Coronavirus SARS-CoV-2 responsible for the disease COVID-19 observed in close-up on the surface of a human respiratory epithelial cell. © M.Rosa-Calatrava / O.Terrier / A.Pizzorno / E.Errazuriz-cerda
Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) (“Innate” or the “Company”) has announced the publication of an article in the scientific journal Nature, written by Innate researchers in collaboration with the Center d’Immunologie de Marseille-Luminy (Inserm, CNRS, AMU), the University Hospitals of Marseille – AP-HM (Hôpital de la Timone and Hôpital Nord), Hôpital Laveran, Aix-Marseille University (AMU), as well as the Marseille Immunopôle / AP-HM immunoprofiling laboratory at the Timone Hospital. The data presented suggests that targeting the C5a-C5aR1 pathway may limit the severe inflammatory response.
This Marseille exploratory research task force, called EXPLORE COVID-19, analyzed the immune cells of patients with Covid-19 at different stages of the disease. The aim of this study was to better understand the immune response in patients and to identify potential new ways to fight viral infection.
The study showed that in patients who progress to a severe form of Covid-19, including those with severe pneumonia or acute respiratory distress syndrome (ARDS), activation of the C5a / C5aR1 pathway (C5a is a highly inflammatory peptide and C5aR1 its receptor).
Specifically, the researchers observed elevated C5a levels and overactivation of C5a-dependent myeloid cells, which are believed to contribute to inflammation in the lungs.
This study focused on the effects of a molecule called avdoralimab (IPH5401), a clinical-stage antibody that blocks C5aR1 (CD88). Avdoralimab prevents the recruitment and activation of myeloid cells induced by C5a. Currently, Innate is evaluating avdoralimab in oncology, providing pharmacokinetic and safety data upstream of its exploration in Covid-19.
The results published in Nature suggest that blocking the C5a-C5aR1 pathway could be considered a potential therapeutic strategy for severe respiratory illnesses associated with SARS-Cov-2. The analysis showed that blocking the C5a-C5aR1 pathway could limit myeloid cell infiltration at inflammatory sites and prevent lung inflammation associated with ARDS in patients with Covid-19.
« There is an urgent need to better understand the evolution of Covid-19 and the associated complement cascade to help improve the prognosis of Covid-19 patients who present with severe symptoms, » comments Pr Eric Vivier, PhD, Scientific Director of Innate Pharma and Professor at the Marseille Luminy Immunology Center (Inserm / CNRS / AMU) and at the AP-HM « This exploratory study encourages us as we are beginning to understand the impact of the immune response on the progression of Covid-19 and the pathways that may modulate this response. »
Based on the results of this study, the Company previously announced the start of an independent clinical trial, named FORCE. This randomized Phase II trial is ongoing, evaluating avdoralimab in a double blind in patients with Covid-19 leading to severe pneumonia.
To read the paper, go to the online publication of Nature.
 Association of Covid-19 inflammation with activation of the C5a-C5aR1 pathway
 FOR Covid-19 Elimination (FOR Covid-19 Elimination)
About the EXPLORE COVID-19 study:
Researchers analyzed the immune response of Covid-19 patients with no or few symptoms, patients requiring oxygen, and a group of critically ill patients requiring prolonged mechanical ventilation. The study involved 82 people: 10 healthy controls and 72 COovid-19 patients, including 10 patients with few symptoms, 34 patients with pneumonia and 28 patients with ARDS.
Avdoralimab in cancer:
Avdoralimab is a therapeutic antibody that specifically binds to and blocks C5aR1 receptors on myeloid suppressor cells (MDSC) and neutrophils. Avdoralimab is currently being evaluated in a Phase I trial in patients with solid tumors, including non-small cell lung cancer or hepatocellular carcinoma.
Avdoralimab in Covid-19:
C5a is believed to be involved in the pathogenesis of acute respiratory distress syndrome by promoting a pro-inflammatory environment, by attracting myeloid cells (neutrophils, monocytes, macrophages) and by stimulating their production of cytokines. Avdoralimab blocks C5aR1 receptors and has the potential to reduce the inflammatory response in the lungs.