An innovative approach targeting the Tie2 pathway: Subcutaneous razuprotafib (AKB-9778) for the treatment of diabetic nephropathy
Razuprotafib (AKB-9778) is a small molecule inhibitor of VE-PTP, the most critical negative regulator of Tie2 in diseased blood vessels. It binds to and inhibits the intracellular catalytic domain of VE-PTP that inactivates Tie2. Inhibition of VE-PTP has shown the ability to activate the Tie2 receptor irrespective of extracellular levels of its binding ligands, angiopoietin-1 (agonist) or angiopoietin-2 (antagonist), and may represent the most efficient pharmacologic approach to restoring Tie2 activation.
Subcutaneous Razuprotafib (AKB-9778) for Treatment of Diabetic Vascular Complications
Razuprotafib (AKB-9778) an investigational drug, patient self-administered via a subcutaneous injection, similar to insulin. Pharmacokinetic studies have shown that razuprotafib is quickly taken into circulation and rapidly reaches the target tissue, the diabetic vasculature. The Phase 2b clinical trial, TIME-2b, studying razuprotafib (AKB-9778) administered once or twice daily versus placebo in patients with NPDR, was completed in March 2019. The study failed to meet its primary endpoint on diabetic retinopathy severity score. However, there was a 20% improvement in UACR in the patients treated twice daily in the 48 week TIME-2b study. A similar improvement of 20% was observed in the earlier 3-month TIME-2 study. Aerpio is now exploring ways to progress the razuprotafib (AKB-9778) for diabetic nephropathy in a Phase 2 study, including possible collaborations with development partners.