Broad-Spectrum Antiviral NV-387 (NV-CoV-2) in Phase 1a/1b Clinical Trial is Highly Effective in an Animal Model for MPox and Smallpox Drug Development

SHELTON, CT / ACCESSWIRE / November 14, 2023 / NanoViricides, Inc. (AMEX:NNVC) (the "Company"), a leader in the development of highly effective antiviral therapies based on a novel nanomedicines technology, reports that its broad-spectrum antiviral drug candidate, NV-387 was highly effective in an animal model that is used in drug development for MPox and Smallpox virus infections in humans.

NV-387 is currently in Phase 1a/1b human clinical trials for COVID-19 indication in India, under sponsorship by our licensee and collaborator, Karveer Meditech, Pvt. Ltd. In addition to broad-spectrum activity against Seasonal Coronaviruses and SARS-CoV-2, NV-387 was previously found to have strong activity against the Respiratory Syncytial Virus (RSV) that was comparable to the last-resort toxic drug Ribavirin. The current study indicates that NV-387 is active against viruses in the genus of Orthopoxviruses as well.

We believe that this broad-spectrum antiviral activity of NV-387 is observed because NV-387 is designed to mimic a host cell membrane bearing "Sulfated Proteoglycans" ("S-PG") family of virus attachment receptors. S-PG receptors taken together are involved in the re-infection lifecycle of more than 90% of human pathogenic viruses.

Thus, we believe that NV-387 has a broad spectrum of antiviral activity that is reminiscent of the antibacterial activity of antibiotics. We believe that the Nanoviricides Platform Technology is poised to revolutionize the fight against viruses just as antibiotics revolutionized the fight against bacterial infections.

Oral NV-387 treatment led to 14 days of survival, matching the 14 days survival on oral Tecovorimat treatment. In contrast, untreated and vehicle-treated animals died in only 8 days, indicating an increase of 6 days, or 75%, in the lifespan for both NV-387 and Tecovirimat, in this lethal model comprising intra-digital infection by the Ectromelia virus into the footpads of mice. Moreover, a formulation combining NV-387 and Tecovirimat, that we call NV-387-m-T, led to a significantly greater survival of 17 days, indicating an impressive increase of 9 days, or 112%, in survival lifespan, in this study. The increase in lifespan in comparison to the untreated animals in such lethal virus infection models serves as a clear primary endpoint indicative of the relative effectiveness of different drugs.

Tecovirimat ("TPOXX^®", SIGA Pharmaceuticals) is an approved smallpox therapeutic. It was mobilized from the US Government stockpile for the treatment of Mpox infection during the recent MPox epidemic. Additional therapeutics that work with Tecovirimat such as NV-387 may reduce the required dosage and dosing period enabling rapid patient recovery.

"We believe that non-dilutive government funding may be possible for the development of a NV-387-based drug for the treatment of Smallpox and Mpox, given these excellent results," said Anil R. Diwan, PhD.

Smallpox-causing Variola virus is considered a significant biodefense threat. While smallpox vaccines are available, their general public health usage has stopped after Smallpox was declared eradicated in 1980, leaving persons under the age of about 45 vulnerable.

Tecovirimat is stockpiled by the Biomedical Advanced Research and Development Authority (BARDA) under Project BioShield. BARDA awarded an original development and procurement contract worth approximately $435 million to SIGA in 2011, followed by another procurement contract in 2018 upon regulatory approval worth approximately $629 million. SIGA announced in July 2023 that it has received new procurement orders of approximately $138 Million for TPOXX from the U.S. Government.

There is significant interest in the development of a smallpox therapeutic drug that works well by itself, as well as in combination with the known drug, Tecovirimat. Tecovirimat has a low barrier of escape; a single mutation in one protein can enable the virus to escape this drug, adding to the significance of additional smallpox drug development.

Since human clinical trials are not feasible for the deadly Variola virus, infection of the related animal viruses in their native species is used for evaluation of drug effectiveness under the FDA "Animal Rule". Variola (Humans), Mpox (Monkeys), Ectromelia (Mice), and Rabbitpox (Rabbits) are some of the closely related pathogenic viruses belonging to the Orthopoxvirus genus (with their native hosts listed in parentheses).

The animal-rule based efficacy studies conducted under GLP conditions substitute for the usual Phase 2/3 human clinical efficacy trials for regulatory approval under the Animal Rule. Additional human safety clinical studies are expected to be required. This pathway may enable rapid regulatory development of NV-387 as a smallpox therapeutic towards approval.

Previously, the Company has reported that NV-387 was highly effective for the treatment of lethal lung infection by the Respiratory Syncytial Virus (RSV). Currently there is no approved treatment for RSV other than ribavirin which is only conditionally approved only for patients with high risk of progressively severe RSV disease, due to significant side effects including hemolytic anemia and kidney failure.

RSV therapeutics is estimated to be a multi-billion-dollar market, as we have previously reported.

We believe that NV-387 works by a novel mechanism of action, that of blocking the re-infection lifecycle of the virus. We believe that NV-387 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 (for example, the S protein, and its products S1 and S2 proteins for coronaviruses), thereby rendering the virus incapable of infecting a cell. In contrast, antibodies are only capable of incompletely decorating the virus.

We believe that NV-387 mimics the "Sulfated Proteoglycans" ("S-PG") family of virus attachment receptors. This family includes heparan sulfate (HSPG), dermatan sulfate (DSPG), chondroitin sulfate (CSPG), and keratan sulfate (KSPG). Over 90% of known pathogenic viruses bind to one or more of these S-PG class attachment receptors. These viruses include Coronaviruses, Paramyxoviruses (RSV - Respiratory Syncytial Virus, and HMPV- human Metapneumovirus), Dengue Viruses, Herpesviruses, Human Papillomavirus (HPV), HIV, Hendra and Nipah Viruses, Ebola and Marburg Viruses, Poxviruses, among others. Therefore, NV-387 may be anticipated to exhibit strong antiviral activity against at least some, if not many, of these viruses.

We believe that the successes of NV-387 as a broad-spectrum antiviral bode well for validating the multiple modalities in which our Nanoviricides Platform Technology can be employed to revolutionize the treatment of viral infections as well as pandemic preparedness response.

We have found that NV-387 is highly active against tested coronaviruses including SARS-CoV-2 in pre-clinical studies. We are continuing to expand our pre-clinical studies to evaluate the antiviral activity of NV-387 against other viruses. We believe that this work would expand the range of indications for NV-387. Such expansion of use of NV-387 would significantly expand the market size and substantially improve the return on investments (ROI).

NV-387 is in Phase 1 human clinical trial as two oral formulations: (i) NV-CoV-2 Oral Syrup, and (ii) NV-CoV-2 Oral Gummies in India. The drug sponsor, Karveer Meditech Pvt. Ltd., is our licensee and collaborator and has the rights to develop and commercialize the drugs in India. As of now, 26 out of a target of 36 healthy human subjects have completed the clinical trial. There were no reports of adverse events or serious adverse events, indicating both of these formulations and the API NV-387 are extremely safe in humans. These results are consistent with our pre-clinical safety/toxicology animal studies.

What is a "nanoviricide"?

A "nanoviricide" is a uniform polymer that self-assembles into nanoscale droplets called "micelles", that carries on its surface mimics of the cell-side receptor of the virus, and that hides in its belly lipid tentacles. It can also hold other guest APIs in its belly if needed. The nanoviricide thus "looks like" a cell to the virus, and the virus is fooled into binding it. Once the virus binds, we believe, the flexible and shape-shifting nanoviricide micelle would spread over the virus particle by virtue of merging the lipid tentacles that are hidden in its belly into the virus surface, in a well known process called "lipid-lipid mixing." We believe this would destabilize the virus particle, uproot the viral glycoproteins required for binding to and entering the host cell, and thus render the virus particle incapable of infecting a cell.

About NanoViricides, Inc.

NanoViricides, Inc. (the "Company") (www.nanoviricides.com) is a development stage company that is creating special purpose nanomaterials for antiviral therapy. The Company's novel nanoviricide^® class of drug candidates are designed to specifically attack enveloped virus particles and to dismantle them. Our lead drug candidate is NV-CoV-2 (API NV-387) for the treatment of COVID-19 disease caused by SARS-CoV-2 coronavirus. Our other advanced candidate is NV-HHV-1 for the treatment of Shingles. The Company cannot project an exact date for filing an IND for any of its drugs because of dependence on a number of factors including external collaborators and consultants. NV-CoV-2 is currently in Phase 1a/1b clinical trial sponsored by our licensee and collaborator, Karveer Meditech, Pvt. Ltd., India.

NV-CoV-2 is our nanoviricide drug candidate for COVID-19 containing the nanoviricide API, NV-387. NV-387 is a broad-spectrum antiviral with strong effectiveness against SARS-CoV-2, seasonal Coronavirus, RSV, Orthopoxviruses, and possibly many other viruses.

NV-CoV-2 does not contain remdesivir. NV-CoV-2-R is our other drug candidate for COVID-19 that is made up of NV-387 with remdesivir encapsulated within its polymeric micelles. The Company believes that since remdesivir is already US FDA approved, our drug candidate encapsulating remdesivir is likely to be an approvable drug, if safety is comparable. Remdesivir is developed by Gilead. The Company has developed both of its own drug candidates NV-CoV-2 and NV-CoV-2-R independently.

The Company is also developing drugs against a number of viral diseases including RSV, oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others. NanoViricides' platform technology and programs are based on the TheraCour^® nanomedicine technology of TheraCour, which TheraCour licenses from AllExcel. NanoViricides holds a worldwide exclusive perpetual license to this technology for several drugs with specific targeting mechanisms in perpetuity for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Rabies, Herpes Simplex Virus (HSV-1 and HSV-2), Varicella-Zoster Virus (VZV), Influenza and Asian Bird Flu Virus, Dengue viruses, Japanese Encephalitis virus, West Nile Virus, Ebola/Marburg viruses, and human Coronaviruses. The Company intends to obtain a license for poxviruses, RSV, enteroviruses, and others as and when the Company determines to further advance the drug development opportunity, if the initial research is successful. The Company's technology is based on broad, exclusive, sub-licensable, field licenses to drugs developed in these areas from TheraCour Pharma, Inc. The Company's business model is based on licensing technology from TheraCour Pharma Inc. for specific application verticals of specific viruses, as established at its foundation in 2005.

As is customary, the Company must state the risk factor that the path to typical drug development of any pharmaceutical product is extremely lengthy and requires substantial capital. As with any drug development efforts by any company, there can be no assurance at this time that any of the Company's pharmaceutical candidates would show sufficient effectiveness and safety for human clinical development. Further, there can be no assurance at this time that successful results against coronavirus in our lab will lead to successful clinical trials or a successful pharmaceutical product.

This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. Actual events could differ materially and substantially from those projected herein and depend on a number of factors. Certain statements in this release, and other written or oral statements made by NanoViricides, Inc., are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. The Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. Important factors that could cause actual results to differ materially from the Company's expectations include, but are not limited to, those factors that are disclosed under the heading "Risk Factors" and elsewhere in documents filed by the company from time to time with the United States Securities and Exchange Commission and other regulatory authorities. Although it is not possible to predict or identify all such factors, they may include the following: demonstration and proof of principle in preclinical trials that a nanoviricide is safe and effective; successful development of our product candidates; our ability to seek and obtain regulatory approvals, including with respect to the indications we are seeking; the successful commercialization of our product candidates; and market acceptance of our products.

FDA refers to US Food and Drug Administration. IND application refers to "Investigational New Drug" application. cGMP refers to current Good Manufacturing Practices. CMC refers to "Chemistry, Manufacture, and Controls". CHMP refers to the Committee for Medicinal Products for Human Use, which is the European Medicines Agency's (EMA) committee responsible for human medicines. API stands for "Active Pharmaceutical Ingredient". "Prodrug" means a chemical that is readily converted into the referenced drug in the body.

Contact:
NanoViricides, Inc.
info@nanoviricides.com

Public Relations Contact:
MJ Clyburn
TraDigital IR
clyburn@tradigitalir.com

SOURCE: NanoViricides, Inc.