Exelixis, Inc. Reports Additional Data From A Phase I Trial Of XL647 In Patients With Advanced Solid Tumors

PRAGUE, Czech Republic, Nov. 9 /PRNewswire-FirstCall/ -- Exelixis, Inc. announces that updated Phase I data from an ongoing trial of XL647 in patients with advanced solid tumors were presented today. Results demonstrate that XL647 is generally well tolerated and shows evidence of antitumor activity. A maximum tolerated dose (MTD) of 4.68 mg/kg has been established and converted to a fixed dose of 350 mg administered orally. Dr. Branimir I. Sikic of the Stanford University School of Medicine Oncology Division and an investigator in the study presented the data in a poster (Abstract #342) at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is being held November 7-10 in Prague, Czech Republic. A Phase II trial of XL647 in patients with advanced (stage IIIB or IV) non-small cell lung cancer (NSCLC) was initiated in August 2006 and is ongoing.

As of August 1, 2005, 41 patients had been enrolled in the trial and were evaluable for safety and tumor response assessments. Investigators report that one patient with a primary diagnosis of NSCLC had achieved a partial response (unconfirmed) that occurred prior to cycle 16 (approximately 7.5 months of treatment) and then developed progressive disease prior to cycle 20. The patient received a total of 19 cycles (9.5 months). Fourteen additional patients have had stable disease for at least three months (NSCLC [3], chordoma [2], adenoid cystic [2], head and neck [2] and one each with adrenocorticoid, mesothelioma, colorectal, ovarian and leiomyosarcoma).

"The number of patients with prolonged stable disease in this trial is encouraging. The initial partial response in one NSCLC patient and the prolonged disease stabilization in the other three NSCLC patients -- all of whom had failed other therapies, appear to support our rationale for evaluating XL647 in a Phase II trial in this indication," said Gisela M. Schwab, M.D., senior vice president and chief medical officer at Exelixis. "The targets of XL647, the EGFR , HER2, and VEGFR2 receptor tyrosine kinases are clinically validated, and the simultaneous inhibition of these targets may hold significant promise."

As reported previously by investigators, the most common treatment-related adverse events seen in the XL647 clinical trial as of August 1, 2005 were grade 1 or 2 rash, diarrhea, nausea, or fatigue. Hematologic toxicities (9.5% of all toxicities), anemia (7.1%) and grade 2 thrombocytopenia (2.4%) were also reported. Two events considered possibly related to study treatment have been reported: a grade 4 pulmonary embolism and a grade 3 elevation in INR in a patient taking concomitant warfarin. Two patients enrolled experienced grade 3 diarrhea that was considered probably related to study treatment. Three dose-limiting toxicities occurred: a grade 3 QTc prolongation (probably related) and two incidences of grade 3 diarrhea.

The XL647 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 that is metastatic or unresectable and for which alternative therapies do not exist or are no longer effective. Patients were enrolled in successive cohorts to receive XL647 orally as a single dose on day 1, followed by 5 continuous daily doses starting on day 4. Patients then continued to receive dosing for 5 continuous days followed by a break with cycles repeated every 14 days. Patients were allowed to stay on-study in the absence of unacceptable toxicity until evidence of disease progression. The primary objective of the Phase I dose escalation trial was to establish a MTD and to assess safety and tolerability of oral administration of XL647. Secondary objectives included PK analyses and tumor response. Tumor response rate was also included as an exploratory endpoint.

About XL647

XL647 is a potent inhibitor of multiple RTKs implicated in driving tumor cell proliferation and tumor vascularization (blood vessel formation). XL647 inhibits the EGF, HER2, and VEGF RTKs, each of which is a target of currently approved cancer therapies. In addition, XL647 inhibits EphB4, an RTK that is highly expressed in many human tumors and plays a role in promoting angiogenesis. In a broad array of preclinical tumor models including breast, lung, colon and prostate cancer, XL647 demonstrated potent inhibition of tumor growth and caused tumor regression. In cell culture models, XL647 retained significant potency against mutant EGFRs that cause resistance to current EGFR inhibitors. XL647 is currently in Phase II clinical trial in patients with non-small cell lung cancer who have had no prior therapy.

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 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.

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//