Work Package (WP) 1 aims to explore and develop novel technologies that enable more accurate detection of drug-induced CV liabilities. Specifically, WP1 will focus on the following technologies to enable more accurate CV safety assessment:
- Novel hiPSC CM in vitro models for early assessment of functional/structural CV toxicity.
- New approaches for measuring CV dynamics in awake socially interacting animals.
- Adopting numerical modelling approaches for in silico simulation and risk evaluation
- Exploring new technologies such as mass spectrometry imaging (MSI), functional imaging, etc. to identify new markers of CV safety.
- Dr. Damiano Lombardi (INRIA Research Centre)
- Dr. Hary Knot (TSE systems)
Adverse CV reactions, which were not predicted by preclinical studies, have been the reason for the discontinuation of drug development programmes in a sizeable number of cases. It is therefore important to better understand the translation of preclinical SP data to the human clinical outcome, to be able to develop novel therapeutic agents with improved safety profiles8. The current ICH 7A strategy for preclinical CV safety assessment entails evaluation of a limited set of parameters (such as the ECG, HR and BP) as part of the core battery (done to GLP). However, for obtaining a detailed in-depth understanding of complex or subtle haemodynamic responses, invasive studies in anaesthetised animals are often warranted. WP2 aims to develop better strategies (by combining in vitro, in vivo, patient and in silico studies) for detecting and understanding emerging CV safety topics. As such, WP2 bridges the technological creativity pursued in WP1 with the requirement of delivering validated SP solutions in WP3. More specifically, WP2 aims to:
- Explore new approaches to evaluate subtle haemodynamic drug-induced changes
- Investigate (late-onset) structural/functional cardiotoxicity
- Identify specific patient populations at risk and develop strategies for (clinical) risk mitigation
- Dr. Jeanette Woolard
- Dr. Emeline Van Cranenenbroeck
Often, promising biomarkers, assays, technologies etc. are developed by academia, but do not reach the stage of maturity requried by regulatory authorities. Indeed, wihtin safety pharmacology standardized procedures and extensive scientific validation is a prerequisite. WP3 aims to bridge this translational gap. WP3 will build upon the expertise of Ncardia, TSE systems, NOTOCORD and Vivonics, which have demonstrated their ability to successfully translate innovative technology into products/services. Furthermore, the pharma partners (UCB Biopharma, Boehringer Ingelheim, AstraZeneca) will add their expertise in validating novel technologies and assays. In brief, WP3 has two major aims:
- Pushing the Technology Readiness Level (TRL) of prototypes and ensuring early regulatory-alignment.
- Scientific validation, interaction with regulatory agencies and eventual implementation of the newly developed SP solutions in drug development for safer medicines.
- Dr. Annie Delaunois
- Dr. Arie Reyerkerck