Scientist Genentech, Inc. South San Francisco, California
Activation of the Tie2 pathway is expected to complement current anti-vascular endothelial growth factor (VEGF) strategies in the treatment of Diabetic Macular Edema where vascular stabilization is crucial. In this presentation I will describe how PK/PD properties of an intravitreally administered anti-Tie2 agonist determined in cynomolgus monkeys were translated to humans using a mechanistic ocular PK/PD modeling approach. In addition, I will demonstrate how the sensitivity analysis exploring the impact of an in vitro bell-shaped activation curve and the extent of retinal penetration on the predicted activity of anti-Tie2 agonist in humans was used to guide the selection of an optimal dose range and dosing frequency for a Phase 1 clinical study.
Learning Objectives:
Use a mechanistic ocular PK/PD model to translate preclinical data to support first-time-in-human dose selection.
Perform sensitivity analysis to explore the impact of drug pharmacological properties on the predicted PK/PD relationship in human.
Understand translational challenges for an intravitreal agonist molecule.
