Monoclonal antibodies for COVID-19 recently took center stage as Regeneron’s experimental cocktail was used to treat President Donald Trump, who went on to rave about it. But that therapy, as is typical for antibody drugs, needs to be injected into the body.
Aridis Pharmaceuticals is working on an inhaled neutralizing antibody for COVID-19 dubbed AR-711, which was discovered using samples from patients who had recovered from COVID-19. The drug successfully cleared signs of SARS-CoV-2 virus from infected hamsters at a far lower dose compared with other experimental monoclonal antibodies, according to results published on preprint site bioRxiv.
Encouraged by the preclinical results, Aridis plans to start testing AR-711 in non-hospitalized mild-to-moderate COVID-19 patients in the first half of next year. If the drug eventually succeeds in human trials, the company could offer a self-administered option for COVID-19, saving patients the need to travel to healthcare facilities for infusions that could take hours to complete.
“Over 90% COVID-19 symptomatic patients are home-bound, under quarantine, and often not treated. While these patients wait, their health can deteriorate, and they could infect those around them,” Aridis CEO Vu Truong, Ph.D., said in a statement. “Having a convenient way to self-medicate with the simplicity of an asthma inhaler where the drug is delivered directly to the infection site can have a transformative impact on patients' lives, expand treatment coverage, and ultimately reduce global transmissibility.”
Most antibodies and vaccines that are being developed by drug companies target the receptor-binding domain (RBD) of the novel coronavirus’s spike protein. This small part plays an important role in viral infection, as it docks to the ACE2 receptors on human cells to gain entry.
A team of scientists from the University of Alabama at Birmingham and the Texas Biomedical Research Institute isolated RBD-specific B cells from recovered patients to produce monoclonal antibodies that can neutralize SARS-CoV-2, the virus that causes COVID-19. One candidate, 1212C2, emerged with potent inhibition of RBD binding to ACE2.
Recent research has shown hamsters to be a good model for COVID-19-related research. So the researchers injected the antibody into hamsters’ abdomens before challenging the animals with SARS-CoV-2.
While control hamsters developed live virus in their nasal cavities and lungs, animals that got 1212C2 before the challenge showed a meaningful viral load reduction after two days, and three of four animals eradicated the virus after four days. The treated hamsters also experienced significantly less lung disease compared with control rodents.
The scientists further modified 1212C2 to increase its half-life and used a proprietary technology to stabilize it to allow for delivery with a nebulizer.
In hamsters, the inhaled version cleared COVID-19 in the lungs of all animals after four days, while all control hamsters had detectable virus in their lungs at that time point. Lung lesions were also significantly decreased in 1212C2-treated hamsters compared with those in the control group.
Injection is the typical approach for administering monoclonal antibodies, but usually less than 0.1% of the injected dose makes it into the fluid lining the lung. That makes it an inefficient delivery vehicle for respiratory infections such as COVID-19, the researchers argue.
Several other teams are exploring inhaled drugs to treat COVID-19. A team led by scientists at the University of Pittsburgh School of Medicine recently developed a drug that’s based on an antibody component 10 times smaller than a full-sized antibody. The drug blocked SARS-CoV-2 in hamsters, and a startup called Abound Bio is looking to move the candidate into clinical trials as an inhaled therapy.
U.K. biotech Synairgen, meanwhile, recently said its inhaled formulation of interferon beta, called SNG001, cut the risk of developing severe COVID-19 by 79% compared to placebo among patients in a double-blind trial. Patients who got the drug were also more than twice as likely to recover from COVID-19.
Gilead Sciences is also testing an inhalable form of its COVID-19 drug remdesivir after the infused version showed it could cut recovery time for hospitalized patients. The hope is that the inhaled formulation could reach less severely ill patients outside the hospital setting.
One potential advantage of Aridis' drug is its dosing. The lowest dose that cleared the virus in hamsters corresponded to an estimated human equivalent strength of 2 mg to 6 mg. “This compares very favorably to other clinical stage COVID-19 mAbs, where up to 8,000 mg are being studied to achieve clinical benefit,” Hasan Jafri, M.D., chief medical officer of Aridis, noted in a statement.
“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,” Truong said.
The company is also pairing AR-711 with another antibody in a cocktail dubbed AR-701, which is being developed as an intravenous treatment for moderate-to-severe hospitalized COVID-19 patients.