REPO4EU News - Nov 2025

REPO4EU News – November 2025 Dear colleague, Welcome to the sixth edition of the REPO4EU Newsletter! With our third official anniversary now in the rearview mirror and the end of the year rapidly approaching, we wanted to take a quick look back at everything that has happened to share the key highlights, stories and breakthroughs that the REPO4EU team has been an active part of in 2025. From the launch of our platform's alpha version and the latest advances on our clinical trials, to exciting future opportunities for networking and collaboration: read on to discover what we have been up to in our journey to make mechanism-based drug repurposing a reality, and to bring safe, effective and affordable therapies to patients. Prof, Harald Schmidt MD, PhD, PharmD Coordinator of REPO4EU – Maastricht University Introducing the next iteration of Drugst.One: our solution for network exploration that turns your tool that outputs a list of genes or proteins into a feature-rich, drug repurposing web application with interactive network visualization. This brand new version is called Drugst.One DREAM (Drug Repurposing through Expert Annotation and Modification), and will provide biomedical experts with a user-friendly toolbox for disease module refinement that does not require bioinformatics expertise and is able to introduce additional network editing features. In the spotlight Try it out Try it out After nearly two years of work and collaboration, the alpha version of our drug repurposing platform is now a reality. We are inviting scientists, clinicians, bioinformaticians, regulatory experts and anyone involved in drug repurposing to take part in the platform’s early testing phase. Sounds interesting? Click the link below to submit your interest and become an early-tester! Register here Register here Drugst.One DREAM – Network exploration and drug repurposing Collaboration opportunities Our 2026 Brussels policy event on March 18, within the European Parliament week, will focus squarely on the central roadblock shared across precision-medicine fields — from rare diseases and repurposed drugs to advanced therapies (ATMPs): the absence of viable reimbursement pathways. Whether a therapy relies on a registered drug that is “too inexpensive” to justify investment, or targets an ultrarare subgroup with limited market size, the result is the same: innovations stall before reaching patients. Building on the concepts presented in our updated HTA abstract, we will convene regulators, HTA bodies, industry partners, and patient organisations to explore new, adaptive reimbursement models that support early evidence, mechanistic stratification, and realworld learning. We will also team up with parallel initiatives from the rare-disease and ATMP communities to drive a unified agenda for sustainable access. The goal is clear: without innovative reimbursement strategies, all of these breakthroughs risk never making it to the clinic. This event aims to change that. Discover our Special Interest Group Discover our Special Interest Group Building on our work in mechanistic disease mapping and patientempowered stratification, we are preparing a new Global Rare Disease Initiative to validate lowcost, mechanism-based therapies across monogenic conditions and high-need patient groups. The concept combines pre-computed disease modules, active patient organisations, and embedded n-offew trial designs to accelerate clinical translation even where evidence is scarce and patient numbers are small. This effort is now taking shape, and we are inviting clinical partners, patient communities, and methodological innovators who want to co-create this next chapter in rare-disease therapeutics. If you would like to engage, now is exactly the right moment to join the conversation. Unlocking reimbursement for precision medicine through policy engagement A global rare disease initiative – Calling partners to shape the next frontier Fresh off the press – Latest news from REPO4EU REPO-HYPER II focuses on patients with resistant hypertension whose elevated blood pressure is linked to a specific molecular pathway also involved in stroke, myocardial infarction, and heart failure. Instead of adding more standard antihypertensive drugs, the trial takes a mechanism-based route that directly addresses the cause of treatment resistance. By targeting this pathway, REPO-HYPER II aims not only to improve blood-pressure control, but also to reduce the risk of the major cardiovascular events that current therapies often fail to prevent. Following favourable assessment by regulatory and ethics authorities, enrolment is expected to begin in Q1/26. The study will provide the clinical-grade evidence needed to validate this strategy and support sustainable reimbursement models—marking a shift toward outcomedriven, precision cardiovascular care. REPO-HYPER II: A mechanism-driven approach for resistant hypertension Systems medicine examines diseases by their underlying molecular processes rather than by the organs in which they appear. By mapping how key proteins interact in disease-defining networks, this approach can reveal treatment options that are both highly precise and tailored to the biology of individual patients. REPO4EU has now submitted a patent application for a new therapeutic concept that targets the core drivers of radioiodine-insensitive thyroid cancer using rationally designed combinations of registered smallmolecule medicines. The same strategy is being extended to diffuse intrinsic pontine glioma (DIPG), one of the most severe childhood brain cancers. This milestone significantly strengthens the REPO4EU IP portfolio and illustrates how mechanism-based, individualised strategies can open entirely new therapeutic pathways for cancers with profound unmet medical needs. A new, mechanism-based approach to high-need cancers Looking back on RExPO25 – our latest conference in Barcelona It’s a wrap – Season 1 of our podcast is now available We can still feel the electricity and the excitement of this year's RExPO - the international conference on Systems Medicine, AI and Drug Repurposing. Researchers, clinicians, policymakers and patient group representatives came together in Barcelona to share knowledge and ideas on how to advance drug repurposing - click the link below to relive the experience. REPO4EU: The podcast brings listeners closer to the latest innovations, research and developments happening in drug repurposing across the globe. The first season, ‘Drug Repurposing Next-Gen’, spotlights the work of PhD researchers, post-docs and young investigators involved in REPO4EU, exploring their role in the project as well as their career journeys. Revisit the conference Revisit the conference Tune in to Season 1 Tune in to Season 1 There is still time to submit your research to the Network and Systems Medicine journal, a Diamond Open Access, peer-reviewed journal focused on interdisciplinary approaches to exploiting the power of big data by applying network science and systems thinking to medicine. Click the link below to learn more about key topics covered by the journal and the editorial board behind it. Calling for papers for our Network and Systems Medicine journal Check it out Check it out © REPO4EU 2025