WINT Windtree Therapeutics Inc

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 an update of istaroxime in both clinical and business development. Istaroxime is a novel first-in-class therapy that is designed to improve systolic contraction and diastolic relaxation of the heart while also increasing blood pressure and maintaining or improving renal function. It has been studied in three positive Phase 2 trials enrolling patients with acute heart failure (AHF) and early cardiogenic shock.

In line with previous guidance, the Company expects its Phase 2 SEISMiC Extension Study in SCAI Stage B early cardiogenic shock patients to complete enrollment in the next several weeks and report topline data by the end of this quarter. Building upon the positive SEISMiC study results, the Extension Study is focused on dose optimization and additional characterization of SERCA2a effects for Phase 3 planning and is expected to enroll up to 30 patients. The study of hospitalized patients with early cardiogenic shock (SCAI Stage B) due to AHF evaluates two-dose regimens of istaroxime compared to placebo. Patients will receive infusions of istaroxime for up to 60 hours, with one group receiving a decreasing istaroxime dose over time and the second group receiving a consistent istaroxime dose. This study will extend the dosing duration compared to the previous positive SEISMiC study, in which study treatment was limited to 24 hours. The Company believes extending the dosing duration of istaroxime has the potential to provide additional benefit and, along with dose titration, is an important factor in determining the optimal dosing regimen to study in late-stage trials. The study is also collecting detailed information related to heart function, particularly associated with the SERCA2a mechanism of action. Istaroxime has not been associated with an increase in cardiac arrhythmias, which the Company believes is a potentially important differentiating characteristic compared to currently used inotropes and vasopressors.

Further, the Extension Study is measuring the effects of istaroxime on blood pressure and cardiac function with the two dosing regimens similar to the improvements seen in the previous SEISMiC study.

The Company is also progressing the start-up of a parallel study in more severe, SCAI Stage C cardiogenic shock patients. SCAI stage C is a more severely ill population than was previously studied in the SEISMiC study. SEISMiC C data will be reviewed after enrollment of up to 20 patients with SCAI Stage C cardiogenic shock due to acute decompensated heart failure. It will be a placebo controlled, double-blinded study with istaroxime being added to current standard of care using inotropes or vasopressors. The effect of istaroxime in addition to these therapies will be assessed for 6 hours followed by withdrawal of the standard of care therapies. The primary endpoint is assessment of systolic blood pressure (SBP) area under the curve over the first 6 hours of treatment. Other key study measurements include: SBP changes at specified timepoints, the vasopressor-inotrope score, progression to SCAI Stage D or E cardiogenic shock, time to treatment failure, arrhythmia assessments, days alive and out of the hospital through day 30, physiologic measures (e.g., cardiac index) and length of stay in the ICU and hospital. The execution of this study will depend on the Company’s ability to obtain adequate resources for its completion.

Finally, the Company announced in January 2024 it entered into a license agreement with Lee’s Pharmaceutical (HK) Limited (“Lee’s”) for the development and commercialization of istaroxime in Greater China, including for AHF and cardiogenic shock. In addition to istaroxime, the agreement also licenses Windtree’s preclinical next-generation dual mechanism SERCA2a activators, and rostafuroxin, a Phase 2 product candidate for hypertension associated with specific genotypes. The agreement provides Windtree potential future milestones up to $138MM plus up to low double digit royalties and full coverage for all development, manufacturing, regulatory and commercialization costs for products in the licensed territory. We expect to provide a development update on Lee’s program later this year. Lee’s is focused on progressing acute heart failure in Greater China while Windtree executes a global cardiogenic shock program.

“We are pleased with our progress in clinical development because of the importance of the high unmet needs in the patient populations we are studying,” said Craig Fraser, CEO and Chairman of Windtree Therapeutics. “Additionally, we are pleased that we have a licensing partner in Lee’s who can help us progress our program in acute heart failure with their resources. We look forward to reporting the topline Extension Study results later this quarter and, with additional resources, continuing our progress with SCAI Stage C study and preparations for Phase 3 readiness.”

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.

Contact Information:Eric Curtisecurtis@windtreetx.com