NANOVIRICIDES INC

Previous wording

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. Actual results may differ materially from results anticipated in these forward-looking statements.

Current wording

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. Actual results may differ materially from results anticipated in these forward-looking statements. We base the forward-looking statements on information currently available to us, and we assume no obligation to update them.

Previous wording

Our first drug candidate, NV-CoV-2, administered orally, has recently completed Phase 1a/1b human clinical trial for the evaluation of safety and tolerability in healthy subjects. NV-387 is the active ingredient in this drug product. There were no reported adverse events, and the drugs were well-tolerated even at the highest level of dosing given multiple times in this trial.

Current wording

NV-387, our most advanced drug candidate, administered orally, has successfully completed Phase I human clinical trial for the evaluation of safety and tolerability in healthy subjects. There were no reported adverse events, and the drugs were well tolerated even at the highest level of dosing given multiple times in this trial.

Previous wording

We plan to further develop this drug, NV-387, as an ultra-broad-spectrum antiviral medication to treat a number of viral infections including Coronaviruses (SARS-CoV-2, MERS-CoV, seasonal coronaviruses, hCoV-NL63), Respiratory Syncytial Virus (RSV), Influenza viruses, other respiratory infections, possibly thus covering all of the “tripledemic” viruses and more with this single drug. We also plan to further develop NV-387 for the treatment of biodefense viruses such as Smallpox/Mpox. This ultra-broad-spectrum antiviral activity of NV-387 is supported by multiple highly lethal animal studies of infections by different viruses.

Current wording

We are now preparing for Phase II human clinical trials to assess effectiveness of NV-387 treatment in a number of different viral diseases in humans. We plan to further develop NV-387, as an ultra-broad-spectrum antiviral medication to treat a number of viral infections including Coronaviruses (SARS-CoV-2, MERS-CoV, Seasonal Coronaviruses, hCoV-NL63), Respiratory Syncytial Virus (RSV), Influenza Viruses, and possibly other respiratory viral infections, thus covering all of the “tripledemic” viruses and more with this single drug.

Previous wording

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.

Current wording

A safe and effective antiviral drug, when approved, with an extensive broad-spectrum activity across multiple, distinct, virus families as observed for NV-387, 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.

Previous wording

We are also developing several other virus-family-specific drug candidates. Of these, 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. Further, we are also developing an oral drug for the systemic treatment of most of the herpesvirus family related infections, including HSV-1 “cold sores” that is based on the same active ingredient as NV-HHV-1. Further, we have drug candidates in HIVCide™ program that have shown substantial antiviral activities in animal studies warranting further clinical development. We have several other drug candidates others at different preclinical drug development stages in our pipeline for the treatment of other viral infections including Dengue viruses, Ebola viruses, etc.

Current wording

We are also developing an oral drug for the systemic treatment of most of the herpesvirus family related infections, including HSV-1 cold sores, HSV-2 and VZV that is based on the same active ingredient as NV-HHV-1. Further, we have drug candidates in HIVCide™ program that have shown substantial antiviral activities in animal studies warranting further clinical development. We have previously worked on Ebola virus drug development, as well as Dengue virus drug development, which are at an early stage.

Previous wording

We believe that we have developed a strong pipeline of drug candidates that, we anticipate, will yield new drug candidates over a very long timeframe into the future, and, we expect, will enable cures of many currently non-curable viral diseases.

Current wording

Thus, we have developed a strong pipeline of drug candidates that, we anticipate, will yield new drug candidates over a very long timeframe into the future, and, we expect, will enable cures of many currently non-curable viral diseases.

Previous wording

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.

Current wording

The drug development process is long and expensive. We do not have any approved drugs on the market as of now. 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.

Previous wording

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. To date, we have financed our drug development programs using equity-based financing from the sale of our shares in private and public instruments including registered direct offerings as well as “At the Market” (ATM) offerings

Current wording

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. To date, we have financed our drug development programs using equity-based financing from the sale of our shares in private and public transactions including registered direct offerings as well as “At the Market” (ATM) offerings.

Previous wording

NV-387 was designed to be and has been found to be an ultra-broad-spectrum antiviral, reminiscent of antibiotics. So far it has been evaluated for antiviral activity in animal models of Coronavirus, RSV, Smallpox, and Influenza infections. In all cases the studies demonstrated positive results for NV-387 treatment that matched or exceeded corresponding available therapeutics or positive controls.

Current wording

NV-387 was designed to be and has been found to be an ultra-broad-spectrum antiviral, reminiscent of antibiotics. So far it has been evaluated for antiviral activity in animal models of Coronavirus, RSV, Smallpox, and Influenza infections. In all cases the studies demonstrated extremely positive results for NV-387 treatment that matched or exceeded corresponding available therapeutics or positive controls.

Previous wording

Coronaviruses: NV-387 was found to effectively reduce the cytopathic effects caused by coronaviruses in cell culture studies without cellular toxicity. It was also found to suppress infection of cells by SARS-CoV-2 pseudovirion as much as a control antibody. NV-387 was found to significantly increase the lifespan of rats infected lethally into the lungs with the coronavirus hCoV-NL63, a model virus stand-in for SARS-CoV-2. Further, the increase in lifespan upon NV-387 I.V. administration was substantially greater than that obtained with Remdesivir I.V. administration. Additionally, NV-387 given orally also increased the lifespan by more than that seen with remdesivir IV administration.

Current wording

**1.**Coronaviruses: NV-387 was found to effectively reduce the cytopathic effects caused by coronaviruses in cell culture studies without cellular toxicity. It was also found to suppress infection of cells by SARS-CoV-2 pseudovirion as much as a control antibody. NV-387 was found to significantly increase the lifespan of rats infected lethally into the lungs with the coronavirus hCoV-NL63, a model virus stand-in for SARS-CoV-2. Further, the increase in lifespan upon NV-387 Intravenous (“IV”) administration was substantially greater than that obtained with remdesivir IV administration. Additionally, NV-387 given orally also increased the lifespan by more than that seen with remdesivir IV administration.

Previous wording

RSV: Oral dosing with NV-387 led to full survival of mice lethally infected with RSV/A2 leading to severe lung disease, whereas the only available drug against RSV, namely ribavirin, showed a limited increase in lifespan. Ribavirin is a highly toxic drug and is given only as a last resort. Two vaccines have recently been approved for protection of persons 60+ years old from RSV infection (Arexvy®, GSK, and Abrysvo®, Pfizer). Abrysvo was recently approved for use in pregnant women for protection of infants. A new antibody, nirsevimab (Beyfortus®) was approved for protection of newborn children at risk of RSV disease, but not for treatment. There is no approved drug for the treatment of RSV infection, other than the last resort drug, ribavirin that has limited effectiveness.

Current wording

**2.**RSV: Oral dosing with NV-387 led to full survival of mice lethally infected with RSV/A2 to cause severe lung disease, whereas the only available drug against RSV, namely ribavirin, showed a limited increase in lifespan. 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, whereas animals in the ribavirin-treated group showed progressive pathology, eventually leading to death. Ribavirin is a highly toxic drug and is given only as a last resort. Two vaccines have recently been approved for protection of persons 60+ years old from RSV infection (Arexvy®, GSK, and Abrysvo®, Pfizer). Abrysvo was recently approved for use in pregnant women for protection of infants. A new antibody, nirsevimab (Beyfortus®) was approved for protection of newborn children at risk of RSV disease, but not for treatment. There is no approved drug for the treatment of RSV infection, other than the last resort drug, ribavirin that has limited effectiveness.

Previous wording

Smallpox/Mpox: Oral dosing with NV-387 led to an increase in lifespan of mice lethally infected with ectromelia virus (a cousin and model stand-in for smallpox/mpox viruses) into lungs that was comparable to treatment with tecovirimat (TPOXX®, SIGA). We also found that in a lethal intradigital footpad infection of mice with ectromelia virus, oral NV-387 treatment led to lifespan improvement comparable to oral tecovirimat treatment. This model is relevant to the skin-abrasion mode of MPox transmission that was found to be dominant in the recent MPox pandemic, and is also found to be operative in the current Congo MPox epidemic. Tecovirimat, approved for Smallpox treatment under the FDA “Animal Rule”, is currently stockpiled under the US Strategic National Stockpile.

Current wording

**3.**Smallpox/MPox: Oral dosing with NV-387 led to an increase in lifespan of mice lethally infected with ectromelia virus (a cousin and model stand-in for smallpox/MPox viruses) into lungs that was comparable to treatment with tecovirimat (TPOXX®, SIGA). In addition, we also found that in a lethal intradigital footpad infection of mice with ectromelia virus, oral NV-387 treatment led to lifespan improvement comparable to oral tecovirimat treatment. This model is relevant to the skin-abrasion mode of MPox transmission that was found to be dominant in the recent MPox pandemic, and is also found to be operative in the current Congo MPox epidemic. Tecovirimat, approved for Smallpox treatment under the FDA “Animal Rule”, is currently stockpiled under the US Strategic National Stockpile.

Previous wording

Influenza: Oral dosing with NV-387 led to a substantially increased lifespan of mice lethally infected with Influenza A/H3N2 compared to the increase in lifespan afforded by treatment with Oseltamivir (Tamiflu®, Roche), Peramivir (Biocryst), or Baloxavir (Xofluza®, Shionogi, Roche), approved drugs against influenza viruses.

Current wording

**4.**Influenza: Oral dosing with NV-387 led to a substantially increased lifespan of mice lethally infected with Influenza A/H3N2 compared to the increase in lifespan afforded by treatment with Oseltamivir (Tamiflu®, Roche), Peramivir (Biocryst), or Baloxavir (Xofluza®, Shionogi, Roche), approved drugs against influenza viruses.

Previous wording

We note that all three approved influenza drugs oseltamivir, peramivir and baloxivir are known to be prone to viral escape by mutations. In contrast, NV-387 as a host-mimetic is highly unlikely to be escaped by the susceptible viruses.

Current wording

We note that all three approved influenza drugs oseltamivir, peramivir and baloxavir are known to be prone to viral escape by mutations. In contrast, NV-387 as a host-mimetic is highly unlikely to be escaped by the susceptible viruses.

Previous wording

Given that, in each of these studies, we have compared the results of treatment with NV-387 with those of approved drugs, and believe that the NV-387 treatment is superior. We believe that NV-387 has strong prospects for regulatory approval in each of these indications.

Current wording

Given that, in each of these studies, we have compared the results of treatment with NV-387 with those of approved drugs, and found NV-387 treatment to be superior. We believe that NV-387 has strong prospects for regulatory approval in each of these indications.

Previous wording

Further, NV-387 also acts as a unique and novel drug delivery vehicle, similar in action to exosomes. Thus, encapsulation of remdesivir in NV-387 enabled oral delivery of NV-387 and the activity of the resulting drug, NV-387-Rp, given orally in lethally infected animals, was found to be superior to that of each of NV-387 and remedesivir (Veklury®, Gilead).

Current wording

Further, NV-387 also acts as a unique and novel drug delivery vehicle, similar in action to exosomes. Thus, encapsulation of remdesivir in NV-387 enabled oral delivery of NV-387 and the activity of the resulting drug, NV-387-g-Rp, given orally in lethally infected animals, was found to be superior to that of each of NV-387 and remedesivir (Veklury®, Gilead).

Previous wording

In the Phase 1a/1b human clinical trial, even at the highest dose level, dosed multiple times, NV-387 was found to be well tolerated, and there were no reported adverse events of the drug when given orally.

Current wording

In the Phase I human clinical trial, even at the highest dose level, dosed multiple times, NV-387 was found to be well tolerated, and there were no reported adverse events of the drug that was given orally.

Previous wording

This clinical trial finding is consistent with the findings that the evaluation of safety of NV-387 in pre-clinical studies demonstrated a No-Observed-Adverse-Effects-Level (NOAEL) at 1,200 mg/Kg, and the Maximum Tolerable Dose level (MTD) at 1,500 mg/Kg in rats, which are very positive numbers. Further, NV-387 was found to be non-mutagenic, non-immunogenic, non-allergenic, and non-genotoxic in pre-clinical studies.

Current wording

This clinical trial finding is consistent with the findings that the evaluation of safety of NV-387 in pre-clinical studies demonstrated a No-Observed-Adverse-Effects-Level (NOAEL) at 1,200 mg/Kg, and the Maximum Tolerable Dose level (MTD) at 1,500 mg/Kg in rats, which are very high numbers (high is good).

Previous wording

KMPL intends on initiating a Phase II clinical trial in India shortly after the Phase I report become available. We are in discussions with subject matter experts in India regarding the best indication to go with in Phase II, with RSV and Influenza as some of the choices.

Current wording

We intend to initiate a Phase II clinical trial in India shortly after the Phase I final report becomes available. We are in discussions with subject matter experts in India regarding the best indication to go with in Phase II; RSV and Influenza being some of the choices.

Previous wording

We also plan on initiating a Phase IIa clinical trial of NV-387 for the treatment of RSV infection under the US FDA (see further below). We are in the process of developing a Pre-IND application to the US FDA for this purpose. Our overall objective of the program is to evaluate NV-387 for commercialization as a treatment of infants to young children. We believe that our Phase IIa clinical trial design will enable us to proceed to a Phase II/III registration clinical trials in infants and young children with RSV infection. We believe that this is an unmet medical need.

Current wording

We also plan on initiating a Phase IIa clinical trial of NV-387 for the treatment of RSV infection under the US FDA (see further below). We are in the process of developing a Pre-IND application to the US FDA for this purpose. Our overall objective of the program is to evaluate NV-387 for commercialization as a treatment of infants to young children. We believe that our Phase IIa clinical trial design will enable us to proceed to a Phase II/III registration clinical trials in infants and young children with RSV infection. This is an unmet medical need.

Previous wording

Each year in the United States, RSV leads to approximately 2.1 million outpatient (non-hospitalization) visits among children younger than five years old, resulting in 58,000-80,000 hospitalizations among children younger than 5 years old, and 100–300 deaths in children younger than five years old, according to the CDC (https://www.cdc.gov/rsv/research/index.html ).

Current wording

Each year in the United States, RSV leads to approximately 2.1 million outpatient (non-hospitalization) visits among children younger than 5 years old, resulting in 58,000-80,000 hospitalizations among children younger than 5 years old, and 100–300 deaths in children younger than 5 years old, according to the CDC (https://www.cdc.gov/rsv/research/index.html).

Previous wording

We believe our unique and successful mimicking of S-PG is responsible for the observed broad-spectrum activity of NV-387. NV-387 is an example of NanoViricides Platform Modality #1 implementation discussed in our Form 10-K Annual report filed with the SEC on October 13, 2023.

Current wording

We believe our unique and successful mimicking of S-PG is responsible for the observed broad-spectrum activity of NV-387. NV-387 is an example of NanoViricides Platform Modality #1 implementation discussed in our Annual report filed with the SEC on September 27, 2024

Previous wording

Our production capacity is anticipated to be more than sufficient for Phase I, Phase II and Phase III human clinical trials for all of our drugs in development.

Current wording

We continue to improve the production processes and production scale. Our production capacity is anticipated to be more than sufficient for Phase I, Phase II and Phase III human clinical trials for all of our drugs in development.

Previous wording

We also have onsite full-fledged chemistry laboratories to enable drug design, discovery, small scale synthesis, testing, and scale-up of drug candidates worthy of further development.

Current wording

We also have on site full-fledged chemistry laboratories to enable drug design, discovery, small scale synthesis, testing, and scale-up of drug candidates worthy of further development.

Previous wording

We are now a clinical stage innovative drug development company, advancing from the research and development (“R&D”) stage into regulatory development of our drug candidates towards commercialization. We have been executing rapidly and efficiently, as well as in a cost-effective and productive manner, resulting in successful completion of the Phase I Safety and Tolerability clinical trial of our drug candidate, NV-CoV-2 (API NV-387). We believe that this successful completion with no reported adverse events, is a very important milestone because NV-387 can now advance into Phase II efficacy clinical trials for multiple antiviral indications. Further, this success validates our entire platform technology as being capable of producing drug candidates that are capable of successfully completing Phase I safety and tolerability studies.

Current wording

We are now a clinical stage innovative drug development company, advancing from the research and development (“R&D”) stage into regulatory development of our drug candidates towards commercialization. We have been executing rapidly and efficiently, as well as in a cost-effective and productive manner, resulting in successful completion of the Phase I Safety and Tolerability clinical trial of our drug candidate, NV-CoV-2 (API NV-387). We believe that this successful completion with no reported adverse events, which is the most desirable outcome from Phase I clinical trial to establish safety and tolerability of the drug candidate NV-387 is a very important milestone enabling NV-387 to advance for multiple antiviral indications into Phase II efficacy clinical trials. Additionally, this Phase I bodes well for our entire platform technology as being capable of producing drug candidates that are capable of successfully completing Phase I safety and tolerability studies.

Previous wording

In addition, our pre-clinical lethal virus infection animal model studies provide us the confidence that the drug candidates we advance into Phase II efficacy clinical trials would have a very high likelihood of success. This is because in these animal studies, the animal model plays the role of a “test tube” where the virus can proliferate, and our drugs are designed to directly attack the virus without interfering with functions of the host animal. Additionally, we design the studies to provide clear readout in terms of survival lifespan that can be used for ranking the activity of each tested drug, including already approved drugs where available.

Current wording

In addition, our pre-clinical lethal virus infection animal model studies provide us the confidence that the drug candidates we advance into Phase II efficacy clinical trials would have a high probability of success. This is because in these animal studies, the animal model plays the role of a “test tube” where the virus can proliferate, and our drugs are designed to directly attack the virus without interfering with functions of the host animal. Additionally, we design the studies to provide clear readout in terms of survival lifespan that can be used for ranking the activity of each tested drug, including already approved drugs where available.

Previous wording

We de-risk drug development heavily in the early stages so that failure at clinical stage would be minimized. We believe our success rate of drug approval would be substantially better than industry averages because of the features of our nanoviricides platform technology and the de-risking strategies we employ in drug development.

Current wording

Our non-clinical programs are designed to minimize the risk of failure of our drug candidates in clinical trials. Specifically, we perform evaluation of antiviral activity in lethal studies in direct comparison with known approved drugs if available, and choose drug candidates that show at least comparable or superior activity to the approved ones. We employ lethal infection studies so that the survival time is a clear indicator of the antiviral activity, and can be used to rank relative activity of drug candidates. We believe our success rate of drug approval would be substantially better than industry averages because of the features of our nanoviricides platform technology and the de-risking strategies we employ in drug development.

Previous wording

We believe that our platform technology enables development of drugs that viruses would not escape from. In fact, during the pre-clinical development in the COVID program, we have successfully screened our drug candidates to be able to protect cells against infection by distinctly different coronaviruses. This broad-spectrum, pan-coronavirus drug development approach was adopted to ensure that our drug candidates should remain effective even as variants of SARS-CoV-2 continue to evolve in the field, just as we had already anticipated at the beginning of the pandemic.

Current wording

We believe that our platform technology enables development of drugs that viruses would not escape from. In fact, during the pre-clinical development in the COVID program, we have successfully screened our drug candidates to be able to protect cells against infection by distinctly different coronaviruses. This broad-spectrum, pan-coronavirus drug development approach was adopted to ensure that our drug candidates should remain effective even as variants of SARS-CoV-2 continue to evolve in the field, just as we had already anticipated at the very beginning of the pandemic.

Previous wording

We mimic the feature on the cellular protein at which the virus binds, and, using molecular modeling, design small molecules that act as “ligands” to bind to the virus surface glycoproteins as though the virus was binding to that cellular protein itself. This host-side chemical signature that the virus uses for infecting cells does not change even as the virus mutates, evolves and generates variants. We chemically synthesize the optimal ligands, and separately attach them to the polymeric micelle scaffold to generate a number of initial “nanoviricide” drug candidates to screen against the virus. Consequently, the nanoviricide is designed to “look like” the cell membrane with copious amounts of sites for the virus to bind to. When initial interaction of a few ligands with the virus particle takes place, the “metstable” nanoviricide micelle is anticipated to shift its shape, inverting itself onto the virus particle promoted by the “lipid-lipid mixing effect” driven by the lipid chains normally on the interior of a nanoviricide micelle and the lipid membrane that is on the virus surface. Such an attack on the virus particle is expected to de-stabilize the virus particle and uproot the surface glycoproteins it uses for fusing with a cell. As a result, the virus would no longer be capable of infecting a cell. This process would result in complete blockage of the “Re-Infection Cycle” of the virus if successful. We call this mechanism “Re-Infection Inhibition”. This mechanism goes beyond the simple neutralization of the virus by antibodies, which requires the human immune system to further take care of the resulting virus-antibody complex. This mechanism also goes beyond the simple blocking of virus entry by small chemical entry inhibitors, which would require extremely high concentrations of the inhibitor to effect complete blockage of each virus particle based on mass-action considerations.

Current wording

We mimic the feature on the cellular protein at which the virus binds, and, using molecular modeling, design small molecules that act as “ligands” to bind to the virus surface glycoproteins as though the virus was binding to that cellular protein itself. This host-side chemical signature that the virus uses for infecting cells does not change even as the virus mutates, evolves and generates variants. We chemically synthesize the optimal ligands, and separately attach them to the polymeric micelle scaffold to generate a number of initial “nanoviricide” drug candidates to screen against the virus. Thus the nanoviricide is designed to “look like” the cell membrane with copious amounts of sites for the virus to bind to. When initial interaction of a few ligands with the virus particle takes place, the “metstable” nanoviricide micelle is anticipated to shift its shape, inverting itself onto the virus particle promoted by the “lipid-lipid mixing effect” driven by the lipid chains normally on the interior of a nanoviricide micelle and the lipid membrane that is on the virus surface. Such an attack on the virus particle is expected to de-stabilize the virus particle and uproot the surface glycoproteins it uses for fusing with a cell. Thus the virus would no longer be capable of infecting a cell. This process would result in complete blockage of the “Re-Infection Cycle” of the virus if successful. We call this mechanism “Re-Infection Inhibition”. This mechanism goes beyond the simple neutralization of the virus by antibodies, which requires the human immune system to further take care of the resulting virus-antibody complex. This mechanism also goes beyond the simple blocking of virus entry by small chemical entry inhibitors, which would require extremely high concentrations of the inhibitor to effect complete blockage of each virus particle based on mass-action considerations.

Previous wording

Mimicking the attachment receptor families may lead to extremely broad-spectrum drug candidates. We call this implementation NanoViricides Platform Technology Modality #1. NV-387 is an example of this Modality #1, namely, Broad-Spectrum Antiviral Re-infection Inhibitors.

Current wording

Mimicking the attachment receptor families may lead to extremely broad-spectrum drug candidates. We call this implementation NanoViricides Platform Technology Modality #1. NV-387 is an example of this Modality #1, namely, Broad-Spectrum Antiviral Re-infection Inhibitors. NV-387 is designed to mimic key features required by viruses of the host-side sulfated proteoglycans that viruses use as attachment receptors.

Previous wording

In fact, we have found in pre-clinical animal studies that both NV-387 and NV-387-g-R were highly effective when given orally in combating a lethal lung infections that models the severe SARS-CoV-2 disease as seen with the delta variant. In comparing the effect on combating the infection by oral treatment versus injectable treatment, we believe that the bioavailability of the oral dosage forms is substantially good, and in the range of many approved oral drugs. In addition, the API NV-387 was found to be highly effective when given orally in the case of lethal lung RSV infection animal model, a lethal smallpox-emulating ectromelia footpad infection mouse model, a lethal smallpox-emulating ectromelia lung infection mouse model, as well as a lethal Influenza A/H3N2 lung infection mouse model, further substantiating the oral bio-availability of NV-387.

Current wording

In fact, we have found in pre-clinical animal studies that NV-387 was highly effective when given orally in combating a lethal lung infections that models the severe SARS-CoV-2 disease as seen with the delta variant. In comparing the effect on combating the infection by oral treatment versus injectable treatment, we believe that the bioavailability of the oral dosage forms is substantially good, and in the range of many approved oral drugs. In addition, the API NV-387 was found to be highly effective when given orally in the case of lethal lung RSV infection animal model, a lethal smallpox-emulating ectromelia footpad infection mouse model, a lethal smallpox-emulating ectromelia lung infection mouse model, as well as a lethal Influenza A/H3N2 lung infection mouse model, further substantiating the oral bio-availability of NV-387.

Previous wording

The injectable formulation of NV-387 is expected to be valuable in the treatment of severe cases. Out-patient single dose injection treatment may be feasible if the effectiveness of NV-387 in human clinical trials matches that observed in pre-clinical animal studies. Further, this injectable formulation is designed to be deliverable also as an aerosol by a simple hand-held nebulizer device directly into the lungs. Such inhalation, as an aerosol, is expected to provide greater benefits to more severe patients by providing high concentration of the drug locally in the lungs where the RSV, SARS-CoV-2, and Influenza viruses cause the most damage in severe cases. The Solution for Injection, Infusion and Inhalation of NV-387 would also be very important in pediatric as well as hospitalized cases.

Current wording

The injectable formulation of NV-387 is expected to be valuable in the treatment of severe cases. Out-patient single dose injection treatment may be feasible if the effectiveness of NV-387 in human clinical trials matches that observed in pre-clinical animal studies. Further, this injectable formulation is designed to be deliverable also as an aerosol by a simple hand-held nebulizer device directly into lungs. Such inhalation, as an aerosol, is expected to provide greater benefits to more severe patients by providing high concentration of the drug locally in the lungs where the RSV, SARS-CoV-2, and Influenza viruses cause the most damage in severe cases. The Solution for Injection, Infusion and Inhalation of NV-387 would also be very important in pediatric as well as hospitalized cases.

Previous wording

We believe that the strong antiviral activity we have observed in cell culture studies and in lethal virus infection animal studies, in comparison to approved drugs is a positive indication of clinical success and potential regulatory approval of NV-387 for the different viral infection indications we are seeking.

Current wording

We believe that the extremely strong antiviral activity we have observed in cell culture studies and in lethal virus infection animal studies, in comparison to approved drugs is a strong positive indication of clinical success and potential regulatory approval of NV-387 for the different viral infection indications we are seeking.

Previous wording

We believe we have demonstrated that we can rapidly develop different types of formulations for different routes of administration, such as injectable, skin cream, lotion, gel, and even oral, because of the inherent strength of the flexible and tailorable Nanoviricide

Current wording

We believe we have demonstrated that we can rapidly develop different types of formulations for different routes of administration, such as injectable, skin cream, lotion, gel, and even oral, because of the inherent strength of the flexible and tailorable Nanoviricide Platform technology. The technology also enables us to develop nasal sprays and bronchial aerosols. We plan to develop the appropriate formulations as necessary.

Previous wording

In the previous quarter, we have approximately doubled our production batch size and capacity for NV-387 manufacture. We believe that this capacity will be sufficient for Phase II/III clinical trials for RSV. The production program for Phase II clinical supply is expected to be commissioned soon.

Current wording

We have initiated the production program for Phase II clinical supply of NV-387 drug products.

Previous wording

During the nine months ended March 31, 2024, (i) we have successfully completed the Phase 1a/1b clinical trial of NV-387 with no adverse events; (ii) we have expanded our manufacturing capacity of nanoviricides drugs in anticipation of multiple clinical trials, and (iii) we have continued to further understand the spectrum of antiviral activity of NV-387 towards obtaining information for regulatory advancement against different antiviral indications.

Current wording

We are also performing additional pre-clinical experiments to further understand the spectrum of antiviral activity of NV-387 towards obtaining information for regulatory advancement against different antiviral indications.

Previous wording

In the non-clinical studies leading to the Phase 1a/1b clinical trial, NV-387 has been found to be non-immunogenic, non-allergenic, non-mutagenic, as well as non-genotoxic in various pre-clinical animal model studies. No adverse effects were reported in GLP Safety-Toxicology studies in multiple animal models including non-human primates (NHP, Cynomolgus monkeys). The NOAEL (No-Observed-Adverse-Events-Level) was 1,200 mg/Kg and MTD (Maximum Tolerable Dose) was 1,500 mg/Kg in rats, which are very high numbers (high is numbers are positive).

Current wording

In the non-clinical studies leading to the Phase I clinical trial, NV-387 was found to be non-immunogenic, non-allergenic, non-mutagenic, as well as non-genotoxic. No adverse effects were reported in GLP Safety-Toxicology studies in multiple animal models including non-human primates (NHP, Cynomolgus monkeys). The NOAEL (No-Observed-Adverse-Events-Level) was 1,200 mg/Kg and MTD (Maximum Tolerable Dose) was 1,500 mg/Kg in rats, which are very high numbers (high is good).

Previous wording

The results of the Phase 1a/1b clinical trial are consistent with these non-clinical findings, with no adverse events reported.

Current wording

The results of the Phase I clinical trial are consistent with our non-clinical findings.

Previous wording

The original plan for the Phase 1a/1b clinical trial was to include COVID patients in Phase 1b-COVID cohorts to obtain initial indications of efficacy and dosage requirement. The healthy subjects portion of the clinical trial, which is the traditional Phase I clinical trial involving the evaluation of single-ascending-dose and multiple-ascending dose of the investigational medical product in healthy subjects was completed in December, 2023. Thereafter, efforts to find COVID patients were continued, and an additional clinical site was added during February 2024. In spite of this, the lack of obtaining PCR-positive COVID patients eligible for enrollment into the clinical trial became the obstacle to this trial. Our diligent efforts to identify COVID-19 participants for the clinical trial have been met with a notable absence of positive cases at the designated clinical trial site(s). Therefore, the Phase 1a/1b clinical trial was closed in April 2024, concluding the study as a traditional Phase I study.

Current wording

The original plan for the Phase 1a/1b clinical trial was to include COVID patients in Phase 1b-COVID cohorts to obtain initial indications of efficacy and dosage requirement. The healthy injected portion of the clinical trial, which is the traditional Phase I clinical trial involving the evaluation of single-ascending-dose and multiple-ascending dose of the investigational medical product in healthy subjects was completed in December, 2023. Thereafter, efforts to find COVID patients were continued, and an additional clinical site was added during February 2024. In spite of this, the lack of obtaining PCR-positive COVID patients eligible for enrollment into the clinical trial became the obstacle. Our diligent efforts to identify COVID-19 participants for the clinical trial have been met with a notable absence of positive cases at the designated clinical trial site(s). Therefore, the Phase 1a/1b clinical trial was closed in April 2024, concluding the study as a traditional Phase I study.

Previous wording

We note that we do not have any information regarding the activity of NV-387 (drug product NV-CoV-2) in COVID from this clinical trial because no COVID patients could be found for enrollment in the study. We believe that NV-387 has strong, clinically relevant, activity in treatment of COVID based on our pre-clinical studies that directly evaluated the activity of NV-387 in comparison with remdesivir, an approved drug for the treatment of COVID, and found that the activity of NV-387 was substantially superior to that of remdesivir.

Current wording

We note that we do not have any information regarding the activity of NV-387 (drug product NV-CoV-2) in COVID from this clinical trial because no COVID patients could be found for enrolment in the study. We believe that NV-387 has strong, clinically relevant, activity in treatment of COVID based on our pre-clinical studies that directly evaluated the activity of NV-387 in comparison with remdesivir, an approved drug for the treatment of COVID, and found that the activity of NV-387 was substantially superior to that of remdesivir.