Equine Polyclonal antibodies Immunotherapy against COVID-19/SARS-CoV2-VOC

The highly contagious SARS-CoV-2 virus has generated an unprecedented pandemic with global dramatic health and socioeconomic consequences that need an urgent mitigation. Despite the progression of the global use of efficient vaccines, an increased transmissibility of variants of concern (VOC) is predominantly observed. The reduced sensitivity of VOCs to neutralizing response could become a serious obstacle for efficient vaccination. The absence of approved specific antiviral therapies for vaccinated-non-responders along with the rare anti-inflammatory therapies, passive immunotherapies with polyclonal immunoglobulins could be considered a part of the solution. The main objective of EPIC-CROWN-2 project is to rapidly assess, in clinical trials (phase IIa/IIb), an EMA-authorized antiviral immunotherapy based on potent and broad equine neutralizing anti-SARS-CoV-2 polyclonal F(ab')2 antibodies in COVID-19 patients, including those infected by VOC. In order to save lives and reduce the use and costs of critical care, this therapeutic solution specifically targets hospitalized COVID-19 patients. To optimize the indications for the treatment, potency and breath of F(ab')2 against variants will be assessed by in vitro and in vivo studies. Prospective studies will respectively be done on immune assessment in treated patients and on mitigation of exacerbated immune responses in vivo. Fab'entech coordinates the EPIC-CROWN-2 consortium formed by an outstanding group of experts of different domains of the project that include clinical trials (HISS, Greece), virology (IMAS12, Spain) and immunopathology models (BNITM, Germany) and immunopathology mitigation (IRD, France). Most of them having already been working together in European projects. Importantly, EPIC-CROWN-2 isin contact with the large European trial network EU-RESPONSE and specifically in the new multinational European Adaptive Platform Trial "SolidAct". This ambitious project should have an important societal and economic impact, by providing a therapeutic solution in fast time to a high medical need.The reduced sensitivity of VOCs to neutralizing response could become a serious obstacle for efficient vaccination. In the absence of approved specific antiviral therapies for vaccinated-non-responders and the scarce anti-inflammatory therapies, passive immunotherapies with polyclonal immunoglobulins could be considered a part of the solution. The main objective of EPIC-CROWN is to rapidly assess, in multicentric clinical trials (phase IIa, 16 patients and IIb, 400 patients), an EMA-authorized antiviral immunotherapy based on potent and broad equine neutralizing anti-SARS-CoV-2 polyclonal F(ab'Äô)2 antibodies in COVID-19 patients, including VOC carriers. In order to save lives and reduce the use and costs of critical care, this therapeutic solution expect to reduce at least by 50% ICUs admissions and a highly significant mortality rate of treated patients. To optimize the indications for the treatment, potency and breath of F(ab'Äô)2 against variants will be assessed in in vitro and in an animal model as well as prospective studies will respectively be done on immune assessment in treated patients and on mitigation of exacerbated immune responses in vivo. Fab'Äôentech will coordinate EPIC-CROWN-2 formed by outstanding experts in different project domains that include clinical trials (HISS, Greece), virology (IMAS12, Spain), and immunopathology models and mitigation (BNITM, Germany - IRD, France). Most of them having already been working together in European projects. Importantly, EPIC-CROWN-2 will be integrated as part of both the large European trial network EU-RESPONSE and the multinational European Adaptive Platform Trial 'ÄúSolid Act".