Research Project
9066982
DESCRIPTION (provided by applicant): Acute ischemic stroke (AIS) is the result of a blood clot in a cerebral artery. It remains a leading killer and the leading cause of long-term disabilit, annually impacting over 700,000 Americans [10]. Because brain tissue rapidly dies, time to reperfusion is critical in both preventing death and improving neurological outcomes. While current annual costs related to ischemic stroke are high in the United States (US), they are projected to increase from $72B in 2013 to $183B by 2030 [14]. Intravenous (IV) administration of tissue plasminogen activator (tPA) remains the standard of care for AIS [15], despite a small ~10% chance for a full recovery and a >65% chance of death or severe disability [16]. While tPA has been proven to offer statistically-significant benefits, albeit low, in AIS [11] [12] [13], the dose- dependent bleeding associated with tPA has resulted in a low ~8% administration rate in the US. As a result, a large majority of stroke victims are greatly underserved despite efforts to improve standards of care. Due to poor fluid dynamics, the effectiveness of all thrombolytic drugs is because of their inability to rapidly diffuse to a clot in the occluded vessel [17]. Pulse Therapeutics, Inc.'s (PTI's) patented and clinically- investigated technology has overcome this limitation in a way that dramatically accelerates tPA delivery to a clot by using non-tPA-attached magnetite particles controlled by an external magnet. This technology is deployed in the emergency department after the baseline CT. However, by attaching the FDA-approved drug tPA to PTI's magnetite particles, the technology promises faster clot lysis (driving better neurological outcomes) at a substantially lower tPA dose (allowing expansion to nearly all ischemic strokes). PTI's objective is to demonstrate dramatic improvements in thrombolysis by attaching tPA to the company's magnetic particles. In Phase I, PTI will attempt to 1) develop optimal magnetite particles with the best- performing tPA coating conjugated to the surface, 2) collect data on the candidate particle's clot lysis rate and proper dosing in vitro, 3) optimize a software algorithm for automated particle collection, and 4) conduct a pre- submission meeting with the FDA. For Phase II, PTI will 5) modify an existing PTI magnet system suitable for use in pre-clinical animal studies, 6) identify the best tPA-coated particle from safety and efficacy GLP preclinical studies, and 7) assemble a data package in preparation for a subsequent FDA IDE submission. The proposed technology has dramatic implications for the treatment of AIS. By delivering tPA directly to the clot's surface via attachment to magnetic particles, clot lysis willto occur faster and result in better neurological outcomes, while drug-related toxicity effects may be eliminated, thereby expanding thrombolytic therapy from the ~30% maximum stroke victims eligible today, to potentially all ischemic stroke victims.
