Kosan Presents Phase I Results on KOS-953 as Multiple Myeloma Treatment at American Society of Clinical Oncology Meeting
Sunday May 15, 7:55 am ET
Proprietary Formulation of 17-AAG Shows Early Signs of Activity and Tolerability
ORLANDO, Fla., May 15 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) today presented preliminary data from a Phase I clinical trial of KOS-953, Kosan's proprietary formulation of the Hsp90 inhibitor 17-AAG, showing early signs of anticancer activity and tolerability in heavily pre-treated patients with relapsed-refractory multiple myeloma. The data were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Fla.
The poster presentation ("Phase I Trial of 17-AAG in Patients with Relapsed Refractory Multiple Myeloma" abstract # 3056), included results from 14 evaluable patients in the ongoing Phase I trial, all of whom had advanced, previously treated multiple myeloma -- cancer affecting the plasma cells, a type of immune system cell that produces antibodies to help fight infection and disease (median number of five prior regimens and 40 percent having failed transplantation). The open-label, dose-escalation trial is designed to determine the maximum tolerated dose, safety profile, pharmacokinetics and recommended Phase II dose of the proprietary formulation of 17-AAG, and is being conducted at the Dana Farber Cancer Institute in Boston, MA; Roswell Park Cancer Institute in Buffalo, NY, and H. Lee Moffitt Cancer Center in Tampa, FL. The trial uses a variety of pharmacodynamic measurements of myeloma and peripheral blood cells to assess the biological activity of KOS- 953.
One MR and one PR, according to Blade criteria, were observed in 14 percent of evaluable patients to date in this dose escalation phase of the trial. In addition, stable disease, after two or more cycles of treatment, has been observed in another 50 percent of evaluable patients. Bone marrow aspirates collected following treatment showed an increase in apoptosis of myeloma cells. KOS-953 was administered at four different dose levels on a twice-weekly schedule every three weeks. One episode of dose-limiting toxicity (Grade 3 elevated liver function test) was observed at the 220 and 340 mg/m(2) dose levels. Other side effects were manageable and included gastrointestinal, liver function abnormalities, myalgias/muscle cramps, and fatigue. Assessment at the 340mg/m(2) dose level continues in an effort to determine the maximum tolerated dose. The pharmacokinetics of KOS-953 are linear with respect to exposure and maximum plasma concentrations over the dose range tested.
"These are encouraging results in patients with advanced, heavily pretreated disease. They support the findings of positive cell-culture and preclinical studies demonstrating that KOS-953 has activity in multiple myeloma, including disease resistant to other agents such as proteosomal inhibitors and immunomodulatory agents," said Kenneth Anderson, M.D., Director, Jerome Lipper Multiple Myeloma Center at Dana Farber Cancer Institute and Kraft Family Professor of Medicine, Harvard Medical School.
KOS-953 is a proprietary formulation of 17-AAG developed by Kosan to improve patient tolerability and provide greater stability compared to the original drug product. In addition to the Phase I single-agent study in multiple myeloma reported today, the formulation is also currently being evaluated in a Phase Ib clinical trial of KOS-953 administered in combination with bortezomib (Velcade®), a recently approved agent to treat relapsed- refractory myeloma. The original formulation of 17-AAG is being evaluated in multiple Phase I, Phase Ib and Phase II clinical trials in a variety of tumor types. These trials are sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) between Kosan and the NCI Cancer Therapy Evaluation Program (CTEP). In 2004, Kosan obtained orphan drug designation for 17-AAG from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for the treatment of multiple myeloma as well as another hematologic cancer, chronic myelogenous leukemia.
Additional 17-AAG ASCO Data
Interim results from an additional study of 17-AAG administered in combination with docetaxel was also presented at the meeting, abstract #3051.
NOTE: Velcade® is a registered trademark of Millennium Pharmaceuticals, Inc.
About Hsp90 Inhibitors
17-AAG is an analog of the polyketide geldanamycin that inhibits Hsp90 (heat shock protein 90), a protein found in high levels in tumor cells. Hsp90 is a molecular "chaperone" which maintains the stability of numerous "client proteins" implicated in tumor growth and metastasis, including protein kinases and transcription factors. By blocking the activity of Hsp90, Kosan's geldanamycin analogs lead to the disruption of the Hsp90-client protein complexes and the degradation of the client proteins. By targeting multiple growth-signaling pathways involved in cancer, these compounds may have potential use in a variety of tumor types, both as single agents and in combination with other signal transduction inhibitors and cytotoxic drugs.
About Kosan
Kosan Biosciences has two first-in-class anticancer agents in Phase II and Phase Ib clinical trials: KOS-862 (Epothilone D) and 17-AAG, a geldanamycin analog and Hsp90 inhibitor. KOS-862, the company's lead drug candidate, has a mechanism of action similar to taxanes and is partnered with Roche in a global development and commercialization agreement, along with a follow-on compound, KOS-1584, currently in Phase I testing. 17-AAG targets multiple pathways required for tumor growth and is being developed in collaboration with the National Cancer Institute, in addition to a second-generation geldanamycin analog, KOS-1022 (DMAG), now in Phase I trials. Kosan's proprietary formulation of 17-AAG, KOS-953, is in Phase I and Phase Ib trials. Kosan has generated a pipeline of potentially significant products for cancer, infectious disease and other therapeutic areas based on its proprietary technologies for discovering, developing and manufacturing polyketide analogs. Polyketides are an important class of natural products that have yielded numerous pharmaceuticals for the treatment of cancer, infectious diseases, high cholesterol, transplant rejection and other diseases. For additional information on Kosan Biosciences, please visit the Company's website at kosan.com .
This press release contains "forward-looking" statements, including statements with respect to the further development and potential safety and efficacy of KOS-953 and 17-AAG in the treatment of cancer. 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 and uncertainties related to the clinical advancement of KOS-953 and 17-AAG and the costs of conducting clinical studies for these product candidates, including the risk that clinical trials for KOS-953 and 17-AAG may not demonstrate safety and efficacy sufficient to obtain the requisite regulatory approvals or to result in a marketable product; Kosan's dependence on its collaborations with Roche for development of its product candidates; and other risks detailed from time to time in the Company's SEC reports, including its Annual Report on Form 10-K for the year ended December 31, 2004, and other periodic filings with the SEC. Kosan does not undertake any obligation to update forward-looking statements. |
