OSI begins clinical development in c-kit / VEGFR program
OSI Pharmaceuticals has initiated a Phase I clinical study of OSI-930, the first drug candidate to emerge from the company's research programme focused on the identification of dual c-kit/VEGFR inhibitors.
OSI Pharmaceuticals has initiated a Phase I clinical study of OSI-930, the first drug candidate to emerge from the company's research programme focused on the identification of dual c-kit/VEGFR inhibitors.
A second agent from this programme, OSI-817, is currently being evaluated in pre-clinical toxicology experiments prior to entry into the clinic. Both these drug candidates are potent tyrosine kinase inhibitors that block cellular signalling through the receptor tyrosine kinases, c-kit and vascular epidermal growth factor receptor (VEGFR, also known as KDR). The agents are designed to target both cancer cell proliferation and blood vessel growth, or angiogenesis. The company anticipates moving both candidates through early stages of development before selecting one of the two candidates for full clinical development in cancer patients.
'Our research efforts are focused on the development of next-generation targeted therapies designed to supplement and complement a portfolio built around Tarceva, our flagship product,' stated Dr Neil Gibson, vice president of research at OSI Pharmaceuticals. 'We believe the kinase inhibitory profile of OSI-930 and OSI-817 offers a unique blend of likely efficacy and side effects that will allow for competitive positioning of this programme.'
This single-centre, open-label, vehicle-controlled Phase I study is scheduled to enrol up to 35 healthy volunteers in the US, and is designed to determine the safety and tolerability of single oral doses of OSI-930. The study will include extensive pharmacokinetic sampling and pharmacodynamic evaluation and will better facilitate the design of an optimal clinical program in cancer patients.
Background
Receptor tyrosine kinases function as key regulators in the control of tumour growth and angiogenesis. Pre-clinical data presented at the 2004 AACR-NCI-EORTC International Conference Molecular Targets and Cancer Therapeutics indicated that the lead compound, OSI-930, in addition to inhibiting VEGFR, is also equally active against both mutant and wild type c-kit in cellular systems. These compounds also have activity in multiple tumour models that are thought to be dependent upon angiogenesis. Combining the inhibition of growth and survival pathways with antiangiogenic activity is designed into translate into a broad range of clinical activity.