This is a continuation of my evaluation of Synta Pharmaceuticals. You can find the first 3 posts in the Synta Pharmaceuticals stock evaluation category.

I won’t cover the rest of Synta’s drugs in too much detail since they are all relatively early in the pipeline, but here’s a synopsis on each:

STA-9090

STA-9090 is an inhibitor of the heat shock protein (Hsp90). Heat shock proteins in cells are responsible for making sure that other proteins fold correctly. Misfolded proteins are usually not functional, so inhibiting heat shock proteins will likely kill the cells. Many cancer cells have elevated levels of Hsp90, so this may be a way to kill cancer cells selectively. There is a lot of redundancy in the heatshock pathway, so I would be a little worried that lowering just one protein may have little effect on cell survival. On the other hand, Synta reports that STA-9090 has high toxicity (not a good thing) in preclinical animal studies, so maybe it does a good job at killing, but isn’t that specific. One advantage of attacking the heat shock proteins is that the drug can likely be used in conjunction with other treatments that affect other pathways, so it might not need to have that high of a kill rate to be effective. Synta expects to file an IND with the FDA in the first half of 2007.

STA-9584

Tumors require blood vessels to grow and even survive. If their network of blood vessels is cut off, the tumor can’t receive nutrients and the cells in the tumor will eventually die. Synta is developing a small molecule which disrupts existing vascular. This approach seems more promising than ant-angiogenesis drugs that just inhibit the formation of new vessels but can’t really kill the cells already in the tumor. The biggest thing to overcome will likely be selectivity (you don’t want to kill all your vascular system). I would imagine that they are planning on using it on tumors that can be injected into.

CRAC Channel Inhibitor

The Calcium Release - Activated Calcium (CRAC) channel is a protein complex on the surface of immune cells. CRAC channels allow calcium to enter the cells which causes activation of T-lymphocytes, mast cells, and other blood cells. The lack of activation allows for suppression of the immune system which could be used to treat graft-versus-host disease (GVHD), allergies, asthma and other immune disorders.

Ability to increase the pipeline

It’s really hard to analyze a companies ability to increase their pipeline. It’s a little bit of luck, and a little bit of skill, but the companies rarely give you a good picture of how much they’ve got of each. They’ve discovered 5 drugs in the 6 years since they were founded, so the rate of discovery seems pretty good. Some other thoughts:

They seem to use small molecules as drugs, which will almost always work better than biologicals (although harder, in my opinion, to find good candidates)

Their chemical library contains over 100,000 compounds for doing high throughput screens, but then again, so does everyone else.

Synta is large enough that they can do in vivo tests of the safety, efficacy, and pharmaceutical properties of candidate compounds in animal models. Not needing to rely on 3rd parties is a definite plus.

So, overall Synta’s preclinical pipeline looks OK. There’s nothing here to blow your pants off, but the drugs are all early in the pipeline. If I had to put my money on one of them, I’d bet on STA-9584, although the CRAC channel inhibitor looks promising as well.

With the analysis of the science for Synta done, next up at babybiotechs.com is the business side of Synta Pharmaceuticals. It may take me longer to plow through this area (since that’s not where my training lies) so please bear with me. I’ll try to keep to the same posting schedule, but the sections might be shorter.

Filed under: Synta Pharmaceuticals (SNTA)