NanoViricides, Inc. (NYSE American: NNVC)’s lead drug candidate NV-387 (drug product NV-CoV-2),  a drug that  treats RSV, COVID-19, Long COVID, Influenza, Bird Flu H5N1, and other respiratory viral infections as well as Monkey-pox, has successfully completed Phase 1 clinical trials in healthy subjects with no reported adverse events, even at the highest and repeated dosages. Remarkably, NNVC has been able to develop NV-387 for oral administration already, as well as for injectable and inhalation formulations to enable many modes of use. The Company is currently focused on advancing NV-387 into Phase II human clinical trials for the treatment of RSV infection.

Susceptible viruses CANNOT escape NV-387, even as they continue to evolve in the field into variants. Why? Because  no matter how much the virus changes, it continues to use the same host-side signature to bind to and cause infection in the hosts, and thus the nanoviricide would be anticipated to continue to be effective even as the virus mutates to generate variants.

Thus NV-387 and other antiviral drugs designed on the nanoviricides platform can be expected to have decades of  effective usability against the target viruses similar to the life of current antibiotics against bacterial infections but in stark contrast to  current antiviral approaches.

A broad-spectrum antiviral drug such as NV-387 would be a highly desirable drug globally because it  would enable treatment by physicians of patients as soon as they present symptoms of a viral disease without waiting for a test to identify a specific type of viral infection. This is reminiscent of how antibiotics are prescribed, without specific infectious agent identification, relying on the ultra-broad-spectrum of the drug.

Over 90% of human pathogenic viruses are known to use one or more "landing sites" that are in the Sulfated Proteoglycans ("SPG") family. A successful host-mimetic nanoviricide drug using SPG as the key feature to attract viruses could theoretically be able to attack most if not all such viruses.

NV-387 is designed to mimic SPG and attack the virus as a cell-mimicking decoy. We have accumulated substantial evidence that in lethal viral infection animal studies, NV-387 demonstrated strong antiviral activity against a range of different virus families, exceeding or matching the activity of known approved drug agents.

The Company’s virus-specific nanoviricides have been created against important viruses such as HIV, Influenza and Bird Flu by choosing highly virus-specific ligands. 

Broad-spectrum nanoviricides have been created that can bind to possibly as many as 90-95% of known viruses. The Company is also developing broad-spectrum nanoviricides to combat several neglected tropical diseases, such as Dengue, Rabies, and Ebola/Marburg.

The nanoviricide technology involves copying the invariant and essential host-side signature and, using this signature, building a direct-acting antiviral that destroys the virus. This design feature of nanoviricides solves the most intractable issue in antiviral response, that of viruses escaping the vaccines, antibodies, and small chemical drugs.

NV-387 is designed using the host-side signature that over 90% of human pathogenic viruses use for creating a successful infection in the human or animal hosts. This means NV-387 is likely to be active against a large number of viruses and could be sufficiently active against many of them to become a successful clinical drug against them.

In fact, the company has already demonstrated that NV-387 is highly effective in preclinical studies against lethal RSV infection as well as against lethal Smallpox-like virus infections!

Ribavirin is the only currently approved drug for RSV infection, that can be used only as a last resort because of its extensive toxicity that limits its effectiveness.

Lethally RSV Infected Animals Orally Treated with NV-387 Showed Normal Lung Histology, Indicating Potential Cure!

NNVC has reported that the antiviral activity of NV-387 against RSV/A2 is strong enough to have resulted in the full survival of lethally infected animals!

In this study, extended dosing of NV-387 given orally was compared with a high dose of ribavirin given orally for the same duration. Two doses were given on the first day of dosing followed by one daily dose for the next 9 days (for a total of 11 doses). NV-387 given by this dosing regimen led to complete survival of the mice beyond the 21 days study period, with no signs of pathology (disease) apparent on the last day of observation. In contrast, ribavirin led to death of all animals by 14 days!

NanoViricides, Inc. (NYSE American: NNVC)  recently revealed that the strong antiviral activity of NV-387 against RSV/A2 is clearly demonstrated by lungs remaining normal and showing no infection-related damage, when treated orally with NV-387, in a lethal lung RSV infection animal model. The animals in only the NV-387 treated group survived completely, as previously reported. 

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.

The complete survival and clear lungs indicate that NV-387 treatment completely protected the animals and could be potentially a cure for RSV infection!

There is no drug for general treatment of RSV infection at present, enabling NV-387 to be a candidate for this $1.8 Billion to $8 Billion annual market size as estimated by GrowthPlus Reports.

NNVC reported that in a lethal animal model of lung infection by Influenza A /H3N2 virus, NV-387 was found to have substantially superior antiviral effects compared to three approved anti-influenza drugs.

The company performed a lethal lung infection study of mice infected with Influenza A/H3N2 that were treated with NV-387 or one of the three approved drugs for direct comparison: Oseltamivir (Tamiflu®, Roche), Peramivir (Rapivab®, Biocryst), and Baloxivir (Xofluza®, Shionogi, Roche). 

In this study, NV-387 Oral treatment led to a survival lifespan of 15 days, compared to 10 days with Oseltamivir Oral treatment, 11 days with Peramivir I.V. treatment, and 11 days with Baloxivir Oral treatment, while the vehicle-treated and untreated (infected) animals survived only 8 days!

Thus the anti-Influenza activity of NV-387 given orally was substantially superior to all three of the approved anti-influenza drugs, namely Tamiflu, Rapivab, and Xofluza.

Given the broad spectrum of antiviral activity of NV-387 against viruses in many different virus families, NNVC believes that its effectiveness against Influenza A/H3N2 is indicative of potential antiviral activity against most if not all Influenza A viruses.

• NV-387 was found to be as effective as ribavirin, the toxic last resort drug, against RSV infection in a lethal lung infection animal model, as reported previously. RSV is a virus particularly threatening to vulnerable infants, young children, older adults, and immunocompromised populations.
  • There is no approved drug for the treatment of RSV infection, except the toxic drug ribavirin which is only indicated for very severe cases due to its severe hemotoxicity. Ribavirin, a highly toxic drug that attacks red blood cells and can cause multi-organ failures, is reserved for use as a last resort only in extremely severe hospitalized cases of RSV. NV-387 was almost as active as ribavirin.
  • RSV is an important pathogenic virus that can cause lethal infection in infants as well as seniors and immunocompromised persons. 
  • Two different vaccines against RSV have been recently approved by the US FDA, but none are for pediatric use at present. Two different antibodies have been approved as prophylactic (i.e. to prevent RSV infection) for babies, but are not approved as therapeutics (i.e. after disease occurs). 
  • There is no safe and effective therapeutic available for RSV. Additionally, NV-387 has been found to be extremely safe in pre-clinical studies. Thus, we believe NV-387 could be a clinical quality drug candidate for the treatment of RSV infections.
• NV-387 was at least as effective as the approved drug tecovitrimat (TPOXX®, SIGA), in a lethal intra-digital infection by ectromelia virus in mice. Importantly, a combined drug made from NV-387 and tecovirimat was more effective than either drug alone, indicating NV-387 "plays well" with tecovirimat and acts by a different mechanism.
  

As biotech stages a big comeback, NanoViricides, Inc. (NYSE American: NNVC) looks well-positioned to be a market disruptor with nontoxic, effective antiviral therapies based on patented nanomedicine technology.

NanoViricides, Inc. (NYSE American: NNVC) is a global leader in the application of nanomedicine technologies to the safe and effective treatment of viruses and their variants INCLUDING drugs against Covid-19, RSV and other respiratory viruses!

Even with a decline since 2022, COVID-19 continues to hospitalize and kill people in the USA – the CDC website states 69,200 hospitalizations and 2,652 deaths since January 1, 2024; the worldwide market size for COVID-19 therapeutics is expected to exceed $16.2 Billion in 2031*.

*Source: Transparency Market Research

The market size for RSV therapeutics was estimated to be $2 Billion in 2023 and is expected to rise to exceed $8.5 Billion by the year 2031**. 

**Source: Growth+ Market Reports.

Analysts have said that the 2023 year-end spurt of biopharma mergers and acquisitions bodes well for the sector this year. The SPDR S&P Biotech ETF, which tracks the sector, had a strong November and December.

The recent AbbVie-ImmunoGen deal “may be the start of more consistent activity we will see in 2024,” RBC Capital Markets analyst Brian Abrahams wrote in a note published late recently. “We do believe we are likely past the XBI bottom and can look to somewhat improved enthusiasm for the group—in part driven by M&A—into 2024.”

AbbVie spent about $18.8 billion on two large deals in a matter of seven days. 

According to an RBC Capital, the cumulative value of biopharma deals in 2023 has been $128 billion, up from $61 billion in 2022. Major acquisitions announced  include Pfizer’s $43 billion deal for the cancer-focused biotech Seagen, and Merck’s $10.8 billion deal for the immunology-focused biotech Prometheus Biosciences.

NV 387 IN CLINICAL TRIALS

The drug, developed in response to the COVID-19 pandemic, demonstrated exceptional safety in clinical trials, even at the highest dose levels, with NO adverse events reported. The unique mechanism of action involves mimicking a cell membrane, encapsulating and blocking the virus.

Beyond COVID-19, the drug also displayed promising results against respiratory syncytial virus (RSV), offering a potential solution for infants and seniors where existing treatments like ribavirin may be contraindicated due to side effects.

The clinical trials involved both oral tablets and oral gummies, catering to various age groups, including pediatrics. NV 387 exhibited broad-spectrum activity against multiple strains of coronaviruses, showcasing effectiveness 10 times greater than remdesivir in preclinical studies.

The ongoing clinical trial progress and positive results position NanoViricides at the forefront of antiviral drug development, marking a significant milestone in their journey from preclinical research since 2005 to clinical trials.

The company believes that NV-387 not only binds to the virus, but fuses with the virus surface, uprooting the glycoproteins that are required for the virus to bind to the human cell (for example, the S protein, and its products S1 and S2 proteins from coronaviruses), thereby rendering the virus incapable of infecting a cell. In contrast, antibodies are only capable of covering the virus, generally incompletely, and require immune system assistance for clearing the resulting complex!