On Sept. 29, 2020, Windtree Therapeutics announced that U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) 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 (ARDS) patients. 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 (ACE2) 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.

• Up to 20 patients with COVID-19 and ARDS and on mechanical ventilation from 4-5 U.S. sites
• Dosing through the endotracheal tube, repeat dosing based on changes in oxygenation
• Planned outcome measures:
  • Physiologic response – oxygenation Index (OI)
  • Lung compliance on the ventilator
  • Clinical parameters including time on mechanical ventilator, days in intensive care unit and mortality (although this first study will not be powered for these measures)
• The Company plans to start the study within the next several weeks and expects recruitment to take 3-6 months (depending on COVID-19 rates at study sites)

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 (ADS) 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.