Kosan Presents Data on KOS-953 From Single-Agent and Combination Clinical Trials in Multiple Myeloma at European Hematology Association Congress
Friday June 3, 3:30 am ET
Heat Shock Protein 90 Inhibitor Shows Early Signs of Activity and Tolerability
STOCKHOLM, Sweden, June 3 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) today presented preliminary data on KOS-953, Kosan's proprietary formulation of the Hsp90 inhibitor 17-AAG, showing early signs of anticancer activity and tolerability when administered as single-agent therapy in a Phase I trial in heavily pre-treated patients with relapsed-refractory multiple myeloma. Clinical data from a Phase Ib combination trial, in which KOS-953 was administered with bortezomib (Velcade®), also showed signs of anti-myeloma activity in bortezomib-naive and -refractory patients. The data were presented at the 10th Congress of the European Hematology Association in Stockholm, Sweden.
The poster presentation ("KOS-953 (A Heat Shock Protein 90 Inhibitor) as Single Agent or in Combination with Bortezomib in Patients with Relapsed Refractory Multiple Myeloma" abstract #0632), included results from 14 evaluable patients in the single-agent trial and six evaluable patients in the ongoing combination trial. All of the study participants had heavily pre-treated multiple myeloma (median number of five prior regimens; approximately half of these having failed transplantation). Both trials are open-label, dose-escalation studies designed to determine the maximum tolerated dose, safety profile, pharmacokinetics and recommended Phase II dose of KOS-953 when given as a single agent or in combination with bortezomib (BZ). These trials are being conducted at the Dana Farber Cancer Institute in Boston, MA; Roswell Park Cancer Institute in Buffalo, NY; H. Lee Moffitt Cancer Center in Tampa, FL and the Arizona Cancer Center in Tucson, AZ (combination trial only). The trials use a variety of pharmacodynamic measurements from bone marrow aspirates and peripheral blood cells to assess the biological activity of KOS-953. Anti-myeloma activity was measured using generally accepted EBMT (Blade) criteria.
In the single-agent trial, 64 percent of the evaluable patients showed either partial response (one patient), minor response (one patient), or stable disease (seven patients after two or more cycles of treatment). In the combination trial, 66 percent of the evaluable patients showed either a minor response (two patients: one in a BZ-naive patient; the second in a BZ-refractory patient) or stable disease (two patients after at least two cycles). In both trials, KOS-953 was administered at escalating dose levels on a twice-weekly schedule every three weeks. In the combination trial, this treatment was preceded by administration of bortezomib. Side effects were manageable and similar for the two trials, including gastrointestinal effects, anemia, rash, myalgias/muscle cramps, and fatigue. Thrombocytopenia was also observed in the combination trial. Pharmacokinetics of KOS-953 are linear with respect to exposure and maximum plasma concentrations over the dose range tested. Bone marrow aspirates collected following treatment showed an increase in apoptosis of myeloma cells, while the peripheral blood cells showed the typical reactive induction of Hsp70, a stress response to biologically active doses of an Hsp90 inhibitor. Dose escalation in both studies is continuing in order to define the recommended dose for future trials.
"We are encouraged by these results demonstrating anti-myeloma activity of KOS-953 in heavily pretreated patients, both as single-agent and in combination with bortezomib. These data underscore the importance of Hsp90 as an anticancer target and suggest that KOS-953 may resensitize multiple myeloma cells from patients who are resistant to bortezomib," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan Executive Vice President, Development and Chief Medical Officer. "Our plan is to continue these trials to their protocol-defined endpoints, defining a tolerable dose with signs of biological activity, with the expectation of moving to larger Phase II trials in myeloma."
Background
Multiple myeloma is a cancer that affects the plasma cells, a type of immune cell that produces antibodies to help fight infection and disease. KOS-953 is a novel formulation of 17-AAG, an Hsp90 inhibitor. In vitro and in vivo studies showed that inhibition of Hsp90 by KOS-953 leads to protein degradation and apoptosis of multiple myeloma cells. By blocking Hsp90 function, KOS-953 markedly enhances the sensitivity of multiple myeloma cells to bortezomib. In addition to the KOS-953 single-agent and combination studies in multiple myeloma reported on today, 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.
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 in the treatment of cancer as monotherapy or in combination with other therapeutics. 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 the costs of conducting clinical studies, including the risk that clinical trials for KOS-953 may not demonstrate safety and efficacy sufficient to obtain the requisite regulatory approvals or to result in a marketable product; 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. |
