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With five drugs in proof-of-concept Phase IIa trials and a sixth ready to enter next year, CombinatoRx Inc. filed for an initial public offering that would raise up to $100 million, though the firm did not specify the number of shares or price per share in its prospectus.

The Boston-based firm wants to trade on Nasdaq under the symbol "CRXX." This spring, CombinatoRx raised $30 million in its third financing round to boost its substantial clinical and preclinical pipeline. (See BioWorld Today, March 4, 2004.)

As its name suggests, the company is focused on pairing approved drugs for diseases, even in cases where neither drug targets the particular condition on its own. The firm's combination high-throughput screening sorts pair-wise combinations from a library of about 2,000 drugs approved in the U.S., Europe and Japan, testing them in cell-based assays that correspond to varying major disorders.

In the immuno-inflammatory area, CombinatoRx has CRx-102, a selective steroid amplifier (SSA) made of prednisolone and dipyridamole; CRx-119, a similar drug that combines prednisolone with amoxapine; and CRx-170, yet another SSA comprising two undisclosed drugs. Others are CRx-140, an enhanced calcineurin inhibitor that brings cyclosporine together with an undisclosed enhancer agent, and CRx-150, a synergistic cytokine modulator pairing two undisclosed drugs.

Those compounds already are in Phase IIa studies. Expected to enter next year is CRx-139, an SSA consisting of prednisolone and an undisclosed selective serotonin reuptake inhibitor.

The SSAs contain a reduced-dose steroid combined with a different second active ingredient that, given with the reduced-dose steroid, apparently enhances the reduced-dose steroid's anti-inflammatory and immuno-modulatory activity without upping the adverse side effects. CombinatoRx said the mechanism of steroid enhancement for each SSA is different, so each product candidate might be useful in treating a separate disease.

Calcineurin inhibitors, such as CRx140, are immuno-modulatory compounds used broadly in organ transplantation to prevent rejection. The oral synergistic cytokine modulator, CRx-150, using two compounds not currently deployed against immuno-inflammatory diseases, might work against the likes of RA, psoriasis, inflammatory bowel diseases and others.

In oncology, the company has CRx-026, a dual-action antitumor agent made of chlorpromazine and pentamidine, in Phase I/II trials, along with some preclinical candidates. In the metabolic area the firm has in preclinical testing diabetes candidates that pair undisclosed compounds.

CombinatoRx lists about $40.3 million in cash, cash equivalents and marketable securities in its prospectus.

SG Cowen & Co. LLC in New York is acting as sole book-running manager, with San Francisco-based Pacific Growth Equities LLC as co-lead manager. SunTrust Robinson Humphrey, of Atlanta, and A.G. Edwards, of St. Louis, are co-managers.

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