Periodic Reporting for period 2 - REPO4EU (Precision drug REPurpOsing For EUrope and the world)
Reporting period: 2024-03-01 to 2025-08-31
REPO4EU – A New Era for Precision Medicine Through Mechanism-Based Drug Repurposing
Modern medicine struggles to cure rather than only relieve symptoms, as most diseases remain poorly understood at the molecular level. Developing new drugs is costly and slow, while innovation for rare and complex diseases has largely stalled.
REPO4EU tackles this by redefining diseases through their causal molecular mechanisms instead of symptoms. Using AI, bioinformatics, and systems medicine, it identifies risk genes and dysregulated networks to guide precise, low-dose drug combinations with fewer side effects.
Instead of discovering new compounds, REPO4EU accelerates therapy development through repurposing existing, approved drugs, cutting years of development time and cost. Building on the successful CIPER pilot, clinical studies such as REPO-HYPER II, REPO-THYROID II, and REPO-DIPG II are now preparing patient-stratified precision trials.
At its core, REPO4EU builds a European open-access platform combining multi-omics data, AI analytics, and validation tools to connect academia, industry, regulators, and patients.
Aligned with the European Health Data Space and EU Pharmaceutical Strategy, REPO4EU advances fair, sustainable, and equitable access to new therapies and establishes the foundation for a permanent European infrastructure (REPOSYSTEM) for open, mechanism-based drug repurposing.
Modern medicine struggles to cure rather than only relieve symptoms, as most diseases remain poorly understood at the molecular level. Developing new drugs is costly and slow, while innovation for rare and complex diseases has largely stalled.
REPO4EU tackles this by redefining diseases through their causal molecular mechanisms instead of symptoms. Using AI, bioinformatics, and systems medicine, it identifies risk genes and dysregulated networks to guide precise, low-dose drug combinations with fewer side effects.
Instead of discovering new compounds, REPO4EU accelerates therapy development through repurposing existing, approved drugs, cutting years of development time and cost. Building on the successful CIPER pilot, clinical studies such as REPO-HYPER II, REPO-THYROID II, and REPO-DIPG II are now preparing patient-stratified precision trials.
At its core, REPO4EU builds a European open-access platform combining multi-omics data, AI analytics, and validation tools to connect academia, industry, regulators, and patients.
Aligned with the European Health Data Space and EU Pharmaceutical Strategy, REPO4EU advances fair, sustainable, and equitable access to new therapies and establishes the foundation for a permanent European infrastructure (REPOSYSTEM) for open, mechanism-based drug repurposing.
REPO4EU, coordinated by Maastricht University, unites over twenty European partners in nine interlinked areas covering AI, pre-clinical and clinical validation, IP, HTA, ethics, and sustainability. Together, they form the backbone of a new European infrastructure for mechanism-based drug repurposing.
The project developed an integrated AI and network-pharmacology toolbox to identify disease modules, causal mechanisms, and matching drugs. This open-access platform—now in alpha testing—enables biomedical scientists to perform advanced bioinformatics analyses through an intuitive interface.
Standardised procedures were created for testing repurposed drug combinations in cell and animal models, ensuring reproducibility and regulatory alignment. Validation began for several rare and complex diseases, confirming the feasibility of the REPO4EU approach.
A pan-European network for investigator-initiated precision trials was established, supported by adaptive design and statistical guidance. Improved sampling and data-integration technologies enable patient recruitment based on mechanistic subtypes and early detection of treatment effects.
The consortium defined the technical and interoperability framework for a unified digital platform integrating data, models, and validation tools. An ethics-by-design process ensures compliance with data protection and integrity standards.
Finally, REPO4EU launched a diamond open-access publishing hub on drug repurposing and systems medicine, marking the transition from conceptual design to operational capability. These achievements establish the foundation for a sustainable European ecosystem accelerating the discovery of affordable, safe, and effective therapies.
The project developed an integrated AI and network-pharmacology toolbox to identify disease modules, causal mechanisms, and matching drugs. This open-access platform—now in alpha testing—enables biomedical scientists to perform advanced bioinformatics analyses through an intuitive interface.
Standardised procedures were created for testing repurposed drug combinations in cell and animal models, ensuring reproducibility and regulatory alignment. Validation began for several rare and complex diseases, confirming the feasibility of the REPO4EU approach.
A pan-European network for investigator-initiated precision trials was established, supported by adaptive design and statistical guidance. Improved sampling and data-integration technologies enable patient recruitment based on mechanistic subtypes and early detection of treatment effects.
The consortium defined the technical and interoperability framework for a unified digital platform integrating data, models, and validation tools. An ethics-by-design process ensures compliance with data protection and integrity standards.
Finally, REPO4EU launched a diamond open-access publishing hub on drug repurposing and systems medicine, marking the transition from conceptual design to operational capability. These achievements establish the foundation for a sustainable European ecosystem accelerating the discovery of affordable, safe, and effective therapies.
REPO4EU advances drug development from trial-and-error to a mechanism-based, data-driven, and sustainable model of precision medicine. It demonstrates that existing drugs can be repurposed according to molecular mechanisms rather than symptoms, cutting cost, time, and failure rates.
A technology-ready platform architecture reached TRL 6, integrating analytical, validation, and clinical-support tools. Using large-scale omics and real-world data, REPO4EU identified disease- and endotype-specific modules that match approved drugs to defined mechanisms, enabling rapid translation into investigator-initiated trials.
The consortium developed DNA- and multiplex-based workflows for rare and cancer therapies, combining AI prediction with laboratory validation—delivering the first mechanism-defined strategies ready for clinical testing.
An ethics-by-design, privacy-preserving data framework ensures responsible use of patient data and broad stakeholder trust. In parallel, HTA methodologies were introduced early in the development pipeline to assess clinical and socio-economic value, guiding reimbursement and policy decisions.
These advances prepare the foundation for REPOSYSTEM, Europe’s future infrastructure for mechanism-based repurposing. Next steps include platform validation through clinical pilots, wider data integration, regulatory alignment on adaptive approvals, and sustainable open-access and public-private models.
Together, these achievements position Europe as a leader in AI-enabled, mechanism-based precision medicine, delivering faster, safer, and more affordable therapies.
A technology-ready platform architecture reached TRL 6, integrating analytical, validation, and clinical-support tools. Using large-scale omics and real-world data, REPO4EU identified disease- and endotype-specific modules that match approved drugs to defined mechanisms, enabling rapid translation into investigator-initiated trials.
The consortium developed DNA- and multiplex-based workflows for rare and cancer therapies, combining AI prediction with laboratory validation—delivering the first mechanism-defined strategies ready for clinical testing.
An ethics-by-design, privacy-preserving data framework ensures responsible use of patient data and broad stakeholder trust. In parallel, HTA methodologies were introduced early in the development pipeline to assess clinical and socio-economic value, guiding reimbursement and policy decisions.
These advances prepare the foundation for REPOSYSTEM, Europe’s future infrastructure for mechanism-based repurposing. Next steps include platform validation through clinical pilots, wider data integration, regulatory alignment on adaptive approvals, and sustainable open-access and public-private models.
Together, these achievements position Europe as a leader in AI-enabled, mechanism-based precision medicine, delivering faster, safer, and more affordable therapies.