Developing innovative biologic treatments for ischemic stroke, ALS, and other neurological diseases and wound healing applications including the treatment of diabetic foot ulcers.
Protein C is synthesized in the liver and is a precursor of activated protein C (APC). APC, a serine protease, has two pathways of activity in the body: an anticoagulant pathway wherein APC inactivates factors Va and VIIIa, and a cytoprotective pathway mediated by interaction with the endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR-1).
The major unwanted side effect of APC is bleeding, which limits its pharmacologic dosing in man. ZZ Biotech is developing a genetically engineered variant of recombinant APC, named 3K3A-APC, that has markedly reduced anticoagulant activity, but preserved cell-protective and anti-inflammatory activities compared to APC.
In animal models of stroke, ALS, neurotrauma, and sepsis, 3K3A-APC therapy has shown an advantage over recombinant APC in enhanced efficacy and reduced risk for bleeding. Additionally, in multiple stroke models in both mice and rats, the addition of 3K3A-APC to tissue Plasminogen Activator (tPA) treatment provides benefits well beyond those found with either agent alone. In rodents, 3K3A-APC is able to reverse the tendency of tPA to produce microbleeds through protection of the endothelial barrier.
The ability of 3K3A-APC to improve outcomes on top of the only drug currently approved for the acute treatment of ischemic stroke is very encouraging. ZZ Biotech is building on these advantages in developing an improved acute treatment for ischemic stroke in humans. 3K3A-APC could potentially have a major impact on the $43B total US annual costs due to stroke.