NanoViricides, Inc. reported that the ultra-broad-spectrum antiviral NV-387, a clinical Phase II stage drug candidate, was found to be effective in protecting lungs from damage in a lethally infected Influenza A H3N2 mouse model. NV-387 Treatment Resulted in Significant Reduction in Lung Infiltration and Lung Cell Death. Lungs of infected animals treated with NV-387, orally or intravenously, showed very limited presence of infiltrating cell-killing immune cells that are known to be an important cause of lung damage, in addition to the direct lung damage from infected cell death caused by the virus itself.

Further, the overall lung damage was significantly reduced upon NV-387 treatment. On day 7 post-infection, NV-387 oral treatment resulted in only about 31% lung infiltration by immune system cells, and NV-387 intravenous treatment resulted in an even lower, about 22%, infiltration rate, whereas the lungs of infected untreated animals had a very high 68% infiltration rate (smaller is better), as determined by micro-histopathology of lung tissues using specific staining techniques. NV-387 Treatment Resulted in Significant Reduction in Mucus Load in the Lungs Additionally, the extent of mucus in the lung tissue was substantially reduced in the case of oral as well as intravenous NV-387 treatment.

The mucus index value in the case of NV-387 oral treatment was about 53, and for intravenous NV-387 treatment it was about 32, as compared to the infected untreated animals that had a mucus index value of 138 (smaller is better). Mucus is secreted by secretory cells in response to viral infection in an attempt to clear the virus, but it results in reduced lung capacity and eventually can lead to pneumonia. Thus reduction in mucus load is an important sign that the progress of the viral infection is arrested.

NV-387 Treatment Resulted in Significantly Greater Survival Improvement Compared to Three Approved Influenza Drug. Previously, we reported from this same animal study that NV-387 treatment led to substantially longer animal survival compared to the three approved influenza drugs, namely Oseltamivir (Tamiflu ®, Roche), Rapivab (Peramivir, BioCryst), and Baloxavir (Xofluza®, Shionogi, Roche). NV-387 treatment, both intravenous and oral, led to increase in survival of animals by a substantial 88% over the infected untreated controls, whereas the three approved drugs only increased survival marginally, by about 25% to 38%.

These results indicate that NV-387 was substantially superior to the three approved influenza drugs in this animal study. The above results demonstrate that NV-387 possesses strong antiviral activity against Influenza viruses. Viral Resistance to NV-387 is Unlikely as Opposed to Known Evolution of Viral Resistance Against Currently Approved Drugs.

Baloxavir resistant mutants were found to develop in as many as 10% of treated patients in its Phase III clinical trials. Oseltamivir resistant mutants are known and circulating, and they exhibit resistance to Peramivir as well. In contrast, even as influenza viruses mutate, they would be highly unlikely to escape NV-387.

This is because NV-387 is an ultra broad-spectrum antiviral that is designed as a host-mimetic. NV-387 Has Completed Phase I Human Clinical Trial. There were no reported adverse events, and there were no dropouts in the Phase I human clinical trial of NV-387, indicative of excellent safety and tolerability of NV-387.

This drug candidate is thus ready for further development in Phase II clinical trials. Host-Mimetic Nanoviricide Drug Candidate NV-387 is Designed to Attack Many Viruses; with Escape of Virus Unlikely. All influenza viruses bind to the host's sulfated proteoglycans ("S-PG") as primary attachment receptors and cellular sialic acids as cognate receptors; the latter enabling entry into cells.

NV-387 is designed to copy the invariant or conserved features of S-PG and present itself like a human cell decoy to the virus. As the virus binds to the NV-387 metamorphic ("shape-shifter") micelle, the NV-387 polymer chains are expected to wrap onto the virus surface, via a well known process called "lipid-lipid fusion", merging the lipid chains of the NV-387 polymer with the lipid coat of the virus particle. This is expected to result in destabilization of the virus, uprooting the H and N proteins from the virus surface, thereby making the virus incapable of attacking human cells.

A safe and effective antiviral drug that the virus would not escape by simple mutations or field evolution is the holy grail of antiviral drug development. We believe that the NanoViricides Platform technology meets this challenge.