What is TGD001?
TGD001 is TargED’s innovative therapy in development for targeted clot breakdown: thrombolysis, localized at the site of thrombosis. TGD001 is a so-called fusion protein consisting of two parts: the catalytic domain of urokinase (also called urokinase-type plasminogen activator) which causes the clot breakdown, and a single-chain antibody (VHH) which acts as an anchor to blood clots. The single-chain antibody ‘anchor’ binds to Von Willebrand Factor (VWF), which is present in all types of blood clots and that sticks these clots together. The targeted approach, by binding to a blood clot, makes that TGD001 acts where it needs to work, not everywhere in the blood. The activator part then locally converts plasminogen, an inactive enzyme precursor that circulates in blood, into enzymatically active plasmin. Plasmin is a naturally occurring enzyme in the body that breaks down thrombi by degrading both VWF and fibrin. Fibrin forms fibers that (with VWF) form the mesh holding the platelets and red blood cells and thus keep the blood clot together. When VWF and fibrin are degraded, the blood clot dissolves and blood flow is restored. Such rapid opening of blood vessels is crucial because no blood flow means that there is no oxygen supply to the downstream tissue. Restoring blood flow thus minimizes cellular and tissue damage. If untreated, such tissue damage is irreversible and may lead to life-long disabilities.
Next to the rapid clot dissolution by TGD001 as observed in animal models of thrombosis, its targeted, local action is important. Plasminogen is everywhere in the blood, but the aim is to have it only activated at the clot, and thereby avoiding unwanted bleeding side effects elsewhere in the body.