SAN ANTONIO, Texas, Dec. 8 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated today announced the initiation of a Phase II clinical trial in patients with HER2-positive metastatic breast cancer, administering KOS-953 in combination with trastuzumab (Herceptin(R)). In addition, interim data from the Phase Ib dose-escalating clinical trial using this combination was presented today at the 28th Annual San Antonio Breast Cancer Symposium. KOS-953 is the Company's proprietary formulation of the heat shock protein 90 (Hsp90) inhibitor, 17-AAG.
The Phase Ib dose-escalating and Phase II clinical trials of KOS-953 in combination with trastuzumab are being conducted at Memorial Sloan- Kettering Cancer Center and Arizona Cancer Center. The Phase II trial will enroll patients with HER2-positive metastatic breast cancer whose disease has progressed following treatment with trastuzumab in either the adjuvant or metastatic setting. In this Phase II trial, patients will receive weekly doses of KOS-953 following the infusion of trastuzumab. The primary objective of the protocol is to assess tumor response using standard RECIST criteria.
The poster presentation ("Trastuzumab and KOS-953 (17-AAG) is Feasible and Active in Patients with Metastatic Breast Cancer: Preliminary Results of a Phase 1/2 Study" -- abstract #1095) included results from 25 patients, including 17 evaluable patients with HER2-positive metastatic breast cancer who had received a median number of three prior trastuzumab-based therapies. A confirmed partial response was observed in a heavily pre-treated patient; three additional patients had tumor regression, including one patient with complete resolution of an adrenal metastasis by FDG-PET imaging. All patients had progressed on multiple prior trastuzumab-based regimens. Nine patients had stable disease that lasted for at least three months. (Four of these patients had stable disease in excess of six months.)
"Preclinical research conducted in the laboratory of Dr. Neal Rosen at Memorial Sloan-Kettering Cancer Center demonstrated the antitumor potential of Hsp90 inhibition in HER2-positive animal models," said Clifford Hudis, M.D., Chief of the Breast Cancer Medicine Service and Associate Attending Physician at Memorial Sloan-Kettering Cancer Center, New York. "The encouraging antitumor activity observed in the dose-escalating trial among heavily pre- treated patients supports continuation of this combination into a Phase II clinical trial."
The Phase Ib clinical trial was designed to determine the recommended Phase II dose and toxicity of KOS-953 in combination with standard doses of trastuzumab. According to the trial protocol, patients received standard weekly doses of trastuzumab followed by KOS-953 in escalating doses. Ten patients received the final recommended Phase II dose of KOS-953. Drug- related toxicities were primarily fatigue and gastrointestinal (nausea, vomiting, diarrhea) that were amenable to supportive care. There was no marrow suppression and minimal hepatoxicity. No cardiovascular toxicity was observed. Pharmacokinetic parameters for KOS-953 in this combination were similar to KOS-953 administered as a single agent; KOS-953 had no effect on the kinetics of trastuzumab.
About Hsp90 Inhibitors
KOS-953 is a proprietary formulation of 17-AAG -- an analog of the polyketide geldanamycin that inhibits Hsp90 (heat shock protein 90). Found in high levels in tumor cells, Hsp90 is a molecular "chaperone" which maintains the stability of numerous "client proteins" implicated in tumor growth and metastasis, including protein kinases and transcription factors. By blocking the activity of Hsp90, Kosan's geldanamycin analogs lead to the disruption of the Hsp90-client protein complexes and the degradation of the client proteins. One of the most sensitive client proteins is the HER2 receptor. By targeting multiple growth-signaling pathways involved in cancer, these compounds may have potential use in a variety of tumor types, both as single agents and in combination with other signal transduction inhibitors and cytotoxic drugs.
In addition to the KOS-953/Herceptin combination trial in metastatic breast cancer reported on today, KOS-953 is also being evaluated in a Phase I single-agent and Phase Ib combination clinical trial with bortezomib (Velcade(R)) in patients with multiple myeloma. The original formulation of 17-AAG is being evaluated in multiple Phase I, Phase Ib and Phase II clinical trials in a variety of tumor types. These 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). In 2004, Kosan obtained orphan drug designation for 17-AAG from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of multiple myeloma as well as another hematologic cancer, chronic myelogenous leukemia.
About Kosan
Kosan Biosciences is advancing two new classes of anticancer agents through clinical development. Kosan's most advanced compound, KOS-862 (Epothilone D), is in Phase II and Phase Ib clinical trials in breast cancer, and its follow-on compound, KOS-1584, is in Phase I clinical trials. These programs are partnered with Roche through a global development and commercialization agreement. Kosan is also developing Hsp90 (heat shock protein 90) inhibitors, in collaboration with the National Cancer Institute (NCI), including 17-AAG, a first generation geldanamycin analog. Kosan's proprietary formulation of 17-AAG, KOS-953, is in Phase I and Phase II clinical trials for multiple myeloma and metastatic breast cancer. In addition, a second-generation geldanamycin analog, KOS-1022 (DMAG), is currently in Phase I clinical trials, in collaboration with the NCI. Kosan has generated a pipeline of additional product candidates for gastrointestinal motility, infectious diseases and cancer based on its proprietary technologies for discovering, developing and manufacturing polyketide analogs. Polyketides are an important class of natural products that have yielded numerous pharmaceuticals for the treatment of cancer, infectious diseases, high cholesterol, transplant rejection and other diseases. For additional information on Kosan Biosciences, please visit the Company's website at www.kosan.com.
This press release contains "forward-looking" statements, including statements with respect to the further development and potential safety and efficacy of KOS-953 in the treatment of cancer. 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, the risk that the U.S. Food and Drug Administration may require changes to the protocols and informed consents for clinical trials of KOS-953, which changes may have a material adverse effect on the timing of, and Kosan's ability to conduct, those clinical trials, risks related to the clinical advancement of KOS-953, including the risk that clinical trials for this product candidate may not demonstrate safety and efficacy sufficient to obtain the requisite regulatory approvals or to result in a marketable product , risks related to the possible determination that an earlier-stage compound, such as KOS-1022, will be more appropriate for commercial development than KOS-953, risks related to the potential for others to develop products containing or based on 17-AAG, risks related to Kosan's dependence on the NCI for the development of its Hsp90 inhibitors 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, 2005 and other periodic filings with the SEC. Kosan does not undertake any obligation to update forward-looking statements.
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc., and Velcade(R) (bortezomib) is a registered trademark of Millennium Pharmaceuticals, Inc.
Kosan Biosciences IncorporatedCONTACT: Susan M. Kanaya, Chief Financial Officer of Kosan Biosciences,+1-510-732-8400, ext. 5227, or kanaya@kosan.com
Web site: http://www.kosan.com/
