NexBio, a US start-up biopharmaceutical company that specialises in developing antiviral agents, has pioneered the development of Fludase (DAS181), an innovative, recombinant drug for the treatment and prevention of influenza.
Fludase completed its initial preclinical development and entered clinical development to determine its efficacy and safety in humans.
In preclinical studies, Fludase displayed potent antiviral activity against clinical influenza isolates, including isolates of the deadly H5N1 strain of avian influenza.
NexBio's Fludase is a recombinant sialidase fusion protein composed of a sialidase catalytic domain derived from actinomyces viscosus, a constituent of the normal oral and gastrointestinal flora in humans, and a cell surface-anchoring domain.
In the human respiratory tract, cell surface sialic acids act as host cell receptors for influenza A and B viruses. Fludase works by removing sialic receptors from the airway epithelium, therefore preventing viral entry into cells of the respiratory epithelium.
As influenza viruses primarily invade cells of the upper and central respiratory tract, Fludase is administered through oral inhalation. The cell surface anchoring-domain of Fludase is designed to attach the sialidase to the respiratory epithelium, thereby increasing retention time and drug potency.
Preclinical in vitro and in vivo studies have shown that Fludase possesses potent antiviral and cell protective properties when combined with a long duration of action.
Prophylactic administration of Fludase significantly improved lung function, lung pathology and survival in mice subjected to influenza viral challenge.
In another in vivo model that closely resembles human influenza infection, administration of Fludase led to a significant inhibition of viral replication (viral shedding) accompanied by reduced signs of inflammation and illness. Crucially, there was no evidence that Fludase was toxic to respiratory cells.
Fludase appears effective in cleaving the sialic acid receptors that are used by both human and avian influenza viruses to invade respiratory epithelial cells. It represents a first-in-class influenza therapy and potentially an important new weapon in the fight against new strains of the influenza virus, including new avian strains.