Development of cell-free protein synthesis platforms for discovery and/or production of biologicals

Citizens and patients will benefit from better access, availability and affordability of pharmaceuticals based on biologicals. Scope: Cell-Free Protein Synthesis (CFPS) has been employed in fundamental biological research for decades, however, interest for the approach as a viable means for drug development and production has only emerged in recent years. The advantages that CFPS provides in terms of efficiency, simplicity, flexibility, cost- and time savings outweigh the hurdles that are still to be overcome for CFPS to become a routine manufacturing system for peptide- or protein-based biologicals. Currently, there are several CFPS systems used that are either based on prokaryotic or eukaryotic cell lysates (including mammalian) or fully synthetic systems consisting of all the molecular machinery necessary to create functional proteins. The choice of a specific lysate is dictated by the target protein and the end-use application. Proteins that require post-translational modification are generally produced using lysates of mammalian cells. Hence systems based on mammalian cells are of particular interest as they combine properties inherent to eukaryotic cells and their ability to produce human-like glycosylated proteins with the advantages of cell-free synthesis. These proteins include antibody fragments, antigens, virus-like particles, cytokines, enzymes, antimicrobial peptides and proteins containing non-natural amino acids. The benefits of CFPS are manifold, from ease of handling and scalability, on-demand launch of production, ability to rapidly switch products, simplified purification to facilitated standardisation and quality control. CFPS needs less energy resources, the manufacturing footprint is less complex and smaller than in cell cultivation and it enables production of proteins that have toxic effects on cells. In addition, CFPS has the potential as an enabling technology for personalised medicines and is amenable to decentralised manufacturing. CFPS has gained even more interest in the recent past owing to advances in synthetic biology and thanks to the rise of Machine-Learning/Artificial Intelligence (ML/AI). The use of generative deep learning and artificial intelligence has high potential in the de-novo design of biomolecules with specific properties of therapeutic and/or preventive nature. CFPS offers here great opportunities to increase the throughput in screening of the de-novo created biomolecules. The application of synthetic biology, potentially also combined with generative AI, and cell-free biosynthesis open up new avenues for the design, discovery and manufacture of therapeutics not only against infectious diseases, but also non-communicable diseases and equally for vaccines. Proposals should address at least two of the following elements: Address the bottlenecks that currently hamper the large-scale deployment of CFPS, i.e. the lack of a quality-by-design approach, the need to fully characterise the underlying cell lysates and their critical quality attributes and the need for better understanding of the correlations between specific cell lysate properties and CFPS process parameters, specific product quality attributes (such as protein folding), and CFPS platform performance. Use synthetic biology techniques for the design of de-novo biomolecules with specific desired properties (antimicrobial, immunogenic, angiogenic, etc.) and develop suitable cell-free systems for the high-throughput screening of the designed biomolecules. Develop novel or optimise existing CFPS platforms for the production of the targeted biomolecule to a Good Manufacturing Practices (GMP) [1] conform process, producing clinical-grade material that can be tested in clinical trials. The demonstration of the superiority of the developed CFPS platform as compared to the current state-of-the art production system for a specific therapeutic peptide or protein would be an asset and participation of start-ups, micro, small and medium-sized enterprises (SMEs) [2] is encouraged. Applicants envisaging to include clinical studies [3] should provide details of their clinical studies in the dedicated annex using the template provided in the submission system. [1] https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en [2] https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32003H0361 [3] 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.

Eligibility and submission conditions

"> General conditions 1. Admissibility Conditions, proposal page limit and layout Admissibility conditions are described in Annex A and Annex E of the Horizon Europe Work Programme General Annexes. Proposal page limits and layout are described in Part B of the Application Form available in the Submission System. 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 Eligibility 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. 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). Subject to restrictions for the protection of European communication networks. Other eligibility 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 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. 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 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 The granting authority may, up to 4 years after the end of the action, object to a transfer of ownership or to the exclusive licensing of results, as set out in the specific provision of Annex 5. 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 HE Programme Guide Model Grant Agreement (MGA) HE MGA Call-specific instructions Information on clinical studies (HE) Additional documents HE Main Work Programme 2026-2027 – 1. General Introduction HE Main Work Programme 2026-2027 – 4. Health HE Main Work Programme 2026-2027 – 15. General Annexes HE Programme Guide 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 Funding & Tenders Portal Terms and Conditions Funding & Tenders Portal Privacy Statement

Programme context

Topics under this destination are directed towards the Key Strategic Orientation 3 “ A more resilient, competitive, inclusive, and democratic Europe ” of Horizon Europe’s strategic plan 2025-2027 [1] . In addition, Key Strategic Orientation 2 “The Digital Transition” and Key Strategic Orientation 1 “ The Green Transition ” are supported. 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: “the EU health industry is innovative, sustainable, and globally competitive thanks to improved uptake of breakthrough technologies and innovations (including social innovations) that make the EU with its Member States and Associated Countries more resilient and less reliant on imports of critical health technologies ” . The health industry is a key driver for growth and has the capacity to provide health technologies to the benefit of patients and providers of healthcare services. The relevant value chains involve a broad variety of key players from supply, demand and regulatory sides. In addition, the path of innovation in health is long and complex. The development of novel health technologies is generally associated with uncertainties and market barriers due to expensive and risky development (e.g. high attrition rate in pharmaceutical development), high quality and security requirements (e.g. clinical performance, safety, data privacy and cybersecurity) and market specificities (e.g. strong regulation, pricing and reimbursement issues). In addition, the growing concern about environmental issues is putting more pressure on this industry. Therefore, there is a need for Research and Innovation integrating various stakeholders to facilitate market access of innovative health technologies (medical technologies, pharmaceuticals, biotechnologies, digital health technologies). In line with the Commission's Political Guidelines for 2024-2029 [2] , and building on the recommendations of the reports by Mario Draghi [3] and Enrico Letta [4] , as well as the “Strategy for European Life Sciences” [5] , this destination will support research and innovation to enhance the competitiveness of the European health industry, thereby reinforcing EU autonomy, consolidating its Single Market, and empowering Europe to effectively address the burden of both communicable and non-communicable diseases. In this Work Programme part, Destination “ Maintaining an innovative, sustainable, and competitive EU health industry ” focuses on collaborative efforts to advance cell-free protein synthesis platforms, ready-to-use point-of-care diagnostics, and regulatory science to support translational development of patient-centred health technologies. The results will support the EU Industrial Policy, with a focus on strengthening the resilience of the single market, addressing the EU’s strategic dependencies, gaining technological sovereignty and accelerating the green and digital transitions. The results will further strengthen the single market, by providing evidence and guidelines for stakeholders and regulators to ensure adoption of innovations, supporting environmental, fiscal and socio-economic sustainability and at the same time fostering healthcare access and reducing health inequities. The results will also support the implementation of the relevant Regulations like those on Medical Devices (MDR) and In-Vitro Medical Devices (IVDR) as well as the general uptake of innovative health technologies by health systems, with a special view to aspects related to ensuring industry competitiveness, fostering innovation and sustainability, while maintaining the high level of quality, safety and efficacy of these health technologies. In view of increasing the impact of EU investments under Horizon Europe, the 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, development and adoption of best practices, or joint communication activities. All topics are open to international collaboration to address global environment and health challenges. Expected impacts : Proposals for topics under this destination should set out a credible pathway to contributing to maintaining an innovative, sustainable and competitive EU health industry, and more specifically to one or several of the following expected impacts: Health industry in Europe and Associated Countries is more competitive and sustainable, assuring European leadership in breakthrough health technologies and open strategic autonomy in essential medical supplies and (digital) technologies, contributing to job creation and economic growth, in particular with small and medium-sized enterprises (SMEs) [6] . Health industry is supported by cross-sectoral Research and Innovation in the context of convergence of health technologies (integrating medical technologies, pharmaceuticals, biotechnologies, digital health, and e-health technologies) while strengthening key market positions. Health industry is working more efficiently along the value chain from the identification of needs to the scale-up and take-up of solutions at national, regional or local level, including through early engagement with patients, healthcare providers, health authorities and regulators ensuring suitability and acceptance of solutions. Citizens, healthcare providers and health systems benefit from a swift uptake of innovative health technologies and services through the provision of evidence and guidelines for stakeholders, policymakers and regulators. These efforts offer significant improvements in health outcomes, also potentially strengthening access to healthcare for all and reducing health inequities while health industry benefits from decreased time-to-market. Citizens, healthcare providers and health systems benefit from increased health security in Europe and Associated Countries due to reliable access to key manufacturing capacity, including timely provision of essential medical supplies and technologies of particularly complex or critical supply and distribution chains. Legal entities established in China are not eligible to participate in both Research and Innovation Actions (RIAs) and Innovation Actions (IAs) falling under this destination. For additional information please see “Restrictions on the participation of legal entities established in China” found in the Annex B of the General Annexes of this Work Programme. 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 [7] 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] https://research-and-innovation.ec.europa.eu/funding/funding-opportunities/funding-programmes-and-open-calls/horizon-europe/strategic-plan_en [2] https://commission.europa.eu/about/commission-2024-2029_en [3] The future of European competitiveness, Mario Draghi: https://commission.europa.eu/topics/eu-competitiveness/draghi-report_en [4] Much more than a market, Enrico Letta: https://www.consilium.europa.eu/media/ny3j24sm/much-more-than-a-market-report-by-enrico-letta.pdf [5] https://research-and-innovation.ec.europa.eu/strategy/strategy-research-and-innovation/jobs-and-economy/towards-strategy-european-life-sciences_en ; https://ec.europa.eu/commission/presscorner/detail/en/ip_25_1686 [6] https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32003H0361 [7] 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).

Hivatkozott dokumentumok

Annex A Horizon Europe Programme Guide Online Manual Standard application form (HE RIA, IA) Standard evaluation form (HE RIA, IA) HE MGA Information on clinical studies (HE) HE Main Work Programme 2026-2027 – 1. General Introduction HE Main Work Programme 2026-2027 – 4. Health 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 Terms and Conditions https://www.consilium.europa.eu/media/ny3j24sm/much-more-than-a-market-report-by-enrico-letta.pdf