Exelixis Files IND Application for XL281
Friday October 13, 6:00 am ET
Next-Generation Kinase Inhibitor Enters Clinical Development
SOUTH SAN FRANCISCO, Calif., Oct. 13 /PRNewswire-FirstCall/ -- Exelixis, Inc. (Nasdaq: EXEL - News) has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration for XL281, a novel anticancer compound designed to potently inhibit the RAS/RAF/MEK/ERK signaling pathway. Mutational activation of RAS occurs in about 30 percent of all human tumors, including non-small cell lung, pancreatic, and colon cancer. XL281 is a specific inhibitor of RAF kinases, including the mutant form of B-RAF, which is activated in 60 percent of melanomas, 24-44 percent of thyroid cancers, and 9 percent of colon cancers.
"XL281 emerged from our strategy to advance novel compounds that potently and selectively inhibit mutationally activated downstream kinases implicated in promoting the growth of specific tumor types," said George A. Scangos, Ph.D., president and chief executive officer of Exelixis. "We have identified five additional next-generation compounds that selectively inhibit key targets in the PI3 kinase, RAS/RAF and JAK/STAT pathways and expect to file IND applications throughout the next nine months."
About XL281
XL281 is a novel small molecule drug designed to specifically inhibit RAF kinases, which lie immediately downstream of RAS and are key components of the RAS/RAF/MEK/ERK kinase signaling pathway. Genetic lesions that activate this pathway are common in human tumors, with activating mutations in K-Ras occurring in 30 percent of tumors and activating mutations in B-RAF occurring in approximately 60 percent of melanomas. The RAS/RAF/MEK/ERK pathway also plays a key role in the transmission of growth-promoting signals downstream of receptor tyrosine kinases. This suggests that deregulation of this pathway plays a pivotal role in the progression of many human tumors, and that inhibition of the pathway may provide clinical benefit in the treatment of cancer. In preclinical studies, XL281 showed potent inhibition of B-RAF, mutationally activated B-RAF and C-RAF, and did not interact with kinases outside of the RAF family. XL281 displays high oral bioavailability and strongly inhibits RAS/RAF/MEK/ERK signaling in human tumor models. This translates into substantial inhibition of tumor growth in preclinical xenograft models of human tumors that overexpress receptor tyrosine kinases or harbor activating mutations in RAS or RAF. Phase I clinical trials of XL281 are expected to initiate in late 2006 or early 2007.
About Exelixis
Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases. The company is leveraging its fully integrated drug discovery platform to fuel the growth of its development pipeline, which is primarily focused on cancer. Currently, Exelixis' broad product pipeline includes investigational compounds in Phase III (XL119, exclusively out-licensed to Helsinn Healthcare S.A), Phase II, and Phase I clinical development for cancer and renal disease. Exelixis has established strategic corporate alliances with major pharmaceutical and biotechnology companies including GlaxoSmithKline, Bristol-Myers Squibb Company, Genentech, and Sankyo. For more information, please visit the company's web site at www.exelixis.com . |
