Tanespimycin is Industry's First Hsp90 Inhibitor to Enter Registration
TIME Registration Program Utilizes New, Proprietary Tanespimycin
HAYWARD, Calif., Aug. 2 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN) today announced that the TIME-2 trial is open and enrolling patients. This marks the opening of Kosan's Tanespimycin in Myeloma Evaluation or "TIME" registration program for its lead Hsp90 inhibitor, tanespimycin (KOS-953). The TIME program includes two clinical trials: TIME-1 and TIME-2. TIME-1 is a pivotal Phase 3 trial to be conducted in a first-relapse patient population. TIME-2, which is designed to be supportive of the TIME-1 trial, is a Phase 2/3 trial in patients with relapsed-refractory disease. TIME-2 also has the potential to support registration in a relapsed-refractory setting. The TIME program will use Kosan's new, proprietary injectable suspension formulation of tanespimycin. Tanespimycin is the first Hsp90 inhibitor to enter a registration program.
"The opening of our TIME registration program is a major achievement for our company and a milestone in the advancement of Hsp90 inhibition, a promising new approach to cancer therapy," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. "We continue to be encouraged by the high level of durable responses we observe when tanespimycin combined with bortezomib (Velcade(R)) is administered to patients with relapsed-refractory multiple myeloma, as well as by tanespimycin's manageable safety profile. We believe that a successful outcome in the TIME-2 trial, together with data from our TIME-1 trial, could potentially support an accelerated registration strategy for tanespimycin in this life-threatening disease."
The TIME clinical program will utilize Kosan's improved, proprietary injectable suspension formulation of tanespimycin injectable suspension. The formulation is designed to provide important benefits, including improved patient safety, due to the elimination of Cremophor(R) and the associated need for steroid premedication to prevent hypersensitivity reactions. Tanespimycin injectable suspension also has a potentially enhanced intellectual property position and permits easier drug preparation and administration compared to the prior formulation.
The TIME-2 clinical trial is being conducted at clinical sites primarily in the US and in Europe and is anticipated to enroll approximately 130 patients. Key aspects of the TIME-2 trial are as follows.
-- The trial is designed to test three different doses of tanespimycin in
combination with the approved dose and schedule of bortezomib
(1.3 mg/m2). The tanespimycin dose groups are 50 mg/m2, 175 mg/m2 and
340 mg/m2. Tanespimycin will be administered twice weekly as a one-hour
intravenous infusion on a cycle of two weeks of treatment every three
weeks (the same schedule as bortezomib).
-- Patients eligible to participate in the TIME-2 trial must have been
treated with and progressed following at least three prior treatments
for multiple myeloma. Prior regimens must include bortezomib and
-- The primary endpoint of the trial is the dose response based on
objective response rate after 4 cycles of treatment. Secondary
endpoints include a comparison of response rate between the dose
groups, progression-free survival, time to treatment failure and
overall survival. Objective response rate in multiple myeloma is
measured primarily by the patient's level of M protein.
Kosan anticipates that the pivotal TIME-1 trial will begin later in 2007 or in early 2008. TIME-1 will be an open-label, randomized, multi-center trial that is designed to enroll over 450 patients with disease relapse following a single prior course of treatment (first-relapse). The trial is designed to compare two groups: patients treated with bortezomib plus tanespimycin and patients treated with bortezomib alone. Tanespimycin will be administered at a dose of 340 mg/m2 and all patients will receive standard doses of bortezomib (1.3 mg/m2). TIME-1 is designed with a primary endpoint of progression-free survival. Kosan anticipates providing more background on the TIME-1 trial design upon initiation.
Tanespimycin has been shown to induce apoptosis of drug-sensitive and drug-resistant multiple myeloma cell lines. Tanespimycin also inhibits expression of various cell surface cytokines, such as IGF-1R and IL-6R, that are involved in growth, survival and drug resistance of multiple myeloma cells. Destabilizing client proteins with tanespimycin while blocking their degradation with bortezomib promotes the accumulation of cytotoxic proteins, leading to cell death.
Kosan reported data from a Phase 1b trial of tanespimycin in combination with bortezomib at the 2007 annual meeting of the American Society for Clinical Oncology (ASCO) on 56 patients enrolled in 7 dose cohorts (100-340 mg/m2 of tanespimycin; 0.7-1.3 mg/m2 of bortezomib; tanespimycin administered via 1-hour infusion following the bortezomib dose 2 times per week every 2 weeks out of 3 weeks). Of these 56 patients, all had received multiple prior chemotherapy regimens (median of 4) and 67% had received bone marrow transplants.
In those patients who received tanespimycin across the range of doses tested and a dose of 1.0 or 1.3 mg/m2 of bortezomib, the overall response rate including complete, partial and minimal responses was, as previously reported, 44% (18 out of 41 patients evaluable for response). Of the 44%, 8 out of 14 patients were bortezomib-nave (57%); 7 out of 16 patients were bortezomib-pretreated patients (44%); and 3 out of 11 patients were bortezomib-refractory (27%). Responses in the bortezomib-refractory patients continue to show prolonged duration (at least 10 months at the time of data presentation at ASCO in June 2007) and meaningful reduction of serum/urinary M-protein (greater than 89%). The combination of tanespimycin and bortezomib was well-tolerated.
Kosan has been granted orphan drug designation for tanespimycin in multiple myeloma in both the US and European Union.
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 in patients with multiple myeloma in a registration program called TIME. Tanespimycin is also being studied in multiple myeloma as monotherapy, in HER2-positive metastatic breast cancer in combination with Herceptin, 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.
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 statements related to the further development and potential safety, efficacy, commercialization and other characteristics of tanespimycin or tanespimycin injectable suspension, Kosan's development plans with respect to tanespimycin, including but not limited to Kosan's plans and timing for the initiation of TIME-2, TIME-2 as a potential registration trial, and potential accelerated registration strategy for tanespimycin. 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 tanespimycin, including the risk that studies may not demonstrate safety and efficacy sufficient to initiate additional clinical trials, continue clinical development on the timing currently anticipated or at all, obtain the requisite regulatory approvals or result in a marketable product; and other risks detailed from time to time in the Kosan'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
Herceptin(R) (trastuzumab) is a registered trademark of Genentech, Inc.
Revlimid(R) (lenalidomide) is a registered trademark of Celgene
Cremophor(R) is a registered trademark of BASF Aktiengesellschaft
|SOURCE Kosan Biosciences Incorporated|
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