Use of PK / PD Knowledge in Guiding Bispecific Biologics Research and Development

Abstract

This chapter describes the different types of bispecific formats as well as the principles used to generate them, before elaborating on the biochemical and pharmacological properties including affinity, avidity, and pharmacokinetics (PK). In addition, assay strategies to measure these compounds and the use of pharmacokinetic/pharmacodynamic (PK/PD) modeling in the design and development of these complex molecules are also covered. Next, the chapter highlights some of the key properties of bispecific antibodies (bsAbs) that may be considered or leveraged while developing these novel and complex therapeutics. The overall PK behavior of the bsAb is strongly dependent on the format. BsAbs based on immunoglobulin G (IgG) may be preferred due to the favorable PK properties (e.g., long serum half‐life) as well as the option to modulate the effector functions. Finally, it presents three case studies to highlight some of the challenges in the research and development of bsAbs.

Non-human primates in the PKPD evaluation of biologics: Needs and options to reduce, refine, and replace. A BioSafe White Paper

“… 3 We focus primarily on monoclonal antibodies (mAb), as they are the most common biologics in development and on the market, but it is worth noting that the principles we describe are also applicable to engineered formats such as multi-specifics or Fc-fusion proteins. 4 …”