Leveraging Europe's Expertise to accelerate Cell Therapy for Type 1 Diabetes

The action under this topic is expected to achieve the following impacts:

• to support the widespread adoption of beta-cell therapy, ensuring long-term efficacy, accessibility, and integration into healthcare systems;
• to accelerate the development of stem cell-based therapies through advancements in manufacturing, preclinical models, regulatory alignment, and predictive tools;
• to strengthen Europe’s position as a leader in beta-cell therapy by fostering innovation hubs and clinical networks;
• scientific and regulatory progress will advance regenerative medicine for other metabolic and autoimmune disorders beyond T1D;
• patients, healthcare providers, regulators, policymakers, and industry stakeholders will all benefit from improved treatments, clearer guidelines, and increased investment;
• boosting European industrial competitiveness by driving innovation in cell-based therapies, fostering cross-sector collaboration, and enhancing Europe’s global leadership in regenerative medicine.

These impacts are expected to advance IHI JU's objectives of improving healthcare quality, accessibility, and sustainability while contributing to European health policies and initiatives.

The action under this topic is expected to contribute to the following EU policies/initiatives:

• The European Health Union: addressing the chronic disease (diabetes) burden; accelerating groundbreaking therapies while drawing on the potential of digital and AI solutions; contributing to modern and innovative health policies (by working on models, tools and pathways enabling the adoption of innovative/breakthrough therapies by European healthcare systems);
• The Pharmaceutical Strategy for Europe: Advancing innovative cell therapies and improving patient access to cutting-edge treatments;
• The EU political priority to boost European competitiveness: establishing Europe as a hub for cutting-edge scientific and research innovation; contributing to the announced EU Biotech Act as a forward-looking framework to leverage the potential that biotechnologies can bring to our economy;
• UN Sustainable Development Goals (SDG 3: Good Health & Well-being): reducing the impact of non-communicable diseases (NCDs) like type 1 diabetes.

The action will also contribute to a number of European policies/initiatives, which include the European Commission’s European Health Data Space Regulation (EHDS)¹ and the EU Artificial Intelligence Act².

¹ _{https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L_202500327}

² _{https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32024R1689}

The action under this topic must contribute to all of the following outcomes:

1. Researchers, industry, and healthcare providers will benefit from a standardised framework for impurity thresholds and manufacturing best practices, ensuring regulatory alignment, facilitating clinical translation, and supporting the scalable production of safe and effective beta-cell therapies for type 1 diabetes (T1D).
2. Regulatory authorities, academic researchers, healthcare professionals (HCP) and industry partners will have access to validated immune-modulating strategies that enhance graft survival and promote immune tolerance, alongside advanced models and biomarkers for assessing engraftment success, metabolic function, and immune responses.
3. Pharmaceutical companies, regulatory bodies, and payers will benefit from established, scalable and cost-effective manufacturing processes for beta-cell therapy, ensuring the production of high-quality, reproducible products that meet regulatory standards and support market approval and reimbursement.
4. Academic researchers, regulatory bodies, and healthcare providers will have improved preclinical models and clearly defined clinical criteria for different patient demographics, ensuring that beta-cell therapies are accessible, safe, and effective across diverse populations.
5. Healthcare providers, industry, and information and communication technology (ICT) companies will utilise AI-driven predictive models and real-time monitoring technologies to enhance the assessment of transplant success, immune responses, and metabolic function, enabling personalised treatment plans, optimised immunosuppression regimens, and reduced therapy failure.
6. Healthcare providers and regulatory bodies will adopt patient-centred clinical endpoints as key indicators of treatment success, accurately reflecting quality of life and disease burden in T1D.
7. Health technology assessment (HTA) bodies, people living with diabetes, payers, and policymakers will benefit from cost-effectiveness assessments, pilot reimbursement programmes, and policy recommendations that enable the establishment of a reimbursement framework, thus paving the way for the adoption of beta-cell therapies for T1D.
8. Healthcare providers, researchers, and policymakers will benefit from training programmes for endocrinologists, diabetologists, and transplant surgeons, enhancing expertise in cell therapy, immunosuppression, and post-transplant care. Collaboration with professional societies will drive the development of clinical pathways, ensuring the generation of appropriate evidence for integrating cell-based therapies into standard diabetes care.
9. Academia, industry, regulatory agencies, patient organisations, people living with diabetes and policymakers will collaborate through fully operational European innovation hubs, facilitating knowledge sharing, driving research advancements, and harmonising regulatory practices to accelerate the adoption and implementation of beta-cell therapies across Europe.
10. People living with diabetes will benefit from all these outcomes, as they will lead to improved treatment options, enhanced long-term health outcomes, better access to innovative therapies, and an overall improved quality of life.

It is expected that certain existing assets will be used as background in this action. Such background assets may include, but are not limited to, cell manufacturing technologies, gene editing platforms, scaffold materials, encapsulation systems, and delivery and release technologies, among others. The exact nature of the background to be brought into the project will depend on the proposals presented by the public consortia. Therefore, beneficiaries intending to participate in this action need to be comfortable with the principle that ownership of specific deliverables / project results which would be considered direct improvements to a beneficiary’s background asset, will need to be transferred back to the beneficiary who contributed the background asset to the project. Provision for and conditions relating to such transfers should be specified in the project’s consortium agreement.

Challenges and Background

T1D is an autoimmune disease that destroys insulin-producing pancreatic beta-cells, leading to lifelong insulin dependence. Despite advances in technology, achieving stable blood glucose levels remains challenging, which increases the risk of severe complications, and this in turn impacts negatively on daily life, work productivity, and mental health, and contributes to stress, anxiety, and depression.

Beta-cell replacement therapy offers a promising path towards a functional cure, but critical challenges must be addressed, including the need for renewable cell sources, optimised islet preparations, standardised manufacturing protocols, robust monitoring tools, sustainable reimbursement models, and trained healthcare professionals to manage complex treatments. These challenges align with key priorities from the Draghi Report , emphasising harmonised regulatory pathways, early engagement with HTA bodies, standardised manufacturing processes, and patient-centred clinical endpoints. Without urgent action, the full potential of beta-cell therapies will remain unrealised.

Key Objectives:

1) Establishing standardised criteria and analytical methods:This objective aims at developing standardised criteria and analytical methodologies to detect, quantify, and characterise unintended bystander cells and impurities in stem cell-derived or beta-cell therapies for T1D. This work is intended to support the field at large by generating reference materials, optimising detection technologies, and defining regulatory-compliant thresholds that can inform future research and development—not to advance a specific product. The focus is on creating translatable, broadly applicable tools and standards that ensure safety, consistency, and quality. Engagement with the European Medicines Agency (EMA) is encouraged to facilitate the regulatory relevance and potential adoption of these methodologies in preclinical and clinical research settings.

2) Enhancing graft survival and immune tolerance:This objective aims at developing immune-modulating strategies that support the long-term survival of beta-cell grafts and promote immune tolerance. This work is intended to generate insights, tools, and models that advance scientific understanding and inform future therapeutic approaches. Activities will include retrospective analyses of human cadaveric islet transplantation cohorts from different European countries and healthcare systems to support biomarker discovery and predictive modelling. Key biomarkers – such as continuous glucose monitoring (CGM) metrics, C-peptide levels, HbA1c, inflammatory cytokines, immune cell subsets, beta-cell-specific autoantibodies, and gene expression profiles – will be explored to identify indicators of graft survival, immune tolerance, and beta-cell function. In addition, a prospective study may be designed to identify novel biomarkers related to glycaemic variability, immune regulation, insulin independence, beta-cell regeneration, and inflammatory pathways. These efforts are aimed at supporting the development of robust monitoring tools and decision-making frameworks, not at advancing a therapeutic candidate toward clinical use.

3) Advancing manufacturing and quality control:The objective is to establish robust cryopreservation techniques that preserve the viability and functionality of beta-cells post-thaw, with an emphasis on the identification and validation of biomarkers to guide and assess these processes. Building on this, the applicants should aim to develop and optimise scalable, cost-effective manufacturing methodologies and quality control frameworks that support the production of consistent, high-quality beta-cell therapy materials in a research and innovation context. The goal is to generate foundational knowledge, technical standards, and reference systems, not to develop specific commercial products. Additionally, the consortium should work toward establishing standardised criteria for the production and quality control of excipient raw materials used in beta-cell therapy delivery systems, to ensure their stability, safety, and suitability for future clinical applications.

4) Streamlining preclinical and clinical development:This objective aims at enhancing preclinical models for allogeneic cell therapies, ensuring standardised approaches and consistent methodologies in transplantation science and surgery. The focus is on harmonised regulatory approval, defining patient demographics for broader accessibility, and tailoring treatment requirements for personalised care. Establishing definitions for insulin independence, investigating and working toward the regulatory acceptance of clinically meaningful endpoints, such as ‘Time in Range (TIR)’ and ‘Time in Tight Range (TiTR)’, and optimising clinical trial design for allogeneic therapies are essential components of the future project.

5) Implementing advanced monitoring and artificial intelligence (AI)-driven predictive tools:Leveraging real-time monitoring technologies like continuous glucose monitoring (CGM) and biosensors to assess transplant success and metabolic function, this objective aims to integrate advanced techniques from various fields, including oncology. Specifically, immune monitoring strategies used in oncology, such as immune checkpoint inhibitors and tumour biomarker profiling, will be explored to enhance the understanding of immune responses in beta-cell transplantation. AI-powered predictive models will personalise treatment plans and optimise immunosuppression regimens. Additionally, non-invasive imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), will track graft survival and immune responses, ensuring better monitoring and management of beta-cell therapies. The action should also reinforce transparency requirements, including model interoperability, data provenance, and traceability of AI decision-making processes.

6) Defining clinically meaningful and patient-centred endpoints using real-world evidence:This objective aims at leveraging real-world data to define clinically meaningful endpoints that capture quality of life and disease burden in T1D. This includes identifying surrogate endpoints to enable clinical trials that demonstrate long-term benefits without requiring extended study durations. Additionally, generating data on the advantages of achieving normoglycemia in individuals already within target glucose ranges will help refine treatment goals and support regulatory decision-making. A small pilot study must be conducted to test these endpoints and gather initial data on their feasibility and impact.

7) Exploring reimbursement models for beta-cell therapies:This objective aims at developing initial cost-effectiveness models that highlight the potential financial and healthcare benefits of beta-cell therapies, focusing on key aspects like reduced complications and improved quality of life. Early-stage collaboration with health technology assessment (HTA) bodies, payers, and policymakers must be sought to help build a foundation for understanding the value of these therapies, laying the groundwork for future integration into healthcare systems across Europe.

8) Integration of cell therapy into diabetes care and collaborative networks:Beta-cell therapies should be integrated into standard diabetes care through specialised training for healthcare providers and the creation of a network of multidisciplinary centres across Europe. Clinical guidelines should be put in place to ensure a smooth transition from current treatments. Additionally, a network of European innovation hubs must be established to foster collaboration, knowledge exchange, and harmonised regulatory approaches, accelerating the development and clinical application of beta-cell therapies. It will also be crucial to collaborate with professional societies to define a clear clinical pathway, ensuring alignment with best practices and optimising patient outcomes across the region.

Additional key considerations:

Applicants are expected to consider a sustainability plan for the maintenance, update, and validation of the project's results beyond the project’s duration to ensure long-term impact and continual improvements.

Applicants are expected to consider the potential regulatory impact of the results and, as relevant, develop a regulatory strategy and interaction plan for generating appropriate evidence as well as engaging with regulators in a timely manner (e.g. national competent authorities, EMA Innovation Task Force, qualification advice).

Applicants are expected to ensure transparent and open dissemination of outcomes, including models and tools, to enable their integration and reuse throughout the wider ecosystem.

Applicants should give adequate consideration in the ethical standards and data privacy frameworks applicable to the use of personal health data and biobanks.

The action funded under this topic is also expected to explore synergies with complementary initiatives to advance research and innovation in Europe, such as NHPIG¹, which is developing the first T1D autoimmune pig model, the Vanguard-project², the Islet-project³, JOIN4ATMP⁴, and relevant Horizon 2020/Europe projects. Furthermore, the project should explore synergies with the European Pancreas and Islet Transplantation Registry (EPITR)⁵, an initiative led by the European Pancreas and Islet Transplant Association (EPITA) to establish a pan-European registry collecting data on individuals who have received pancreas or islet transplants. By leveraging their insights and networks, the project aims to strengthen the impact of beta-cell therapy development, ensuring that these collaborations contribute to a more comprehensive and effective approach to tackling T1D through cell-based therapies.

¹ _{https://www.nhpig.eu/}

² _{https://vanguard-project.eu/}

³ _{https://isletproject.eu/}

⁴ _{https://www.join4atmp.eu/}

⁵ _{https://esot.org/epita/epita-epitr/}