HAYWARD, Calif., Dec. 14 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated today presented preliminary data from a Phase 2 clinical trial showing that tanespimycin (KOS-953) in combination with trastuzumab (Herceptin(R)) demonstrated clinically meaningful antitumor activity, including both partial responses and extended stabilization of disease, in patients with trastuzumab-refractory HER2-positive metastatic breast cancer. Preliminary data from the ongoing trial were presented in a poster at the 29th Annual San Antonio Breast Cancer Symposium. The poster was entitled, "Phase 2 trial of Trastuzumab (T) and KOS-953 (17-AAG) in Patients (pts) with HER2-Positive Breast Cancer: Preliminary Results," and was presented by Shanu Modi, M.D., Breast Cancer Medicine Service, Memorial Sloan- Kettering Cancer Center. Clifford A. Hudis, M.D., Chief, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, was the senior author on the study.
"The demonstration of clinical benefit with tanespimycin combined with trastuzumab, in patients with trastuzumab-refractory HER2-positive metastatic breast cancer, is quite promising," said Dr. Hudis. "The encouraging evidence of tolerability and activity from this Phase 2 trial strongly support the continued development of an Hsp90 inhibitor as a potential treatment for patients with breast cancer whose disease has proven to be resistant to conventional therapy."
"We believe that these favorable Phase 2 results with tanespimycin, our first-generation Hsp90 inhibitor, establish an important proof-of-concept for Hsp90 inhibition in the treatment of breast cancer and set the stage for advancing into later-stage trials," said Robert G. Johnson, Jr., M.D., Ph.D., President and Chief Executive Officer of Kosan. "We believe that our second-generation Hsp90 inhibitor, alvespimycin HCl, is optimally suited for further development in breast cancer due to its enhanced pharmaceutical properties including greater potency, longer half-life, ease of formulation and oral bioavailability. A Phase 1/2 trial of alvespimycin in combination with trastuzumab is ongoing and we plan to initiate later-stage trials with alvespimycin in patients with HER2-positive metastatic breast cancer in the first half of 2007. We will continue to develop tanespimycin on a registration path as a treatment for multiple myeloma where the compound has demonstrated promising clinical activity to date."
Phase 2 Tanespimycin Results
Tanespimycin is an Hsp90 inhibitor that has demonstrated the potential to disrupt the activity of multiple oncogenes and cell signaling pathways implicated in tumor growth, including HER2, a key pathway in breast cancer.
The Phase 2 trial of tanespimycin in combination with trastuzumab was designed to determine the objective response rate by RECIST in patients with HER2-positive metastatic breast cancer with tumor progression during treatment with one trastuzumab-containing regimen immediately prior to entering the trial. The dosing schedule for tanespimycin was a two-hour weekly intravenous infusion of 450 mg/m2 administered along with the standard dose of trastuzumab. Of the 12 patients enrolled in the trial, all had one prior trastuzumab containing regimen, and many patients had been heavily pre-treated with additional non-trastuzumab-based cytotoxic chemotherapy. Patients had a median of three prior cytotoxic regimens and four patients had received prior hormonal therapy.
Of the eight patients evaluable for efficacy, five (63%) showed signs of clinical benefit (one patient with stable disease was still active in Cycle 3 and was too early to assess for efficacy).
* One patient with documented progressive disease in the liver prior to study while being treated with trastuzumab/vinorelbine had a confirmed partial response (53% tumor shrinkage by RECIST) and continues on study (Cycle 9+);
* One patient with documented progressive disease on study for one year post-trastuzumab treatment had an unconfirmed partial response (35% tumor shrinkage by RECIST) and continues on study (Cycle 3+); and
* Three patients who received 4-6+ cycles of treatment had stable disease; one with a 20% decrease in measurable disease.
The tanespimycin plus trastuzumab regimen was generally well tolerated. Grade 1 and 2 toxicities included fatigue, diarrhea, nausea, vomiting, and Grade 3 toxicity was seen in 3 patients (2 patients with headache, 1 patient with fatigue), all of which were manageable and reversible.
Future Development Plans
Kosan plans to initiate further trials in HER2-positive metastatic breast cancer using alvespimycin HCl (KOS-1022), a second-generation Hsp90 inhibitor. Alvespimycin has enhanced pharmaceutical properties: longer half-life that allows more flexible dosing; increased potency, enabling potentially lower dosing; good oral bioavailability, and water solubility, enabling ease of formulation. Alvespimycin is currently being tested in several clinical trials: Phase 1b (intravenous formulation) in combination with trastuzumab in HER2+ metastatic breast cancer; Phase 1 (oral formulation), as a single agent in solid tumors; and Phase 1 (intravenous formulation) as a single agent in hematological tumors. The compound has demonstrated promising clinical results to date. Kosan anticipates initiating a Phase 2 trial of alvespimycin as a single agent in HER2-positive metastatic breast cancer in the first half of 2007, with subsequent Phase 2/3 trials in HER2-positive metastatic breast cancer in combination with trastuzumab.
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) (bortezomib) and HER2-positive metastatic breast cancer in combination with Herceptin(R) (trastuzumab). 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. 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 but are not limited to statements relating to the further development and potential safety, efficacy and registration of Kosan's product candidates, tanespimycin and alvespimycin; and Kosan's development plans for its product candidates, including but not limited to Kosan's plans with respect to initiations of clinical trials for tanespimycin and alvespimycin and the timing thereof. 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 Kosan's clinical candidates, 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; risks related to Kosan's and its collaborators' ability to timely commence and complete clinical trials; 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 IncorporatedCONTACT: Gary S. Titus, Chief Financial Officer, +1-510-731-5373, ortitus@kosan.com, or Jane Green, +1-510-731-5335, or mobile,+1-415-652-4819, or green@kosan.com, both of Kosan Biosciences Incorporated
Web site: http://www.kosan.com/
