Drug development at Aerpio.

Tie-2 Activators

Watch a short video about AKB-9778

AKB-9778 Summary

Healthy cells that line blood vessels are essential for human well being. Compromises to the integrity of the vasculature can lead to blood proteins and other components leaking into the tissues, a condition known as vascular (or capillary) leak syndrome. Vascular leak can be localized to a single tissue (as in retinopathy and macular edema), or it can be systemic leading to life-threatening consequences such as cerebral and pulmonary edema, hypotension and shock.

Vascular stabilization may provide extraordinary benefits in a wide variety of diseases, including diabetes (particularly diabetic vascular complications), oncology, and systemic vascular leak syndromes such as sepsis. In addition, vascular stabilization may reduce vascular leak associated with a number of cancer treatments.

AKB-9778 is a small molecule, Tie-2 activating agent that effectively blocks vascular leak and pathologic angiogenesis in multiple disease conditions. It is initially being developed for the treatment of diabetic macular edema.

How AKB-9778 Works

Tie2 signaling is responsible for stabilizing blood vessels and maintaining vascular integrity. Tie2 is the receptor for the Angiopoietin family of growth factors and Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2) are the natural Tie2 agonist and antagonist, respectively. A growing body of literature shows that levels of circulating Ang2 dramatically increase in a number of disease states involving vascular leak and pathologic angiogenesis. By binding to the Tie2 receptor, Ang2 inhibits Tie2 signaling which in turn compromises vascular integrity and promotes vascular leak and pathologic angiogenesis (see video). The HPTP enzyme, which is the target of AKB-9778, acts as a negative regulator, or brake, at the Tie2 receptor. AKB-9778 works by inhibiting HPTP and effectively removes this negative regulation on the Tie2 receptor. This action restores Tie2 signaling and overcomes the effects of the Angiopoietin-2.

Indications for AKB-9778

Vascular leak can occur in any tissue or organ in the body, and it can happen either locally (e.g. macular edema) or throughout the entire body all at once, as occurs in sepsis. In collaboration with investigators world-wide, Aerpio has demonstrated the efficacy of AKB-9778 in a wide range of animal models of human disease. The efficacy in vascular diseases of the eye (retinopathy and macular edema) has been particularly impressive. Therefore, Aerpio will initially develop AKB-9778 for diabetic macular edema as there remains considerable unmet medical need. As we gain human experience, the number of indications will be significantly expanded.

Publications about AKB-4924

VE-PTP inhibitor AKB-9778 mitigates IL-2-induced VLS and interacts positively with IL-2 against melanoma and renal cancer tumors in mice

Read the abstract.