Core insights – Pre-clinical validation of scientific questions
Welcome to REPO4EU: Core insights
Our brand new article series where we bring you closer to our project's core innovations and results.
Preclinical validation
A brief introduction
In the pharmaceutical world, clinical trials play the role of the ultimate “reality check”. However, they are incredibly expensive, time-consuming and involve the most precious variable of all: human lives. Thus, de-risking the path to clinical phase via effective pre-clinical validation lies at the heart of REPO4EU’s ambition.
Within the REPO4EU project, we aim to secure a massive head start for all repurposing projects by providing robust validation of the preclinical hypotheses, generated through advanced bioinformatics, in silico-based target identification, and computational drug predictions. Preclinical validation moves a prediction into living systems, and this exact bridge between computational approaches and mechanistically relevant cellular and animal models, which mimic human disease endotypes, ensures a strong scientific foundation for each drug candidate.
Our goal is to identify the most promising drug repurposing opportunities and ensure that only rigorously validated candidates advance to clinical stages. This approach builds a more precise, safer, and faster highway, accelerating the path from computational discovery to real-world therapeutic impact, while also prioritizing patient safety.
The road so far
From digital blueprints to validated biological evidence
REPO4EU envisions a future where drug repurposing evolves into a precise, mechanism-driven discipline, firmly based on validated biological evidence. The progress achieved so far through database development, validation pilots, and methodological guidelines, directly supports this vision.
One of our most significant milestones to date is the development of a comprehensive open-access, user-friendly database of cellular and animal disease models, specifically designed to capture the ones with the highest translational potential. This resource acts as a “compass” for researchers, helping them to pinpoint the most appropriate models for validating computational predictions. By strengthening the bridge between in silico predictions and experimental testing, we ensure that the transition is both seamless and scientifically sound.
To demonstrate the power of our approach, REPO4EU has launched validation pilots in three high-stakes medical areas: thyroid cancer, diffuse pontine glioma (DIPG), and infectious diseases. These pilots serve as an essential testing phase providing clinically relevant proof-of-concept studies on repurposing hypotheses before moving to the clinical trials.
Beyond data and testing, we have also developed methodological guidelines for identifying the most appropriate disease models (both cellular and animal), selecting promising repurposable drug candidates, and defining the rationale for combination therapy strategies using a network‑pharmacology approach. Fostering a culture of collaboration, transparency and FAIR (Findable, Accessible, Interoperable and Reusable) data that accelerates the translation of preclinical findings into life-saving clinical scenarios, the guidelines will be made openly accessible to the global scientific community.
Looking ahead
Towards a robust preclinical validation framework
REPO4EU’s commitment to a transformed medical landscape remains the primary force guiding our work. By systematically connecting bioinformatic predictions with clinically relevant models, we are laying the groundwork for an open-access and scientifically rigorous pipeline. Within our platform, the flagship output of our project, stakeholders will be able to access validated tools, disease models, and decision‑making frameworks that bridge the critical gap between computational discovery and clinical application.
Through this infrastructure, we ensure that repurposing strategies are not only innovative but also precise, reproducible, and ready for regulatory consideration. We are redefining the standards for preclinical validation across Europe and beyond, moving away from fragmented research toward a unified, transparent ecosystem.
And we remain laser–focused on our long-term vision, where drug repurposing accelerates therapeutic development, reduces costs, mitigates risks, and ultimately delivers patient-centered solutions to some of the most pressing health challenges worldwide.
Building on the significant progress achieved so far, we embrace the work required to maximize translational impact as an opportunity for further growth and innovation. Maintaining the translational relevance of disease models and ensuring that cell and animal systems reflect the complexity and diversity of human disease, remains one of our central scientific imperatives. Equally important is the integration of heterogeneous data sources, from computational predictions and preclinical models to clinical datasets, which calls for advanced frameworks for harmonization and interpretation. Another crucial step toward enabling downstream clinical validation is effectively aligning methodologies with regulatory requirements.
Beyond these structural challenges, the scientific landscape itself is constantly evolving. Advances in disease endotyping and in our understanding of drug mechanisms demand ongoing methodological refinement to ensure that preclinical strategies remain up to date and clinically meaningful. Addressing these challenges will be essential to ensure we continue delivering robust, safe, and translatable outcomes that advance the goals of REPO4EU.
Behind the scenes
Meet our multidisciplinary experts’ alliance
The strength of REPO4EU lies in its collaborative engine bringing together diverse expertise to transform computational theories into clinical realities.
Our preclinical validation team, led by Maastricht University, leverages their leading expertise and long-standing experience in preclinical experimentation and animal models to drive reliable validation of drug repurposing candidates. RUMC and UZH contribute specialized knowledge in thyroid cancer and DIPG, providing both animal models and clinical insights that support scientific translation. UHAM contributes essential expertise in viral infectious disease models, while BioLizard ensures methodological statistical rigor to support reliable results. To bridge preclinical data with clinical application, HMPC and 3DPX play a key role in supporting the clinical translation of findings. Finally, GeneSurge is responsible for integrating complex datasets and guiding scientific decision-making.
Collectively, we form a multidisciplinary framework that ensures evidence-based progression of drug candidates.
About our platform
Discover our platform and explore its key features
Become an early tester now!
Follow the link to sign up for our platform's alpha release
Core insights - Transforming drug repurposing through real-world data-driven Artificial Intelligence
Welcome to REPO4EU: Core insights
Our brand new article series where we bring you closer to our project's core innovations and results.
What is real-world data-driven Artificial Intelligence?
A brief introduction
Artificial Intelligence (AI) has undeniably emerged as the definitive revolution of our era, fundamentally reshaping the global landscape by collapsing the distance between human intent and execution. Within the REPO4EU project, AI is far more than a buzzword; it represents a profound paradigm shift. By synergizing AI with systems biology and network pharmacology, we aim to move beyond symptom-based treatments to redefine diseases through mechanism-based endotypes, generating robust, data-driven hypotheses for drug repurposing.
The complexity of this field requires the seamless integration of vast, heterogeneous data: from drug targets’ information, signaling pathways and protein-protein interactions to gene-disease associations, gene expression, and adverse drug effects. Consequently, REPO4EU is developing a comprehensive knowledge base aiming to bring these diverse data sources together into a harmonized, interoperable framework that supports downstream analyses and decision-making. This framework serves as the foundation for uncovering the molecular mechanisms of diseases and identifying promising drug targets and compounds for repurposing. These hypotheses are further refined through advanced in- silico workflows and subsequently validated in pre-clinical and clinical studies.
The road so far
Towards a robust repurposing framework powered by AI
A key achievement of the REPO4EU project is the expansion of the NeDRex database, which serves as our foundational knowledge base and is an integral part of the REPO4EU platform. This extensive, continuously updated resource provides the structural backbone for downstream analyses. To ensure our framework remains at the cutting edge of computational drug repurposing, we carried out an extensive literature collection, review, and categorization, now maintained and expanded through automated search queries and specialized AI-driven tools.
Building upon this data-rich foundation, we have developed a sophisticated suite of computational workflows and software tools, which includes:
- A fully automated pipeline for disease module inference and drug repurposing hypothesis generation.
- A dedicated chemoinformatics pipeline.
- A tool for selecting high-confidence, disease-associated gene sets
- A drug repurposing tool leveraging Graph Neural Networks (GNNs), as well as a web-based application for refining and exploring putative disease mechanisms.
Collectively, these advancements empower a continuous cycle of discovery, enabling the generation of high-precision drug repurposing hypotheses that are systematically refined and validated through a rigorous integration of computational and experimental evidence.
Looking ahead
Envisioning new industry standards
As we move forward, REPO4EU remains committed to a vision where AI and bioinformatics are not merely experimental additions but foundational pillars of the drug development pipeline. Our ultimate goal is to embed these technologies into the industry standard, enabling the identification and validation of mechanism-based, patient-tailored therapies with unprecedented speed and accuracy.
However, the path to a standardized model is defined by its challenges as much as its opportunities. Mechanistic drug repurposing is inherently complex, requiring a sophisticated interdisciplinary blend of expertise, advanced computational methods, and access to high-quality, diverse datasets. To generate meaningful in-silico hypotheses, we must maintain access to high-quality, diverse, and harmonized datasets —a task made more difficult by the fact that disease mechanisms and patient responses are highly idiosyncratic. Furthermore, the rapid evolution of the AI field demands constant iteration and requires constant adaptation of our tools and methods. Critically, while AI acts as a powerful catalyst for discovery, it should not become a replacement for human expertise, but a collaborative tool that augments the researcher’s ability to navigate the biological maze instead.
To overcome the challenges and stay true to our vision, we must and will continue refining our tools and workflows and foster collaboration across disciplines, to ensure that precision drug repurposing evolves from a specialized research effort into a routine, life-saving component of global clinical innovation.
Behind the scenes
Meet our Experts’ team
A multidisciplinary powerhouse of academic, clinical, and industry partners (STALICLA, University of Hamburg, University of Vienna, Brigham and Women’s Hospital, Technical University of Madrid, BioLizard, Maastricht University, Radboud University Medical Center, University of Zurich), led by the Technical University of Munich, contributes specialized expertise to the development of the REPO4EU AI-driven repurposing framework.
By integrating foundational data with specialized expertise in patient stratification and chemoinformatics, infectious diseases, and rare disease mechanisms, we transform fragmented information into actionable medical intelligence. This synergy is further sharpened by advanced in-silico validation and clinical endotyping, ensuring every hypothesis is grounded in real-world plausibility.
Together, we form a cohesive ecosystem dedicated to bridge computational modeling, clinical insight, and translational application towards a new life-saving era for patients.
About our platform
Discover our platform and explore its key features
Become an early tester now!
Follow the link to sign up for our platform's alpha release
RExPO25: The 4th International Conference on Systems Medicine, AI & Drug Repurposing
On 24-26 September 2025, representatives from the entire drug repurposing ecosystem gathered in Barcelona for RExPO25, the fourth edition of the international series of conferences organised and hosted by REPO4EU.
Under the premise of being at the heart of latent discussions shaping the future of medicine, this year’s conference brought together leading voices from academia, industry, policy, HTA bodies and patient-focused organisations to explore how systems medicine, artificial intelligence and innovative regulatory and reimbursement approaches can accelerate drug repurposing for the benefit of patients across Europe.
Building on the momentum of previous editions, RExPO offered once again a truly interdisciplinary programme, reflecting on how far the field has matured and how close repurposing is to delivering real-world clinical and societal impact, according to RExPO25 Co-chairs Harald Schmidt, Head of Pharmacology at Maastricht University and REPO4EU Coordinator, and Emrey Guney, CTO and Head of Discovery & Data Science at STALICLA.
“Over the years organising this conference, we have learned a lot about the challenges, the use cases and the stakeholders involved. We are now entering a phase where we see validations, specifically in cancer and Alzheimer’s trials, and the focus is increasingly on precision and clinical proof. This year, we really tried to cover all of this in a broad and interdisciplinary manner,” explained Prof. Schmidt.
From computational discovery to clinical validation
The RExPO25 agenda spanned the full drug repurposing pipeline, from advanced computational methodologies and systems biology approaches, to clinical validation and implementation.
Over 60 international speakers, spread across 15 sessions, delivered talks highlighting how AI-driven modelling, multi-omics integration and network-based approaches are enabling researchers to identify new therapeutic indications for diseases that have yet to find a viable cure – one that targets the root cause, and not merely treats its symptoms.
Several speakers emphasised that the field is now moving beyond proof-of-concept towards tangible clinical evidence, but also stressed the importance of maintaining robust, trustworthy frameworks when applying AI in biomedicine.
“We are living in an incredible moment where many developments are crystallising into reality. The computational capacity in Europe is growing, and artificial intelligence is at the centre of this, but we must keep an equilibrium — with trusted frameworks, scientific rigour and an understanding of real clinical constraints,” said Alfonso Valencia, Director of the Life Sciences department at Barcelona Supercomputing Center.
“We need drugs to treat diseases, but developing drugs is a complex challenge. This is where the idea of repositioning drugs from one indication to another is extremely powerful, but if we want to do this in a more effective way, we still need more knowledge,” added Prof. Valencia during his RExPO25 Honorary Lecture.
Regulation, reimbursement and access: confronting the real hurdles
Beyond scientific and technological advances, RExPO25 placed strong emphasis on the role of regulation, health technology assessment (HTA), reimbursement and market access — which are deemed amongst the community as some of the biggest hurdles for bringing repurposed medicines to patients.
Some of the experts representing payers and HTA bodies brought critical perspectives to the conversation. For instance, Sibylle Reichert, Executive Director at International Association of Mutuals (AIM), reinforced the fact that protecting universal access to healthcare is crucial in Europe, which means medicines must remain affordable, accessible and available. “That’s why reimbursement organisations are such important players in this space,” she said.
Following this thread, the discussions underscored that science, regulation and reimbursement cannot be treated as separate worlds, as Anja Schiel, Senior Advisor at Norwegian Medicinal Products Agency (NOMA), put it: “You cannot disconnect science from reimbursement decisions. Repurposing is a no‑brainer when it comes to savings and equity, but collaboration and knowledge transfer across stakeholders is essential.”
Also reflecting on the need to balance accessibility with incentives for innovation, Lynn Durham, CEO and Founder of STALICLA, highlighted that researchers operating in this space believe in the common good, but they operate in a system that is strongly tied to regulation and private investment.
“That’s why we need to strike a balance between accessible pricing and acceptable returns, so that drug repurposing can be sustainable,” Durham added.
Looking ahead — together
A recurring theme throughout RExPO25 was the need for systems-level thinking and collective innovation. Speakers repeatedly highlighted that no single discipline, sector or stakeholder can advance drug repurposing alone. This collaborative spirit was reflected not only in the programme but also in the openness of discussions across collectives that have traditionally worked in silos.
As the fourth edition of RExPO concluded, one message was clear: drug repurposing is no longer a niche concept, but a powerful and increasingly validated strategy to address unmet medical needs more efficiently. The challenge now lies in scaling these successes through coordinated scientific, regulatory and economic frameworks, built by many hands working together.
RExPO25 also reinforced the role of REPO4EU as a central platform for this dialogue, and set the stage for the next steps towards making repurposed, precision therapies accessible to patients across Europe.
About RExPO25
RExPO25, the 4th edition of our international series of conferences dedicated to Systems Medicine, Artificial Intelligence and Drug Repurposing, took place in Barcelona on 24-26 September 2025.
Revisit the conference
Curious to learn more? Watch our video compilation for RExPO25