Nanoviricides Can Encapsulate Small Chemicals as Guests, Enabling Improved Pharmacokinetics and thus Activity of the Guest
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).
We have also developed our own, patent-pending replication inhibitor antiviral agents that can be encapsulated in NV-387 for improved antiviral activity in animal models, with the objective of curing long-term (long COVID) and lifelong (HSV-1, HSV-2, VZV, others) viral infections.
Clinical Development Program: NV-387 Phase I Clinical Trial
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.
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).
Further, NV-387 was found to be non-mutagenic, non-immunogenic, non-allergenic, and non-genotoxic in IND-enabling 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, when approved. This is in contrast to available antiviral therapeutics that, limited by their toxicity and metabolic effects, cannot be given to many pools of patients.
Further Clinical Development of NV-387 Towards Drug Approvals: Multiple Indications for NV-387 Against Different Viral Infections Enable Maximizing Return on Investments While Fulfilling Unmet Medical Needs
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.
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.
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).
In light of the WHO public health emergency declaration regarding the MPox epidemic in Central Africa, we have begun efforts to progress NV-387 for Phase II evaluation of efficacy in the treatment of MPox virus infection. This is an unmet medical need since there is no drug available for the treatment of MPox infection given the failure of tecovirimat in clinical trial.
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.
Multiple indications of NV-387 enable us to maximize return on investments. The Phase I safety and tolerability clinical trial would be generally applicable across all indications. All of IND-enabling non-clinical studies would also be reused, with the addition of animal model antiviral activity studies for the specific indication. The Chemistry, Manufacture, and Controls for the drug substance would remain substantially the same and potentially the drug product sections also could be reused.