LONDON ¿ Celltech Group plc said partner Merck & Co. Inc. is taking Celltech Group plc¿s second-generation phosphodiesterase-4 inhibitor into Phase II development as a novel oral treatment for both asthma and chronic pulmonary disease.

Peter Allen, chief financial officer, told BioWorld International, ¿Commercially speaking, this could be huge. It is a product that would be the follow-on for Singulair, a Merck drug selling more than $1 billion. Our expectations [for the PDE4 inhibitor should] be similar.

¿We have got a good royalty rate and also have the possibility of co-investing, which we will look at when Phase II is complete,¿ he said. Celltech will receive double-digit royalties on worldwide sales, and can obtain a share of the profits by contributing to Phase III development costs and foregoing part of the royalty entitlement.

Celltech signed the PDE4 collaboration with Merck in 1994. The deal included #31.5 million (US$45.6 million) in milestones, of which #15.5 million has been received to date. Allen would not comment on whether moving the compound into Phase II would trigger a further milestone payment.

First-generation PDE4 inhibitors failed because they caused nausea and emesis. Celltech¿s inhibitors are free of these side effects. Clinical proof of concept was demonstrated in Phase IIa trials of CDP 840, a PDE4 inhibitor that was free of emetic side effects but did not show great efficacy. Allen said the compound Merck is now taking into Phase II is more potent.

Celltech, based in Slough, UK, has a second collaboration on PDE4 inhibitors in asthma with Schering-Plough Corp., which is currently in Phase I. The collaboration was set up with Chiroscience plc prior to Celltech¿s takeover of Chiroscience.

At the same time, Celltech said it is halting development of CDP 860 in the treatment of restenosis, saying results of a pilot Phase II study involving 145 patients did not justify its further development. ¿With restenosis, even if CDP 860 worked well you are up against some very large clinical trials, because improvements brought about by coated stents make it more difficult to show efficacy,¿ Allen said.

CDP 860 is an antibody fragment that binds specifically to the platelet-derived growth factor beta receptor, and recent research suggests inhibition of this receptor may provide a novel anticancer strategy. As a result Celltech plans to begin a Phase II study in 2002 assessing CDP 860 in solid tumors, in combination with standard chemotherapy.

Celltech also announced two new antibody-based compounds are entering clinical trials in 2002. CDP 484, an antibody fragment that blocks the effects of the pro-inflammatory protein interleukin-1-beta, will be progressed in rheumatoid arthritis and other immunity-related and inflammatory disorders. Neutralization of IL-1-beta as an effective treatment for rheumatoid arthritis is supported by the recent approval of Amgen Inc.¿s Kineret. Kineret has a short half-life and requires daily injection, while CDP 484 is pegylated and is expected to have a long duration of effect.

CDP 791, which blocks a growth factor receptor involved in angiogenesis in solid tumors, will be developed as a novel cytostatic agent.

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