PRAGUE, Czech Republic, Nov. 9 /PRNewswire-FirstCall/ -- Exelixis, Inc. announces that the first results from an ongoing Phase I trial of XL184, a small molecule inhibitor of multiple receptor tyrosine kinases (RTKs) implicated in tumor cell growth and angiogenesis, including c-MET and VEGF were reported today. Preliminary results from this ongoing study indicate that XL184 is generally well tolerated and no dose-limiting toxicities have been reported to date. Additionally, the compound appears to have a very long half-life, which may allow for dosing flexibility. Dr. Razelle Kurzrock of the Division of Cancer Medicine and Department of Radiology at The University of Texas M. D. Anderson Cancer Center and an investigator on the study presented the data in a poster (Abstract #405) at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is being held November 7-10 in Prague, Czech Republic.
As of October 6, 2006, 21 patients had been enrolled in the trial, of which 18 were evaluable for safety and pharmacokinetic analyses. To date, there have been six XL184-related adverse events reported. None of these events was dose-limiting and further dose escalation is currently ongoing. The pharmacokinetic profile of XL184 showed a long half life of 59.1 - 98.3 hours. This was independent of dose and duration of treatment. As reported by the investigators, there were three patients with some improvement in disease measures. One patient with carcinoid carcinoma had a reported decrease in tumor size (20%), one patient with cutaneous T cell lymphoma had improvement in skin lesions, and one patient with medullary thyroid carcinoma had a decrease in serum tumor markers. Three additional patients have achieved prolonged stable disease of at least three months (carcinoid carcinoma [2] and metastatic parotid tumor [1]).
“XL184 has been generally well tolerated and exhibits a favorable pharmacokinetic profile,” said Gisela M. Schwab, M.D., senior vice president and chief medical officer of Exelixis. “Further dose escalation is currently ongoing and we eagerly anticipate progress of this program.”
Additional Information
Exelixis’ clinical investigators will discuss clinical data on XL999, XL880, XL820 and XL184 in conjunction with data presentations at the conference. The discussion will take place in Prague at 6:00 p.m. (local time) / 12:00 p.m. (ET) / 9:00 a.m. (PT) on Thursday, November 9, 2006. The discussion will be webcast and archived and may be accessed in the Event Calendar page under Investors at www.exelixis.com . Additionally, the XL184 poster presented at the conference may be accessed in the Pipeline page at www.exelixis.com upon the conclusion of the conference.
About the Trial
This Phase I, nonrandomized, open-label, dose-finding trial is being conducted in patients aged 18 years or older with histologically confirmed advanced solid malignancy or lymphoma that is metastatic or unresectable and for which alternative therapies do not exist or are no longer effective. Patients receive two cycles of an oral dose of XL184 daily for 5 consecutive days with a 9-day observation period. Primary endpoints of the trial are to evaluate safety and tolerability of XL184; determine the maximum tolerated dose (MTD) of XL184; and to evaluate the plasma pharmacokinetics of XL184 administered orally to patients with advanced malignancies. Secondary endpoints are to assess the preliminary anti-tumor activity after repeat administration of XL184 and to assess the effects of XL184 on vascular permeability in patients enrolled at the MTD. An evaluation of the pharmacodynamic effects of XL184 is being conducted as an exploratory endpoint.
About XL184
XL184 is a novel, orally administered, small molecule anticancer compound that in preclinical models has demonstrated potent inhibition of both the hepatocyte growth factor receptor (Met) and the vascular endothelial growth factor receptor 2 (VEGFR2). XL184 has also exhibited potent inhibition of other important RTKs that have been implicated in various forms of cancer including mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (Flt3) and the endothelial cell RTK receptor (Tie-2). In preclinical efficacy studies, XL184 has inhibited tumor growth and induced the regression of large tumors in a broad range of human tumor xenograft models including breast cancer, lung cancer and glioma. In laboratory studies, XL184 has demonstrated good oral bioavailability and pharmacokinetic properties.
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, Wyeth Pharmaceuticals and Sankyo. For more information, please visit the company’s web site at www.exelixis.com .
This press release contains forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “slated,” “goal,” “promising” 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 potential failure of product candidates to demonstrate safety and efficacy in clinical testing, which could prevent or significantly delay regulatory approval; the ability to complete and initiate trials at the referenced times; the ability to conduct clinical trials sufficient to achieve a positive completion; 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, 2006 and other filings with the Securities and Exchange Commission. The company 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.
Exelixis, Inc.
CONTACT: investors, Charles Butler, Director, Corporate Communications,+1-650-837-7277, or cbutler@exelixis.com, or media, Soleil MaxwellHarrison, Senior Manager, Corporate Communications, +1-650-837-7012, orsharrison@exelixis.com, both of Exelixis, Inc.
Web site: http://www.exelixis.com//
