NanoViricides Inc. (NNVC)

[changes_iv]

The Deadliest Virus
Did a scientist put millions of lives at risk—and was he right to do it?
By Michael Specter
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Last December, the National Science Advisory Board for Biosecurity, a panel of science, defense, and public-health experts, was asked by the Department of Health and Human Services to evaluate Fouchier’s research. The panel recommended that the two principal scientific journals, Science and Nature, reconsider plans to publish information about the methods used to create the H5N1 virus. It was the first time that the Advisory Board, which was formed after the anthrax attacks of 2001 to provide guidance on “dual use” scientific research, which could both harm and protect the public, had issued such a request. “We are in the midst of a revolutionary period in the life sciences,” the advisers wrote. “With this has come unprecedented potential for better control of infectious diseases and significant societal benefit. However, there is also a growing risk that the same science will be deliberately misused and that the consequences could be catastrophic.” The Times published an editorial that echoed the Advisory Board’s concern, and even questioned the purpose of the experiments: “We believe in robust research and almost always oppose censorship. But in this case the risks—of doing the work and publishing the results—far outweigh the benefits.” The journal New Scientist agreed: “ONE MISTAKE AWAY FROM A WORLDWIDE FLU PANDEMIC.” Television talk shows and the Internet pulsated with anxiety.

The widespread alarm led Science and Nature to agree to postpone publication. Fouchier’s virus, which now sits in a vault within his securely guarded underground laboratory in Rotterdam, has fundamentally altered the scope of the biological sciences. Like the research that led to splitting the atom and the creation of nuclear energy, the knowledge that his experiment has provided could be used to attack the public as well as to protect it.

“Terror is not an unjustified reaction to knowing this virus exists,” Osterholm, who serves on the Advisory Board, told me. “We have no room to be wrong about this. None. We can be wrong about other things. If smallpox got out, it would be unfortunate, but it has a fourteen-day incubation period, it’s easy to recognize, and we would stop it. Much the same is true with SARS. But with flu you are infectious before you even know you are sick. And when it gets out it is gone. Those researchers have all of our lives at the ends of their fingers.”
http://www.newyorker.com/magazine/2012/03/12/the-deadliest-virus

Bird Infections with Highly-Pathogenic Avian Influenza A (H5N2), (H5N8), and (H5N1) Viruses: Recommendations for Human Health Investigations and Response
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Vaccination

No human vaccines for HPAI (H5N1), (H5N2), or (H5N8) are available in the United States. Efforts are underway to develop vaccines against these HPAI H5 viruses. Seasonal influenza vaccines do not provide any protection against human infection with HPAI H5 viruses.
http://emergency.cdc.gov/han/han00378.asp

NanoViricides, Inc. - FluCide(TM)

The Company believes that its FluCide™ drug candidate will be effective against most if not all influenza viruses, including the H7N9 bird flu, H3N2 or H1N1 epidemic viruses, H5N1 bird flu, seasonal influenzas, as well as novel influenza viruses. This is because FluCide is based on the Company’s biomimetic technology, mimicking the natural sialic acid receptors for the influenza virus on the surface of a nanoviricide® polymeric micelle. It is important to note that all influenza viruses bind to the sialic acid receptors, even if they rapidly mutate. The FluCide drug candidates have already shown strong effectiveness against H1N1 and H3N2 influenza viruses in highly lethal animal models. The injectable FluCide drug candidate has shown 1,000X greater viral load reduction as compared to oseltamivir (Tamiflu®), the current standard of care, in a highly lethal influenza infection animal model. The Company believes that these animal model results should translate readily into humans.

NanoViricides has also developed an oral drug candidate against influenza. This oral version was found to be dramatically more effective than oseltamivir (TamiFlu®) in animals given a highly lethal level of influenza virus infection. This oral FluCide may be the very first nanomedicine that is effective when taken by mouth.

Read more:
http://finance.yahoo.com/news/nanoviricides-president-dr-diwan-presented-120000451.html

http://www.prnewswire.com/news-releases/nanoviricides-provides-an-update-on-its-progress-over-the-last-quarter-300061129.html
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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.
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No failures in 5000 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

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Ultra-High Throughput Synthesis of Nanoparticles with Homogeneous Size Distribution Using a Coaxial Turbulent Jet Mixer (2014)

High-throughput production of nanoparticles (NPs) with controlled quality is critical for their clinical translation into effective nanomedicines for diagnostics and therapeutics. Here we report a simple and versatile coaxial turbulent jet mixer that can synthesize a variety of NPs at high throughput up to 3 kg/d, while maintaining the advantages of homogeneity, reproducibility, and tunability that are normally accessible only in specialized microscale mixing devices. The device fabrication does not require specialized machining and is easy to operate. As one example, we show reproducible, high-throughput formulation of siRNA-polyelectrolyte polyplex NPs that exhibit effective gene knockdown but exhibit significant dependence on batch size when formulated using conventional methods. The coaxial turbulent jet mixer can accelerate the development of nanomedicines by providing a robust and versatile platform for preparation of NPs at throughputs suitable for in vivo studies, clinical trials, and industrial-scale production.
http://pubs.acs.org/doi/abs/10.1021/nn501371n

Optimizing the discovery and clinical translation of nanoparticles: could microfluidics hold the key? (2014)
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In summary, microfluidic platforms have shown a strong potential to expedite the discovery and clinical translation of NPs by providing powerful tools for high-quality NP production, high-throughput combinatorial NP synthesis and improved in vitro screening. In microfluidic NP synthesis, physicochemical properties of NPs that determine their in vivo fate can be precisely controlled in a reproducible manner. Moreover, microfluidic platforms enable creation of NP libraries for selection of optimal NP formulations by high-throughput combinatorial NP synthesis and screening. Microfluidic screening assays can better mimic physiological conditions, promising to reduce the burden of extensive in vivo studies and enabling better investigations into how NPs interact with tissues and organs. However, like any emerging technology, microfluidics faces many challenges including lack of standardization, often low user-friendliness and insufficient robustness. However, rapid progress is being made in this field – from 2000 to 2013, the number of publications dealing with microfluidics and NPs (according to Scopus search) increased from approximately 3 per year to over 400 per year! With these efforts, it is highly likely that these shortcomings will be overcome in due course.

What, then, will be the extent of the impact of the contributions of microfluidics to nanomedicine? Certainly improved quality of NPs is desirable; yet, it is unclear to what extent it translates to better clinical outcomes. More in vivo experiments are needed to answer questions regarding how sensitively in vivo fates of NPs are correlated to NP physicochemical properties and their heterogeneity. Nevertheless, the first targeted NP to enter clinical trials already uses a microfluidic emulsification process for clinical scale production of NPs [4], which enables application of high shear stress that results in smaller and more homogeneous NPs. Use of nanoprecipitation for commercial production of NPs still needs additional development; although high-throughput micro/millifluidic devices are available for rapid nanoprecipitation, some properties (e.g., drug loading and stealth layer coverage) of NPs prepared by nanoprecipitation methods may be suboptimal. There is still ample room for further development of microfluidic processes for NP synthesis, and the potential of microfluidics to create complex, multifunctional NPs for nanomedicine remains largely unexplored. Microfluidics-enabled combinatorial synthesis and screening for optimizing NPs has already been undertaken by several research groups. Here, issues of scalability are of less concern and the output is primarily in the form of research knowledge regarding behavior of different types of NPs. Microfluidic approaches will likely continue to be adopted and applied to understanding and optimization of NPs for diverse applications. However, the impact of better in vitro screening may be more substantial in the long run. If organ-on-a-chip technology indeed proves to be able to reduce the time and costs associated with in vivo studies, it will revolutionize the development process for therapeutics including NP drug carriers. So, coming back to the question – does microfluidics hold the key? Although microfluidics may not be indispensable for progress in nanomedicine, all indicators point to a future where microfluidics will play a major role in facilitating each step in the discovery and translation of NPs to clinical impact.
http://www.futuremedicine.com/doi/full/10.2217/nnm.14.73