Next generation advanced therapies to treat highly prevalent and high burden diseases with unmet medical needs

The recent development of advanced therapies has been hampered by the lack of robust research on certain key parameters e.g. safety, upscaling, immunity, potency assays, cost-effectiveness, and early on in development. This topic aims to ensure that the next wave of advanced therapies, based on either pluripotent stem cells, gene editing or RNA, are established in a timely fashion and in accordance with the appropriate regulatory standards for further clinical testing. It will support preclinical research platforms for disorders with high prevalence and burden[[As defined by www.who.int/medicines/areas/priority_medicines/en/]] that tackle the bottlenecks currently encountered in the field, ensuring that promising advanced therapies can reach the market within the next decade. Applicants should justify the disease or disorder to be targeted with its prevalence level, the related burden and unmet needs. Applicants could propose activities in one or several of the following areas, and should take into consideration the Oviedo Convention, eligible actions and ethical principles as defined by the Horizon Europe Framework Programme [[https://data.consilium.europa.eu/doc/document/ST-6692-2021-ADD-3/en/pdf]]:

• Method development for the production and differentiation of pluripotent stem cells[[Definition: Embryonic stem cells and induced pluripotent stem cells are pluripotent stem cells. www.nature.com/subjects/pluripotent-stem-cells.]] (defined as cells that can give rise to cells from all three embryonic germ layers), to include defining appropriate potency assays. Complementary activities to assess mode of action, safety, in vivo validation or upscaling procedures could be considered.
• Development and validation of biological assays and methods that can demonstrate efficacy, delivery, specificity, and safety (including off-target effects) of genome editing products in targeted cells and tissues (e.g. base editing, prime editing, transcription activator-like effector nucleases, zinc-finger nucleases, clustered regularly interspaced short palindromic repeats). Complementary activities to assess in vivo validation or upscaling procedures could be considered.
• Development and validation of novel RNA-based therapeutics targeting non-communicable diseases. Complementary activities to assess mode of action, delivery, safety, in vivo validation and/or upscaling procedures could be considered.
• Study, analysis and tackling of different immune responses, taking into account factors like sex and age, generated by any of the above-mentioned advanced therapies in vivo, facilitating regulatory approval for next phase of research and development.