Washington Editor

Synta Pharmaceuticals Corp. and GlaxoSmithKline plc (GSK) are partnering to develop and commercialize a product for metastatic melanoma in a deal worth more than $1 billion.

Under the agreement, the companies will share the U.S. responsibility to develop and commercialize Synta's lead compound STA-4783, a first-in-class, small-molecule, oxidative stress inducer, for metastatic melanoma, the most deadly form of skin cancer.

London-based GSK will have exclusive responsibility for development and commercialization of the compound elsewhere.

The deal calls for Lexington, Mass.-based Synta to receive an up-front cash payment of $80 million. The biotech firm also will be eligible to receive potential milestone payments of up to $135 million for events leading to approval of STA-4783 in metastatic melanoma, further development and regulatory milestones of up to $450 million across various indications and up to $300 million in potential commercial milestone payments based on achieving certain net sales thresholds.

Synta will continue to fund all development of STA-4783 for metastatic melanoma in the U.S., and the companies will share responsibility and costs for development of the compound in other indications.

Under the terms, GSK also may buy up to $45 million of Synta's common stock.

"This is a transformational deal for the company," Synta CEO Safi Bahcall told BioWorld Today. "It gives us terrific resources to advance not only our first drug but all drugs in the company."

STA-4783, which has received fast-track status from the FDA, kills cancer cells by elevating oxidative stress levels beyond a breaking point, triggering programmed cell death.

Results of a 21-center, double-blind, randomized, controlled Phase IIb clinical trial in 81 patients with metastatic melanoma showed that STA-4783 in combination with paclitaxel doubled the median time patients survived without their disease progressing compared with paclitaxel alone.

STA-4783 is entering a pivotal, confirmatory Phase III clinical trial involving 630 patients with metastatic melanoma, Bahcall said.

The Phase III trial design mirrors that of the Phase II study, which includes an experimental arm of patients being administered STA-4783 in combination with paclitaxel and a control arm of patients receiving paclitaxel only, he explained.

The study is being conducted in 150 centers in at least 15 countries, Bahcall added.

"Our goal has always been to get the data from this Phase III trial to the FDA in the early part of 2009, which would put us in a position to get to market in two years from now," Bahcall said.

If the product achieves FDA approval, it would be the first novel, small-molecule drug for the treatment of metastatic melanoma to enter the U.S. market in 30 years, he noted.

"There's enormous desperation and a sense of urgency in the field for anything that can make a difference," Bahcall said.

About 60,000 people are diagnosed with melanoma annually, and nearly 8,200 people in the U.S. alone will die this year from the disease, according to the American Cancer Society.

Melanoma accounts for about 5 percent of all skin cancers but causes about 75 percent of all skin cancer-related deaths. The incidence of the disease has increased more rapidly than any other cancer during the past 10 years.

Since it released results of its Phase IIb study this spring that showed a "striking benefit" and "very promising signs of a survival advantage" for patients who received the drug, Synta has "seen a great deal of enthusiasm by investigators and patient groups" about STA-4783, Bahcall said.

Competition from firms seeking to partner on the drug was stiff, he declared.

The firm chose GSK for the deal, Bahcall said, because of the pharmaceutical giant's strength in the oncology market and the company's "clear enthusiasm, commitment and sense of urgency they felt for this program."

Synta also plans to study STA-4783 in Phase II trials in patients with other tumor types, he noted, adding that the firm will announce plans for those studies in the coming weeks.

Synta has four other compounds in preclinical and clinical development, two of which are targeting cancer and two for inflammation, Bahcall noted.

Shares of Synta (NASDAQ:SNTA) dropped 93 cents Wednesday, or 9 percent, to close at $9.32.