On Jun. 17, 2020, Aclaris Therapeutics announced that the FDA had allowed an investigational new drug application to evaluate ATI-450, its oral investigational MK2 inhibitor compound, in hospitalized patients with COVID-19. Aclaris suppored an investigator-initiated trial of ATI-450 for cytokine release syndrome (CRS) in 36 hospitalized patients with COVID-19, and provided funding and clinical drug supply to the University of Kansas Medical Center, the sponsor of the trial. The primary endpoint was the proportion of subjects who were free from respiratory failure by day 14.

ATI-450 has been observed to regulate pro-inflammatory cytokines associated with CRS.  Pharmacodynamic analysis from the first-in-human study using an ex vivo lipopolysaccharide (LPS) stimulation model demonstrated dose-dependent reduction of TNFα, IL1β, IL6 and IL8.   Further analysis using this LPS model showed marked inhibition of additional cytokines linked to CRS, including GM-CSF, IL2, IFNγ and MIP1α.  Furthermore, anti-inflammatory activity for ATI-450 was observed in a rat model of airway neutrophilia induced by inhaled LPS.  In addition, anti-viral^1,2,3 and anti-fibrotic^4,5 activity has been observed following blockade of the MK2 pathway in preclinical studies.

“Many of the investigational drugs that are being evaluated to treat CRS target a single cytokine,” said Dr. David Gordon, Chief Medical Officer of Aclaris. “We believe inhibiting multiple cytokines has the potential to achieve clinical benefits in patients with CRS, and this study will explore if ATI-450 is an effective approach in these patients. Thanks to KUMC, who are sponsoring this trial, we are able to evaluate ATI-450 as a potential treatment for COVID-19 at this critical time without impacting our ongoing clinical development programs. If successful, we hope to further explore the role that ATI-450 may have in helping patients with COVID-19 and addressing the healthcare challenges of the pandemic.”