Kosan Biosciences Incorporated has initiated a phase I multi-centre trial of an oral formulation of KOS-1022 (DMAG), a second-generation heat shock protein 90 (Hsp90) inhibitor. KOS-1022 is the first-reported Hsp90 inhibitor to be administered orally to patients with cancer.

"Initiation of clinical testing of an oral formulation of KOS-1022 complements the development programme for intravenous KOS-1022 and is an important step in our Hsp90 inhibitor programme. In addition, given the convenience of oral dosing compared to intravenous dosing, the capsule formulation of KOS-1022 will allow us to investigate whether more continuous inhibition of Hsp90 will lead to enhanced anti tumour activity," said Daniel V. Santi, Kosan chairman and chief executive officer.

According to the company release, the phase I clinical trial of oral KOS-1022 will evaluate the safety, pharmacokinetics, pharmacodynamics, and bioavailability of escalating doses of KOS-1022 in patients with advanced solid tumours, as well as assess any preliminary evidence of anti tumour activity. The clinical trial will be conducted at the University of Colorado Health Science Centre and the Presbyterian Hospital Medical Centre at the University of Pennsylvania.

Intravenous KOS-1022 is currently being evaluated in a company-sponsored phase I clinical trial in patients with haematologic malignancies as well as multiple phase I clinical studies in patients with advanced solid tumours sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement between Kosan and the NCI Cancer Therapy Evaluation Programme. Because of the complementary nature of oral and intravenous KOS-1022, Kosan plans to continue to develop both formulations.

In addition to oral and intravenous KOS-1022, Kosan's first-generation Hsp90 inhibitor, a proprietary formulation of 17-AAG (KOS-953), is being investigated by Kosan in a Phase II clinical trial in combination with trastuzumab (Herceptin) in patients with Her2 positive breast cancer, as well as clinical trials in patients with relapsed refractory multiple myeloma (both as single-agent and in combination with bortezomib (Velcade). Kosan may initially seek approval for KOS-953, in combination with Velcade, to treat relapsed refractory multiple myeloma. In 2004, Kosan obtained orphan drug designation for 17-AAG from both the US Food and Drug Administration and the European Medicines Agency for the treatment of multiple myeloma as well as another haematologic cancer, chronic myelogenous leukaemia.

KOS-1022 and 17-AAG are analogs of the polyketide geldanamycin that inhibit Hsp90. KOS-953 is Kosan's proprietary formulation of 17-AAG. Hsp90 is a molecular 'chaperone,' which maintains the stability of numerous 'client proteins' implicated in tumour growth and metastasis, including protein kinases and transcription factors.

Kosan Biosciences is advancing two new classes of anticancer agents through clinical development. Kosan is developing Hsp90 (heat shock protein 90) inhibitors in collaboration with the NCI. Kosan's proprietary formulation of 17-AAG (KOS-953) is in phase I and II clinical trials for multiple myeloma and Her2 breast cancer.