Anchored in IP licensed exclusively tio the firm by the University of North Carolina, Chapel Hill (UNC-CH) , Vascular Pharmaceuticals (VPI) is organized around a first in class monoclonal antibody (mAb) VPI-2690B, a subcutaneously administered humanized mAb for use in the treatment of diabetic nephropathy. VPI-2690B targets the αVβ3 integrin receptor which is involved in aberrant cellular signaling that occurs in the presence of high glucose and leads to damage to several key cell types involved in maintaining kidney filtration. The firm's lead program is that binds to a unique molecular target, the C-loop domain sequence within the αVβ3 receptor, a component of the insulin-like growth factor-I (IGF-I) signaling pathway. The levels of the ligands that bind to αVβ3 are markedly increased in diabetes and this abnormal αVβ3 activation leads to pathologic changes that result in decreased renal function. Inhibition of ligand binding with VPI-2690B restores αVβ3 activation to normal. αVβ3 is expressed in limited cell types including smooth muscle, endothelial, and podocytes, making it an attractive target for selective antagonism. Animal studies in a diabetic pig model with VPI-2690B resulted in statistically significant improvement in pathologic changes such as glomerular basement membrane thickening and podocyte effacement. The key pathophysiologic change that indicates a loss of the normal renal filtration barrier, e.g. proteinuria, was also normalized following
