BASEL, Switzerland and HAYWARD, Calif., Feb. 27 /PRNewswire-FirstCall/ -- Roche and Kosan Biosciences Incorporated announced today that the companies have selected their second-generation epothilone R1645 (KOS- 1584) to advance into a Phase 2 clinical development program exploring clinical activity and safety in multiple solid tumor types. While the first- generation compound R1492 (KOS-862) demonstrated meaningful objective response rates in metastatic breast cancer and non-small cell lung cancer, the companies have decided to discontinue its development and focus resources on advancing R1645.
As a second-generation epothilone R1645 is designed to have greater safety, efficacy and an enhanced pharmaceutical profile. In Phase 1 dose escalation trials, R1645 was well tolerated and demonstrated antitumor activity against ovarian and non-small cell lung cancers. On the basis of R1645’s tolerability and antitumor activity in multiple tumor types, Roche and Kosan have agreed to rapidly advance this compound into later-stage development.
“Phase 1 results encouraged us to support the expanded clinical development of R1645,” said Peter Hug, Global Head of Pharma Partnering for Roche. “We look forward to working further with Kosan on the Phase 2 program exploring the therapeutic potential of R1645 in multiple solid tumor types.”
“R1645 (KOS-1584) combines the optimal properties of Kosan’s proprietary epothilone D class with properties of other epothilones to produce an active, well-tolerated and easily formulated anticancer agent,” said Robert G. Johnson, Jr., M.D., Ph.D., Kosan’s President and Chief Executive Officer. “With the ongoing support from our partner Roche, we can continue our broad- based clinical program for the development of improved epothilones such as KOS-1584, which we believe ultimately has the potential to compete successfully in the large taxane market.”
Kosan and Roche established a global development and commercialization agreement for epothilones to treat cancer in September 2002. Under the terms of the agreement, Roche will fund development activities and have the worldwide exclusive rights to market and sell R1645 if approved. Kosan will co-develop and have the right to co-promote the product in the U.S. Kosan is eligible to receive additional payments upon achievement of certain clinical, regulatory and commercial milestones. Kosan will receive royalties on sales and may further increase such royalties through a buy-in option at a later stage of clinical development.
About R1645 (KOS-1584)
Kosan has reported data from two Phase 1 clinical trials of KOS-1584 using different dosing regimens. In both of these trials, R1645 demonstrated meaningful antitumor activity and a high level of tolerability. Both of these trials are ongoing with the goal of identifying the recommended Phase 2 dose and regimen.
In a Phase 1 open-label clinical trial of R1645 being administered as a single agent on a weekly dosing schedule, antitumor activity was observed in 17% of 37 patients with advanced solid tumors who had been heavily pre-treated (median of five prior chemotherapy regimens). One confirmed partial response (44% tumor shrinkage by RECIST) was observed in a patient with non-small cell lung cancer. One patient with advanced refractory ovarian cancer had a 40% decrease in CA125 tumor marker, and four patients experienced 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 and were most frequently gastrointestinal.
In an open-label Phase 1 trial of R1645 being administered as a three-hour intravenous infusion every three weeks, conducted in 45 patients with advanced solid tumors, antitumor activity was seen in 29.5% of patients. One patient with ovarian cancer (six prior therapies) had an unconfirmed partial response (31% tumor shrinkage by RECIST) with 62% decline in CA125 after the second cycle. Twelve patients experienced stable disease after four or more cycles, including one patient with ovarian cancer who had a 28% decrease in CA125 after six cycles of treatment. In this trial, R1645 was well tolerated. Common toxicities were primarily gastrointestinal (grade 1 and 2) and fatigue.
About Epothilones
Epothilones are anticancer agents which inhibit cell division with a mechanism of action similar to taxanes, one of the most widely used classes of chemotherapeutic agents. Epothilones have demonstrated activity in taxane- sensitive and taxane-resistant tumors. Kosan’s epothilones are designed to be superior to other epothilones, having the potential to overcome multi-drug resistance, to be synergistic in combination with other therapies and have a broad therapeutic index against a wide range of tumors.
About Roche as a Partner
Roche is a valued partner to around 80 companies worldwide. During the past two years, Roche has led the pharmaceutical industry in the number of clinical compound deals signed. In 2006, Roche entered into nine partnerships to jointly develop products for optimal patient benefit and value. Recent collaborations have complemented the company’s autoimmune disease franchise and oncology research pipeline, the latter being in line with a diagnostics collaboration strengthening Roche’s position in personalized medicines. This continued collaboration with Kosan strengthens Roche’s oncology portfolio and has the potential to bring important new treatment options to cancer patients.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai. Additional information about the Roche Group is available on the Internet (www.roche.com).
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 combination with Herceptin(R). 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 antitumor agents. KOS-1584 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.
NOTE: Velcade(R) (bortezomib) is a registered trademark of Millennium Pharmaceuticals, Inc.
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Forward-Looking Statements
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 commercialization of R1645 (KOS-1584); and Kosan’s and Roche’s development plans for R1645 (KOS-1584), including but not limited to plans with respect to initiations of clinical trials 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 development of R1645 (KOS-1584), including the risk that studies may not demonstrate safety and efficacy sufficient to initiate clinical trials, continue clinical development, 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.
Kosan Biosciences Incorporated
CONTACT: Jane M. Green, Vice President, Corporate Communications of Kosan,office, +1-510-731-5335, or mobile, +1-415-652-4819, or green@kosan.com; orRoche-Europe, Amanda Gett of Roche Pharma Partnering, 41 61 687 5269, oramanda.gett@roche.com
