EXPLORE COVID-19 Study
Given our scientific expertise in innate immunity, we conducted an exploratory translational study, called EXPLORE COVID-19, in collaboration with La Timone, North and Laveran hospitals and the Marseille Immunopôle/AP-HM immunoprofiling laboratory at La Timone hospital, Marseille, to analyze immune cells in COVID-19 patients at different stages of the disease.
Through this analysis, our goal was to better understand the impact of the immune response on the evolution of COVID-19 and pathways able to modulate this response. This has included a focus on Innate Pharma targets that may have a role in controlling viral infection or SARS-Cov2-induced inflammation.
Please click here to read the press release that was issued on April 3, 2020.
EXPLORE Study Results
On July 29th, results from the EXPLORE translational study were published in Nature. In a paper entitled, “Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis,” researchers revealed several key findings.
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.
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.
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, and the findings 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.
Based on these findings, we announced the start of a Phase II clinical trial with avdoralimab to test its potential to reduce the inflammatory response in the lungs (further detail below – FORCE Study).
Please click here to read the press release issued on July 29, 2020.
Additional results from the EXPLORE study were published on July 1st in Cellular and Molecular Immunology. This publication, entitled, “Identification of druggable inhibitory immune checkpoints on Natural Killer cells in COVID-19,” focuses on the expression of CD39, NKG2A and PD-1 inhibitory receptors on NK cells. The study suggests that blocking therapeutic antibodies targeting these molecules already used for cancer immunotherapy could be repurposed to fight COVID-19 infection. These results support exploring blocking therapeutic antibodies targeting these molecules in COVID-19 (see below – IMMUNONCOVID-20 Study).
On April 28, 2020, we announced that the first patient was dosed in a randomized, double-blind Phase II clinical trial, evaluating the safety and efficacy of our anti-C5aR antibody, avdoralimab, in COVID-19 patients with severe pneumonia.
The primary objective of this investigator-sponsored trial, named FORCE (FOR COVID-19 Elimination), is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by ARDS.
Please click here to read the press release.
A controlled, randomized, study will explore monalizumab and avdoralimab, amongst other treatment arms, to investigate the potential efficacy against COVID-19 in cancer patients with mild symptoms and pneumonia respectively.
The main objective of this study, sponsored by Centre Léon Bérard, Lyon, named IMMUNONCOVID-20, is to compare versus standard of care short-term mortality rates in advanced or metastatic cancer patients who are positive for COVID-19 treated with a chloroquine analog (GNS561), an anti-PD1 (nivolumab), an anti-NKG2A (monalizumab), an anti-IL-6R antibody (tocilizumab) or an anti-C5aR (avdoralimab).
Innate Pharma has obtained funding under the PSPC-COVID call for projects to support the Company’s COVID-19 research and development activities. This initiative is operated on behalf of the State by Bpifrance as part of the Programme d’investissements d’avenir (PIA), led by the Secrétariat général pour l’investissement (SGPI). Click hereto read the press release.