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 predominant symptoms include respiratory symptoms with a dry cough, sore throat, high fever, fatigue, muscle pain, and breathing problems. Roughly, 80% of COVID-19 population is asymptomatic or recovers from the disease without needing hospitalization. Unfortunately, some people become seriously ill with pneumonia, kidney failure, multi-organ failure and even death. Older people and those with comorbidities are more at risk of developing severe COVID-19. Currently, only limited treatment options are available against COVID-19.

Our focus

Niclosamide has a well-established safety profile having been used as an oral compound for decades and validated by UNION's years of research on the molecule and its derivatives. Unfortunately, the oral FDA-approved formulation of niclosamide is not suitable for the treatment of SARS-CoV-2 due to its low bioavailability. Hence, UNION has developed its novel formulation to circumvent this issue.

Our new treatment candidate (UNI91104 and UNI91103) for COVID-19 is currently in clinical testing. By delivering a novel formulation of niclosamide directly to the lungs via inhalation and the nasal cavity via a nasal spray, high local exposures can be achieved where the viral burden is the greatest. As the primary site of viral infection occurs along the respiratory tract, UNI91104 administered intranasal and via inhalation can limit viral replication at clinically relevant target tissues while keeping systemic exposure low to reduce the risk of side effects.

Mechanism of Action

Niclosamide is a compound with broad-spectrum antiviral efficacy. Recent studies have identified niclosamide as one of the most potent inhibitor of SARS-Cov-2 in an in vitro compound screen. One study1 conducted by Institute 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. Niclosamide’s great potential as a promising treatment candidate has been emphasized in a recent in vivo study. Further studies showed that niclosamide acts on mechanisms of the human cell to prevent viral replication suggesting it might also be effective against emerging variants of SARS-CoV-2.

·   1https://www.biorxiv.org/content/10.1101/2020.03.20.999730v2.full.pdf

·   2https://www.biorxiv.org/content/10.1101/2020.09.24.310490v1

Secondary pharmacology of niclosamide: Bronchodilatating and anti-inflammatory activity

In addition to the direct antiviral effect, niclosamide exhibits bronchodilating and anti-inflammatory activity. Recent publications indicate that niclosamide dilate the airways and ease chronic respiratory conditions and asthma. Niclosamide has also been reported to suppress inflammatory cells 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's Phase 1 results in Lancet publication: https://www.sciencedirect.com/science/article/pii/S2666776221000612

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


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