NanoViricides, Inc. Pan-coronavirus COVID-19 Drug Candidates Are Highly Effective in Pre-clinical Animal Studies in Support of FDA Pre-IND Application

SHELTON, CT / ACCESSWIRE / March 9, 2021 / investorsHub NewsWire -- NanoViricides, Inc. (NYSE American: NNVC) (the "Company"), a leader in the development of highly effective antiviral therapies based on a novel nanomedicines technology, reported today on the strong effectiveness of its two COVID-19 clinical drug candidates in an animal model of coronavirus infection.

The Company is preparing a pre-IND application encompassing its two clinical drug candidates for the treatment of COVID-19 infected patients. Of these, NV-CoV-2 is the Company's broad-spectrum anti-coronavirus drug candidate based on its nanoviricides® platform that is expected to be capable of attacking most, if not all, SARS-CoV-2 variants and other coronaviruses. In addition, the Company is also developing NV-CoV-2-R that combines (1) the power of NV-CoV-2 to attack and potentially dismantle the virus particles outside cells, and (2) the power of remdesivir to block further production of virus particles inside cells. Blocking the complete lifecycle of the virus in this manner could provide a cure for the viral disease. The Company intends to perform human clinical studies to establish the effectiveness of NV-CoV-2 and NV-CoV-2-R in treating COVID-19 viral infection.

Both NV-CoV-2 and remdesivir are broad-spectrum drugs and are expected to be effective against most, if not all, variants of the coronavirus that continue to emerge in the field, based on pre-clinical studies. The broad-spectrum effectiveness of the Company's drug candidates is very important as coronavirus variants that may evade antibodies and cause disease in spite of vaccination are becoming widespread as the COVID-19 global pandemic is progressing into its second year. The need for antiviral drugs that are developed against coronaviruses is now well recognized (Read in Buzzfeed News1).

NV-CoV-2 and NV-CoV-2-R were found to be highly effective against a fully lethal direct-lung coronavirus infection in rats based on multiple indicators:

Survival: While rats in the untreated infected group succumbed to the disease in 5 to 6 days, the rats in the NV-CoV-2 treatment group survived for 14 days, and the rats in the NV-CoV-2-R treatment group survived for 16 days. In contrast, rats treated with remdesivir formulated in SBECD (comparable to the FDA-approved Veklury® formulation of remdesivir) survived for only 7.5 days. The total dose of remdesivir was 90mg/kgBW for the remdesivir treated group, and it was 80mg/kgBW when encapsulated in the NV-CoV-2-R group. Thus compared to treatment with remdesivir, treatment with the Company's drug candidate NV-CoV-2 extended the lifespan by approximately four times more days. Further, treatment with the Company's other drug candidate NV-CoV-2-R extended the lifespan by approximately five times more days.

Body Weight: Both NV-CoV-2 and NV-CoV-2-R protected the animals from body weight (BW) loss that results from the infection and immune response, in addition to the substantially increased survival, in this lethal coronavirus infection model. NV-CoV-2 group lost only about 7% BW (12.5 g/animal) at day 13, and the NV-CoV-2-R group lost as little as ~1.8% BW (3g/animal) at day 13. In contrast, the remdesivir group had already lost ~17% BW (30g/animal) by day 7 and succumbed to the disease soon thereafter.

Additional studies on histopathology of organs and blood chemistry are in progress.

These results clearly indicate strong effectiveness of NV-CoV-2 as well as NV-CoV-2-R in fighting the coronavirus lung infection and its ill effects, as compared to the FDA-approved drug remdesivir.

The (1) significant improvement in lifespan by a factor of four to five, and (2) the significant prevention of body weight loss, upon treatment with NV-CoV-2 as well as NV-CoV-2-R as compared to treatment with the FDA-approved remdesivir are important indicators for potential human clinical success of the Company's drug candidates.

The Company studied the effectiveness of these drugs against the human coronaviruses h-CoV-NL63 (NL63) that uses the same ACE2 human cellular protein as receptor to gain entry into cells as do all variants of SARS-CoV-2 and SARS-CoV-1. Additionally, the human pathology of NL63 infection closely mimics that of SARS-CoV-2, albeit with limited disease severity. NL63 is a circulating human coronavirus that can be used in BSL2 labs. NL-63 is therefore being used as a model for anti-SARS-CoV-2 drug development in various labs including ours (see Chakraborty and Diwan for a review2).

Remdesivir (Veklury®, Gilead) has shown relatively weak effectiveness in animal and clinical studies in contrast to its strong effectiveness in cell culture studies. This has been related by scientists to the metabolism of remdesivir in the blood stream that causes loss of effectiveness. The Company has developed the drug candidate NV-CoV-2-R by encapsulating ("hiding inside") remdesivir into NV-CoV-2. The Company believes that this encapsulation should protect remdesivir from bodily metabolism and thereby significantly increase its clinical effectiveness.

The strong effectiveness of NV-CoV-2 and NV-CoV-2-R drug candidates in this animal model is consistent with their previously reported effectiveness in cell culture studies against infection of two human coronaviruses, hCoV-NL63, which was used in this animal efficacy study, and hCoV-229E, another circulating coronavirus that uses a distinctly different receptor, namely APN. In contrast, while remdesivir was highly effective in the cell culture studies, it was not very effective in this animal efficacy study, a result that is consistent with human clinical studies of remdesivir.

The effectiveness of NV-CoV-2-R observed in this study can be understood as a combination of (a) the improvement in the effectiveness of remdesivir due to encapsulation, and (b) the effectiveness of NV-CoV-2 by itself.

NV-CoV-2-R, the Company believes, is an excellent demonstration of the power of the nanoviricides platform technology that enables combining multiple modalities seamlessly into a single drug.

The Company believes that these in vivo study results support a potential synergistic improvement in the drug effect as a result of combining the two different mechanisms of attacking (i) the virus reinfection cycle and (ii) the virus replication cycle simultaneously.

The Company has developed NV-CoV-2 and NV-CoV-2-R based on its platform nanoviricides® technology. This approach enables rapid development of new drugs against a number of different viruses. A nanoviricide is a "biomimetic" - it is designed to "look like" the cell surface to the virus. The nanoviricide technology enables direct attacks at multiple points on a virus particle. It is believed that such attacks would lead to the virus particle becoming ineffective at infecting cells. Antibodies in contrast attack a virus particle at only two attachment points per antibody.

It is anticipated that when a virus comes in contact with the nanoviricide, not only would it land on the nanoviricide surface, binding to the copious number of ligands presented there, but it would also get entrapped because the nanomicelle polymer would fuse with the virus lipid envelope, harnessing a well known biophysical phenomenon called "lipid-lipid mixing". In a sense, a nanoviricide drug acts against viruses like a "venus-fly-trap" flower does against insects. Unlike antibodies that tag the virus and require the human immune system to take over and complete the task of dismantling the virus, a nanoviricide is a nanomachine that is designed to not only bind to the virus but also complete the task of rendering the virus particle ineffective.

In addition, the nanoviricide technology also simultaneously enables attacking the rapid intracellular reproduction of the virus by incorporating one or more active pharmaceutical ingredients (APIs) within the core of the nanoviricide. The nanoviricide® technology is the only technology in the world, to the best of our knowledge, that is capable of both (a) attacking extracellular virus, thereby breaking the reinfection cycle, and simultaneously (b) disrupting intracellular production of the virus, thus blocking the complete lifecycle of the virus, enabling complete control of a virus infection.

The Company has developed NV-CoV-2-R based on this encapsulation capability that is built into its nanoviricide NV-CoV-2. The Company has chosen to encapsulate remdesivir as the participating drug for blocking the viral replication cycle. Remdesivir is approved by the US FDA for the treatment of patients hospitalized with COVID-19. Encapsulation of remdesivir in the Company's nanoviricide envelope is believed to protect it from metabolism in the body. This protection can be expected to lead to significant enhancement in the effectiveness of remdesivir itself (in the encapsulated form), by potentially increasing both the effective remdesivir concentration and its duration of action. This could be an additional favorable effect for the Company's anti-coronavirus drug candidate NV-CoV-2-R. Remdesivir is sponsored by Gilead. The Company is developing its drug candidates independently at present.

  1. Dan Vergano, "We have vaccines for COVID-19. Why don't we have good treatments? - 'Everyone was looking for a quick fix,' Anthony Fauci told BuzzFeed News." Read in BuzzFeed News (March 6, 2021), https://www.buzzfeednews.com/article/danvergano/coronavirus-treatments-antivirals-fauci .

  2. A. Chakraborty and A. Diwan (2020). "NL63: A Better Surrogate Virus for studying SARS- CoV-2". Integr Mol Med, 2020, vol.7, pp 1-9, doi: 10.15761/IMM.1000408.

About NanoViricides

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-HHV-101 with its first indication as dermal topical cream for the treatment of shingles rash. In addition, we are developing a clinical candidate for the treatment of COVID-19 disease caused by SARS-CoV-2 coronavirus. The Company cannot project an exact date for filing an IND for this drug because of its dependence on a number of external collaborators and consultants.

The Company is now working on tasks for completing an IND application. The Company is currently pursuing two separate drug candidates for the treatment of COVID-19 patients. NV-CoV-2 is our nanoviricide drug candidate that does not encapsulate remdesivir. NV-CoV-2-R is our other drug candidate that is made up of NV-CoV-2 with remdesivir encapsulated in it. 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 intends to re-engage into an IND application to the US FDA for NV-HHV-101 drug candidate for the treatment of shingles once its COVID-19 project moves into clinical trials, based on resources availability. The NV-HHV-101 program was slowed down because of the effects of recent COVID-19 restrictions, and re-prioritization for COVID-19 drug development work.

The Company is also developing drugs against a number of viral diseases including 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 and Ebola/Marburg viruses. The Company has executed a Memorandum of Understanding with TheraCour that provides a limited license for research and development for drugs against human coronaviruses. The Company intends to obtain a full license and has begun the process for the same. 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 disclose the risk 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.

Contact:
NanoViricides, Inc.
info@nanoviricides.com

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

SOURCE: NanoViricides, Inc.