Denali Therapeutics has announced that its partner Sanofi has started dosing of a small molecule RIPK1 inhibitor, DNL758, in a Phase Ib clinical trial involving hospitalised adults with severe Covid-19 lung disease.
RIPK1, a receptor-interacting serine/threonine-protein kinase 1, serves as a signaling protein in the TNF receptor pathway, which modulates inflammation and cell death in body tissues.
In severe Covid-19 patients, a RIPK1 inhibitor is expected to reduce the exaggerated immune response to SARS-CoV-2 and limit any tissue damage caused by excessive inflammation.
The randomised, double-blind, placebo-controlled Phase Ib study is designed to assess DNL758’s safety and impact on the immune system in severe Covid-19 cases.
The study will be completed in January next year and is expected to enrol around 67 participants.
Denali Therapeutics CEO Ryan Watts said: “We know that inhibition of RIPK1, a known target in the TNF-pathway, can significantly modulate the body’s immune response.
“Our partner Sanofi is expanding its clinical investigation of DNL758 into patients with severe Covid-19. We are proud to stand with Sanofi in this effort, with the aim to contribute solutions in the fight against this terrible pandemic.”
Denali and Sanofi collaborated in October 2018 for the global development and commercialisation of RIPK1 inhibitors.
Apart from Covid-19, the company are evaluating DNL788 in CNS indications and DNL758 in peripheral inflammatory indications.
Sanofi agreed to develop and commercialise DNL758, as well as cover all costs related to the drug candidate, while Denali is eligible for development and sales milestones and sales royalties.
Earlier this month, Sanofi and Regeneron Pharmaceuticals reported that a Phase III trial of rheumatoid arthritis drug Kevzara failed to meet its primary and key secondary endpoints in Covid-19 patients who required mechanical ventilation in the US.