Onyx receives milestone payment

Onyx Pharmaceuticals, from Richmond, CA, US, will receive $500,000 from its collaborator, Pfizer Inc, who has initiated Phase I clinical trials for an anti-cancer compound discovered during the two companies' research collaboration.

Pfizer is managing and funding all clinical development and commercialisation activities for this compound, known as PD332991. In exchange, Onyx will receive a high single-digit royalty if PD332991 is commercialised. Onyx will also receive milestone payments associated with the achievement of certain clinical and regulatory events.

This novel compound is intended to intervene in the misregulated cell cycle of tumour cells by inhibiting a key enzyme, cyclin-dependent kinase 4 (cdk4). The normal cell cycle consists of distinct phases during which the cell's DNA is copied and the cell divides. Cdks are enzymes that operate as switches to move the cell through these stages by controlling protein phosphorylation. PD332991 is a cdk4 inhibitor active in the initial stage (G1) of the cell cycle, a phase where most human tumours have abnormal regulation. It is anticipated that blocking cdk4 activity may provide an approach to inhibiting proliferation of tumour cells at a key step in the cell cycle, one where cancer cells become distinct from normal cells.

Earlier this year, at the annual meeting of the American Association for Cancer Research (AACR), Pfizer researchers reported that PD332991 is a highly selective and potent cdk4 inhibitor. It was shown to arrest the cell in the G1 phase of the cell cycle, preventing it from entering the S phase, the step where the cell's DNA is replicated. Pfizer researchers demonstrated that oral administration of PD332991 resulted in marked tumour regression in in vivo models. Thus it appears that PD332991 has the potential to shrink tumours, as well as to prevent tumour growth.