NNVC: NanoViricides Begins Clinical Trial of NV-CoV-2
AMEX:NNVC
In June 2023, NanoViricides, Inc. (AMEX:NNVC) announced the initiation of a Phase 1a/b safety and efficacy clinical trial of NV-CoV-2, the company’s development candidate for the treatment of COVID-19 and other coronavirus infections. The trial is evaluating two oral formulations of the compound: NV-CoV-2 oral syrup and Nv-CoV-2 oral gummies. This is an important inflection point for NanoViricides of initiating clinical-stage operations following a long development timeline of their unique nanoviricides platform technology as a pre-clinical company.
The Phase 1a portion of the trial is assessing the safety and tolerability of the two formulations: a single dose of 500 mg, 1000 mg, or 2000 mg of the oral gummy or a single dose of 10 mg/kg, 20 mg/kg, or 40 mg/kg of the oral syrup. The Phase 1b portion in healthy volunteers will assess multiple doses of each formulation. Additionally, in another part of the Phase 1b treatment, COVID patients with mild to moderate COVID-19 will be dosed once every alternate day for five dosing days. The primary endpoint is the safety and tolerability of NV-CoV-2 while a key secondary endpoint is to evaluate the PK/PD of the two NV-CoV-2 formulations. A secondary endpoint from the COVID patients is to determine the optimal dosing regimen for the next Phase 2 efficacy clinical trial.
On August 21, 2023, the company announced that 26 of the target 36 healthy volunteers have completed the Phase 1a single ascending dose (SAD) portion of the study. In addition, 17 of the target 36 healthy volunteers have completed the Phase 1a multiple ascending dose (MAD) part of the clinical trial. Thus far, there have been no adverse events or serious adverse events in the SAD or MAD studies in either the NV-CoV-2 oral syrup or the NV-CoV-2 oral gummies.
NanoViricides CRO partner, PristynCR, India, has requested approval from the Ethics Committee to begin recruitment into the Phase 1b COVID patient treatment part of the clinical trial. Based on the encouraging safety data seen thus far in healthy volunteers, we are confident that approval to begin treating COVID patients will be granted soon.
The SARS-CoV-2 virus continues to mutate and generate new variants faster than vaccines can be produced, thus necessitating the development of safe and effective antiviral therapies. Even as booster doses of vaccines developed against Omicron XBB variants are about to enter the market, the newer EG.5 variant is now dominant in the U.S. Further, another variant-under-monitoring, BA.2.86, has been found across the globe. BA.2.86 carries more than 30 mutations over its predecessor, and with this much change the new booster shots are generally not expected to be effective against this variant. On the other hand, the currently approved COVID-19 antiviral therapies have multiple drawbacks, including their effectiveness, safety profiles, and what patient populations are eligible for treatment.
The excellent safety profile and novel mechanism of action of NV-CoV-2 supports testing it in all patient populations.
Background on NV-CoV-2
NV-CoV-2 is based on the company’s core nanoviricide® technology, which utilizes molecular mimicry to bind virus particles and prevent their entry into the cell. The following figure gives an overview of how the nanoviricide technology works. Initially, the nanoviricide binds to the virus particle through a ligand (small molecule, peptide, or antibody fragment) that mimics the receptor utilized by the virus to gain cellular entry. Following binding of the virus, the nanoviricide fuses with the lipid-coated surface of the virus through phase-inversion and “lipid-lipid mixing”. This results in encapsulation of the virus particle and its destruction. Since the binding site on the human cellular receptor for a particular virus does not change, despite mutations occurring to the receptor binding domain and other areas of the virus, it is thought that nanoviricides will not be susceptible to viral mutations that can render other treatments ineffective.
Previously published preclinical work evaluated the pharmacokinetic (PK) properties and efficacy of NV-CoV-2 (Chakraborty et al., 2022). To measure the PK properties of NV-CoV-2, a direct ELISA assay was developed to quantitatively detect NV-CoV-2 in biological matrices. A non-GLP study was conducted to determine the systemic exposure of NV-CoV-2 when administered to rats once a day for five days (Days 0, 1, 3, 5, and 7) over an 8-day period. This is summarized in the following table.
Each compound was delivered through a slow-push IV injection. Blood samples to measure systemic exposure were collected at 0, 0.08, 0.5, 1, 2, 4, 8, and 24 hours after the 1st and 5th injections. The results are shown in the following table. NV-CoV-2 was detected in rat plasma with an initial increase that peaked between 4-8 hours post-dose and decreased below the limit of detection (0.25 µg/mL) between 24- and 48-hours post-dose.
Additional data showing the effectiveness of each of those compounds was discussed in our previous article and is summarized in the following table. Rats treated with NV-CoV-2 or NV-CoV-2-R following a lethal dose of hCoV-NL63 had a dramatic improvement in survival, near normal lung histopathology, and reduced organ toxicity.
Licensing Agreement with Karveer Meditech Pvt. Ltd.
In April 2023, NanoViricides announced a licensing agreement with Karveer Meditech Pvt. Ltd., Kolhapur, India, that grants Karveer the right to commercialize NV-CoV-2 and NV-CoV-2-R in India. Karveer is conducting the clinical trials of NV-CoV-2 in India. Importantly, NanoViricides will have full rights to the data generated in the clinical trials and may use the data in other jurisdictions as needed.
NV-387 Effective in RSV Animal Model
NanoViricides recently reported that NV-387, the active ingredient of NV-CoV-2, showed strong efficacy in an animal model of lethal lung infection with Respiratory Syncytial Virus (RSV). RSV is a common contagious respiratory virus that typically causes mild cold-like symptoms (runny nose and cough) in the majority of people that contract it. However, in rare instances RSV can cause severe disease or death in vulnerable individuals, including premature or very young infants, children with chronic lung disease, or people over the age of 65.
NanoViricides tested the efficacy of NV-387 in a lethal RSV lung infection model in NSG mice. Mice treated with vehicle survived seven days, those treated with ribavirin survived 16 days, and those treated with NV-387 survived 15 days. These results were seen when NV-387 was dosed by injection or orally.
Two vaccines (Arexvy, Abrysvo) as well as a monoclonal antibody (Beyfortus) have recently been approved for RSV prevention. Arexvy and Abrysvo are approved for use in adults 60 years of age and older to prevent or reduce the severity of RSV infection. Abrysvo was also recently approved for expectant mothers at 32 to 36 weeks gestational age for the prevention of RSV in their infants. Beyfortus competes with and is expected to be superior to another monoclonal antibody, Synagis, that is approved to prevent severe RSV infection in high-risk children and infants (those born prematurely and are less than 6 months of age or who have a chronic lung condition or a certain type of heart disease and are less than 24 months of age). Ribavirin, an antiviral nucleoside analog, is conditionally approved to treat individuals infected with RSV at high risk of progressing to severe disease. However, it causes a number of side effects including nausea, vomiting, anemia, mood changes, and can lead to severe organ toxicities (liver, kidney, spleen, others).
There is a clear unmet medical need for the treatment of RSV infections and NV-387 could become a highly acceptable and viable option.
Conclusion
NanoViricides is now a clinical stage company following the initiation of the Phase 1a/b safety and efficacy trial of NV-CoV-2. The early safety data from the trial is very encouraging as there have been no reports of adverse events or serious adverse events in the first cohorts of healthy volunteers administered either formulation of the drug. We look forward to full results from this trial and next steps for the COVID-19 program. The results reported by the company for the RSV infection model are encouraging and show that NV-387 may be effective against a wide range of pathogenic viruses We look forward to updates on this program and future directions for NV-387’s development.
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