Pixantrone Shows Activity in a Preclinical Study of Experimental Autoimmune Myasthenia Gravis (EAMG)

Results reported in The Journal of Immunology

SEATTLE, February 11, 2008 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) announced that pixantrone was shown to reduce the severity of clinical manifestation in the animal model of the autoimmune disease myasthenia gravis (MG). MG is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body due to autoantibodies acting against the Acethylcholine Receptor. The preclinical study was published in The Journal of Immunology (180:2696-2703, 2008) by Fulvio Baggi, M.D. and Renato Mantegazza, M.D., of the "Carlo Besta" Neurological Institute Foundation in Milan. The study compared pixantrone with the related drug, mitoxantrone, an agent currently approved to treat severe multiple sclerosis, also an autoimmune disease that attacks the central nervous system. In the current study, pixantrone was found to be more effective than mitoxantrone at improving both the laboratory and the clinical manifestations of the MG equivalent in rats. The authors concluded that "pixantrone [is] a promising immunosuppressant agent suitable for clinical investigation in myasthenia gravis, although additional experiments are needed to confirm its safety profile in prolonged treatments."

Current therapeutic treatment options for myasthenia gravis include corticosteroids and immunosuppressive drugs, both of which are effective in most patients. However, some patients do not respond to the standard treatments, and side effects may limit prolonged administration. Mitoxantrone has a broad immunosuppressive effect, but has cumulative cardiotoxicity and prolonged treatment can result in a decrease in left ventricular ejection fraction (LVEF -- the amount of blood the heart pumps out with each beat) or, rarely, congestive heart failure. Pixantrone's mechanism of action is similar to that of mitoxantrone -- both act as DNA intercalating agents and inhibit topoisomerase II, but preclinical data indicate that pixantrone is less toxic to the heart than mitoxantrone and prolonged administration may be possible.

"These results are intriguing, and, like the earlier data in animal models of multiple sclerosis, suggest that pixantrone may be of clinical utility in patients with severe myasthenia gravis or multiple sclerosis. We have been approached by European cooperative groups interested in performing clinical trials in both of these diseases," said Gabriella Pezzoni, Ph.D., Scientific Director of Cell Therapeutics Inc.'s European branch, and one of the investigators in the preclinical study on EAMG.

About the Preclinical Study

In an in vitro rodent model, pixantrone demonstrated a dose-dependent inhibition of T cell responses up to complete suppression of the proliferation in EAMG. EAMG was induced in subject animals using acetylcholine (T-cell) receptor, the autoantigen at the neuromuscular junction. The animals were randomly assigned to four treatment groups -- 1) preventive pixantrone (PIX)group, starting four days after immunization, 2) therapeutic PIX group, starting four weeks after immunization, 3) therapeutic mitoxantrone (MTX) group, starting four weeks after immunization, and 4) vehicle-treated animals as control groups. Doses of both pixantrone and mitoxantrone were equal to one-fourth of LD10 for single i.v. injection in animals. Although both pixantrone and mitoxantrone improved clinical symptoms, reduced weight loss and increased muscle acetylcholine receptor content compared with vehicle-treated rats, pixantrone appeared to be more effective at equitoxic doses.

About Pixantrone

Pixantrone is an investigational agent under development for the potential treatment of various hematological malignancies. It was developed to improve the activity and safety of the anthracycline family of anti-cancer agents. Anthracyclines have been shown to be very active clinically in a number of tumor types. However, they are usually associated with cumulative heart damage that prevents them from being used in a large proportion of patients. Pixantrone has been designed to reduce the potential for these severe cardiotoxicities, as well as to potentially increase activity and permit simplified administration compared to the currently marketed anthracyclines.

About Cell Therapeutics, Inc.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit http://www.cticseattle.com.

This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of pixantrone include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with pixantrone in particular including, without limitation, the potential failure of pixantrone to be tested in or have comparable results in human clinical trials of myasthenia gravis, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling pixantrone, and the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.

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Posted: February 2008

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