By Matthew Willett

Cambridge Antibody Technology plc said Thursday it and Genzyme General took the lead in the race to develop and commercialize antibodies for TGF-beta, antibodies that could have therapeutic values ranging from cancer to fibrosis to wound closure.

Their broad collaboration to develop and commercialize human monoclonal antibodies, two of London-based CAT's and one of Cambridge, Mass.-based Genzyme's, encompasses all indications other than ophthalmic uses, including small-molecule antagonists, which CAT will license to Genzyme for milestones and royalties.

The deal is for revenue sharing on commercialized products, and Genzyme will make a $20 million equity investment in CAT, buying it a stake of about 1 percent in CAT, for CAT shares at #44.59 (US$65.15) apiece.

CAT Medical Director David Glover said the debate to compete or to collaborate with Genzyme ended when it became obvious that collaboration would carve a solid leadership position.

Between them, the companies have MAb candidates that act on all three transforming growth factor-betas with therapeutic potential.

CAT's two therapeutics involved in the deal are advanced candidates, but are restricted by the TGF-beta varieties they modulate. CAT-152 and CAT-192 modulate TGF-beta 2 and TGF-beta 1, respectively. Genzyme's 1D11, also on the table in this deal, modulates all three TGF-betas.

CAT's TGF-beta 1 modulator, in fact, completed a Phase I trial evaluating safety in normal volunteers earlier this year, and CAT-152 yielded positive results in a Phase I/IIa trial evaluating it for efficacy in treatment of post-operative scarring in patients undergoing surgery for glaucoma.

A multicenter Phase II trial for CAT-152 is under way, and CAT retained rights to ophthalmic indications for the compounds involved in the collaboration.

Other therapeutics from the collaboration probably won't move into the clinic for another five years, Glover said.

"One of the things we were looking at is whether to compete with each other, and we knew we were ahead, about two years ahead, but the result was this collaboration and pooling our expertise and intellectual property and product candidates," Glover told BioWorld Today. "We believe that with those three candidates we can cover clinical situations where blocking TGF-beta 1 is appropriate, where blocking TGF-beta 2 is appropriate and where blocking TGF-beta 1, 2 and 3 is appropriate."

CAT takes a weighted revenue from the deal, having offered more technology and more advanced research to the collaboration, according to Glover, but Genzyme officials said theirs is a profitable role as well.

"There's a great overlap of technology in the companies with the core technologies from each company on TGF-beta itself and what controls it," Genzyme General Vice President of Corporate Development Alan Walts said. "It made a great deal of sense to combine forces and collaborate to look at human antibodies."

Though there are other modulatory avenues for regulating transforming growth factor-beta, including antisense technology and small-molecule therapies, the companies both said MAbs from phage display identification processes are the most accepted and the most promising.

"There are other approaches that could be used. Small molecules are one of those areas that have been explored," Walts said. "Antibodies are well known in the industry, and have demonstrated commercial success in other areas. It's a proven technology."

And the technology has broad reach in the clinic. Glover said the function of TGF-beta in the body is wide.

"TGF-beta is a molecule that has many activities, some good and some bad," he said. "When you produce excess TGF-beta in any part of the body, it leads to the production of excess scar tissue, fibrosis in internal organs."

Fibrosis often causes organ transplant situations in patients with cirrhosis of the liver or fibrosis of the kidneys or lungs. TGF-beta inhibition could aid in treatment of early stage fibrosis, in addition to other indications.

"Outside fibrosis are certain forms of cancer, where TGF-beta serves to promote growth of a tumor or promotes angiogenesis, the formation of new blood vessels. It fuels tumor growth or protects the tumor from attack so the blocking of TGF-beta may have application in certain forms of cancer," Glover said.

Beyond cancer, even, he added, are the ophthalmic indications of a TGF-beta antagonist antibody through its potential to inhibit scarring.

"Paradoxically, on the surface of the skin or on the eye, for example, TGF-beta serves to slow surface healing, and if we can block it we can accelerate healing of the skin and can promote rapid healing," Glover said. "There are a huge number of applications here, and that's another reason behind having a partnership. One could exploit this on one's own, but it would take forever and take tremendous resources. We'll have a better opportunity to take advantage of it with a partnership."

That advantage is an obvious and far-reaching one, Glover said.

"We're first, second and third, basically," he said. "I don't believe there are any other monoclonal antibodies against TGF-beta in development."

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