Expected Outcome:
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.
Scope:
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.
