New inhaled treatment may lead to self-administered therapy for COVID-19

An inhaled treatment against the SARS-CoV-2 virus may lead to a future self-administered therapy for COVID-19, the pandemic that has killed more than 1 million people worldwide.

The highly neutralizing fully human monoclonal antibody treatment has successfully eradicated the SARS-CoV-2 virus from infected animals at a greater than 100-fold lower dose than other COVID-19 monoclonal antibodies reported to date.

It was jointly discovered at the University of Alabama at Birmingham and the Texas Biomedical Research Institute, San Antonio, and it has been licensed for development to Aridis Pharmaceuticals Inc., San Jose, California.

Combining a highly potent monoclonal antibody with direct delivery to the lungs, which are the main target of the COVID-19 virus, achieved impressive efficacy in animal models. The therapeutic dose we observed corresponds to an estimated adult human equivalent efficacious dose of 1 to 3 milligrams. In contrast, other clinical stage COVID-19 monoclonal antibodies require up to 8,000 milligrams to achieve clinical benefits."

Hasan Jafri, MD, Chief Medical Officer, Aridis

Vu Truong, Ph.D., CEO of Aridis, noted that most COVID-19 patients are homebound, often with no treatment options. "Having a convenient way to self-medicate -; with the simplicity of an asthma treatment, where the drug is delivered directly to the infection site -; can have a transformative impact on the lives of patients, including their morbidity and mortality, treatment coverage, and ultimately reduction in transmissibility," Truong said.

Jafri says Aridis plans to evaluate the therapeutic treatment with the monoclonal antibody, called AR-711, in non-hospitalized, mild to moderate COVID-19 patients in a global study, beginning in the first half of 2021.

The monoclonal antibody was jointly discovered by research teams led by James J. Kobie, Ph.D., associate professor in the UAB Department of Medicine Division of Infectious Diseases, Mark Walter, Ph.D., a professor in the UAB Department of Microbiology, and Luis Martinez-Sobrido, Ph.D., a professor at the Texas Biomedical Research Institute.

Aridis Pharmaceuticals, a biopharmaceutical company focused on the discovery and development of novel anti-infective therapies to treat life-threatening infections, developed the proprietary stabilized formulation for the inhaled treatment and engineered the molecule to be long-acting, so that it can remain effective for up to 6 months or longer.

Details of the monoclonal antibody are in pre-publication in the BioRxiv repository. Aridis has announced that:

• AR-711 is directed against the conserved receptor-binding domain region of the original SARS-CoV-2 virus and its newly emerging variants, including the currently prevalent strain G614.

• AR-711 was originally known as monoclonal antibody 1212C2 by researchers at UAB and Texas Biomed. It is currently being developed by Aridis as an inhaled, self-administered treatment for non-hospitalized patients suffering from mild to moderate COVID-19.

• An inhalable treatment that can be self-administered using a wide variety of commercially available nebulizers can facilitate broader coverage in non-hospitalized settings and at a scale not achievable using the conventional inpatient intravenous infusion treatments.

• In the animal challenge study, golden Syrian hamsters were pre-infected with SARS-CoV-2 before a single inhalation exposure at three dose levels of AR-711. Efficacy was demonstrated as a reduction or eradication of viral load in the nasal cavity (turbinates) and lungs at two and four days following treatment. AR-711 eradicated the SARS-CoV-2 virus at all dose levels, with the lowest lung-deposited dose of approximately 0.03 milligrams per kilogram.

In other details, the monoclonal antibody has a high affinity for the SARS-CoV-2 protein with a dissociation constant of 104 picomolar, and it has a 50 percent neutralizing titer against the live SARS-CoV-2 virus of 32 nanograms per milliliter in vitro.

Journal reference:

Piepenbrink, M. S., et al. (2020) Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters. BioRxiv.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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