New research suggests targeting C5a-C5aR1 axis could limit severe inflammatory response
Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) (“Innate” or the “Company”) today announced the publication of a Nature paper entitled, “Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis,” authored by Innate researchers in partnership with scientists from Hôpitaux Universitaires de Marseille AP-HM (La Timone and North Hospitals), Laveran Hospital, Aix Marseille University, the Centre d’Immunologie de Marseille-Luminy (Inserm, CNRS, AMU) and Marseille Immunopole/AP-HM immunoprofiling laboratory at La Timone Hospital.
This Marseille-based exploratory research taskforce, named EXPLORE COVID-19, analyzed immune cells in COVID-19 patients at different stages of the disease. The goal of the study was to gain translational insights to better understand the immune response in COVID-19 patients and identify potential targets to fight the viral infection.
The study found that patients who progress towards severe COVID-19 disease, including those with severe pneumonia and acute respiratory distress syndrome (ARDS), exhibit an activation of the C5a/C5aR1 pathway. Specifically, researchers observed high levels of circulating C5a and over-activation of the C5a-dependent myeloid cell pathway, which is believed to contribute to inflammation in the lungs.
This research also focused on avdoralimab (IPH5401), a clinical-stage monoclonal antibody that blocks C5aR1 (CD88). Avdoralimab prevents C5a-induced myeloid cell recruitment and activation. Innate is currently investigating avdoralimab in oncology, which provided pharmacokinetic and safety data prior to investigation in COVID-19.
The findings published in Nature suggest that the C5a-C5aR1 axis blockade could be considered as a potential therapeutic strategy for severe respiratory disease associated with SARS-Cov-2 infection. The analysis found the C5a-C5aR1 axis blockade as a means of limiting myeloid cell infiltration at inflammatory sites and preventing the excessive lung inflammation associated with ARDS in COVID-19 patients.
“There is an urgent need to better understand COVID-19 disease progression and the associated complement cascade to help improve the prognosis of COVID-19 patients who present severe symptoms,” said Pr. Eric Vivier, PhD, Chief Scientific Officer at Innate Pharma and Professor at AP-HM, Aix-Marseille University and Centre d’Immunologie de Marseille-Luminy (Inserm/CNRS/AMU). “We are encouraged by this exploratory study, as we’re beginning to understand the impact of the immune response on the evolution of COVID-19 and pathways able to modulate this response”
Based on findings from this study, the Company previously announced the launch of an investigator-sponsored trial named FORCE (FOR COVID-19 Elimination). This is a randomized, double-blind Phase II clinical trial to further explore avdoralimab in COVID-19 patients with severe pneumonia, which is currently ongoing.