Newly-Developed Enzyme Could Treat Mysterious Multisystem Complications of COVID-19

Scientists have developed a first-in-class DNASE1L3 enzyme analog, NTR-441, that has the potential to rapidly and systemically clear neutrophil extracellular traps (NETs) for severe cases of COVID-19.

The enzyme has been developed by Neutrolis (Cambridge, MA, USA), a biotechnology company developing therapeutics that target neutrophils, the most abundant immune cells in the body. NTR-441, an engineered analog of the natural NET-destroying enzyme DNASE1L3, is the world's first investigational drug that can be systemically delivered to accurately target NETs.

NETs are a fundamental arm of the immune system and play an important role in chronic and acute diseases. NETs are sticky, web-like structures made of chromatin—DNA studded with structural proteins—and expelled by suicidal neutrophils. NETs block air sacs and blood vessels in the lungs, trigger hyperinflammation and blood clotting (thrombosis), potentially causing irreversible end-organ damage and death.

Several independent investigators have observed NETs in the lungs of autopsied COVID-19 patients, and observed that NETs biomarkers in patient blood correlate with the clinical severity of COVID-19. In patients with severe COVID-19, the circulating levels of DNASE1L3 are not adequate to counteract the rapid and systemic formation of NETs. NTR-441 has the potential to systemically clear NETs in the vasculature and end organs like the lungs in patients suffering from severe COVID-19.

"We believe NETs are the common factor that explains the mysterious multisystem complications of COVID-19," said Toby Fox, Ph.D., Chief Executive Officer and Co-Founder of Neutrolis. "Our lead compound, NTR-441, and other molecules from our Chromatinase platform are the only drugs currently in development that could systemically remove NETs from the body. Thanks in part to competitive funding from the National Institutes of Health (R43HL150944), we will test whether NTR-441 is effective in ARDS, the most lethal manifestation of COVID-19."

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