Kosan's Second-Generation Hsp90 Inhibitor, DMAG, Enters Clinic
Wednesday July 21, 7:32 am ET
HAYWARD, Calif., July 21 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) announced today the initiation of the first Phase I clinical trial of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (DMAG), in cancer patients with advanced solid tumors. DMAG is a second-generation Hsp90 inhibitor that is highly potent and water soluble, and has good oral bioavailability. Kosan's first-generation Hsp90 inhibitor includes an original drug substance 17-AAG in a DMSO and egg lecithin vehicle and a new formulation, KOS-953, both of which are being evaluated in the clinic. The DMAG clinical trial is 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).
The Phase I DMAG study will be undertaken at three major cancer centers under the supervision of principal investigator Dr. Ramesh Ramanathan of the University of Pittsburgh Medical Center. The open label Phase I trial will establish the safety, pharmacokinetics, and pharmacodynamics of escalating doses of DMAG in cancer patients for whom there is no acceptable alternative therapy. The study will evaluate two dose escalation schedules on a 21-day cycle: (1) daily times five and (2) daily times three. In addition, the plasma pharmacokinetics and pharmacodynamics of DMAG in blood cells and, when available, tumor tissue will be investigated. Additional Phase I studies on different schedules are planned.
DMAG 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 DMAG binds to Hsp90, it disrupts the Hsp90-client protein complexes, leading to degradation of the client proteins. Concurrent with the DMAG study, multiple Phase II monotherapy and Phase Ib combination clinical trials are planned to continue to evaluate 17-AAG and KOS-953.
"We are particularly enthusiastic about this study because of the enhanced properties DMAG has shown in preclinical studies," said Daniel V. Santi, M.D., Ph.D., Chairman and Chief Executive Officer of Kosan. "In cooperation with CTEP, we now have two first-in-class drug candidates in the clinic targeting this new mechanism of action."
About Kosan
Kosan Biosciences has two first-in-class anticancer agents in Phase II clinical trials. KOS-862 (Epothilone D) is in Phase II and Phase Ib clinical trials and is partnered with Roche in a global development and commercialization agreement. 17-AAG, Kosan's lead geldanamycin analog, is in Phase II and Phase Ib clinical trials, and DMAG, its second-generation geldanamycin analog, is in Phase I. Both compounds are being developed in collaboration with the National Cancer Institute. Kosan's proprietary formulation of 17-AAG, designated KOS-953, is in Phase I. KOS-953, 17-AAG and DMAG are polyketide inhibitors of Hsp90 and interrupt several biological processes implicated in cancer cell growth and survival. Kosan's focus is on an important class of natural products known as polyketides. Polyketides are a class of natural products that have yielded numerous important pharmaceuticals for the treatment of cancer, infectious diseases, high cholesterol, transplant rejection and other diseases. Kosan applies its expertise and proprietary technologies to generate polyketide analogs and increase the production yields of polyketides, resulting in 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. |
