The treatment has successfully eradicated SARS-CoV-2 virus from infected animals at a 100-fold lower dose than other COVID-19 monoclonal antibodies reported to date. It was jointly discovered at UAB and the Texas Biomedical Research Institute, San Antonio, and 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,” said Dr. Hasan Jafri, chief medical officer at Aridis. “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.”
Vu Truong, 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 said Aridis plans to evaluate the therapeutic treatment with the monoclonal antibody, called AR-711, in nonhospitalized, mild to moderate COVID-19 patients in a global study beginning in 2021.
The monoclonal antibody was discovered by research teams led by James J. Kobie, associate professor in the UAB Department of Medicine Division of Infectious Diseases, Mark Walter, professor in the UAB Department of Microbiology, and Luis Martinez-Sobrido, 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 six months or longer.
Details of the monoclonal antibody are in pre-publication in the BioRxiv repository. Aridis has announced that:
- AR-711 was originally known as monoclonal antibody 1212C2 by researchers at UAB and Texas Biomed. It is being developed by Aridis as an inhaled, self-administered treatment for nonhospitalized 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 nonhospitalized settings and at a scale not achievable using the conventional inpatient intravenous infusion treatments.
- In the animal challenge study, hamsters were infected with SARS-CoV-2 before a single inhalation exposure at three dose levels of AR-711. Efficacy was demonstrated as reduction or eradication of viral load in the nasal cavity and lungs at two and four days following treatment. AR-711 eradicated SARS-CoV-2 virus at all dose levels, with the lowest lung-deposited dose of approximately 0.03 milligrams per kilogram.
Co-authors of the BioRxiv post, “Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters,” are Michael Piepenbrink, UAB Department of Medicine, Division of Infectious Diseases; and Jun-Gyu Park and Fatai Oladunni, Texas Biomedical Research Institute.
Other authors, along with co-authors Kobie, Martinez-Sobrido and Walter, are Ashlesha Deshpande, Madhubanti Basu, Sanghita Sarkar, Nathaniel Erdmann and Paul Goepfert, UAB Department of Medicine, Division of Infectious Diseases; Andreas Loos, Jennifer Woo, Phillip Lovalenti, Derek Sloan and Truong, Aridis Pharmaceuticals; and Chengjin Ye and Kevin Chiem, Texas Biomedical Research Institute.