Rezolute is developing RZ402, a small molecule plasma kallikrein inhibitor (PKI) for use in diabetic macular edema (DME). This is a severe complication of diabetes marked by progressive vision loss and blindness. As a once-daily oral therapy, RZ402 is potentially positioned to improve compliance and treatment outcomes for patients with DME.

Diabetes is the leading cause of new blindness in the United States, with DME contributing greatly to this vision loss. Consistently high blood sugar levels can cause diabetic retinopathy, a complication characterized by damage to the blood vessels in the eye and fluid leakage into the light-sensitive tissue known as the retina. The accumulation of fluid may lead to DME, or swelling of the macula, the part of the retina responsible for sharp, straight-ahead vision.

Currently available treatments for DME involve frequent burdensome injections into the eye (anti-VEGF therapies) or invasive laser surgery. Up to 50% of patients do not have an adequate response to anti-VEGF therapies, and many are unable to adhere to the prescribed injection frequency.

Plasma levels of the enzyme kallikrein have been shown to be elevated in the eyes of patients with DME. Elevation of kallikrein is associated with increased inflammation, vessel leakage and excess blood vessel growth. RZ402 is a small molecule inhibitor of plasma kallikrein that has shown the potential to prevent the onset of and reverse vascular leakage in multiple rodent models. Target concentrations were exceeded for 24 hours following oral dosing of RZ402 in monkeys and dogs, supporting the potential for once daily dosing in humans.