Promising Data From Phase I Trial Of Exelixis, Inc.' XL880 Presented At Cancer Conference

PHILADELPHIA, Nov. 15 /PRNewswire-FirstCall/ -- Exelixis, Inc. today reported preliminary results of a Phase I trial of XL880 in patients with advanced solid tumors. Study results demonstrate that XL880 has been generally well tolerated to date with evidence of biologic and clinical activity. Patient accrual in this trial is ongoing. The data were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

Thirteen patients thus far have been treated at three dose levels (0.1, 0.2 and 0.4 mg/kg). No grade 1-4 toxicities have been observed. The maximum tolerated dose (MTD) has not yet been reached. Preliminary pharmacokinetic (PK) analysis indicates that systemic drug exposure and peak plasma levels (Cmax) increased generally dose-proportionally with increasing XL880 dose. Terminal half-life values were approximately 60 hours. Continued dose escalation is ongoing.

One patient with hereditary papillary renal cell carcinoma (HPRCC), a tumor driven by over-expression of c-met, has experienced a 15 percent reduction in tumor volume after failing multiple other therapies.

Dr. Paul Eder, Clinical Director, Experimental Therapeutics Program at the Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, and Dr. Patricia LoRusso, Professor of Medicine at Wayne State University and Director of Developmental Therapeutics at the Karmanos Cancer Center are clinical investigators in the study. Both investigators presented the data in a poster, titled "A Phase I study of a novel spectrum-selective kinase inhibitor (SSKI), XL880, administered orally in patients with advanced solid malignancies," (Abstract A245).

George A. Scangos, Ph.D., president and chief executive officer of Exelixis said, "We are very encouraged by these data and believe they provide evidence in support of the potential clinical utility of XL880. What is most encouraging is that the response observed in the patient with HPRCC suggests that the compound's activity against c-met is consistent with the cancer biology on which it was developed. We believe that if we can provide similar benefit to other patients with this disease, we may have a potentially rapid path to registration," continued Scangos.

"These are early but encouraging data," said Dr. Eder, an investigator conducting the trial. "XL880 is the first inhibitor of c-met to enter clinical development, and we have seen evidence of clinical activity in a patient with a type of tumor in which c-met is a known driver of growth and proliferation. The data available to date suggest that c-met may be a promising new target for the treatment of cancer and support the continued clinical evaluation of XL880," continued Eder.

About the Trial

The primary objective of each Phase I dose escalation trial was to establish a MTD and to assess safety and tolerability of oral administration of XL880. Secondary objectives included PK analyses and tumor response. Patients with advanced solid malignancies were enrolled in successive cohorts to receive XL880 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 XL880

XL880 is an orally available Spectrum Selective Kinase Inhibitor TM (SSKI) designed to target multiple receptor tyrosine kinases (RTKs) implicated in the development, progression and spread of cancer. The primary targets of XL880 are the hepatocyte growth factor (ligand for Met) and vascular endothelial growth factor RTK families, although platelet-derived growth factor receptor (PDGFR), c-KIT, FLT3 and Tie-2 are also inhibited. Activation or overexpression of Met has been documented as a negative prognostic indicator in patients with various carcinomas, and in patients with multiple myeloma, glioma and other solid tumors. Activation of Met by mutation is the causitive factor in an inherited kidney cancer syndrome, hereditary papilliary renal cell carcinaoma. Mutational activation of Met has also been found in sporadic kidney cancer, lung carcinomas and head and neck carcinomas. Met is a key driver of tumor cell growth, motility, invasion, metastasis and angiogenesis. XL880 is the first orally bioavailable small molecule Met inhibitor to enter the clinic.

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 www.exelixis.com.

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 to conduct Phase 1 clinical trials for XL784, XL647, 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 cbutler@exelixis.com

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