COVID-19


The most recently discovered coronavirus - SARS-CoV-2 - causes the current pandemic resulting in severe effects on global health and economy. The full clinical understanding of COVID-19 is not entirely known, but classic symptoms show respiratory symptoms with a dry cough, sore throat, high fever, fatigue, muscle pain, and breathing problems. Roughly, 80% recover from the disease without needing hospital treatment; unfortunately, some become seriously ill with pneumonia, kidney failure, multi-organ failure and even death. Older people and those with underlying medical problems seem to be more at risk of developing these critical conditions. Currently, only limited treatment options are available against COVID-19.

Our focus

UNION has developed a new treatment candidate (UNI91104) for COVID-19 that is currently in clinical testing. By delivering a novel formulation of niclosamide directly into the lungs via inhalation, high local exposures can be achieved to the pulmonary tissue eradicating virus particles. As the viral infection is largely driven by pulmonary infection, the UNI91104 pulmonary administration via inhalation can directly and efficiently target the disease while keeping systemic exposure low to avoid safety concerns. Niclosamide has a well-established safety profile as it has been used as an oral compound for decades and validated by UNION's years of research on the molecule and its deviates.

Mechanism of Action

Niclosamide is a compound with broad-spectrum antiviral efficacy and especially against SARS-CoV-2 by inhibiting viral replication. Recent studies have identified niclosamide as one of the most potent inhibitors of SARS-Cov-2 based on in vitro studies. One studie1 conducted by Institut Pasteur Korea, an infectious disease-focused non-profit research institute, identified niclosamide as the most potent FDA approved inhibitor of SARS-Cov-2 with >40x higher potency than remdesivir. Unfortunately, the oral FDA-approved formulation of niclosamide is not suitable for the treatment of SARS-CoV-2 due to its low systemic bioavailability. Hence an inhalation treatment targeting the central site of SARS-CoV-2 displays apparent potential and supported in a recent study2 that emphasizes the high potential of niclosamide, especially as an inhalation treatment.

Secondary pharmacology of niclosamide: Bronchodilatating and anti-inflammatory activity

In addition to the direct anti-viral effect, niclosamide exhibits bronchodilating and anti-inflammatory activity. Recent publications indicates that niclosamide dilatate the airways and ease chronic respiratory condition and asthma. Niclosamide has also been reported to suppress inflammatory states in vitro by modulating the activation of dendritic cells and repressing the expression of proinflammatory cytokines. This anti-inflammatory activity has been confirmed in UNION therapeutics sponsored clinical trials in patients with moderate atopic dermatitis.
These secondary activities of niclosamide could be beneficial in COVID-19 patients that can suffer from both excessive inflammatory response and airway constriction.

Publications

UNION has published a peer review article in The Lancet contributing to a better clinical understanding of COVID-19 pathology: Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: A systematic review and meta-analysis.


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