Advancing cell secretome-based therapies
HORIZON Research and Innovation Actions
Basic Information
- Identifier
- HORIZON-HLTH-2025-01-TOOL-02
- Programme
- Cluster 1 - Health (Single stage - 2025)
- Programme Period
- 2021 - 2027
- Status
- Closed (31094503)
- Opening Date
- May 22, 2025
- Deadline
- September 16, 2025
- Deadline Model
- single-stage
- Budget
- €40,000,000
- Min Grant Amount
- €6,000,000
- Max Grant Amount
- €8,000,000
- Expected Number of Grants
- 5
- Keywords
- HORIZON-HLTH-2025-01-TOOL-02HORIZON-HLTH-2025-01Health-related biotechnologyInterventional clinical trialsMedical biotechnologyPhysiology (including cytology)Regenerative medicine
Description
This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination “Developing and using new tools, technologies and digital solutions for a healthy society”. To that end, proposals under this topic should aim to deliver results directed towards and contributing to several of the following expected outcomes:
- Researchers and biopharmaceutical developers work together with clinicians striving to translate innovative therapeutic approaches into healthcare solutions.
- Producers of innovative health technologies use standardised manufacturing processes.
- Healthcare providers get access to a new type of innovative therapies with demonstrated health benefits as compared to traditional treatments.
- Patients benefit from innovative therapies for conditions for which there are currently no or only insufficient therapeutic strategies.
- Health systems ultimately benefit from improved patient outcomes, superior to the current standard of care.
Secretome-based therapies have emerged as a promising alternative to cell-based therapies. The secretome of cells is defined as the repertoire of molecules and biological factors that are secreted into the extracellular space and has been shown to be a key factor for therapeutic activity due to its paracrine effects. The potential to manufacture, store and use secretome factors as off-the-shelf products, while maintaining the therapeutic benefits of cells but with fewer safety concerns, has placed the secretome at the forefront of regenerative medicine. Different cell secretomes or parts thereof have been the subject of clinical trials, but there is currently no regulatory-approved secretome-based therapy owing to several challenges. Currently, for the majority of secretome-based therapies, the main bottlenecks are: the incomplete understanding of their mode of action, their reproducibility due to a lack of standardised manufacturing processes and a lack of potency- and quality assurance assays. Additional limitations are the characterisation of the bioactive factors and the optimisation of the delivery strategies.
Proposals submitted under this topic should tackle the above-mentioned issues and pave the way to secretome-based therapies that are safe, efficacious, and regulatory-approved for human use. The activities should cover secretomes or their parts that are derived from human cells and comprise all the following elements:
- The selection of a secretome-based therapy whose main mechanism of action has been elucidated in in-vitro and/or in-vivo models prior to the start of the proposed work. The selected secretome or its chosen bio-active components (extracellular vesicles, trophic factors, organelles, RNA, proteins, peptides, etc.), including those that are potentially harmful, should have been characterised and its/their therapeutic activity should already have been demonstrated in relevant pre-clinical models. All types of human cells may be used as underlying parent cells.
- All activities that are necessary to ensure regulatory and ethical approvals enabling the conduct of the clinical study. This may comprise the full characterisation, standardised analytical methods, further pre-clinical studies in relevant models (pertinent to the targeted disease or disorder) and appropriate quality assurance assays including computational approaches, organoids and organ-on chips/microfluidic systems.
- Establishment of a manufacturing protocol for the selected secretome or its components, including all the steps of the biogenesis: parent cells selection, their pre-conditioning and bio-processing (isolation, expansion, cultivation in bioreactors), processing of the conditioned media, the extraction of the secretome or its components (isolation, purification, storage, distribution) and its/their delivery to target site in the human body (mode of administration, final formulation).
- Definition of relevant quality criteria for and establishment of a fully GMP-conform[1] production process that enables to carry out clinical trials of the proposed secretome-based therapy.
- Carrying out of all the above-mentioned activities in close interaction with and in compliance with all requirements of the relevant competent authorities, allowing to perform clinical trials.
- Conduct of an interventional randomised controlled clinical trial comprising phase 1 and phase 2 to generate scientific evidence demonstrating safety and efficacy of the proposed secretome-based therapy.
- Applicants are expected to deliver no later than at month 12 of the project the documentation needed for the GMP-conform production (e.g. SOP - Standard Operating Procedures) and no later than at month 24 the documentation needed for the conduct of the clinical trial (e.g. IMDP[2]), enabling to get the regulatory approval for the clinical trial. The overall goal is to perform and finalise the phase 1 and phase 2 clinical trials during the lifetime of the project and further achieve authorization of the proposed secretome-based therapy.
- Optionally and if essential for the chosen secretome-based therapy, the work should also include an engineering step of the secretome to achieve the desired profile for increased safety and improved therapeutic effect. To this end, the secretome or its bioactive component(s) may be modified either pre- or post-biogenesis, by use of classical methods on the parent cells, except their genetic modification, or by physico-chemical modification of the bio-active secretome component. The effected modifications of the secretome should lead to the improvement of the functional properties/features and/or of the delivery to target site (organ, tissue, etc.) for the bioactive secretome component. All these modifications should not alter the main mechanism of action and retain the proposed secretome-based therapy within the boundaries of substances of human origin[3]. The therapeutic effect of the secretome or its components should come from its/their endogenous capabilities and functionalities; exogenous loading with drugs (using the secretome or its components as drug carrier), be it pre- or post-biogenesis, is not in scope.
All types of diseases, dysfunctions or health impairments may be targeted, preference should be given to conditions that affect larger patient populations[4] and/or represent a high burden on public health systems.
Sex differences should be taken into consideration, both with regard to the parent cells and for the targeted therapeutic application. Participation of small and medium-sized enterprises (SMEs) is strongly encouraged and if an exploitation strategy is developed, it should commit to a first deployment in the EU.
Proposals should consider the involvement of the European Commission's Joint Research Centre (JRC) as a potential interface between research activities and pre-normative regulatory science and in relation to the potential validation of test methods fit for regulatory purpose. In that respect, the JRC will consider collaborating with any successful proposal and this collaboration, when relevant, should be established after the proposal’s approval.
Applicants should provide details of their clinical studies[5] in the dedicated annex using the template provided in the submission system. As proposals under this topic are expected to include clinical studies, the use of the template is strongly encouraged.
[1] Good Manufacturing Practice (GMP): https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/gmp
[2] Investigational Medicinal Product Dossier - European Medicines Agency: https://www.ema.europa.eu/en/requirements-quality-documentation-concerning-biological-investigational-medicinal-products-clinical-trials-scientific-guideline
[3] Blood, tissues, cells and organs - European Commission (europa.eu): https://health.ec.europa.eu/blood-tissues-cells-and-organs_en
[4] Diseases with a high frequency (e.g.: incidence or prevalence) or high DALY (Disability-Adjusted Life Years)
[5] Please note that the definition of clinical studies (see introduction to this work programme part) is broad and it is recommended that you review it thoroughly before submitting your application.
Destination & Scope
Topics under this destination are directed towards the Key Strategic Orientation 2 “The Digital Transition” and Key Strategic Orientation 3 “A More Resilient, Competitive, Inclusive, and Democratic Europe” of Horizon Europe’s strategic plan 2025-2027.
Research and Innovation supported under this destination should contribute to the following expected impact, set out in the strategic plan impact summary for the Health Cluster: “Health technologies, data, new tools, and digital solutions are applied effectively thanks to their inclusive, ethically sound, secure and sustainable delivery, integration and deployment in health policies and in health and care systems.”
The Health Cluster will continue work to develop and stimulate the uptake of new technologies and digital solutions to improve healthcare and health systems. This includes using technology to help people better understand and use health information, promote healthier lifestyles, improve pandemic/epidemic preparedness, prevent diseases, provide better diagnoses and more personalised treatments and care solutions, and improve access to health and care systems while making sure that even groups with limited access to good healthcare can benefit. The Cluster will help the EU ensure leadership in breakthrough health and medical technologies and achieve open strategic autonomy in essential medical supplies and digital innovations. By collecting and analysing health data across borders and creating human-centred health technologies, including the use of Artificial Intelligence (AI), research can improve and personalise medical care for different patients, increasing patient safety and leading to better health outcomes and wellbeing.
Support for Research and Innovation is needed on the large spectrum of tools and technologies for biomedical research, prevention, diagnosis, therapy and health monitoring. This includes enabling technologies not least innovative biotechnological approaches. The emergence of the European Health Data Space will create an additional boost to cross-border, data-driven approaches and innovation, e.g. for personalised medicine or patient safety. High-quality health data (incl. real world data) combined with digital technologies, modelling and AI tools, have a high potential for advancing biomedical Research and Innovation. Emerging and disruptive technologies using tools like new genomic techniques and AI tools, offer big opportunities for transforming healthcare, but also depend on the capacity to collect, integrate and interpret large amounts of data and on their compatibility with appropriate regulatory frameworks. Such technologies can provide better and more cost-efficient solutions with high societal impact, tailored to the specific healthcare needs of the individual. However, novel tools, technologies and digital approaches face specific barriers and hurdles in piloting, implementing and scaling-up before reaching the patient, encountering additional challenges such as public acceptance and trust. The development and uptake of new technologies for high-quality healthcare will need to draw on multiple disciplines and require cross-sectoral cooperation among all those concerned, including end-users (patients, healthcare providers and workforce, researchers, regulatory bodies, policymakers, and funders). These interactions will help address unmet needs via integrated tools, hybrid health technologies and digital solutions (including those with limited commercial interest). It will also support the design and development of health products and services tailored to the needs of specific population groups, thereby improving patient outcomes and reducing health inequalities.
This destination aims to promote the development of novel tools, technologies and digital solutions for prevention, diagnosis and therapy with the goal to improve health outcomes, while taking into consideration the rights of the individual, safety, effectiveness, appropriateness, accessibility, comparative value-added and fiscal sustainability as well as issues of ethical, legal and regulatory nature.
In this work programme part, Destination “Developing and using new tools, technologies and digital solutions for a healthy society” is driven by two key Commission policies, the “Biotechnology and Biomanufacturing Strategy[1]” and the “Artificial Intelligence Strategy[2]” and will focus on the development and use of innovative biotechnological tools for the improvement of the therapeutic arsenal of healthcare against diseases where there are currently no or only insufficient therapeutic strategies, on the development of Generative Artificial Intelligence models to help researchers in their activities to deliver new knowledge for advancing biomedical research and on the technology transfer of biotechnology-derived therapeutics from discovery to approved products. In particular, the topics under this destination will support activities aiming at: cellular and cell-free therapeutic approaches employing either genetic modifications or more classical techniques for improving the safety and therapeutic performance of these therapies, including their testing in clinical studies; development of generative AI models based on large-scale multi-modal health data for better understanding of diseases and their management thanks to the enhancement of biomedical discoveries and more personalised treatment solutions; bridging the gap between pre-clinical and clinical development stages of therapeutics developed through biotechnological methods and giving special emphasis on small and medium-sized enterprises (SMEs). In this context, specific attention is given to support the objectives of the Strategic Technologies for Europe Platform (STEP), adopted by the Commission in March 2024, which aims to boost investments in critical technologies in Europe (see introduction to this work programme part).
Under this destination, actions will support interdisciplinary Research and Innovation activities involving a broad spectrum of actors from different sectors, who will strive for the convergence of health technologies, combining medical technologies, pharmaceuticals, Advanced Therapy Medicinal Products (ATMPs) and digital health technologies, that will lead to integrated health solutions for the benefit of healthcare providers and patients.
In view of increasing the impact of EU investments under Horizon Europe, the European Commission welcomes and supports cooperation between EU-funded projects to enable cross-fertilisation and other synergies. This could range from networking to joint activities such as the participation in joint workshops, the exchange of knowledge, the development and adoption of best practices, or joint communication activities. Opportunities for such activities and potential synergies exist between projects funded under the same topic but also between other projects funded under another topic, Cluster or pillar of Horizon Europe (but also with ongoing projects funded under Horizon 2020). In particular, this could involve projects related to European health research infrastructures (under pillar I of Horizon Europe), the EIC strategic challenges on health, the European Innovation Ecosystems (EIE) interregional networks on health and EIT-KIC Health (under pillar III of Horizon Europe) or in areas cutting across the health and other Clusters (under pillar II of Horizon Europe), like, for instance, with Cluster 4 “Digital, Industry and Space” on digitalisation of the health sector or key enabling technologies.
Expected Impacts:
Proposals for topics under this destination should set out a credible pathway towards the development and use of new tools, technologies and digital solutions for a healthy society, and more specifically to one or several of the following impacts:
- Europe’s scientific and technological expertise and know-how, its capabilities for innovation in new tools, technologies and digital solutions, and its ability to take-up, scale-up and integrate innovation in healthcare is world-class.
- Citizens benefit from targeted and faster research resulting in safer, more sustainable, efficient, cost-effective and affordable tools, technologies and digital solutions for improved (personalised) disease prevention, diagnosis, treatment and monitoring for better patient outcome and wellbeing, in particular through increasingly shared health resources (interoperable data, infrastructure, expertise, citizen/patient driven co-creation)[3].
- The EU gains high visibility and leadership in terms of health technology development, including through international cooperation.
- The burden of diseases in the EU and worldwide is reduced through the development and integration of innovative diagnostic and therapeutic approaches, personalised medicine approaches, digital and other people-centred solutions for healthcare.
- Both the productivity of health Research and Innovation, and the quality and outcome of healthcare is improved thanks to the use of health data and innovative analytical tools, such as artificial intelligence (AI) supported decision-making, in a secure and ethical manner, respecting individual integrity and underpinned with public acceptance and trust.
- Citizens trust and support the opportunities offered by innovative technologies for healthcare, based on expected health outcomes and potential risks involved.
The protection of European communication networks has been identified as an important security interest of the Union and its Member States. Entities that are assessed as high-risk suppliers[4] of mobile network communication equipment (and any entities they own or control) are not eligible to participate as beneficiaries, affiliated entities and associated partners to topics identified as “subject to restrictions for the protection of European communication networks”. Please refer to the Annex B of the General Annexes of this Work Programme for further details.
[1] Commission Communication on Building the future with nature: Boosting Biotechnology and Biomanufacturing in the EU; COM(2024) 137 final: https://research-and-innovation.ec.europa.eu/document/download/47554adc-dffc-411b-8cd6-b52417514cb3_en
[2] Commission Communication on Artificial Intelligence for Europe; COM(2018) 237 final: https://digital-strategy.ec.europa.eu/en/policies/european-approach-artificial-intelligence; https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=COM:2018:237:FIN
[3] Commission Communication on the digital transformation of health and care; COM(2018) 233 final
[4] Entities assessed as “high-risk suppliers”, are currently set out in the second report on Member States’ progress in implementing the EU toolbox on 5G cybersecurity of 2023 (NIS Cooperation Group, Second report on Member States’ progress in implementing the EU Toolbox on 5G Cybersecurity, June 2023) and the related Communication on the implementation of the 5G cybersecurity toolbox of 2023 (Communication from the Commission: Implementation of the 5G cybersecurity Toolbox, Brussels, 15.6.2023 C(2023) 4049 final).
Eligibility & Conditions
General conditions
1. Admissibility Conditions, Proposal page limit and layout
2. Eligible Countries
Eligible Countries are described in Annex B of the Work Programme General Annexes.
A number of non-EU/non-Associated Countries that are not automatically eligible for funding have made specific provisions for making funding available for their participants in Horizon Europe projects. See the information in the Horizon Europe Programme Guide.
3. Other Eligible Conditions
In recognition of the opening of the US National Institutes of Health’s programmes to European researchers, any legal entity established in the United States of America is eligible to receive Union funding.
The Joint Research Centre (JRC) may participate as member of the consortium selected for funding.
If projects use satellite-based earth observation, positioning, navigation and/or related timing data and services, beneficiaries must make use of Copernicus and/or Galileo/EGNOS (other data and services may additionally be used).
Other Eligible Conditions are described in Annex B of the Work Programme General Annexes.
4. Financial and operational capacity and exclusion
Financial and operational capacity and exclusion are described in Annex C of the Work Programme General Annexes.
5a. Evaluation and award: Award criteria, scoring and thresholds
Evaluation and award: Award criteria, scoring and thresholds are described in Annex D of the Work Programme General Annexes.
5b. Evaluation and award: Submission and evaluation processes
The thresholds for each criterion will be 4 (Excellence), 4 (Impact) and 4 (Implementation). The cumulative threshold will be 12.
Evaluation and award: Submission and evaluation processes are described in Annex F of the Work Programme General Annexes and the Online Manual.
5c. Evaluation and award: Indicative timeline for evaluation and grant agreement
Evaluation and award: Indicative timeline for evaluation and grant agreement are described in Annex F of the Work Programme General Annexes.
6. Legal and financial set-up of the grants
Legal and financial set-up of the grants are described in Annex G of the Work Programme General Annexes.
Specific conditions
Specific conditions are described in the specific topic of the Work Programme.
Application and evaluation forms and additional documents:
Application and evaluation form templates
Standard application form (HE RIA, IA) - the application form specific to this call is available in the Submission System
Standard evaluation form (HE RIA, IA) - will be used with the necessary adaptations
Guidance
Model Grant Agreements (MGA)
Call-specific instructions
Additional documents
HE Main Work Programme 2025 – 1. General Introduction
HE Main Work Programme 2025 – 4. Health
HE Main Work Programme 2025 – 14. General Annexes
HE Framework Programme 2021/695
HE Specific Programme Decision 2021/764
EU Financial Regulation 2024/2509
Decision authorising the use of lump sum contributions under the Horizon Europe Programme
Rules for Legal Entity Validation, LEAR Appointment and Financial Capacity Assessment
EU Grants AGA — Annotated Model Grant Agreement
Funding & Tenders Portal Online Manual
Support & Resources
Online Manual is your guide on the procedures from proposal submission to managing your grant.
Horizon Europe Programme Guide contains the detailed guidance to the structure, budget and political priorities of Horizon Europe.
Funding & Tenders Portal FAQ – find the answers to most frequently asked questions on submission of proposals, evaluation and grant management.
Research Enquiry Service – ask questions about any aspect of European research in general and the EU Research Framework Programmes in particular.
National Contact Points (NCPs) – get guidance, practical information and assistance on participation in Horizon Europe. There are also NCPs in many non-EU and non-associated countries (‘third-countries’).
Enterprise Europe Network – contact your EEN national contact for advice to businesses with special focus on SMEs. The support includes guidance on the EU research funding.
IT Helpdesk – contact the Funding & Tenders Portal IT helpdesk for questions such as forgotten passwords, access rights and roles, technical aspects of submission of proposals, etc.
European IPR Helpdesk assists you on intellectual property issues.
CEN-CENELEC Research Helpdesk and ETSI Research Helpdesk – the European Standards Organisations advise you how to tackle standardisation in your project proposal.
The European Charter for Researchers and the Code of Conduct for their recruitment – consult the general principles and requirements specifying the roles, responsibilities and entitlements of researchers, employers and funders of researchers.
Partner Search help you find a partner organisation for your proposal.
Latest Updates
Call HORIZON-HLTH-2025-01 closed on 16 September 2025. 749 proposals were submitted. The breakdown per topic is:
- HORIZON-HLTH-2025-01-DISEASE-01: 30 proposals
- HORIZON-HLTH-2025-01-DISEASE-03: 15 proposals
- HORIZON-HLTH-2025-01-DISEASE-04: 76 proposals
- HORIZON-HLTH-2025-01-DISEASE-05: 7 proposals
- HORIZON-HLTH-2025-01-DISEASE-06: 158 proposals
- HORIZON-HLTH-2025-01-DISEASE-07: 83 proposals
- HORIZON-HLTH-2025-01-CARE-01: 118 proposals
- HORIZON-HLTH-2025-01-TOOL-01: 57 proposals
- HORIZON-HLTH-2025-01-TOOL-02: 35 proposals
- HORIZON-HLTH-2025-01-TOOL-03: 82 proposals
- HORIZON-HLTH-2025-01-TOOL-05: 25 proposals
- HORIZON-HLTH-2025-01-IND-01: 58 proposals
- HORIZON-HLTH-2025-01-IND-02: 5 proposals
Evaluation results are expected to be communicated on Wednesday 21 January 2026 at the earliest.
Please note that due to a technical issue, during the first days of publication of this call, the topic page did not display the description of the corresponding destination. This problem is now solved. In addition to the information published in the topic page, you can always find a full description of the relevant destination in the Work Programme 2025 part for "Health". Please select from the work programme the destination relevant to your topic and take into account the description and expected impacts of that destination for the preparation of your proposal.