A preclinical program focused on Aurora kinase inhibitors brought Rigel Pharmaceuticals Inc. its fifth oncology deal, this one signed with Serono SA and worth up to $160 million.

Geneva-based Serono gains an exclusive license to develop and commercialize product candidates from the program everywhere, except Japan - although Serono could include that region at any time within two years. Rigel's lead candidate, R763, could move into clinical trials in 2006 if the company files an investigational new drug application as planned in December.

"For Rigel, this is a very important deal. It's our largest deal to date, and it's for a project that's the most advanced to date," said Raul Rodriguez, the South San Francisco-based company's executive vice president and chief operating officer. "This is a program that we think has tremendous potential and so we wanted to have a very aggressive partner. This amount of money is tremendous for us."

Terms call for Rigel to receive $25 million in initial payments - a $10 million license fee and a $15 million equity purchase at a premium to the market price that will give Serono less than a 3 percent stake in the company. Additional development and sales-based milestone payments for R763 bring the total value of the deal up to $160 million, not including royalties.

In early studies, R763 has been shown to inhibit proliferation and trigger apoptosis in several tumor cell lines, including those found in the cervix, lung, pancreas and prostate. With the agreement, Serono will cover all further development and commercialization costs of R763, as well as other product candidates that come out of the program.

"We're going to file the IND - Rigel is responsible for that effort in December of this year, which means in the first half of next year we could conceivably start trials," Rodriguez told BioWorld Today. He expects Serono will keep the same development timeline. "They wouldn't be paying this much money for a program if they were going to sit on it," he added. "They're going to be aggressive with it."

When Aurora kinase is overexpressed, it can cause cells to develop an abnormal number of chromosomes. At elevated levels, it is associated with cancers of the breast, bladder, colon, ovary, head and neck, and pancreas. By inhibiting it, a compound like R763 can arrest cell division and promote apoptosis. Rigel discovered R763 using its cell-based PAD assays applied to tumor cell lines.

"We are going to have the second most advanced Aurora kinase to go forward," Rodriguez said. "We have a product that is very potent and more selective, and ours is both oral and [intravenous], and the other one that's ahead of us is just I.V."

Vertex Pharmaceuticals Inc., of Cambridge, Mass., and partner Merck & Co. Inc., of Whitehouse Station, N.J., started a Phase I study of its Aurora kinase inhibitor VX-680 in January. The study is evaluating the product's safety and tolerability when administered in multiple cycles to patients with solid tumors refractory to prior chemotherapy treatment. Vertex and Merck signed their deal in June 2004. (See BioWorld Today, June 23, 2004.)

Also working in the Aurora kinase space are Sunesis Pharmaceuticals Inc., of South San Francisco, and Avalon Pharmaceuticals Inc., of Germantown, Md., to name a few.

While Serono is well known for its work in reproductive health, it has products positioned in the neurology, metabolism and growth and psoriasis markets. Only recently has it begun to establish new therapeutic areas of focus, including oncology. The company, which had worldwide revenues of $2.5 billion in 2004, currently has 30 ongoing development projects.

If R763 reaches the market, it could have blockbuster potential for Serono and Rigel, because it appears to work in so many different types of cancer.

"Taxotere and Taxol have been used in an equally broad number of tumor types as this," Rodriguez said, "and they have had well over $1 billion in sales."

In the pipeline, Rigel has three product development programs, including R763 for cancer, as well as R112 for allergy and asthma, and R406 for rheumatoid arthritis.

The Serono deal is its fifth collaboration in oncology, which is added to partnerships signed with New Brunswick, N.J.-based Johnson & Johnson on cell cycle inhibition; Basel, Switzerland-based Novartis AG on anti-angiogenesis targets; Tokyo-based Daiichi Pharmaceutical Co. Ltd. on a specific ubiquitin ligase target; and with Merck on various ubiquitin ligase targets. (See BioWorld Today, Jan. 15, 1999; Aug. 1, 2001; Aug. 13, 2002; and Nov. 16, 2004.)

Rigel also entered a deal with New York-based Pfizer Inc. earlier this year focused on preclinical work with IgE receptor inhibitors in respiratory mast cells to treat allergic asthma and other diseases. (See BioWorld Today, Jan. 21, 2005.)

Pfizer holds an option to license Rigel's Phase II rhinitis drug, R112. In August, the company enrolled the first patient in a 375-patient study comparing the compound with placebo and Beconase AQ (beclomethasone) nasal spray over a seven-day period. The trial should be complete in early December. Rigel also completed a Phase I study earlier this year of R788, its solid oral form of R406 (an oral liquid), for rheumatoid arthritis. A Phase I/II trial in RA patients is expected to begin in the first half of next year.

Rigel's stock (NASDAQ:RIGL) rose 27 cents Tuesday to close at $23.31.