Coronary artery disease is the world’s leading cause of death. The field has long focused on lipid management, but inflammation drives a deeper failure: the loss of the heart’s capacity to grow its own collateral vessels. Collaterals in the heart are a network of natural by-passes that supply blood and oxygen when larger vessels become blocked. Collateral circulation is a key determinant of symptoms and prognosis, and no therapies have successfully been developed in this domain.
VEGF-A165 is a master regulator of vascularization in coronary artery disease. In normal myocardial tissue it is spliced to VEGF-A165a, which enables vessel growth, and to a lesser extent VEGF-A165b, which reduces vessel growth. Under normal circumstances, the balance between 165a and 165b is tightly regulated.
However, in cardiovascular disease, inflammation shifts splicing towards VEGF-A165b, which blocks the growth of vessels.
ISM-001 selectively removes VEGF-A165b to restore the natural signaling balance that enables healthy vascularization in the heart. VEGF-A165b was first identified in 2001 by Professor David Bates, Scientific Founder, and has since been validated in more than 100 publications from more than 80 independent laboratories worldwide.
Coronary artery disease blocks the body’s own signal to grow new vessels. Isomab is developing a first-in-class antibody antagonist to restore that ability – so the heart can rebuild its own circulation.
ISM-001 is a first-in-class humanized IgG monoclonal antibody that selectively neutralizes VEGF-A165b. It is the product of a structured humanization and optimization cascade, rendering it ready for clinical use.
In validated preclinical models, ISM-001 has demonstrated target engagement and promoted collateral vessel development in myocardial tissue.