Assistant Managing Editor

Amgen Inc. is expanding its early clinical pipeline with the addition of a CCR4 antibody licensed from Kyowa Hakko Kogyo Co. Ltd. in exchange for $100 million up front and up to $420 million in milestones.

The deal, set to close early next quarter, gives the Thousand Oaks, Calif.-based biotech worldwide rights, except for certain Asian areas, to KW-0761, a humanized antibody targeting CCR4, a chemokine receptor that binds to the TARC and MDC ligands and helps regulate T-cell migration. Developed using Kyowa's Potelligent technology platform, which is designed to enhance the activity of antibodies, KW-0761 already has shown some promising results in preclinical and Phase I testing.

"We were impressed with the studies [Kyowa] had done on this molecule," said Anne McNickle, senior manager of corporate communications at Amgen. She cited preclinical results demonstrating the ability of the drug to deplete CCR4-positive T cells in lymphoma and leukemia.

And in a Phase I study in healthy volunteers with seasonal allergic rhinitis, "a single dose of 0.003 mg/kg [of KW-0761] showed marked reduction of CCR4-positive T cells and Th2 cytokine level," she told BioWorld Today.

Since CCR4 is found mainly on the Th2 (T-helper type 2) cells and regulatory T cells in normal conditions, it is implicated in both inflammatory diseases and in cancer. Terms of the licensing deal grant Amgen immediate rights to KW-0761 in non-oncology indications and allow the company the option to expand into oncology following Kyowa's completion of a Phase IIa trial. In that case, Amgen would reimburse Kyowa for development costs.

Kyowa has started Phase I testing in Japan with KW-0761 in adult T-cell leukemia and lymphoma and adult peripheral T-cell lymphoma patients, and "to date," McNickle said, "several subjects have shown clinical response."

Tokyo-based Kyowa will retain rights to the drug in Japan, China, Korea and Taiwan. In addition to the up-front and milestone payments, the company would receive from Amgen double-digit royalties on any product sales.

For Amgen, the latest in-licensing deal "falls right in line with our current strategy," McNickle said. "The fact that the molecule has shown activity in inflammation and oncology puts it right in the middle of our core areas."

The firm's pipeline includes up-and-coming drugs Nplate (romiplostim), set to be reviewed by an advisory panel this month for approval in idiopathic thrombocytopenic purpura, and the much anticipated denosumab, which only last month reported positive data from a nonpivotal trial, showing a 40 percent improvement in bone mineral density in osteoporosis patients over Merck & Co. Inc.'s Fosamax (alendronate). Additional denosumab Phase III data are expected later this year.

A Phase III trial is ongoing with motesanib diphosphate in first-line non-small-cell lung cancer, with additional Phase II programs in thyroid and breast cancers. That drug, an anti-angiogenic compound that targets the vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, became part of Amgen's potential $1 billion deal signed last month with Takeda Pharmaceutical Co. Ltd. (See BioWorld Today, Feb. 5, 2008.)

The company also has multiple Phase II programs under way targeting indications such as cancer, Type II diabetes, asthma and rheumatoid arthritis.

The Kyowa deal is not expected to impact Amgen's financial guidance for the year. The company anticipates 2008 capital expenditures to total about $1 billion and projects annual earnings per share to fall within the $4 to $4.30 range. As of Dec. 31, its cash and marketable securities came to $7.2 billion.

Amgen's stock (NASDAQ:AMGN) closed Thursday at $44.24, down $1.01.