National Cancer Institute Research Identifies Unique Mechanism of Brostallicin's Anti-Tumor Effectiveness

CTI acquired worldwide rights to brostallicin when it acquired privately-held Systems Medicine LLC in 2007. Published in the journal Molecular Cancer Therapy (Mol Cancer Ther 2009;8(7) July 2009; 1985-94), the researchers utilized preclinical studies to provide clues into tumor susceptibility mechanisms for brostallicin, a synthetic DNA minor grove binder, and to identify differences between brostallicin and trabectedin (Yondelis(R); ET-743), which is a natural marine product approved in Europe. Unlike other chemotherapy agents, including trabectedin, the NCI research indicates that the tumor cell DNA damaging effects of brostallicin are enhanced by high tumor glutathione levels, a hallmark of drug-resistant tumors. Brostallicin was shown to affect DNA in both dividing and quiescent cells. Its actions can be followed by induction of a specific DNA binding protein foci that can be detected in circulating blood cells. Importantly, brostallicin was active in a trabectedin-resistant cell line.

"These preclinical data provide important further insights into the specific bio-marker (tumor glutathione levels) that increases the probability of achieving improved anti-tumor effectiveness by careful selection of patients who are most likely to benefit, and is consistent with our focus on personalized approaches to cancer drug development," said Jack Singer, M.D., Chief Medical Officer at CTI. "This may be of particular importance in patients with relapsed 'triple-negative' breast cancer, ovarian, or colorectal cancer following treatment with platinum containing regimens where high glutathione levels are associated with chemotherapy resistance."

About Brostallicin

Brostallicin, a novel synthetic second-generation DNA minor groove binder, has shown potent cancer killing activity, and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies, in preclinical experimental tumor models. Brostallicin binds covalently to DNA within the DNA minor groove, interfering with DNA division and leading to tumor cell death. More than 200 patients have been treated with brostallicin in single-agent and combination studies. Brostallicin had predictable and predominantly hematologic toxicities. Activity was demonstrated in a number of solid tumor types. A phase II study of brostallicin in relapsed/refractory soft tissue sarcoma met its pre-defined activity and safety hurdles and resulted in a first-line phase II study that is currently being conducted by the European Organization for Research and Treatment of Cancer (EORTC).

About Systems Medicine (SM)

In July 2007, CTI acquired Systems Medicine, a privately-held oncology company, in a stock-for-stock merger. SM applies a systems biology approach to drug development, combining pharmacogenomics and bioinformatics with experienced preclinical, clinical, and regulatory expertise to find and exploit a specific cancer's 'context of vulnerability.' Specifically, SM defines the molecular and genetic alterations (context) that cause cancer cells to be particularly sensitive (vulnerable) to a drug or combination of drugs--the "context of vulnerability."

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 www.CellTherapeutics.com.

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