This is part two of the Investment report for Synta Pharmaceuticals.

Melanomas

Synta’s main drug is called STA-4783 which treats melanomas. Melanomas (skin cancer) affect 1 in almost 60 adults in the US in their lifetime. It affects over 60,000 people in the US every year and causes approximately 8,000 deaths. Since melanomas are on the surface and easily accessible, small tumors that haven’t spread (stages 0, I, and II) can be removed with with surgery. Drugs are mainly be used to treat stages IV and V cancers which have spread (become metastatic). Median survival for the late stage metastatic cancers is 6-9 months, so there is certainly a need for drugs to treat this stage of cancer.

STA-4783

Cancer cells often have higher levels of oxygen in them since they are actively growing. Once inside a cell STA-4783 acts on enzymatic pathways that increase oxygen radicals. These pathways change O₂ into O* (with extra electrons). The O* cause damage within the cell which results in an increased expression of heat shock proteins. The heat shock protein 70 (Hsp70) is expressed on the surface of the cell which stimulates the immune system (NK cells) to attack the tumor. Additionally, the O* can damage proteins, the DNA backbone, and cell membranes which, with enough damage, can cause the cell to initiate it’s own programed cell death (apoptosis). Because cancer cells typically contain more oxidative stress, the STA-4783 can act selectively by pushing cancer cells beyond the threshold required for programed cell death.

STA-4783 is administered intravenously (while the patient is hooked up to an IV) in combination with paclitaxel (Taxol), a microtubule inhibitor. Early phase I and II trials with 300 patients suggest that it works independently of the taxanes and that their combined effect is more than either of them individually (they have a synergistic effect). The early clinical data suggest that STA-4783 has low toxicity. Double blind phase 2b trials demonstrate a doubling of progression-free survival (PFS). They are setting up a large phase 3 trial right now and the FDA has given them fast track status for STA-4783, so hopefully a decision on approval will be quicker than normal.

Melanomas aren’t the only cancer cells with elevated oxygen levels. This drug therefore has potential to be used to treat other cancers. Synta reports pre-clinical data that suggests it is at least partially effective on breast, lung, lymphoma, and colon cancer cells as well. Additionally it can be combined with other treatments that are currently used (assuming they don’t act on the same oxygen radical stimulating pathway). They are planning to start phase two trials for other cancers (ovarian and/or non-small cell lung cancer) in 2007.

Next up on Babybiotechs.com: Synta’s IL-12/IL-23 Inhibitor, STA-5326

Filed under: Synta Pharmaceuticals (SNTA)