NNVC: NanoViricides Technology Ready to Enter the Clinic
NYSE:NNVC
NanoViricides (NYSE:NNVC) is a biopharmaceutical company that is developing a novel approach to treating viral infections. The technology has been in development for over 15 years and theoretically can be applied to treat any viral infection. While multiple pre-clinical proof-of-concept development candidates have been produced over the years, the company is currently focused on a therapy for SARS-CoV-2 infection and recently announced a licensing agreement with a company in India to begin clinical evaluation. This is an important inflection point for NanoViricides as it is now transitioning to clinical-stage operations following a long development timeline as a pre-clinical company.
The company’s core nanoviricide® technology utilizes molecular mimicry to bind virus particles and prevent their entry into the cell. A nanoviricide consists of a ligand (small molecule, peptide, or antibody fragment) that mimics the receptor utilized by a virus to gain cellular entry. This ligand is covalently attached to a flexible polymer backbone comprised of polyethylene glycol (PEG) and alkyl chains. The PEG forms a hydrophilic shell while also conferring non-immunogenicity. The alkyl chains make up the flexible core. Multiple chemically reactive sites allow for “packaging” of one or more active pharmaceutical ingredients within the core of the nanoviricide. This structure then forms a flexible nanomicelle via self-assembly. Upon encounter with a target virus, binding occurs between the ligand displayed on the nanoviricide micelle and the viral receptor protein. The micelle then fuses with the lipid-coated surface of the virus through phase-inversion and “lipid-lipid mixing”, a well-studied physicochemical effect. This is shown in the following figure. 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.
As opposed to most other antiviral agents under development that only target the intracellular life cycle of viruses, nanoviricides attack the virus outside the cell and can be loaded with antiviral agents to work synergistically inside the cell as well. The company recently published results showing that encapsulation of remdesivir inside a nanoviricide resulted in increased plasma half-life and greater efficacy compared to a nanoviricide without remdesivir (discussed further below).
The nanoviricide platform technology could prove to be effective against a wide variety of viral pathogens, and the company has already developed nanoviricides against SARS-CoV-2, herpes viruses (varicella-zoster virus, herpes simplex virus-1, herpes keratitis), influenza, human immunodeficiency virus, and mpox (including other poxviruses). The company is currently focused on treating SARS-CoV-2, both because the virus continues to kill people all over the world and also because it can serve as an excellent proof-of-concept for the nanoviricide platform. SARS-CoV-2 has now entered a world-wide endemic phase and this and other coronavirus infections are expected to keep continuing every year, similar to influenza.
Another advantage of the nanoviricide platform is that the drugs can be administered through a variety of different routes, including intravenously, orally, or through inhalation. For the SARS-CoV-2 program, the company is currently focused on two oral formulations: oral gummies and an oral syrup. Each of those could be utilized to treat mild-to-moderate COVID-19 infections in patients that are not hospitalized. The company has also developed injectable and inhalation formulations for use in hospitalized patients that are expected to follow into clinical development later.
Proof-of-Concept for SARS-CoV-2 Nanoviricide
Recently, NanoViricides published preclinical results for the company’s nanoviricide targeting SARS-CoV-2 (NV-CoV-2) in PLoS One (Chakraborty et al., 2022). For these experiments, the human coronavirus h-CoV-NL63 (which can cause a severe form of common cold that can result in lung disease similar to SARS-CoV-2) was used since it utilizes the same ACE2 cellular receptor as SARS-CoV-2 and it can be studied in a BSL2 laboratory (as opposed to SARS-CoV-2, which must be studied in a BSL3 laboratory). Following infection with 104 CoV-NL63 viral particles directly into the lungs, untreated rats died in approximately five days. NV-CoV-2 was administered through a tail vein IV once a day on days 0, 1, 3, 5, and 7. The following figure shows that animals treated with NV-CoV-2 survived for 13-14 days compared to only 7.5 days for those treated with just remdesivir and 5 days for the control groups. The figure on the bottom shows that a higher number of treatments was associated with longer survival.
In a second experiment, remdesivir was encapsulated inside the nanoviricide (NV-CoV-2-R). Rats treated with vehicle in this experiment survived 7.7 days compared to rats treated with a single dose of NV-CoV-2-R that survived 8.8 days. When rats were treated with NV-CoV-2-R for three and five days they survived for 13.9 and 18 days, respectively.
In regards to safety, IV administration of NV-CoV-2 in rats at doses of 25, 50, and 100 mg/kg did not affect respiratory function, alter neurobehavior, or cause changes in body temperature in a GLP study, thus indicating that the treatment was well tolerated. In addition, IV administration of NV-CoV-2 at doses of 25, 37.5, and 50 mg/kg in cynomolgus monkeys in a GLP study did not have any relevant effect on heart rate, arterial blood pressure, cardiac rhythm, or ECG parameters.
Licensing Agreement with Karveer Meditech Pvt. Ltd.
On April 4, 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 has begun clinical development and evaluation of those two drugs and has obtained regulatory permissions to conduct clinical evaluation of them in India. We anticipate the clinical trials getting underway in India in the near future. Importantly, NanoViricides will have full rights to the data generated in the clinical trials and may use the data in other jurisdictions as needed. We anticipate the trial enrolling patients with mild to moderate SARS-CoV-2 infection. The study will evaluate both the safety and efficacy of both of the oral formulations of NV-CoV-2.
The Future
The technology described above can be utilized to combat a wide array of viral pathogens, with SARS-CoV-2 chosen as the lead program based on the ongoing pandemic and as-yet-unmet medical need for effective therapies. However, given the similarities in the way SARS-CoV-2 and other coronaviruses infect cells, it is conceivable that NV-CoV-2 may be applicable not just to the current and future variants of SARS-CoV-2, but other coronaviruses as well. The company’s preclinical data supports that NV-CoV-2 was effective against other coronaviruses. In addition, as described above NanoViricides has a pipeline of anti-viral drug candidates that could be brought into the clinic once the proper funding has been secured.
One of the differentiating factors for NanoViricides is the fact it is one of the few biopharmaceutical companies its size to have its own cGMP-compliant manufacturing facility. The company can produce enough material in that facility to conduct its clinical trials and a single batch production run can produce enough material to treat approximately 1,000 patients. The current production capacity is sufficient for the first-in-human SARS-CoV-2 trial along with the potential clinical trials of NV-HHV-1 skin cream for the treatment of shingles. Owning the manufacturing facility enables the company to be vertically integrated and not rely on outside firms for crucial parts of the business. It is a significant competitive advantage to have the research, design, and production capabilities all in-house.
In the current environment having enough funding is critical as many smaller biopharmaceutical companies are having a difficult time raising additional funds. NanoViricides has enough cash to fund operations for at least the next 12 months. By that time the company should have the first clinical results which, if positive, should make future fund-raising efforts easier.
Conclusion
It’s been a long road for NanoViricides as the company has been developing various preclinical assets for more than a decade. However, the company is now ready to move its first development candidate into clinical testing and we look forward to the results of those studies later this year. Positive results would be important not just for a potential treatment for SARS-CoV-2, but also as a proof-of-concept for the nanoviricide platform technology and could lead to follow-on clinical trials to treat other viruses shortly thereafter.
SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR.
DISCLOSURE: Zacks SCR has received compensation from the issuer directly, from an investment manager, or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks SCR provides and Zacks SCR receives quarterly payments totaling a maximum fee of up to $40,000 annually for these services provided to or regarding the issuer. Full Disclaimer HERE.
