Kosan Biosciences (KOSN)

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Kosan Receives Completed Special Protocol Assessment for TIME-1 Pivotal Phase 3 Trial of Tanespimycin in Multiple Myeloma
Tanespimycin is the First Hsp90 Inhibitor to Enter Registration Trials

HAYWARD, Calif., Sept. 6 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN) today announced that it has successfully reached a binding agreement with the U.S. Food and Drug Administration (FDA) on the design of its TIME-1 clinical trial, a pivotal Phase 3 trial of its Hsp90 inhibitor tanespimycin as a treatment for patients with multiple myeloma. Through the FDA's Special Protocol Assessment (SPA) process, Kosan and the FDA have reached agreement on overall protocol design, primary efficacy endpoints and data analysis as well as aspects of expected labeling if the data from the pivotal trial are supportive and tanespimycin is approved by the FDA. This pivotal Phase 3 protocol, as well as the overall development program, have also completed the 'Scientific Advice' process with the centralized European Medicines Agency (EMEA).

Kosan's registration program for tanespimycin, called Tanespimycin in Myeloma Evaluation or TIME, has been initiated and 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-1 will evaluate the clinical benefit of adding tanespimycin to bortezomib and compare these results to those seen with single-agent bortezomib. The Special Protocol Assessment Kosan has completed applies to the TIME-1 trial. 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. The TIME-2 trial also has the potential to support registration in the relapsed-refractory setting. Kosan has initiated the TIME-2 trial, which is enrolling patients, and expects to initiate the TIME-1 trial at the end of 2007 or early 2008.

'Kosan's successful completion of both the Special Protocol Assessment process with the FDA and Scientific Advice from the EMEA for our TIME-1 trial provides us with a clear roadmap to registration in major countries around the world for this potentially important new treatment for patients with multiple myeloma,' said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. 'We believe that Kosan's TIME program is the most advanced Hsp90 inhibitor clinical program in the industry, underscoring Kosan's leadership in this promising new class of anticancer therapies. We appreciate the widespread support we have received from the US and international myeloma clinician and patient communities.'

About TIME

The TIME clinical program utilizes Kosan's improved, proprietary injectable suspension formulation of tanespimycin. The injectable suspension 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-1 trial will be an open-label, randomized, multi-center trial conducted in the US and in Europe that is designed to enroll over 450 patients with relapse of multiple myeloma 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. TIME-1 is designed to include an interim analysis of safety and efficacy to be conducted based on predefined criteria. Kosan anticipates providing more information on the TIME-1 trial design upon initiation.

The TIME-2 clinical trial is being conducted at clinical sites primarily in the US and in Europe and is designed to enroll approximately 130 patients with relapsed-refractory multiple myeloma. The trial is designed to test three different doses of tanespimycin in combination with the approved dose and schedule of bortezomib (Velcade(R)) (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 lenalidomide (Revlimid(R)). 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 three 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.

About the Special Protocol Assessment

As stated in the Prescription Drug User Fee Act (PDUFA) and FDA's Guidance for Industry Special Protocol Assessment, '...having agreed to the design, execution, and analyses proposed in protocols reviewed under this process ... the Agency will not later alter its perspective on the issues of design, execution, or analyses unless public health concerns unrecognized at the time of protocol assessment under this process are evident. Thus, documented special protocol assessments should be considered binding on the review division and should not be changed at any time...' assuming that the sponsor follows the protocol agreed-upon with the Agency, the sponsor has provided appropriate information to the Agency to support the protocol, the sponsor and the Agency agree to modify the protocol or a substantial scientific issue is identified after clinical testing has begun. In the absence of these developments, 'completion of a SPA with FDA provides binding agreement relative to design and analysis of key Phase 3 trial(s) such that positive final results can lead to full NDA/ BLA approval.' For more information about the Agency's Special Protocol Assessment process, see, http://www.fda.gov/cder/guidance/3764fnl.htm.

About Tanespimycin

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. When used in combination with bortezomib, the destabilization of 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 18 responding patients (44%), 8 out of 14 patients were bortezomib-naïve (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.