Santhera, Cold Spring Harbor Lab to Investigate Lonodelestat in COVID-19-related ARDS

Santhera Pharmaceuticals has entered into a collaboration agreement with Cold Spring Harbor Laboratory (CSHL) to investigate the potential of lonodelestat (POL6014), a potent inhibitor of human neutrophil elastase (hNE), as a therapeutic intervention for COVID-19-related acute respiratory distress syndrome (ARDS).

Researchers at CSHL are part of a recently formed consortium of international non-clinical and clinical experts called the ‘NETwork to target neutrophils in COVID-19’. This NETwork will study the role of neutrophils and neutrophil extracellular traps (NETs) in the pathology of COVID-19 as well as hNE and other targets for intervention for the purpose of treating COVID-19.

NETs are macromolecular structures of DNA and proteins that neutrophils can expel, for example during severe inflammation. hNE is released by neutrophils when they form NETs. There are clear similarities between the clinical presentation of severe COVID-19 and diseases known to involve NETs, such as ARDS. On this basis, the NETwork has developed the rationale that excess NETs may play a major role in COVID-19 and that inhibition of hNE may be a therapeutic strategy to antagonize NETs in COVID-19 patients.

Santhera will provide lonodelestat and intellectual support for the scientists at CSHL who will conduct the non-clinical research program. The work is expected to further validate hNE as a target and shed light on this clinical stage compound as a potential agent also in COVID-19.

“There is a strong scientific rationale that inhibition of hNE may interrupt a neutrophil-driven inflammatory cascade that leads to ARDS in COVID-19 patients” said Mikala Egeblad, PhD, Associate Professor at Cold Spring Harbor Laboratory, New York. “Based on previous work with lonodelestat in models of ARDS and acute lung injury, we were very encouraged about the potential of lonodelestat. Our own research in non-clinical models will start immediately and we are delighted that Santhera has offered their support in our efforts to find a potential novel treatment that could be investigated in patients with COVID-19.”

“We would like to thank CSHL and collaborating clinicians that have approached us to support their efforts to further explore and understand the role of hNE in relation to ARDS in COVID-19,” said Kristina Sjöblom Nygren, MD, Chief Medical Officer and Head of Development of Santhera.

Lonodelestat (previously known as POL6014) is a highly potent and selective peptide inhibitor of human neutrophil elastase (hNE). In preclinical studies lonodelestat was effective in animal models of neutrophil activation in lung tissue and of acute lung injury (ALI). Lonodelestat is an investigational drug which completed Phase 1 single dose escalation studies in healthy volunteers and patients with cystic fibrosis (CF) and is currently investigated in a multiple ascending dose study in CF patients. Current data demonstrated that single dose inhalation of lonodelestat can lead to high drug concentrations within the lung, resulting in inhibition of hNE in sputum of patients, an enzyme associated with lung tissue inflammation.

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