Kosan Presents Phase 1 Data Showing Antitumor Activity and Safety Profile of Epothilone KOS-1584 at AACR/NCI/EORTC Meeting
HAYWARD, Calif., October 23, 2007 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated presented updated data today from a Phase 1 clinical trial showing that KOS-1584/R1645, an epothilone under co-development with Roche, demonstrated antitumor activity and tolerability in patients with solid tumors. KOS-1584/R1645 showed signs of activity in patients with non-small cell lung, ovarian, breast, prostate, pancreatic, head and neck and colon cancer. The Phase 1 trial explored two different schedules of KOS-1584/R1645 using escalating doses. Data reported today were from a trial investigating weekly dosing schedules (weekly 2 weeks out of 3 weeks and weekly 3 weeks out of 4 weeks). Common toxicities were generally low-grade and manageable.
Data from the Phase 1 trial of KOS-1584/R1645 were presented in a poster titled, "Optimization of the Phase 2 Dose of KOS-1584 (a Novel, Synthetic Epothilone) via Weekly Administration," by Howard Burris, M.D., Sarah Cannon Research Institute, Nashville, TN, at the 2007 Annual Meeting of the American Association for Cancer Research/National Cancer Institute/European Organization for Research and Treatment of Cancer (AACR/NCI/EORTC).
"We believe that KOS-1584 has the potential to achieve best-in-class status in the emerging epothilone market as well as to compete in the established taxane market," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. "We look forward to our planned commencement of a Phase 2 clinical program for KOS-1584 toward the end of 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/R1645 when administered to patients with advanced solid tumors (who have no standard therapy options) on two dosing schedules. The Phase 1 trial enrolled 60 patients investigating a wide range of doses from 0.8 mg/m2 to 25 mg/m2 on the 3 of 4 week schedule and 16 to 30 mg/m2 on the 2 of 3 week schedule; the 1-hour and 3-hour durations of infusion were included on both schedules. Indications of antitumor activity included:
-- 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 withdrew after 10 months (10 cycles) and remains in PR over one year later; -- 1 patient with breast cancer (3 prior regimens, active on study at Cycle 5) experienced a 40% reduction in tumor marker CA-15.3, 42.5% reduction in CA27,29 and 30% reduction in CEA; -- 1 patient with advanced ovarian cancer (4 prior regimens) had 40% tumor marker CA125 decrease and 20% shrinkage of nodal disease (on study for 6 cycles); -- 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); -- 1 patient with pancreatic cancer had a 39% decrease in CA19-9 after 4 cycles; and -- 6 patients had stable disease (3 or more months), including those with head and neck, pancreatic, colon, breast and non-small cell lung cancers.
Common drug related toxicities varied depending on dose and dose schedule, and were predominantly gastrointestinal symptoms, primarily diarrhea, that were generally manageable with supportive care. Grade 3 neuropathy was limited to one patient at the recommended dose on the 4-week schedule and two patients at the highest doses tested on the 3-week schedule. The recommended Phase 2 dose will be based on clinical activity, dose intensity, side effect profile and schedule compatibility with established chemotherapy regimens: 36 mg/m2 every 3 weeks; or 25 mg/m2 twice every 3 weeks depending on data from expanded dose cohorts.
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. Tanespimycin (KOS-953) is being tested in combination with bortezomib (Velcade(R)) in patients with multiple myeloma in a registration program called TIME. Tanespimycin is also being studied in HER2-positive metastatic breast cancer in combination with trastuzumab (Herceptin(R)), and as monotherapy in metastatic melanoma. Intravenous and oral formulations of Kosan's second-generation Hsp90 inhibitor, alvespimycin (KOS-1022), are being evaluated in Phase 1 clinical trials in hematological cancers and in HER2-positive metastatic breast cancer.
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.
Kosan's motilin agonist compound, KOS-2187, licensed to Pfizer, is in a Phase 1 safety trial, with plans to pursue development in gastroesophageal reflux disease (GERD).
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include but are not limited to the further development, including the planned commencement of a Phase 2 clinical program, and potential safety, efficacy, commercialization and other characteristics of KOS-1584/R1645. 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 Kosan's expectation that additional financing will be required, Kosan's current partnering arrangement with Roche and the highly uncertain nature of the progress and results of Kosan's testing of KOS-1584/R1645, including the risk that studies may not demonstrate safety and efficacy sufficient to initiate additional clinical trials, continue clinical development, obtain the requisite regulatory approvals or result in a marketable product, and other risks detailed from time to time in Kosan's SEC reports, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 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.
Posted: October 2007