NANOVIRICIDES, INC._JUNE 30, 2025
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 10-K
☒ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
FOR THE FISCAL YEAR ENDED JUNE 30, 2025
Commission File Number 001-36081
NANOVIRICIDES, INC.
(Name of Business Issuer in Its Charter)
1 CONTROLS DRIVE, SHELTON, CONNECTICUT, 06484
(Address of principal executive offices)
203-937-6137
(Issuer’s telephone number, including area code)
SECURITIES REGISTERED PURSUANT TO SECTION 12(b) OF THE ACT: NONE
SECURITIES REGISTERED PURSUANT TO SECTION 12(g) OF THE ACT:
COMMON STOCK, PAR VALUE $0.00001 PER SHARE NYSE AMERICAN
(Title of Class) (Name of exchange on which registered)
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.
Yes ☐No☒
Indicate by a check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.
Yes ☐No☒
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Yes☒ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).
Yes☒ No ☐
Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K. ☒
Indicate by check mark whether the Company is a larger accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant has filed a report on an attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 726(b)) by the registered public accounting firm that prepared or issued its audit report. ☐
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act.).
Yes ☐ No ☒
On September 27, 2025 there were approximately 17,431,000 shares of common stock of the registrant issued and outstanding.
The aggregate market value of the voting stock held on December 31, 2024, by non-affiliates of the registrant was approximately $21,530,000 based on the closing price of $1.43 per share, as reported on the NYSE American on December 31, 2024, the last business day of the registrant’s most recently completed fiscal second quarter (calculated by excluding all shares held by executive officers, directors and holders known to the registrant of five percent or more of the voting power of the registrant’s common stock, without conceding that such persons are “affiliates” of the registrant for purposes of the federal securities laws).
Table of Contents
TABLE OF CONTENTS
PART I
Item 1. Business 3
Item 1A. Risk Factors 61
Item 1B. Unresolved Staff Comments 82
Item 1C. Cybersecurity 82
Item 2. Properties 83
Item 3. Legal Proceedings 83
Item 4. Mine Safety Disclosures 83
PART II
Item 6. Selected Financial Data 84
Item 7A Quantitative and Qualitative Disclosures About Market Risk 91
Item 8. Financial Statements and Supplementary Data 91
Item 9A. Controls and Procedures 92
Item 9B. Other Information 92
PART III
Item 10. Directors, Executive Officers, Promoters and Corporate Governance. 94
Item 11. Executive Compensation 97
Item 14. Principal Accountant Fees and Services 104
PART IV
Item 15. Exhibits, Financial Statement Schedules 105
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PART I
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
This Report contains forward-looking statements within the meaning of the federal securities laws. All statements other than statements of historical fact made in this report are forward looking. In particular, the statements herein regarding industry prospects and future results of operations or financial position are forward-looking statements. These include statements about our expectations, beliefs, intentions or strategies for the future, which we indicate by words or phrases such as “anticipate,” “expect,” “intend,” “plan,” “will,” “we believe,” “Company believes,” “management believes” and similar language. These forward-looking statements can be identified by the use of words such as “believes,” “estimates,” “could,” “possibly,” “probably,” “anticipates,” “projects,” “expects,” “may,” “will,” or “should,” or other variations or similar words. No assurances can be given that the future results anticipated by the forward-looking statements will be achieved. Forward-looking statements reflect management’s current expectations and are inherently uncertain. The forward-looking statements are based on the current expectations of NanoViricides, Inc. and are inherently subject to certain risks, uncertainties and assumptions, including those set forth in the discussion under “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in this report. Our actual results may differ materially from results anticipated in these forward-looking statements.
Investors are also advised to refer to the information in our previous filings with the Securities and Exchange Commission (SEC), especially on Forms 10-K, 10-Q and 8-K, in which we discuss in more detail various important factors that could cause actual results to differ from expected or historic results. It is not possible to foresee or identify all such factors. As such, investors should not consider any list of such factors to be an exhaustive statement of all risks and uncertainties or potentially inaccurate assumptions.
Although these forward-looking statements reflect the good faith judgment of our management, such statements can only be based upon facts and factors currently known to us. Forward-looking statements are inherently subject to risks and uncertainties, many of which are beyond our control. As a result, our actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors, including those set forth below under the caption “Risk Factors.” For these statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. You should not unduly rely on these forward-looking statements, which speak only as of the date on which they were made. They give our expectations regarding the future but are not guarantees. We undertake no obligation to update publicly or revise any forward-looking statements, whether as a result of new information, future events or otherwise, unless required by law.
Glossary of Terms
Nano - When used as a prefix for something other than a unit of measure, as in “nanoscience,” nano means relating to nanotechnology, or on a scale of nanometers (one billionth of a meter or greater).
Viricide - An agent that reliably deactivates or destroys a virus.
Nanoviricide TM - An agent that is made by attaching ligands against a certain virus or family of viruses to a nanomicelle based on the Company’s patent-pending and proprietary technologies.
Ligand - A short peptide or chemical molecule fragment that has been designed to specifically recognize one particular type of virus.
Micelle - an aggregate of molecules in a solution, such as those formed by detergents.
Nanomicelle - A term coined to describe the micelles formed from the backbone polymer of a nanoviricide sans attached ligands.
Pendant polymeric micelles - A polymeric micelle forms from a polymer whose chemical constitution is such that even a single chain of the polymer forms a micelle. A pendant polymer is a polymer that has certain units in its backbone that extend short chains branched away from the backbone. Pendant Polymeric Micelles therefore are polymeric micelle materials that are a class of pendant polymers, and naturally form exceptionally well-defined, self-assembling, globular micelles with a core-shell architecture.
Mutations - The ability (of a virus) to change its genetic structure to avoid the body’s natural defenses. Mutant viruses are created from a parent virus strain through a process of natural selection under pressure as it replicates in a host.
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P-Value - In statistical hypothesis testing, the p-value is the probability of obtaining a result at least as extreme as that obtained, assuming that the null hypothesis is true; wherein the truth of the null hypothesis states that the finding was the result of chance alone. The fact that p-values are based on this assumption is crucial to their correct interpretation. The smaller the p-value, the greater is the probability that the observed study results and the comparison control are distinct, and therefore that the study results are not a result of chance alone.
More technically, the p-value of an observed value observed of some random variable T used as a test statistic is the probability that, given that the null hypothesis is true, T will assume a value as or more unfavorable to the null hypothesis as the observed value observed. “More unfavorable to the null hypothesis” can in some cases mean greater than, in some cases less than and in some cases further away from a specified center value.
Investigational New Drug Application (Investigational New Drug (“IND”) - The process of licensure of a new drug in the US goes through several steps. A simplified explanation of these steps is as follows. Initially a Company may file a pre-IND application to seek meetings with the United States Food and Drug Administration (FDA) for guidance on work needed for filing an IND application. The Company obtains data on the safety and effectiveness of the drug substance in various laboratory studies including cell cultures and animal models. The Company also obtains data on chemical manufacturing of the drug substance. These and certain additional data are used to create an IND that the Company files with the FDA. After the FDA approves an IND application, the Company may conduct human clinical studies. A Phase I human clinical trial is designed typically to evaluate safety of the drug and maximum permissible dosage level. A Phase II human clinical trial that follows is designed to evaluate effectiveness of the drug against the disease in a small cohort of patients. A Phase III human clinical trial thereafter is designed to evaluate effectiveness and safety in larger groups of patients, often at multiple sites. The Company may then submit an NDA (New Drug Application) with the data collected in the clinical trials. The FDA may approve the NDA. Once the NDA is approved, the Company can sell the drug in the USA. European countries have similar processes under the European Medicines Agency (EMA). Other countries have similar processes.
SAR - Structure-Activity-Relationship study. When an initial lead drug compound is found that has activity, further studies on drug compounds obtained by suitably modifying it are performed with the goal of improving efficacy, safety, or both. Such studies are called SAR studies.
ITEM 1: BUSINESS
Organization and Nature of Business
NanoViricides, Inc. (the “Company”, “NanoViricides”, “we,” or “us”) was incorporated in Nevada on April 1, 2005, and redomiciled to Delaware effective May 30, 2023. Our corporate offices are located at 1 Controls Drive, Shelton, Connecticut 06484 and our telephone number is (203) 937-6137. Our Website is located at http://www.Nanoviricides.com. We do not incorporate by reference into this Annual Report the information on or accessible through our website, and you should not consider it part of this Annual Report.
On September 25, 2013, the Company’s common stock began trading on the New York Stock Exchange American under the symbol, “NNVC”.
We are a clinical stage company with our first drug ready to enter Phase II human clinical efficacy trial, having successfully completed Phase Ia/Ib human clinical safety and tolerability trial. Based on our nanoviricidesTM platform technology, we also have several additional drug candidates in various stages of pre-clinical development, including IND-filing stage and late stage IND-enabling non-clinical studies. We have no customers, products or revenues to date, and may never achieve revenues or profitable operations.
We are engaged in developing a class of drugs, that we call nanoviricidesTM, using a platform technology based on the application of nanomedicine technologies to the complex issues of viral diseases. This approach enables rapid development of effective new drugs against a number of different viruses, that the viruses are highly unlikely to escape even as they evolve rapidly in the field, solving an important problem in attacking viruses. The virus evolution is known to generate viruses that escape the traditional antiviral approaches vaccines, antibodies and small chemical drugs.
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NanoViricides Technology Platform Target Product Profile in Brief
We are a clinical stage company developing (a) host-mimetic, and (b) direct-acting, nanomachines capable of dismantling a targeted virus, (c) without assistance from the human immune system.
These distinctive features that set nanoviricides apart from the entire world of current antiviral approaches are made possible by our novel nanoviricide chemical nanomachine design. After decades of development, this novel nanoviricide technology has now successfully reached clinical stage and regulatory processes towards approval of drugs for commercialization.
NV-387, Phase II-Ready Broad-Spectrum Nanoviricide Drug Development Against Multiple Viruses
Our first clinical stage drug candidate, NV-387, has completed Phase Ia/Ib human clinical trial for the evaluation of safety and tolerability in healthy subjects. NV-387 is the active ingredient in the two drug product formulations labeled “NV-CoV-2 Oral Syrup” and “NV-CoV-2 Oral Gummies” that we developed for the treatment for COVID infection. In this clinical trial for safety and tolerability in healthy human adult subjects: (a) there were no drop-outs, (b) there were no reported adverse events, and (c) the drugs were well-tolerated even at the highest level of dosing given multiple times. These results are indicative of safety and tolerability that have been successfully achieved for NV-387. The Clinical Study Report, a final document resulting from this clinical trial is in draft stages nearing completion. We anticipate its submission to the regulatory agency in India soon.
NV-387 is a uniquely broad-spectrum antiviral drug that has demonstrated strong activity in lethal lung infection animal model studies of Coronavirus, RSV, Influenza and even an Orthopoxvirus model for Smallpox and MPox, and most recently, even in a humanized mice model for Measles. These distinct types of viruses share a common feature; that they all utilize heparan sulfate proteoglycan (HSPG) or related Sulfated Proteoglycans (S-PG) as the first “attachment receptor” to which they bind and thereby prepare to attack the cells and cause infection. Each of these viruses then differ in the specific receptor(s) on the cell that the virus uses for attacking the cell, called the “cognate receptor(s)”, and thereby fuse with the cell and enter the cell initiating infection.
NV-387 is designed to mimic the essential, invariant, feature of S-PG onto which the virus lands first as it infects a human cell. Thus, NV-387 is designed to interfere at the earliest possible step before the virus can even infect a cell. Over 90% of human pathogenic viruses are known to use sulfated proteoglycans (“S-PG”) such as heparan sulfate proteoglycans (HSPG), dermatan sulfate, chondroitin sulfate, and others. This enables an extremely broad potential range of viruses that NV-387 could effectively address as an antiviral drug.
This extremely broad antiviral spectrum of NV-387 is reminiscent of the broad antibacterial spectrum of antibiotics such as penicillin and we believe NV-387 could revolutionize the treatment of viral infections the same way that penicillin revolutionized the treatment of bacterial infections.
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Antibiotics such as penicillin directly attack the bacterial surface and thereby kill the bacteria. Similarly, NV-387 is designed to directly attack the viral surface and destroy the virus particle. Similar to antibiotics that possess a broad-spectrum to treat bacterial infections, NV-387 could be a much needed, ultra-broad-spectrum, direct acting, antiviral agent to treat multiple different viral infections.
We believe that a safe and effective antiviral drug, when approved, with an extensive broad-spectrum activity across multiple, distinct, virus families is an unmet medical need. Currently available broad-spectrum antivirals such as Remdesivir, Ribavirin, Cidofovir, etc. suffer from extensive and varied dose-limiting toxicities, and thereby present limitations on eligible patient populations as well as on clinical effectiveness.
NV-HHV-1, Clinical-Ready Drug Candidate and the HerpeCideTM Program
We are also developing several other virus-family-specific drug candidates, by mimicking the common cellular cognate receptors of viruses.
NV-HHV-1 is designed to attack all herpesviruses that use the cognate receptor on cells called the “Herpesvirus Entry Mediator” (HVEM, also called CD270 and TNFRSF14) for cell entry.
NV-HHV-1, developed as a skin cream for the treatment of Shingles rash, has completed non-clinical safety/pharmacology studies required for a U.S. Food and Drug Administration (“FDA”) Investigational New Drug (“IND”) submission. We believe that the NV-HHV-1 skin cream, when approved, can also be additionally indicated to treat HSV-1 “cold sores” and HSV-2 “genital ulcers” based on successful animal studies.
Additionally, we are developing an oral drug for the systemic treatment of most of the herpesvirus family related infections, including HSV-1 “cold sores” and HSV-2 “genital herpes” that is based on the same active ingredient as NV-HHV-1.
HSV-1 infection is known to be associated with and possibly a cause of the neurodegenerative disease, Alzheimer’s disease (AD). Current therapies for HSV are limited in effectiveness and most of them target the DNA replication part of the virus. NV-HHV-1, with a mechanism orthogonal to the current therapies, could lead to a substantial improvement in the overall anti-HSV effectiveness and thereby could provide an option for blocking further neurodegeneration in AD.
NV-HIV-1, A Novel Mechanism Anti-HIV Drug Candidate and the HIVCideTM Program
We developed NV-HHV-1 to attack HIV by mimicking the conserved binding of HIV to the CD4 cell surface cognate receptor. This drug has shown remarkable effectiveness in animal studies in SCID-Hu-Thy-Liv implanted humanized mouse model for HIV. Given that Delta-CCR5- subjects are HIV-resistant, and that bone marrow transplant from such patients has led to effective cure of HIV, we believe it is possible that NV-HIV-1 itself or a further modified form to include mimicking the CCR5 portion, could lead to a drug that is close to a cure for HIV infection.
Other Drug Development Programs in the Pipeline
We have several other drug candidates at different preclinical drug development stages in our pipeline for the treatment of other viral infections including Dengue viruses, Ebola viruses, etc.
NanoViricides Owns Facilities with Fully Integrated Development and Manufacturing Capabilities
NanoViricides is one of a few pharmaceutical drug developers with its own facilities that support the entire drug development process from design and discovery, to chemical synthesis, to initial antiviral evaluation (in cell culture models), to scale-up of drug candidates, to set-up and cGMP-compatible manufacture drug substances. Our facility also supports cGMP-compatible formulation, filling, labeling and finished packaging of drug products. In addition, we also have well-equipped analytical laboratories that support both R&D development and cGLP compatible analytical testing and characterization of drug substances and drug products in the same facility. The facility is located at 1 Controls Drive, Shelton, CT.
Having such integrated facility available enabled us to develop the NV-CoV-2 COVID drug (that contains the active pharmaceutical ingredient NV-387) from concept to completion of safety/pharmacology studies required for clinical trials within a matter of just one year.
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The Phase Ia/Ib human clinical trial began in June 2023 and the healthy subjects treatment and observation part was completed as of the end of December 2023. The clinical trial drug products, NV-CoV-2 Oral Syrup, and NV- CoV-2 Oral Gummies which are two oral formulations of the active ingredient NV-387, were manufactured at our Shelton, CT campus, and then shipped to and received by Karveer Meditech Pvt. Ltd. (“KMPL”) our collaborator. Under the agreement with KMPL, we will pay for the expenses of the clinical trials, and in return we will benefit from having the data and reports made available for regulatory filings in other territories of the world. Upon commercialization by KMPL in India, we will receive royalties from KMPL equal to 70% of sales net of costs to unaffiliated third parties.
We have already manufactured the clinical drug substance NV-387 for the first Phase II clinical trial at this facility. The clinical drug product for this Phase II clinical trial is also planned for production at our own cGMP-compatible facility. A pilot run was completed recently, subsequent to the reporting period of this annual report.
We depend upon external parties, that may be collaborators, consultants, and sub-contractors, for the regulatory development of drug candidates including animal efficacy studies, non-clinical safety/pharmacology studies, regulatory requirements assessments, and regulatory affairs such as advice on regulatory strategy, regulatory documentation, design of clinical trials, preparation of clinical trial applications, as well as conducting clinical trials and preparing required reports.
Strong Intellectual Property and Collaborative Relationships
Our “nanoviricide” platform-based drugs are based on several patents, patent applications, provisional patent applications, and other proprietary intellectual property held by TheraCour Pharma, Inc. (“TheraCour”), to which we have broad, exclusive licenses. The licenses are to entire fields and not to specific compounds. In all, we have exclusive, worldwide licenses for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Herpes Simplex Virus (HSV-1 and HSV-2), Influenza and Asian Bird Flu Virus, Dengue viruses, Ebola/Marburg viruses, Japanese Encephalitis virus, viruses causing viral Conjunctivitis (a disease of the eye) and Ocular Herpes (restated). In all cases, the discovery of ligands and polymer materials, formulations, chemistry and chemical characterization, as well as process development and related work (the “Development Activities”) will be performed by TheraCour, a related party substantially owned by Dr. Anil Diwan, under the same compensation terms across various agreements between the parties, with no duplication of costs allowed. Upon commercialization, NanoViricides will pay 15% of net sales to TheraCour, although these licenses do not specify the terms of milestone payments during clinical development that are customary in the pharmaceutical industry. In addition, we have perfected a license for the field of Varicella Zoster Virus (“VZV License”) infections i.e. Shingles and Chickenpox (the “Shingles License”), and another one for the field of treatment of SARS-CoV-2 infections (the “COVID License Agreement”); both of which specify the same terms for the Development Activities as the prior agreements, and further specify certain milestone payment terms specifically for the individual fields, details of which have been disclosed at the time the agreements were entered into. We have later amended the COVID License on February 12, 2024, so that any cash milestone payments that remained un-earned or unpaid by that date would not be payable in cash until the Company receives sufficient revenue from its commercialization activities including out-licensing, collaborations, co-development agreements, and commercialization, as more fully described in the amendment to the COVID License Agreement (“Amendment to the COVID License Agreement”). Certain milestone payments were made under the VZV License as well as under the COVID License Agreement prior to the Amendment to the COVID License Agreement, details of which have been disclosed. We negotiate and license specific verticals of therapeutic applications from TheraCour if promising drug candidates are found in early research and development against a virus target. TheraCour has not denied any such licenses when requested.
We executed a Memorandum of Understanding (“MOU”) with TheraCour on September 23, 2024, subsequent to the reported period, whereby we have obtained a right of first refusal for all antiviral drug developments including unlicensed developments that occur during the course of the Development Activities as specified in our license agreements, and have set out the process of development of drugs for unlicensed viral indications towards completion of appropriate license agreements. The Company and TheraCour have also agreed in this MOU that any cash milestone payments related to development activities, that are awardable, will become payable only upon NanoViricides having sufficient revenue, as defined in and more fully described in the Amendment to the COVID License Agreement referred to above, thereby including the provisions previously incorporated in the Amendment to the COVID License Agreement, to all present and future license agreements.
We have out-licensed NV-CoV-2 and NV-CoV-2-R for further clinical drug development and commercialization in the territory of India to KMPL, a company of which Dr. Anil Diwan is a passive investor and advisor, enabling KMPL to sponsor our drug products originally developed for COVID treatment, namely NV-CoV-2 Oral Syrup and NV-CoV-2 Oral Gummies into Phase I human clinical trial.
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Our Plan for Regulatory Development and Commercialization of Our Drugs
Our most advanced drug candidate at present is the broad-spectrum antiviral drug NV-387.
NV-387’s Broad Antiviral Spectrum Cuts Across Virus Families
NV-387 is the active pharmaceutical ingredient of both the oral formulations, namely NV-CoV-2 Oral Syrup and NV-CoV-2 Oral Gummies drug products. In various animal models of lethal virus infection challenge, NV-387 was found to lead to substantial increase in survival, compared to even approved drugs where available, indicating potential for successful clinical regulatory development as a treatment for a number of viruses. Additional criteria studied in these animal models also further bolstered these expectations of potentially successful regulatory development. The viruses we have tested and found to support expectations of potentially successful regulatory development include RSV and Influenza in addition to Coronaviruses, covering the so-called “tripledemic” viruses with a single drug to treat them. In addition, similar strong results were found for treatment with NV-387 of orthopoxvirus infection in animal models, both by dermal route, as well as by direct lung infection route. Additionally, strong results were found for treatment with NV-387 of lethal Measles virus lung infection in a humanized hCD150-knock-in mouse model. In the animal model studies, the dermal infection route models MPox infection, whereas the lung infection route models potential bioterrorist attack with Smallpox virus.
The above mentioned broad-spectrum antiviral effect of NV-387 as found in animal models of lethal virus challenge infection suggests that NV-387 is eligible for regulatory clinical development as a potential treatment for RSV, Influenza, MPox and Smallpox, as well as Measles, in addition to Coronaviruses, based on the current data at hand. It is possible that NV-387 may have similar antiviral effect against many other viruses, something that we plan on continuing to evaluate as our programs advance. This expectation is based on the mechanism of NV-387 in that it mimics sulfated proteoglycan structures associated with host cells that are used by over 90% of human pathogenic viruses as attachment receptors.
The viruses we have tested NV-387 against cut across different virus types, including RNA viruses as well as DNA viruses of different kinds. We are not aware of any other antiviral drug in development that has such a broad spectrum of activity, and safety/tolerability in humans that would potentially allow use across the entire human population.
We have developed a regulatory strategy for NV-387 that we believe would take NV-387 into commercialization stage in the most cost-effective manner and in the most rapid manner. To this end, we are devising Phase II clinical trials for NV-387 against MPox, an “Orphan” disease in the USA, as well as an innovative “basket-type” clinical trial to assess effectiveness of NV-387 against a range of viruses in a single clinical trial.
Phase II Clinical Trial for Evaluating NV-387 for the Treatment of MPox
We are working on initiating a Phase II clinical trial for NV-387 as a treatment for MPox disease caused by the MPXV virus in the Democratic Republic of Congo (DRC). We have obtained a preliminary approval from the Ethics Committee of the regulatory agency in charge for the African region, namely ACOREP, for this clinical trial. We have signed up a Clinical Trial Research Organization (CRO) to help develop the clinical protocol and conduct the clinical trial. With the CRO, we have identified sites for the clinical trial and have engaged one site in particular, which we believe will be able to provide all of the patients recruitment as needed for the Phase II clinical trial. We are now in the process of developing a clinical trial application.
In addition to the Phase II clinical trial to evaluate the safety and effectiveness of NV-387 treatment in MPox patients, we are also planning another Phase II clinical trial to evaluate the potential of NV-387 as an emperic antiviral therapeutic for acute and severe-acute viral respiratory infections (Viral ARI and SARI).
Phase II Clinical Trial for Assessing the Potential of NV-387 as a Revolutionary “Emperic” Antiviral Therapeutic
NV-387 is likely to become an “emperic therapy” for respiratory viral infections, similar to how amoxicillin has become the go-to empiric therapy for respiratory bacterial infections, if its activity that was observed in numerous animal model studies against respiratory infections holds up in the human clinical setting. This is very important for viral diseases, because the first 48 hours are crucial for successful treatment of such viral infections, as seen from notations in the product labels for a number of anti-influenza drugs such as oseltamivir (Tamiflu®, Roche), Zanamivir, and others. Regrettably, at present, antivirals are prescribed only after testing and determination of the causative agent, because the drugs are specific to the virus. This results in the loss of the window of opportunity
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for best impact, not accounting for the fact that patient already suffers for a couple of days hoping for recovery before seeking physician’s help.
In contrast to the current one-drug-one-bug antiviral agents, we believe that NV-387 could be prescribed when a patient presents with respiratory symptoms consistent with a viral infection without testing for specific virus, analogous to how antibiotics for respiratory bacterial infections are prescribed, i.e. as an emperic, first-line therapy. This will become possible if NV-387 demonstrates effectiveness in a properly designed clinical trial against a majority of viral respiratory infections. To this end, we are designing a so called “basket-type”, adaptive, clinical trial to evaluate the effectiveness of NV-387 administered in respiratory viral infections regardless of what the causative virus is. This Phase II clinical trial will enable us to obtain definitive data regarding effectiveness of NV-387 against at least two of the most prevalent viruses during the clinical trial at the trial sites, with substantially indicative data against many others.
We are therefore planning an adaptive, “basket-type”, Phase II clinical trial for the evaluation of NV-387 as a treatment for Viral Acute or Severe Acute Respiratory Infections (Viral-ARI or Viral-SARI). We believe we will obtain definitive data against Influenza, RSV, and Coronaviruses, or at least two of these three viruses, as well as substantially indicative data against the adenoviruses, echoviruses, picornaviruses, rhinoviruses (generally regarded as common cold viruses), and many others that infect by the respiratory route, in this single clinical trial. This would substantially save on costs of conducting clinical trials, and would open up the path for confirmatory Phase III clinical trials to potentially enable a variety of antiviral indications if successful.
NV-387 Has Been Formulated for Several Routes of Administration
We found that NV-387 is effective when orally administered in animal studies, unlike other known nanomedicines that are limited to injectable routes. We developed a soft solid “Oral Gummies” formulation of NV-387. This formulation has the advantage that it dissolves by itself in the mouth, eliminating the need to swallow a hard tablet. This is important for many of the diseases we are targeting. Sore throat from respiratory viral infections, Mouth Ulcers, in the case of MPox, or even old age or very young age, makes tablet swallowing difficult. Our gummies formulation can be readily administered to such patients.
We have also developed an injectable formulation primarily for use in severe cases that do not require hospitalization, an I.V. infusion formulation, that would be preferred for hospitalized patients with I.V. central line, as well as a solution for direct lung inhalation using an off-the-shelf nebulizer, which would provide most concentrated drug action at the site of the most severe infection, namely in the lungs. We plan on performing clinical trials for these cases after the two Phase II studies above are completed.
Benefits of Our Regulatory Approach for NV-387 – Orthopoxviruses – MPox, Smallpox, Biodefense
The Phase II MPox clinical trial in DRC is expected to provide first evidence of efficacy of NV-387 in a viral disease in humans.
MPox was declared as a global Public Health Emergency of International Concern (“PHEIC”) by the World Health Organization (WHO) around May 2022 that was canceled about a year later. This PHEIC was caused by spill-over of the MPox Clade II virus from Africa into European countries and into the USA.
The MPox Clade II continues to cause cases in the USA even in 2025 and is an “Orphan” disease in the USA. It is less severe and less lethal than its cousin, MPox Clade I, that is endemic in regions of Africa including DRC. A new variant of Clade I, namely I.b, caused a severe epidemic leading to a Public Health Emergency of Continental Security by the Africa CDC on August 13, 2024, followed by a new PHEIC declaration by the WHO on the following day. The WHO has rescinded the PHEIC declaration on September 5, 2025, citing decrease in cases in DRC and nearby regions previously affected, whereas the Africa CDC has voted to continue the PHECS designation on September 3, 2025, due to continued spread of the MPox virus into new countries in the region, as well as rise in cases in several regions neighboring to the previous hot zones.
Smallpox is designated as an important bioterrorism target in the USA and other countries. There are two drugs currently approved for smallpox in the USA. Tecovirimat (TPOXX®, SIGA) was approved earlier, with substantial US Government funding during development, and is stockpiled in the US Strategic National Stockpile (SNS). Replenishment orders have amounted to hundreds of millions of dollars per year. Brincidofovir (TEMBREXA, previously Chimerix, now Emergent Bio) was approved more recently for Smallpox and is also now in the SNS. Both tecovirimat and brincidofovir were developed using the US FDA “Animal Rule” pathway, since clinical trials with human volunteers for Smallpox are considered unethical.
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Tecovirimat inhibits the release of the virus from infected cells after replication, whereas brincidofovir inhibits the synthesis of the viral DNA. A single point mutation in the virus protein VP-37 is known to cause resistance to tecovirimat. Brincidofovir is said to have a higher bar of resistance to mutation in viruses. Brincidofovir, according to its prescribing information,1 (i) carries a “Black Box Warning” due to observed increase in mortality in an unrelated disease clinical trial upon extended use; (ii) was found to cause diarrhea in 40% of patients, with 5% discontinuations; (iii) was found to cause elevations in hepatic (i.e. liver) transaminases and bilirubin; (iv) is considered a human carcinogen; (v) may cause embryonic or fetal harm; and (vi) may irreversibly impair fertility. Tecovirimat was tried in a clinical trial called PALM007 for treatment of MPox and the results announced by the US NIH stated that while it was found to be safe and well tolerated, it was not superior to the placebo, in August 20242. In a separate international Phase III clinical trial called UNITY, tecovirimat failed to demonstrate improvement over placebo as reported on July 17, 20253. Brincidofovir has entered a clinical trial called MOSA for treatment of MPox in January 2025, and interim results were anticipated in Q1 2025, according to the press release by Africa CDC4. The current status of this brincidofovir for MPox clinical trial is not publicly known.
At present, there is no drug approved for the treatment of MPox.
Thus, clearly there is a need for a safe and effective drug against Smallpox that would be of interest to the US Government as well as other international agencies. There is potential for drug development funding by the US Government as well as potential for revenues in several hundred million dollar range for a successful drug upon approval for biodefense stockpiling. Additionally, the market size for a successful treatment for MPox in the developed world is expected to be significant, and together with the rest of the world, globally, it would be a significant opportunity.
We are seeking non-dilutive funding for progressing NV-387 towards regulatory approval for treatment of Smallpox under the US FDA “Animal Rule”. We believe that positive data, if the Phase II of NV-387 for treating MPox is successful, would go a long way towards the goal of approval of NV-387 for Smallpox as well, because MPox is an orthopoxvirus closely related to the Variola virus that causes Smallpox.
We believe our animal model study results for the lethal orthopoxvirus infection via the dermal infection route as well as via direct inhalation of viral particles into lungs are sufficiently robust to generate confidence to anticipate positive outcome from the proposed Phase II clinical trial of NV-387 for the treatment of MPox.
We plan on applying for an “Orphan Drug Designation” from the US FDA for the use of NV-387 for the treatment of MPox. We also plan on applying for an “Orphan Drug Designation” from the US FDA for the use of NV-387 for the treatment of Smallpox.
The Orphan drug designation has several advantages, including waiver of certain PDUFA FDA fees, tax credit for research and development, as well as a seven year exclusivity after approval. The Orphan designation is also expected to enable important FDA engagement and potentially rapid reviews.
We plan on filing IND with the US FDA for the use of NV-387 for the treatment of MPox as well as Smallpox, which are both Orthopoxviruses. As of now, we have not formally engaged with the US FDA for these initiatives.
Benefits of Our Regulatory Approach for NV-387 – Viral-ARI, Viral-SARI
As stated above, the Phase II clinical trial to evaluate NV-387 as a treatment for viral respiratory infections is expected to provide substantial data on safety and effectiveness of NV-387 against a large number of viral targets. Importantly, we anticipate that it will provide data on the effectiveness of NV-387 in Influenza, RSV as well as Coronaviruses.
1 https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214460s000,214461s000lbl.pdf.
2 https://www.nih.gov/news-events/news-releases/antiviral-tecovirimat-safe-did-not-improve-clade-i-mpox-resolution-democratic-republic-congo.
3 https://mpx-response.eu/large-international-trial-unity-reports-no-clinical-benefit-from-tecovirimat-for-mpox-resolution/
4 https://africacdc.org/news-item/enrollment-starts-in-africa-cdc-led-mpox-therapeutic-study-mosa/.
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Influenza is a multi-billion dollar market, and it is also an important initiative for the US Agency known as BARDA. Currently available treatments, namely oseltamivir (Tamiflu® , Roche), peramivir (Rapivab®, BioCryst), baloxavir (Xofluza®, Shionogi, Roche) and others are all known to be susceptible to virus escape by simple mutations. Thus there is an unmet medical need for an Influenza treatment that the virus cannot escape from. We note that in lethal lung infection animal model of Influenza, NV-387 was found to be substantially superior to each of the three approved drugs listed above. This leads us to believe that NV-387 would be able to go through regulatory clinical trials for Influenza viruses successfully and would be able to receive regulatory approvals.
There is no drug approved for the treatment of RSV infection, other than ribavirin which is only used in extreme cases due to its severe toxicity. We note that in lethal lung infection animal model of RSV, NV-387 was found to completely cure treated animal. This leads us to believe that NV-387 would be able to go through regulatory clinical trials for RSV successfully and would be able to receive regulatory approvals.
We therefore plan on further developing NV-387 in a regulatory process towards treatment of pediatric patients with RSV infection, an unmet medical need.
Having a single drug with broad applications enables us to minimize the regulatory development workload, minimize costs, as well as develop rapid timelines due to common or overlapping workload across the various indications. We believe this would lead to significantly robust commercial footing as well as significantly improved returns on investments if and when NV-387 reaches commercialization resulting in revenues.
NV-387 for Measles Treatment
Measles outbreaks are increasing globally. In particular, USA has seen over 1400 confirmed cases in 2025 with three fatalities5. Measles was declared eliminated in the USA as of 2000, with only travel-related cases occurring sporadically. Additionally, Canada has seen an increase of over 20x in measles cases since 2024, with more than 4,200 cases reported by the end of July 20256. In 2024, measles cases in Europe rose to over 32,000 from slightly less than 4,000 cases in 20237. There were approximately 360,000 confirmed cases of measles globally in 2024 according to WHO8. Measles continues to be an important disease for children despite a highly effective vaccine.
Measles virus is perhaps the most contagious virus known. Because of this, 95% of population vaccination level is required to ensure population immunity (“herd immunity”). This number has become increasingly difficult to achieve for several reasons. There is an increasing population of immune-compromised persons, as well as persons with auto-immune conditions, that may not benefit from the vaccine. There is also vaccine hesitancy that has increased significantly worldwide since the COVID-19 pandemic. Erosion of population’s trust in public health agencies and officials has substantially increased as well.
Additionally, the current measles virus vaccine is a live attenuated vaccine that dates back to 1968. The measles virus has evolved substantially since then, although this vaccine continues to remain effective, and vaccine breakthrough is estimated to be about 5% of cases. Nevertheless, there are data suggesting that vaccine breakthrough is increasing and in some episodes could be substantially greater than 5%9, indicating a partial virus escape.
Measles infection can lead to what is known as “immune amnesia” in some patients. Since measles virus attacks the immune cells responsible for creating and maintaining immunity against infectious agents, a severe bout of measles can lead to the wipe-out of the very memory immune cells that provide protection from previously experienced infectious agents, making the subject fully vulnerable again. This is why, even though measles itself has low fatality rates (estimated at 0.1% to 0.3%), it is important to keep this virus at bay from public health perspective.
5 https://www.cdc.gov/measles/data-research/index.html.
6 https://health-infobase.canada.ca/measles-rubella/.
7 https://www.ecdc.europa.eu/en/news-events/measles-rise-again-europe-time-check-your-vaccination-status.
8 https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Fimmunizationdata.who.int%2Fdocs%2F librariesprovider21%2Fmeasles-and-rubella%2Fglobal-mr-update.pptx%3Fsfvrsn%3D3547ebab_9&wdOrigin=BROWSELINK
9 https://pmc.ncbi.nlm.nih.gov/articles/PMC11209263/.
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A treatment for measles is therefore an important unmet medical need, as more of the global population becomes vulnerable to measles, and as the measles virus is likely on the cusp of escaping, at least partially, the current measles vaccine.
There is no approved treatment for measles. Vitamin supplementation was found to be beneficial in setting of nutritional deficiencies. Ribavirin, a highly toxic drug, is recommended by CDC for severe hospitalized cases but is not approved.
We performed a humanized animal model study to evaluate the effectiveness of NV-387 in lethal respiratory infection by measles virus. In this study, we found that NV-387 was able to increase the survival lifespan of the lethally infected mice significantly. We believe that this data provides sufficient rationale for a physician to use NV-387 for the treatment of a case of measles under a FDA pathway called the Physician-Initiated IND. We plan on providing the supporting datasets to enable such Physician-Initiated IND process.
With the small number of cases globally, development of drug specifically for measles is not economically viable to undertake. However, an indication for the use of NV-387 for the treatment of measles is viable in the context of a FDA rare disease pathway.
NV-387 for treatment of measles would be eligible for an Orphan Drug Designation with attendant benefits in the USA.
Other Drug Programs
In addition, we have a strong and wide drug pipeline developed over a number of years. NV-HHV-1, our drug candidate formulated as a skin cream for the treatment of Shingles, has completed regulatory required safety-pharmacology studies towards filing a US FDA IND for this drug. NV-HHV-1 skin cream could be further developed for the indications of HSV-1 cold sores treatment and HSV-2 genital ulcers treatment. In addition, we are developing a single systemic drug that would potentially be indicated for the treatment of HSV-1, HSV-2 as well as Shingles and Chickenpox viruses.
NV-HIV-1 has demonstrated anti-HIV activity in the standard SCID-Hu-Thy-Liv mouse model of HIV infection that we believe is strong enough to warrant further regulatory development of this drug candidate. In all, we have been working on over forty different viral disease indications with the purpose of developing drug candidates that are well-differentiated from existing drugs if any against these indications as described further down in this report.
Our other drug candidates are at earlier pre-clinical development stages.
Our Commercialization Strategy
The drug development process is long and expensive. As of the date of this report, we do not have any approved drugs on the market. We have no customers, products or revenues to date, and may never achieve revenues or profitable operations. We continue to add to our existing portfolio of products through our robust internal discovery and clinical development programs.
We believe we have developed several assets worthy of partnering for further regulatory development and commercialization. We seek to partner and out-license our drug candidates for these purposes. Such partnering may potentially involve initial license fees, milestone payments, and royalty payments to us that could result in an early revenue stream prior to commercial product sales.
Our business plan is based on developing the drug candidates into regulatory approvals, and partnering and sub-licensing for commercialization of the drugs whenever possible. We have begun the process of actively seeking partnerships by retaining a consulting firm, Aagami, Inc., based in Illinois. Aagami specializes in developing pharma collaborations primarily with Indian and Japanese big pharma companies, and also world-wide. We anticipate adding business development efforts in the western countries as we further develop NV-387 into a Phase II clinical trial. A Phase II clinical trial is designed for the evaluation of effectiveness of a drug for its indication and is considered a “proof-of-concept” in humans that the drug is likely to succeed in regulatory approvals. Prior to entering clinical trials, we have developed substantial “proof-of-concept” information regarding our drug candidates in relevant animal models.
We plan on seeking non-dilutive grants and contracts funding for our drug candidates that are responsive to bio-defense and pandemic-preparedness objectives, in particular, the drug development of NV-387 for Smallpox under the US FDA Animal Rule. However, there can be no assurance that we will be able to obtain grants or funding for these projects or that it will be on terms favorable to us.
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There is no guarantee that we will be successful in partnering our drug candidates or obtaining non-dilutive funding for furtherance of our drug development programs. We plan on continuing drug development on our own all the way through regulatory approvals if successful collaborations are not established. We plan on continuing to finance our efforts using equity-based financing, at least until an appropriate collaboration with a suitable pharma company for one or more indications of our drug candidates takes place.
To date, we have financed our drug development programs using equity-based financing from the sale of our shares in private and public offerings including registered direct offerings as well as “At the Market” (ATM) offerings.
The Nanoviricide Platform Technology in Brief
“Resistance is Futile”: NanoViricide Platform Promises Antiviral Drugs That The Virus Is Unlikely To Escape Even As It Evolves
The greatest “pain” or intractable problem in antivirals development has been that viruses rapidly evolve to evade the vaccines, antibodies, and small therapeutics that are the traditional antiviral approaches. Small changes in enzymes attacked by the small chemical antivirals lead to antiviral drug resistance. Small changes in the virus “antigens” lead to resistance to vaccines and antibodies, because these antiviral approaches are highly specific to the antigens that they are designed against. Antibodies are extremely specific and therefore even minor changes in the virus tend to make them ineffective. Antibodies and vaccines are readily evaded by viruses under the evolutionary pressure in a natural process itself.
We believe this is now common knowledge after the COVID pandemic.
In contrast, novel nanoviricideTM platform technology enables a host-mimetic, direct-acting, antiviral nanomachine drug which the virus cannot escape even as it evolves.
Our novel nanoviricide class of drug candidates are designed to specifically attack and dismantle enveloped virus particles, by mimicking the host-side features that the virus particle lands on as it infects a host cell. In spite of even relatively large changes in a specific virus’s surface glycoproteins as it evolves, the viral glycoprotein continues to retain, and often enhances, its ability to attach to specific host-side “attachment” receptors, and thereafter by transferring to a more specific “cognate receptor” on the cell to gain cell entry and cause infection. For example, Influenza viruses use Heparan Sulfate Proteoglycan (HSPG) as “Attachment Receptor” and Sialic Acid (or sialylated glycoproteins) as the “Cognate Receptor.”
Nanoviricides mimic either the attachment receptors or the cognate receptors and present a large number of viral binding sites on each nanoviricide polymeric micelle. Further, the nanoviricide polymeric micelle is designed to “look like” a cell to the virus.
Even as new virus variants develop that evade existing antibodies and vaccines, the variants continue to bind to their cellular attachment receptor(s) and the cellular cognate receptor(s) at the same sites and in the same manner, despite changes in the viral glycoprotein itself. Thus, if we design the ligands correctly, the nanoviricide would continue to be effective even as the virus keeps changing in the field, in stark contrast to antibodies and vaccines that readily lose effectiveness as the virus evolves.
A nanoviricide is a “biomimetic” - it is designed to appear to the virus like the cell surface bearing the sites that the virus binds to. The nanoviricide technology enables direct attacks at multiple points on a virus particle. Since the host-side or cell-side binding sites for a given virus do not change despite mutations and other changes in the virus, we believe that the virus would be highly unlikely to escape our drug candidates even as a virus changes rapidly as it evolves.
Therefore, we believe that our unique host-mimetic approach would result in a nanoviricide drug that a virus cannot escape even as it changes in the field, because it will continue to use the same host-side landing site features (attachment receptors and/or cognate receptors) despite all the changes in its own glycoproteins that bind to those features, if the virus-binding ligands we design for the nanoviricide drug perform as designed.
As described further below, the Nanoviricides Platform provides for modalities that can result in potential cures for viruses that do not establish latent virus infection in humans.
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A NanoViricide is a Nanomachine that Does Not Require Competent Immune System and Completes the Task of Dismantling Virus Particles Without Host Machinery Involvement
There are two principal parts to a virus’s lifecycle. The first is to infect a new cell, called “Re-Infection” in virology (the very first virus acquisition, from an external source, is called the “Primary Infection”). The second is to replicate in the infected cell, make new virus particles and then egress into bodily fluids outside the cell, called “Replication.” Most small chemical drugs are designed to affect the replication part, and must go into cells, raising toxicity concerns or reduced safety margins as they interfere with the cellular machinery. Thus, almost all currently existing nucleoside/nucleotide drugs are toxic by their very nature to varying extents.
Vaccines and antibodies have been regarded as the standard pillars of antiviral medical countermeasures. Vaccines generate antibodies, and antibodies (from vaccine or externally applied drug), block the virus by directly binding to it, but these countermeasures are (a) highly specific and thus readily escaped by viruses, and (b) require the human immune system to be in good shape. Vaccines depend upon the patient’s immune system to generate new antibodies, whereas antibodies depend upon the patient’s immune system for proper destruction of the virus particle that the antibody “tells” the immune system to “take care of this enemy.”
Nanoviricides, in contrast, do not require the patient to have a functionally good immune system because a nanoviricide is designed as a complete nanomachine that completes the task of dismantling the virus particle. This is important because most persons with good immune systems, when infected with a virus, experience only mild infections, and may not even notice symptoms. Persons with an immune system that is not sufficiently active are the ones that would suffer severe viral infections. Additionally, viruses have evolved to block various steps in the human immune system response, thus derailing the immune system once the infection takes hold.
NanoViricide Drugs Are Designed To Act By A Novel Mechanism of Action, “Re-Infection Inhibition”, To Reduce Viremia
A nanoviricide exposes a very high density of virus binding sites on its surface, in contrast to a human cell. Thus, a virus would be more likely to be captured by the nanoviricide than to bind to a cell. As the nanoviricide polymeric micelle interacts with the virus particle, the nanoviricide is capable of binding to the virus at multiple points, and while doing so, wrapping itself around the virus by virtue of a well-known physical chemistry effect called “lipid-lipid mixing.” In the process, the specific glycoproteins that the virus uses for binding to the cell (for example, the HIV gp120, RSV-G protein, Influenza H and N proteins, Coronavirus S or “Spike” protein) are expected to be neutralized and dismantled. It is believed that such attack would lead to the virus particle becoming ineffective at infecting cells.
Therefore, we call this novel mechanism of action of nanoviricide by the name “Re-Infection Inhibition.”
Nanoviricides are designed to work by binding to and eliminating virus particles from the blood stream, just as antibodies do, only potentially much better. Treating a patient that has a viral infection with a nanoviricide against that virus is expected to result in reduction in viremia. Reduction in viremia is an important goal in diseases caused by all viral infections. Nanoviricides are designed to accomplish this using a “Bind-Engulf-Destroy” strategy to eliminate the free virus.
It is important to realize that the flexible, “shape-shifting” nanoviricides nanomedicines show substantial advantages over hard sphere nanoparticles in this antiviral drug application as the nanoviricides enable lipid-lipid mixing with the viral envelope and can wrap around or merge with the virus surface. Hard sphere nanomaterials such as dendritic materials (dendrimers), nanogold shells, silica, gold or titanium nanospheres, polymeric particles (such as PLA-PLGA, others), etc., were never designed to be capable of completely enveloping and neutralizing the virus particle.
NanoViricides Platform is Designed for Safety
We create the polymer that makes the nanoviricide micelle by using naturally metabolizable and safe components. Additionally, the antiviral ligands that we attach to the base polymer are designed using molecular modeling (or “in-silico” design) while using generally safe component chemicals and chemistries.
The nanoviricide polymer structure is designed to directly attack the virus particles outside the cell. Therefore, we believe that interference from such nanoviricide drug with cellular machinery is likely to be minimal, thereby resulting in improved safety over drugs that must enter cells and interfere with cellular processes such as most available small chemical antivirals.
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We believe that our approach for improved drug safety is validated by the demonstration of strong relevant results in animal studies of NV-387 for safety and tolerability. In a safety/toxicity evaluation of single injection in rats, NV-387 was found to have a No-Observed-Adverse-Effect-Level (NOAEL) of 1,200 mg/Kg/dose, and a Maximum Tolerated Dose (MTD) of 1,500 mg/Kg/dose, which are considered to be relatively high numbers. A drug with higher values of NOAEL and MTD is safer than one with a lower values.
Further, in the non-clinical GLP safety/toxicology studies in relevant animal models, NV-387 was found to lead to no reportable observations (i.e. no adverse events) in respiratory and neurological studies in rats and cardiotoxicity studies in a non-human primate model (cynomolgus monkey). Intravenous infusion of NV-387 did not have any toxicologic effects on cardiac rhythm or ECG morphology in cynomolgus monkeys. Intravenous infusion of NV-387 did not affect respiratory function and no significant neuropharmacological or behavioral effects were observed in rats. Body temperature was not affected by the drug treatment in either the rat or the NHP animal model study. All of these results are indicators that the drug NV-387 was well-tolerated in these animal models and thereby enabled us to obtain regulatory approvals to begin Phase Ia/Ib human safety/tolerability studies in healthy subjects.
NV-387 was found to be non-immunogenic, non-allergenic, non-mutagenic, and non-genotoxic. As such carcinogenicity studies are not required.
Consistent with the above non-clinical data, in a Phase Ia/Ib clinical trial evaluating the safety and tolerability of NV-387 treatment in healthy adult human subjects, there were no discontinuations, there were no adverse events reported, and there were no serious adverse events reported, even at the highest dosage levels in both single dosing and multiple dosing protocols.
Nanoviricides Platform Has Enabled Industry-Leading Orally Available Nanomedicines And Multiple Routes of Administration
We found that unlike almost all other nanomedicine platforms, our nanoviricide NV-387, the active pharmaceutical ingredient (API) of NV-CoV-2, demonstrated strong activity when administered orally in multiple animal models. Most nanomedicines do not possess significant oral bioavailability and therefore they have to be administered as injections or infusions. This oral bioavailability of our nanoviricides distinguishes our technology from almost all of the rest of the nanomedicines world.
We developed two different oral formulations of NV-387, namely “NV-CoV-2 Oral Syrup” and “NV-CoV-2 Oral Gummies.” The latter is a semi-solid fixed-dose form. The oral syrup enables body-weight-based dose titration as needed for pediatric treatments. Both of these formulations have been evaluated in the Phase Ia/Ib human clinical trial of NV-387.
The oral dosage forms are expected to provide wide-spread adoption across the entire population from children to senior citizens, and special cases such as immune-compromised patients outside the hospital. The Oral Gummies fixed dosage form has the advantage that it is suitable even for patients that cannot swallow the usual hard tablets or capsules, because it slowly dissolves in the mouth as it is absorbed.
We have also developed a NV-387 formulation called “NV-387 Solution for Injection, Infusion and Inhalation.” We believe treatment of severe cases that are not yet hospitalized would be best performed by an injection. Hospitalized patients would benefit most from the 100% bio-availability of the injection route, and may be dosed with an infusion if larger quantity of dosing is warranted.
Importantly, the same injectable solution can be readily delivered directly into the lungs as a fog created using standard portable battery operated nebulizer devices. This enables direct and quick action at the most important site of infection by a respiratory virus such as coronaviruses, RSV, influenzas, human meta-pneumovirus (hMPV), certain adenoviruses, and others, that can lead to severe pneumonia.
Thus, the unique versatility of the Nanoviricide Platform has enabled creation of a drug NV-387 in multiple formulations that allow usage across all segments of the population from children to healthy adults to geriatric patients, as well as administration across all levels of disease severity from at-home mild to moderate cases (oral syrup and oral gummies) and out-patient moderate-to-severe cases (injections), to in-patient severe cases (injections and infusions), to in-patient severe-to-morbid cases (infusions and inhalations).
Nanoviricides Represent the Next Generation Development Beyond Classical Immunotherapeutics (Antibodies and Vaccines)
Our nanoviricide technology relies on copying the human cell-surface receptor to which the virus binds, and making small chemicals that are called “ligands” that will bind to the virus in the same fashion as the host side attachment receptor or the cognate receptor (see below). These ligands are chemically attached to the base polymer or “nanomicelle,” to create a nanoviricide.
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When a nanoviricide nanomicelle “sees” a virus particle, several of these ligands associated with the nanomicelle are expected to bind to the virus particle. Once bound to the virus, it is thought that the nanoviricide would wrap itself around the virus, and the interior lipidic chains of the nanoviricide would merge into the lipid envelope of an enveloped virus, thus destabilizing the virus, in a “nano-Velcro” effect. This attack is expected to result in loss of the viral glycoproteins that the virus uses to bind to cell and to fuse with the cell membrane, thus rendering the virus particle non-infectious.
A class of small molecules called entry inhibitors exists. These drugs are designed to bind to the virus to stop it from binding to cells. A very large number of these small molecules must simultaneously attack the virus particle for the particle to be fully inhibited – a task that has very low probability in vivo (“kinetic hurdle”). Also, for small molecules to possess sufficient affinity to the virus particle, they must be designed to be very specific to the viral glycoprotein structures. Therefore, entry inhibitors can be rapidly rendered ineffective as the virus changes.
Antibodies can bind a virus particle at only a maximum of two attachment points per antibody. Several antibodies are required to simultaneously bind to the virus particle to neutralize it, in contrast to a nanoviricide that is expected to bind to the virus at multiple points.
For an antibody to be successful as an antiviral drug, as many as ten to fifteen antibodies must bind to saturate the virus surface. Therefore successful antiviral antibodies are highly specific to the virus glycoproteins and rapidly become ineffective as the virus changes.
The resulting antibody-virus complex then may be subject to the complement protein system in the bloodstream, or it may bind to antibody-receptors on human immune cells. Thus, the human immune system needs to be functional for an antibody to be effective as a “drug”.
In a sense, antibodies only “flag” the virus particle as foreign. In contrast, a nanoviricide would complete the job of making the virus particle non-infectious, without any help from the human immune system.
Almost any virus that causes pathology in humans is able to do so because it has developed intelligent and complicated pathways for disabling the human immune system at one or more points. This may be one of the reasons why many antiviral antibodies fail in the field use. Additionally, viruses readily escape antibodies by mutations, and, in some cases, reassortment. Such viral escape from antibodies has been witnessed in almost every viral epidemic, be it HIV/AIDS, the Influenza pandemic of 2009, the Ebola epidemic of 2014-15, or the COVID epidemic that is continuing now as a perennial phenomenon. In contrast, despite mutations and other changes, a virus is unlikely to escape a nanoviricides drug designed against it.
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 on the nanomicelle, but it would also get entrapped because the nanomicelle polymer would turn around and fuse with the virus lipid envelop, 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 thereafter 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.
Thus, the Nanoviricide Platform technology can be viewed as the next step in evolution of antibody-based approach, taking into account and eliminating the limitations of antibodies.
Drug Manufacturing and Quality Control Considerations Are Inherent in the Design of a Nanoviricide
Uniform Polymer Nature Of The Nanoviricide Polymer Enables Simplified Nanomedicine Manufacturing Quality Assurance
A major problem in the field of nanomedicines as well as lipid-nanoparticles (LNPs) has been that most nanomedicines and LNPs have been found to be notoriously difficult to manufacture in a consistent manner from batch to batch. This is because of the complexity inherent in making large molecules, the very nature of polymer and particle making processes, particularly in the case of block-copolymers that are commonly employed, and the fact that many nanomedicines and particularly LNPs are mixtures of multiple components.
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The Nanoviricide Platform technology has been designed from the ground up to enable consistent manufacture and control. Thus, the nanoviricide backbone is a “homopolymer” (i.e. it is made up of a single repeating unit or monomer), which enables a naturally uniform structure. This is unlike block-copolymers wherein there is structural heterogeneity along the polymer chain that is generally difficult to control and characterize. In addition, the nanoviricide polymer is designed to dynamically and naturally self-assemble into micelles in a solution. Also, the virus-binding ligands are chemically attached to the polymer. The extent of attachment can be characterized by analytical techniques that we have developed and continue to develop as needed. Further, we use specialized techniques in the polymer processing to minimize any contamination with endotoxins or other foreign particles as well as to remove impurities. The final nanoviricide solutions are sterile filtered using standard membrane filtration processes.
Formulation is Inherent in the Design Aspect of a Nanoviricide
Since developing our lead clinical drug candidate API NV-387, development of its formulations, injectable, infusion, inhalation, oral syrup, and oral gummies (semi-solid form) was relatively quick, accomplished within months, including formulation design and scale-up with cGMP-compliance manufacturing considerations. Similarly, since declaring our shingles clinical candidate, NV-HHV-1, its formulation as a skin cream for topical treatment of shingles rash, and scale-up, and cGMP-compliant manufacture was accomplished relatively rapidly, within a few months.
In the nanoviricide approach, the nanomicelle polymeric backbone itself takes care of the formulation aspects. The nanomicelle is designed to optimize the drug for its intended route of administration, be it injectable, skin cream, eye drops, or even oral. Thus, no specific or extensive formulation development is expected to be required during drug development.
In contrast, formulation development for novel drugs in normal pharmaceutical paradigm often takes years. In particular, formulation development with nanomedicines or LNPs generally takes longer than that for small chemical drugs, due to inherent complexities discussed earlier.
Thus, the Nanoviricides Platform has been designed from the ground up to enable simplifications in processes and analyses that need to be implemented in order to develop robust, reproducible, and scalable processes.
NanoViricide Platform Enables Drugs That Can Be Designed To Block the Complete Virus Lifecycle, Thus Enabling Potential Cure for Non-Latency Viruses
A nanoviricide is made by chemically covalently linking a “nanomicelle” - a globular polymeric micelle with pendant lipid chains inside - to one or more different small chemical ligands designed to mimic the cellular receptor to which the virus binds. In addition, the nanoviricide can carry additional active pharmaceutical ingredients (APIs), which may be chosen to affect the intracellular virus life cycle. Thus, the nanoviricide platform enables construction of complete virus-killing nanomachines that block the virus from entering the cell as well as that block further production of the virus inside the cell.
We are implementing the nanoviricides platform in different modalities leading to different types of drugs to meet the different challenges of different viruses and enable cures for viral diseases.
Nanoviricides Platform Modality 1: Broad-Spectrum Antiviral “Reinfection Inhibitors”
There are certain classes of cellular features that a very large number of viruses commonly use to get access to cells. As a first step, the virus binds to one so called “Attachment Receptor(s).” This allows the virus to concentrate near the target cells, and enables the virus particles to latch onto more specific receptors on the cell surface itself that are termed “Cognate Receptor(s).” Some viruses can directly fuse with the cell membrane without such a cognate receptor.
The attachment receptors employed by most viruses fall into very few families. One such family is “Sulfated Proteoglycans (S-PG),” or “Glycosaminoglycans (GAGs).” We loosely include a number of sulfated proteoglycan types in this “S-PG class”. They differ in exact structures but share a number of commonalities. This family includes proteoglycans that have attached onto them heparan sulfate (HSPG), dermatan sulfate (DSPG), chondroitin sulfate (CSPG), or keratan sulfate (CSPG). 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, among others.
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For many of these viruses there are no antivirals available, or the antivirals have limited applicability. Nanoviricides that mimics the host-side S-PG can be expected to be capable of attacking many of these viruses, enabling very broad-spectrum antiviral agent. This is reminiscent of the development of beta-lactam antibiotics starting with penicillin, that have broad-spectrum antibacterial properties because they attack a common feature of a large number of bacteria, the peptidoglycan cell wall.
NV-387, our clinical drug candidate, is the first example, to our knowledge, of such a broad-spectrum antiviral agent. NV-387 was designed using our knowledge of the commonalities in this S-PG class of attachment receptors for mimicking the host-side S-PG common motif that is used by viruses for attachment. A developed small chemical ligands that embody the characteristics of this common motif, and attached them to the base nanomicelle polymer to create NV-387. Thus, NV-387 is designed as a broad-spectrum antiviral agent. After its success in attacking multiple unrelated coronaviruses, we have undertaken a program to expand the potential indications of NV-387. Effectiveness in any of these additional indications would enable direct entry into Phase II/III clinical trials for that indication now that a Phase I clinical trial of NV-387 has been completed, after the final clinical trial report for this clinical trial becomes available.
In July 2023, we reported that NV-387 was found to demonstrate increase in survival upon treatment with NV-387 indicating antiviral effectiveness against a lethal RSV infection in a mouse model study. Subsequently, in May 2024, we reported that in a subsequent study with improved dosing regimen, NV-387 was able to lead to complete survival of the animals lethally infected with RSV, and that the lungs of the NV-387 treated animals did not show lung damage caused by the RSV. In contrast, ribavirin treatment did not protect the lungs of the RSV infected animals leading to their death with a small increase in survival over the untreated animals.
In June 2024, we reported that NV-387 treatment was found to demonstrate increase in survival, substantially surpassing the increase that occurred upon treatment with three of well-known approved anti-influenza drugs, a parameter used for indicating antiviral effectiveness, in a lethal Influenza A/H3N2 lung infection mouse model study. We believe that these results suggest that NV-387 promises to be effective against the “bird flu” influenza virus H5N1 (and other similar H5Nx viruses) as well. In fact, it is well-known that the highly pathogenic avian influenza (HPAI) viruses carry a “polybasic site” that possesses HSPG binding capability. Therefore, HPAI viruses can be expected to be susceptible to NV-387.
In the reported year, we have also reported on the antiviral activity of NV-387 in animal models relevant to Smallpox/Mpox (orthopoxvirus) infections, measured by increase in survival in relevant lethal virus-challenge animal models. MPox has caused sporadic epidemics in the Western world, and a more pathogenic strain, MPOX CladeI/Ib is currently causing an epidemic in certain parts of Central Africa, which has led the WHO to declare it a “public health emergency of international concern” (PHEIC). Smallpox is considered a bioterrorism threat. Of note, tecovirimat, approved for Smallpox treatment in the USA, has failed to show effectiveness in an NIH co-sponsored international clinical trial for the treatment of MPOX Clade 1 infections (https://www.nih.gov/news-events/news-releases/antiviral-tecovirimat-safe-did-not-improve-clade-i-mpox-resolution-democratic-republic-congo). Therefore, we believe it would be of interest to assess whether NV-387 has effectiveness in MPOX infected patients.
We intend, subject to financing, to further explore the effectiveness of NV-387 against many other important human pathogenic viruses that are known to utilize S-PG attachment receptors. For example, Nipah virus causes sporadic lethal outbreaks in India and Bangladesh in particular. We would like to explore if NV-387 can be an effective drug against Nipah and the related Hendra viruses (henipaviruses). Additionally, Ebola and Marburg viruses (filoviruses) are also known to utilize HSPG attachment factor. We would like to explore if NV-387 can be an effective drug against filoviruses. Filoviruses are important for the US Department of Defense as well as from Biodefense perspective. Currently there is no approved treatment for filoviruses or for henipaviruses. Such expansion of use of NV-387 would significantly expand the market size, provide much needed medical countermeasures for public health protection globally, and substantially improve the return on investments (ROI).
Another important class of attachment receptors is Sialic Acids (SA). We are working on developing broad-spectrum antivirals mimicking SA. SA is well known as the initial site of binding for Influenza viruses, as well as many of the infectious Adenoviruses and many other viruses.
It would be very difficult for a virus to become resistant to a nanoviricide that mimics the virus’ attachment receptor. This is firstly because the nanoviricides based on mimicking attachment receptors are broad-spectrum in nature, capable of antiviral effect against not just a specific virus type or subtype, strain or variant, but entire families of viruses (as defined in the virus classification system), and secondly, because, no matter how much a virus mutates or changes, its binding to the host-side receptor(s) does not change.
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Nanoviricides Platform Modality 2: Specific, Highly Effective, Antiviral “Reinfection Inhibitors”
Choosing a specific antiviral ligand that mimics the cognate receptor on the host cell that is used by the virus would lead to specific nanoviricide agents that would attack the viruses that use that particular cognate receptor. This technique is what we call Modality 2.
In addition to developing bio-mimetics of the broad-spectrum attachment receptors, we have also developed nanoviricides that mimic the specific cognate receptor(s) used by a particular type of virus to develop highly specific drugs against that type of virus.
Our antiviral drug candidate NV-HHV-1 is based on mimicking the cognate receptor HVEM (“herpesvirus entry mediator”) that is known to be used by HSV-1 and HSV-2. We found that NV-HHV-1 demonstrated antiviral activity against VZV (Varicella Zoster Virus) in human skin patch infection model studies, although it was not then known whether VZV uses HVEM as the cognate receptor. VZV causes chickenpox in children and immune-compromised persons, and its reactivation causes Shingles in adults. NV-HHV-1 has completed pre-clinical IND-enabling studies as a skin cream for the treatment of VZV Shingles. During the development of NV-HHV-1, nanoviricides made with the same or related ligands as the one used in NV-HHV-1 were found to have demonstrated antiviral activity against HSV-1 in cell culture studies as well as in lethal infection animal model studies. Since HSV-2 also uses HVEM as entry receptor, we believe NV-HHV-1 should be effective against HSV-2 as well. In addition to developing NV-HHV-1 for the indications involving infection by VZV, HSV-1, and HSV-2, we further plan to explore the activity of NV-HHV-1 against other herpesviruses such as CMV and EBV as well.
Additionally, we have developed drug candidates in the HIVCideTM Program that mimic the cellular CD4 binding site used by HIV to gain cell entry. Another important HIV cognate receptor is CCR5. The Nanoviricides Platform enables using mimics of one or more cellular receptors attached into a single nanoviricide drug. Thus, this platform has the capability of mimicking both the CD4 binding site and the CCR5 binding site of HIV on one nanoviricide, which is expected to enable the most effective drug against HIV. The only countable number of patients that have been “cured” of HIV were recipients of stem cells that possess a modified CCR5 lacking its HIV-binding region, attesting to the importance of mimicking both CD4 and CCR5 simultaneously.
Attacking the “Achilles Heel” of the Virus- Unchanging Ability of the Virus to Bind to Its Cognate Receptor on Cell
We strive hard to develop virus-binding small chemical ligands that mimic the cognate cellular receptor of the virus, using rational design and molecular modeling strategies and our internal, accumulated expertise. Some viruses use more than one receptor. The nanoviricide platform technology allows use of different ligands on the same nanoviricide drug to be able to attack such difficult viruses.
It would be very difficult for a virus to become resistant to a nanoviricide that mimics the virus’ cognate cellular receptor. This is because, no matter how much a virus mutates or changes, its binding to the cellular receptor does not change. If the virus does not bind to the nanoviricide efficiently, it would likely have lost its ability to bind to the cellular receptor efficiently as well, resulting in an attenuated version with limited pathogenicity.
Nanoviricides Platform Modality 3: Nanoviricides Platform Enables Cures for Viruses that Do Not Become Latent
To date most viral infections do not even have effective drugs, let alone cures.
Most viruses do not become latent in the human body. Such viruses have a relatively simple life cycle: after a virus is transmitted to the person and infects some cells, it replicates inside the infected cell (the replication part), thereafter the new virus copies exit the cell and then infect new cells (the “re-infection” part) thus starting the cycle over again. If both parts of the life cycle can be blocked effectively, then such a virus infection can be readily cured. The Nanoviricide Platform Modality 3 enables such cures.
In this modality, the nanoviricide technology simultaneously enables attacking the external virus particle, as well as blocking the rapid intracellular reproduction of the virus by incorporating one or more APIs within the “belly” 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, thereby enabling complete control of a virus infection.
The nanoviricides built using Modality 1 as well as Modality 2 can be employed to add the replication-inhibition capability in this manner.
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NV-CoV-2-R, our other drug in development for treatment of coronaviruses contains the API NV-387-R. This API is made up of remdesivir encapsulated within the belly of the polymeric micelles of NV-387. While NV-387 is designed to directly attack the virus outside the cell, the remdesivir component is known to block the virus replication inside the cell. By blocking both of these pathways, NV-387-R would result in a cure of the viral infection. Remdesivir is a broad-spectrum antiviral agent that has been approved for COVID-19 and has shown strong pre-clinical activity against many RNA viruses. Its clinical activity is limited by its rapid metabolism in the bloodstream. NV-387 holds remdesivir like in a bottle and releases it slowly, thus limiting the metabolism and enhancing the pharmacokinetics and thereby the effectiveness of remdesivir.
Remdesivir, sponsored by Gilead, is a known antiviral drug that has received full FDA approval for treatment of COVID-19 and has received Emergency Use Authorization (“EUA”) in many countries. We are developing NV-CoV-2-R on our own, independent of Gilead.
We have also developed other drugs based on this concept of curing the viral infection. One such drug is NV-387-Rp, which contains a modified and improved form of Remdesivir. Another drug is NV-387-Ribvp, which contains a prodrug of Ribavirin. Ribavirin is a highly toxic but highly effective antiviral drug. It is approved in the USA only for the treatment of RSV infection as a drug of last resort. However, it is used in the case of many viral infections for which no antivirals are known in severe hospitalized cases. NV-387-Ribvp is expected to enable cures for such viruses by combining the Re-Infection Inhibition activity of NV-387 with the Replication Inhibition activity of Ribavirin, while at the same time enabling lower doses of Ribavirin to stay well below its toxicity level.
Nanoviricides Platform Modality 4: Nanoviricides Platform Has the Capability to Enable Cures for Viruses that Do Become Latent
HIV and many viruses in the herpesviridae family form “latent reservoirs” in human cells making them difficult to cure. HIV and the class of lentiviruses achieve this by directly copying its genomic information into the human chromosomal DNA itself. Two of the herpes viruses, namely HHV-6A and HHV-6B, are known to copy their genetic information into the telomere region of the chromosome, shortening the number of cell divisions the modified cell can undergo, effectively a phenomenon of aging. All other herpesviruses create episomal islands in the cell’s nucleus which are their own “factories” for making progeny copies. The nanoviricides technology platform can be harnessed against these viruses in another different modality that can potentially produce cures. We are working on such cures of latent viruses in our research and development (“R&D”) projects.
Broad and Expanding Pipeline Based on the Nanoviricide Platform Technology – in Brief
Our powerful Nanoviricides Platform technology has enabled us to develop several drug candidates against a large number of different viruses that could be further improved into clinical drug candidates, thus building a very broad drug pipeline that may lead to exponential growth of the Company upon the approval of our first drug candidate. While our first drug candidate, NV-387, is now in human clinical trials, and another one, NV-HHV-1, is awaiting to go into the clinic, over the years we have developed more than ten drug candidates that, we believe, can be rapidly moved into the clinical stage, for nearly forty different antiviral drug development programs. Our progress to clinic is limited by our resources. We anticipate that once our first drug goes successfully through Phase I and Phase II clinical trials thereby proving our capabilities and our Nanoviricides Platform technology, the Company, assuming it acquires the necessary financings, could enter a phase of exponential growth and rapid clinical development of additional candidates thereby transforming the way viral infections are treated.
We have several drugs in our pipeline, enabled by our strong and extensive nanoviricide technology platform. Of these, NV-387 has completed a Phase Ia/Ib Clinical Trial in healthy subjects with no adverse events reported in both the single-dose and multiple-dose portions of the clinical trial, and we have now received a draft Phase I report that is in quality review from the CRO and the clinical trial manager, KMPL. Absence of any reportable adverse events is considered an excellent indication that the drug is safe and well tolerated in the Phase Ia/Ib clinical trial.
Presently, our focus is on the two separate Phase II clinical trials for NV-387 for the treatment of (i) MPox Virus Infection, and (ii) Viral Acute and Severe-Acute Respiratory Infections (Viral ARI and SARI). We are preparing the clinical trial application for the Phase II MPox trial and we have already obtained preliminary approval from the regulatory ethics committee for the clinical protocol in the Democratic Republic of Congo (DRC). In addition, we have already developed a draft clinical protocol for the Phase II Viral ARI and SARI clinical trial that is now in planning stage.
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We plan on further commercial development of NV-387 as a pediatric RSV treatment once additional resources to support the RSV clinical program become available. We plan on re-engaging our HerpeCide program and our HIV program when sufficient resources become available.
We also plan on further developing NV-387 for the treatment of Smallpox as a biodefense application, via the US FDA “Animal Rule”. Our work in developing NV-387 for MPox is providing enabling datasets towards approval of NV-387 as a treatment for smallpox because both of these are orthopoxviruses. We are seeking non-dilutive funding for the development of NV-387 for smallpox, a bioterrorism threat.
Additionally, we believe that NV-387 may have effectiveness against many other viruses including viruses that do not have current treatments such as Henipaviruses (Hendra and Nipa viruses), filoviruses (Ebola and Marburg viruses), other hemorrhagic viruses of interest to the Department of Defense, among others. NV-387 mimics Sulfated Proteoglycans that more than 90% of human pathogenic viruses utilize as the first landing site in causing an infection. We plan on seeking collaborations with labs that can broadly test our drugs against multiple viruses as well as non-dilutive funding for such developments.
We also have several additional pre-clinical drug development programs including NV-HHV-1 and related candidates for Herpes Simplex Viruses (HSV-1 that causes cold sores, and HSV-2 that causes genital ulcers), NV-HIV-1 and related candidates for HIV/AIDS, other candidates for Influenza viruses and Dengue viruses, that we plan to advance further towards clinical drug candidates as they progress further when financial resources become available. Thus, we have a strong and broad pipeline that is expected to continue to result in highly effective drug candidates against a number of viral diseases.
We also have several additional pre-clinical drug development programs including Herpes Simplex Viruses (HSV-1 that causes cold sores, and HSV-2 that causes genital ulcers), HIV/AIDS, Influenza, Dengue viruses, and Ebola/Marburg, that we plan to advance further towards clinical drug candidates as they progress further. Thus, we have a strong and broad pipeline that is expected to continue to result in highly effective drug candidates against a number of viral diseases.
We are now at the stage of clinically harnessing the development of Modality 1 and Modality 2 nanoviricides drugs. To recap, Modality 1 drugs mimic Attachment Receptors and possess a very broad spectrum of antiviral activity that includes a large number of different types of viruses. Modality 2 drugs mimic Cognate Receptors and possess a very strong antiviral activity against a set of specific types of viruses. In both cases, the targeted viruses are highly unlikely to escape the drug by evolving variants. NV-387, a Phase II-ready clinical stage drug candidate, is an example of Modality 1 nanoviricides,whereas NV-HHV-1 and NV+HHV-2 are examples of Modality 2 nanoviricides.NV-HHV-1 has completed IND-enabling studies as a Skin Cream for the treatment of Shingles.
We have also continued R&D on Modality 3 nanoviricide drugs that promise potential cures for non-latency viruses. As examples of this technology, NV-387-Rp and NV-387-Ribvp have shown strong effectiveness against Coronaviruses and RSV in animal models respectively, and are expected to be highly active against a number of other viruses based on the known activities of their components. We plan on developing these Modality 3 potential cures of a number of viral diseases after the Modality 1 and Modality 2 drugs.
Overall, since our founding, we have worked on development of approximately 40 different indications of different viral diseases in a number of drug development programs. In the process, we have built an extensive library of both the (i) Nanoviricides Platform know-how and (ii) the actual synthesized chemical drugs.
Additional details of our drug pipeline can be found in this Annual Report in the section “NanoViricides Drug Pipeline” further below.
NanoViricides Drug Development Process
Our drug programs begin from initial R&D to understand the virus and advance to design antiviral medical countermeasures. Then we chemically synthesize selected potential small molecules to act as the ligands that mimic the cellular receptor(s) of both Modality 1 (broad spectrum) type as well as Modality 2 (specific to the virus family) type, to bind to the virus. Separately we have been engaged in evolving and optimizing various versions of the nanoviricide backbone polymer. We then choose some of the select polymers and attach the selected antiviral ligands chemically to the polymer to create a library of antiviral nanoviricides. We then evaluate these antivirals in cell cultures against the target viruses. We further evaluate selected antiviral ligands from this screen in animal model studies. We then down-select from the effective drug candidates about five to seven candidates for further development based on a number of
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considerations including the level (or potency) and spectrum of activity, any likely issues with safety/tolerability, drug stability, pharmacokinetics, pharmacodynamics, ease of manufacturing, ease of formulations, and the desired routes of administration.
Along the way, we refine the methods of preparation of these drug candidates, from chemical synthesis all the way to formulation and packaging of the final drug product, developing and implementing the Chemistry, Manufacture and Controls information for the resulting drug substances as well as the potential drug products.
The selected candidates then undergo additional studies. Typically about two of them are advanced into IND-enabling GLP Safety/Tolerability studies. One of these is then selected for further evaluation in human clinical trials.
NanoViricides, Inc. is a Fully Integrated Pharma Company
We have strived to minimize the risks inherent in the drug development process. One of the major risks is the manufacture of our nanoviricide drug candidates in a manner to produce consistently quality drugs.
NanoViricides c-GMP-capable Kilogram-Scale Manufacturing Facility for Drug Substance and Drug Products
Manufacturing of drug products for sale, as well as for late stage clinical trials is required to be performed in FDA-registered cGMP manufacturing facilities. Manufacture of drugs for earlier stage clinical trials as well as for IND-enabling GLP Safety/Toxicology studies needs to be performed in a c-GMP-compliant manner.
We discovered early in our development that the existing contract manufacturing operations in the pharmaceutical industry have very limited expertise that would be applicable to our kind of drugs. In order to speed up nanoviricide drug development, save on costs, and ensure quality, we have set up our own manufacturing facility that can scale from discovery quantities of a few grams to clinical trials quantities of a few kilograms.
We believe we are one of the very few small pharmaceutical drug innovators that possess its own cGMP or cGMP-capable manufacturing facility. With our Shelton, Connecticut campus and pilot-scale cGMP-capable manufacturing facility, we have now demonstrated that we are in a position to rapidly advance our drug candidates into clinical trials, produce the pre-clinical “tox package” batches, and the clinical drug substance batches, as well as the completely finished and packaged clinical drug product batches.
We have produced and plan to continue to produce our nanoviricide drugs for clinical trials in this facility. We have the capability to produce sufficient drugs for about 1,000 patients in a single batch of production, depending upon dosage. This production capacity is anticipated to be sufficient for the Phase II clinical trials of NV-387 for MPox, for Viral ARI/SARI, as well as for RSV. In general, the manufacturing capacity is sufficient for all of the anticipated clinical trials of our drug candidates in the near future. Further, this cGMP-compliant manufacturing capacity is anticipated to be sufficient for commercialization of NV-387 for treatment of pediatric RSV subsequent to required regulatory approvals thus enabling rapid market entry and future revenue generation.
Our cGMP-compliant manufacturing facility is equipped with Class 100 (ISO 5), Class 1,000 (ISO 6), and Class 10,000 (ISO 7) clean room suites for injectables and other manufacturing operations as appropriate.
We have in-house all the capabilities necessary for formulation, filling and finishing of our drug products in the following forms: (i) oral syrup, (ii) oral gummies (semi-solid form), (iii) skin creams and (iv) ointments. We plan to either employ an external Contract Manufacturing Organization (CMO) for our injectable drug products for clinical trials, or develop in-house injectables manufacturing capabilities utilizing our existing Class 10,000 (ISO 7) clean room suites with Class 100 (ISO 5) enclosures housed inside them, as and when required.
We believe that we are in compliance with all material environmental regulations related to the manufacture of our products.
NanoViricides State-of-the-Art Nanomedicines Characterization Lab Supports In-Process QC, Release Testing of Manufactured Drug Substance, Drug Products, as well as R&D
We have a state-of-the-art nanomedicines characterization facility in-house in the same campus that has all the capabilities necessary for in-process quality control as well as release testing and quality assurance of our drug products and for supporting our manufacturing
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operations as well as our R&D operations. We also have a Bio-Analytical laboratory that we use for various quantitative and semi-quantitative analyses.
NanoViricides BSL2 Virology Lab for Evaluation of Drug Candidates in Cell Culture Studies
In addition to the cGMP-capable manufacturing facilities, we have also brought in-house the capability for testing of our nanoviricide drug candidates against a number of viruses in cell culture studies for early evaluation. We have built a Biological Safety Level-2 (BSL2) Virology Laboratory with attendant cell culture and biochemistry capabilities in our campus in Shelton, CT, certified by the State of Connecticut. We are able to perform drug efficacy and safety studies in cell cultures for multiple different viruses at the same time in this facility, in isolated lab rooms.
We can also study antivirals against certain BSL3 and BSL4 viruses in this facility by developing what are called “pseudovirions.” Pseudovirions are virus particles that cannot replicate, but that have the surface glycoprotein of the virus that we want to study (e.g. H5 for H5Nx Bird Flu, GP for Ebola, Marburg, S for SARS-CoV-2, etc.) on a viral backbone that is a BSL2 compatible virus. We only require and employ pseudovirions technology where the resulting virus particles cannot replicate. The pseudovirion systems allow evaluation of drug candidates that block the entry of the virus particle into cells, such as entry inhibitors, antibodies, and nanoviricides.
We have developed in-house cell culture screening capability for developing drug candidates against human Coronaviruses (h-CoV) including SARS-CoV-2 pseudovirions, VZV, HSV-1 and HSV-2, Influenzas, HIV, RSV, Ectromelia Mousepox Virus (a model for MPox and Smallpox viruses), and pseudovirion technology for Ebola/Marburg viruses, among others. We believe that this internal screening enables speedy evaluation of a much larger number of candidates than external collaborations allow. We believe this has significantly improved our ability to find highly effective ligands and performing structure-activity-relationship studies of the same in a short time period.
External CROs for GLP and Non-GLP Animal Model Studies, Regulatory Affairs Support, and Clinical Trials
We depend upon external collaborators and Contract Research Organizations (“CROs”) for all of our animal studies that include antiviral efficacy studies, safety and tolerability studies, in both GLP and non-GLP practices. We also depend upon external collaborators and CROs for completing our regulatory filings, designing suitable clinical protocols, as well as for conducting human clinical trials, compiling the resulting data, biostatistics evaluations, and preparation of reports for regulatory filings. We plan on bringing some of the regulatory affairs capabilities in-house in the near future in order to speed up our regulatory processes.
NanoViricides Campus – Fully Owned Asset Group
All of the facilities described above, the land, building, improvements, and equipment, are fully owned by NanoViricides, Inc. This forms a significant and stable part of our long term assets, accounting for over $6.8 million in long term assets post-depreciation and amortization as of June 30, 2025. The replacement cost of these assets was estimated, in April 2024, at $18 million by a third party consultant, which we believe is a low-end estimate.
We believe NanoViricides, Inc. is one of a few innovation-led small pharma companies that has or is close to having a fully integrated pharmaceutical operation from drug discovery to drug product manufacturing. This sets us apart in the field by substantially de-risking our development programs as well as enabling time and cost savings in the new drug development process.
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Fiscal Year 2025 in Review
In the fiscal year 2025, we have achieved a substantial level of accomplishments. We have focused on evaluating the broad spectrum of antiviral activity of NV-387. We have been able to significantly expand the potential indications of viral infections wherein NV-387 could be a drug candidate worthy of pursuing into clinical trials, to include the respiratory viral infections RSV and Influenza, in addition to the coronaviruses, as well as Smallpox/Mpox, and now to include Measles virus.
During this year, we have focused on developing a cost-effective regulatory strategy for NV-387. We have reprioritized our development plans based on our resources.
We have engaged in a number of activities necessary for initiating our very first Phase II clinical trial(s) of NV-387, which is for the evaluation of NV-387 as a treatment of MPox. We are developing the Clinical Trial Application at present, and we have already obtained a preliminary approval for our clinical trial protocol for this clinical trial from the regulatory agency in charge, namely ACOREP in DRC.
We have also developed a clinical trial protocol for a novel, adaptive, “basket-type” Phase II clinical trial for the evaluation of NV-387 as a treatment of viral acute and severe-acute respiratory infections. We are now planning this clinical trial. In this single clinical trial, we anticipate generating data on the effectiveness and safety in patients of NV-387 against a number of different respiratory viruses, including Influenza viruses, RSV, Coronaviruses, human MetaPneumovirus (hMPV), and many others. In particular, we believe the data in adult subjects will enable a Phase II clinical trial of NV-387 in pediatric population (children).
We have improved the manufacturing process of NV-387. In doing so, we have approximately doubled the production scale of the drug substance NV-387 resulting in a batch size producing approximately 6kg of the purified drug substance with a 10kg scale feasible.
We have developed and validated improved methods for the quantitation of drug substance related impurities.
We have developed and validated a new and improved method for analysis of NV-387 in biological samples such as animal and human plasma, which is required for pharmacokinetic studies.
We have improved the process of manufacturing the drug product NV-387 Oral Gummies, which we plan to take into the first Phase II clinical trials. We have improved the NV-387 Oral Gummies formulation for organoleptic properties, by improving its color, flavor, taste, and mouthfeel.
We have engaged a CRO, identified and engaged a clinical trial site, and obtained initial permission from the Ethics Committee for the proposed Phase II clinical trial for evaluation of NV-387 for the treatment of MPox in DRC.
We have also performed preliminary work and developed a clinical trial protocol for a first-of-a-kind, innovative, adaptive, “basket-type” Phase II clinical trial for the simultaneous evaluation of NV-387 for effectiveness against a number of respiratory viruses in a single clinical trial.
We have engaged in efforts to obtain non-dilutive funding for several of the developments related to NV-387 that would be of interest to various governmental agencies.
NV-387 Phase Ia/Ib Human Clinical Trial
NV-387 was developed during the COVID pandemic in a very rapid timeframe. In just about a year, we went from design and synthesis to completing the required non-clinical GLP safety pharmacology studies in animals by January 2021. The progress slowed down primarily due to lack of internal regulatory expertise and dependence on external consultants that became unavailable. We successfully completed a Clinical Trial Application for the simultaneous evaluation of two oral drug products containing the same API NV-387, namely NV-CoV-2 Oral Syrup and NV-CoV-2 Oral Gummies, sponsored by our licensee, collaborator, and clinical trial manager, Karveer Meditech Pvt. Ltd. (KMPL) who sponsored the drug in India, with a local CRO, around September 2022, and KMPL obtained regulatory permission for the clinical trial towards the end of January 2023.
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The Phase Ia/Ib clinical trial began with the first human dosing in June 2023. The healthy subjects part of the clinical trial, comprising both Phase Ia – Single Ascending Dose – Healthy Subjects, and Phase Ib – Multiple Ascending Dose – Healthy Subjects was completed with discharge of the last subject around December 2023. There were no dropouts and no reported adverse events. These results are generally taken as indicators that a drug is well-tolerated under the conditions of treatment in a clinical trial.
The results of this Phase Ia/Ib healthy subjects part of the clinical trial are consistent with the results of the non-clinical studies in multiple animal models in which good tolerability was observed and no respiratory, cardiological, or neurophysiological effects were found.
The clinical trial application for this clinical trial was submitted during the COVID-19 pandemic and for expediency towards use of the drug in the pandemic, a separate part of the clinical trial for the treatment of COVID-19 patients with NV-387 was also proposed. Upon completion of the Healthy Subjects part, the Sponsor and the CRO went through tremendous efforts and obtained regulatory permission to add another site where a COVID-19 wave was going on during January 2024. However, by the time all of the approvals required to start enrollment were completed, the COVID-19 wave was completely gone. After performing a large number of RT-PCR tests on potential subjects with respiratory symptoms, with all tests turning up negative results for SARS-CoV-2, this second part of the clinical trials was canceled due to the inability to find patients to enroll in spite of adding a second site. The second site was subsequently closed around April/May 2024.
Concurrently data upload and crosschecking activities for the healthy subjects Phase Ia/Ib part were completed. After appropriate external audits, the drug sponsor is now getting ready to close the first clinical trial site where the healthy subjects part was executed. Thereafter, subsequent to database lock, statistical analysis of the observations of the subjects will be performed. These include a number of parameters including clinical observations, blood chemistry, and specific organ-related blood chemistry parameters, among others.
A draft Clinical Study Report (CSR) for this clinical trial comprising all of the studies has been compiled recently by the CRO and it is undergoing quality reviews as of the date of submission of this Annual Report. We anticipate completion of this process within a few weeks and submission of the final CSR to the Indian regulatory body, namely, The Central Drugs Standard Control Organisation of India (CDSCO).
Evaluating the Broad Antiviral Activity Spectrum of NV-387 Against Multiple Different Types of Viruses
As the Phase Ia/Ib clinical trial in India for evaluation of safety and tolerability of NV-387 in healthy subjects got under way, we embarked on determining whether NV-387 could be sufficiently active to be chosen as a clinical drug candidate against many different types of viruses other than coronaviruses. This work has spanned several years, and is cited here because it is important to understand the effectiveness of NV-387 in animal models in order to understand our development program for NV-387.
NV-387 was designed as a Sulfated Proteoglycan (S-PG) Mimetic. Over 90% of human pathogenic viruses are known to use heparan sulfate proteoglycan (HSPG) in particular as an attachment receptor to enable them to infect cells. NV-387 mimics the critical feature that the viruses look for in not just HSPG but other related S-PGs such as Chondroitin Sulfate (used by the Chikengunya virus), Dermatan Sulfate (used by Human Papilloma Viruses - HPV), among others. HSPG is used by almost all respiratory viruses. We therefore focused on viruses that use HSPG for our first studies. In particular, we studied activity of NV-387 in animal models of lethal lung infections by the respiratory viruses RSV and Influenza. Since orthopoxviruses are known to bind to HSPG, we also evaluated activity of NV-387 against lethal infection by the model mousepox virus (Ectromelia) that is used as a part of the US FDA Animal Rule for the development and approval of Smallpox therapeutics.
Activity of NV-387 in Lethal Lung RSV Infection in Mice – NV-387 Oral Treatment Appears to Have Cured Lethal Lung RSV Infection Based on Complete Survival and No Lung Damage
In the first animal trial, we compared the effect of NV-387 given as both injectable and as oral treatment in mice infected lethally into the lungs with RSV A2 virus. We found that NV-387 demonstrated excellent anti-RSV activity, almost matching the activity of ribavirin
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as shown in the table below. Ribavirin is the only drug currently approved for treatment of RSV infection. However it is used only as a last resort drug because of its significant toxicities, including hematological and nephrological (kidney) adverse effects.
Survival Lifespan of Lethally Infected Mice - Lung Infection with RSV A2
Treatment Survival, Days Increase in Survival, Days Increase in Survival, %
Vehicle for Injection 7 0 -
Vehicle for Oral 7 0 -
Treatment of lethally infected mice in this study with NV-387 or ribavirin led to statistically equivalent positive effect on the outcome of the disease. Since ribavirin is highly toxic, the activity of NV-387 demonstrated in this study is of great significance.
Importantly, NV-387 given orally at approximately twice the total dose of NV-387 given as an injection produced equivalent results in terms of effect on animal survival. Thus, the oral bioavailability of NV-387 can be estimated, in terms of actual biological effects, to be approximately 50% based on this animal study. We believe that this level of effective bioavailability is excellent and it would permit development of NV-387 as an oral drug for treatment of RSV infection.
We reported on this study in a press release dated July 11, 2023.
Encouraged by the results of this animal trial, we initiated a new trial with oral dosing of NV-387 extended to ten days with two doses on first day for a total of eleven doses. We also increased the dosing of ribavirin in this second animal trial. The results of this trial are shown in the table below.
NV-387, Oral Complete Cured Cured No Lung Damage
Ribavirin, Oral 14 6 75% Immune Infiltration, Pneumonia
Vehicle, Oral 8 0 0% Immune Infiltration, Pneumonia
We were pleasantly surprised to find that the increased oral dosing of NV-387 led to complete survival of all of the lethally lung-RSV-infected mice, well beyond the 21 day study length, and they remained healthy until final sacrifice as per protocol at 30 days. The performance of oral ribavirin was similar to its performance in the previous trial, and possibly slightly worse, indicating that the dosing level of ribavirin in this trial might be close to evidencing its toxicity.
We reported on these results in a press release on May 14, 2024.
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Further analysis of gross histology as well as micro- histopathology of lungs from the animals treated with NV-387 compared to ribavirin was also conducted.
The lethally RSV-infected animals in the NV-387-treated group showed no lung damage in lung histo-pathology study at all-time points during the study, including at the end of the study. This demonstrates that the NV-387 oral treatment completely protected the animals from the lethal effect of RSV infection. These results are consistent with the complete and healthy survival of the animals.
In contrast, lethally infected animals in the ribavirin oral treatment group showed progressive lung pathology, demonstrating progressive inflammation in the lung tissue which resulted in moderate levels of inflammation as well as infected cells in the inflammatory infiltrate on day 10, increasing to severely infected lungs with alveolitis and severe pneumonia by day 13. All animals in the ribavirin-treated RSV infected group died by 14 days as shown in the table.
These lung histo-pathology results in conjunction with the complete survival of NV-387 orally treated animals support our belief that NV-387 oral treatment led to complete cure of the lethal RSV infection in mice in this animal trial.
We reported on these results in a press release on May 20, 2024.
Based on these results, we have determined to seek regulatory approval for a Phase II human clinical trial for the evaluation of efficacy of oral NV-387 treatment in RSV infection.
Activity of NV-387 in Lethal Lung Influenza Infection in Mice - NV-387 Treatment Resulted in Significantly Greater Survival Improvement Compared to Three Approved Influenza Drugs, and Significantly Increased Protection of Lungs from Virally Induced Damage
We evaluated the activity of NV-387 given orally (twice on first day then once daily, 8 days, total 9 doses) in comparison with the three approved drugs, oseltamivir (Tamiflu®, Roche) given orally (twice daily for 8 days), baloxavir (Xofluza®, Shionogi, Roche) given orally as a single dose, and peramivir (Rapivab®, Biocryst) given by tail-vein injection once daily for 8 days. The survival lifespan results are shown in the table below.
Treatment Survival, Days Increase in Survival, Days Increase in Survival, %
Oseltamivir (Tamiflu), Oral 10 2 25%
Peramivir (Rapivab), Injection 11 3 38%
Baloxavir (Xofluza), Oral 11 3 38%
Vehicle, Oral 8 0 -
We were pleasantly surprised to find that the NV-387 oral treatment led to nearly 2.5 to 3 three times more increased survival compared to the three approved drugs, by 7 days, whereas the three approved drugs led to a survival of only 2 to 3 days over vehicle-treated animals that survived 8 days.
We reported on these results in a press release dated May 6, 2024.
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We also studied the effect of NV-387 treatment on the lung mucus index, as well as lung immune cell infiltration in this animal trial. Lung mucus index is a parameter that measures the lung congestion and relates to pneumonia symptoms. Lung immune cell infiltration relates to virally induced lung damage that is actually caused by the cytotoxic cells of the immune system that kill infected cells. The results are shown in the table below.
Treatment Lung Mucus Index % Immune Cell Infiltration
Untreated Infected Control 138 68%
We found that NV-387 significantly reduced lung mucus index, as well as cell-killing immune cell infiltration into the lungs. The results indicate that NV-387 oral treatment resulted in significant reduction in lung infiltration and lung cell death. Lungs of infected animals treated with NV-387, orally, 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 found to be significantly reduced upon NV-387 treatment.
The results further indicated that NV-387 treatment resulted in significant reduction in mucus load in the lungs. The extent of mucus in the lung tissue was substantially reduced in the case of NV-387 treatment a positive finding. The mucus index value in the case of NV-387 oral treatment was about 53, as compared to the infected untreated animals that had a mucus index value of 138. 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.
These results indicate that NV-387 treatment led to a significant level of protection of lungs in Balb-c mice lethally infected with Influenza A H3N2 virus.
We reported on these results in a press release on June 20, 2024.
Given the broad range of activity of NV-387 against different types of viruses, we believe that these results of activity of NV-387 against Influenza A/H3N2 lead us to believe that NV-387 likely possesses significant activity against other influenza viruses as well, including high path avian influenza (HPAI; H5Nx Bird Flu).
It is important to note that resistance against small chemical influenza drugs has emerged. The amantadine class of drugs is now largely ineffective. Oseltamivir resistant mutants are known. Peramivir is not used very much for various reasons. In a Phase III clinical trial of baloxavir, over 10% of the patients were found to have the virus evolved into resistant mutants.
Thus NV-387 with its broad spectrum and unlikely escape of virus is expected to become an important weapon in the treatment of influenza virus infections.
Activity of Oral NV-387 in Lethal Intra-digital Poxvirus Infection in Mice Matched that of Approved Drug Tecovirimat; Activity of Combination of NV-387 and Tecovirimat was Significantly Better than Either Drug Alone
We conducted evaluation of activity of NV-387 compared to the approved drug tecovirimat (TPOXX®, SIGA) in a lethal model of mousepox (ectromelia) virus intra-digital footpad infection in mice. This model emulates the virus infection by transfer of virus via skin
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abrasion, a mode of infection that has been found to be the dominant mode in Mpox virus epidemics in the West. The results are shown in the table below.
Treatment Survival, Days Increase in Survival,Days Increase in Survival,%
Tecovirimat (TPOXX), Oral 14 6 75%
Vehicle, Oral 8 0 -
In this trial, we found that the activity of NV-387 matched that of tecovirimat, the approved drug for smallpox which was used in the recent MPox epidemics in the West. Both drugs led to approximately 75% increase in survival of the animals. Moreover, treatment with an oral co-formulation of NV-387 and tecovirimat together developed by us (that we call NV-387-m-T, “m” for “mixed-in”), led to a significantly increased survival improvement of about 112% compared to either drug given alone.
We reported on these results in a press release dated November 14, 2023.
Activity of Oral NV-387 in Lethal Lung Poxvirus Infection in Mice Matched that of Approved Drug Tecovirimat; Activity of Combination of NV-387 and Tecovirimat was Significantly Better than Either Drug Alone
We also conducted evaluation of activity of NV-387 compared to the approved drug tecovirimat (TPOXX®, SIGA) in a lethal model of mousepox (ectromelia) virus lung infection in mice. This model emulates the virus infection that would be caused in the case of aerosolized virus, a mode of infection likely in a potential bio-terrorism attack, and that was also observed in natural smallpox epidemics. The results are shown in the table below.
Treatment Survival, Days Increase in Survival, Days Increase in Survival, %
Tecovirimat (TPOXX), Oral 16 8 100%
Vehicle, Oral 8 0 -
In this trial, we found that the activity of NV-387 substantially matched that of tecovirimat, the approved drug for smallpox which was used in the recent MPox epidemics in the West. Both drugs led to approximately 85-100% increase in survival of the animals. Moreover,
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treatment with an oral co-formulation of NV-387 and tecovirimat together developed by us (that we call NV-387-m-T, “m” for “mixed-in”), led to a significantly increased survival improvement of about 138% compared to either drug given alone.
We reported on these results in a press release dated May 8, 2024.
Activity of Oral NV-387 in Lethal Lung Infection by Measles virus in humanized CD150-knock-in Mice Indicates NV-387 Would be a Drug Candidate for Treatment of Measles for Regulatory Development
We performed a study to evaluate the potential effectiveness of NV-387 in a lethal lung viral infection caused by measles virus in humanized hCD150+(knock-in) mice. Measles requires the human CD150 cognate receptor to be expressed on the immune cells to cause productive infection. Therefore, it was necessary to use humanized mice.
We hypothesized that NV-387 could be an effective candidate because measles virus first binds to the HSPG as attachment receptor, concentrating next to cells to mount an attack by binding to the CD150.
In this lethal humanized animal model of respiratory infection with measles virus, NV-387 increased survival of animals to 17 days on average compared to 7.4 days in untreated animals, an increase of 130%. There were no signs of toxicity from the drug NV-387. Additionally, dose-dependent increase in survival was observed. These data demonstrate that NV-387 could be an effective drug for the treatment of measles.
We published these data in a press release on July 21, 2025.
Development Program for NV-387
With this broad-spectrum activity of NV-387 against a large number of substantially different types of viruses, we have now developed a cost-effective strategy for further development of NV-387 towards commercialization that would potentially enable non-dilutive funding, rapid approval pathways, and early revenues.
Smallpox, Biodefense, and the US FDA Animal Rule
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.
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. SIGA booked approximately $85 million in sales in the first 6 months of 2025 and disclosed additional awards of $27 million to support further development and manufacturing of tecovirimat according to their press release in August, 2025. These numbers clearly indicate the revenue potential for a smallpox treatment.
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 virus 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).
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The animal-rule based efficacy studies conducted under GLP conditions substitute for the usual Phase II/III human clinical efficacy trials for regulatory approval under the Animal Rule. Additional human safety clinical studies are expected to be required.
The Animal Rule pathway is expected to enable rapid regulatory development of NV-387 as a smallpox therapeutic towards approval. In addition, the data from our Phase II clinical trial evaluating NV-387 as a treatment of MPox, assuming positive results, should enable approval of NV-387 for treatment of smallpox as well, since both are orthopoxviruses.
MPox is a Potential Global Pandemic Threat and There is No Effective Treatment – An Unmet Medical Need
MPox is the disease caused by infection by the virus called MPXV (Monkeypox virus). A first declaration of Public Health Emergency of International Concern (PHEIC) for MPox Clade II was made by the WHO in July 2022, and it continued for approximately one year thereafter. Spread of MPXV Clade II from African countries into the Western World led to this declaration, which is short of a declaration of a pandemic. MPXV Clade II is contagious but requires sustained bruising skin contact. It has remained limited, driven primarily by sexual contact, in the MSM and associated population in the Western World, including the USA. This ongoing outbreak of Clade 2 MPox has spread to 122 countries and is now considered endemic, including in the Western World.
MPox Clade Ia is endemic in many African countries including the DRC. A rapid increase in cases of MPox prompted the Africa CDC to declare a regional Public Health Emergency of Continental Security (PHECS) on August 10, 2024. Children were the majority of cases associated with this new outbreak, caused MPox Clade Ib, a new variant of Clade I, unlike previous outbreaks that primarily affected adults. WHO followed with a new PHEIC declaration on August 14, 2024. The virus continued to rage through DRC and spread through neighboring countries. Initial scattershot vaccination effort in DRC using Jynneos did not control the spread of the virus. The PHEIC was ended by the WHO on September 5, 2025, but the Africa CDC has continued the regional PHECS declaration citing new surges emerging in Ghana, Liberia, Kenya, Zambia, and Tanzania, with fresh introductions of the virus reported in Malawi, Ethiopia, Senegal, Togo, The Gambia, and Mozambique (https://africacdc.org/news-item/mpox-still-a-continental-emergency-africa-cdc-advisory-group-recommends/ ).
The MPox virus circulating in DRC and neighboring regions is of Clade Ia and Clade Ib subtypes, with the latter predominant. Clade Ib is more transmissible of the two, which is why it has resulted in a sustained epidemic. The MPox Clade Ia case fatality rate (CFR) is about 3%-11%whereas the CFR for Clade Ib is about 1%. The MPox Clade IIb is the virus causing continuing cases in the Western world, which causes a much less severe disease than Clade Ia/Ib and has a very low CFR, according to CDC. Sporadic cases of Clade I in the Western World continue to occur. Six separate travel-related MPox Clade I cases were reported in the USA that did not result in any further spread, since November 2024, according to the CDC (https://www.cdc.gov/mpox/situation-summary/index.html ).
MPox Clade II primarily causes localized rash that is very painful and persists for several days or months. MPox Clade I generally causes rash all over the body, and also inside the oral cavity, which is very painful and also affects the ability of the patient to swallow, causing food intake issues and leading to hospitalization.
A 2-dose vaccine called Jynneos (Bavarian Nordic), originally developed for smallpox (caused by the Variola virus) has been approved for MPox. Jynneos is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus.
While vaccination has started in DRC, overall, the uptake of available vaccines has remained lower than anticipated due to logistical, operational, and financial barriers, according to the report of the International Health Regulations (2005) (IHR) Emergency Committee for MPox of the WHO on June 5, 2025.
There is no treatment for MPXV Clade II or for Clade I, and this remains an unmet need. Tecorimat, approved for smallpox under the US FDA Animal Rule, failed in clinical trial to demonstrate efficacy. Brincidofovir entered a clinical trial for evaluation as a treatment for Mpox in January 2025, and was expected to have topline results available by March 2025. The status of this clinical trial is unknown. Brincidofovir is not applicable across all population because of several side effects and a black box warning as described in its prescribing information.
NV-387 was found to have strong activity against an animal model of orthopoxvirus infection which is a standard model used for both Smallpox and MPox therapeutics developments. NV-387 activity in the dermal infection model as well as the direct lung infection model was at least equivalent to that of tecovirimat. Based on the broad spectrum of activity of NV-387, this drug is not expected to carry the
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liability of virus escape by a single point mutation that is known to be possible upon treatment with tecovirimat. NV-387 treatment did not result in any reportable adverse events in a Phase I clinical trial in healthy subjects, indicating excellent safety, unlike the black-box-warning and adverse event liabilities described in the brincidofovir prescribing information.
Thus we believe that NV-387 has a high likelihood of success as a treatment for MPox in the Phase II clinical trial. If successful, the dataset generated would also help towards approval of NV-387 as a treatment for smallpox.
NV-387 Has a High Likelihood of Success as a Treatment of Smallpox – Biodefense Application
Further, we believe that NV-387 is a strong potential candidate for approval as a treatment for smallpox under the US FDA Animal Rule, based the animal study data. If approved, there is potential of significant revenues in hundreds of millions of dollars as well as help with manufacturing and further advanced development of NV-387 from US Government agencies.
The Importance of Treatment for RSV Infection in Pediatric Population – An Unmet Medical Need
Each year in the United States, an estimated 58,000–80,000 children younger than five years old are hospitalized due to RSV infection. Globally, RSV is a common cause of childhood Acute Lower Respiratory Infection (ALRI, which includes pneumonia) and a major cause of hospital admissions in young children. Globally in 2015, 33 million episodes of RSV-ALRI, resulted in about 3.2 million hospital admissions, and 59,600 in-hospital deaths in children younger than five years. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than six months old.
There are No Effective Treatments for RSV
Three vaccines have recently been approved for RSV prophylaxis. Arexvy (GSK), and Abrysvo (Pfizer) were approved in May 2023 for use in adults over 60 years of age and both reduced severity of RSV infection. Mresvia (Moderna), an mRNA vaccine, was approved for medical use in the United States in May 2024. Abrysvo also received approval for use by pregnant women at 32-36 weeks of pregnancy in order to confer protective antibodies against RSV to the fetus for protection of infant when born despite concerns regarding premature childbirths. There are no RSV vaccines currently approved for infants and children.
However, there are no effective therapeutics for RSV to date. Ribavirin is conditionally approved only for patients with high risk of progressively severe RSV disease, due to significant side effects including hemolytic anemia and kidney failure. Synagis (palivizumab), an antibody, is approved only as a prophylactic in children and infants at high risk of severe RSV infection, but it is not approved for treatment of RSV infection. Nirsevimab (Beyfortus, AstraZenecka), another antiviral monoclonal antibody, has been approved for the prevention of RSV lower respiratory tract disease in newborns and infants during their first RSV season that requires a single dose to confer season-long protection from RSV infection. None of these drugs are approved for treatment of RSV infection after it occurs.
Market Size of RSV Therapeutics is Expected to Hit $8.73 Billion by 2031
In June 2023, GrowthPlus Reports reported that the market size for RSV therapeutics was worth $1.8 billion in 2022, and is expected to grow at a CAGR of 18.9%, reaching $8.73 billion by 2031 (https://www.growthplusreports.com/report/respiratory-syncytial-virus-rsv-therapeutics-market/8519).
NV-387 for the Treatment of Influenza Infections
The market size for Influenza and Bird Flu is estimated at $4.6 billion in 2024, growing to an estimated $5.9 billion in three years, at a rate of 8.5% as reported by DelveInSight (https://www.delveinsight.com/report-store/influenza-a-infections-market? utm_source=cision&utm_medium=pressrelease&utm_campaign=spr). In case a pandemic occurs, reality may outrun such projections by magnitudes, as was seen with the COVID pandemic.
NV-387 Phase II for Viral Acute and Sever-Acute Respiratory Infections (Viral ARI and SARI)
We are planning a novel, adaptive “basket-type” clinical trial of NV-387 for the treatment of viral respiratory infections. In a single clinical trial, we will be able to generate data regarding the effectiveness and tolerability of NV-387 in patients affected by a number of different viral infections that include Influenza viruses, RSV, Coronaviruses (including SARS-CoV-2 that caused COVID-19 pandemic),
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hMPV, as well as certain other viruses. We can then utilize the data to strategize further development for specific indications as well as for further development as an emperic antiviral therapy. In particular, we plan on utilizing the data from adult RSV patients to further the development of NV-387 as a treatment for pediatric RSV patients.
Strong Market Potential of NV-387
Thus, we believe NV-387 alone may propel NanoViricides towards great success in a near-term horizon. We plan to license or co-develop our various drug candidates against multiple viral diseases to other pharma companies. In addition, we plan to seek non-dilutive funding for the development of drugs that are of interest for biodefense.
Our IND-Ready Drug Candidate, NV-HHV-1 Skin Cream for the Treatment of Shingles
We have previously developed NV-HHV-1 and formulated it as a skin cream for the treatment of Shingles rash, NV-HHV-1 has completed IND-enabling studies. We plan on undertaking further development of NV-HHV-1 into human clinical trials once our NV-387 based drug candidates progress further in clinical trials.
Licenses, Patents, Trademarks, Proprietary Rights: Intellectual Property
Licenses from TheraCour
Our drug development business model was formed in May 2005 with a license to the patents and intellectual property held by TheraCour Pharma, Inc. (TheraCour) that enabled creation of drugs engineered specifically to combat viral diseases in humans. This exclusive license from TheraCour serves as a foundation for our intellectual property. We have a worldwide exclusive license to this technology for several field of application verticals with specific targeting mechanisms for the treatment of a number of human viral diseases. TheraCour owns approximately 21% of our voting capital stock and, Anil Diwan, our Founder, President and Executive Chairman, owns approximately 90% of TheraCour’s capital stock.
Our drug candidates are licensed from TheraCour, and are developed by TheraCour for the Company on the basis of several patents, patent applications, provisional patent applications, and other proprietary intellectual property know-how held by TheraCour. Unlike usual pharma industry licenses that are specified for single chemical entities or for groups of similar chemical entities, our licenses are specified for the vertical application field of use, thereby providing us with a large universe of diverse development candidates under the same umbrella. Further, the licenses are held by NanoViricides for worldwide use and can be sub-licensed. The licenses can revert only in the case of a default by NanoViricides. The terms of default are such that, effectively, TheraCour would be able to take the licenses back only in the event that NanoViricides declares insolvency and inability to conduct its business.
We have exclusive licenses from TheraCour for drug candidates derived from and based on TheraCour’s technologies for several viruses. In 2005, we obtained a license from TheraCour for the treatment of the following human viral diseases: Human Immunodeficiency Virus (HIV/AIDS), Influenza including Asian Bird Flu Virus (INF), Herpes Simplex Virus (HSV-1 and HSV-2), Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), and Rabies. Thereafter, on February 15, 2010, we entered into an TheraCour-Nanoviricides Additional License Agreement (“Additional License Agreement”) with TheraCour granting the Company the exclusive licenses for technologies developed by TheraCour for the additional virus types for Dengue viruses (DENV), Japanese Encephalitis (JEV), West Nile Virus (WNV), viruses causing viral Conjunctivitis (a disease of the eye) and Ocular Herpes Keratitis, and Ebola/Marburg viruses. While herpes simplex viruses were already specified as licensed previously, the term “ocular herpes keratitis” was added to this additional license agreement at the specific request of the Company for clarity only. In addition, we completed the process of licensing the VZV (shingles, chicken pox virus) field from TheraCour in November 2019. We further completed the process of licensing antivirals for the field of human coronavirus indications in September 2021 under the COVID agreement. As in the past, as and when advised by counsel, we will seek additional licenses to verticals of antiviral fields from TheraCour. To date, TheraCour has not withheld any licenses for antiviral nanomedicines that NanoViricides has requested.
We retain worldwide exclusive rights to commercially develop, commercialize, and market the licensed products. We pay TheraCour for the R&D work asked to be performed by the Company to develop these drugs, their chemistries, formulations, and manufacturing processes, substantially at cost, with a certain fee as specified in the license agreements. We may perform initial developmental testing by ourselves and through third parties, such as academic labs, government institutions, contract research organizations, for safety and effectiveness, among other tests. The Company may perform further IND-enabling advanced pre-clinical studies using third parties,
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such as contract research organizations, usually on clinical drug candidates. We expect to perform human clinical trials using contract research organizations with expertise in such clinical trials. We intend to sponsor the drugs for commercialization activities and obtain the rights of commerce under various regulatory authorities for its own use.
We focus our research and clinical programs on specific anti-viral therapeutics and are seeking to add to its existing portfolio of products through our internal discovery and clinical development programs and through an in-licensing strategy. To date, we have not commercialized any product.
For all the licensed fields, we control the research and work TheraCour performs on our behalf and no costs may be incurred without the prior authorization or approval by us.
The TheraCour technologies and patents required for execution of our work in the licensed fields and licensed products are automatically licensed to us even if such technologies and patents are developed after the license agreements themselves.
Patents, Patent Applications, Proprietary Rights
Patents and other proprietary rights are essential for our operations. If our drugs are protected by a properly designed and enforceable patent, it can be more difficult for our competitors to use our technology to create competitive products and more difficult for our competitors to obtain a patent that prevents us from using technology we create. As part of our business strategy, in conjunction with TheraCour, we actively seek patent protection both in the United States and internationally and intend to file additional patent applications, when appropriate, to cover improvements in our compounds, products and technology. We also rely on trade secrets, internal know-how, technological innovations and agreements with third parties to develop, maintain and protect our competitive position. Our ability to be competitive will depend on the success of this strategy.
A new international PCT patent application regarding coronavirus drug candidates, PCT/US21/39050, entitled “Self-Assembling Amphiphilic Polymers As Anti-Covid-19 Agents,” was filed under the Patent Cooperation Treaty (PCT) on June 25, 2021. An additional international PCT patent application that builds on this application regarding coronavirus drug candidates, PCT/US22/35210, entitled “Self-Assembling Amphiphilic Polymers As Anti-Covid-19 Agents,” was filed on June, 28, 2022, with a requested priority date of the 2021 application. Our anti-COVID drugs are based on polymeric micelle nanomedicine technologies developed by TheraCour and its affiliate, AllExcel, Inc. (“AllExcel”). The inventors at AllExcel have filed these two broad PCT patent applications that form the basis of our two lead drug candidates, namely, NV-CoV-2 and NV-CoV-2-R. These new patent applications cover the new technologies, compositions, formulations, processes, manufactured products, and methods of use, among other specifics.
The nominal expiry date for patents resulting from these two PCT applications would be 20 years, after filing and if issued, i.e. June 24, 2041, and could be extended in certain countries under regulatory extensions to as late as into the year 2043, providing a significant commercial runway.
We believe that our drugs by themselves may be eligible for patent protection. We, in conjunction with TheraCour, plan on filing patent applications for protecting these drugs when we have definitive results that enable clinical drug development. We believe this strategy would maximize the available commercial patent life for many of our future drugs well beyond 2043. We intend to file the patent application for HerpeCide before entering human clinical trials, as we have done for our Coronavirus program. The estimated expiry date for the HerpeCide patents, if and when issued, would be no earlier than 2044-2049.
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The Company has licenses to key patents, patent applications and rights to proprietary and patent-pending technologies related to our compounds, products and technologies (see Table 1), but we cannot be certain that issued patents will be enforceable or provide adequate protection or that pending patent applications will result in issued patents.
We have previously announced certain important issuances of patents on the TheraCour® technology underlying our Nanoviricides® drugs. A total of at least 61 patents have been issued globally, on the basis of the first two international PCT patent families that cover the fundamental aspects of the platform technology we license from TheraCour. Additional patent grants are expected to continue as the applications progress through prosecution processes. All of the resulting patents have substantially broad claims. These patents have nominal expiry dates in 2026 to 2029.
The patent expiry dates can be further extended in several countries and regions for the additional allowances due to the regulatory burden of drug development processes, or other local considerations, such as licensing to a local majority held company. Many countries allow up to five years extension for regulatory delays.
We believe that the novel compositions disclosed in these patent applications, and additional proprietary intellectual property provide the necessary features that enable the development of nanoviricides. We believe that no other published literature materials or existing patents are capable of providing all of the necessary features for this development, to the best of our knowledge. However, we have no knowledge of the extensive active internal developments at a number of companies in the targeted therapeutics area.
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