Washington Editor

Ligand Pharmaceuticals Inc. and Eli Lilly and Co. agreed to extend their collaboration built around developing peroxisome proliferation activated receptor modulators for Type II diabetes, cardiovascular disorders and possibly other metabolic diseases.

The decision to extend the agreement to November 2004 marks the second time the companies have continued the deal originally signed in 1997. (See BioWorld Today, Oct. 21, 1997.)

Lilly has the authority to extend it one more time, Michael Watts, director of investor relations and corporate communications at San Diego-based Ligand, told BioWorld Today.

So far, the collaboration has netted three products, all of which are in clinical trials.

The most advanced is a product called LY818, a peroxisome proliferation activated receptor (PPAR) being studied in Type II diabetes and metabolic diseases.

When LY818 reached the Phase II level in March, Lilly, of Indianapolis, paid Ligand a $1.5 million milestone.

Lilly pays the research and milestone funding (up to $10 million per product) in exchange for exclusive worldwide marketing rights. Lilly also is responsible for development and registration of products emerging from the deal.

Revenues from Lilly thus far include $14.1 million in 2002, $13.7 million in both 2001 and 2000, and $9.1 million in 1999.

The collaboration has produced two other Phase I products. The most advanced is LY929, which entered Phase I in mid-2002 for the treatment of Type II diabetes, metabolic diseases and dyslipidemias. The other is LY674, which entered Phase I late last year for dyslipidemias. According to the companies, additional product candidates will follow.

In a prepared statement, Andres Negro-Vilar, Ligand's senior vice president for research and development and chief scientific officer, referred to the deal as the company's most prolific research collaboration. "With LY818 in Phase II studies, LY929 and LY674 in Phase I and other PPARs moving rapidly toward the clinic, we have an extraordinary opportunity to bring to market products with enhanced activity and broader therapeutic profiles for Type II diabetes and cardiovascular disorders."

Also, he said, recent scientific publications have elucidated the key role that members of the PPAR family play in obesity and associated disorders.

PPARs are a subfamily of intracellular receptors that regulate glucose and lipid homeostasis. They are important in enhancing cellular responses to insulin, and in fat tissue stores and metabolism.

The original agreement between the companies was meant to include development of Targretin, an oral and gel product used for treating all stages of refractory cutaneous T-cell lymphoma. Lilly dropped Targretin to focus on diabetes, and Ligand went on to win FDA approval of the product. (See BioWorld Today, Feb. 19, 1999; Dec. 30, 2000; and June 30, 2000.)

Currently, Ligand is conducting Phase III studies of Targretin in non-small-cell lung cancer.

Elsewhere in the pipeline, Ligand and its partners are studying second-generation selective estrogen receptor modulators in various Phase III trials. The candidates are lasofoxifene, a product being studied by New York-based Pfizer Inc. in osteoporosis and breast cancer prevention; and bazedoxifene and bazedoxifene/Premarin, products being evaluated separately by Madison, N.J.-based Wyeth in osteoporosis and menopausal symptoms, respectively.

Ligand's stock (NASDAQ:LGND) closed Friday at $8.99, down 17 cents.