KOSAN'S HSP90 INHIBITOR SHOWS ANTITUMOR ACTIVITY

Kosan Biosciences has presented results from a dose-escalating, Phase Ib clinical trial of its lead Hsp90 inhibitor, tanespimycin (KOS-953), in combination with bortezomib (Velcade) showing a high degree of antitumor activity and tolerability in patients with multiple myeloma who had previously progressed following treatment with multiple conventional therapies. The data were presented at the American Society of Hematology annual meeting.

Hsp90 is a protein chaperone that binds to several sets of signaling proteins, known as "client proteins." These client proteins include a "who's who" list of cancer-relevant targets such as mutated p53, Bcr-Abl, Raf, ErbB2 and other kinases. Disruption of the Hsp90-client protein complexes leads to proteasome-mediated degradation of client proteins and cell death.

The objective of the trial was to define a Phase II dose of tanespimycin in combination with bortezomib in patients with relapsed, refractory multiple myeloma, as well as to assess pharmacokinetic and pharmacodynamic parameters. Dose escalation in the trial ranged from 100 to 340 mg/m2 for tanespimycin and from 0.7 to 1.3 mg/m2 for bortezomib. Patients received tanespimycin via a one-hour infusion two times per week for two weeks out of three weeks, following the bortezomib dose.

Data on 30 patients, with a median of 60 years of age, were reported. Of these 30 patients, 23 received a dose of at least 1.0 mg/m2 of bortezomib and were evaluable for efficacy. All of these patients had received multiple prior chemotherapy regimens, and 67 percent had received bone marrow transplants. Of the 30 patients, nine had not seen prior bortezomib, and five patients were bortezomib-refractory. At the time of this data presentation, the first six dose cohorts were evaluable (tanespimycin at doses of 100 mg/m2 through 275 mg/m2).

In patients who received 1.0 mg/m2 of bortezomib or more, the overall response rate was 57 percent (13 out of 23 patients), with an overall rate of complete and partial responses of 35 percent (eight out of 23 patients).