ADME and Translational Pharmacokinetics / Pharmacodynamics of Therapeutic Proteins: Applications in Drug Discovery and Development

Improve the discovery and development of protein drugs

Since entering clinical studies, monoclonal antibodies have become a critical part of drug treatment regimens with more than 30 approved for clinical use and hundreds under development. Some of them have become treatments of choice, in particular in areas such as oncology and immune–mediated inflammatory diseases. Nevertheless, limitations inherent in the canonical monospecific IgG–based monoclonal antibodies have prompted exploration of alternative molecular formats, such as antibody drug–conjugates (ADCs), bi– or multi–specific versions of antibodies. However, there is still scarcity of knowledge and data and lack of consistent strategies in effectively taking those candidate biologics from preclinical to clinical development. Recent years, though, have seen much progress in understanding the ADME (absorption, distribution, metabolism and excretion) of therapeutic biologics and how this knowledge is used to transition from preclinical to early clinical development.

With an emphasis on the theoretical and practical aspects of ADME for therapeutic proteins, this book helps readers strategize, plan and implement end–to–end translational research for biologic drugs. Chapter authors writing from the frontlines of biologics research and development cover topics that include similarities and differences in ADME characteristics between small molecule drugs and therapeutic biologics, the types of therapeutic biologics (monoclonal antibodies, fusion proteins, pegylated proteins, vaccines or proteins with different scaffolds like ADCs and bispecifics) and their unique ADME properties, and how protein engineering alters and optimizes ADME and PK/PD properties of therapeutic proteins.

A complete and valuable reference and resource for anyone working in the biopharmaceutical field, ADME and Translational Pharmacokinetics / Pharmacodynamics of Therapeutic Proteins offers features that include:

 Details about ADME and PK/PD (pharmacokinetic / pharmacodynamics) modeling for biologic drugs
 Comparison of small molecules with biologics, giving a lessons–learned perspective
 Mechanistic insight in target–driven and local PK/PD in sites of action like tumors and the brain
 Case studies about leveraging ADME to improve end–to–end biologics drug development
 Current thinking and strategies on biosimilar development from ADME and PK/PD standpoints
 Regulatory expectations and industry perspectives for biologic development in USA, EU, and Japan

Honghui Zhou is a Senior Director and Janssen Fellow, at Janssen Research & Development, LLC and head of the Pharmacological and Translational Modeling Department. Board–certified by the American Board of Clinical Pharmacology and a Fellow of American Association of Pharmaceutical Scientists (AAPS) and American College of Clinical Pharmacology (ACCP), Dr. Zhou has authored more than 180 peer–reviewed scientific papers, book chapters, and conference abstracts and co–edited the book Drug–Drug Interactions for Therapeutic Biologics (Wiley, 2013).

Frank–Peter Theil heads nonclinical development at UCB Pharma. Dr. Theil has authored and co–authored 40 research publications, three book chapters and he has given numerous invited presentations at national and international scientific meetings. He is a member of the American Association of Pharmaceutical Scientists (AAPS) and American Society of Clinical Pharmacology and Therapeutics (ASCPT).