Periodic Reporting for period 1 - REPO4EU (Precision drug REPurpOsing For EUrope and the world)
Berichtszeitraum: 2022-09-01 bis 2024-02-29
REPO4EU - A new era for medicine and a fast track to new drug therapies
Medicine itself is sick. We hardly understand any disease concerning its molecular cause. Hence, we can treat only symptoms but not cure, which is why so many diseases become chronic. Moreover, developing new drug therapies has become increasingly prone to failure and thus risky and costly overall. In several areas, the pharmaceutical industry has almost completely retracted. In parallel, there are too few non-industry investigator-initiated trials.
REPO4EU overcomes these roadblocks in efficacy and precision by fundamentally redefining what we call a disease, namely rare diseases, by causal risk genes. This allows precise mechanism-based diagnosis and both precise and curative drug therapy. To speed up this process beyond the current 12-15 years for drug discovery, this revolutionary approach to medicine is combined with the repurposing of already registered drugs for new indications. This skips the several yearlong discovery, safety, and early development phases so that REPO4EU’s technologies can immediately be applied in low-cost, high-precision investigator-initiated clinical trials.
Our team of world-leading scientists achieves this by bringing recent breakthroughs in bioinformatics, systems medicine, and AI on real-world big data to redefine diseases mechanism-based. Patients with symptoms are stratified according to their underlying causal mechanism, the endotype. These are small, dysregulated signaling networks that are corrected by combining 2-3 drugs in very low doses ensuring efficacy and low side effects. REPO4EU enables rapid, small, precise, innovatively designed clinical trials, prioritizing patient-defined outcomes with high safety and operational excellence.
REPO4EU’s goal is to establish and grow an industry-level online open-access platform for mechanism-based precision drug repurposing in all areas of medicine, with a global outreach. This platform is planned to operate as a European infrastructure for crucial information, training, matchmaking, and valorization in this new approach to medicine and sustainable drug repurposing.
Medicine itself is sick. We hardly understand any disease concerning its molecular cause. Hence, we can treat only symptoms but not cure, which is why so many diseases become chronic. Moreover, developing new drug therapies has become increasingly prone to failure and thus risky and costly overall. In several areas, the pharmaceutical industry has almost completely retracted. In parallel, there are too few non-industry investigator-initiated trials.
REPO4EU overcomes these roadblocks in efficacy and precision by fundamentally redefining what we call a disease, namely rare diseases, by causal risk genes. This allows precise mechanism-based diagnosis and both precise and curative drug therapy. To speed up this process beyond the current 12-15 years for drug discovery, this revolutionary approach to medicine is combined with the repurposing of already registered drugs for new indications. This skips the several yearlong discovery, safety, and early development phases so that REPO4EU’s technologies can immediately be applied in low-cost, high-precision investigator-initiated clinical trials.
Our team of world-leading scientists achieves this by bringing recent breakthroughs in bioinformatics, systems medicine, and AI on real-world big data to redefine diseases mechanism-based. Patients with symptoms are stratified according to their underlying causal mechanism, the endotype. These are small, dysregulated signaling networks that are corrected by combining 2-3 drugs in very low doses ensuring efficacy and low side effects. REPO4EU enables rapid, small, precise, innovatively designed clinical trials, prioritizing patient-defined outcomes with high safety and operational excellence.
REPO4EU’s goal is to establish and grow an industry-level online open-access platform for mechanism-based precision drug repurposing in all areas of medicine, with a global outreach. This platform is planned to operate as a European infrastructure for crucial information, training, matchmaking, and valorization in this new approach to medicine and sustainable drug repurposing.
REPO4EU is coordinated by Harald Schmidt, Maastricht University. The project is composed of nine interconnected work areas:
• Real-World Data Driven Artificial Intelligence
• Pre-clinical validation
• Technology readiness
• Precision patient recruitment technology
• Intellectual Property (IP)strategy and business development (BD)
• Health technology assessment (HTA)
• Precision clinical validation
• Ethics-by-design and Data Protection
• Platform building and Sustainability
They are supported by seven project advisory boards.
During Period 1, several significant achievements were made, advancing the field of drug repurposing and network pharmacology. These accomplishments include the development of a comprehensive collection of tools, data sources, and representation standards, along with the discovery of indication-specific modules and mechanism-based drug repurposing workflows. Standard operating procedures were established for evaluating the effects of network pharmacology therapies, applicable to various cell types and, if necessary, animal models. Additionally, critical technologies and data were assessed and prepared to ensure readiness for research and applications.
Advanced sampling and assay technologies were developed to improve patient recruitment and monitoring processes. To understand the needs and perspectives of various stakeholders involved in drug repurposing, a survey was conducted. A systematic review and interview study identified the challenges in drug repurposing and health technology assessment, providing potential solutions.
A network for Phase I and Phase II investigator-initiated clinical trials was established, accompanied by a handbook and a statistical compendium, which include innovative precision designs for clinical trials. A comprehensive ethics-by-design review process was implemented to ensure all research and developments adhere to ethical standards. Furthermore, a diamond open-access publication portal was launched, dedicated to sharing research on network medicine and drug repurposing.
Finally, detailed specifications were outlined for a unique interactive infrastructure that will serve as the central platform for drug repurposing efforts. These achievements mark a significant step forward in making drug repurposing more efficient and effective, ultimately aiming to improve treatments for various medical conditions.
• Real-World Data Driven Artificial Intelligence
• Pre-clinical validation
• Technology readiness
• Precision patient recruitment technology
• Intellectual Property (IP)strategy and business development (BD)
• Health technology assessment (HTA)
• Precision clinical validation
• Ethics-by-design and Data Protection
• Platform building and Sustainability
They are supported by seven project advisory boards.
During Period 1, several significant achievements were made, advancing the field of drug repurposing and network pharmacology. These accomplishments include the development of a comprehensive collection of tools, data sources, and representation standards, along with the discovery of indication-specific modules and mechanism-based drug repurposing workflows. Standard operating procedures were established for evaluating the effects of network pharmacology therapies, applicable to various cell types and, if necessary, animal models. Additionally, critical technologies and data were assessed and prepared to ensure readiness for research and applications.
Advanced sampling and assay technologies were developed to improve patient recruitment and monitoring processes. To understand the needs and perspectives of various stakeholders involved in drug repurposing, a survey was conducted. A systematic review and interview study identified the challenges in drug repurposing and health technology assessment, providing potential solutions.
A network for Phase I and Phase II investigator-initiated clinical trials was established, accompanied by a handbook and a statistical compendium, which include innovative precision designs for clinical trials. A comprehensive ethics-by-design review process was implemented to ensure all research and developments adhere to ethical standards. Furthermore, a diamond open-access publication portal was launched, dedicated to sharing research on network medicine and drug repurposing.
Finally, detailed specifications were outlined for a unique interactive infrastructure that will serve as the central platform for drug repurposing efforts. These achievements mark a significant step forward in making drug repurposing more efficient and effective, ultimately aiming to improve treatments for various medical conditions.
Technology-ready and visible
The project's impact is enabled by its state-of-the-art advancements, technical validation, and outreach-related key results. In period 1, several significant achievements have contributed to this impact, including the identification of disease and endotype modules that enable precision drug repurposing, achieving a technology readiness level of at least 6 for the drug repurposing platform, and developing DNA- and multiplex-based drug repurposing workflows for innovative precision cancer therapy. The project has also explored the role of HTA in drug repurposing and how it can overcome potential barriers. Additionally, the privacy-friendly processing of patient data has been emphasized to ensure better acceptance and wider use of the platform.
Global dissemination efforts have been extensive, mobilizing a total of 1.4K and 6K followers on social media for REPO4EU and the coordinator, respectively. Daily content has included over 460 posts, ten blog entries, and three newsletter issues. These efforts have been further boosted by the annual RExPO conference series and seven national dissemination events under the REPO4EU On Tour label. Moreover, eight preprints, five peer-reviewed papers in international journals, three white papers, and 93 items in conference proceedings have been produced, showcasing the project's comprehensive outreach and dissemination strategy.
The project's impact is enabled by its state-of-the-art advancements, technical validation, and outreach-related key results. In period 1, several significant achievements have contributed to this impact, including the identification of disease and endotype modules that enable precision drug repurposing, achieving a technology readiness level of at least 6 for the drug repurposing platform, and developing DNA- and multiplex-based drug repurposing workflows for innovative precision cancer therapy. The project has also explored the role of HTA in drug repurposing and how it can overcome potential barriers. Additionally, the privacy-friendly processing of patient data has been emphasized to ensure better acceptance and wider use of the platform.
Global dissemination efforts have been extensive, mobilizing a total of 1.4K and 6K followers on social media for REPO4EU and the coordinator, respectively. Daily content has included over 460 posts, ten blog entries, and three newsletter issues. These efforts have been further boosted by the annual RExPO conference series and seven national dissemination events under the REPO4EU On Tour label. Moreover, eight preprints, five peer-reviewed papers in international journals, three white papers, and 93 items in conference proceedings have been produced, showcasing the project's comprehensive outreach and dissemination strategy.