A potentially best-in-class candidate for the prevention and treatment of COVID-19

UNION is developing niclosamide, a small molecule with potent and broad-spectrum anti-infective properties, initially in COVID-19 but with broader potential in other respiratory infections. Niclosamide has a host-targeting dual mode-of-action (MoA), which reduces viral replication in cells and helps cells to clear viruses through an increase in autophagic flux. Niclosamide has demonstrated a 40-fold higher in vitro potency against SARS-CoV-2 compared to remdesivir in preclinical studies undertaken during 2020 and has been demonstrated in vitro to be effective against a range of COVID-19 variants.

Niclosamide is a salicylanilide introduced into clinics in the early 1960s as an oral treatment for tapeworm infections and is currently marketed in several European and developing countries. Niclosamide in its oral form has poor systemic availability limiting its use as a treatment for respiratory viruses. Therefore, UNION has developed a concentrated liquid formulation of niclosamide that allows for delivery as a nasal spray to the upper respiratory tract (niclosamide nasal spray). For respiratory infections, such as COVID-19, this allows for a local delivery of niclosamide directly to the site of infection, either as a potential treatment or, prior to infection, as a prophylactic agent.

Mild-to-Moderate

+ 0 M

13,4M suffers from Psoriasis in the US, EU5 and Japan

PDE4 inhibitor

Dermatology market and include
topical roflumilast cream

PDE4 Market and include
topical roflumilast cream

Moderate-to-servere

= 0 M

People in the US suffer from Psoriasis

TNF-Q + 11-17

Plaque psoriasis and atopic
dermatitis

Acim quam ratem eos dis ma
doluptatist

Checkpoint-for Psoriasis

= 0 M

People in EU5 suffer from Psoriasis

Keratinoc

Exerting anti-inflammatory effect
reducing psoriasis scale formation

PDE4 Market and include
topical roflumilast cream

Niclosamide development programs

Niclosamide nasal spray a completed Phase 1 testing in healthy volunteers (ClinicalTrials.gov Identifier: NCT04576312) during 2020. The nasal spray has been selected for an ongoing COVID-19 platform study (PROTECT-V). 

  • PROTECT-V, led by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and funded by Kidney Research UK, LifeArc, Addenbrookes Charitable Trust, Kidney Research UK and UNION, is ongoing and was initiated in February 2021, and investigates the use of niclosamide nasal spray prophylaxis in immunocompromised populations (specifically kidney patients).
    ClinicalTrials.gov Identifier: NCT04870333 

 

The niclosamide nasal spray has potential also for post-exposure prophylaxis and early treatment of COVID-19, although this is not currently being tested in clinical trials.

Publications

Jurgeit et al. (2012): Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects, PLOS Pathogens

Weiss et al. (2020): Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: A systematic review and meta-analysis, EBioMedicine, a subjournal of The Lancet.  

Jeon et al.  (2020): Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs, ASM Journals

Backer et al. (2021): A randomized, double-blind, placebo-controlled phase 1 trial of inhaled and intranasal niclosamide: A broad spectrum antiviral candidate for treatment of COVID-19, The Lancet Regional Health Europe. 

Weiss et al. (2021): Niclosamide shows strong antiviral activity in a human airway model of SARS-CoV-2 infection and a conserved potency against the Alpha (B.1.1.7), Beta (B.1.351) and Delta variant (B.1.617.2), PLOS One.

Braga et al. (2021): Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia, Nature

Singh et al. (2022): Niclosamide – a promising treatment for COVID-19, British Journal of Pharmacology.

Weiss et al. (2022): Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial, Clinical and Translational Medicine.

Cairns et al. (2022): Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19, JAMA Network (specifically kidney patients).