HAYWARD, Calif., June 5 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated reported encouraging interim clinical data on KOS-862 and KOS-1584, the company’s most advanced epothilone drug candidates. The data were presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta, Georgia.
Epothilones are anticancer agents with a taxane-like mechanism of action that have demonstrated activity in taxane-resistant tumors. KOS-862 has a broad therapeutic index that differentiates it from other compounds in the class and has demonstrated activity in non-small cell lung cancer and breast cancer. KOS-1584 is a second-generation compound with increased potency, favorable tissue distribution, and ease of formulation. Kosan is developing its epothilone compounds in collaboration with Roche.
“The Kosan/Roche collaboration has been very productive, resulting in meaningful clinical advances in these two drug candidate programs,” said Robert. G. Johnson, Jr., M.D., Ph.D., Kosan’s Chief Executive Officer. “Our first-generation epothilone, KOS-862, continues to demonstrate a favorable safety profile with activity in advanced cancers, especially breast cancer. We are especially encouraged by the first clinical data presented on KOS-1584, our second-generation compound, which has shown early anti-tumor activity with minimal toxicity to date.”
KOS-862: Interim Results from a Phase Ib Clinical Trial in Combination with Herceptin(R)
Interim results were presented from a Phase Ib dose-escalating clinical trial of KOS-862 administered in combination with trastuzumab (Herceptin(R)) in patients with HER-2 metastatic breast cancer (measurable disease was not required at entry). Of 13 patients who received weekly doses of KOS-862 (at 75, 80, or 100 mg/m2) in combination with Herceptin(R) (at registered dose) after previously failing treatment with chemotherapy, anti-tumor activity was observed in three patients, including one confirmed and one unconfirmed partial response, and one patient with a greater than 90 percent reduction in a tumor marker. KOS-862 was well-tolerated with no dose-limiting toxicities observed at the highest dose; only one patient discontinued the study due to drug-related toxicity. Adverse events were mostly Grade 1 or 2, with three Grade 3 incidents of sensory neurological toxicities and one Grade 3 diarrhea.
These data were presented in a poster session on Sunday, June 4, by Javier Cortes, M.D., of Hospital Universitaro Vall D’Hebron, Barcelona, Spain.
A Phase II clinical trial evaluating KOS-862 at 100 mg/m2 in combination with the standard recommended dose of Herceptin(R) is ongoing.
KOS-1584: Interim Results from a Phase I Single-Agent Clinical Trial to Define Phase II Dose
A Phase I clinical trial of KOS-1584 as a single agent was conducted in patients with advanced solid tumors. Patients received KOS-1584 weekly in dose escalations from 0.8 to 20 mg/m2. No dose-limiting toxicity has been observed. Indications of anti-tumor activity included a 13 percent tumor shrinkage in one patient with non-small cell lung cancer and a 40 percent decrease in tumor marker in a patient with advanced highly-refractory ovarian cancer. Patient recruitment and dose escalations are continuing with the goal of defining the maximum tolerated dose of KOS-1584 on this weekly dosing schedule.
These results were presented in a poster session on Sunday, June 4, by Alison Stopeck, M.D., of the University of Arizona, Tucson, Arizona. “KOS-1584’s potency, lack of premedications to prevent hypersensitivity reactions and safety profile to date are promising within the epothilone class and suggest a higher level of tolerability and potential efficacy may be achievable,” said Dr. Stopeck. “We look forward to further clinical study of this novel epothilone to determine its safety and potential clinical benefit.”
An additional Phase I open-label trial of KOS-1584 is being conducted in patients with advanced solid tumors to determine maximum tolerated dose, dose-limiting toxicity and recommended Phase II dose schedule. In this trial, KOS-1584 is being administered once every three weeks in dose escalations from 0.8 to 20 mg/m2. In the 36 patients treated to date, no drug-related dose-limiting toxicities have been observed. Preliminary evidence of anti-tumor activity has been observed, with an unconfirmed partial response in ovarian cancer. Updated data on the every third week dosing schedule will be presented in an oral session on Tuesday, June 6, 2006, by Miguel Villalona- Calero, M.D., of Ohio State University, Columbus, Ohio.
About Kosan
Kosan Biosciences is a biotechnology company advancing two new classes of anticancer agents through clinical development -- Hsp90 (heat shock protein 90) inhibitors and epothilones. Kosan is leveraging its proprietary discovery platform to generate a pipeline of potentially significant product candidates, primarily in the area of oncology.
Kosan’s Hsp90 inhibitors have a novel mechanism of action targeting multiple pathways involved in cancer cell growth and survival. KOS-953 is Kosan’s proprietary formulation of 17-AAG, a geldanamycin analog. The agent is currently in Phase I and II clinical trials, primarily for multiple myeloma and HER2-positive breast cancer. In addition, intravenous and oral formulations of Kosan’s second-generation Hsp90 inhibitor, KOS-1022, are being evaluated in Phase I clinical trials.
Epothilones inhibit cell division with a mechanism of action similar to taxanes, one of the most successful classes of anti-tumor agents. KOS-862 is currently being studied in a Phase II single-agent clinical trial in patients with metastatic breast cancer, as well as a Phase II combination trial with Herceptin(R). KOS-1584, a second candidate designed to improve pharmacokinetics, is in Phase I clinical trials in patients with solid tumors. Kosan’s epothilone program is partnered with Roche through a global development and commercialization agreement.
For additional information on Kosan Biosciences, please visit the company’s website at www.kosan.com.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995 (the “Act”). Such forward-looking statements include statements relating to the further development and potential safety and efficacy of KOS- 862 and KOS-1584. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. There are a number of important factors that could cause the results of Kosan to differ materially from those indicated by these forward-looking statements, including, among others, risks related to the clinical advancement of KOS-862 and KOS-1584, including the risk that clinical trials may not demonstrate safety and efficacy sufficient to obtain the requisite regulatory approvals or to result in a marketable product; Kosan’s dependence on its collaboration with Roche for development of its epothilone product candidates; the possible determination that an earlier-stage compound, such as KOS-1584, will be more appropriate for commercial development than KOS-862; and other risks detailed from time to time in the Company’s SEC reports, including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2006 and other periodic filings with the SEC. Kosan does not undertake any obligation to update forward- looking statements.
NOTE: Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Kosan Biosciences Incorporated
CONTACT: Robert G. Johnson, Jr., M.D., Ph.D., Chief Executive Officer ofKosan Biosciences, +1-510-732-8400, ext. 5243, or johnson@kosan.com
Web site: http://www.kosan.com//
