HAYWARD, Calif., June 4 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated presented data from a Phase 1 clinical trial showing that KOS-1584/R1645, an epothilone under co-development with Roche, demonstrated promising antitumor activity and tolerability in patients with solid tumors. KOS-1584/R1645 showed activity in 32% of patients (13 of 41 evaluable) including activity in patients with non-small cell lung, ovarian, breast, prostate, head and neck and other cancers. Common toxicities were generally low-grade and manageable. Data from this ongoing trial were presented on Sunday, June 3, 2007, in a poster titled, “Phase 1 Trial of KOS-1584 (a Novel Epothilone) Using Two Weekly Dosing Schedules,” by Howard Burris, M.D., Sarah Cannon Research Institute, Nashville, TN, at the 2007 Annual Meeting of the American Society of Clinical Oncology (ASCO).
“Epothilones are promising anticancer agents due to their taxane-like mechanism of action and demonstrated activity in taxane resistant tumors,” said Dr. Burris. “Kosan’s novel epothilone is of particular interest due to its level of antitumor activity in patients with highly refractory disease and manageable side effect profile. This promising compound warrants continued development.”
“KOS-1584/R1645 is a highly potent compound with attractive pharmaceutical properties, including a long half-life, large volume of distribution, wide therapeutic index and ease of formulation that has demonstrated encouraging activity in Phase 1 trials,” said Robert G. Johnson, Jr., M.D., Ph.D., Kosan’s President and Chief Executive Officer. “We believe that KOS-1584/R1645, based on our novel epothilone D backbone, has the potential to be superior to other epothilones currently in development and ultimately emerge as a meaningful competitor in the taxane market. We look forward to initiating a robust Phase 2 clinical program, with the support of our partner Roche, later in 2007.”
Phase 1 Trial Results of KOS-1584
The Phase 1 trial was designed to define the maximum tolerated dose, dose- limiting toxicity and recommended Phase 2 dose, and to assess early activity of KOS-1584 when administered to patients with advanced solid tumors (no standard curative therapy options). The Phase 1 trial dose schedules initially included a 1-hour weekly infusion for 3 weeks out of 4, and weekly for 2 weeks out of 3. More recently, a dose schedule of a 3-hour infusion was initiated on both weekly schedules (2 out of 3 weeks, 3 out of 4 weeks) to allow reduced Cmax (reduced peak exposure) with similar overall exposure enabling maximization of dose intensity.
A total of 50 patients have been enrolled in the Phase 1 trial. Indications of antitumor activity were observed in 32% of patients evaluable for efficacy, including,
-- 1 confirmed partial response (PR) in a patient with advanced non-small cell lung cancer (3 prior chemotherapy regimens); this patient had 44% tumor shrinkage by RECIST, and withdrew after 10 months (10 cycles) while still in PR; -- 1 patient with advanced ovarian cancer (4 prior regimens) had 40% CA125 decline and 20% shrinkage of nodal disease; -- 1 patient with advanced prostate cancer had 94% reduction in PSA and improved nodal disease after cycle 2 and was on study for 6 months (6 cycles); and -- Patients with stable disease (3 or more months) include those with head and neck, prostate, ovarian, breast, non-small cell lung, colon, pancreatic and cervical cancers.
Common drug related toxicities on the 1-hour, 3-week and 4-week schedules were similar and were predominantly gastrointestinal symptoms and fatigue.
-- On the 4-week, 1-hour infusion schedule, dose-limiting toxicity was primarily diarrhea observed at 20 and 25 mg/m2; no dose-limiting toxicity was observed at 16 mg/m2. Grade 3 peripheral neuropathy was observed in only 2 patients. -- On the 3-week schedule, 3 patients received a 1-hour infusion (16 mg/m2) and no dose-limiting toxicity was observed. -- On the 3-week schedule, no Grade 3 diarrhea was seen in the 6 patients receiving the 3-hour infusion at 20 mg/m2. A Grade 3 increase in liver function tests was observed in a patient with progressive liver disease.
Dose escalation is continuing on both the 3-week, 3-hour infusion schedule (currently at 25 mg/m2) and on the 4-week, 3-hour infusion schedule (currently at 20 mg/m2).
A second Phase 1 trial is currently exploring a single 3-hour infusion every 3 weeks (36-42 mg/m2). In this trial partial responses have been observed in patients with pancreatic and ovarian cancers and signs of activity in approximately 25% of patients, including a partial response in a heavily-pretreated patient with ovarian cancer (6 prior therapies; 31% tumor shrinkage by RECIST; 53.7% CA125 decline at end of study) and stable disease in patients with pancreatic, ovarian, non-small cell lung cancers and sarcomas.
Roche and Kosan plan to advance KOS-1584/R1645 into Phase 2 trials in the second half of 2007. The final dose and schedules for the Phase 2 trials will be based on clinical activity, dose intensity, side effect profile and schedule compatibility with established chemotherapy regimens.
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-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 http://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 the further development and potential safety, efficacy, commercialization and other characteristics of Kosan’s epothilone, KOS-1584[/R1645]; and 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 KOS-1584[/R1645], 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 March 31, 2007, and other periodic filings with the SEC. Kosan does not undertake any obligation to update forward-looking statements.
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: Jane Green, VP, Corporate Communications of Kosan BiosciencesIncorporated, +1-510-731-5335, mobile: +1-415-652-4819, green@kosan.com
Web site: http://www.kosan.com/
