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CombinatoRx Publishes Data on Selective Amplification of Synergistic Combination Drug Candidate

-- In Vivo Research Demonstrates Amplification of Anti-Inflammatory Activity without Amplification of Side-Effects --

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan 28, 2009 - CombinatoRx, Incorporated (Nasdaq: CRXX) today announced the publication of new in vivo research in Arthritis Research and Therapy on a systems biology based strategy that selectively amplifies the anti-inflammatory activity of very low dose glucocorticoids in immune cells without modulation of pathways associated with glucocorticoid toxicity. This research, which was conducted by CombinatoRx scientists, demonstrates that the multi-target mechanism of low dose prednisolone (a glucocorticoid) combined with dipyridamole (a cardiovascular agent) creates a dissociated activity profile with an increased therapeutic window through selective amplification of glucocorticoid-mediated anti-inflammatory signaling. The combination suppressed release of pro-inflammatory mediators, including TNF-α, IL-6 and others, from human peripheral blood mononuclear cells and mouse macrophages. After 8 weeks of oral dosing in mouse models, the immune-specific amplification of prednisolone's anti-inflammatory activity by dipyridamole did not extend to glucocorticoid-mediated adverse effects including corticosterone suppression.

“This research demonstrates the utility of a systems biology approach to identifying novel therapeutics that are pathway, or multi-target, focused,” said Alexis Borisy, President and CEO of CombinatoRx. “Earlier attempts by the pharmaceutical industry at steroid dissociation using medicinal chemistry have shown mixed results because the anti-inflammatory activity and adverse effects of glucocorticoids do not break cleanly along mechanistic lines of transcription activation and repression. The systems biology approach leverages multi-target action to amplify glucocorticoid activity selectively within the unique network context of inflammatory cells, rather than attempting to dissect various aspects of glucocorticoid receptor biology.”

About CombinatoRx

CombinatoRx, Incorporated (CRXX) is pioneering the new field of synergistic combination pharmaceuticals. Going beyond traditional combinations, CombinatoRx creates product candidates with novel mechanisms of action, striking at the biological complexities of human disease. The CombinatoRx proprietary drug discovery technology provides a renewable and previously untapped source of novel drug candidates. The Company was founded in 2000 and is located in Cambridge, Massachusetts.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 concerning CombinatoRx, its product candidates, their clinical potential and its drug discovery technology. These forward-looking statements about future expectations, plans and prospects of CombinatoRx involve significant risks, uncertainties and assumptions, including risks related to the unproven nature of the CombinatoRx drug discovery technology, the Company's ability to initiate and successfully complete clinical trials of its product candidates, potential difficulty and delays in obtaining regulatory approval for the sale and marketing of its product candidates, the Company's ability to obtain collaboration partners or additional financing or funding for its research and development and those other risks that can be found in the "Risk Factors" section of the CombinatoRx Annual Report on Form 10-K on file with the Securities and Exchange Commission and the other reports that CombinatoRx periodically files with the Securities and Exchange Commission. Actual results may differ materially from those CombinatoRx contemplated by these forward-looking statements. These forward looking statements reflect management's current views and CombinatoRx does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release.

Posted: January 2009