INTERIM PHASE 2 DATA FOR EXELIXISâ€™ XL880 SHOW ANTI-TUMOR ACTIVITY IN PAPILLARY RENAL CELL CANCER
Tumor shrinkage observed in nearly 80% of patientsÂ
San Francisco, CA â€“ October 24, 2007 â€“ Exelixis today reported encouraging data from an ongoing phase 2 trial of XL880, an inhibitor of MET and VEGFR2 kinases, in patients with papillary renal cell carcinoma (PRC). Of 19 patients with measurable disease evaluable for tumor responses, 15 (79%) have had a decrease in tumor size (4-33%), including one patient with a partial response. All 19 evaluable patients with at least one post-baseline tumor assessment have had stable disease for at least three months, including 12 patients with stable disease for six months to 15+ months. Results of preliminary analyses of plasma biomarkers and tumor samples are consistent with inhibition of angiogenesis and proliferation and an increase in apoptosis. Data were presented today in a poster session (Abstract #B249) at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, which is being held October 22-26, 2007 in San Francisco.
â€œThe phase 2 trial of XL880 in PRC was supported both by the biology of the disease, which frequently is associated with activating mutations or amplifications in MET, and the favorable responses observed in patients with PRC in the reported phase 1 study of the compound,â€ said Michael Morrissey, Ph.D., Exelixisâ€™ president of research and development. â€œWe believe that todayâ€™s data, which show that the significant majority of patients on study have experienced tumor shrinkage with prolonged duration of stable disease, highlight the potential utility of XL880 and its potent effects in modulating both MET and VEGFR2 in the clinical setting. We are excited about the potential therapeutic utility of modulating these targets in a variety of solid tumor types.â€
As of October 10, 2007, a total of 21 patients have been enrolled in this ongoing study: Five with activating MET mutations and 16 with wild type MET. Sixteen patients were evaluable for safety endpoints. The majority of adverse events (AEs) (72%) related to XL880 were Grade 1; 21% were Grade 2 and 5% were Grade 3 or higher. The Grade 3 AEs were hypertension in three patients. There were no Grade 4 or 5 adverse events that were judged related to XL880 treatment. A total of 15 serious adverse events (SAEs) in seven patients were reported, of which three were considered related to XL880 (two events of vomiting in one patient and hypertension in another patient).
Preliminary pharmacodynamic analyses in 11 patients show statistically significant changes in PIGF, VEGF-A, sVEGFR2 and EPO, markers of anti-angiogenic activity, following administration of XL880. A potential plasma marker of MET inhibition, sMET, was statistically significantly increased in all 11 patients. XL880 also demonstrated growth inhibition and induction of apoptosis comparing pre- and post-XL880 tumor biopsies from one patient. Preliminary pharmacokinetic analyses were consistent with results from the phase 1 trial.
Also at the AACR-NCI-EORTC conference, investigators presented results of a phase 1 study of XL880 in patients with advanced solid tumors (Abstract #B248). Consistent with data previously reported from this study, XL880 was generally well tolerated when given daily over a 28-day cycle. Ten of 22 patients showed stable disease for at least three months. In a preliminary analysis of samples of 21 patients in this clinical trial, statistically significant anti-angiogenic pharmacodynamic marker changes have been detected, consistent with effects observed with other anti-angiogenic agents. This finding is also consistent with observed hypertension.
Pursuant to the product development and commercialization agreement between Exelixis and GlaxoSmithKline (GSK), GSK has the option, after completion of clinical proof-of-concept by Exelixis, to elect to develop up to three compounds in Exelixis' product pipeline from among XL784, XL880, XL184, XL820, XL999, XL844, XL228, XL281 and XL418. On September 14, 2007, Exelixis announced that it had submitted a comprehensive XL880 data package to GSK for review. GSK has 90 days from the submission date to review the data package and determine if it will select the compound for further clinical development and commercialization.
About the Phase 2 Trial of XL880 in PRC
The multi-center open-label phase 2 study is designed to enroll up to 34 patients with hereditary or sporadic papillary renal cell carcinoma. Eligible patients are stratified retrospectively in Stratum A (one or more of the c-Met germ line mutations) and Stratum B (patients with no c-Met germ line mutations). XL880 is administered at 240 mg/day for five days during a 14-day cycle. Patients may continue in the study in the absence of progressive disease and unacceptable toxicity. Primary objectives of the study are to determine best-confirmed response rate and to evaluate safety and tolerability of XL880 administered orally for five consecutive days every two weeks. Secondary objectives are to assess progression-free survival, overall survival, and duration of response and to continue characterizing the pharmacokinetic and pharmacodynamics profiles of XL880.
XL880 has attractive pharmaceutical properties, with high solubility and oral bioavailability. In preclinical studies, XL880 inhibited its targets with nanomolar potency, and retained potent activity against mutationally activated forms of MET found in hereditary papillary renal cell carcinomas. The compound also demonstrated dose-dependent tumor growth inhibition in models of breast cancer, colorectal cancer, non-small cell lung cancer, and glioblastoma, and has been shown to cause substantial tumor regression in all models tested. Significantly, a single dose of XL880 completely inhibited tumor growth for 21 days in a glioblastoma model. Three phase 2 trials of XL880 are ongoing in patients with papillary renal cell carcinoma, gastric cancer and head and neck cancer.
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 2 and phase 1 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 Daiichi-Sankyo. For more information, please visit the company's web site at http://www.exelixis.com.
This press release contains forward-looking statements, including without limitation statements related to the future development and potential efficacy of XL880. Words such as "believe," "will" 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 lengthy, costly and uncertain process of clinical testing of XL880 and Exelixisâ€™ other compounds, the potential failure of XL880 and Exelixisâ€™ other compounds to demonstrate safety and efficacy in clinical testing and risks related to Exelixisâ€™ dependence on and relationship with GlaxoSmithKline. These and other risk factors are discussed under "Risk Factors" and elsewhere in Exelixisâ€™ Quarterly Report on Form 10-Q for the quarter ended June 30, 2007 and its 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 Exelixisâ€™ expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.