Less than a year ago, Eli Lilly and Co. and Isis Pharmaceuticals Inc. signed a deal for Isis' antisense technology worth as much as $400 million. On Tuesday the companies expanded that deal, opening it up to include specific gene targets for cancer and adding to its total value.

Indianapolis-based Lilly licensed Affinitac (formerly ISIS 3521) in the initial agreement, a product in Phase III studies for non-small-cell lung cancer. That trial is ongoing, but what has been seen thus far prompted the growth of the deal. (See BioWorld Today, Aug. 23, 2001.)

"The reason for the expansion in the cancer area is that we are encouraged by the early clinical trial results with Affinitac," said Terra Fox, spokeswoman for Lilly. "We are interested in using antisense technology to reach cancer targets that are considered undruggable by other methods."

Frank Bennett, vice president of antisense research at Isis, said Lilly "saw an opportunity to expand its use of antisense into another indication."

The deal calls for work on several preclinical antisense compounds, including ISIS 23722, which are directed at cellular regulators of apoptosis. Bennett, calling ISIS 23722 "exciting from our prospective," said the compound is a late-stage research target Isis has been developing. The companies will collaborate on the research, and if the product heads into the clinic, Lilly would license it outright.

Overall, "the targets can be applied broadly, and the plan is to look broadly in a number of [cancer] indications," he said.

While unable to disclose the specifics of fiscal compensation, Bennett said the new deal "augments the financials" of the original agreement.

Affinitac is an inhibitor of protein kinase C-alpha. Its Phase III trials in non-small-cell lung cancer patients are survival studies, which makes projecting timelines for completion difficult, Bennett said. But the company expects to see data by late 2002 or early 2003.

Isis' alicaforsen (ISIS 2302), an ICAM-1 inhibitor, is in a Phase III trial in Crohn's disease patients. The company is planning to initiate a second Phase III trial in Europe in the near future. A new drug application filing would depend on the enrollment speed of both trials, but Isis said it anticipates the data should support a filing in 2004 or 2005.

Isis, of Carlsbad, Calif., has 13 antisense products in its development pipeline, including the two Phase III products and six in Phase II work.

When the initial deal was announced in August, Isis' stock (NASDAQ:ISIS) ended the day at $14.89, up nearly 50 percent. It closed Tuesday at $8.30, up 30 cents. The biotechnology sector, like other segments, has been battered as of late, but there is nothing wrong with antisense, Bennett said. And with $292 million in cash and short-term investments as of March 31, Isis has the financial means "to withstand the down market we have right now," he said.

"The story in the technology area is as good as ever," he said. "We continue to see the power in the technology and exploit it."