Razuprotafib (AKB-9778): Tie2 Activation for Prevention and Treatment of ARDS due to COVID-19
The Tie2/angiopoietin pathway activation plays a key role in maintaining normal endothelial function and vascular stability. Over the past decade, reduced Tie2 activation has been implicated in the pathophysiology of a variety of acute and chronic conditions characterized by endothelial dysfunction, vascular injury and inflammation, including acute respiratory distress syndrome (ARDS).
- Razuprotafib is a novel small molecule Tie2 activator that enhances endothelial function and stabilizes blood vessels, including pulmonary and renal vasculature.
- Subcutaneous (SC) razuprotafib restores Tie2 activation and improves vascular stability in multiple animal models of vascular injury and inflammation, including LPS induced pulmonary and renal injury, polymicrobial sepsis and IL-2 induced cytokine storm.
- In clinical trials, SC razuprotafib has shown clear evidence of target engagement and vascular stabilization with excellent safety profile in healthy volunteers and diabetic patients (n = 352) dosed SC twice daily for up to 48 weeks.
In summary, razuprotafib restores Tie2 activation to stabilize the vasculature providing breakthrough potential for reducing the severity of COVID-19 associated pulmonary and vascular pathology resulting in fewer patients requiring ventilator support, decreased time in ICU on ventilator support and more rapid and complete recovery with concomitant reduction mortality. Additionally, razuprotafib together with emerging antiviral drugs could provide the optimal combination of host and virus targeted therapy for prevention and treatment of COVID‑19 and COVID-19 related ARDS.
Two phase 2 clinicals trials, I-SPY COVID-19 and RESCUE, are slated to begin recruiting patients in Q3/4 2020 in patients with critical and moderate to severe COVID-19, respectively.