The Science

Stroke is caused by the interruption of blood supply to the brain, due to a thrombus in one of the main cerebral arteries or hemorrhage. Stroke-associated death and mortality is directly dependent on the size of the stroke. That, in turn, is determined by the size of brain supplied by the occluded artery, and by the extent of post-stroke edema, that results in brain compression. It estimated that 50% of the stroke damage is due to the loss of blood supply and 50% due to subsequent edema and inflammation development.

Current stroke treatment strategies rely on lytics to lyse the clot in case of thrombotic strokes (90% of all strokes) and reperfusion therapies to open the clogged vessels.  No therapies are available for hemorrhagic strokes (~10% of the total). 

Unfortunately, the majority of stroke victims are not eligible for either of these front line therapies.

Stroke-associated edema: Stroke-associated tissue damage results in a local inflammatory response that, in turn, leads to production of VEGF, the primary mediator of vascular leakage. Stroke-associated inflammation and edema development follows the stroke, with peak edema formation (and brain compression) occurring for up to a week or so post-stroke. 

We have developed a therapeutic approach that is able to block both the cerebral inflammation and vascular leakage/ edema formation without affecting regular blood vessel function . Our data indicate that our proprietary antibodies can reduce stroke size in a mouse model; 60 minutes after initiation of stroke, VST BIO therapy reduced stroke by 35% and edema size by about 50% (Figure A-B). More significantly, antibody, stroke-associated mortality was completely eliminated at 24hrs, and drastically reduced at 72hrs. In ApoE-/- mice on a high fat diet, VST BIO therapy reduced the incidence of hemorrhagic transformation.

We have now developed human mAbs that is functionally equivalent to the antibody used in mice that fully blocks VEGF permeability activity in vitro and in humans. Antibody therapeutics represent a well characterized and understood class of drugs, with 100 antibody therapies approved in the U.S.

In a large NHP stroke model (MCAO), a single iv bolus of VST MAb 4 6 hrs after initiation of stroke resulted in a significant reduction of stroke volume (i.e cerebral damage) by 80% at day 1 and 50-60% at day 3 post stroke. This again shows in a clinically relevant animal model the therapeutic value of his innovative approach acute stroke even when therapy is initiated late after presentation. We believe VB-001 effectiveness can extend to >24 hours after the initiation of stroke, especially in large vessel occlusions.