NanoViricides Inc. (NNVC)

[changes_iv]

A Problem-Free Life is a Fantasy Not Worth Feeding
This work situation reminds me of Jonathan Fields’ recent interview with Garden Cafe founder and owner Bart Potenza. Potenza has flourished in the hyper-competitive New York City restaurant field for 25 years with his signature vegan restaurant. And what does Potenza think about most hours of the work day?

About equipment. Whether or not the restaurant equipment will fail at the last minute and compromise customers’ dining experience.

Fantasizing about a problem-free, suffering-free life is a trap for aspiring creatives. If you’re prone to escape problems, avoid the creative life.
- See more at: http://www.creativitypost.com/create/the_problem_solving_paradox_of_creativity#sthash.zHMbWchg.dpuf

[It doesn't matter what kind of business you are in, the creative embrace complexity. Scientists embrace complexity to solve problems and some of NanoViricides, Inc. new hires are likely involved in that particular process. No reason to fret about this or BASi. BASi has 40 plus years of experience in the business and I am sure they embrace complexity as well.]

PEG has a toxicological profile of very low concern and is well tolerated at high doses after chronic and acute administration. The PEG associated with a biological molecule itself should provide no extra concern because the toxicity versus exposure relationship in animals and humand has been thoroughly investigated and metabolism/excretion is well understood. Based on the comparisons of PEG exposure from PEGylated biological products and the exposures of PEG associated with toxicity, the therapeutic index is large (=600-fold). The metabolism of PEG is limited to metabolic modification of the hydroxyl group, and the data available suggest that the metabolites seen in humans are seen in animals. Also, for PEGs typically used on biologicals, metabolism will not play a major role in PEG elimination. In light of these data, PEG metabolites do not represent a significant issue, especially when combined with the low overall exposure to PEG discussed above.

Studying the metabolism of PEGylated biologics will represent a significant challenge. First, radiolabeling of PEG associated with a biological molecule is not a viable option. Second, the doses of these PEGylated biologicals are usually very low. Third, PEG is present in a range of products that humans are routinely exposed to. The detection of trace exposures of PEG metabolites produced from PEGylated biologicals will be impossible against the background of PEG and its metabolites present as a result of routine exposure. Moreover, because the products of metabolism are the same regardless of the route of administration, because metabolism represents a minor route of clearance, and because data demonstrate that PEG exposures considerably higher than those possible from PEGylated biologicals are required for toxicity, any additional experiments seem unjustified and of very limited value.

The data presented in this article indicate that, assuming toxicological evaluation of a biological molecule of interest is completed in an appropriate species and satisfactory therapeutic windows are achieved, the PEG associated with a protein or other biological molecule does not represent a significant additional unquantified risk to humans, because of 1) the low exposures involved, 2) the low toxicity profile of PEG, and 3) the similarity of the metabolites that are formed in all species.

Further studies to elucidate the metabolism of the PEG associated with a biological molecule in humans will not provide any more information to place into context the safety of PEG, and such studies may not even be possible. http://dmd.aspetjournals.org/content/35/1/9.full

[Bets on margin need to be concerned with facts that were presented at the 3rd Annual Influenza Research and Development.]

West Haven, Conn.--(BUSINESS WIRE)--

NanoViricides, Inc. (NYSE MKT:NNVC) (the “Company”) reports that its President, Dr. Anil Diwan, was invited to present the FluCide™ data at the 3rd Annual Influenza Research and Development Conference on Friday, July 11, at 0850 am. The Conference ran from July 9-11 at the Hyatt Regency in Boston, MA, and was held by GTC Bio (https://www.gtcbio.com/conferences/influenza-research-and-development-agenda).

Dr. Diwan discussed the nanoviricides® technology platform, and presented the pre-clinical data on the Company’s first drug candidate, NV-INF-1, Injectable FluCide™, to treat all influenza infections in hospitalized patients. Influenza A H1N1 infected animals treated with FluCide survived the full 21-day observation period, whereas animals treated with 40mg/kg/d oseltamivir phosphate (Tamiflu®) survived only 8 days in this highly lethal study. Influenza A/WS/33/ (H1N1) virus was used in this study. The highly lethal infectious dose of 1M viral particles at time 0 h followed by another 1M virus particles at 23h that was employed caused uniform lethality in 5 days in untreated mice. Body weight began to decline in the infected, untreated mice, by days 2-3 days and continued to decline until death. The Oseltamivir-treated mice maintained body weight only through day 5, which declined thereafter until death. Similar to the survival results, the mice treated with NV-INF-1 maintained their body weight substantially longer, through day 14. NV-INF-1 demonstrated an unparalleled 1,000-fold reduction in lung viral load compared to untreated animals on day 4 in this lethal animal model study. Moreover, the lung viral load was suppressed to this baseline level through 13 days or longer, with a slight increase on day 19. In contrast, the current standard of care, oseltamivir, (Tamiflu®, Roche) exhibited only a 2-fold reduction in lung viral load at day 4, that rapidly rose by approximately 2X on day 7. Similar to the reduced virus titers, on day 4 the lungs from mice that were treated with NV-INF-1 showed a substantially lower lung weight (healthy) and displayed a markedly reduced presence of virus-induced lesions as compared to the untreated control and oseltamivir. Also similar to lung virus titers, the reductions in lung lesions in animals treated with NV-INF-1 were maintained at least through 13 days.

Dr. Diwan also discussed the extremely high safety of NV-INF-1 observed in preliminary safety/toxicology studies. He noted that no significant changes in all observed parameters were found even at the maximum feasible dose of approximately 2,700 mg/kg/d repeatedly given for five consecutive days.

He also presented the data on NV-INF-2, the Company’s current oral anti-influenza drug candidate. NV-INF-2 has the same antiviral ligand as NV-INF-1, but a different polymeric backbone that has enabled significant oral effectiveness. NV-INF-2 has been evaluated in a mouse model of influenza virus infection using two different influenza virus a strains, A/WS/33/ (H1N1) and A/W/67 (H3N2v). NV-INF-2 treated mice survived as long as 14.5 days in an H1N1 lethal infection study, and for 15.6 days in an H3N2 lethal infection study. Oseltamivir treated animals died in only 7.6 days in H1N1 infection study, and in 9.6 days in the H3N2 study. The lethal infection viral dose and protocol was chosen such that the untreated animals died in 5 days in both H1N1 and H3N2 studies. Similar to substantially increased survival, NV-INF-2 also exhibited substantially superior reduction in lung viral titer and protection of lungs from lesions.

The data indicates that both NV-INF-1 and NV-INF-2 are highly effective, broad-spectrum, anti-influenza drugs. The Company has shown that they are effective against both group I and group II influenza A viruses.

Dr. Diwan also reported that the Company is successfully scaling up production of NV-INF-1 for the GLP Safety/Toxicology study at its current facilities. In addition, he reported that construction of the Company’s new facility capable of cGMP production of all of the Company’s nanoviricides drug candidates for human clinical batches is now complete. Facility testing and validation are in progress.

The market size for an effective influenza drug for treating severely ill hospitalized patients has been estimated in the billions of dollars, worldwide, depending upon the therapeutic value and cost savings. Currently, there is no effective therapeutic available for this indication. The Company believes that it could supply a substantial portion of the demand for this drug from its new small scale cGMP clinical drug facility. This drug is currently in IND-enabling studies.

This broad-spectrum FluCide drug is expected to work against most, if not all, forms of influenza virus, including epidemic, pandemic (e.g. H1N1/2009), high path influenzas such as H3N2, H7N9, and “bird flu” such as H5N1.
The total market size addressed by the Company’s current drug programs is estimated at about $50 billion. In addition to Injectable FluCide, the Company is working on five more commercially important drug candidates, namely: DengueCide™, HerpeCide™, HIVCide™, Oral FluCide™ for out-patients, and a broad-spectrum antiviral drug for viral diseases of the external eye. All of our programs are for therapeutics to treat viral infections. Our drugs are expected to be useful as prophylactics as well. DengueCide has recently received orphan drug designation by the US FDA as well as the European EMA.
Read more: http://finance.yahoo.com/news/nanoviricides-president-dr-diwan-presented-120000451.html

[And today those are the undisputed F-A-C-T-S. Our anti-influenza drugs are independent from the host's immune system. NanoViricides, Inc. therapeutic drugs are only targeting the life-threatening virus in the host.]

No failures in 6000 plus animals and...

"...we don't anticipate any in humans because remember, we are agnostic to the host...we don't care if you are a man, a mouse, a whale, or a salamander. As long as you have a virus in your circulation, we destroy it!"~ Dr. Eugene Seymour, CEO of NanoViricides, Inc.

We are now working to optimize all of the processes involved in the production of FluCide. Equipment needed for this task is being acquired, and is being installed by factory representatives as it arrives. Some items have lead times of 6 to 8 weeks for delivery. We are working as quickly as possible on setting up the production processes at our new state of the art c-GMP-capable manufacturing facility in Shelton, CT.
http://www.prnewswire.com/news-releases/nanoviricides-provides-an-update-on-its-progress-over-the-last-quarter-300061129.html

NanoViricides Files Quarterly Report for Period Ending 2015-03-31
...
Scale-up of the FluCide™ anti-influenza drug candidate is progressing well. We are continuing the CMC studies (see below) on FluCide production processes. These studies are necessary to enable further scale-up from the current multi-100g scale of production to kg-scale production of our nanoviricides drug candidates. The 1kg-scale production is being set up at our new Shelton, CT facility and headquarters.
...
We are now progressing to a 1kg scale-up of FluCide, and enabling in-process control instrumentation. We need to make approximately 2.5Kg of our FluCide drug candidate for further Tox Package studies because of the excellent safety demonstrated by this drug candidate in safety and toxicology studies in both mouse and rat animal models. CMC stands for "Chemistry, Manufacture, and Controls," and relates to being able to make the drug substance and the drug product in a reproducible fashion, batch after batch. CMC programs for nanomedicines are relatively complex compared to those of small molecules. We have focused on developing scalable, reproducible processes from the very onset, which has helped us minimize the process development time.
http://www.prnewswire.com/news-releases/nanoviricides-files-quarterly-report-for-period-ending-2015-03-31-300084664.html