NanoViricides Inc. (NNVC)

[changes_iv]

It is a fact that our small company, NanoViriricdes, Inc. is advancing towards the completion of Safety/Toxicology Studies/GLP.

WEST HAVEN, CONNECTICUT -- Wednesday, October 1, 2014 -- NanoViricides, Inc. (NYSE MKT: NNVC) (the "Company") reports that it has shipped FluCide™ to BASi for the start of toxicology studies. NanoViricides has chosen BioAnalytical Systems Inc. Toxicology Services ("BASi") of West Lafayette, Indiana to perform our safety/toxicology studies as needed for an IND submission of the Injectable FluCide drug candidate.
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Injectable FluCide was found to be extremely safe in mice in a preliminary safety study. This study showed no evidence of any adverse events even at the maximum tolerable dose level. 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.
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Injectable FluCide is our first drug candidate, designed to treat hospitalized patients with severe influenza. As noted above, it has been found to be extremely safe. In addition, it was found to be highly effective in combatting a highly lethal influenza A virus infection in mice. It was found to be highly effective against both Influenza A/H1N1 (same subtype as the 2009 pandemic), as well as Influenza A/H3N2 (another pandemic/epidemic strain).

http://www.nanoviricides.com/press%20releases/2014/NanoViricides%20Reports%20FluCide%20Samples%20Were%20Shipped%20To%20BASi%20For%20Start%20of%20Safety%20Toxicology%20Studies%20Also%20Reports%20That%20Ebola%20Drug%20Candidates%20are%20Being%20Synthesized.html

Phases I and II of Safety/Tox studies completed in 2014 with excellent results...

NanoViricides Files Quarterly Report for Period Ending 2014-12-31
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The Company has previously reported that the initial safety and toxicology studies of FluCide™ in a rat model were completed at BASi, Inc., subsequent to the reporting period. These studies have continued to demonstrate an excellent safety profile for our injectable FluCide drug candidate, at doses up to 300mg/kg given for 14 days (total 4,200mg/kg).

http://www.nanoviricides.com/press%20releases/2015/NanoViricides%20Files%20Quarterly%20Report%20for%20Period%20Ending%2020141231.html

The production of FluCide(TM) material, for the third and final phase of tox studies, continues...

...In addition, we continue to perform step-wise scale up of production to enable multi-kg batches of our injectable anti-Influenza drug candidate for IND-enabling “Tox Package” studies. These studies are estimated to require up to 2.5 kg of the drug substance. We plan on scaling up from the 200g scale to 500g scale and then to 1kg scale. We may be able to combine several batches at either the 500g scale or at the 1 kg scale, provided that they are sufficiently equivalent in the characterization studies, in order to prepare a single master batch for further Tox Package studies. In the meantime, we have already performed preliminary safety/toxicology studies in rats using 200g material produced in our older R&D facilities in West Haven, CT. These studies have demonstrated excellent safety of FluCide. Previously, we have performed preliminary safety studies in mice as well. Those studies demonstrated excellent safety of FluCide. This led to the calculation of a very large quantity for our ensuing “Tox Package” studies for this drug candidate.

June 1, 2015, 9:47 PM
FluCide

Phase I and II of tox successfully completed

Making material for last Phase in large animals
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Had FluCide not turned out to be so incredibly safe, we would have been done with tox by now. Incredibly safe is not a bad thing at all!

Eugene Seymour MD MPH
Chief Executive Officer
NanoViricides, Inc
[e-mail]
www.nanoviricides.com
310-486-5677
"NNVC" on the New York Stock Exchange

We are making the FluCide(TM) material for the third and final phase of the Safery/Tox studies, once we reach the 2~2.5kg needed, it will be shipped to BASi and soon enough Phase III of Safety/Tox studies will begin and complete with the expected excellent results we've observed in the past. This goes to prove, once again, what many in the scientific community already knew...

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

PEG is the backbone of all nanoviricides(R) drugs and this is very important because...

Under 505b, tox for FluCide becomes tox for everything that follows. For the second tox following FluCide, they will only need to show bioequivalence, that is, a bridge study would be required to demonstrate that a system processes EbolaCide, DengueCide, X-Cide, in the same way as FluCide. Since FluCide will most probably already be in clinical trials, the second and maybe third X-Cide for clinical trials will need only a bridge study in Phase 1 to advance to Phase 2/3, again that would be an abbreviated PK study showing bioequivalence in processing versions of nanomicelles. ~ BigKahuna

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"I suppose" the "con blogger", "Pump Terminator", could soon be coming out of his closet to reiterate everything he has blogged about our small company in the past, plus an update on why he/she/they believe the risk has jumped from 80% to 99%. "I must confess", I feel pretty confident the sociopath/white-collar criminal will not be outdoing himself and instead rely solely on minimum wage cons/alias/anonymous posters.

Recent “Bear” Attack
As many of you know, a malicious and possibly criminal attack on our common stock was carried out on February 11, 2014, through the publication of a false and misleading article on Seeking Alpha. The intent of the article was to dramatically drive down our stock price. The article resulted in a highly increased daily trading volume of eight million shares, approximately 20 times our daily average. The information we have gathered suggests that this was an organized attack using false and inaccurate information designed to benefit short sellers in the stock. We have reported this conduct to the regulatory authorities and have retained legal counsel to investigate both the website that hosted this article and the anonymous blogger who authored it.

www.nanoviricides.com/2014-ceo-letter.pdf