West Coast Editor

Three academic scientists jointly won the 2004 Nobel Prize for research into ubiquitin ligases, and Rigel Pharmaceuticals Inc. is taking home an "award" of its own - a deal with Merck & Co. Inc. to investigate the new class of drugs for cancer therapies and others.

Unlike some arrangements in which "a small company does something and throws it over the wall," the Merck setup is "a highly collaborative deal," said Donald Payan, vice president and chief scientific officer of South San Francisco-based Rigel.

"They put a lot of value on the team here," he said. "It's not going to be a relay race." Rigel's stock (NASDAQ:RIGL) closed Monday at $28.72, up 62 cents.

Rigel gets cash up front and funding for research scientists for two and a half years, plus milestone payments for preclinical and clinical events. Analyst Mark Augustine with Credit Suisse First Boston in New York estimated the value of the research funding at $15 million. Whitehouse Station, N.J.-based Merck will handle worldwide development and commercialization of any resulting compounds, paying royalties to Rigel.

The deal is based on a number of new targets designated by Merck and do not include Rigel's current ligase targets. Rigel may nominate its own targets for inclusion in the effort, too.

Ubiquitin ligases are enzymes that regulate protein degradation within the cell, which can affect such functions as cell division, obviously a key element in fighting cancer.

In October, the Royal Swedish Academy of Sciences awarded the Nobel Prize in chemistry for "the discovery of ubiquitin-mediated protein degradation" to Israeli scientists Aaron Ciechanover and Avram Hershko, of the Israel Institute of Technology, and Irwin Rose, of the University of California at Irvine.

"There is competition," Payan acknowledged. "There is a lot of work all over the world right now in academic labs." On the company side, he pointed to Millennium Pharmaceuticals Inc., of Cambridge, Mass., which "historically had a large effort in this area."

Millennium's Velcade (bortezomib) for multiple myeloma was approved in May 2003.

"It's a small molecule that blocks the proteasome, which is the final disposal apparatus for proteins that are destined to be chewed up," Payan noted. "We're going further upstream to look at how the system is fine-tuned in selected disease mechanisms."

Last year, Newtown, Pa.-based AxCell Biosciences Corp. entered a research collaboration with Celgene Corp., of Warren, N.J., to study the role of ubiquitin ligases in cancer and inflammation. AxCell is a subsidiary of Princeton, N.J.-based Cytogen Corp. (See BioWorld Today, Jan. 22, 2003.)

Rigel, Payan said, has been working in the area for three or four years.

"We have two issued patents that cover ubiquitin ligase screening in the U.S., and that means pretty much anyone who wants to screen a ubiquitin ligase has to come to us," he said, adding that he is "aware of some of the large pharmas that have been sniffing around, trying to get some traction in this field, [which is] where the kinase field was 10 to 15 years ago."

Ubiquitin ligases for cancer probably won't be tested in humans for another three to five years, Payan said. "I don't think it's going to be earlier than three years," he told BioWorld Today, adding that "we have molecules of our own, other ligases in inflammation, that are not part of the [Merck] deal."

Rigel last made news over the summer when favorable data from a Phase II study with its allergic rhinitis compound, R112, sent the firm's stock soaring more than 37 percent. The drug, discovered by Rigel, binds to an intracellular target (syk, a kinase that regulates IgE receptor signaling) in mast cells and interrupts the signal from the IgE receptor, blocking all major pathways triggered in an allergic attack. (See BioWorld Today, Aug. 3, 2004.)

Raul Rodriguez, chief operating officer for Rigel, told BioWorld Today the company is talking with would-be partners for lead product R112 now and could have news by the end of the year.

Next year, the firm will conduct more trials, either expanded Phase II or Phase II/III studies. "We need to test it over longer period of times and different dosing regimens," he said.

Payan noted R112's "remarkably rapid onset of activity. We want to nail that down, because it could be an important strategic advantage over steroids. We'd like to know what is the maximum response we're going to see over time," he said, adding that a head-to-head study with "one of the standard nasal steroids" could be in the offing.