. He has contributed to the development and commercialization of five pharmaceutical products, most recently KeytrudaTM for which he and the CMC team were honored with the ACS Heroes of Chemistry Award in 2021. Dr. Roush has served the Biochemical Technology (BIOT) division of the American Chemical Society for over 20 years, serving as Industrial Co-Chair, session chair at 11 ACS National Meetings, Secretary, Treasurer, and Chair of the Division. He was recognized as an ACS Fellow in 2019.