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.

Filed under: Synta Pharmaceuticals (SNTA) | 4 Comments »

The only way to figure out the future value of a biotech company is to figure out how much they might make off of their drugs in clinical trials if they get approved by the FDA. Today, I’ll take a look at the markets for two of Synta’s potential drugs: STA-4784 and Apilimod. If you need to get caught up, check out the rest of the posts in the Synta Pharmaceuticals stock evaluation category.

STA-4784

STA-4784 will start phase 3 clinical trials for melanoma, but it’s mechanism of action (stimulating the production of oxygen radicals) isn’t specific to melanomas; in theory the drug should work for many different cancer types and in combination with many different current cancer treatments. It certainly has the potential to be a blockbuster after they get additional label indications (which I believe requires additional clinical trials, but doctors can choose to prescribe it off label before that).

STA-4784’s biggest competition for melanoma treatment will be with dacarbazine/DTIC and interleukin 2, the only two drugs currently approved by the FDA. It will also have to compete with drugs that are used off label by dermatological oncologists to treat melanoma including cisplatin, temozolomide, vincristine, carmustine, and melphalan.

The patents for STA-4784 expire in 2022 (and possibly later if they can get cancer type specific patents), so, if it’s approved in 2009, they will have quite a large window of exclusivity before they need to compete with generics.

Aplimod

Aplimod is probably not in as good of a position to compete since there are quite a few imunosuppressant drugs available to treat chronic inflammatory diseases including injectable TNF alpha-antagonists (Remicade, Enbrel, and Humira) and broadly immunosuppressive small molecule agents including corticosteroids and azathioprine.

There are also two injectable anti-IL-12 antibody drugs (CNTO-1275 and ABT-874) currently in clinical trials, but, since Apilimod is taken orally, it has an advantage over those products in my opinion.

The patents for Aplimod run out in 2021, but FDA approval is at least a couple of years away, so this one might not have as many years of exclusivity as STA-4784.

I’m having a horrible time trying to figure out how much the drugs that they would compete against currently make.  I can’t seem to find the size of the markets anywhere. Does anyone have an idea of where I can find this information?

Filed under: Synta Pharmaceuticals (SNTA) | 1 Comment »