Plasma Kallikrein Inhibitor (PKI) Portfolio


Plasma Kallikrein Inhibitor (PKI) Portfolio

In August 2017, AntriaBio exclusively licensed ActiveSite Pharmaceuticals' oral plasma kallikrein inhibitor portfolio for use in human and animal health, including targeting the treatment of diabetic macular edema and other plasma kallikrein-mediated diseases such as hereditary angioedema.

Diabetic macular edema is the primary cause of vision loss in working-age adults globally. It results from a breakdown of the blood-retinal barrier and an increase in Retinal Vascular Permeability (RVP) caused by a diverse group of conditions, including diabetes. An estimated 750,000 individuals in the U.S. and another six to nine million worldwide have diabetic macular edema. These numbers are expected to grow as the incidence of diabetes increases globally. Current treatment approaches in the U.S. directly target the VEGF pathway and are dominated by anti-VEGF agents such as ranibizumab, bevacizumab and aflibercept, which must be injected into the eye by retinal specialists on a monthly or bimonthly basis. The extent of therapeutic benefit received from these agents directly correlates with adherence to this administration route and regimen, which is a significant burden for both patients and their healthcare providers, leading to high rates of non-adherence to treatment regimens and ultimately, sub-optimal therapeutic outcomes.

Plasma kallikrein has been shown to be a mediator of increased RVP in animal models of diabetes and hypertension. VEGF-induced RVP and retinal edema in rodents can be significantly reduced by pharmacologic inhibition or genetic knockout of plasma kallikrein. ActiveSite's lead development candidate is an orally-administered small molecule plasma kallikrein inhibitor, which has been shown to normalize RVP in clinically-relevant animal models of macular edema as effectively as an anti-VEGF agent, thereby supporting its potential as stand-alone therapy for macular edema resulting from diabetes and other causes.