Windtree Therapeutics provides update on istaroxime clinical development and upcoming clinical trial data.

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 II trials enrolling patients with acute heart failure (AHF) and early cardiogenic shock.

In line with previous guidance, the Company expects its Phase II 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 III 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 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 II product candidate for hypertension associated with specific genotypes. The agreement provides Windtree potential future milestones up to $138 Million 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 III readiness.”