By Randall Osborne

Vertex Pharmaceuticals Inc. has struck a deal with Kissei Pharmaceutical Ltd. to collaborate on Vertex's p38 mitogen-activated protein (MAP) kinase program, which treats inflammatory and neurological diseases. To Vertex, the agreement could mean as much as $22 million.

Kissei will provide a $4 million down payment, $11 million more over a three-year period, and additional funds when a clinical candidate enters development.

Vertex, of Cambridge, Mass., is developing drugs based on small molecule inhibitors of p38 MAP kinase, an enzyme associated with the inflammation and death of cells.

Inhibitors of MAP kinase block production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). These are cytokines that, in high levels, are associated with an array of diseases, including rheumatoid arthritis, osteoporosis and atherosclerosis. They also play a role in stroke-related cell death and in diseases such as Alzheimer's and Parkinson's.

The pact with Kissei, of Matsumoto, Japan, comes just over a week after Vertex announced the end of another partnership. That pact, with Alpha Therapeutic Corp., of Los Angeles, was to develop an oral treatment for disorders such as sickle-cell anemia (see BioWorld Today, Sept. 3, p. 2).

Kissei, along with Glaxo Wellcome P.L.C , of London, also is collaborating with Vertex on development of the HIV protease inhibitor VX-478.

In June, Vertex teamed with Eli Lilly and Co., of Indianapolis, to develop protease inhibitors for treating the hepatitis C virus. Lilly agreed to provide as much as $40 million and made a $10 million equity investment in Vertex.

The Kissei and Lilly partnerships represent "a new kind of deal for us," said Vertex spokeswoman Lynne Brum. "We have a significant manufacturing option as well as a co-promotion option. We can capture a higher proportion of the sales dollar in comparison with the royalty deal. [With Kissei,] we can participate in the manufacture of bulk drug supply for Japan and the Far East."

Another Vertex collaboration is with BioChem Therapeutic Inc., a wholly owned subsidiary of BioChem Pharma Inc., of Laval, Quebec. Under way is development of a multidrug resistance inhibitor that would re-sensitize cancer patients' tumor cells to chemotherapy treatments. A Phase II clinical trial has begun to evaluate the drug Incel (biricodar dicitrate), also known as VX-710. Incel will be administered with paclitaxel to about 55 patients whose ovarian cancer is not responding to paclitaxel alone. About 27,000 women, most of them near age 60, are diagnosed with ovarian cancer every year. About 15,000 of them die annually.

Phase I/II results showed Incel reduced to half the necessary dose of paclitaxel, a widely used antitumor agent. *