NNVC - Why so special?

Not surprisingly one of the most frequently asked questions to me is about NanoViricides, if it is still my #1 Stock pick for 2009? Yes it is. What follows is a mini-treatise on what makes NanoViricides so special, courtesy of Dr. FG who posts frequently on the NNVC iHub board.

I've compiled a list of some recent answers given by him to FAQ's about the company and its prospects. But first, a partial excerpt from the Jain PharmaBiotech Report describing the science of NanoViricides.

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Re-published with permission from Dr. FG over at iHub:
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Excerpt from 2009 Jain Report: Structure and function of nanoviricides


NanoViricides are polymeric micelles, which bind to multiple virus-surface-receptors as antiviral agents.They are different from any of the other micellar nanotechnologies as there are no metal particles attached and the micelles can penetrate the virus and bind to multiple sites for effective destruction of the virus.

Mechanism of action of NanoViricides

For a virus to infect a cell, it needs to bind to more than one site. For example, binding of HIV only to CD4 on T cells is insufficient to cause sustained disease; it needs HIV binding to at least two and possibly three different sites on the T cell and that too, at multiple points. For an antiviral to be effective, it should match the strategy to bind to more than one site on the virus. Ideally it should block all of these to prevent virus from infecting the cell and multiplying. Most of the current antiviral drugs have a single mechanism of action and block a single receptor. Drug combinations from different categories are required to increase the number of receptors blocked. Still this is not fully effective.

In contrast to other approaches, a NanoViricide™ micelle can recognize and bind to more than one type of binding site on the virus. The NanoViricide™ system enables design of a drug that binds to more than one type of site - currently as many as three different sites, on the virus - for a highly effective attack. NanoViricides Inc terms this as "multi-specific targeting".

A NanoViricide™ drug goes much further than just blocking all of the binding sites of the virus. The base material of a NanoViricide™ is a specially designed polymeric micelle material. It has the ability to disassemble an HIV particle by itself. Thus, after coating the virus particle, the NanoViricide™ loosens the virus particle, and weakens it. Some virus particles will even fall apart (uncoat). This provides a further therapeutic benefit. NanoViricides plans to enhance the viral disassembly capabilities of the NanoViricides™ by attaching specially designed "molecular chisels" to the NanoViricide™. Once the NanoViricide™ micelles coat the virus particle, the attached "molecular chisels" will go to work. They literally insert themselves into the virus coat at specific vulnerable points and pry apart the coat proteins so that the virus particle falls apart readily. The mechanism of action of NanoViricide is depicted schematically in Figure 4-1.

This description is a simplification. There is no fully adequate explanation of the observed efficacy because the mechanisms of action of nanomaterials as drugs and particularly, NanoViricides in vivo, are multiple and somewhat complex. Targets for this approach include influenzas, HIV, HCV, rabies and other viruses.

Advantages of NanoViricides

NanoViricides have been compared to current approaches to viral diseases, which are seldom curative and some of the advantages include the following:

§ Specific targeting of the virus with no metabolic adverse effects on the host.
§ The biological efficacy of NanoViricides drugs may be several orders of magnitude better than that of of usual chemical drugs. This in itself may limit the potential for mutant generation.
§ There are also other key aspects of the design of NanoViricides that are expected to lead to minimizing mutant generation.
§ Nanoviricides are safe because of their unique design and the fact that they are designed to be biodegradable within the body.
§ The new technology enables rapid drug development against an emerging virus, which would be important for global biosecurity against natural as well as man-made (bioterrorism) situations. It is possible to develop a research drug against a novel life-threatening viral disease within 3-6 weeks after the infection is found, i.e. as soon as an antibody from any animal source is available.
§ It is possible to make a single NanoViricide drug that responds to a large number of viral threats by using targeting ligands against the desired set of viruses in the construction of the drug.It is possible to “tune” the specificity and range (spectrum) of a NanoViricide drug within a virus type, subtype, or strain, by appropriate choices of the targeting ligand(s).
§ The safety of NanoViricide drugs is proven now as they specifically attack the virus and not the host.
§ A variety of formulations, release profiles and routes of administration are possible.
§ Low cost of drug development, manufacture, distribution.

NanoViricide drug candidates are currently in preclinical studies. Clinical trials are planned. Initially injectable products are considered to be most effective but alternative routes of administrations such as nasal sprays and bronchial aerosols can also be developed. Various Nanoviricide products will be described further along with relevant viral diseases.

Advantages of Nanoviricides over vaccines are

§ Nanoviricides work where vaccines fail and are effective even when the immune system is impaired such as in AIDS.
§ Nanoviricides work where effective vaccines are unavailable
§ Sufficient short term protection for an individual outbreak cluster-
§ Treatment can be started after infection
§ No need to vaccinate whole world population for control of a viral epidemic

Advantages of Nanoviricides over immunoglobulin therapies are

§ Fully chemical, room-temperature stable NanoViricides can be made against many diseases.
§ Nanoviricides based on antibody fragment conjugates do not require humanized antibodies. Antibodies from virtually any source can be used for developing NanoViricides, thus significantly reducing time and cost of development.

Immunoglobulin therapies require the patient's immune system (complement system) to function well, which is often not the case in advanced disease states. NanoViricides function completely independently of the human immune system while accomplishing the same goal of reduction in viremia.
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FAQ's from Dr. FG:

>>And how many products do we presently have in animal testing now?

Presently testing--HIV, Rabies, EKC/Herpes. Scheduled or in testing--Ebola, Dengue, Flu/AviFlu.

>>How many do we think are in round two?

In round 2--HIV, Rabies, EKC/Herpes. We think also--Ebola, AviFlu. Ebola may be back in round 1 if the current testing is with a significantly altered version.

>>What's involved in completing a tox package?

Since the drug has never been tried on Humans before, the IND approval will be based entirely on the total results in animal testing. So, since so far test animals haven't shown reactions at therapeutic levels in the histological exams, pretty much increasing the dosage until 1) counter indications occur such as rashes, lesions, weight loss, loss of appetite, etc; and, 2) they begin to die. The test subjects will also be examined for other toxicity factors such as tissue damage, carcinomas, etc. Each test will run about a month plus data evaluation. Could be 1 test or could be 4 or more tests. It all depends on how the nanoviricide is classified. Considering its composition my best guess is it will be classified with monoclonals. That would be a fairly rapid tox workup.

>>The EKC testing took over a year to set up only and the testing in Japan has taken longer.

Some take longer and some much less time. The first EKC tests took less than 4 months from concept to protocol to results and data. The second round should start shortly, but is out of the hands of NNVC's management. As far as Japan goes, who knows what is happening there and do we really care? I'd say that with a major pharma MTA and potential exclusive world market, Japan's testing is far less important.

Ebola took only a few months, while Dengue has taken years due to funding, mishaps and probably politics. HIV has taken almost a year for the second round, while Rabies took a year, then only a few months for the second round, which was then greatly expanded back last October or November. So, generally, who knows, really.

>>I'm also bugged a bit that the stock we all think has so much potential to make history(and us rich) is NOT reflecting much of that potential after having been around for 3+ years,...

Though I agree with you in spirit, in reality who has ever heard of a biotech atrtup with 4 to 6 drugs still in pre-clinical studies, with no licenses (yet) valued at $70 million? Since the technology apears to be the only standard for valuation here, there has to be something to this technology to hold at that cap, yes?

One of the complaints I've heard from some VCs is they don't want to hand over $5 million at rates above 30 cents a share, and managenet doesn't want to dilute at rates anywhere near 30 cents a share.

>> I'd love to see $1 become the floor too.

And $1 seemed to be the floor (certainly 80 cents) way back last fall before the complete world econ collapse dragged the SP down with it. Where's the floor now? Maybe we will see it more clearly tomorrow.

>>Willing to wait the 2-3 years I think it will take for this to [finally] unfold.

So am I but with certain benchmarks in place. At least one product must complete another round of animal testing in the next 60 days. At least 1 product much complete a tox package by end of Q1 2010. At least one product must enter Phase-1 clinical studies by NNVC fiscal year end 2009/2010. Everything else in the interim will be a bonus.

>>The upfront and milestone payments from GSK to SNTA are different from the Royalty payments or "the split" that SNTA would receive IF/WHEN Elesclonal ever made it to the market, right?

Yes, the royalty payment (RP) is structured differently and separately from the milestone (MP) or "benchmark" payments.

The first deal will likely not get a big upfront payment, though I can see it easily between $5 million and $15 million. The second or third deal will likely be much larger. Part of the valuation for the upfront involves

1) risk, the perception of likelihood that the drug will make it through the process of approval

2) the current stage of development: Is the technology pre-development? Pre-clinical? Clinical? Has a tox package been done? Human trials? Phase-1? -2? 3?

3) Total market valuation and competition, a $10 billion dollar market is obviously more valuable than a $500 million market, and a market that already has 5 drugs is going to be less valuable than one that has no one and no current cures.

4) Amount of market penetration expected after approval, in a competitive market is the drug expected to have significantly greater efficacy? Or, will it simply compete against existing therapies and treatments?

5) The role the technology and/or drug plays in the expected final treatment. If the technology is one part of several combined technologies then the valuation will be lower than if it is considered the primary or single technology for a final treatment. If the drug is the technology, then it would have even greater value.

6) The track record of the company, has the company licensed other technologies? Does it have any of those technologies in process to approval? On the market?

The MP is also based on the above, with the addition of each defined milestone having added valuation based on the significance of the milestone as the technology or drug winds through the process.

The RP is based on the same valuations as the upfront payment. It also is usually structured with bonuses and bump-ups as defined by market penetration, total market and gross sales. Royalties might start out at 3% for sales under $50 million, then bump to 7% for sales between $50 million and $100 million and then 10% for all sales in excess of $100 million.

Let's do some amateur evaluating:

Looking at EKC/Herpes-cide, there are no effective treatments and currently no competition. The market is estimated to be between $1 billion and $5 billion with a likelihood of $2 to $3 billion (EKC alone is estimated to be greater than $1 billion). The technology offered is the drug. The drug is expected to ultimately emerge from trials and achieve market approval. The drug is not expected to go through a lengthy process for approval like cancer or influenza treatments.

On the other hand, the drug is still pre-clinical and pre-tox package. The drug may have to go through minor adjustments during the process to approval. There are competing technologies already in clinical trials, but have not yet emerged to FDA approval. The company has not established a track record and is still in the pioneering stage.

Here's what I get for EKC-Cide based mostly on looking at other licenses from 2005 and 2008:

Upfront payment- between $5 million and $15 million. The higher end will be more likely if NNVC has completed the tox package ahead of the final deal.

Benchmark totals- should range between $150 and $700 million over a 2 to 5 year period. This one is harder to call as there are so many factors, and especially that lack of a track record.

Royalty payment structure- Base RP between 5% and 10%. Bump-ups could make upper sales range payments 15% and as much as 25%. Most likely upper sales RP will be between 15% and 18% for this first drug.

Now do the same for amateur evaluation for HiveCide.