By Brady Huggett

Neurocrine Biosciences Inc. topped itself by signing a research, development and commercialization agreement with GlaxoSmithKline plc for corticotropin-releasing factor receptor antagonists, calling it the ¿largest collaboration in Neurocrine¿s history.¿

Financial details on the deal were limited, but a trip down Neurocrine¿s collaboration hallway reveals trophies like the 1996 $74 million deal with Eli Lilly and Co., of Indianapolis; the 1999 $78 million agreement with Wyeth-Ayerst Laboratories; and the $100 million alliance with Tokyo-based Taisho Pharmaceuticals Ltd., revamped in late 2000. Those deals can¿t compare to what Neurocrine has accomplished now, said its president and CEO, Gary Lyons. (See BioWorld Today, Oct. 22, 1996; March 4, 1999; and Dec. 13, 2000.)

¿This is much larger than those,¿ he said. ¿It¿s the best deal we have done.¿

Centered in the collaboration is Neurocrine¿s lead corticotropin-releasing factor (CRF) receptor 1 antagonist, NBI-34041, currently in Phase I development for anxiety and depression. Lyons offered up how that compound may progress, but tempered his remarks with the reminder that a steering committee will have the final say.

¿The multidose Phase I trial should start next month and we should have data by year¿s end, and then rapidly move into Phase II early next year for both indications,¿ he said.

What the companies did release was that Neurocrine will receive up-front fees and early milestone payments totaling $25.5 million. It also will get annual fees for four years ¿ with an option for a fifth year ¿ and is eligible to receive three-pronged milestone payments, based on the application of CRF antagonists in the gastrointestinal and mood disorder areas, as well as an undisclosed area. One compound could conceivably work through more than one area, Lyons said. Also, there are separate milestones for each product that makes its way into development for each affliction, a key for San Diego-based Neurocrine.

¿That was important to us,¿ Lyons said. ¿We didn¿t want to look at this as an outlicensing, but as an active research collaboration.¿ That meant finding someone to accept the CRF-R1 and CRF-R2 antagonists on the merits of both their use in mood disorders as well as their activity in gastrointestinal diseases.

¿We went out and narrowed the field down substantially,¿ Lyons told BioWorld Today. ¿We wanted someone that was guaranteed to focus on the irritable bowel side of things as well as [mood disorders]. Glaxo was equipped to do that.¿

GlaxoSmithKline, of London, saw a chance to break into a burgeoning field.

¿This is an exciting development because we are talking about an entirely new class of compounds,¿ Mary Anne Rhyne, spokeswoman for GlaxoSmithKline, told BioWorld Today. ¿I believe this collaboration has the potential to make the most of both companies¿ strengths, to the ultimate benefit of patients.¿

That new class of compounds, Lyons explained, governs how a person reacts to stress.

¿CRF is a master molecule that regulates the body¿s response to stress,¿ he said. ¿What we have done is clone the CRF receptors that we own exclusively and we have developed drugs that block those receptors. The advantage is, we believe this neurotransmitter is the most direct route to mood disorders, so we are hopeful this will be a first-line therapy. Until this is validated in a Phase II trial, we can¿t definitively say that, but we feel that way and obviously so does Glaxo.¿

Glaxo feels that way enough to designate two of its eight Centers of Excellence toward the collaboration, one located in Verona, Italy, and the other being its GI Center of Excellence in the United Kingdom, Lyons said.

Underneath NBI-34041, Neurocrine has secondary compounds as support.

¿Typically, we move three to five compounds into backup status so we can compare those among themselves and to the clinical candidates to tease out differences,¿ Lyons said. ¿Assuming all goes well, we would move the best of those into Phase I as well, in the first part of next year.¿

Looking ahead, Lyons laid out what he would like for the end result of the collective work.

¿What we would hope to see is multiple components in various stages of development for anxiety and depression, as well as irritable bowel,¿ he said. ¿And we would like to have proof of concept on CRF-R2 antagonists.

¿We think this will be the largest CRF effort in the world,¿ he added.

Neurocrine¿s stock (NASDAQ:NBIX) dropped $1.68 Tuesday to close at $32.77.

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