Windtree Completes Enrollment of Phase 2b Study of Istaroxime in Early Cardiogenic Shock

Windtree Therapeutics, Inc. (“Windtree” or the “Company”) (NasdaqCM: WINT), a biotechnology company focused on advancing early and late-stage innovative therapies for critical conditions and diseases, today announced it has successfully completed enrollment in its SEISMiC Extension Phase 2b study of istaroxime in early cardiogenic shock caused by heart failure. The study is evaluating the ability of istaroxime to improve heart function and low blood pressure in the setting of early cardiogenic shock due to heart failure. The Company is looking to extend the positive results on these parameters as observed in the Company’s first SEISMiC Phase 2 clinical study that was previously reported. In addition, the Company hopes that the study results will substantiate the encouraging observations from the Company’s Phase 2 clinical study, indicating istaroxime has a favorable renal profile and does not increase cardiac arrhythmias. The SEISMiC Extension Study is utilizing longer dosing duration and tapering the dosing to assess the potential benefits.

Istaroxime is a novel first-in-class therapy that has demonstrated the ability to improve systolic contraction and diastolic relaxation of the heart while also increasing blood pressure and maintaining or improving renal function in patients with compromised cardiac function in three positive Phase 2 trials enrolling patients with acute heart failure (AHF). Cardiogenic shock is a serious condition that can occur when AHF patients continue to deteriorate and the heart cannot pump enough blood and oxygen to the brain, kidneys, and other vital organs. Mortality rates are significant and, depending on severity, range from 7% to 40% in the U.S. There is a lack of satisfactory pharmacological intervention to reverse the condition as available therapies have unwanted side effects such as risk for arrhythmias, decreased blood pressure, and renal dysfunction that limit their usefulness and position them as “rescue medicines” for severe cases. The cardiogenic shock worldwide total market value is estimated to be $1.25 billion per year.

The SEISMiC Extension Study in cardiogenic shock was conducted in the U.S., Europe and Latin America and is expected to build upon the positive results from the Company’s first SEISMiC Phase 2 clinical study. The SEISMiC Extension Study is focused on dose optimization and additional characterization of istaroxime’s novel SERCA2a mechanism and its potential benefits in cardiogenic shock patients. The study includes hospitalized patients with early cardiogenic shock (SCAI Stage B) due to AHF and evaluates two different dose regimens of istaroxime compared to placebo. Patients received infusions of istaroxime for up to 60 hours, with one group receiving a decreasing istaroxime dose over time and the second group receiving a constant istaroxime dose. This study has extended the istaroxime dosing duration compared to previous studies where treatment was limited to 24 hours and has the potential to provide additional benefit and, along with dose titration, is an important factor in determining the optimal dosing regimen to utilize in a late-stage trial. The study is also collecting detailed information related to cardiac function and additional safety information on cardiac arrhythmias. Istaroxime has not been associated with an increase in cardiac arrhythmias, which the Company believes is a potentially important differentiating characteristic compared to commonly used current drug therapies.

“Completing enrollment in the SEISMiC Extension Study is an important step in advancing the istaroxime program to Phase 3, along with the ongoing SEISMiC C study in more severe cardiogenic shock patients” said Steve Simonson, MD, Chief Medical Officer and Senior Vice President of Windtree. “We look forward to announcing topline results from the SEISMiC Extension Study by the end of the month and plan to present this data at a major medical meeting in the very near future.”

About IstaroximeIstaroxime is a first-in-class dual-mechanism therapy designed to improve both systolic and diastolic cardiac function. Istaroxime is a positive inotropic agent that increases myocardial contractility through inhibition of Na+/K+- ATPase with a complimentary mechanism that facilitates myocardial relaxation through activation of the SERCA2a calcium pump on the sarcoplasmic reticulum enhancing calcium reuptake from the cytoplasm. Data from multiple Phase 2 studies in patients with early cardiogenic shock or acute decompensated heart failure demonstrate that istaroxime infused intravenously significantly improves cardiac function and blood pressure without increasing heart rate or the incidence of cardiac rhythm disturbances.

About Windtree Therapeutics, Inc.Windtree Therapeutics, Inc. is a biotechnology company focused on advancing early and late-stage innovative therapies for critical conditions and diseases. Windtree’s portfolio of product candidates includes istaroxime, a Phase II candidate with SERCA2a activating properties for acute heart failure and associated cardiogenic shock, preclinical SERCA2a activators for heart failure and preclinical precision aPKCi inhibitors that are being developed for potential in rare and broad oncology applications. Windtree also has a licensing business model with partnership out-licenses currently in place.

Forward Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are based on information available to the Company as of the date of this press release and are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. Examples of such risks and uncertainties include, among other things: the Company’s ability to secure significant additional capital as and when needed; the Company’s ability to achieve the intended benefits of the aPKCi asset acquisition with Varian Biopharmaceuticals, Inc.; the Company’s risks and uncertainties associated with the success and advancement of the clinical development programs for istaroxime and the Company’s other product candidates, including preclinical oncology candidates; the Company’s ability to access the debt or equity markets; the Company’s ability to manage costs and execute on its operational and budget plans; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; risks related to technology transfers to contract manufacturers and manufacturing development activities; delays encountered by the Company, contract manufacturers or suppliers in manufacturing drug products, drug substances, and other materials on a timely basis and in sufficient amounts; risks relating to rigorous regulatory requirements, including that: (i) the U.S. Food and Drug Administration or other regulatory authorities may not agree with the Company on matters raised during regulatory reviews, may require significant additional activities, or may not accept or may withhold or delay consideration of applications, or may not approve or may limit approval of the Company’s product candidates, and (ii) changes in the national or international political and regulatory environment may make it more difficult to gain regulatory approvals and risks related to the Company’s efforts to maintain and protect the patents and licenses related to its product candidates; risks that the Company may never realize the value of its intangible assets and have to incur future impairment charges; risks related to the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates, if approved; the economic and social consequences of the COVID-19 pandemic and the impacts of political unrest, including as a result of geopolitical tension, including the conflict between Russia and Ukraine, the People’s Republic of China and the Republic of China (Taiwan), and the evolving events in Israel and Gaza, and any sanctions, export controls or other restrictive actions that may be imposed by the United States and/or other countries which could have an adverse impact on the Company’s operations, including through disruption in supply chain or access to potential international clinical trial sites, and through disruption, instability and volatility in the global markets, which could have an adverse impact on the Company’s ability to access the capital markets. These and other risks are described in the Company’s periodic reports, including its Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

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