Thursday, November 17, 2005

NNVC Valuation

If NNVC were to reach the valuation of Genentech, based on the current float each share of NNVC would be worth $5,000.

If NNVC were to reach the valuation of Amgen, based on the current float each share of NNVC would be worth $5,000.

If NNVC were to reach the valuation of Amylin, based on the current float each share of NNVC would be worth $200.

If NNVC were to reach the valuation of the average Biotechnology stock, based on the current float each share of NNVC would be worth $70.


NNVC is trading today at $1.15.

A

19 comments:

sid said...

i just wish it would stay at the end of the day where it is in the middle. why do all those daytraders HAVE to take profits ?

Allan said...

maybe the more important questions are who is buying all that stock off the hands of the daytraders into the close everyday and what do they know?

ted said...

Allan,

The micelle technology had already yielded an approved drug which proved that the technology is safe and systemic. The modifications that Diwan has made over the past twelve years to specifically target viruses is the final hurdle.
And we know from interviews that Diwan has already tested this viricidal form of the technology ("certain proof of principle").

He has been in collaboration with scientists from MIT which is a endorsement by the company he keeps. News reports have recently highlighted the possible dangerous side effects of tamiflu, so there is definitely plenty of room for improved anti-virals.

sid said...

thanks be to the market god(s), who did heed my quiet call ~~~~

ilene said...

Ted,

I am trying to find out more about nnvc's technology. Can you provide a link to something which will explain it specifically and in great detail?

Thanks, Ilene

Ted said...

http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=1&f=G&l=50&d=PG01&S1=%22Diwan%2C+Anil%22&OS="Diwan,+Anil"&RS="Diwan,+Anil"
Once upon a time I learned how to post a link so that it could be accessed. I think that day is gone for now. In case this doesn't get you to the site (and it probably won't) I'll give you directions.

Take a left to google, type in US patent office. Find the choice that says published applications and... something else. Anyway choose that one and type in (quotes necessary) "Diwan, Anil".
He and his colleagues from the University of Massachusetts (not MIT as I had erroneously written earlier) have an extensive application which explains the technology and it's uses. It's quite a read. Enjoy!

ted said...

Or just go to www.uspto.gov, click on search under patents, and on the next screen click on quick search under patent applications.
On the next screen type in "Diwan, Anil" and the next screen will list two patent applications.

I hope this helps.

ilene said...

Ted,

Thanks, I'm reading the patent you found, copying and pasting got me to it. Were you able to picture the polymer - what it looks like molecularly? (This goes to the question of what exactly do they have a patent on, and how valuable is it?)

I didn't get very far before being confused, e.g., claim 1: "What is claimed is:

1. A polymer comprising a structure represented by: 6wherein R is hydrogen, a linear or branched alkyl group, a linear or branched alkenyl group, or an aryl group; wherein said alkyl, alkenyl, or aryl group is unsubstituted or substituted with one or more heteroatomic functional groups; R' is hydrogen, an acyl group, an antibody fragment, a chemomimetic functional group, an immunoconjugate, a ligand for a biological target, or 7wherein R'" is a hydroxyl group, an alkoxyl group, or a primary or secondary amino group; n is at least 1; and m is at least 1."

I also found another patent link: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=/netahtml/srchnum.htm&r=1&f=G&l=50&s1=6,521,736.WKU.&OS=PN/6,521,736&RS=PN/6,521,736

I don't know the difference between these. However, claim 1 is this:

What is claimed is:

1. A polymer comprising a structure represented by: ##STR6##

wherein

R is hydrogen, a linear or branched alkyl group, a linear or branched alkenyl group, or an aryl group; wherein said alkyl, alkenyl, or aryl group is unsubstituted or substituted with one or more heteroatomic functional groups;

In this particular patent, this symbol: ##STR6## is used frequently with different numbers instead of "6" contained within.

One of the links may be to a patent and one to a patent application, however it looks like the one to the application is dated later (July 31, 2003) than the one to the patent (Feb. 18, 2003) which doesn't make sense.

Also, I was wondering what is FluCide - the drug which is being delivered with the use of the polymer. Any ideas?


Ilene

Ted said...

Ilene,

I can picture the general micelle structure, which is more widespread than I thought. A few companies are working with it. I didn't really attempt to visualize the description in the patent. It seemed like they were describing a figure that wasn't included for us to see.

I'm not sure if this is the theracour patent anyway. Re-reading Diwan's bio, I came to the conclusion that we were looking at the old patent. That patent was already approved and covers older versions of the technology.

ilene said...

Ted,

I can picture the general micelle structure also, and PEG is used with other drugs now. I can't evaluate how unique, special, unreproduceable (by others attempting to create a similar drug delivery system) their polymer, nanoviricide(TM), is.

I can't find studies showing how effective it is in delivering a drug into a targeted cell, and releasing the drug inside. Their latest press release reported that they demonstrated the "polymer, which is unique and proprietary to NanoViricides, has been effectively tested for any toxic symptoms or for any ill effects in laboratory animals. The preliminary results were successful." So, the polymer was non-toxic. But I still haven't been able to find: 1) evidence that demonstrates that the polymer does what they believe, 2) what FluCide is, the active drug for treating flu, 3) what ligands they are going to use to "specifically target H5N1 (avian flu) as well as common influenza viruses?"

If they have an effective flu drug, while the polymer technology and selection of ligands are in developmental stages, wouldn't we want to see some data showing that FluCide is effective against flu? Have you found anything on that?


It seemed like they were describing a figure that wasn't included for us to see.

Yeah.

I'm not sure if this is the theracour patent anyway. Re-reading Diwan's bio, I came to the conclusion that we were looking at the old patent. That patent was already approved and covers older versions of the technology.

I got that impression also. I think I'll copy what I'm writing here and send it to them.

Ilene

ilene said...

In reviewing this, I'm a little confused. They call FluCide a vaccine, which suggests the ligands are the antigens on the viral surface to stimulate the immune system. And they describe it as follows:

FluCide: "Targeted nanoviricides against Bird Flu and Common Influenza to completely neutralize and disable the virus particles in the bloodstream and in the lungs."

And they say, re. the studies:

"In the second part we will study the ligands that target FluCide-I(TM) to H5N1 and common influenza viruses. Thereafter, we will study the efficacy of FluCide-I(TM) itself against H5N1 and common influenza."

which sounds more like FluCide is targeted against H5N1 -- how is it targeted against the virus?

Ted said...

Ilene,
It is targeted by attaching ligands to the nanoparticle that bind specifically to the H5N1 virus. It's not a vaccine, it's an anti-viral. It doesn't stimulate the immune system. That's listed in the patent. It's not immunogenic.
The patent did discuss the mechanism by which the active ingredient is encapsulated in the nanoparticle and delivered to the cell, where the particle breaks open and the drug is delivered into the cytoplasm. However, I was under the impression that the nanoviricide doesn't actually travel into the cell. It removes the virus from the bloodstream.
From what I've read, it seems that the advantage of the technology is that the nanoparticle is inert and that ligands can be added to the particle to give it specificity. Obviously the specificity of an antibody is the ideal. We'll get an idea shortly as to how close they've come.
As far as studies go, as a private company are they necessarily obligated to release the results of their research to the public? What sources have you checked for possible publication?
Finally, I think it would be a great idea to e-mail them your questions. I would like to learn more about the technology too.

ilene said...

Hi, Ted,

I emailed them some questions yesterday.

It is targeted by attaching ligands to the nanoparticle that bind specifically to the H5N1 virus.

In that case, what do you think the ligands are that they're attaching to the nanoparticle?


The patent did discuss the mechanism by which the active ingredient is encapsulated in the nanoparticle and delivered to the cell, where the particle breaks open and the drug is delivered into the cytoplasm.

I don't remember that discussion specifically, but at some point I started reading very fast. It seems that the drug gets into the cells in cell culture, allowing for a lower dose compared to the free drug. I don't know how well these in vitro studies correspond to effects you would see in an animal, where you have a huge variety of cells, besides the ones you're targeting.


From what I've read, it seems that the advantage of the technology is that the nanoparticle is inert and that ligands can be added to the particle to give it specificity. Obviously the specificity of an antibody is the ideal.

Yes, I couldn't figure out what ligands they're using for what purposes, e.g., antibody would get the particle to the virus, antigens would stimulate an immune response (though that doesn't appear to be what they're doing with flucide).


As far as studies go, as a private company are they necessarily obligated to release the results of their research to the public? What sources have you checked for possible publication?

I don't think there's any obligation, but scientists typically publish their work, and there are a lot of benefits to that -- generating funding for the project, getting expert feedback, strengthening their claim to the intellectual property. It is general practice.

Ted said...

Ilene,
I don't know that much about virus receptors. Viruses generally have receptors that allow the virus to attach to cells. Nanoviricides is studying what ligands the H5N1 strain binds to. Then it will attach these ligands to the nanoparticle.

The drugs that use micelle technology already on the market are a proof of principle. Theracour is a modification of that technology which has proven to be safe and systemic. It also seems that from their patent, that they had already tested it in animals, but maybe I was misreading it.

Nanoviricides Inc appears to be taking a different approach than most companies. For instance, when most companies go public, they go the IPO route. Perhaps they are going the unorthodox route in their approach to conducting their research.

In the end, they will be taking the standard route to producing a drug - through the FDA. I look forward to a report of the company's response of your e-mail!

ilene said...

Ted,

I forgot to mention I've done google searches and www.pubmed.com searches. E.g., to look for the viral receptor: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed



Nanoviricides is studying what ligands the H5N1 strain binds to. Then it will attach these ligands to the nanoparticle.



This is an example of where I have questions -- not knowing more, I'd expect a considerable amount of studies on the ligand, years of their work in this area.

http://www.fluwikie.com/index.php?n=Science.InfluenzaPrimerII#cell


The importance of the HA glycoprotein goes beyond the immune system response. If the HA and NA proteins only function was to be a target for the immune system the virus would have no use for them and in fact they would be a detriment. The HA protein also functions as the key to getting in to the locked door of the host cell. Here’s how it works.


The HA glycoprotein of the virus has a special region, called the receptor binding site, that can attach to a host cell if that cell has a specific receptor molecule. Host respiratory cells also have lipid bilayers studded with glycoproteins. The receptor molecule for influenza A virus is a host cell glycoprotein with a side chain tipped with a particular kind of sugar called a sialic acid. The specific sialic acid characteristic of human cells is N-acetylneuraminic acid (NeuAc) and when attached to the cell’s glycoprotein via yet another sugar called galactose it is a potential receptor for attachment of the influenza A virus via the HA protein spike. It is ‘potential’ because there is one additional subtlety here. It depends upon how the NeuAc sialic acid is attached to the galactose. There are several possible linkages, of which two, the α-(2,3) and the α-(2,6) linkages, are important for influenza virus recognition. The numbers and the Greek letter tell which atoms are connected to which on the sialic acid and the galactose.


It was thought that bird respiratory and intestinal tract cells had NeuAc- α-(2,3)-Gal linkages while human respiratory tract cells had NeuAc- α-(2,6)-Gal linkages, although it now appears human respiratory tracts have both, although on different cell types. It seems true, however that avian influenza viruses prefer the former and human influenza viruses the latter. Pigs have both types of linkages which is why they are thought to be an important mixing vessel for genetic reassortments and recombinations, since the pig can be co-infected by both human and avian viruses. Thus a change in the HA binding site via a mutation that would allow efficient binding to a human receptor could cause a virus that previously was efficiently transmitted among birds to be transmitted from person to person. This is rather neat, but unfortunately it isn’t the whole story. Other factors also seem to be involved in determining host specificity of influenza viruses. We also know avian viruses can infect humans, although less efficiently. Thus there is more to it and it is an unfinished story.



http://effectmeasure.blogspot.com/2005/10/how-far-genetically-to-human-h5n1.html

And:

Influenza subverts the system. The hemagglutinin spike holds a key to the cell-surface receptor, allowing the virus to bind with it. The receptor interprets the virus as a messenger molecule, and the virus is hauled in. The cell's fate is sealed.

Not so fast. When the virus is first inhaled, the hemagglutinin molecule is not a perfect key - it's got extra pieces on it that must be cut off.

Organisms cleave molecules with enzymes. In the gut, large lipid (fat) molecules are cleaved by lipases; proteins are cleaved by proteases. One such protease is trypsin.

Cells of the upper respiratory tract must also cleave proteins, and also contain trypsin.

Trypsin only cleaves molecules of just the right shape - another "lock-and-key" situation. H1 hemagglutinin is just the right shape. Trypsin in the lung carves off the excess, and creates a perfect key to the lung cell's receptors.

Influenza normally infects only the trypsin-bearing cells of the upper respiratory tract. Other proteases, borne by other cells, cannot cleave hemagglutinin.

In 1997, an H5N1 virus mutated, giving its hemagglutinin a shape that could be cleaved by several human proteases, allowing H5N1 to infect our species, and to infect a variety of cell types, making it more deadly than ordinary flu. H5N1 from birds in Hong Kong infected humans, killing half of them. Similar infections have recurred several times since.

A flu virus must have a combination of abilities before it can become pandemic - a world-wide epidemic.

Accumulating mutations, H5N1 now has most of them. Should H5N1 evolve the ability to be transmitted human-to-human (rather than by much-less-efficient bird-to-human transmission), it could fuel the next pandemic.

From: http://www.theunion.com/article/20051014/TODAYSFEATURE/110140115


The drugs that use micelle technology already on the market are a proof of principle. Theracour is a modification of that technology which has proven to be safe and systemic. It also seems that from their patent, that they had already tested it in animals, but maybe I was misreading it.

I don't think it's in the patent, but I was less than thorough in my reading of it.




I'll let you know when I hear back from them.

Ted said...

Ilene,
Actually I was wrong in saying they will be taking the standard route to drug approval. Even with the FDA they're attempting an unorthodox approach, hoping to get approved in months rather than years. Also meeting with officials of the Vietnamese government was a unique idea. This company is taking an unusual approach in all facets of the business.
Great article on the description of virus receptors and the mutation of H5N1! Perhaps these are the binding proteins they will target and find a ligand for. You can understand from the article why the FDA would want to speed up the approval process.
I think theracour did years of work developing and testing the nanoviricide against viruses, but obviously not against H5N1. They're obviously expressing confidence in the ability of their technology to target almost any virus. I take this to mean that they have been able to demonstrate neutralization of a wide range of viruses in the lab.

ilene said...

Ted, I've gotten two responses from the company and I will send them to you in email... there's some language within that makes me hestitent to post them on a message board. My email is ilenecar@yahoo.com. - Ilene

Ted said...

Ilene,

I e-mailed you this afternoon. Let me know if you don't receive it.

ilene said...

To clarify why I didn't post the response on the blog, there was this language at the bottom. It seems strange, but there it is:

> ....Unless otherwise explicitly
>permitted by the sender, the receiver or reader of this message is hereby
>notified that any use, dissemination, distribution or reproduction of this
>communication is strictly prohibited. If the reader of this message is not
>the intended recipient, the reader is hereby notified that any use,
>dissemination, distribution or reproduction of this communication is
>strictly prohibited.