Abstract CPR Therapeutics Inc. is developing the first multimodal automated system for cardiopulmonary resuscitation (CPR). This technology integrates and synchronizes multiple pump-mechanisms with enhanced defibrillation, and will be the first device to improve outcomes of patients in cardiac arrest with a number-needed- to-treat predictive of commercial success. It will do this while enhancing patient and provider safety. Nationally, approximately 650,000 individuals suffer cardiac arrest each year. Fifty years after the description of CPR, survival is generally below 10%, and a significant fraction of resuscitated patients are left with neurologic impairment. Remarkably, the standard-of-care remains manual chest compressions performed by rescuers with their hands. It has been estimated that the societal costs related to out-of-hospital cardiac arrest alone may be in excess of $33 billion a year in the US. Without question, clinically effective improvements in CPR are among the greatest unmet medical needs. All previous attempts at effective CPR devices have: 1) focused on only one enhancement at a time, 2) had disappointing outcomes in randomized trials, 3) cause skeletal injuries in most patients, and 4) provide no benefit over manual CPR. In a series of pilot studies, CPR Therapeutics demonstrated that combinations of cardiac output- and venous return-enhancing techniques may offer additive or even synergistic benefits to hemodynamics. As envisioned, the Company’s multifunctional system is based on the concept that multiple CPR pump mechanisms, combined with synchronization of defibrillation and pulseless electrical activity (PEA) CPR, will synergize both the hemodynamics and electrophysiology. These approach should significantly improve real-world clinical outcomes. In this Direct-to-Phase II project, CPR Therapeutics will: 1) Design and build a 3rd generation porcine test-bed capable of high-fidelity millisecond control of the multimodal CPR pump-mechanisms, 2) Optimize the system configuration and component designs in a porcine model of ventricular fibrillation, and 3) Design and build a human clinical prototype under a design-control and Quality Management System (QMS). This device will be subjected to structural and functional bench testing in anticipation of filing for an FDA IDE. In addition to the development of the technology, the project’s scope-of- work will add significantly to our basic science knowledge of the interactions between CPR pump-mechanisms and patient-component synchronizations.