Ischemic Stroke Indication Overview

Review of Current Approved Treatments and the Unmet Need for a Thrombosis Modulating and Neuroprotective API

The Acute Ischemic Stroke (AIS) Indication

Ischemic stroke is caused by intravascular thrombus formation obstructing cerebral blood flow. AIS affects millions of people every year with increasing incidence as populations age. Despite recent improved prophylactic and therapeutic intervention with endovascular thrombectomy, ischemic stroke is still a major cause of death and disability worldwide. Currently, the only approved therapeutic for AIS is intravenously administered recombinant tissue Plasminogen Activator (tPA). Following AIS, tPA supports break down of fibers of thrombus fibrin, which may partially restore blood flow. There is no approved therapy to arrest thrombus formation or to inhibit the acquisition of fibrin in occluding thrombi following AIS. Similarly, there is no approved drug to protect brain tissue from lack of blood flow and oxygen following AIS and no drug to limit the damaging effects of infiltrating neutrophils and neutrophil extracellular traps (NETs). It is known that Aryl hydrocarbon receptor (AhR) antagonism can mitigate cellular damage associated with cerebral ischemia and reperfusion (I/R) injury due to AIS.

Boulder BioScience (BBS) has developed an API candidate for AIS treatment. The mechanisms of action (MoA) for the API include inhibitory modulation of the Aryl Hydrocarbon Receptor (AhR) and inhibition of neutrophil activation and NET formation. As a ligand of the AhR, the API provides a first-in-class neuroprotector small molecule for AIS and Traumatic Brain Injury (TBI). As a non-toxic kinase inhibitor, the API fills an unmet need for an inhibitor of neutrophil driven brain injury in AIS. Both of these genomic and non-genomic MoAs limit early phase AIS brain damage. When used alone or in conjunction with currently approved tPA and endovascular thrombectomy, the BBS drug products are candidates to improve patient functional outcome in AIS.