PREDICT
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. 01.01.2019 Title
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
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 01.01.2019 Title
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