Allen J. Sedman Lecture
Pharmaceutical Sciences Seminar Series
Wednesday, April 12, 2023
NCRC Building 10 Research Auditorium or
Meeting ID: 932 7742 8228
5th Allen J. Sedman Lecture
“Application of mechanistic PK/PD modeling to guide
the discovery of antibodies and antibody fragments”
Joseph P. Balthasar, Ph.D.
David and Jane Chu Endowed Chair in Drug Discovery and Development
School of Pharmacy and Pharmaceutical Sciences
University at Buffalo
Abstract: Pharmacokinetic/pharmacodynamic (PK/PD) research is traditionally pursued during drug development (i.e., after drug candidates have been selected) or after drug approval and marketing. This lecture will discuss opportunities for using PK/PD modeling to assist in drug discovery. Examples will be provided for the application of PK/PD to guide each of the major objectives of the discovery process, including: (a) target identification / validation with discussion of use of mechanistic PK/PD modeling to assist in the identification and validation of the Fc receptor of the neonate (FcRn) as a drugable target for treatment of auto- and allo-immune conditions, (b) use of PK/PD to guide hit-to-lead engineering for anti-idiotypic distribution enhancers (AIDEs) that improve antibody distribution within solid tumors, and (c) use of PK/PD concepts to guide lead-optimization for payload-binding selectivity enhancers (PBSEs) that are designed to improve the therapeutic index of antibody-drug conjugates (ADCs). Most of the focus for the lecture will be placed on recent research relating to the use of AIDEs to improve the efficacy of trastuzumab conjugates in the treatment of mouse models of human HER2+ tumors, and relating to the use of PBSE to improve the safety and therapeutic index of MMAE ADCs (e.g., brentuximab vedotin, enfortumab vedotin, trastuzumab vedotin, polatuzumab vedotin) and DM4 ADCs (e.g., mirvetuximab soravtansine, 7E7 [anti-CD123]-DM4).
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