Core Insights - Windtree Therapeutics is advancing istaroxime, a dual-mechanism therapy for cardiogenic shock, following positive interim analysis results from the SEISMiC C Phase 2 study [1][4][5] - The study demonstrated that istaroxime maintains a safety profile consistent with previous trials, showing no new safety signals and physiological improvements [1][3] Group 1: Study Overview - The SEISMiC C Study is a global, placebo-controlled, double-blinded trial assessing istaroxime in patients with severe cardiogenic shock (SCAI Stage C) [2] - Istaroxime was added to standard care, including inotropes and vasopressors, and showed potential advantages in efficacy and safety compared to existing therapies [2][4] - The interim analysis included the first 20 patients, revealing no new safety concerns or excess arrhythmias [3] Group 2: Istaroxime Profile - Istaroxime is a first-in-class therapy designed to enhance both systolic and diastolic cardiac function, improving myocardial contractility and facilitating relaxation [5] - Previous Phase 2 studies indicated that istaroxime significantly improves cardiac function and blood pressure without increasing heart rate or causing significant rhythm disturbances [5] Group 3: Company Background - Windtree Therapeutics operates with multiple divisions, including a cryptocurrency treasury strategy and therapeutic pipelines, actively seeking long-term development partners [6]

Core Insights - The SEISMiC C Study is the third study in the istaroxime cardiogenic shock development program, focusing on SCAI Stage C patients who are more severely ill [1][2] - Windtree Therapeutics has reached the planned enrollment of 20 patients for the interim analysis in the SEISMiC C study [1][3] - The study is a global, placebo-controlled, double-blinded trial assessing the safety and preliminary efficacy of istaroxime in combination with standard care [2][3] Study Design and Objectives - The primary endpoint is the systolic blood pressure profile over the first six hours of treatment, with additional measurements including cardiac function and vasopressor-inotrope score [2] - The interim analysis will focus on preliminary safety and tolerability, with no statistically significant efficacy signal expected at this stage [2] Company Strategy and Future Plans - The SCAI Stage C study is considered valuable for Phase 3 readiness of istaroxime, targeting an important patient population for future studies [3] - The company aims to differentiate istaroxime from currently available treatments and is progressing towards bringing the drug candidate to market [3] Product Information - Istaroxime is a first-in-class dual-mechanism therapy designed to improve both systolic and diastolic cardiac function, showing promise in previous Phase 2 studies [4] - The drug acts as a positive inotropic agent, enhancing myocardial contractility and facilitating myocardial relaxation [4] Company Overview - Windtree Therapeutics, Inc. is focused on becoming a revenue-generating company across multiple growing industries [5]

Table of Contents As filed with the Securities and Exchange Commission on April 19, 2023. Registration No. 333-269775 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Amendment No. 3 to FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 WINDTREE THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware (State or other jurisdiction of incorporation or organization) 2836 (Primary Standard Industrial Classification Code Number) 94-3171943 (I.R.S. Em ...