In the reported year, we believe we have completed the IND-enabling pre-clinical drug development tasks pertaining to NV-CoV-2. Subsequently, we have received reports of all of the studies conducted externally. We have compiled the document called "Investigator's Brochure" pertaining to NV-CoV-2 that summarizes the developments and a potential clinical path for further discussion with a Clinical Research Organization (CRO).
We are now working on preparation of an Investigational New Drug (IND) application for filing with the US FDA. Our part of this application including primarily (i) Chemistry, Manufacture and Controls (CMC) information and (ii) Safety/Toxicology and Anti-viral Studies is substantially ready, and is being formatted into the appropriate IND formats. In addition, we are working on engaging a Clinical Research Organization (CRO) for completing the proposed clinical trials information section of the IND, and for executing the human clinical trials. Once this information is added to the IND application, we will be able to file the IND application.
Subsequent to the reported period, we have commissioned cGMP-compliant manufacture of the Drug Product formulations of NV-CoV-2 for use in the anticipated Phase 1 / 2 human Clinical trials.
We believe that NV-CoV-2 works by a novel mechanism of action, that of blocking the re-infection cycle of the viral disease. We believe that NV-CoV-2 not only binds to the virus, but fuses with the virus surface, uprooting the glycoproteins that are required for the virus to bind to the human cell (S protein, and its products S1 and S2 proteins), thereby rendering the virus incapable of infecting a cell. In contrast, antibodies are only capable of decorating the virus, generally incompletely.
In addition, as new variants have arisen a number of antibodies and antibody cocktails that have been developed and have received Emergency Use Authorizations (EUA) from the US FDA have had their EUA's revoked due to loss of effectiveness. The antibodies that continue to hold EUA are known to have significantly reduced activities against the newest Omicron variants that have begun to spread in the UK-Europe region, and are expected to reach the USA in a matter of months. We had clearly anticipated this problem of antibodies right at the beginning of the pandemic.
We developed NV-CoV-2 as a broad-spectrum, pan-coronavirus drug that is active not only against SARS-CoV-2, but also against other unrelated coronaviruses. As such, we believe it is highly unlikely that the generation of new variants of SARS-CoV-2 would allow the variant to escape NV-CoV-2. We believe this is exactly the kind of drug that is needed to combat the pandemic effectively and to be able to live with the virus, as a global society, as the SARS-CoV-2 virus is moving towards an endemic phase.
We were pleasantly surprised with the strong anti-viral effectiveness of orally administered NV-CoV-2 in our animal studies. We have therefore developed two oral formulations of this drug, (i) NV-CoV-2 Oral Syrup, and (ii) NV-CoV-2 Oral Gummies. We believe that these formulations should provide highly effective treatment of SARS-CoV-2 variant infection in mild to moderate COVID-19 cases.
Additionally, we have developed (iii) NV-CoV-2 Solution for Injection, Infusion and Inhalation. We believe that infusion of NV-CoV-2 solution formulation in hospitalized cases is likely to be one of the best available treatments for COVID-19. We plan on studying injection rather than infusion, for its simplicity, and applicability to out-patient treatment (i.e. without hospitalization), which would be highly useful in the underdeveloped world populations. We believe that a combination of NV-CoV-2 given by infusion together with NV-CoV-2 given by direct lung inhalation would be a highly effective protocol for the treatment of severe lung disease caused by SARS-CoV-2. The inhalation, performed with a simple hand-held device, would deliver high concentrations of the drug directly at the sites of viral injury in lungs, enabling the strongest possible attack on the virus.
In addition to the strong effectiveness, the strong safety that we have observed in multiple animal models is suggestive that NV-CoV-2 can be used for treating children as well as adults, potentially spanning the age range potentially from infants to over 80 years old patients. If so, NV-CoV-2 would be the only oral drug with applicability to the entire human population. In contrast, remdesivir (Veklury(R), Gilead) is approved only for hospitalized patients, and Paxlovid(R) (Pfizer) was recently found to be not effective in patients less than 65 years old patients with no existing co-morbidities.
In addition to NV-CoV-2 itself as a drug to combat COVID-19, we are also developing another SARS-CoV-2 drug candidate, NV-CoV-2-R, which encapsulates remdesivir inside NV-CoV-2. While remdesivir substantially blocks the replication of the virus inside cells, NV-CoV-2 is designed to block the virus outside cells by entrapping it and thereby not allowing it to infect the cells in the first place. Thus, NV-CoV-2-R is designed to block both the intra-cellular life cycle of the virus and the extra-cellular life cycle of the virus. Blocking both lifecycles should enable complete control of the viral disease, promising a potential cure. Remdesivir, sponsored by Gilead, is a known antiviral drug that has received full US FDA approved for treatment of COVID-19 and has received EUA in many countries. We are developing NV-CoV-2-R on our own, independently of Gilead.
We intend to develop NV-CoV-2 through Phase1/2a clinical trials first, and anticipate clinical development of NV-CoV-2-R thereafter.
NV-CoV-2 and NV-CoV-2-R were found to be highly effective against a totally lethal coronavirus lung infection in an animal model study in rats based on multiple indicators. Treatment with the standard remdesivir formulation extended lifespan by only 2 days, while treatment with NV-CoV-2 and NV-CoV-2-R extended the lifespan by 8.5 and 10.5 days respectively; an extremely significant improvement attesting to a very strong effectiveness of our drug candidates.
NV-CoV-2 was found to be effective in cell cultures against infection by several unrelated coronaviruses, including SARS-CoV-2 pseudovirions (see the Company's press release dated October 11, 2021 for details). These studies have established that both NV-CoV-2 and NV-CoV-2-R are broad-spectrum, pan-coronavirus drugs and therefore would remain effective even as variants emerge.
In animal studies, our drugs NV-CoV-2 and NV-CoV-2-R have both exceeded the effectiveness of remdesivir, which is approved for treatment of severe hospitalized cases of COVID-19, and has shown substantial clinical benefit in clinical trials in moderate to severe COVID-19 patients. If the strong effectiveness of NV-CoV-2 and NV-CoV-2-R observed in animal studies is borne out in human clinical trials, then our drugs would be substantially more effective than existing therapies.
Previously, the Company has completed pre-clinical development of its lead drug candidate for the treatment of shingles rash, namely, NV-HHV-101. The Company intends to re-engage this program with filing an IND and performing clinical trials for NV-HHV-101 regulatory approvals after our COVID-19 program.
“The two most powerful warriors are patience and time.” - Leo Nikolaevich Tolstoy
