Lucinactant (KL4 Surfactant)

Lucinactant (KL4 Surfactant)

Windtree’s lucinactant (KL4 surfactant) is a synthetic surfactant that is structurally similar to human pulmonary surfactant and contains a proprietary synthetic peptide KL4 (sinapultide), a 21-amino acid peptide that is designed to imitate the essential attributes of the human surfactant protein B (SP-B). SP-B is one of four known surfactant proteins and is the most important for proper functioning of the respiratory system.

Surfactant is a natural lubricant produced by specialized cells in the lung called alveolar Type 2 cells and is critical for proper lung function. Surfactant helps keep the lungs from collapsing when exhaling and also improves oxygen transfer to the blood.

Windtree’s lucinactant can be given either through an endotracheal tube or via a proprietary aerosolized delivery system. It has the potential to mitigate surfactant deficiency and inactivation that can occur as a result of infectious diseases that affect the lung, such as COVID-19.

Preclinical data demonstrated that lucinactant may possess other beneficial properties, including modulation of the inflammatory process, antimicrobial properties, and lack of immunogenicity1

LUCINACTANT (KL4 SURFACTANT) FOR COVID-19 ASSOCIATED LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME

Surfactant is an essential component of healthy lungs to keep them fully expanded and functional. Without a sufficient amount of surfactant, alveoli collapse, requiring more effort to breathe and gas exchange worsens. The SARS-CoV-2 infection and resulting COVID-19 can cause serious lung injury resulting in ARDS, a life-threatening lung dysfunction with no approved drug therapies and where surfactant abnormalities are a known characteristic of the condition.

The SARS-CoV-2 virus uses the angiotensin-converting enzyme 2 (ACE2) receptor for entry into host cells. ACE2 is a surface molecule on alveolar Type 2 cells in the lungs. Type 2 cells are responsible for the natural surfactant production in the lung. Damage or loss of Type 2 cells in COVID-19 lung injury may result in impaired surfactant production leading to a loss of lung compliance, impaired gas exchange and increased likelihood of respiratory failure.

  1.  Wolfson, M.R., Wu, J., Hubert, T.L., Gregory, T.J., Mazela, J., & Shaffer, T.H. (2012), “Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS.” Pediatr Res, 72(4), 375-383; Black C, Leon C, Pluim J. Bactericidal properties of the novel, peptide-containing surfactant – Surfaxin®. Pediatric Academic Societies, Honolulu, HI, May, 2008. E?PAS2008:633756.11; and Clayton RG, Cochrane CG, Gregory TJ. Surfaxin® (lucinactant) does not induce an immune response in a standardized preclinical model. Pediatric Academic Societies, Honolulu, HI, May, 2008. E?PAS2008:633756.12.

Preclinical and clinical evidence shows surfactant replacement therapy has the potential to:

Improve

  • Lung function
  • Gas exchange and oxygenation
  • Lung compliance

Decrease

  • Inflammation in the lung
  • Decrease lung damage and facilitate recovery
  • Decrease need for mechanical ventilation

Lucinactant has been studied in preclinical models of acute lung injury, including in highly pathogenic H5N1 viral pneumonia, and has demonstrated structural and functional beneficial effects.2

Windtree is currently conducting a Phase 2 study evaluating changes in physiological parameters in COVID-19 patients who are intubated and mechanically ventilated for associated lung injury and ARDS. The aim of the study is to establish the dosing regimen, tolerability, and functional changes in gas exchange and lung compliance after lucinactant administration.

  • Up to 20 patients with COVID-19 and ARDS on mechanically ventilation from 4-5 U.S. sites
  • Dosing is through endotracheal tube with a target of 80 mg/TPL/kg and repeat dosing based on improvement in oxygenation
  • Outcome measures include:
    • Physiologic response – oxygenation Index
    • Lung compliance on the ventilator
    • Clinical parameters including time on mechanical ventilator, days in intensive care unit and mortality

More information about the ongoing clinical trial can be found here.

If study outcomes are favorable, Windtree may potentially consider 2 expanded trials:

  1. Expanded study in ventilated patients to establish outcomes
  2. Aerosolized delivery to avoid mechanical ventilation (similar to our respiratory distress syndrome studies)
  1. Segal, R., Tyson, W. S., Weinstein, L. A., Gregory, T. J., & Li, Y. (2018). Aerosolized KL4 Surfactant for Mitigating Highly Pathogenic Avian (H5N1) Influenza-Induced Acute Lung Injury and Mortality. In D107. HOST PATHOGEN INTERACTIONS (pp. A7567-A7567). American Thoracic Society.