NanoViricides Inc. (NNVC)

[changes_iv]

What a Bad Flu Season Could Cost the U.S. Economy
This year's unusually potent flu is bad news for most employers but great for drugstores
by John Tozzi
December 10, 2014 — 11:04 AM EST

This year's flu season looks worse than usual. The Centers for Disease Control (CDC) warned last week that the dominant influenza virus right now, H3N2, typically signals a severe flu season, resulting in more deaths and hospital trips than average. Even worse: About half of the H3N2 viruses detected so far are different strains from the ones included in this year's vaccine, which means flu shots will be less effective.

The resulting misery for millions of Americans is also lousy news for the economy. Flu incurs direct costs, such as the price of medical treatment, and indirect costs, such as lost productivity when workers stay home sick. There's also the cost of lost life: Influenza kills between 3,000 and 49,000 people in the U.S. each year, generally older people, young children, or people with medical conditions such as lung or heart disease that make them vulnerable to complications. The CDC recommends that everyone (except infants less than six months old) get vaccinated, especially those considered high-risk because of other health conditions...



Tallying the total cost of flu is difficult. In a 2007 article published in the journal Vaccine, CDC researchers put the total economic burden at $87 billion annually, in 2003 dollars, counting a statistical measure that puts a dollar value on lost life. Among the costs: 3.1 million days patients spend in hospitals, 10 times as many doctors visits, and 44 million days of missed work. The estimates come with a high level of uncertainty, though: Researchers calculated the total cost in a range from $47 billion to $150 billion a year. The CDC is updating these numbers, but there's no telling when they'll be ready...
http://www.bloomberg.com/news/articles/2014-12-10/flu-what-a-bad-influenza-season-could-cost-the-us-economy

Health officials hope new flu vaccine is more effective than last one
...
Both the injected vaccine and the nasal spray vaccine will be newly formulated for the coming flu year, in the hope that it will provide better coverage than their predecessors.

The U.S. Centers for Disease Control and Prevention said on Friday the vaccine for the 2015-2016 flu season will protect against a specific strain of the Type A H3N2 virus, which was missing in the 2014-2015 vaccine.

The trivalent vaccine will protect against a type of influenza B as well as H3N2 and the H1N1 virus that caused the 2009 pandemic, CDC said in a report in its publication Mortality and Morbidity Weekly Report. The quadrivalent vaccine will cover those viruses as well as a second Type B strain, it said.

According to the report, the change in the composition of the vaccine is driven by a host of factors, including surveillance around the world of dominant flu viruses.

Health officials hope the new vaccine mix proves to be more protective than the current vaccine, which only was about 19 percent effective across all age groups and 15 percent effective in children, CDC said earlier this year.

Flu season normally lasts from October to May. Vaccine manufacturers need six months to develop a supply for the coming year, CDC said.

Determining the composition of the seasonal flu vaccine is a combination of viral detective work and informed guessing. The H3N2 flu strain last year "drifted," or mutated, and by the time epidemiologists saw what was in circulation, it was too late to change the vaccine recipe given to manufacturers.

One potential problem is whether the current avian flu epidemic, which has wiped out 45 million turkeys and chickens in the Midwest, will have an impact on production. The flu vaccine is made several ways, but primarily by injecting the virus into a fertilized chicken egg, which provides a rich environment for the development of the virus. It then is extracted for the vaccine.

Liz Power, a spokeswoman for Novartis, one of the vaccine manufacturers, said the outbreak hasn't affected its production because it also used a cell culture process that uses animal cells, not chicken eggs, in the production of the vaccine.

Another vaccine manufacturer, GlaxoSmithKline, said it uses eggs from farms in Canada and Germany dedicated to production solely for vaccines, it said in a statement. The company is monitoring the outbreak and is reinforcing biosafety standards, it said.

"This method of production has the potential to yield large quantities of vaccine quickly, which is beneficial in the event of a pandemic," Power said.

CDC called the current flu season "moderately severe," and said the flu was tough this year on senior citizens. The rate of hospitalizations for people 65 and older with the flu was the highest it has been since the agency began tracking hospitalizations by age group in 2005, it said.

Nationwide, nearly 18,000 people were hospitalized with the flu, and 141 young children died from complications from the flu, the CDC report said.

In New Jersey, Department of Health data show that hospitals reporting patients with influenza-like symptoms shot up in mid- to late December, and beganfalling about a month later.

Spokeswoman Donna Leusner said flu activity started early in the season, which begins in the fall, and kept health providers busy throughout the season. The department's data show 102 outbreaks in long-term care homes for the season.

New Jersey's contribution to the 2015-2016 flu vaccine is through its monthly surveillance reports sent to CDC, she said.

Despite the low effectiveness rate for the flu vaccine in the 2014-2015 flu season, CDC still recommends getting a vaccine. There is no guarantee it will work, but the vaccine usually provides a protective benefit around 60 percent to 65 percent...
http://www.nj.com/healthfit/index.ssf/2015/06/new_flu_vaccine_formula_readied_for_the_coming_flu.html

[...they are guessing?...guessing?]

Big Pharma

Big Pharma is the nickname given to the world's vast and influential pharmaceutical industry and its trade and lobbying group, the Pharmaceutical Research and Manufacturers of America or PhRMA. These powerful companies make billions of dollars a year by selling drugs and medical devices.

Big Pharma wields enormous influence over the prescription drug and medical device markets around the globe. In fact, in the United States, the industry contributes heavily to the annual budget of the U.S. Food and Drug Administration (FDA), which is charged with regulating drugs and devices made by those same companies.

The industry demonstrates its power, political might and social influence over the nation’s governments and agencies, its health care systems, its doctors and hospitals, as well as the psyche of the American people. With the help of staggering profits and 1,100-plus paid lobbyists, the industry has gained powerful leverage on Capitol Hill.

From 1998 to 2013, Big Pharma spent nearly $2.7 billion on lobbying expenses — more than any other industry and 42 percent more than the second highest paying industry: insurance. And since 1990, individuals, lobbyists and political action committees affiliated with the industry have doled out $150 million in campaign contributions...
http://www.drugwatch.com/manufacturer/

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

[No drug/vaccine company out there has pre-clinical data like that of NanoViricides, Inc.]

[On Apr 6, 2015...]

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.

We are happy to announce that our Biological Characterization Group has now completely moved to our Shelton, CT campus. We are implementing a phased move to Shelton so that there is minimal impact on our continuing operations. We plan on continuing to use our West Haven facility to maximize R&D efforts on our large number of drug development programs.
http://www.prnewswire.com/news-releases/nanoviricides-provides-an-update-on-its-progress-over-the-last-quarter-300061129.html

[On May 18th, 2015...]

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.nanoviricides.com/press%20releases/2015/NanoViricides%20Files%20Quarterly%20Report%20for%20Period%20Ending%202015-03-31.html

[Can we say we are now making material, the first 1kg of identical batches for the last phase (Phase III)of tox 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

MersCide

Waiting for Public Health England to request the drug (sitting on the shelf) for testing. They got distracted by the Ebola outbreak

EbolaCide

Making more drug for continuation of the testing by USAMRIID

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

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Microfluidic multiplexer -- cycling inlets with single rinse [Folch lab]

Microfluidic Platform for Combinatorial Synthesis and Optimization of Targeted Nanoparticles...
...
Microfluidics, the science and technology of manipulating nanoliter volumes in microscale fluidic channels, has impacted a range of applications including biological analysis, chemical synthesis, single cell analysis, and tissue engineering.8 In nanomedicine, microfluidics has enabled the synthesis of Nanoparticles (NPs) with narrower size distributions, improved batch-to-batch reproducibility, and higher drug loadings.9, 10 Some key advantages of microfluidics include simplicity and reproducibility of device fabrication, and potentially lower cost of materials due to the ability to handle small volumes. These advantages make the use of microfluidics ideal for the development of a platform that enables rapid synthesis and optimization of NPs.11

In the present work, inspired by the rapid, combinatorial synthesis of small molecules12, 13 and novel biomaterials,14 we have developed a microfluidic platform for the rapid, combinatorial synthesis of NPs. Previously, we developed a microfluidic device that used 3D hydrodynamic focusing to create NPs of different sizes, in a reproducible manner, using 4 different polymeric precursors.15 However, the device did not have the capability to mix precursors prior to nanoprecipitation and was not amenable to high-throughput screening. Here, we developed a fully integrated microfluidic device with a multi-inlet micromixer16 to allow for programmable and systematic mixing of a large number of precursors before nanoprecipitation occurs. As a proof of concept, we demonstrate that this system allows for the synthesis of NPs with a wide range of properties, with batch-to-batch reproducibility, by combining over 15 different NP precursors in different ratios. For each formulation, we produced merely tens of micrograms of NPs, enough for rapid in vitro evaluation. Next, we show the rapid NP evaluation capabilities of the platform by synthesizing 45 different formulations with different sizes and surface composition, screening them for macrophage uptake in vitro, and comparing the results with in vivo pharmacokinetic studies. Finally, we use the microfluidic system to synthesize targeted and non-targeted NPs with the same size and charge, and compare their tumor accumulation in vivo. These studies have broad implications in nanomedicine, where such a platform could be used to rapidly optimize promising novel lipid and polymeric NPs and move them quickly to pre-clinical studies.