Roivant Sciences has engaged with regulators in the United States, Europe, and Asia to rapidly advance the clinical development of gimsilumab for the treatment of acute respiratory distress syndrome (ARDS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Gimsilumab is a clinical-stage, fully human monoclonal antibody targeting granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF is a pro-inflammatory cytokine found to be up-regulated in the serum of COVID-19 patients according to recent data from patients in China. The percentages of GM-CSF-expressing CD4+ T cells (Th1), CD8+ T cells, NK cells, and B cells have been observed to be significantly higher in the blood of ICU-admitted COVID-19 patients when compared with healthy controls. These reported immunological changes also appear to be more pronounced in ICU-admitted COVID-19 patients versus non-ICU patients.

GM-CSF boosts the expression of pro-inflammatory cytokines such as TNF, IL-6, and IL-23 in addition to promoting the differentiation of Th1/17 cells and the polarization of macrophages to a M1-like phenotype3. Increased levels of GM-CSF result in positive feedback which further elevates these inflammatory mediators. In severe patients infected with COVID-19, it has been suggested that GM-CSF could be the key link between the 'pulmonary syndrome-initiating capacity' of pathogenic The cells and the feedback loop of inflammatory monocytes – which in turn secrete additional GM-CSF and IL-62. Taken together with the differentially elevated levels of GM-CSF observed in seriously ill COVID-19 patients, GM-CSF's breadth of activity and its potential role as a central driver of pathology make it a promising target for clinical research.

"Up-regulation of GM-CSF appears to characterize progression to ARDS and death in COVID-19," said Dr. Elizabeth Volkmann, founder and co-director of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease Program. "Targeting GM-CSF represents a promising strategy for curbing lung damage while allowing time for the virus to clear. It is my hope that gimsilumab will reduce mortality from COVID-19 and help improve the lives of those affected by this emerging public health crisis."

Gimsilumab has been tested in numerous non-clinical studies and two clinical studies, including a 4-week Phase 1 study of a subcutaneous formulation in healthy volunteers conducted by Roivant which completed dosing last month. Gimsilumab has demonstrated a favorable safety and tolerability profile based on data collected to date, with no serious adverse events reported.

Roivant will prioritize trials of gimsilumab in patients with COVID-19 instead of a Phase 2 trial in a separate disease area which had been previously planned. Clinical trials of gimsilumab in patients with COVID-19 will commence upon approval by relevant regulatory authorities.

COVID-19 is an infectious disease caused by SARS-CoV-2. COVID-19 has become a global pandemic, with over 200,000 confirmed cases and over 8,000 deaths reported to date. Patients with severe cases of COVID-19 experience severe viral pneumonia that can progress to acute respiratory distress syndrome (ARDS) and death.

ARDS is an acute, life-threatening inflammatory lung injury characterized by hypoxia – a lack of oxygen to the tissue – and stiff lungs due to increased pulmonary vascular permeability. ARDS necessitates hospitalization and mechanical ventilation. A rapid increase in patients with ARDS presents a major challenge for the global public health system given limited hospital beds and ventilators. When implementing standard of care, including mechanical ventilation, ARDS has an overall mortality rate of 41%6.

Gimsilumab is a clinical-stage, fully human anti-granulocyte-macrophage colony stimulating factor (GM-CSF) monoclonal antibody. GM-CSF is a cytokine implicated in many autoimmune disorders that acts as a pro-inflammatory signal, prompting macrophages to launch an immune cascade that ultimately results in tissue damage.

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