Data From Phase I Trial Of Exelixis, Inc.’ XL647 Presented At Cancer Conference

PHILADELPHIA, Nov. 15 /PRNewswire-FirstCall/ -- Exelixis, Inc. today reported data from a Phase I trial of XL647 in patients with various advanced solid tumors. Study results demonstrate that XL647 has been generally well tolerated to date with evidence of biologic and clinical activity. Dr. Heather Wakelee, Instructor of Medicine, Stanford University presented the results of the Phase I trial of XL647 in a poster, titled “A Phase I dose-escalation and pharmacokinetic (PK) study of a novel spectrum- selective kinase inhibitor (SSKI), XL647, in patients with advanced solid malignancies,” (Abstract A261), at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

Thirty-one patients to date have been treated across eight dose levels (0.06, 0.12, 0.19, 0.28, 0.39, 0.78, 1.56 and 3.12 mg/kg) and are available for safety analysis. XL647 was generally well tolerated. Fatigue, nausea and diarrhea, which were mild to moderate and transient, were the most commonly reported adverse events. The maximum tolerated dose (MTD) has not yet been reached and dose escalation continues. Preliminary PK analysis indicates that XL647 shows approximately dose-proportional exposure, with a mean time to maximal concentration (Tmax) of approximately 6-9 hours and an elimination half-life of approximately 70 hours. Cycle number ranges from one to 21.

To date, 1 patient with non-small-cell lung cancer (NSCLC) treated at the lowest dose had a partial response and 7 others (NSCLC [n=2], chordoma [n=2], adenoid cystic carcinoma, adrenocortical carcinoma, colorectal) have had prolonged stable disease (>3 months).

“These data are very exciting and demonstrate the excellent tolerability of XL647 at dose levels that showed tumor responses in our preclinical studies. We have just seen our first potential dose-limiting toxicity, Grade 3 diarrhea. In addition, an episode of Grade 2 skin rash was reported after the poster was finalized. We will move forward to establish an MTD and phase II dosing schedule,” said George A. Scangos, Ph.D., president and chief executive officer of Exelixis. “We are also very encouraged by the signals of activity that we have seen in this Phase I trial, and will initiate a Phase II program in non-small-cell lung cancer and breast cancer very soon,” continued Scangos.

“The favorable safety profile to date, long-half life and tumor effects observed following treatment with XL647 are encouraging, and suggest that effective and tolerable dosing regimens may be feasible with this novel compound,” said Dr. Wakelee. “These results support the evaluation of XL647 in Phase II trials,” continued Wakelee.

About the Trial

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. The study enrolled patients with advanced solid malignancies 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.

About XL647

XL647, an orally available Spectrum Selective Kinase Inhibitor(TM) (SSKIs), is a potent inhibitor of receptor tyrosine kinases (RTKs) that are 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 causes tumor regression. In cell culture models XL647 retains significant potency against mutant EGFRs that are resistant to current EGFR inhibitors.

About Exelixis

Exelixis, Inc. is a biotechnology company dedicated to the discovery and development of novel therapeutics that will potentially enhance the care and lives of patients with cancer and other serious diseases. The company is leveraging its fully integrated gene-to-drug platform to fuel the growth of its proprietary drug pipeline. Exelixis’ development pipeline covers cancer and metabolism and is comprised of the following compounds: XL119 (becatecarin), for which a multinational Phase 3 clinical trial in bile duct tumor is ongoing and which has been exclusively licensed to Helsinn Healthcare S.A. with rights to reacquire commercial rights for North America; XL784, which is being advanced as a treatment for renal disease and is currently in a Phase 1 clinical trial using a newly developed capsule formulation of the compound; XL647, XL999, XL880, XL820, XL844 and XL184, anticancer compounds currently in Phase 1 clinical trials; and multiple compounds in preclinical development for diseases including cancer and various metabolic and cardiovascular disorders. Exelixis has established broad corporate alliances with major pharmaceutical and biotechnology companies including GlaxoSmithKline (GSK) and Bristol-Myers Squibb Company. Pursuant to a product development and commercialization agreement between Exelixis and GSK, GSK has the option, after completion of Phase 2a clinical trials by Exelixis, to elect to develop a certain number of compounds in Exelixis’ product pipeline, which may include XL784 and the cancer compounds identified in this press release (other than XL119), thus potentially triggering milestone payments and royalties from GSK and co-promotion rights by Exelixis. For more information, please visit the company’s web site at

This press release contains forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “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 potential failure of product candidates to demonstrate safety and efficacy in clinical testing; the ability of the company to complete Phase 1 and initiate Phase 2 clinical trials for XL647 at the referenced time, the ability to conduct Phase 1 clinical trials for XL784, XL999, XL880, XL820, XL844 and XL184 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, 2005 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 and the Exelixis logo are registered U.S. trademarks.

Exelixis, Inc.

CONTACT: Charles Butler, Associate Director, Corporate Communications ofExelixis, Inc., +1-650-837-7277, or