Personalized Medicine Approach Based on Genotype Demonstrated for ChemGenex Therapeutics' Phase I/II Anticancer Compound Quinamed -amonafide dihydrochloride-.

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MENLO PARK, Calif.--(BUSINESS WIRE)--June 8, 2004

Pharmacogenomic Results in Patients with Solid Tumors Presented

at ASCO 

Results of a Phase I/II trial that used patient genotyping to determine dosing of Quinamed(TM) (amonafide dihydrochloride), an experimental cancer drug under development by ChemGenex Therapeutics, were presented today at the 2004 Annual Meeting of the American Society of Clinical Oncology.

"Amonafide is a topoisomerase II inhibitor that is extensively metabolized by N-acetyltransferase-2 (NAT-2) to an active metabolite that is nearly as potent as the parent compound," said John Kuhn, Pharm.D., Professor, Departments of Pharmacology and Medicine, University of Texas, San Antonio, the senior author of the presentation. "Previous studies with this drug used phenotyping to determine a relationship between dose-limiting hematological toxicities and whether a patient was a slow or fast metabolizer of the drug. Now genotyping offers a new level of sophistication and precision for determining the appropriate dose of amonafide to maximize efficacy while minimizing the drug's toxicity."

The open-label, dose-escalation study was conducted in 32 patients with a variety of solid tumor types by researchers at The University of Texas Health Science Center (San Antonio, TX), The Sarah Cannon Cancer Center and Tennessee Oncology (Nashville, TN), and The University of Louisville (Louisville, KY). The clinical researchers determined the recommended dose to be 400 mg/m2/week in patients whose genotype indicated they were slow acetylators of the drug, with escalation to 500 mg/m2 possible with minimal toxicity. In patients whose genotype indicated they were intermediate or fast acetylators, researchers determined the recommended dose to be 320 mg/m2/week. Evaluable responses were observed in three patients with gastrointestinal stromal tumor (GIST), prostate, and ovarian cancers, respectively. Enrollment in the Phase II portion of the trial continues in patients with GIST, prostate, breast, and ovarian, cancer to confirm preliminary anti-tumor activity in these cancers with the recommended Quinamed dose.

The investigators initiated dose escalation at 400 mg/m2 intravenous on days 1, 8, and 15 every 28 days. They obtained patient blood samples for acetylator genotyping (NAT-2 genotype) and began to encounter dose-limiting toxicities (primarily hematologic) at 500 mg/m2. Patient genotype results were then correlated with observed toxicities before enrolling subsequent patients who were dosed according to their genotype (slow versus intermediate/rapid acetylator). The investigators observed differences between slow and intermediate/fast NAT-2 genotypes for a variety of pharmacokinetic parameters.

"This study clearly demonstrates the value that personalized medicine offers for the treatment of cancer, where there is a narrow window between an efficacious dose and one which produces side-effects that can limit a patient's treatment," said Dennis Brown, Ph.D., ChemGenex Therapeutics president and chief executive officer.

About CHEMGENEX THERAPEUTICS www.chemgenex.com

ChemGenex Therapeutics is a Menlo Park, California based biopharmaceutical company focused on developing and marketing novel small molecule therapeutics for the treatment of cancer and related conditions. ChemGenex Therapeutics optimizes the development of small molecule therapeutics by using proprietary technologies from discovery through development to reduce risk and increase the likelihood of clinical success. ChemGenex Therapeutics' overall strategy is to exploit the growing understanding of cancer biology and the human genome to achieve targeted clinical development of next generation anti-cancer drugs. Its current product portfolio includes two product candidates in clinical trials and others in late-stage pre-clinical development. Quinamed(TM) (amonafide dihydrochloride), is currently undergoing Phase II clinical testing in solid tumors. Ceflatonin(TM) (homoharringtonine), is in Phase II trials with patient enrollment in chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS). Three other compounds, CGX-2101, CGX-6001B and CGX-273, are in late-stage pre-clinical development. On April 26, 2004, ChemGenex Therapeutics and AGT Biosciences of Australia announced their intent to merge. Once the merger is complete, the combined company will be known as ChemGenex Pharmaceuticals and will have operations in Menlo Park, California and Melbourne, Australia.

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