May 24th - 26th, 2022 | Boston
Applied BioMath Presence
Presentation: Mechanistic modeling to optimize doses for receptor crosslinking and checkpoint blockade: a case study with a 41BB/ PDL1 bispecific antibody
Presenter: Alison Betts, PhD, Vice President of Scientific Collaborations and Fellow of Modeling & Simulation
Presentation Time: TBA
- ATG-101 is a bispecific antibody that crosslinks tumor-expressed PD-L1 to T-cell-expressed 4-1BB, thereby selectively activating T-cells infiltrating solid tumors while inhibiting immune checkpoints.
- ·To activate 41BB, the molecule requires to crosslink tumor cells and T cells to form trimeric complexes ("trimers'), which have a bell-shaped relationship with dose. To block PDL1, the molecule must achieve sufficient target coverage (>90%). These opposing pharmacologys can complicate dose selection.
- ·Learn how a mechanistic model was developed, calibrated and benchmarked to preclinical in vitro and in vivo data, and used to predict both optimal trimer formation and PDL1 receptor occupancy to guide rational clinical dose selection.