Proposals should focus on group(s) of rare diseases with commonalities, such as shared biological features, possibly within the same and/or across different medical areas within the rare diseases landscape. 

The proposals should address most of the following research activities:

• Establish multidisciplinary collaborations between all relevant stakeholders by integrating disciplines, technological developments and existing knowledge. Integrate harmonised data from multiple sources (i.e. natural history studies/clinical trials, multi-omics, medical imaging, registries etc.) by utilising data analytics and/or other suitable methods, with the aim to understand the pathophysiology/heterogeneity of the rare diseases concerned and to identify therapeutically actionable mechanisms.
• Develop and utilise relevant preclinical models and/or innovative tools/technologies to: verify molecular/cellular pathways/genes that can be therapeutically targeted, increase the confidence in the targets selection and/or perform toxicity studies.
• Develop and/or execute innovative clinical trials designs for small populations and novel approaches to assess and monitor the safety and efficacy of the proposed interventions. Such approaches may include but are not limited to: biomarkers defining robust surrogate and clinical endpoints; artificial intelligence tools/medical devices/biosensors/ companion/ complementary diagnostics for defining reliable patient reported outcomes; modelling and simulation and in-silico trials methodologies.
• Carry out preclinical proof-of-concept (PoC) studies and/or multinational interventional clinical studies to demonstrate the safety and efficacy of the therapeutic interventions under study. Applicants should propose a clear exploitation pathway through the different necessary steps (research, manufacturing, regulatory approvals and licensing, IP management etc.) in order to accelerate marketing authorisation and uptake by the health systems.

The therapies to be developed may include a broad family of therapeutic interventions such as small molecule(s), advanced therapy medicinal products, repurposing of existing medicinal products, including non-pharmacological interventions and/or their combinations, as relevant.
The topic will support proposals covering several different stages in the continuum of the innovation pathway (i.e. translational, preclinical, clinical research, validation in the clinical and/or real-world setting etc.), as relevant.

SME(s) participation is encouraged with the aim to strengthen the scientific and technological basis of SME(s) and valorise their innovations for the benefit of people living with a rare disease.