Exelixis Inc has submitted an investigational new drug application (IND) to the US FDA for XL999, a proprietary novel anticancer compound. Pre-clinical studies with XL999 have demonstrated potent inhibition in vivo against multiple receptor tyrosine kinases (RTKs) that are implicated in tumour angiogenesis, or the development and maintenance of tumour vasculature. Pending clearance by the FDA, the company intends to initiate a phase 1 clinical trial, said a company release.

XL999 is one of several Spectrum Selective Kinase Inhibitors (SSKI) in Exelixis' product pipeline. Each SSKI has a different RTK inhibition spectrum, and each has the potential to achieve efficacy through simultaneous inhibition of multiple RTKs. Pre-clinical studies have shown that XL999 simultaneously inhibits the FGFR, VEGFR, PDGFR and Flt3 RTKs with high levels of potency and demonstrates excellent activity in target-specific cellular functional assays. XL999 has demonstrated potent anti-tumour activity in a variety of pre-clinical models of solid tumours as well as a Flt3-driven model of leukaemia.

"This IND application is the second we have filed this year, which is the direct result of the productivity of our R&D groups," said George A. Scangos, president and chief executive officer. He added, "Together with XL119, which recently began a pivotal Phase 3 study, XL784, which has successfully completed a phase 1 study, XL647, which has begun a phase 1 study, and a rich portfolio of pre-clinical development compounds, XL999 is part of a growing, high-quality pipeline of compounds that we intend to advance rapidly into and through clinical trials. Our goal is to leverage our significant expertise in biology, drug discovery, and development to generate a diverse portfolio of anti-cancer compounds with substantial therapeutic and commercial potential. This IND application is one more sign that we are executing on our vision of becoming a major cancer therapeutics company."

The phase 1 clinical trial of XL999 will be an open-label, dose escalation study conducted in cancer patients. The study is designed to measure the safety, tolerability, pharmacokinetics, pharmacodynamics and biological activity of XL999 following a single intravenous administration. The study will be conducted at a major medical centre in the United States.

Pursuant to a product development and commercialisation agreement between Exelixis and GlaxoSmithKline (GSK), GSK has the option, after completion of phase 2a clinical trials, to elect to develop a certain number of the cancer compounds in Exelixis' product pipeline (other than the company's cancer compound XL119), which may include XL999, thus potentially triggering milestone payments and royalties from GSK and co-promotion rights by Exelixis.