Innovative Voltage-Activated Ultrasound Imaging Agent for Selective Myocardial Enhancement

ABSTRACT Significance: Heart disease is the leading cause of death in the United States and coronary heart disease (CHD), which impacts approximately 18M Americans, is the most common form of heart disease. CHD can cause chest pain and shortness of breath, increases the likelihood a person will experience a myocardial infarction and accounts for 1 of every 7 deaths in the United States. The Problem: It is challenging to visualize myocardial perfusion without expensive centralized equipment, exposure to ionizing radiation and/or invasive coronary angiography. The Solution: A voltage- activated ultrasound imaging agent call Electrast™ that can transform the way cardiologists diagnose and monitor CHD. Unlike other ultrasound enhancement agents, Electrast™ is in an inactive state as it circulates through the bloodstream and is selectively activated in viable, perfused myocardium by the electrical depolarization wave that makes the heart beat, allowing clinicians to assess the microperfusion of the heart at the bedside in real time without the need for ionizing radiation. Preliminary Data: Proof-of-principle validation data demonstrating that Electrast™ can selectively enhance myocardial tissue has been generated in small (rodent) and large (swine) animal studies. Specific Aims: This project will support the scale-up and cGMP manufacturing work necessary to produce sterile Electrast™ for the preclinical safety, toxicity and verification and validation testing required to secure approval of a Phase I Investigational New Drug (IND) application for Electrast™ from the FDA. In Specific Aim 1 the team will validate in swine that Electrast™ provides selective enhancement of viable, perfused myocardium using core perfluorocarbon droplets synthesized by microfluidization in place of sonication and comprised in part or in full of C4F10 in place of pure C5F12. In Specific Aim 2 will support transfer of manufacturing to a current good manufacturing practices (cGMP)-certified contract organization for scale-up and production of a 10 L lot of sterile Electrast™ that meets specified product release criteria for particle size, concentration, and stability. Finally, in Specific Aim 3 Sonnest will confirm, via internal and third-party testing, that Electrast™ meets the company’s product specification and release criteria and FDA pre-clinical safety and toxicity requirements for approval of a Phase I IND application. Expected Outcomes: At the end of this Direct to Phase II SBIR Grant, Sonnest will have validated cGMP manufacturing to make Electrast™ at scale, robust preclinical safety and toxicity data, and an approved IND for the Phase I clinical investigation of Electrast™. .