HAYWARD, Calif., Nov. 10 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated today presented encouraging antitumor and safety data from two Phase 1 trials of KOS-1584, a second-generation epothilone. KOS-1584 is being evaluated in two Phase 1 trials using different dosing regimens with the goal of defining the recommended Phase 2 dose and to assess safety, pharmacokinetics, pharmacodynamics and early evidence of antitumor activity. Data on KOS-1584 were presented in posters at the 18th EORTC-NCI-AACR Symposium on “Molecular Targets and Cancer Therapeutics,” being held in Prague, Czech Republic. The conference is organized by the European Organization for Research and Treatment of Cancer (EORTC) in conjunction with the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR).
Epothilones are anticancer agents with a taxane-like mechanism of action that have demonstrated activity in taxane-resistant tumors. 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.
“We believe that our epothilone D class compounds have the potential to outperform other epothilones in development, achieve best-in-class status and compete effectively in the taxane market,” said Robert G. Johnson, Jr., President and Chief Executive Officer. “The attractive drug properties of KOS-1584 combined with demonstrated anticancer activity in patients with refractory disease and the potential to overcome taxane resistance reaffirm our confidence in the therapeutic promise of this new class of agents.”
“Phase 1 Trial of Novel Epothilone, KOS-1584, Using a Weekly Dosing Schedule:" Poster by Howard Burris, M.D., Sarah Cannon Cancer Center, Nashville, Tennessee
A Phase 1 open-label clinical trial of KOS-1584 administered as a single agent on a weekly dosing schedule was conducted in 37 patients with advanced solid tumors. Patients received KOS-1584 via one-hour weekly (three weeks out of four) intravenous infusion in dose escalations from 0.8 to 25 mg/m2. Indications of antitumor activity were observed in 17% of these heavily pre-treated patients (median of five prior chemotherapy regimens) and included:
-- One confirmed partial response in a patient with non-small cell lung cancer who had been heavily pre-treated and had 44% tumor shrinkage by RECIST;
-- One patient with advanced refractory ovarian cancer who had a 40% decrease in CA125 tumor marker; and
-- Four patients with stable disease over four or more cycles of treatment (greater than or equal to 16 weeks).
Common toxicities were generally low-grade and typical of a cytotoxic agent. The current dose-limiting toxicity appears to be diarrhea. KOS-1584 has attractive pharmacokinetic properties including a half-life of 20-25 hours and a large volume of distribution suggesting good tissue penetration.
The Phase 1 trial of KOS-1584 administered weekly is continuing in order to define the recommended Phase 2 dose.
“Safety and Pharmacokinetic (PK) Trial of KOS-1584, a Novel Analog of Epothilone D:" Poster by Miguel Villalona-Calero, M.D., Ohio State University, Columbus, Ohio
An open-label Phase 1 trial of KOS-1584 administered as a three-hour intravenous infusion every three weeks in dose escalations from 0.8 to 36 mg/m2 was conducted in 45 patients with advanced solid tumors. Indications of antitumor activity were seen in 29.5% of patients and included:
-- One patient with ovarian cancer (six prior therapies) who had an unconfirmed partial response (31% by RECIST) with 62% decline in CA125 after cycle 2;
-- 12 patients with stable disease after 4 or more cycles, including one patient with ovarian cancer who had a 28% decrease in CA125 after six cycles of treatment.
KOS-1584 was well tolerated. Common toxicities were primarily gastrointestinal (grade 1 and 2) and fatigue. One patient experienced a dose-limiting toxicity (back, joint and breathing pain) at the highest current dose (36mg/m2). The cohort is being expanded to gain further experience at this dose level.
The Phase 1 trial of KOS-1584 administered every three weeks is continuing in order to define the recommended Phase 2 dose.
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.
Hsp90 inhibitors have a novel mechanism of action targeting multiple pathways involved in cancer cell growth and survival. Kosan’s proprietary formulation of tanespimycin (KOS-953) is currently in Phase 1 and 2 clinical trials, primarily for multiple myeloma in combination with Velcade(R) and HER2-positive metastatic breast cancer. In addition, intravenous and oral formulations of Kosan’s second-generation Hsp90 inhibitor, alvespimycin (KOS-1022), are being evaluated in Phase 1 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 2 single-agent clinical trial in patients with HER2-positive metastatic breast cancer, as well as a Phase 2 combination trial with Herceptin(R). KOS-1584, a second candidate designed to improve pharmacokinetics, is in Phase 1 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, efficacy and commercialization of Kosan’s epothilones, 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; 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 September 30, 2006 and other periodic filings with the SEC. Kosan does not undertake any obligation to update forward-looking statements.
NOTE: Velcade(R) (bortezomib) is a registered trademark of Millennium Pharmaceuticals, Inc.
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Kosan Biosciences Incorporated
CONTACT: Gary S. Titus, Chief Financial Officer, +1-510-731-5373, ortitus@kosan.com, or Jane Green, +1-510-731-5335, or +1-415-652-4819, orgreen@kosan.com, both of Kosan
Web site: http://www.kosan.com/
