1. PREDICT

2. The BTS systems biology software platform
The BTS Systems Biology software platform allows the integration of dynamic models at the cellular scale into whole-body PBPK models at the organism level. Thereby, multiscale models can be constructed which simultaneously consider the distribution of compounds and the resulting cellular response at the tumor level.
Title

3. Project Plan PREDICT molecular and cellular level tumor/organ
identification of new drugable targets
optimization of efficacy & ADME-Tox
animal safety
First in Man dose
human safety
efficacy vs. placebo
efficacy vs. benchmark
Target identification & validation
Lead identification & optimization
Preclinical development
Clinical
phase I
Clinical
phase II
Clinical
phase III
molecular and cellular level
tumor/organ
whole body
scFv-TRAIL
PREDICT
reference drug A
literature
reference drug B
• Project Application ‘PREDICT’, Towards Predicting Effective Treatment of Cancer, Lars Küpfer

4. Milestones and deliverables
scFv-TRAIL
refinement of protein PBPK model and compartementalized tumor model
develop concepts for cross-species extrapolation of biologicals (incl. gene expression data)
model and simulate experimental data of project with a murine multiscale model (incl molecular, cell and tumor level)
comparative assessment candidates (e.g., imatinib, sorafenib, sunitinib or gefitinib)
identify suitable (pre-)clinical trial data based on literature research
develop multiscale PK/PD models (incl. modules from project partners where reasonable)
develop model-based concepts for clinical translation by posterior analysis of existing trial results (incl. cell lines, xenografts and patients)
evaluate potential of therapeutic protein used in PREDICT in hypothetical FIM studies
Title

5. A New Compartmental Gastro-Intestinal Tract Model
Detailed mechanistic description of the GI tract including physiological representation of gut lumen and mucosa allows for a more detailed implementation and improved translation of several processes
multiple applications can transit at any time
active processes such as glucose transporters (apical and basolateral)
representation of food to account for food effect
mucosal blood flow provides physiological absorption into the blood stream
transit and absorption of oral drugs
entero-hepatic cycling
Thelen et al., 2011a,b,c
15 June, 2011
REACTION Review, Brussels