Micromet Inc.'s potential €120 million (US$161 million) development deal with Nycomed A/S - plus €5 million up front - jump-starts the preclinical MT203 program, giving the GM-CSF neutralizer better odds against a similar antibody already in Phase I/II trials against rheumatoid arthritis by KaloBios Pharmaceuticals Inc.

Shares of Micromet (NASDAQ:MITI) jumped 12.2 percent on the news, closing May 24 at $2.75, up 30 cents. MT203, like privately held KaloBios' unpartnered KB002, targets the cytokine granulocyte macrophage colony-stimulating factor, and MT203 is expected to enter the clinic next year. Both antibodies could work against such lucrative indications as RA, multiple sclerosis, psoriasis, asthma and chronic obstructive pulmonary disease.

There are differences, noted Micromet President and CEO Christian Itin. KaloBios' antibody is chimeric, whereas Micromet's is human - although what that means in practice remains to be seen, he acknowledged. "If you have a choice, you'd rather not be putting in a protein drug that has murine sequences, which is what KaloBios is doing," Itin said. Officials at KaloBios, of Palo Alto, Calif., could not be reached.

From Roskilde, Denmark-based Nycomed, Micromet stands to get reimbursements and milestone payments as the program moves along, plus royalties on sales of MT203 and any other products developed under the deal. Micromet mainly will be responsible for preclinical work and making MT203 ready for early trials. Nycomed carries the ball the rest of the way, commercializing the compound worldwide and reimbursing Micromet for MT203 expenses.

GM-CSF spurs production of granulocytes and macrophages by stem cells, and as a drug - Leukine (sargramostim), from Montville, N.J.-based Berlex Inc. - can help people with suppressed immune systems. But blocking the naturally occurring protein also might help in certain diseases, too. Another company wise to the approach is London-based AstraZeneca plc, which gained an early stage GM-CSF program in the $1.1 billion buyout of Cambridge Antibody Technology, though that compound targets the receptor rather than the ligand, Itin said.

He compared the growing GM-CSF research, which started in early 2000, to enthusiasm for drugs against tumor necrosis factor (TNF). "There are probably others that are going to pick it up," he said. Approved anti-TNF compounds include Enbrel (etanercept, Amgen Inc. and Wyeth Pharmaceuticals Inc.), Remicade (infliximab, Centocor Inc.), Humira (adalimumab, Abbott Laboratories). Although much work still needs to be done, Itin said the "big difference in the immunogenicity" between Remicade and Humira - with the latter superior - also might show up when Micromet's drug is compared with KaloBios'. Chronic ailments such as RA call for dose hikes over extended periods, he pointed out.

Anti-TNFs shut down T cells and B cells, "which takes care of one part of the immune system," Itin said, but the more chronic effects of RA, such as cartilage destruction, come mainly as a result of action by macrophages and other cells. "We were looking for specific ways to inhibit these cells," Itin said. "Obviously, [anti-TNFs] can't get there, and interleukin-1 can't really be specifically inhibiting those cell types, either."

At first, Micromet was "looking for ways to go after the other side of the equation," but investigation has shown - preclinically - that blocking GM-CSF could be not only a "very potent way of shutting down the innate arm of the immune system, but also seems to be able to influence the production of TNF as well," Itin said.

"We have to make the argument in the absence of clinical data, but the way we thought about [MT203] is that we should be at least complementary to anti-TNFs, and we may also be straight competitive" with them, he said, adding the decision on the first indication to try has not formally been made.

Around the start of the year, Nycomed finished its €4.6 billion takeover of Altana Pharma AG, the pharmaceutical arm of Altana AG, of Bad Homburg, Germany, which gave Nycomed plenty of know-how in the areas of inflammatory and respiratory disease, and made the firm "a really good fit" as a partner for Micromet, Itin said.

About a year ago, CancerVax Corp., of Carlsbad, Calif., and Micromet AG, of Munich, Germany, completed their merger, and changed the combined company's name to Micromet Inc., in a deal disclosed at the start of 2006.

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