WAYNE, PA — Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates for immuno-inflammatory diseases, announced that the FDA has allowed an investigational new drug application to evaluate ATI-450, its oral investigational MK2 inhibitor compound, in hospitalized patients with COVID-19.
Aclaris is supporting an investigator-initiated trial of ATI-450 for cytokine release syndrome (CRS) in 36 hospitalized patients with COVID-19, and will provide funding and clinical drug supply to the University of Kansas Medical Center (KUMC), the sponsor of the trial. The trial will be led by co-investigators Gregory Gan, M.D., Ph.D. and Deepika Polineni, M.D., M.P.H. The trial is a Phase 2a, randomized, double-blind, placebo-controlled trial to investigate the safety and efficacy of ATI-450, when used in addition to standard of care therapy. The primary endpoint is the proportion of subjects who are free from respiratory failure by day 14.
“CRS leads to the release of multiple inflammatory cytokines such as IL1β, IL6 and TNFα, which precedes acute respiratory distress syndrome, and is associated with significant morbidity and mortality in patients with COVID-19. ATI-450, a novel oral compound, has demonstrated that it targets the expression of inflammatory cytokines in a Phase 1 clinical trial in healthy volunteers. Therefore, we believe that ATI-450 may be an innovative approach to managing this disease,” said Dr. Gan. As further noted by Dr. Polineni, “By mitigating CRS, important clinical outcomes such as oxygenation in patients with COVID-19 would be improved which could result in the reduced need for ventilation in patients in the intensive care setting.”
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-viral1,2,3 and anti-fibrotic4,5 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.”
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