American Association of Pharmaceutical Scientists National Biotechnology Conference Short Course: Translational Challenges in Developing Antibody-Drug Conjugates

Abstract

The American Association of Pharmaceutical Scientists (AAPS) National Biotechnology Conference Short Course “Translational Challenges in Developing Antibody-Drug Conjugates (ADCs),” held May 24, 2012 in San Diego, CA, was organized by members of the Pharmacokinetics, Pharmacodynamics and Drug Metabolism section of AAPS. Representatives from the pharmaceutical industry, regulatory authorities, and academia in the US and Europe attended this short course to discuss the translational challenges in ADC development and the importance of characterizing these molecules early in development to achieve therapeutic utility in patients. Other areas of discussion included selection of target antigens; characterization of absorption, distribution, metabolism, and excretion; assay development and hot topics like regulatory perspectives and the role of pharmacometrics in ADC development. MUC16-targeted ADCs were discussed to illustrate challenges in preclinical development; experiences with trastuzumab emtansine (T-DM1; Genentech) and the recently approved brentuximab vedotin (Adcetris®; Seattle Genetics) were presented in depth to demonstrate considerations in clinical development. The views expressed in this report are those of the participants and do not necessarily represent those of their affiliations.

Keywords: :

• ADC
• pharmacokinetics
• linker
• trastuzumab emtansine
• brentuximab vedotin

Note

K.T. wrote and prepared the manuscript for publication. K.T, S.B., D.L., W.M., S.K., B.M., H.E., J.T., H.Z., and M.G. wrote and reviewed the manuscript. S.B., D.L, and M.G. organized and moderated this short course. S.B., D.L., W.M., S.K., H.E., J.T., H.Z., and M.G. presented during the short-course and served as panelists for the panel session.

Potential Conflicts of Interest

K.T., S.B., and W.M are employed by Novartis Pharmaceuticals and declare no competing financial interests. D.L., and S.K., are employed by Genentech. J.T. is currently employed at UCB Pharma Ltd and was formerly employed by Genentech during the development of Trastuzumab emtansine. H.E. is employed by ImmunoGen, Inc. H.Z. is employed by the US. Food and Drug Administration. M.G. is employed by Bristol-Myers Squibb and was formerly employed by Genentech during the development of trastuzumab emtansine. B.M. is employed by the University of Tennessee.

Acknowledgments

The authors acknowledge and thank AAPS- NBC for supporting the short-course and recognize the scientists dedicated to the defining the ADC development path. The authors would like to acknowledge Benjamin Guiastrennec who assisted in the preparation of Figure 1.