Eureka Therapeutics’ InvisiMask™ Human Antibody Nasal Spray can provide 10 hours of protection from SARS-CoV-2 virus in animal models, according to preclinical results released today. Now it’s heading to clinical trials.
Photo courtesy of Eureka Therapeutics.
Eureka Therapeutics’ InvisiMask™ Human Antibody Nasal Spray can provide 10 hours of protection from SARS-CoV-2 virus in animal models, according to preclinical results released today. Now it’s heading to clinical trials.
Importantly, the nasal spray is designed as an over-the-counter, at-home prophylactic against COVID-19. As such, it protects users by neutralizing the SARS-CoV-2 virus from airborne droplets and particles in the nasal cavity.
“We envision a daily nasal spray that functions like an invisible mask in slowing the spread of COVID-19,” said Cheng Liu, Ph.D., President and CEO of Eureka Therapeutics.
The company envisions the InvisiMask nasal spray as a complement to vaccines, therapeutics and other preventive measures such as face masks.
“While vaccines and therapeutics have many benefits, they also have shortcomings. In the case of vaccines, the recipient’s immune system needs to mount an effective immune response upon vaccination to provide protection. This may not be the case for everyone, and not everyone (i.e. people with severe allergies) is suitable to be vaccinated,” Liu said. “Moreover, it is still undetermined how long the protection from infection lasts after vaccination with the various SARS-CoV-2 vaccines.”
InvisiMask is designed to provide an additional layer of protection, even after someone has been vaccinated. Therapeutics, on the other hand, are given to people only after they have become infected with the virus.
This platform technology could play an important role in helping life return to normal, even after vaccines become widely available.
“You want to go out, so you wear a face mask and spray InvisiMask into each nostril to provide additional protection. It takes only a few seconds. The antibody stays in the nasal cavity and protects you from SARS-CoV-2,” Liu told BioSpace.
In the study, mice receiving the lowest dose – 25 μg – received at least 10 hours of protection despite being exposed to the highest viral load (107 virus particles administered intra-nasally). The mice had no infections in the nasal cavity or the lungs even seven days after being dosed with the SARS-CoV-2 pseudovirus. No adverse events were observed.
This is promising news, despite being preclinical data. If InvisiMask is successful in human trials, it provides another layer of security in addition to face masks, social distancing and vaccines. It is not a therapeutic, however.
“We decided, instead of focusing on therapeutics, to prevent the virus from entering the body in the first place,” Liu said.
Therefore, InvisiMask could be used in situations in which masks are impractical (like playing sports), as a complement to vaccines, or as a precaution for at risk populations (such as the elderly, immunocompromised patients, and young children), and those who do not respond well to vaccines.
InvisiMask is a proprietary, engineered human antibody nasal spray that delivers SARS-CoV-2 neutralizing antibodies directly to the nasal passages, where most COVID-19 infections enter the body.
The compound combines the best properties of IgG and IgA. IgG is easy to manufacture but has a shorter half-life in the mucosa. By engineering IgG antibodies to bind to mucins (as does IgA) in the airway epithelium, their half-lives in the mucosa were extended while maintaining its ability to be scaled up easily for commercial manufacturing.
“Mucin glycoproteins, produced by the mucus-producing cells in the epithelium or submucosal glands, are the major macromolecular constituent of mucus,” the paper explained. Eureka scientists hypothesized that binding to mucin – essentially, to mucus – would help the InvisiMask remain in the respiratory tract mucosa.
The molecule features a genetically-engineered Fc domain to increase its binding affinity to mucin, thus extend the retention time of the antibody in the mucosa. The modified antibody retains its high binding affinity to the S1 spike protein of SARS-CoV-2 and thus prevent the virus from binding to the ACE2 receptors on cells, infecting them and triggering an infection. It also neutralizes the viral infection.
“Compared to unmodified antibody, InvisiMask using Fc-engineered antibody showed higher in vitro potency in blocking viral infection in cell-based assays. Furthermore, InvisiMask also demonstrated in vivo protection of hACE2-transgenic mice from SARS-CoV-2 pseudovirus virus infection when administered intranasally,” Liu said.
As the paper noted, “The EU126 clone (InvisiMask) can efficiently inhibit pseudoviral infection of the hACE2-expressing 293F cells. Furthermore, EU126 can bind to various mutated forms of the S1 spike protein, as well as inhibit their binding to hACE2. The S1 protein mutations tested include that of the most infectious strain, SARS-CoV-2 D614G.”
In tests, the compound bound to and inhibited more than 20 SARS-CoV-2 variants, including the highly infectious D614G mutation. Users, therefore, will be protected from infection even as the virus changes.
Compared to a therapeutic, the dosage for a nasal spray is approximately 10,000 times less, which makes manufacturing more efficient and expands access.
“Our goal is to make InvisiMask available over the counter for self-administered, at-home use,” Liu said.
“It’s important not to cause immunogenicity,” he continued. Therefore, Eureka used a human antibody rather than an animal-derived antibody or foreign peptide as the spike protein binder to reduce the risk of adverse effects.
InvisiMask is expected to be safe to use daily for months at a time, or longer, to neutralize coronavirus.
At this point, it is stable for two weeks in a nasal spray formulation when stored at 37°C (98.6°F), and much longer when stored at room temperature. No special conditions are required for distribution, therefore.
Eureka is preparing an Investigational New Drug application for the FDA. That agency recently granted Emergency Use Authorization (EUA) to use anti-SARS-CoV-2 antibodies intravenously as therapeutics for COVID-19 patients. Eureka hopes to initiate human trials in early 2021.
