17-AAG Phase I and Ib Combination Trial Results Reported at the American Society of Clinical Oncology Meeting
Sunday June 6, 9:00 am ET
NEW ORLEANS, June 6 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) announced today that four Phase I and Ib clinical trials investigating the use of 17-allylamino-17-demethoxy-geldanamycin (17-AAG) are being presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in New Orleans. All four clinical trials are sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) between Kosan and the NCI Cancer Therapy Evaluation Program (CTEP).
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In today's session (8:00 A.M. to 12 Noon, Room 291, Escalator 7), the results of three clinical trials are presented: "A phase I pharmacokinetic (PK) and pharmacodynamic (PD) trial of weekly 17-allylamino-17 demethoxygeldanamycin (17AAG, NSC-704057) in patients with advanced tumors" (Presenter: Ramesh K. Ramanathan, M.D., Poster #22, Abstract #3031); "A phase I trial of 17-allylamino-geldanamycin (17AAG) in patients with advanced cancer" (Presenter: Charles Erlichman, M.D., Poster #21, Abstract #3030); and "Phase 1 pharmacokinetic and pharmacodynamic trial of docetaxel and 17AAG (17-allylamino-17-demethoxygeldanamycin)" (Presenter: David B. Solit, M.D., Poster #23, Abstract #3032). The first two posters describe Phase I experience with weekly and twice weekly dosing of 17-AAG, respectively. In Dr. Ramanathan's presentation, 17-AAG was found to be well tolerated and the recommended Phase II dose (RP2D) was 295 mg/m2 given weekly three out of four weeks. In the poster by Dr. Erlichman, reporting on the investigation of 17-AAG in patients with advanced cancer, the maximum tolerated dose (MTD) was determined to be 220 mg/m2 when given twice weekly for two out of three weeks. Dr. Solit presented an update on the combination trial of 17-AAG plus docetaxel. The combination was well tolerated at the dose levels studied: 17-AAG (375 mg/m2) and docetaxel (70 mg/m2) day 1 of 21 day cycle with dose escalation continuing.
17-AAG inhibits Hsp90 (heat shock protein 90), a protein chaperone that binds to signaling proteins, known as "client proteins." These client proteins include a "who's who" list of cancer-relevant targets such as mutated p53, Bcr-Abl, Her2, Akt, Raf-1, and others. When 17-AAG binds to Hsp90, it disrupts the Hsp90-client protein complexes, leading to their degradation. All of the trials used a variety of pharmacodynamic measurements of peripheral blood cells and often tumor tissue or cells to assess the biological activity of 17-AAG against client proteins considered critical in the progression of this disease. To date, there are over twenty approved clinical trials sponsored by the NCI and four planned Kosan-sponsored trials that will investigate the use of 17-AAG as monotherapy or in combination.
In tomorrow's session (June 07, 2004 from 8:00 a.m. to 12 Noon) the following presentation is scheduled: "A phase I trial of gemcitabine (Gem), 17-allylaminogeldanamycin (17-AAG) and cisplatin (CDDP) in solid tumor patients" (Presenter: Paul Haluska, M.D., Ph.D., Poster #M8, Abstract #3058).
About Kosan
Kosan Biosciences has two lead product candidates: KOS-862 and 17-AAG, including its proprietary formulation of 17-AAG designated KOS-953. Both compounds are derived from an important class of natural products known as polyketides. KOS-862 is in Phase II and Phase Ib clinical trials and is partnered with Roche in a global development and commercialization agreement. 17-AAG is being evaluated in multiple Phase I and Phase Ib clinical trials in collaboration with the National Cancer Institute. KOS-953 and 17-AAG are polyketide inhibitors of Hsp90 and interrupt several biological processes implicated in cancer cell growth and survival. By applying its expertise and proprietary technologies to generate polyketide analogs and by increasing the production yields of polyketides, Kosan has created a robust pipeline of potentially significant products for cancer, as well as for infectious disease and other therapeutic areas. For additional information on Kosan Biosciences, please visit the Company's website at www.kosan.com. |
