Periodic Reporting for period 1 - NICHILD (Feasibility of a secretome factory to treat paediatric interstitial lung disease)
Période du rapport: 2023-04-01 au 2024-09-30
Despite their astonishing clinical success on adults, there are still no mesenchymal stem cell (MSC)-based products approved for paediatric use. Preclinical studies support a potential beneficial role of MSCs therapy to prevent progression of diseases called childhood interstitial lung disease (ChILD). However, MSCs still suffer from the cost of culturing and storage and lack of cell populations standardization for quality and quantity, donor-related factors, protocols for isolation, in vitro expansion, and lastly delivery procedures and dosing. Our goal is to standardize and automatize the production of MSCs secretome and validate it for its translation to paediatric use to treat ChILD. We explore the feasibility of a “secretome factory” based on expansion of MSCs in a micro scaffold called nichoid.
To achieve these goals, in this PoC we validated the main key performance indicators of the production process and we prepared a go-to-market strategy for the secretome biodrug. Our main outcomes regarding the technicl feasibility are: replicates on several donors of a nichoid-based secretome production line; standard operating procedures (SOP) for the secretome production process in full compliance with the GMPs in the sector of biological drugs; establishment of secretome quality parameters obtained through a comprehensive characterization; and demonstration in vitro of the safety and therapeutic efficacy in the pathologies studied. We also assessed a business model for the secretome biodrug, considering a five-year development roadmap. We obtained an official designation for the biodrug, and we identified the regulatory pathway required to obtain drug authorization and initiate clinical trial activities. We identified the target population, we analysed freedom to operate, and we completed a health technology assessment analysis.
This project aimed to establish quality parameters for a bioproduct obtained from cells expanded on a 3D scaffold, instead of expanded on plastic, for the first time. Through a detailed proteomic analysis of BM-MSCs and their secretome when cultured inside the Nichoid scaffold, we could compare the new bioproduct to the standard from flat culture. Our findings suggest that the Nichoid environment significantly influences gene expression and protein secretion profiles, reflecting potential quality markers for the efficacy and safety of BM-MSC-derived products.
Furthermore, this project focused on a class of paediatric diseases with limited approved medications, for which therapies are based on off-label drugs with significant side effects. Current paediatric treatments focus on supportive care (oxygen therapy, ventilation, and physiotherapy) and symptom management rather than curing the disease. We show here that the Nichoid secretome promotes wound healing, it's non toxic and product quality is maintained after storage. We estabished a regulatory pathway, target population, intellectual property strategy, health technology assessment and a business plan to advance the TRL of a new therapeutic product for paediatric patients. The outcome of this project will provide a national and international reference point for the industrial production of MSCs secretome to treat ChILD and then extending this approach to treat adult patients with ILD, and potentially other pathologies, including chronic intestinal disease and osteoarticular diseases.
Furthermore, this project focused on a class of paediatric diseases with limited approved medications, for which therapies are based on off-label drugs with significant side effects. Current paediatric treatments focus on supportive care (oxygen therapy, ventilation, and physiotherapy) and symptom management rather than curing the disease. We show here that the Nichoid secretome promotes wound healing, it's non toxic and product quality is maintained after storage. We estabished a regulatory pathway, target population, intellectual property strategy, health technology assessment and a business plan to advance the TRL of a new therapeutic product for paediatric patients. The outcome of this project will provide a national and international reference point for the industrial production of MSCs secretome to treat ChILD and then extending this approach to treat adult patients with ILD, and potentially other pathologies, including chronic intestinal disease and osteoarticular diseases.