ThromboGenics announced that positive preclinical data on plasma kallikrein (PKal) inhibitors in diabetic macular edema (DME) have been published in The Journal of Medicinal Chemistry.
ThromboGenics has identified highly selective bicyclic peptide inhibitors of PKal, which were chemically modified to optimize for potency and stability. These novel PKal inhibitors were generated using Bicycle Therapeutics’ Bicycles technology platform. The positive outcomes of PKal inhibitors on tissue edema, studied in a paw swelling model and in a preclinical diabetic retinopathy (DR) disease model (streptozotocin-induced vascular leakage into the retina), supports their development as possible treatments for DME and DR via a VEGF-independent mechanism.
The preclinical study confirmed that the bicyclic peptides have nanomolar to picomolar potencies, are stable in biological matrices and reported prolonged retention in the eye together with in vivo efficacy in diabetic models of retinal vascular permeability.
The article ‘Stable and Long-Lasting, Novel Bicyclic Peptide Plasma Kallikrein Inhibitors for the Treatment of Diabetic Macular Edema’ can be consulted online here.
Jean Feyen, PhD, CSO of ThromboGenics nv comments: “We are pleased that our cutting-edge research has been published in the prestigious Journal of Medicinal Chemistry. These preclinical data further validate the science and potential of PKal inhibitor THR-149 in addressing edema as a key disease hallmark of DR, ahead of its planned entry into the clinic this year.”
ThromboGenics is on track to start a phase 1 study evaluating THR-149 for DME in H1 2018.