Inhaled Antibody from Convalescent COVID-19 Patients Could Be More Potent Treatment for SARS-Cov-2 Lung Infection

Positive preclinical efficacy data of a highly effective inhaled treatment has lent support to a proposed self-administered therapy for COVID-19 patients that could be more potent than injected monoclonal antibodies in treating those suffering from lung infection due to the SARS-Cov-2 virus.

Aridis Pharmaceuticals (San Jose, CA, USA) has developed a highly neutralizing monoclonal antibody AR-711, discovered from convalescent COVID-19 patients, that successfully eliminated all detectable SARS-CoV-2 virus in infected animals at substantially lower doses than parenterally administered (injected) COVID-19 monoclonal antibodies (mAb). The potency of AR-711 and its direct delivery to the lungs by inhaled administration may facilitate broader treatment coverage and dose sparing not achievable by parenteral administration.

AR-711 is a fully human immunoglobulin 1, or IgG1, monoclonal antibody discovered from screening the antibody secreting B-cells of convalescent COVID-19 patients. It exhibits high affinity for SARS-CoV-2 spike protein, approximately 10-fold or higher than mAb candidates currently in late stage clinical testing. AR-711 is directed against the conserved receptor-binding domain (RBD) region of the original SARS-CoV2 virus and its newly emerging variants including the currently prevalent strain G614. The monoclonal antibody is engineered to be long-acting in blood for up to six to 12 months.

AR-711 is stabilized using a proprietary formulation designed to protect the mAb from the physical stresses imparted by commercial nebulizer delivery devices on protein drugs. 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 conventional inpatient IV infusion treatments.

In the animal challenge study, golden Syrian hamsters were pre-infected with SARS-CoV-2 before a single inhalation exposure of AR-711 liquid aerosols. AR-711 eliminated detectable SARS-CoV-2 virus at all dose levels tested, with the lowest lung deposited dose of 0.03 mg/kg.

"As we expected, combining a highly potent monoclonal antibody with direct delivery to the lungs, which is the main target of the COVID-19 virus, achieved impressive efficacy in these animal models. The therapeutic dose that we observed corresponds to an estimated adult human equivalent efficacious inhaled dose of 2 to 6 milligrams (mg) per dose. This compares very favorably to other clinical stage COVID-19 mAbs, where up to 8,000 mg are being studied to achieve clinical benefit," said Hasan Jafri, M.D., Chief Medical Offer of Aridis.

"The exceedingly low drug dose that achieved therapeutic efficacy is particularly exciting, as it provides a unique opportunity to meaningfully reduce treatment costs and hospitalization burden at a potential magnitude not previously achievable with mAb therapies. We are excited to bring an entirely new treatment paradigm to the COVID-19 fight," said Vu Truong, Ph.D., Chief Executive Officer of Aridis Pharmaceuticals.

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