29 September 2020 - - The United States Food and Drug Administration has accepted US-based biotechnology and medical device company Windtree Therapeutics, Inc's (NASDAQ: WINT) Investigational New Drug application for a Phase 2 clinical trial studying lyo lucinactant, its KL4 surfactant drug, in COVID-19 associated lung injury and acute respiratory distress syndrome patients, the company said.

Lucinactant is also used in the company's drug and device combination development program called AEROSURF, being developed for treating preterm infants with Respiratory Distressed Syndromes.

The SARS-CoV-2 virus causing COVID-19 uses the angiosten-converting enzyme 2 receptor for entry into host cells. ACE2 is a surface molecule on alveolar Type 2 cells in the lungs. The Type 2 cells are the source of surfactant production in the lung.

Damage or loss of Type 2 cells and the viral pneumonia often associated with COVID-19 may result in impaired surfactant production leading to a loss of lung compliance and impaired gas exchange.

This increases the likelihood of ARDS that may manifest by respiratory failure and the need for mechanical ventilation. 

There are no approved drug therapies for ARDS, yet surfactant abnormalities are a known characteristic of the condition.

The company believes its synthetic KL4 surfactant may have the potential to mitigate surfactant deficiency and resist the widespread surfactant destruction that can occur as a result of COVID-19 associated lung injury.

The initial study will evaluate changes in physiological parameters in COVID-19 patients who are intubated and mechanically ventilated for associated lung injury and ARDS.

The study will establish the dosing regimen, tolerability, and functional changes in gas exchange and lung compliance after KL4 surfactant administration.

The study is being guided by co-principle investigators from the Brigham and Womens Hospital in Boston and Duke University Medical Center in North Carolina.

If the initial Phase 2 study results demonstrate adequate safety/tolerability and efficacy on physiological variables, Windtree would plan to initiate two additional clinical trials.

One study would more fully assess the impact of KL4 surfactant on clinical endpoints such as time on mechanical ventilation, time in the ICU, mortality.

The second study would be to utilize the company's novel and proprietary Aerosolized Delivery System to aerosolize and deliver the KL4 surfactant noninvasively in COVID-19 patients that are at high risk of respiratory failure with an intent to avoid mechanical ventilation, similar to the company's respiratory distress syndrome studies in preterm infants.

Further details will be available at a future date.

Windtree Therapeutics, Inc. is advancing multiple late-stage interventions for acute cardiovascular and pulmonary disorders to treat patients in moments of crisis.

Using new clinical approaches, Windtree is developing a multi-asset franchise anchored around compounds with an ability to activate SERCA2a, with lead candidate istaroxime being developed as a first-in-class treatment for acute heart failure and early cardiogenic shock in heart failure.

Windtree is also developing AEROSURF as a non-invasive surfactant treatment for premature infants with respiratory distress syndrome, as well as evaluating other uses for its synthetic KL4 surfactant for the treatment of acute pulmonary conditions including lung injury due to viral, chemical and radiation induced insults.

Also in its portfolio is rostafuroxin, a novel precision drug product targeting hypertensive patients with certain genetic profiles.