Biomira Inc has selected PX-866 as its next clinical development candidate. PX-866 is an inhibitor of the phosphatidylinositol-3-kinase (PI3 kinase)/ PTEN/AKT pathway, an important survival signaling pathway that is activated in many types of human cancer, including glioblastoma. Preclinical data presented this past weekend at the American Association of Cancer Research (AACR) annual meeting demonstrate that PX-866 has activity in an intracranial model of glioma.

"The preclinical data for PX-866, including those presented at AACR, are very promising and warrant advancing this small molecule compound to clinical development," said Robert L. Kirkman, president and chief executive officer of Biomira. "The data presented this weekend are particularly compelling, as they provide evidence of PX-866 activity in an intracranial model of glioma, a disease that accounts for 77 per cent of all malignant brain cancers and is refractory to conventional therapies. We are in the process of completing preclinical studies designed to support the expected filing of an investigational new drug (IND) application for PX-866 later this year. Expanding and advancing our clinical pipeline is a key priority for Biomira, and we are on track to have four programs in clinical development by the end of 2007."

The magnitude of the inhibition depended on the status of PTEN in the cell lines, with PTEN-negative cells showing greater sensitivity to PX-866. Treatment with PX-866 inhibited activation of AKT and other downstream targets of PI3K. A dose-dependent increase in autophagy, a type of programmed cell death, was observed and PX-866 also inhibited invasive and angiogenic capabilities of cultured glioma cells. In animals, PX-866 inhibited subcutaneous tumour growth by 84 percent after 4 weeks of oral dosing and increased median survival of animals with intracranial tumours. The authors conclude that PX-866 is a highly promising PI3 kinase inhibitor in glioblastomas and other tumours with aberrant PTEN/PI3K expression, which include advanced ovarian, breast and prostate cancers, as well as lung and head and neck cancers.