Systems approaches for the discovery of combinatorial therapies for complex disorders

Research should aim to understand at systems level the pathophysiology of a disorder in groups of patients responding well or poorly to particular therapies and further develop combinatorial therapies tailored to the needs of individuals or stratified patient groups.

Projects should focus on already available and/or authorised therapies and have access to standardized biobank samples derived from retrospective or currently running clinical studies. These patient samples should be re-analysed with modern high-throughput technologies. The existing and newly produced data should be integrated using systems approaches, which could combine sub-cellular/cellular and/or organ level in-silico models and network analysis as appropriate, and used to build more sophisticated computational frameworks to predict patient responses to combinatorial therapies. These predictions should be validated in pre-clinical and clinical studies[[http://ec.europa.eu/research/participants/data/ref/h2020/other/legal/templ/h2020_tmpl-clinical-studies_en.pdf]] taking into account sex and gender differences. Funding of late stage clinical trials is not within the scope of this topic.

Applicants should include a thorough data management plan for transnational data sharing to enable the computational analysis and it is strongly recommended to adhere to the state-of-the-art international standards and to the general concepts of the FAIR[[https://www.force11.org/group/fairgroup/fairprinciples]] principles.

The topic invites proposals in complex disorders of high prevalence and of a high economic burden (rare diseases are excluded). SME participation is strongly encouraged.

The Commission considers that proposals requesting a contribution from the EU of between EUR 4 and 6 million would allow this specific challenge to be addressed appropriately. Nonetheless, this does not preclude submission and selection of proposals requesting other amounts.

Many complex disorders pose a challenge to identify the most effective therapeutic interventions because current therapies often target specific aspects of a disease, without achieving complete control or the best possible results for patients. Due to the multiple causes of such diseases and the heterogeneity between patients, approaches directed at single targets have had limited efficacy, overlooking important factors involved in disease pathophysiology. Hence, a promising therapeutic approach to meet this challenge is to combine different therapies, while increasing therapeutic efficacy in a cost-effective manner.

• New concepts of combinatorial therapies for complex disorders tailored to the needs of individuals or stratified patient groups.
• Improved efficacy and take-up in the clinical setting in comparison to established therapeutic interventions.
• Enable the development of personalised medicine.
• Increased research & innovation opportunities in this industry intensive field, particularly for SMEs.