Cardiovascular disease (CVD) is one of the major diseases in Europe and the Western world, killing over 2 million people per year in Europe alone and is the foremost cause of premature mortality and disability-adjusted life years, representing an annual economic cost of approximately € 192 billion in direct and indirect healthcare expenses. The available therapies are insufficient to fulfil the need. The introduction of statins has reduced morbidity and mortality of atherosclerosis by 30%, however a large untreatable residual cardiovascular risk remains even in cohorts of treated patients.
Currently, many targets for CVD treatment have been selected based on mechanism of action and inference of functions in cellular models to clinical systems, and lack the rigorous clinical validation needed to maximize the chance for successful clinical drug development. Consequently, new drugs that modulate the activity of such targets fail later in clinical development by lack of efficacy or induction of safety liabilities due to off-targets effects.
To increase the success rate for clinical development of novel therapies in CVD, we will follow an innovative approach by using:
- Independent and large-scale population studies from which novel targets with strong correlation to clinical phenotypes are deduced;
- Translational disease-mimicking models to validate novel drug targets;
- High quality human biobanks to confirm the molecular relevance of targets in diseased cardiovascular tissues;
- A stringent pharmaceutical drug discovery process for prioritization of drugable targets.
An important concept, in line with the changed pharmaceutical business model, is that these steps can best be executed by a functional network of clinical academic centers and specialized SMEs under the guidance of established and experienced drug discovery researchers from industry that brings together the right components and expertise to execute such a modular target discovery process.