NANOVIRICIDES INC

Previous wording

While broad-spectrum antivirals such as Remdesivir, Ribavirin, Cidofovir, etc. are known, all of them suffer from extensive and varied dose-limiting toxicities, and thereby present limitations on eligible patient populations as well as on clinical effectiveness.

Current 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.

Previous wording

We are a clinical stage company with our first drug in Phase 1a/1b clinical trial and several additional drug candidates in various stages of pre-clinical development, including IND-preparation 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 continue to add to our existing portfolio of products through our internal discovery and clinical development programs and also seek to do so through an in-licensing strategy.

Current 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.

Previous wording

1 https://finance.yahoo.com/news/respiratory-syncytial-virus-rsv-therapeutics-093200835.html?soc_src=social-sh&soc_trk=ma

Current wording

RSV is an important disease particularly for infants and children under six years of age, as well as for older persons and immunocompromised patients. A recent report by Growth Plus Reports estimated the global respiratory syncytial virus (RSV) therapeutics market to grow from $1.8 Billion in 2022 at a CAGR of 18.9%, reaching $ 8.73 billion by 2031 (https://finance.yahoo.com/news/respiratory-syncytial-virus-rsv-therapeutics-093200835.html?guccounter=1 ).

Previous wording

In contrast, NV-387 has been found to be safe in the Phase 1a/1b on-going human clinical study even at the highest dose level, with no adverse events. This is consistent with the finding that it was extremely safe in pre-clinical studies. As an example of its safety, the No-Observed-Adverse-Effects-Level (NOAEL) is found to be 1,200 mg/Kg, and the Maximum Tolerable Dose level (MTD) is 1,500 mg/Kg in rats. Further, NV-387 was found to be non-mutagenic, non-immunogenic, non-allergenic, and non-genotoxic in pre-clinical studies. We therefore anticipate that NV-387 can be given to patients across all patient population, in age from infants to seniors, including immunocompromised persons, patients with co-morbidities, and others.

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 positive numbers. Further, NV-387 was found to be non-mutagenic, non-immunogenic, non-allergenic, and non-genotoxic in pre-clinical studies.

Previous wording

We anticipate that NV-387 formulations would be expected to be eligible for the development of Poxvirus therapeutics under the FDA “Animal Rule”. The Animal Rule program requires well-controlled GLP studies in specific animal poxvirus infection models as replacement of the Phase II/III human clinical trials, and expanded Phase I human clinical trials to elucidate safety of the drug in human use. We plan to seek non-dilutive government funding for this indication.

Current wording

Additionally, we anticipate that NV-387 would be expected to be eligible for the development of Poxvirus therapeutics under the FDA “Animal Rule”. The Animal Rule program requires well-controlled GLP studies in specific animal poxvirus infection models as replacement of the Phase II/III human clinical trials, and expanded Phase I human clinical trials to elucidate safety of the drug in human use. We plan to seek non-dilutive government funding for this indication.

Previous wording

NV-387 is designed to mimic a common “attachment factor” family that we refer to as the “Sulfated Proteoglycans (S-PG)”, to which a large number of viruses bind as the first step in infecting a cell (reviewed in 3). 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 glycosaminoglycans (“GAG”s), and proteoglycans containing heparan sulfate (HSPG), dermatan sulfate (DSPG), chondroitin sulfate (CSPG), and keratan sulfate (CSPG), among others. 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, Chickengunya Virus, Herpesviruses, Human Papillomavirus (HPV), HIV, Hendra and Nipah Viruses, Ebola and Marburg Viruses, Poxviruses, among others. Thus, a large number of virus families use these S-PG family attachment receptors to concentrate next to cells and thereby efficiently infect cells, with different virus families having preferences to one or more of such attachment factors.

Current wording

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, Chickengunya Virus, Herpesviruses, Human Papillomavirus (HPV), HIV, Hendra and Nipah Viruses, Ebola and Marburg Viruses, and Poxviruses, among others (Cagno V, Tseligka ED, Jones ST, Tapparel C. Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias? Viruses. 2019 Jul 1;11(7):596. doi: 10.3390/v11070596. PMID: 31266258; PMCID: PMC6669472). Thus, a large number of virus families use these S-PG family attachment receptors to concentrate next to cells and thereby efficiently infect cells, with different virus families having preferences to one or more of such attachment factors.

Previous wording

A safe and effective antiviral drug that the virus would not escape by simple mutations or field evolution is the holy grail of antiviral drug development. We believe that the NanoViricides Platform technology meets this challenge.

Current wording

A safe and effective antiviral drug that the virus would not escape by mutations or field evolution is the holy grail of antiviral drug development. We believe that the NanoViricides Platform technology meets this challenge.

Previous wording

NanoViricides is one of a few biopharma companies that has its own cGMP-compliant manufacturing facility. We have manufactured multi-Kg scale clinical supply of drug substances as well as the oral drug products for NV-CoV-2 at our own facility, from synthesis all the way to fill-finish-labeling and packaging, simplifying and expediting the cGMP-compliant manufacturing operations. Our production capacity is anticipated to be more than sufficient for Phase I, Phase II and Phase III human clinical trials for our anti-coronavirus and anti RSV drugs in development, as well as for the anticipated clinical trials of NV-HHV-1 skin cream for the treatment of shingles, and any other anticipated clinical trials that we may engage into. This in-house cGMP production capability is expected to result in significant cost savings across all our programs.

Current wording

We believe our capabilities in manufacturing clinical drug products are now well established. We have manufactured multi-Kg scale clinical supply of drug substances as well as the oral drug products for NV-CoV-2 at our own facility, from synthesis all the way to fill-finish-labeling and packaging, simplifying and expediting the cGMP-compliant manufacturing operations.

Previous wording

Manufacturing nanomedicines, especially under cGMP conditions, has been identified as a strong risk, and has led to failure of several nanomedicines programs. NanoViricides co-founder Dr. Anil Diwan and our team have employed considerations for cGMP manufacture of our nanomedicines right from the design, development and optimization of the drug candidates, the polymers and ligands that go into them, as well as the processes employed right from the small research scale to the initial process verification batches. The team has successfully and rapidly translated from the research scale production of several grams drug substance to Kg-scale cGMP-compliant manufacture for two different drug candidates, namely NV-HHV-1 and NV-CoV-2, in three different formulations, namely skin cream, oral syrup, and oral gummies, in a very short time span. This includes manufacture of the active ingredient (drug substance), the formulated drug products, and packaged drug products for clinical trials usage.

Current wording

Manufacturing nanomedicines, especially under cGMP conditions, has been identified as a major risk, and has led to failure of several nanomedicines programs. NanoViricides co-founder Dr. Anil Diwan and our team have employed considerations for cGMP manufacture of our nanomedicines right from the design, development and optimization of the drug candidates, the polymers and ligands that go into them, as well as the processes employed right from the small research scale to the initial process verification batches.

Previous wording

NanoViricides is Fully Equipped for Rapid Antiviral Drug Development from Discovery to cGMP Drug Product Delivery for Clinical Trials

Current wording

NanoViricides is Fully Equipped for Rapid Antiviral Drug Development from Discovery to cGMP Drug Product Delivery for Clinical Trials; Which Makes NanoViricides a “FIPCO”

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 advancing our first drug candidate, NV-CoV-2 into human clinical trials. We believe that taking our first drug candidate through Phase 1a/1b human clinical trials is a very important milestone in that it essentially validates our entire platform technology as being capable of producing drug candidates worthy of human clinical trials, and potentially of success in those clinical trials.

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, 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.

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 very 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 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. 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.

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. 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.

Previous wording

The NanoViricides Platform Technology: (ii) Promising Potential Cures for Infections by Non-latency Viruses 6

Current wording

The NanoViricides Platform Technology: (ii) Promising Potential Cures for Infections by Non-latency Viruses

Previous wording

Additionally, we are the only company that, to the best of our knowledge, is developing antiviral treatments that are designed to (a) directly attack the virus and disable it from infecting human cells (i.e. block the “Re-Infection Cycle”), and (b) simultaneously block the reproduction of the virus that has already gone inside a cell (i.e. block the “Replication Cycle”). Together, this strategy of a two-pronged attack against the virus, both inside the cell and outside the cell, and thus blocking the complete lifecycle of the virus, can be expected to result in a cure for coronaviruses and other viruses that do not become latent. We call this implementation, namelyencapsulation of other active ingredients within the polymeric micelle of the virus-targeted nanoviricide (which can be based on either Modality #1 or Modality #2), the NanoViricides Platform Technology Modality #3.

Current wording

Additionally, we are the only company that, to the best of our knowledge, is developing antiviral treatments that are designed to (a) directly attack the virus and disable it from infecting human cells (i.e. block the “Re-Infection Cycle”), and (b) simultaneously block the reproduction of the virus that has already gone inside a cell (i.e. block the “Replication Cycle”). Together, this strategy of a two-pronged attack against the virus, both inside the cell and outside the cell, and thus blocking the complete lifecycle of the virus, can be expected to result in a cure for coronaviruses and other viruses that do not become latent. We call this implementation, namely encapsulation of other active ingredients within the polymeric micelle of the virus-targeted nanoviricide (which can be based on either Modality #1 or Modality #2), the NanoViricides Platform Technology Modality #3.

Previous wording

As an example of the Modality #3, we have developed NV-387-R, which comprises NV-387 that encapsulates Remdesivir, a known broad-spectrum antiviral drug that is already approved for COVID treatment of hospitalized patients. Although approved, the clinical effectiveness of Remdesivir is limited by its bodily metabolism. It is well known that this drug is highly active in cell culture studies, but the clinical results do not match the expectations corresponding to its cell culture effectiveness. We developed NV-387-R to overcome this issue and we have demonstrated that encapsulation within NV-387 successfully improves the PK/PD (pharmacokinetics and pharmacodynamics) profile of Remdesivir 4. The increased circulating lifetime and also concentration of intact Remdesivir should improve its effectiveness. Additionally, NV-387-R affords the synergistic effects of attacking the virus lifecycle by two orthogonal mechanisms, going well beyond the effects of Remdesivir alone. In NV-387-R, one component, NV-387, is designed to block the “Re-Infection Cycle”, and the encapsulated guest component, Remdesivir is known to block the “Replication Cycle”. Thus NV-387-R is designed to block the entire lifecycle of many viruses, not just coronaviruses.

Current wording

As an example of the Modality #3, we have developed NV-387-g-R, which comprises NV-387 that encapsulates Remdesivir, a known broad-spectrum antiviral drug that is already approved for COVID treatment of hospitalized patients. Although approved, the clinical effectiveness of Remdesivir is limited by its bodily metabolism. It is well-known that this drug is highly active in cell culture studies, but the clinical results do not match the expectations corresponding to its cell culture effectiveness. We developed NV-387-g-R to overcome this issue and we have demonstrated that encapsulation within NV-387 successfully improves the PK/PD (pharmacokinetics and pharmacodynamics) profile of Remdesivir. The increased circulating lifetime and also concentration of intact Remdesivir should improve its effectiveness. Additionally, NV-387-g-R affords the synergistic effects of attacking the virus lifecycle by two orthogonal mechanisms, going well beyond the effects of Remdesivir alone. In NV-387-g-R, one component, NV-387, is designed to block the “Re-Infection Cycle”, and the encapsulated guest component, Remdesivir is known to block the “Replication Cycle”. Thus NV-387-g-R is designed to block the entire lifecycle of many viruses, not just coronaviruses.

Previous wording

This total attack on the complete lifecycle of the virus is expected to result in the most effective drug candidates. It is now well accepted that multiple antivirals together produce better effectiveness than single ones individually. Our strategy goes beyond simply a mix of multiple antivirals. Our unique, shape-shifting nanomedicine technology leads to substantial improvement in the pharmacokinetic properties of the guest antiviral drug. We have demonstrated this capability in the case of NV-387-R, as discussed above, wherein encapsulation of Remdesivir within the polymeric micelles of NV-387 protects the former drug from bodily metabolism in animal studies. This allows higher concentrations of the guest drug to be reached and simultaneously extends the effectiveness time period in comparison to the standard Veklury® (Gilead) formulation. The resulting drug, NV-387-R has not only significantly improved characteristics for its Remdesivir component, but additionally provides the novel re-infection blocking mechanism of NV-387; together enabling complete block of the viral lifecycle, which would potentially result in a cure.

Current wording

This total attack on the complete lifecycle of the virus is expected to result in the most effective drug candidates. It is now well accepted that multiple antivirals together produce better effectiveness than single ones individually. Our strategy goes beyond simply a mix of multiple antivirals. Our unique, shape-shifting nanomedicine technology leads to substantial improvement in the pharmacokinetic properties of the guest antiviral drug. We have demonstrated this capability in the case of NV-387-g-R, as discussed above, wherein encapsulation of Remdesivir within the polymeric micelles of NV-387 protects the former drug from bodily metabolism in animal studies. This allows higher concentrations of the guest drug to be reached and simultaneously extends the effectiveness time period in comparison to the standard Veklury® (Gilead) formulation. The resulting drug, NV-387-g-R has not only significantly improved characteristics for its Remdesivir component, but additionally provides the novel re-infection blocking mechanism of NV-387; together enabling complete block of the viral lifecycle, which would potentially result in a cure. (Chakraborty A, Diwan A, Chiniga V, Arora V, Holkar P, Thakur Y, et al. (2022) Dual effects of NV-CoV-2 biomimetic polymer: An antiviral regimen against COVID-19. PLoS ONE 17(12): e0278963. https://doi.org/10.1371/journal. pone.0278963.)

Previous wording

In fact, we have found in pre-clinical animal studies that both NV-CoV-2 and NV-CoV-2-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 as well as a lethal smallpox-emulating ectromelia footpad infection mouse model, further substantiating the oral bio-availability observed in the coronavirus study results.

Current 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.

Previous wording

These findings have enabled us to develop oral formulations of NV-CoV-2 for human clinical trials. We have successfully developed orally active formulations of our COVID drug candidates, in an oral syrup form, as well as an oral gummies (“Chewable Soft Solids”) form. We believe that for mild to moderate disease, for pediatric, and older patients, the oral syrup and gummies forms would be highly advantageous over tablets, capsules, injections, infusions, or lung inhalations.

Current wording

These findings have enabled us to develop oral formulations of NV-387 for human clinical trials. We have successfully developed orally active formulations of our NV-387 in an oral syrup form, as well as an oral gummies (“Chewable Soft Solids”) form. We believe that for mild to moderate viral infection disease, for pediatric, and for geriatric patients, the oral syrup and gummies forms would be highly advantageous over tablets, capsules, injections, infusions, or lung inhalations.

Previous wording

The injectable formulation of NV-CoV-2 (API 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-CoV-2 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 SARS-CoV-2 viruses cause the most damage. Injectable, Infusion and Inhalation formulation of NV-387 would also be very important for the treatment of RSV infections, especially for severe infections in pediatric 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 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.

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 Platform technology. The technology also enables us to develop nasal sprays and bronchial aerosols. We plan to develop the appropriate formulations as necessary.

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

Previous wording

Importantly, in the reported 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 clinical trials for COVID or Phase II/III clinical trials for RSV. The production program for Phase II clinical supply is expected to be commissioned soon.

Current 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.

Previous wording

Healthy Subjects Part of the Phase 1a/1b Human Clinical Trial of NV-CoV-2 (API NV-387), a Broad-Spectrum Antiviral Drug, is Completed Successfully

Current wording

The Phase 1a/1b Human Clinical Trial of NV-CoV-2 (API NV-387), a Broad-Spectrum Antiviral Drug, in Healthy Subjects, is Completed Successfully with No Adverse Events

Previous wording

On January 29, 2024, we reported that the healthy subjects part of the Phase 1a/1b human clinical trial of NV-CoV-2, under the sponsorship of KMPL, our licensee and collaborator, has completed. All subjects have been successfully discharged. There were no discontinuations. All dosage levels at all dosing instances were well tolerated. There were no adverse events. Thus the drug NV-387 was found to be safe for both single dosing and for repeat dosing even at amounts as high as 40 mg/Kg, including a first “loading” dose at 80mg/Kg. The data are undergoing internal audit. After this, the data will be provided for biostatistical analysis.

Current wording

All subjects were successfully discharged. There were no discontinuations. All dosage levels at all dosing instances were well-tolerated and there were no adverse events. Thus the drug NV-387 was found to be safe for both single dosing and for repeat dosing even at amounts as high as 40 mg/Kg, including a first “loading” dose at 80 mg/Kg.

Previous wording

Additionally, the pharmacokinetics human plasma samples from these SAD and MAD healthy human subjects were shipped from India under appropriate conditions and have been received by the bioanalytical lab in the USA.

Current wording

Additionally, the pharmacokinetics human plasma samples from these SAD and MAD healthy human subjects were shipped from India under appropriate conditions and have been received by the bioanalytical lab in the USA. We are now awaiting the human PK data and report.

Previous wording

Previously 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 leading to the clinical trials. 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 indicate excellent safety.

Current 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).

Previous wording

The strong safety and tolerability of NV-387 demonstrated in human clinical trial implies that it can be used: (i) across all ages from pediatrics to seniors; (ii) irrespective of co-morbidities such as diabetes, other pre-existing diseases, or immune compromised status of the individual; and (iii) at all levels of disease severity, from mild/moderate to severe to very severe (hospitalized patients). This capability of NV-387 is analogous to the highly successful antibiotics against bacteria.

Current wording

The results of the NV-387 Phase 1a/1b clinical trial indicate that NV-387 can be used: (i) across all ages from pediatrics to seniors; (ii) irrespective of co-morbidities such as diabetes, other pre-existing diseases, or immune compromised status of the individual; and (iii) at all levels of disease severity, from mild/moderate to severe to very severe (hospitalized patients).

Previous wording

In contrast, currently available antiviral drugs have substantial limitations on the patient populations that they can be used in. For example, of the two remaining approved drugs for treatment of COVID, Paxlovid which is given orally, is not indicated for the treatment of COVID-19 in patients without a risk factor for progression to severe COVID-19, whereas Remdesivir can only be used in hospitalized cases.

Current wording

In contrast, currently available antiviral drugs have substantial limitations on the patient populations that they can be used in. For example, of the two remaining approved drugs for treatment of COVID, Paxlovid which is given orally, is not indicated for the treatment of COVID in patients without a risk factor for progression to severe COVID-19, whereas Remdesivir can only be used in hospitalized cases. Similarly ribavirin, indicated for RSV infection and other viral infections, is only indicated as a last resort because of severe toxicities. Other antivirals such as Cidofovir, Brincidofovir, etc. also have limitations due to toxicities.

Previous wording

NanoViricides Broad-Spectrum Antiviral Drug NV-387 Was Found To Be Effective Against RSV Lethal Lung Infection

Current wording

NanoViricides Broad-Spectrum Antiviral Drug NV-387 Was Found To Have Strong Antiviral Activity Against RSV Lethal Lung Infection Leading to Full Survival of Lethally Infected Animals, Indicating A High Success Probability for Regulatory Approval After Appropriate Clinical Trials

Previous wording

On July 11, 2023 we reported that NV-387 was found to be effective in an animal model of lethal lung pneumonia caused by RSV infection. Importantly, both oral and intravenous administrations of NV-387 were effective almost matching the effectiveness of the toxic drug Ribavirin. There is currently no safe and effective drug approved for RSV. The market size for RSV therapeutics is estimated by GrowthPlus to grow at a CAGR of 18.9%, reaching $8.73 billion by 2031, representing a significant commercial opportunity.

Current wording

On July 11, 2023 we reported that NV-387 was found to possess strong antiviral activity in an animal model of lethal lung pneumonia caused by RSV infection. Importantly, both oral and intravenous administrations of NV-387 were effective almost matching the effectiveness of the toxic drug Ribavirin. We believe that there is currently no safe and effective drug approved for RSV.

Previous wording

RSV causes severe infections primarily in infants and young children, persons over age of 60 and immune-compromised persons. Each year in the United States, an estimated 58,000–80,000 children younger than 5 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 5 years. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months.

Current wording

RSV causes severe infections primarily in infants and young children, persons over age of 60 and immune-compromised persons. Each year in the United States, an estimated 58,000–80,000 children younger than 5 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 6 months.

Previous wording

Two 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. There are no vaccines currently approved for infants and children.

Current wording

Two 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. There are currently no vaccines approved for infants and children.

Previous wording

However, there are no safe and effective therapeutics for RSV to date. Ribavirin, a highly toxic drug, 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), and recently approved Beyfortus (nirsevimab) are antibodies approved only for prophylactic use in children and infants at high risk of severe RSV infection, but neither is approved for treatment of RSV infection, which remains an unmet medical need.

Current wording

To our knowledge, there are no safe and effective therapeutics for RSV to date. Ribavirin, a highly toxic drug, 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), and recently approved Beyfortus (nirsevimab) are antibodies approved only for prophylactic use in children and infants at high risk of severe RSV infection, but neither is approved for treatment of RSV infection, which remains an unmet medical need.

Previous wording

NV-387 Was Found To Be Effective In A Lethal Infection Animal Model That Is Used In Drug Development for MPox and Smallpox Virus Infections In Humans

Current wording

NV-387 Was Found To Have Strong Antiviral Activity In Lethal Infection Animal Models Used In Drug Development for MPox and Smallpox Virus Infections In Humans

Previous wording

On November 14, 2023, we reported on the on-going smallpox-emulating animal model studies of efficacy of NV-387 treatment. We reported that oral NV-387 treatment was as effective as the approved drug tecovirimat (TPOXX®, SIGA Pharmaceuticals) in a lethal model comprising intra-digital infection by the ectromelia virus into the footpads of mice, resulting in a 14-days survival in both treatments, as opposed to 8 days survival of vehicle-treated or untreated animals, based on the on-going work on this project. Moreover, combined treatment with both NV-387 and tecovirimat resulted in a significantly improved survival of 17 days in this study. Tecovirimat is the drug approved for smallpox under “animal rule” and is stockpiled by the Biomedical Advanced Research and Development Authority (BARDA). It was mobilized from the stockpile during the recent MPox epidemic. BARDA is interested in development of additional poxvirus therapeutics as per a recent Broad-Agency Announcement (BAA). There is significant interest in the development of a smallpox therapeutic that works well by itself, as well as in combination with the known drug, tecovirimat. Tecovirimat has a low barrier of escape, a single mutation in one protein can enable the virus to escape this drug, adding to the significance of additional smallpox drug development.

Current wording

Tecovirimat is the drug approved for smallpox under “animal rule” and is stockpiled by the Biomedical Advanced Research and Development Authority (BARDA). It was mobilized from the stockpile during the recent MPox epidemic. BARDA is interested in development of additional poxvirus therapeutics as per a recent Broad-Agency Announcement (BAA). There is significant interest in the development of a smallpox therapeutic that works well by itself, as well as in combination with the known drug, tecovirimat. Tecovirimat has a low barrier of escape, a single mutation in one protein can enable the virus to escape this drug, adding to the significance of additional smallpox drug development.

Previous wording

We believe that it may be possible for us to obtain non-dilutive grants and contracts based funding for the development of NV-387 as a therapeutic for poxviruses under the FDA “Animal Rule” provision, which requires specific animal model studies as substitutes for Phase 2/3 human clinical efficacy studies, and an extended Phase 1 human safety study.

Current wording

We believe that it may be possible for us to obtain non-dilutive grants and contracts based funding for the development of NV-387 as a therapeutic for poxviruses under the FDA “Animal Rule” provision, which requires specific animal model studies as substitutes for Phase II/III human clinical efficacy studies, and an extended Phase I human safety study.

Previous wording

SIGA announced in July 2023 that it has received new procurement orders of approximately $138 million for TPOXX from the U.S. Government. Previous acquisitions of TPOXX have totaled close to a billion dollars, indicating the significant commercial value for a Smallpox/Mpox drug.

Current wording

In July, 2023, SIGA announced that it has received new procurement orders of approximately $138 million for TPOXX from the U.S. government. Previous acquisitions of TPOXX have totaled close to a billion dollars, indicating the significant commercial value for a Smallpox/Mpox drug.

Previous wording

Thus, NV-CoV-2 (NV-387) addresses an unmet medical need for broad-spectrum, safe and effective antiviral drug against multiple threats. In addition to the above reported work, we have been working on a number of background tasks that feed into the regulatory pathway. Further, we have re-initiated the FluCide™ program this quarter with a limited engagement, while focusing our primary work on advancing the regulatory development of NV-387, and expansion of indications of NV-387.

Current wording

Thus, NV-387 addresses an unmet medical need for broad-spectrum antiviral drug against multiple threats. In addition to the above reported work, we have been working on a number of background tasks that feed into the regulatory pathway.

Previous wording

Previously, we have developed a clinical drug candidate NV-HHV-1 and formulated it as a skin cream for the treatment of Shingles. We plan on undertaking clinical trials of NV-HHV-1 after NV-CoV-2 clinical trials. We have performed cGMP-like manufacture of both the active pharmaceutical ingredient (API NV-HHV-1, the nanoviricide against VZV), and the fully formulated skin cream (the

Current wording

Previously, we have developed a clinical drug candidate NV-HHV-1 and formulated it as a skin cream for the treatment of Shingles. We plan on undertaking clinical trials of NV-HHV-1 after NV-387 RSV Phase II clinical trials. We have performed cGMP-like manufacture of both the active pharmaceutical ingredient (the API in NV-HHV-1 i.e. NV-360), and the fully formulated skin cream (the drug product candidate), at our own facilities at ~1Kg scale (API basis) with attendant significant time, project management, and cost savings as opposed to going to an external contract manufacturer. Approximately 10Kg of fully formulated drug product was manufactured. We believe this scale is sufficient for the requirements of Phase I and Phase II human clinical trials of NV-HHV-1.

Previous wording

Both the safety and effectiveness of any new drug has to be determined experimentally. The safety of a nanoviricide drug is expected to depend upon the safety of the nanomicelle portion as well as the safety of the antiviral ligand. We have observed excellent safety of our injectable SARS-CoV-2 drug candidates, as well as of the Shingles skin cream drug candidate. This leads us to believe that the nanomicelle backbones of these drug candidates that were evaluated in preliminary safety studies should be safe in most if not all routes of administration.

Current wording

Both the safety and effectiveness of any new drug has to be determined experimentally. The safety of a nanoviricide drug is expected to depend upon the safety of the nanomicelle portion as well as the safety of the antiviral ligand. We have observed excellent indications in the evaluation of safety of our broad-spectrum antiviral drug candidate NV-387 as well as that of NV-360, our herpesvirus family specific antiviral drug candidate to date in non-clinical studies including IND-enabling safety pharmacology studies. Further, NV-387 has successfully completed Phase 1 human clinical trial with no adverse events, indicating an excellent level of safety. The final determination of safety and efficacy of a drug rests with the regional drug regulatory authority such as the US FDA, EU EMEA, India CDSCO/DCGI, UK MHRA and others.