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Exelixis Files IND Application for Novel Anticancer Compound XL880

Posted on: 12/16/2004

Exelixis Files IND Application for Novel Anticancer Compound XL880

Press Release Source: Exelixis, Inc.

Thursday December 16, 3:38 pm ET

SOUTH SAN FRANCISCO, Calif., Dec. 16 /PRNewswire-FirstCall/ -- Exelixis, Inc. (Nasdaq: EXEL - News) has submitted an investigational new drug application (IND) for XL880, a novel, orally administered small molecule for the treatment of cancer. In pre-clinical studies, XL880 demonstrated potent inhibition of the Met and VEGFR2 (KDR) receptor tyrosine kinases (RTKs) which play synergistic roles in promoting tumor growth and angiogenesis. Pending clearance by the U.S. Food and Drug Administration (FDA), Exelixis intends to initiate a Phase I clinical trial in the first quarter of 2005.

"To our knowledge, XL880 will be the most advanced small molecule inhibitor of Met in clinical development. Although Met is a promising target, discovery of Met inhibitors suitable for clinical development has been challenging. We believe XL880 represents a novel and potentially effective approach, simultaneously targeting Met and VEGFR2, to treat various forms of cancer," said George A. Scangos, Ph.D., president and chief executive officer of Exelixis. "XL880 is the third Spectrum Selective Kinase Inhibitor(TM) (SSKI) for which we have filed an IND this year, and we anticipate additional INDs in 2005 and beyond. I am excited about the potential of this high quality pipeline of compounds, and Exelixis is committed to moving these compounds forward as quickly as possible."

In addition to VEGF and Met, XL880 has potent activity against other RTKs that have been implicated in various forms of cancer including KIT, platelet-derived growth factor (PDGF) receptors, FMS-like tyrosine kinase 3 (FLT3), and Tie-2.

Role of Met in Cancer Biology

Preclinical data provide three reasons why inhibition of Met should be an effective cancer therapy. First, activated Met potently promotes cancer cell growth and survival. Second, activation of Met in tumor cells increases their motility and invasiveness, in turn facilitating cancer cell invasion. Third, activation of Met promotes tumor angiogenesis, which facilitates tumor growth, survival, invasion, and dissemination.

Activation or overexpression of Met has been documented as a negative prognostic indicator in patients with bladder, breast, cervical, gastric, ovarian, head and neck, nasopharyngeal, thyroid, liver and lung carcinomas, and in patients with multiple myeloma and glioma as well as hereditary and sporadic papillary renal carcinomas and other solid tumors.

Role of VEGFR2

Pharmacologic inhibition of VEGF signaling in preclinical models results in inhibition of both tumor angiogenesis and tumor growth. Inhibition of VEGF with bevacizumab (Avastin), a monoclonal antibody directed against VEGF, combined with chemotherapy has been shown to improve overall survival in patients with metastatic colorectal cancer.

Met and VEGFR2

In addition to their individual roles, there is evidence that Met and VEGFR2 cooperate to promote tumor angiogenesis. First, both Met (on tumor cells and potentially on endothelial cells) and VEGF are induced in response to tumor hypoxia. Second, activated Met can indirectly promote angiogenesis and tumor growth by upregulating VEGF expression. The synergy between these two targets strongly support the potential utility of a single combined inhibitor such as XL880.

Pursuant to a product development and commercialization 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 compounds in Exelixis' product pipeline (other than the company's cancer compound XL119), which may include XL880, thus potentially triggering milestone payments and royalties from GSK and co-promotion rights by Exelixis.

About Exelixis

Exelixis, Inc. is a leading genomics-based drug discovery company dedicated to the discovery and development of novel therapeutics across various therapy areas. The company is leveraging its fully integrated gene-to-drug platform to fuel the growth of its proprietary drug pipeline. Exelixis' development pipeline currently covers cancer and metabolism and is comprised of the following compounds: XL119 (becatecarin), for which a Phase 3 clinical trial has been initiated in patients with bile duct tumors; XL784, initially an anticancer compound, which has completed a Phase 1 clinical trial and is currently being developed as a treatment for renal disease; XL647 and XL999, which are currently in Phase 1 clinical trials; XL880, which has a newly pending IND application; and XL820, XL844 and XL184, anticancer compounds that are potential IND candidates; and multiple compounds in preclinical development for diseases including cancer, lipid disorders, hyperlipidemia and congestive heart failure. Exelixis has established broad corporate alliances with major pharmaceutical and biotechnology companies, including GlaxoSmithKline (GSK) and Bristol-Myers Squibb Company. Other partners include Merck & Co., Inc., Schering-Plough Research Institute, Inc., Cytokinetics, Inc., and Scios Inc. For more information, please visit the company's web site at

This press release contains forward-looking statements, including without limitation all statements related to the pending IND application or Exelixis' clinical development program for XL880, the therapeutic and commercial potential of XL119, XL784, XL647, XL880, XL999, XL820, XL844 and XL184, other compounds in the Exelixis preclinical pipeline and its program in metabolic diseases. Words such as "believes," "anticipates," "plans," "expects," "intend," "will," "slated," "goal" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Exelixis' current expectations. Forward-looking statements involve risks and uncertainties. Exelixis' actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation the ability of the company to successfully conduct the clinical trials for XL119, XL647 and XL999; the ability of the company to advance additional preclinical compounds into clinical development; the uncertainty of the FDA approval process; and the therapeutic and commercial value of the company's compounds. These and other risk factors are discussed under "Risk Factors" and elsewhere in our quarterly report on Form 10-Q for the quarter ended September 30, 2004 and other filings with the Securities and Exchange Commission. Exelixis expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward- looking statements contained herein to reflect any change in the company's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

NOTE: Exelixis and the Exelixis logo are registered U.S. trademarks. Spectrum Selective Kinase Inhibitor is a trademark of Exelixis, Inc.

-------------------------------------------------------------------------------- Source: Exelixis, Inc.

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