Shelton, CT – January 27, 2021 — NanoViricides, Inc. (NYSE American: NNVC) (the “Company”) a global leader in the development of highly effective broad-spectrum antiviral therapies based on a novel nanomedicines platform, today discusses the current developments in the COVID-19 pandemic and the Company’s exciting accomplishments related to it.
“We welcome the strong engagement of President Biden and his new administration’s commitment to combat this once-in-a-century pandemic with new approaches and fresh ideas,” said Anil R. Diwan, PhD, President of the Company.
We would like to note that the scientific community at large and regulatory efforts to date have remained focused on (a) vaccines, (b) antibodies, and (c) re-development of pre-existing drugs. Even as alarm bells were raised by renowned scientists regarding the likelihood of escape mutations and the limitations of any vaccines and antibody therapies in combating a rapidly evolving global viral pandemic, there has been an effort to downplay these risks at all levels. This has left the world now grappling with a situation where vaccines are being rolled out even as virus variants that are highly likely to be resistant to current vaccines and antibody drugs have already been found to be spreading rapidly. Current vaccines are now assumed to require constant updates and re-inoculation campaigns to keep up with ongoing changes in the virus. Attention needs to be focused instead on broad-spectrum antiviral therapeutics that minimize the possibility of virus variants escaping the drug, thereby making the costly ongoing development of vaccine updates, their deployment and re-inoculation campaigns unnecessary.
NanoViricides believes it is very likely the only company with a platform technology that enables development of drugs that viruses would not escape. In fact, we have successfully screened our COVID-19 drug candidates to be able to protect cells against infection by distinctly different coronaviruses. This broad-spectrum drug development approach was adopted to ensure that our drug candidates should remain effective even as future variants of SARS-CoV-2 evolve in the field, as was already anticipated by us at that time.
Additionally, NanoViricides is the only company that, to the best of our knowledge, is developing antiviral treatments designed to (a) directly attack the virus and disable it from infecting human cells, and (b) simultaneously block the reproduction of the virus that has already gone inside a cell. Together, this strategy of a two-pronged attack against the virus, both inside the cell and outside the cell, can be expected to result in a cure for coronaviruses and other viruses that do not become latent.
The Company’s nanoviricides® platform technology is based on biomimetic engineering that copies the features of the human cellular receptor of the virus. No matter how much the virus mutates, all virus variants bind to the same receptor in the same fashion. It appears that the later variants of SARS-CoV-2 may have evolved to bind to the human cellular receptor ACE2 more strongly, in general, based on published datasets. Thus, if these features of the cellular receptor are appropriately copied, the resulting nanoviricide drug would remain effective against current and future variants of the virus.
Our current drug candidates to combat the COVID-19 pandemic are designed to attack not only SARS-CoV-2 and its current and future variants, but also many other coronaviruses, and will be useful even after the pandemic is over, because several coronaviruses are endemic in human populations.
Our COVID-19 drug candidates successfully entered core safety pharmacology studies required prior to any human clinical trials around October/November, 2019. These studies have now been completed and we are anticipating the report from the external CRO shortly. We are now working on preparing a pre-IND application for filing with the US FDA as soon as possible. Additionally, we are actively seeking opportunities to engage appropriate sites for human clinical trials, and we are engaged in the preparation of clinical trial protocols and other activities that would be necessary for filing of an IND with the US FDA.
The need for the broad-spectrum nanoviricide SARS-CoV-2 drug cannot be overstated in the current circumstances and the present status of the pandemic. To understanding this, we are providing a short review of the current state of the pandemic below:
Strong government support led to rapid emergency use approval, and later full approval, of an already known antiviral drug now called Veklury (remdesivir, Gilead) early on. Strong fiscal support and regulatory enablements from the government also led to the emergency use approval of two different antibody drugs, one from Regeneron (REGN-CoV-2, a monoclonal antibody cocktail containing two different antibodies), and one from Eli Lilly (bamlanivimab, a single antibody for restricted use) in the fastest ever drug development timeframe. All of these antibody drugs target the viral Spike protein that binds to the human cellular receptor, ACE2.
Even stronger commitments and strong government support led to the fastest ever emergency use approval of two vaccines, both employing nanotechnology; one by Pfizer-BioNTech, and one by Moderna, with additional vaccines in development. All of these vaccines target the original 2019-nCoV-Wuhan variant, and all but a few target primarily its Spike protein.
Yet, as the vaccines are undergoing deployment, several new virus variants of tremendous concern have already emerged. Additional virus variants will continue to emerge at an even faster rate because of the widespread dissemination of the virus with many patient bodies serving as virus factories providing historically the biggest ever opportunities for the virus to escape existing vaccines and antibody drugs. Failure of vaccines and antibody drugs is therefore certain; the only question is how long will it be before the vaccines become substantially ineffective.
Replacing current vaccine with a new vaccine, as has been suggested, would be an endless game of chasing a rapidly changing epidemic that would be costly and also would remain substantially non-responsive to the threat, since the virus will continue to remain many steps ahead of the vaccine.
It is well known that viruses, particularly RNA viruses, mutate rapidly, and that such changes produce “variants” that can escape from vaccines as well as from antibody drugs. SARS-CoV-2 has a repair mechanism that retains some fidelity during reproduction, and therefore it changes less rapidly than Influenza A viruses or HIV. Nevertheless, given the significant penetration of the virus into human population, and the very high viral loads achieved in severe cases of the infection, the virus has a huge opportunity to change. Additional virus variants will undoubtedly continue to emerge at an even faster rate because of the widespread dissemination of the virus through many patients, their bodies effectively serving as “factories”. This important concern, voiced by several eminent scientists, has not been regarded with the seriousness it deserves by supporting and enabling rapid regulatory development of broad-spectrum anti-coronavirus drugs.
The world has already witnessed at least five important SARS-CoV-2 variants with significant impact, as a result of the large number of persons becoming infected. The very first important variant, namely D614G, replaced the original Wuhan strain completely and rapidly during the first wave of the pandemic itself. In the current second wave, we have seen emergence of the lineage B.1.1.7 variant from United Kingdom (Kent and London), the N501Y-V.2 (also called lineage B.1.351) from South Africa, and the P.1 variant (also called lineage B.1.1.248) from Brazil. California has seen lineage B.1.429 /(CAL.20C) variant become dominant in Los Angeles county recently, with over 50% of the infections. It appears to be replacing the earlier dominant CAL.20G variant. Several additional variants have been identified. New variants continue to be identified at a rapid pace as viral genome sequencing efforts are accelerated.
Each of these five variants arose independently and in distinct geographic areas, and yet they share many common features, including a number of mutations in the receptor-binding region of the coronavirus Spike protein. It appears that the 501Y mutation in the spike protein leads to stronger binding to the human cellular receptor ACE2, allowing the virus to infect more productively, and has become more common in later variants. It appears that the E484K mutation, along with other mutations, present in the South African and Brazilian variants, may result in escape from vaccines and antibodies.
A major concern is the fact that the variants that are now becoming dominant have an accumulation of multiple mutations. This is predictive of such variants being more resistant to drugs and vaccines. They are likely to have been selected against drug pressure or immune system pressure, and thus would likely have resistance to antibody drugs, as well as other commonly used drugs, as suggested by eminent scientists. Further, it is now known that some of the new variants can cause infection of a previously recovered coronavirus patient, and sometimes may lead to more severe disease than the earlier infection. Such new variants can be logically expected to be resistant to antibodies as well as vaccines. Additionally, it has already been found or suspected that many of the new variants are or are expected to be resistant to existing antibody drugs. Given the known weak effectiveness of available antibody drugs, even a small resistance would likely allow a variant to escape the current antibody drugs.
Of note, the currently approved drugs, namely remdesivir, the Regeneron antibody cocktail, or the Eli Lilly single antibody drug, had demonstrated only moderate effectiveness in clinical trials. Remdesivir reduced the length to recovery in severe disease cases in hospitalized patients by approximately six days, from 18 days to 12 days in a clinical trial, NIAID ACIT-1, reported in its European (CHMP) Product Information. The Regeneron drug dosing in a clinical trial was at 2.4g or 8g of total antibody, while the Eli Lilly antibody drug dose in the combination therapy clinical trial was at 5.6g, although single antibody therapy dosages from 700mg upwards are also being evaluated. These high dosage levels are indicative of relatively weak effectiveness. The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for the Regeneron REGN-COV-2 cocktail, and also to a Eli Lilly single antibody bamlanivimab (LY-CoV555) with both authorizations restricted to the treatment of mild to moderate COVID-19 only. Thus, further loss of effectiveness of the existing drugs as new variants emerge would have devastating consequences.
Vaccines, it is now clearly apparent, are neither the great hope nor panacea that the scientific community had once thought for this pandemic. The South African variant, 501Y.v2 is of great concern as scientists believe it may escape current vaccines. Its mutations are also shared by the Brazilian variant, P.1. Vaccinated persons coming down with SARS-CoV-2 infection has already been witnessed. As more variants emerge, existing vaccines would very likely lose effectiveness. An additional concern is that some of the variants are expected to result in greater total fatality numbers. A more contagious variant would cause more number of cases and thus greater number of fatalities. A more lethal variant would lead to a greater proportion of infected patients dying (i.e. a greater case fatality rate). The UK B.1.1.7 variant is currently estimated by the UK scientific advisory body, namely New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG), to be highly contagious (transmissible), infectious, and more lethal than previous variants.
The SARS-CoV-2 virus, despite its current and future variants, is extremely unlikely to escape a broad-spectrum anti-coronavirus drug like the one being developed by NanoViricides. This is in complete contrast with drugs based on antibodies, antibody cocktails, as well as with preventative vaccines.
NanoViricides has been developing broad-spectrum anti-coronavirus drug candidates since the early reports of the new virus from China, then known as 2019-nCoV. We were able to bootstrap this development using our knowledge gained in the earlier endeavors working on SARS-CoV-1 and MERS coronaviruses.
NanoViricides has been able to conduct this novel drug development at an accelerated pace because of the benefits of its platform technology. We were able to bootstrap our SARS-CoV-2 drug development efforts using the c-GMP-compatible manufacturing processes developed for our then flagship NV-HHV-101 drug candidate for shingles dermal treatment. Further, NanoViricides has a tremendous advantage in that the Company has its own cGMP-capable manufacturing facility in Shelton, CT. This facility is capable of producing approximately 4kg of the COVID-19 drug per batch. We anticipate that this scale would be sufficient for human clinical trials, and possibly for initial introduction under Compassionate Use, Emergency Use Authorization or similar regulatory approval.
“We are well poised and are advancing the fight against the coronaviruses with a weapon that has perhaps the best characteristics for succeeding in taming this pandemic,” said Anil R. Diwan, PhD, President and co-Founder of NanoViricides, Inc., and co-Inventor of its platform technologies and drug candidates.
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 performing required safety pharmacology studies and completing an IND application. The Company believes that since remdesivir already is 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 our own drug candidates 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 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. 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.