This webinar will introduce a quantitative systems pharmacology (QSP) model of targeted anabolic growth factors for intra-articular injection for the treatment of diseased joints which was created during a collaboration between Applied BioMath and AbbVie. The QSP model was used to systematically map out drug- and target-parameter space to:
- Identify tradeoffs between target and drug properties
- Maximize therapeutic window and tissue targeting
- Identify key missing data
- Benchmark targeted anabolic growth factors vs. untargeted anabolic growth factors already in clinical
Species specific models (rat, dog and human) were developed to enable cross species translation, and integration of preclinical data. Model analysis and simulation was used to identify the efficacy receptor turnover rate as a key parameter for establishing dose feasibility. This differentiated between some potential targets for where high receptor turnover rate may make dosing a challenge. The model also enabled the identification of the requirements for the targeting epitope and targeting arm affinity to maximize therapeutic window and tissue targeting.