Mechanistic PK/PD modeling to address early-stage biotherapeutic dosing feasibility questions
Published in mAbs
Published in mAbs
Applied BioMath Assess™ can be used to optimize the design of CD3 bispecific T-cell engagers by evaluating the risk of on-target, off-tumor toxicities and to make an early prediction about therapeutic index and projections of effective and tolerable doses for T-cell engagers in solid tumors. In this case study, we will demonstrate the ability to predict the on-target, off-tumor toxicity observed for solitomab, a drug that failed to meet its end points due to dose limiting toxicity.
Bispecific drugs have great potential to improve tissue selectivity through avid binding interactions, but introduce non-trivial drug design parameters that must be considered as part of target selection and lead identification.
This case study demonstrates how to use Applied BioMath Assess™ to identify the level of avidity required for a drug to have a favorable efficacy and therapeutic index. It also illustrates how drug design decisions can benefit from modeling and simulation due to non-trivial impacts on drug behavior.