Kosan Biosciences Incorporated has initiated a company-sponsored phase Ib clinical trial to investigate KOS-953, Kosan's proprietary formulation of 17-AAG in combination with bortezomib (Velcade), a recently approved agent to treat relapsed/refractory myeloma.

The phase Ib clinical trial will evaluate the safety of the combination and determine an appropriate dose and schedule for the use of KOS-953 in combination with Velcade. Dr. In addition to standard measures of response, investigators will monitor changes in client proteins as a pharmacodynamic marker of activity during treatment to verify the anticipated effects on the Hsp90 (heat shock protein 90) client proteins in the patients' myeloma cells and to insure adequate drug exposure.

The KOS-953 formulation of 17-AAG developed by Kosan replaces the DMSO-egg lecithin vehicle in the original drug product with the aim to improve patient tolerability and provide greater stability.

"We are particularly enthusiastic to explore KOS-953 in myeloma patients because the anti-myeloma activity observed both in vivo and in vitro with 17-AAG in preclinical models is very impressive," said Daniel V. Santi, chairman and CEO at Kosan Biosciences.

The original formulation of 17-AAG is being evaluated in multiple phase I, Phase Ib and in a variety of tumour types in phase II clinical trials sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) between Kosan and the NCI Cancer Therapy Evaluation Programme (CTEP). As previously announced, Kosan is also evaluating KOS-953 as a monotherapy for multiple myeloma, official statement from Kosan said.

17-AAG inhibits Hsp90, a protein chaperone that binds to signalling proteins, known as "client proteins." These client proteins include a "who's who" list of cancer-relevant targets such as mutated p53, Bcr-Abl, Her2, Akt, Raf-1, and others. In myeloma, it includes IL-6 and IGF-R1. When 17-AAG binds to Hsp90, it disrupts the Hsp90-client protein complexes, leading to their degradation and ultimately, cell death.

Velcade is approved for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Velcade is currently approved in the United States, 27 European Union states, Argentina and Korea. Velcade is being co-developed by Millennium and Johnson & Johnson Pharmaceutical Research & Development, L.L.C.