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NanoViricides announced that it has nominated a clinical drug candidate for the treatment of COVID-19, thus further advancing its COVID-19 program closer to human clinical trials. The company has accelerated its drug development program for COVID-19 with the goal of creating the most effective medicine to obtain regulatory approval for emergency use in the COVID-19 pandemic in the shortest timeline feasible, after achieving proof of concept of broad-spectrum anti-coronavirus effectiveness of test candidates. A curative treatment for a virus such as SARS-CoV-2 coronavirus would require a multi-faceted attack that shuts down the ability of the virus to infect host cells and simultaneously and the ability of the virus to multiply inside the host cells. The nanoviricide platform enables direct multi-point attack on the virus that is designed to disable the virus and its ability to infect new cells. At the same time, a nanoviricide is also capable of carrying payload in its "belly" that can be chosen to affect the ability of the virus to replicate. The nanoviricide is designed to protect the payload from metabolism in circulation. Thus, the nanoviricide platform provides an important opportunity to develop a curative treatment against SARS-CoV-2, the cause of COVID-19 spectrum of pathologies. The clinical candidate the company has chosen is identified as NV-CoV-1-R. It is made up of a nanoviricide that we have found to possess broad-spectrum anti-coronavirus activity, now identified as NV-CoV-1, and remdesivir encapsulated inside the core of NV-CoV-1. NV-CoV-1 itself is designed to attack the virus particles themselves, and possibly would also attack infected cells that display the virus antigen S-protein, while sparing normal cells that do not display the S-protein. Additionally, remdesivir is understood to attack the replication cycle of the virus inside cells. Thus the combined attack enabled by NV-CoV-1-R on the virus could prove to be a cure for the infection and the disease, provided that the necessary dosage level can be attained without undue adverse effects. Human clinical trials will be required to determine the safety and effectiveness of NV-CoV-1-R. Remdesivir is a well-known antiviral drug that has been approved for emergency use treatment of SARS-CoV-2 infection or COVID-19 in several countries. NV-CoV-1 is a novel agent that is being used as an adjuvant to remdesivir in creating NV-CoV-1-R, to improve the overall effectiveness. It is well known that remdesivir suffers from rapid metabolism in circulation that breaks down the prodrug to its nucleoside form which is not readily phosphorylated. The company anticipates that encapsulation in NV-CoV-1 may protect remdesivir from this rapid metabolism. If this happens, the effective level and stability of remdesivir in the body would increase. This increase may lead to increased effectiveness if there are no adverse effects. Such increased effectiveness, if found, may also allow reduction in the required dosage of remdesivir in the encapsulated form, i.e. as NV-CoV-1-R. In this sense, NV-CoV-1 can be viewed to act as an adjuvant that enhances the effect of remdesivir, a known antiviral against SARS-CoV-2.

NanoViricides reported on the presentation by Anil Diwan, its president and executive chairman, at the LD 500 investor conference. Diwan presented the company's progress in developing a drug to attack the SARS-CoV-2 virus that causes COVID-19 spectrum of diseases. The company said, "He summarized the Company's progress since embarking into this endeavor with very limited resources since about January, 2020, and boot-strapping on its past work against coronaviruses. Dr. Diwan stated that the Company is close to declaring a clinical candidate for treating patients infected with SARS-CoV-2. The Company has previously reported that its development candidates have shown to be effective against multiple coronaviruses in the Company's own BSL2 Virology Lab, and have also shown to be highly effective in an animal study to combat infection by a related coronavirus that uses the same ACE2 receptor as does SARS-CoV-2. Dr. Diwan stated that this broad-spectrum effectiveness against coronaviruses provides scientific reasoning that even as a field coronavirus strain mutates, our drug candidates would continue to remain effective, unlike antibodies and vaccines. In addition, our current development candidates against COVID-19 have also been shown to be extremely safe in animal studies. Their effectiveness in cell culture and animal models has led us to believe that they are worthy of human clinical development. Subsequently, the Company has completed CMC ("Chemistry, Manufacture, and Controls") studies that would be required for an IND ("Investigational New Drug) application to the U.S. FDA. The Company is also in the process of drafting sections of an IND for COVID-19 drug candidate. The Company is currently conducting studies to finalize its clinical candidate.Dr. Diwan further stated the Company's intent of developing an integrated approach to combat SARS-CoV-2 that could potentially result in a cure for the virus. The virus lifecycle is a convolution of two parts: (a) re-infection of a host cell by external virus (after primary infection from outside the host body), and (b) replication (i.e. production of new virus particles) in infected cells and egress of the newly produced virus particles to feed back into the (a) re-infection cycle, completing the loop. Dr. Diwan explained that if both parts of the virus lifecycle are blocked, then a virus infection would be cured, except in the case of latent viruses. A nanoviricide(R) is uniquely capable of accomplishing this task of integrated attack against both the re-infection and replication mechanisms, as the Company has previously stated. The nanoviricide is already designed to block the re-infection cycle part. In addition, it can carry in its "belly", a payload that can block the replication cycle part.NanoViricides has accelerated its anti-coronavirus program to develop a "second generation" nanoviricide against coronaviruses that is designed to block both re-infection and replication cycles, in addition to the current development of the "first generation" anti-coronavirus drug intended to block the re-infection cycle part. The Company accelerated these efforts due to both the severity of the pandemic, and the difficulty of curing the SARS-CoV-2 infection as exemplified by several recent unsuccessful or partially successful clinical studies. In particular, the Company has successfully encapsulated remdesivir inside its current development drug candidates. The resulting drug, which is expected to be superior to remdesivir alone, as well as many other drugs, is already in pre-clinical testing, Dr. Diwan disclosed... Soon after it files an IND for a COVID-19 drug candidate, the Company intends to re-engage its NV-HHV-101 shingles drug candidate clinical trials program towards IND filing. The Company has put the shingles program on hold due to perceived difficulties in conducting proposed shingles clinical trials during the COVID-19 pandemic. The Company is near finalizing the selection of clinical trial sites and finalizing clinical trial protocols for the shingles IND filing. The NV-HHV-101 drug candidate is expected to open up a billion dollar market for the shingles treatment space, and also lead to further development of drugs against other herpesviruses such as HSV-1 that causes "cold sores" and HSV-2 that causes genital herpes. The multiple indications enabled by the HerpeCide(TM) program drug candidates may potentially address a several billion dollar marketspace."

NanoViricides announced that safety and tolerability of the drug candidates it is developing against SARS-CoV-2 to treat COVID-19 spectrum of diseases was observed in an animal model. The company said the nanoviricides drug candidates tested in this safety/tolerability study have previously shown strong effectiveness against lung infection by a SARS-CoV-2 like coronavirus, namely, hCoV-NL63, in an animal study as previously reported by the company. Three different drug candidates at three different dosage levels and vehicle control were administered to separate groups of mice intravenously in the Safety-Tolerability study. Clinical observations and gross post-mortem studies have been completed. The tested drug candidates were safe and well tolerated, thereby clearing the path for further development towards a treatment for SARS-CoV-2 infection that has caused the current COVID-19 pandemic. Nanoviricides are designed to act by a novel mechanism of action, trapping the virus particle. Antibodies, in contrast, only label the virus for other components of the immune system to take care of. It is well known that the immune system is not functioning properly at least in severe COVID-19 patients. Additionally, it is well known that viruses escape antibody-drugs via mutations. The company's "nanoviricide" drug candidates, in contrast, are designed to be broad-spectrum, and therefore virus escape by mutations is expected to be unlikely. In this Safety/Tolerability Study, there were no clinical signs of immune or allergic reactions such as itching, biting, twitching, rough coat, etc. Further, there were no observable changes in any organs including large intestine or colon on post mortem in gross histology. The only reportable changes observed were, in the high dosage groups of two of the three drug candidates tested, associated with the non-absorption of water, in the colon. This is consistent with the clinical observation of very loosened stools in the same groups. In clinical usage, the drug candidates are not anticipated to be administered in such high levels. The objective of this study was to discover the dosage level at which such an effect may occur. Sixteen mice in each group were administered one of the three drug candidates at one of the three dose levels, and additionally, one group was administered vehicle control, for seven days by daily tail-vein intravenous infusion in this blinded study with additional evaluations on eighth day. This non-GLP safety/tolerability study was conducted under GLP-like conditions. The company believes that loose or very loose stools at very high dosages in such a study is an expected and acceptable side effect of the polyethylene glycol, or PEG, moiety, which forms the backbone of the nanoviricides drug candidates. PEG is used prior to colonoscopy in humans to promote loose stools and internal cleaning of the intestines, by causing non-absorption of water. The company has previously reported that these drug candidates have shown strong effectiveness in a lethal lung infection model in rats using a coronavirus that uses the same ACE2 receptor as SARS-CoV-2 which causes COVID-19, namely hCoV-NL63. The company has found that hCoV-NL63, which causes a milder disease than SARS-CoV-2, causes substantially similar clinical pathology in this efficacy animal model as has been reported for SARS-CoV-2 associated lung infections in humans. In this previously reported lethal direct-lung-infection model efficacy study, animals in all groups developed lung disease which later led to multi-organ failures, a clinical pathology resembling that of the SARS-CoV-2. Reduction in loss of body weight at day seven was used as the primary indicator of drug effectiveness. Rats were infected directly into lungs with lethal amounts of hCoV-NL63 virus particles and then different groups were treated separately with five different nanoviricides drug candidates, remdesivir as a positive control, and the vehicle as a negative control. The treatment was intravenous by tail-vein injection once daily for five days, except in the case of remdesivir wherein it was by tail-vein injection twice daily. In this efficacy study, animals treated with the five different nanoviricides showed significantly reduced body weight loss. The body weight loss in female animals ranged from only 3.9% to 11.2% in the different nanoviricide-treated groups, as compared to 20% in vehicle-treated control group, and 15.2% in a remdesivir-treated group. The body weight loss in male animals ranged from 8% to 10.9% in the different nanoviricides-treated groups, as compared to 25% in the vehicle-treated control group, and 18.6% in remdesivir-treated group. Smaller numbers mean less loss in body weight compared to starting body weight in the group, and indicate greater drug effectiveness. The effectiveness of nanoviricide drug candidates in the lung-infection model is consistent with the effectiveness observed in cell culture studies against infection of both hCoV-NL63, which was used in the efficacy study, and hCoV-229E, another circulating coronavirus that uses a distinctly different receptor, namely APN. Prior to filing for human clinical trials, NanoViricides plans on requesting a pre-IND Meeting with the FDA for regulatory guidance.

The company continues to advance its first drug candidate, namely NV-HHV-101 skin cream, for the treatment of shingles rash as its first indication, towards human clinical trials. The company is now in the process of writing and completing its first IND, or investigational new drug, application to the FDA, which includes protocols for human clinical studies, with the help of its several regulatory consultants. This application covers the indication of the company's drug, namely, NV-HHV-101 skin cream for the treatment of shingles rash, caused by VZV, or varicella-zoster virus. The IND-enabling and required pre-clinical studies have been completed, and reports of almost all of the analyses of the samples resulting from these studies are being circulated between parties involved for completion. The company is in the process of identifying and selecting appropriate partners and collaborators for the intended Phase1/2a human clinical studies for this drug candidate. The company cannot project an exact date for filing an IND because of its dependence on a number of external collaborators and consultants and the effects of recent COVID-19 restrictions. The company has undertaken cGMP manufacture of the drug product, namely, NV-HHV-101 skin cream, indicated for the topical treatment of shingles rash, for supplying anticipated Phase I human clinical trials at its own facility. The Company has industry-leading internal expertise in the cGMP manufacture of complex nanomedicines drugs, right from simple starting materials to formulated drug products

NanoViricides reported that it has signed a Memorandum of Understanding, or MoU, with respect to anti-viral treatments for coronavirus derived human infections with TheraCour Pharma. NanoViricides said in a release, "The MoU specifically provides a limited, exclusive license to all research and development in the Field for further research and development purposes towards human clinical trials. NanoViricides intends to retain an independent consultant for the evaluation of the assets in order to develop the full license agreement. NanoViricides has been working on drug development to treat the SARS-CoV-2 infection in COVID-19 patients since January, 2020. Prior to this, the Company had engaged in limited research and development work for the treatment of MERS coronavirus during 2014 which allowed for rapid drug candidate identification against SARS-CoV-2. The MERS coronavirus program was set aside as the 2014 outbreak remained contained. The Company has found that the broad-spectrum anti-coronavirus drug candidates that it is developing were several times more effective than favirpravir in cell culture assays against two different coronaviruses, namely hCoV-229E, and hCoV-NL63. These circulating coronaviruses use distinctly different, but related cellular receptors, namely APN for hCoV-229E and ACE2 for hCoV-NL63. The Company believes the fact that these nanoviricides anti-coronavirus drug candidates are highly effective against two distinctly different coronaviruses that use different cellular receptors is very significant. Specifically, it provides a rational basis to scientists indicating that even if the SARS-CoV-2 coronavirus mutates, the nanoviricides can be expected to continue to remain effective. The Company has also found that these drug candidates showed strong effectiveness in an animal model of human coronavirus disease, potentially superior to remdesivir in this particular model, although no firm conclusions to that effect can be drawn with the limited dataset at present. The Company employed hCoV-NL63 in this animal study, because hCoV-NL63 binds to the same cell receptor, namely ACE2, as does SARS-CoV-2 and the 2002-03 SARS-CoV. NL-63 causes clinical pathology in humans that is similar to SARS-CoV-2, but much milder. Thus this virus is expected to be a good surrogate for SARS-CoV-2. The Company believes that it now has broad-spectrum anti-coronavirus drug candidates that are worthy of human clinical trials based on their effectiveness in cell culture and animal models. Importantly, nanoviricides are designed to act by a novel mechanism of action, trapping the virus particle like the "Venus-fly-trap" flower does for insects. Antibodies, in contrast, only label the virus for other components of the immune system to take care of. It is well known that the immune system is not functioning properly at least in severe COVID-19 patients. Prior to filing for human clinical trials, NanoViricides plans on conducting studies to further determine the effectiveness against SARS-CoV-2, perform drug development studies for safety/toxicology, and request a pre-IND Meeting with the FDA for regulatory guidance. Human coronavirus NL63 uses the same ACE2 receptor as the SARS-CoV-2 that causes CoVID-19. Both in terms of its clinical pathology, and its receptor usage, it is known to be very similar to SARS-CoV-2, except much milder. Therefore the Company believes hCoV-NL63 is a good surrogate model for therapeutics development against SARS-CoV-2. HCoV-NL63 can be studied in a BSL2 lab whereas SARS-CoV-2 currently requires a BSL3 or BSL4 facility."