Kosan Biosciences Incorporated has presented the important preclinical data on its anticancer compound 17-AAG (17-allylamino-17-demethoxygeldanamycin), a heat shock protein 90 (Hsp90) inhibitor at the 46th Annual Meeting of the American Society of Haematology (ASH) in San Diego.
KOS-953, Kosan's proprietary formulation of 17-AAG was shown to have in vitro and in vivo activity against a broad spectrum of multiple myeloma cells, including cells that are both sensitive and resistant to cytotoxic chemotherapeutics, the proteasome inhibitor bortezomib, and thalidomide or its derivatives, an official statement said here.
KOS-953 is currently being evaluated in multiple myeloma patients in a single-agent phase I clinical trial and a Phase Ib combination trial with
bortezomib (Velcade).
The poster, entitled "Anti-Tumour Activity of KOS-953, a Cremophor-Based Formulation of the Hsp90 Inhibitor of 17-AAG", presents work conducted by Dr. Constantine Mitsiades, at the Dana Farber Cancer Institute. In in vitro studies, KOS-953 triggered the depletion of several key kinases, such as Akt and Raf, leading to tumour cell sensitization to several chemotherapeutics, including cytotoxics and bortezomib. In an in vivo study, treatment with KOS-953 was associated with prolongation of overall survival of mice, and was well tolerated. The study evaluated KOS-953 in a mouse model of diffuse multiple myeloma bone lesions and utilized whole-body fluorescence and bioluminescence imaging to follow the treated mice.
According to Robert G. Johnson, Jr., executive VP, Development and CMO, "These data generated by our colleagues at the Dana Farber Cancer Institute provide further evidence that KOS-953/17-AAG may be an effective treatment modality for patients with multiple myeloma and confirm the potential added benefit of combining KOS-953 with other agents such as bortezomib. We look forward to the results of the ongoing clinical trials in 2005."
Results from a number of other preclinical studies of 17-AAG are also being presented at the ASH meeting, demonstrating the compound's activity in leukaemia cells and the potential for effectively combining 17-AAG with other novel chemotherapeutics such as histone deacetylase inhibitors and tyrosine kinase inhibitors.