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Baby Biotechs | Investing in Small Biotechnology Stocks

NeurogesX to Buy or Not

This is the third and final part of Drew Waight’s guest series evaluating NeurogesX for investment. Thanks to Drew! If anyone else would like to do a guest series about a recent IPO, shoot me an e-mail (it’s in the about section).

NeurogesX financial details (2006):
Burn Rate: $30million
Liquid Assets: $14million
IPO price: $11.00
Raised in IPO:$44million

Fortunately in the case of NeurogesX we are looking at a company completing two secondary phase 3 trials so we don’t have to speculate too much about either the chances of their lead product, NGX-4010, being tolerated or effective. In addition this makes the financials a little easier to read as it’s relatively safe to assume that they will be able to get some revenue should the FDA fast track their NDA application expected to file in 2008.

Financials

As of December 31, 2006, NeurogesX has a deficit accumulated during the development stage of $127.5 million, and they further believe there is enough working capital to meet their obligations through the first half of 2007. Management plans to continue to finance the company’s operations with a combination of equity issuances, debt arrangements and revenues from collaborations with pharmaceutical companies, technology licenses and, in the longer term, product sales and royalties. In reference to the IPO, the S-1 states that Neurogesx plans to spend $40 million from the net proceeds to fund R&D. This roughly breaks down into $25 million to finish off NGX-4010 clinical and regulatory program for PHN and HIV-DSP, $10 million for NGX-4010 development for PDN program and the remaining $5 million for a new opioid analgesic product candidate. Looking at the above numbers it’s easy to guess that NGSX didn’t raise as much as expected during their initial public offering of 4 million shares. The shares were offered at $11 (after being reduced from $13) and closed down at $10.25 on the first day. Given the small amount of working capital, this indicates that even if NeurogesX continues to operate at their 2006 levels they won’t even have enough cash for two years. If this isn’t a problem it certainly is cutting it closer than I’m sure the management would have liked. Regardless, as was covered in the last post, NeurogesX plans to file their MAA with the EMEA this year, and, should this be successful, they would theoretically have the funds necessary to take NGX-4010 to the U.S. market at least for PHN and HIV-DSP.

NeurogesX Final Thoughts

NeurogesX stock price decreased nearly 30% in the first week of trading. Even though it is not atypical in biotech to see a drop in price the week following the IPO, it is possible to draw some logical conclusions as to why the stock has fallen. First of all, understanding the product NGX-4010, while actually straightforward, is a convoluted process in terms of gathering together previous studies and intellectual property. Combine this with the fact that there is no publicly available analysis of NeurogesX and very little “buzz” on the trade sites or blogosphere. The result of this marginally unexciting IPO is probably a cursory glance at the financials, which, to say the least, are less than optimal. Therefore from a financial standpoint investing in NeurogesX should give one some apprehension. However, from a market and science perspective this is a company holding the intellectual property license on a topical transdermal patch with high concentration of a natural compound for two underserved medical conditions. Because of this, even without two successful phase 3 trials, I would give NGX-4010 a much better chance of FDA approval than any small molecule or biologic. It is because NGX-4010 is so relatively close to being a product that I firmly believe that the ~$8 share price is substantially undervalued. That being said, I feel it would be less than prudent to bank on NGX-4010 being approved for PDN stateside, (however generously that would effect the market cap) due to the reasons explained previously. Personally I can’t think of a reason high concentration capsaicin should work some neuropathies and not others, but I’m in the business of investing my money and not gambling on unknowns. In summation, the largest risk involved with what I have just described as a bargain share price for a company with post-phase 3 treatments is going to come down to the financials. We all like a little wiggle room should things take longer than expected and I don’t feel that NeurogesX is leaving themselves that much. Conversely, I would be surprised that a company this close to the goal would ever be allowed fall short.

Update

Since writing this article (Editor’s note: I was really slow getting it up) NeurogesX finished the second phase III trial of NGX-4010 for PHN and the stock surged to ~9$. Conversely during the first quarter ending in March they posted a wider loss totaling $11.4 million. Both of these events continue to support my synopsis of NGX-4010 being a promising therapeutic despite NeurogesX’ less than optimal financials.

NeurogesX’s Pipeline

This is a continuation of the guest series by Drew Waight analyzing NeurogesX for investment.

Last time I covered the therapeutic market area of neuropathic pain, which is NeurogesX’s major area of focus. This time I’ll be doing the due diligence on their first product candidate NGX-4010, and it’s safe to say that the entire company rests with the fate of this therapeutic. NGX-4010 is a non-narcotic analgesic formulated in a topical (transdermal) patch containing an 8% concentration of synthetic capsaicin. Capsaicin is released from the patch and absorbed into the skin without significant absorption into the bloodstream.

The chemical capsaicin is popularly known as the compound which gives hot chili peppers their spicy properties and natural concentrations range from 0.1% to 1% w/w. Chemically known as trans-8-methyl-N-vanillyl-6-nonenamide, it is a highly selective agonist for the transient receptor potential vanilloid receptor 1 (TRPV1). TRPV1 is a ligand-gated, nonselective, cation channel preferentially expressed in nociceptive sensory nerves. TRPV1 responds to noxious stimuli, including capsaicin, heat, and extracellular acidification, and integrates simultaneous exposures to these stimuli.

Intellectual Property

Low doses of capsaicin cream have long been used successfully for relief of neuropathic pain. However the first published study to use high doses (5-10%) in combination with regional anesthesia (to numb the normal burning sensation accompanying such high dose) was published in 1998 from UCSF. This study showed that at these levels of capsaicin, 90% of patients (N=10) were relieved from neuropathic pain from 1 to 18 weeks. Interestingly, in 1996, prior to the publication, three of the authors of the study patented the use of high percentage capsaicin with the Regents of the University of California as an assignee on the patent. Subsequently, the first author on the above study, Dr Wendye Robbins, was issued another patent in 1997 (again UC Regents were the assignee) whereby local anesthetic was administered through the use of a transdermal patch containing the high concentration of capsaicin. Dr. Robbins founded NeurogesX in 2000, licensing the patents from the University of California.

That pretty much brings us up to speed on the intellectual property with one final important caveat. The first patent outlining the use of high concentration capsaicin was issued to three authors, and two of the three were not UCSF faculty and so did not assign their patent rights to the University of California. Anesiva, a company focused on the development and commercialization of treatments for pain, including injection or infiltration of a capsaicin derivative for post-surgical pain, osteoarthritis or interdigital neuroma, has licensed from one of the non-assigning inventors the right to use the technology under the method patent.

So NeurogesX has the worldwide exclusive license for a high concentration capsaicin transdermal patch. The use of high-concentration capsaicin itself is not exactly in the public domain but neither does NeurogesX have exclusive worldwide rights. Therefore, it goes without saying any investment in NeurogesX is banking on the utility of the transdermal patch method of capsaicin delivery. As it turns out the only current alternatives to a transdermal patches are a topical creams which of course have the drawback of wildly inaccurate dosing (FDA won’t approve) and injection such as Anesiva is developing for post surgical pain.

Pipeline

Now that we’ve covered the therapeutic market and the intellectual property let’s move on to the pipeline. NGX-4010 has completed two phase 3 clinical trials that have met their primary endpoints, one in PHN and one in HIV-DSP. The results demonstrated that a single 30 or 60 minute application of NGX-4010, depending on the indication, may provide at least 12 weeks of clinically-meaningful pain relief. NeurogesX expects to file a marketing authorization application in Europe for NGX-4010 in 2007 based upon existing clinical trial data, and if the safety and efficacy of NGX-4010 are confirmed by two ongoing pivotal Phase 3 clinical trials, they intend to file a new drug application in the United States in 2008. Furthermore NGX-4010 is currently in phase 2 clinical trials for PDN.

The Neurogesx story is fairly straightforward for a biotech company. First, the therapeutic market is underserved in terms of an easily administered, but long lasting, transdermal patch. Secondly, the intellectual property situation is not ideal but NeurogesX has 30% of the license for high-concentration capsaicin and a monopoly on the patch delivery. Finally we are looking at a late stage development pharmaceutical which needs secondary phase 3 studies before filing the NDA.

That being said, the elephant in the room here is the indication for PDN. By far the biggest opportunity in a therapeutic for neuropathic pain exists for this disorder. Apparently NeurogesX plans to file the broad label authorization for NGX-4010 MAA in Europe in 2007, and use the proceeds from the European market to fund the ongoing trials for PDN domestically. The nuances of this approach are probably known only to the management and the underwriters, but I will try to read between the lines considering the information publicly available on the clinical trials. It seems that patients with PDN were involved in the original Phase I/II tolerability studies of NGX-4010. These patients reported a 32% decrease in pain, but for some reason the PDN clinical program has been halted awaiting the IPO filing. I read this as there being complications with the performance of NGX-4010 in the original phase 2a trial, perhaps the longevity of relief seen with PHN was not paralleled in the PDN case, but anything is possible. At any rate I feel NeurogesX is playing the PDN indication fairly close to the vest, and this must be noted because, as mentioned above, this is clearly the lions share of the peripheral neuropathy market.

Next time I’ll wrap up with the Neurogesx financial situation and put it all together for a final verdict.

Background for NeurogesX and Neuropathic Pain

This is a guest series from Drew Waight a graduate student at NYU. Leave him a comment if you like his analysis and maybe he’ll send another one in. I should be back in August when I’ve finally made my escape from the lab and no longer have two jobs. Until then, you can catch my analysis of big biotech (and pharma too) at The Fool.

NeurogesX

Website: http://neurogesx.com
IPO date: 05/02/2007
Market Cap : $101 million
Shares Outstanding : 12.49mln
Float: 10.23mln

Neurogesx (NGSX) is a biopharmaceutical company developing and commercializing novel pain management therapies. More specifically, their main niche involves the area of neuropathic pain. Let’s take a closer look at the details and prevalence of this affliction, focusing specifically on the treatments NGSX has in the pipeline.

Therapeutic Areas

Neuropathic pain is caused by diseases or trauma that produce lesions in the central (e.g., stroke, spinal cord injury, multiple sclerosis [MS]) or peripheral (e.g., surgery, diabetic neuropathy, herpes zoster) nervous system. Peripheral neuropathy (neural damage in the extremities) is the most common which mainly affects the feet and legs. The most recent studies suggest that more than two million adults in the U.S. suffer from neuropathic pain.

Post-herpetic neuralgia (PHN) constitutes about 200k cases per year. In this disorder, factors such as age, illness, stress or medications can reactivate an otherwise dormant chickenpox virus (varicella-zoster), causing shingles (herpes zoster). The virus travels along nerve fibers, causing pain. When the virus reaches the skin, it produces a rash and blisters. These cases of shingles usually heal within a month, however in roughly 20% of cases the patient continues to feel pain long after the rash and blisters heal. This pain is known as postherpetic neuralgia.

Painful HIV-Associated Neuropathy (HIV-DSP) is among the most common of the pain syndromes afflicting HIV-infected individuals. It is thought that nearly one third of people with HIV/AIDS experience some peripheral nerve damage caused either by the virus itself, by certain drugs used in the treatment of HIV/AIDS, or by secondary complications from the disease.

Almost 16 million Americans had diabetes in 2005. Of these “complications” 60-70% of diabetics have mild to severe forms of nervous system damage. While the first sign of diabetic neuropathy is usually numbness, Painful diabetic neuropathy (PDN) often manifests in the form of a burning or other painful sensation most commonly in the feet and lower extremities.

Treatment

Over the counter analgesics such as acetaminophen and non-steroidal anti-inflammatory drugs have not been shown to be highly effective in the treatment of neuropathic pain. The treatments that are available for the above conditions are largely similar and the common underlying mechanism of action is reduction of neuronal hyperexcitability. Topically, Capsaicin creams derived from natural chili pepper plants have long been known to provide temporary relief. Similarly, Lidocaine (topical local anesthetic) patches are also effective for pain management. Both of these treatments last between 4 and 12 hours however, and require multiple applications per day. Both tricyclic antidepressants (TCA) and serotonin reuptake (SSRI) inhibitors are used to treat neuropathic pain, it should be noted that while generally SSRIs are safer for use in the general population, they have less consistent effects than the TCA class. Finally, anticonvulsants such as phenytoin (Dilantin), carbamazepine (Tegretol) and gabapentin (Neurontin) are frequently prescribed for neuropathic pain and have been shown to be effective in double-blind placebo controlled studies. Some caveats to the anticonvulsant class of medications include a relatively notorious list of adverse side-effects and unpredictable response to the treatment.

In summary, the therapeutic focus on neuropathic pain does in fact constitute an area of unmet medical needs. The major diseases which cause the neuropathies above (herpes zoster, HIV and especially diabetes) are ubiquitous illnesses which are not predicted to be decreasing in the future. Furthermore, treatment for these neuropathies (with the exception of topical agents), largely revolve around the secondary analgesic effects of neurological pharmacologics which in some cases may be beneficial if the patient is already depressed. Nevertheless, it seems there is still plenty of room in the market for a more subtle topical treatment option such as Neurogesx has developed.

Next time: Neurogesx flagship product, the trans-capsaicin patch. I’ll also cover their clinical trial status and scientific patents protecting their quasi-novel approach to management of neuropathic pain disorders.

5 Questions You Should Ask Yourself Before Investing in a Biotech Company

Do I understand the science? If you don’t understand the science behind the drugs, you can’t possibly figure out whether the drugs are any good.  Don’t have a science background? Find a friend; perhaps your friend Brian will help?

How is the company going to increase sales of existing drugs? OK, so here at BabyBiotechs, we don’t get to ask this question all that often. But if the company you are investing in has products on the market, then it needs to have a plan for increasing sales.  Increasing sales (hopefully) results in increased profits, which should result in increased stock price.

How many drugs are in the pipeline?  Not every drug in the pipeline is going to get FDA approval.  Heck, most of the drugs won’t get FDA approval.  For the most part, the more potential drugs the better. Although if the company doesn’t have an income stream, a large pipeline will result in a high burn rate, so the pipeline really needs to be inline with cash in the bank.

What’s the market for the drugs in its pipeline? In order to figure out how much money the company could make in the future, you need to know how much the drug is worth if it’s approved by the FDA.  It’s essentially an educated guess, based on the current drugs on the market and how much market share the newly approved drug(s) could take.

How many people work at the company?  I know what your thinking, “That’s number 5? I can think of 101 questions that are far more important than knowing how many people work there.”  And that’s exactly the point.  You should study a company until you understand every minute detail of the company.  Then and only then you should be turning over your hard earned money.

This post is part of the top 5 group writing project. If you have a blog, feel free to participate.  If you’d like to read more top 5’s, here’s yesterdays submissions. Hsien has a good one about 5 cool things you can do with your DNA.

Omrix Pharmaceuticals’ Passive Immunotherapy Product Line

This is part 3 of the review of Omrix Biopharmaceuticals stock.  Apearently this wasn’t insanely obvious since some people asked via e-mail, but I don’t own any shares in the companies I review. That’s kind of the point of doing the review.  If you’re reading this later than when it was first published I might have decided to buy the stock (go ahead and skip to the decision post, I don’t mind), but my articles weren’t written as a promotion of the stock.

Passive immunotherapy is pretty much what you’d guess from the name.  It’s passive because the patient’s body isn’t doing it, and immunotherapy is essentially antibodies attacking an infection.  So, you inject antibodies (imunoglobulin) from some other source into the patient who can’t make their own.

The patients can’t make their own antibodies for a variety of reasons and therefore the antibody product that they’re given varies; Omrix has 3 antibody products currently in production.

  • IVIG (Intravenous immunoglobulin) is a general antibody product for patients that have been immunocompromised due to diseases or disorders. It’s currently only available in Israel, but Omrix is doing a combined Phase 1/2/3 to get FDA approval.
  • VIG (Vaccinia immunoglobulin) is used to treat patients that are experiencing complications due to small pox vaccinations.  As you can imagine, this isn’t a big market since not that many people are given the vaccine, and an even smaller number have complications.  But governments are paying for it (since it’s mostly military that get the vaccine), so Omrix did have $21.2 million in sales in 2006 from a UK government contract.  But this product might have wide ranges in sales depending on government contracts.  They are also developing a concentrated version of the product, HT-VIG, which would allow it to be administered as a shot instead of an hour-long intravenous infusion.
  • HBIG (Hepatitis B immunoglobulin) is used to prevent reinfection for patients that have a liver transplant after chronic HepB infection causes liver failure — it’s kind of a waste to reinfect the donated liver.

Omrix also has an antibody product in clinical trials:

  • WNIG (West Nile virus immunoglobulin), as you can probably guess, is for patients who have been infected with the West Nile virus. It’s in phase 1/2 trials and has orphan drug status which should help with competition if receives FDA approval.

While I would have figured that there was a greater market for Omrix’s biosurgery products, the immunotherapy product line actually had larger sales ($11.4 million) in the fourth quarter of 2006 than the biosurgery products ($4.3 million).  This is mainly due to the $6.0 million from the UK government contract for VIG.

I’ll look at the financials in more detail next time.

Omrix’s Biosurgical Products (OMRI)

Now I’m no surgeon, but I can guess that during surgery, there’s a lot of blood (actually, come to think of it, that’s part of the reason that I’m not a MD).  Generally speaking, bleeding isn’t a good thing; Omrix’s biosurgical products and pipeline are designed to stop the bleeding (herein referred to by it’s clinical name, hemostasis).

Now how do you promote hemostasis in surgery? Well, the same way you do if you cut yourself when you’re shaving:

  1. If it’s a small cut, you let the proteins in the blood form a clot (scab).  Essentially fibrinogen, a protein in the blood stream, combines with another protein in the blood stream, thrombin, to form a clot.  Omrix’s Evicel (marketed as Quixil outside the U.S.) is essentially purified fibrinogen.  Since it’s purified from human plasma, it contains naturally occurring proteins as part of its biological active component (BAC), which help form a clot that sticks to the wound better.  Omrix is also in phase 3 trials for purified thrombin, the other component of the clot, which results in a much slower hemostasis (preferred in some types of surgery).
  2. If the cut is a little bigger or won’t stop on its own, you put a bandage on it.  Omrix has designed a biodegradable patch that contains purified fibrinogen.  The patch, which is in phase 1 clinical trials, is designed for high bleeding situations, like the emergency room, where the high flow/pressure from a wound rips a fibrinogen induced clot right off.

From my reading, it looks like they don’t have a patent on fibrinogen.  Although they may have a patent on their purification process.  Since they’re in a highly competitive field, they need to give the doctors a reason to buy their brand over any others.  Omrix’s main advantage is that they purify fibrinogen out of human plasma while other competitors purify it out of cows, potentially causing the immune system to have to work overtime to fight off the perceived foreign infection.  They’ve also packaged the fibrinogen in an easy to use form that can be stored at 4 degrees Celsius (refrigerator) for extended periods of time resulting in reduced waste of the product.

Omrix’s other competitive advantage in that they are good at purifying proteins out of human plasma.  This same type of purification is used to create their passive imunotherapy product line, which I will talk about next time.

***********
My first article, a Take on Affymetrix, is up at The Motley Fool.  They’re trying to expand their biotechnology coverage, so here’s where you can find all their articles on stocks and personal finance although viewing them through the feed might be a better option since it will give you a little blurb that tells you what the article is about.

And grab my feed while you’re at it.

Writers Wanted

I’ve been hired as a freelance writer covering biotech companies for The Motley Fool, so posting frequency may drop off a little while I figure out my dual roles.  I think this blog has potential and I don’t want to see it die (actually I’d like to see it grow), so if there’s anyone out there who’s interested in writing analysises on babybiotechs.com, please let me know via e-mail (it’s in the about page).  The revenue sharing from the ads won’t pay the mortgage (unless you live in a trailer down by the river, then maybe it will cover it), but it will get you exposure, which might land you a job like it did me.

If any of the big boys want to promote this offer on their blogs, I’d be grateful.

Aside: The Investors Blog Network Festival featuring some great posts about investing is up at BioHealth Investor.

Background for Omrix Biopharmaceuticals

The review of Omrix was a requested by a reader. If you would like me to review a relatively new biotech stock, you can e-mail me at hotmail.com with the username biologyfool before the at sign. If you include the info on this page in the e-mail, your chance of the stock getting reviewed will go up exponentially since it’s a big pain in the butt to copy and paste this information; I do it because it gives us a place to begin and those that read the review later, a place to catch up.

I’m really looking forward to this review since they’ve actually got products. A P/E is so novel for this blog.

Basic Info

Stock symbol:OMRI
Website:http://www.omrix.com/
IPO date: 4/21/06 with a second offering 12/15/06
Total shares outstanding: 14.9 million including 3.9 million from the IPO and 1.7 from the second offering
Market Cap: $638 million as of 4/23/07
Other reviews:There’s quite a few here.

Drugs/Platforms

Drugs currently approved:

Evicel a fibrin sealant used as an adjunct to hemostasis in liver surgery in US
Quixil a fibrin sealant used as a general adjunct to hemostasis in Europe, Israel and several other countries.
IVIG an antibody product for treating immune deficiency and autoimmune diseases approved in Israel.
VIG an antibody based product for treating smallpox vaccination related complications.
HBIG antibodies against hepatitus B to prevent reinfection after liver transplant.

Drugs in trials:

Increasing Evicel’s indication label to include general surgical use in the US and Europe has completed phase 3 clinical trials and expecting FDA approval decision in the second half of this year and EU approval submission in the second quarter of this year.
Fibrin Patch being developed with Ethicon, a Johnson & Johnson company, for use in the Emergency room and surgery for stopping severe bleeding. Phase 1 trials have just begun.
Thrombin is a stand alone adjunct to hemostasis for general sergical use, primarily neurosurgery in phase 3 clinical trials, which is also being developed with Ethicon. Approval is expected in the second half of this year.
Aeris for lung volume reduction is in phase 2 trials.
IVIG is in combined phase 1, 2, and 3 trials for approval in the US
WNIG an antibody product for treating West Nile Virus is in combined phase 1/2 trials.

Drugs in development:

HT-VIG a high concentration form of VIG hasn’t started clinical trials, but presumably it would be a combined study since VIG is already approved.

Financials

Income: $23 million for 2006
Cash on hand: $81 million (as of the end of 2006) including $34.1 million from the IPO and $51.4 million
Burn Rate: None; remember their earning money! R&D was $3.3 million in 2006

Rosetta Genomics: Final decision, buy or hold off?

This is the sixth in a series of posts analyzing Rosetta Genomics stock.

The best thing that Rosetta Genomics has going for it is that it has a huge amount of intellectual property. They have patents on (or have licensed rights to) hundreds of miRNAs. Essentially, at this point, an investment in Rosetta Genomics is an investment in miRNAs. If you believe that miRNAs are useful for diagnostic tests or as targets for therapeutics, then you should invest in the (self described) leader of the industry.

The hardest part is determining how to value the stock. Since they have partners for almost every project and the details of the partnerships aren’t disclosed, it’s difficult to determine what the potential income is for the diagnostic tests they’re developing. (I’m ignoring the potential income from their therapeutics pipeline since that’s years away.)

That being said, I think there’s potential in miRNAs as a diagnostic test. I’ll predict that the first test to get approved will be for measuring the aggressiveness of a tumor and not for detection. The limiting factor, in my opinion, will be their ability to purify enough miRNAs to detect differences in the expression levels. Clearly it’s much easier to get enough cells for measuring miRNA levels in a resected tumor than getting enough miRNA from tumor cells that are sluffed off into the blood stream, which would be required for a blood test for cancer detection.  On the other hand, they (or at least their PR people) seem to think they’ve got it down.

I’m going to take a small stake in the company. I think it’s likely that there won’t be much movement on the stock (maybe a drift downward) until they announce that they are starting clinical validation of their first diagnostic product. It’s not clear how quickly that will occur and I don’t want to miss the boat, but I also don’t want to park a lot of money in a stock that’s moving sideways, so the position will be small. As of this writing it’s at $6.50/share which is below it’s IPO price of $7/share.  It’s been trading in the $6.50-$7.00 range for the last month, so I will try to buy on one of the dips.

Inhibiting the Inhibitor - miRNAs as Therapeutic Drug Targets

This is the fifth in a series of posts analyzing Rosetta Genomics stock.

Most drugs that target proteins work by inhibiting the protein’s function. It’s simply a function of biology; it’s much easier to design a drug that will interfere with a protein’s function than it is to make it overactive. But sometimes (many times actually), it would be nice to make a protein overactive in order to fight a disease. For instance, overexpressing a tumor suppressor might kill tumor cells. Sometimes this is possible if the protein has a natural protein inhibitor. By inhibiting the inhibitor, you can stimulate the protein whose function you want to increase.

Since miRNAs are natural inhibitors of protein expression, inhibiting them causes increased activity of the protein. In cancers, miRNAs are often overexpressed, so they make good potential drug targets. Rosetta Genomics is working with Isis Pharmaceuticals, who has experience with inhibiting RNA molecules in vivo, on miRNA inhibitors to treat liver cancer. The inhibition is carried out by complementary synthetic molecules that bind to the miRNAs and prevent them from binding to the mRNA, resulting in expression from those mRNAs. To date they have discovered 5 miRNAs that have elevated levels in tumor samples compared to normal tissue. They are currently trying to inhibit these miRNAs in tissue culture cells (in vitro) before they move into mouse models (in vivo). I’m a little worried that the level of miRNA inhibitors required for them to see an effect on tumor growth might be greater than is achievable in vivo, but Isis Pharmaceuticals has been able to inhibit miRNAs in the liver of mice, so perhaps my fears are unwarranted.

If anyone reading this is at the AACR meeting in LA this week, stop by Rosetta’s poster and get the current information on the project. Then leave a comment or e-mail me at hotmail.com with biologyfool before the @ with the scoop.

Rosetta Genomics is also working on miRNA inhibitors for infectious disease. Some viruses encode miRNAs and others cause overexpression of human miRNAs after infection. Both of these can serve as potential targets to attack the infection. For instance, they have demonstrated in vitro that the inhibition of Epstein-Barr virus (EBV) microRNAs inhibits viral replication. With collaborators (mostly in academia), they are also working on finding miRNA inhibitors to fight infection of HIV and hepatitis C virus.

All of their research on therapeutics is still in initial stages. Since microRNA inhibitors are fairly innocuous, Rosetta Genomics might be able to do a combined phase 1/2 trial. But even in that case, the therapeutics are still many years away. Hopefully some of their diagnostic test will gain approval and fund their clinical trials.