Replies to post #115440 on NanoViricides Inc. (NNVC)

[changes_iv]

Influenza is among the nine deadliest viruses in the world.

During a typical flu season, up to 500,000 people worldwide will die from the illness, according to WHO. But occasionally, when a new flu strain emerges, a pandemic results with a faster spread of disease and, often, higher mortality rates.

The most deadly flu pandemic, sometimes called the Spanish flu, began in 1918 and sickened up to 40 percent of the world's population, killing an estimated 50 million people.

"I think that it is possible that something like the 1918 flu outbreak could occur again," Muhlberger said. "If a new influenza strain found its way in the human population,and could be transmitted easily between humans, and caused severe illness, we would have a big problem."
http://www.livescience.com/48386-deadliest-viruses-on-earth.html

NanoViricides President Dr. Diwan Presented FluCide Data at the 3rd Annual Influenza Conference held by GTC Bio on Friday, July 11

WEST HAVEN, CONNECTICUT -- Monday, July 14, 2014 -- NanoViricides, Inc. (NYSE MKT: NNVC) 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 indicate 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.

http://www.nanoviricides.com/press%20releases/2014/NanoViricides%20President%20Dr.%20Diwan%20Presented%20FluCide%20Data%20at%20the%203rd%20Annual%20Influenza%20Conference%20held%20by%20GTC%20Bio%20on%20Friday,%20July%2011.html

Commissioning and validation of a new pharmaceutical facility should be considered the optimal goal, as the ROI is not realized until the facility can make product. Budgets and timelines usually become the target focus through a majority of traditional construction projects, sometimes leaving the commissioning and validation of the facility as the final area of focus [3].
www.pharmamanufacturing.com/articles/2004/41/

It is important to note:

1) NanoViricides, Inc. started the process to commission the new state-of-the-art multi-kilogram Pilot Plant in Shelton, CT, to produce FluCide(TM)/GLP, sometime in Jan 2015
2) On Mar 31, 2015 - We are now progressing to a 1kg scale-up of FluCide(TM), and enabling in-process control instrumentation--- CMC studies to enable further scale-up from the current multi-100g scale of production to kg-scale production. 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.

-We are now making the FluCide(TM) material for third and final/Phase III of Safety/Toxicology Studies in large animals!

June 1, 2015, 9:47 PM

FluCide

Phase I and II of tox successfully completed

Making material for last Phase in large animals

...

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

Dr. Milton Boniuk, an independent director/insider, an astute and highly successful businessman and entrepreneur, in addition to being an accomplished eye surgeon, educator, and administrator, is buying NNVC stock with great frequency and confidence!
http://ih.advfn.com/p.php?pid=nmona&article=68529003
http://ih.advfn.com/p.php?pid=nmona&article=68325023
http://ih.advfn.com/p.php?pid=nmona&article=68296181
http://ih.advfn.com/p.php?pid=nmona&article=69004844


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We know that BIND Therapeutics is using combinatorial synthesis to produce their 100nm Accurins(R) but, what is NanoViricides, Inc. using to produce their 20nm Nanoviricides(R)?

About Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study.

Abstract

Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and reproducibility in physicochemical properties of NPs compared to bulk synthesis methods. However, applications of microfluidic synthesis are typically limited to in vitro studies due to low production rates. Herein, we report the parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a multilayer microfluidic system to enhance the production rate without losing the advantages of reproducibility, controllability, and robustness. Using parallel 3D HFF, polymeric poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) NPs with sizes tunable in the range of 13-150 nm could be synthesized reproducibly with high production rate. As a proof of concept, we used this system to perform in vivo pharmacokinetic and biodistribution study of small (20 nm diameter) PLGA-PEG NPs that are otherwise difficult to synthesize. Microfluidic parallelization thus enables synthesis of NPs with tunable properties with production rates suitable for both in vitro and in vivo studies.

FROM THE CLINICAL EDITOR:

Applications of nanoparticle synthesis with microfluidic methods are typically limited to in vitro studies due to low production rates. The team of authors of this proof-of-principle study reports on the successful parallelization of NP synthesis by 3D hydrodynamic flow focusing using a multilayer microfluidic system to enhance production rate without losing the advantages of reproducibility, controllability, and robustness.
http://www.ncbi.nlm.nih.gov/pubmed/23969105

D.9.2 Explain the use of combinatorial and parallel chemistry to synthesize new drugs IB ChemistryHL