22/03/2025
9:00 – 10:00
Introduction to clinical pharmacology of biologics
- Clinical pharmacology of biologics: rationale of unique PKPD characteristics
- General considerations and guidelines for safe FiH starting dose calculation
10:00 – 11:00
MABEL approach for FiH dose selection: to be or not to be
- Establishing minimal anticipated biological effect level (MABEL) criteria for biologics: current perspectives and recommendations
- Step-by-step calculation of FiH dose for bispecific mAb based on MABEL using R statistics and “Simurg” infrastructure
- Beyond “conservative” MABEL approach: is the selected dose optimal?
Break
11:15 – 13:00
Model-based analysis of in vitro cytotoxicity data
- Obligatory properties of bispecific antibodies: affinity Vs avidity
- Diverse conditions of in vitro data: how to account for incubation time, E:T ratio, various cell lines, etc
- Quantifying “immunological synapse”: T-cell dependent cellular cytotoxicity (TDCC) mode
13:00 – 14:00
Lunch Break
14:30 – 16:30
Translational QSP modeling – from in vitro to human
- Translational QSP model development to predict exposure-efficacy and exposure-safety relationships in patients R statistics and “Simurg” infrastructure – from exploratory data analysis to advanced diagnostics
- Implementing local and global sensitivity analyses: step towards virtual populations generation
- Model-based calculation of pharmacology active and safety doses for FiH trials via virtual patient populations
- Quick look at MID3 approaches in support of bispecific Ab development: towards sequential preclinical/clinical data integration via QSP approach
16:30 – 17:00
