Our most advanced program is a first-in-class small molecule specifically targeting plasminogen activator inhibitor (PAI-1) bound to its stabilizing protein, vitronectin. Past efforts to develop inhibitors of PAI-1 targeted only the active conformation, yet were ineffective against the vitronectin-bound protein complex, the predominant form found in the circulation. Our approach was to screen novel drug candidates in a proprietary high throughput assay designed to identify small molecules that exhibited activity in blood and tissues, and that effectively inhibited PAI-1 in complex with vitronectin.
The lead molecule inhibits PAI-1 in human plasma through direct target engagement, establishing activity against a translational clinical biomarker. Efficacy has been demonstrated in multiple preclinical models of pulmonary fibrosis, fibrosis in other organs, and in venous and arterial thrombosis. The lead molecule is orally bioavailable, with a supportive pharmacokinetic and toxicology data package.
Our biopharmaceutical programs have focused initially on the critical role of serpins in inflammatory disease. Our most advanced biopharmaceutical is specifically engineered to modulate the enzymatic activity of neutrophil extracellular traps in inflammatory disease, and has implications for intercepting diseases in which neutrophils play a key role, including idiopathic pulmonary fibrosis, immunomodulation in cancer, and diabetes.