Humanigen Inc (OTCMKTS:HGEN) announced Monday that it is exploring clinical-stage strategies and partnerships to evaluate whether lenzilumab may reduce or prevent cytokine storm resulting from the coronavirus infection (COVID-19).
A recent pre-publication titled "Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus," supports the hypothesis that cytokine storm-induced immune mechanism have contributed to patient mortality with the current pandemic strain of coronavirus, according to a statement.
The severe clinical features associated with COVID-19 and other coronaviruses result from an inflammation-induced lung injury requiring intensive care unit (ICU) care and mechanical ventilation. This lung injury is a result of cytokine storm resulting from a hyper-reactive immune response. The lung injury that leads to death is not directly related to the virus but appears to be a result of a hyper-reactive immune response to the virus triggering a cytokine storm that can continue even after viral titers begin to fall.
The authors of the study assessed samples from patients with severe pneumonia resulting from COVID-19 infection to identify whether inflammatory factors such as GM-CSF, IL-6, IFN-gamma and TNF-alpha were implicated.
The authors noted that steroid treatment in such cases has been disappointing in terms of outcome, but suggest that a monoclonal antibody that targets GM-CSF may prevent or curb the hyperactive immune response caused by COVID-19.
Humanigen said it believes that the authors' findings are clearly worthy of further investigation, suggesting that to reduce or eradicate ICU care and prevent deaths from COVID-19 infection, an intervention may be needed to prevent cytokine storm.
Lenzilumab has been shown to prevent cytokine storm in animal models and this work has been published in peer-reviewed publications. Patients are soon expected to be enrolled in a clinical study to determine lenzilumab's effect on cytokine storm associated with the hyperactive immune response associated with CAR-T therapy in collaboration with Kite Pharma.
"These data confirm previously published data from the SARS and the MERS outbreaks, caused by strains of coronavirus different from the current COVID-19 strains, which indicated that severe pneumonia in SARS and MERS resulted from cytokine storm,” said CEO Dr Cameron Durrant.
“These new data also suggest that GM-CS F may be a critical triggering cytokine in the increased mortality in the current coronavirus pandemic. Humanigen has pioneered the field of GM-CSF neutralization and published data related to lenzilumab neutralization of GM-CSF and amelioration of cytokine storm in animal models. We have also completed two Phase I and two Phase II studies with lenzilumab, including in patients with severe respiratory impairment where lenzilumab demonstrated benefit."
Durrant continued: "We expect to commence patient enrollment in the joint Kite Pharma/Humanigen ZUMA-19 study to examine the impact of lenzilumab to reduce cytokine storm, amongst other measures, in the context of CAR-T. With our extensive intellectual property in GM-CSF neutralization, Humanigen is positioned to evaluate lenzilumab's potential role as part of a response to the coronavirus crisis and is actively exploring clinical-stage strategies and partnerships in this regard."
Contact the author: [email protected]
Follow him on Twitter @PatrickMGraham