New trial and New Study of New Combination

[RandyW]

Exelixis Initiates Phase 1/2 Trial of XL184 in Patients With Non-Small Cell

Lung Cancer

-First Combination Study of a MET and EGFR Inhibitor-

SOUTH SAN FRANCISCO, Calif., Jan. 7 /PRNewswire-FirstCall/ -- Exelixis,

Inc. (Nasdaq: EXEL) today announced that it has initiated a phase 1/2 trial of

XL184 in patients with non-small cell lung cancer (NSCLC) who have had

progressive disease while on a regimen containing erlotinib.

XL184 is a small molecule that simultaneously inhibits the MET, RET and

VEGFR receptor tyrosine kinases. In the initial phase 1 part of the study,

safety and pharmacokinetics of combining XL184 with erlotinib will be

evaluated. The primary endpoint of the phase 2 part of the study is overall

response rate. Secondary endpoints include progression-free survival, overall

survival and pharmacodynamics.

"XL184 is a potent inhibitor of MET, and MET amplification has been shown

to play an important role in the development of resistance to EGFR inhibitors

in NSCLC," said Michael Morrissey, Ph.D., president of research and

development of Exelixis. "Our preclinical data suggest that XL184 effectively

inhibits growth of cancer cells that have become resistant to EGFR inhibitors

through activation of the MET signaling pathway. XL184 also potently inhibits

VEGFR, which is a validated target in the treatment of NSCLC. The compound has

shown encouraging anti-tumor activity in an initial phase 1 trial and we are

executing a phase 2 clinical development program, and are planning on

initiation of a pivotal trial for XL184 in medullary thyroid cancer in 2008."

The phase 1/2 study of XL184 is expected to enroll up to 86 NSCLC patients

who have had disease progression while on erlotinib. The phase 1 portion of

the study will evaluate dose escalation of XL184 in combination with

erlotinib, both administered daily. Patients in the first cohort will receive

a dose of XL184 that is below the maximum tolerated dose (MTD) identified in

the ongoing phase 1 trial of XL184, in combination with erlotinib. Subsequent

cohorts will receive erlotinib in combination with escalating doses of XL184

until the MTD is reached. In the phase 2 portion of the study, patients will

be randomized to receive XL184 at the MTD alone or in combination with

erlotinib. Additionally, correlative studies will evaluate MET amplification

and EGFR mutational status. MET and EGFR signaling activity will be assessed

in tumor and surrogate tissue.

Data from an ongoing phase 1 trial of XL184 in patients with advanced

malignancies were presented in October 2007 at the 2007 AACR-NCI-EORTC

International Conference on Molecular Targets and Cancer Therapeutics

(Abstract #A152). Investigators reported that anti-tumor activity had been

observed in a variety of cancers at doses that are not associated with

significant toxicity. There were 33 patients available for safety,

pharmacokinetic and tumor response analyses as of the June 22, 2007 cutoff;

further data were also provided for six additional patients after the cutoff.

Of seven patients with medullary thyroid cancer (MTC), three had partial

responses (two confirmed and one unconfirmed) as of the date of the AACR-NCI-

EORTC Conference. In addition, as of such date, six of the seven patients had

tumor shrinkage and one had non-measurable disease. All seven assessable

patients with MTC experienced a rapid decrease in plasma levels of calcitonin,

a marker frequently elevated in MTC, and six of the seven patients had a

decrease in the tumor marker carcinoembryonic antigen. All seven MTC patients

remain on study. In addition, one patient with a neuroendocrine tumor has an

unconfirmed partial response. In total, 15 patients with various malignancies

have had stable disease lasting from 3 - 20 months, including nine patients

with stable disease for more than six months.

To date, five dose-limiting toxicities (DLTs) have been reported,

including Grade 3 palmar/plantar erythema (hand-foot syndrome), Grade 3 AST

elevation, Grade 3 ALT elevation, and Grade 3 lipase elevation in patients

dosed at 11.52 mg/kg (intermittent dosing schedule), as well as a DLT of Grade

2 mucositis in a patient dosed at 265 mg (daily dosing schedule). Serious

adverse events (AEs) considered possibly or probably related to XL184 include

one report each of Grade 3 fatigue and Grade 3 pulmonary embolism. Dose

escalation continues in order to determine a maximum tolerated dose (MTD).

About XL184

XL184 is a novel, orally administered, small molecule anticancer compound

that in preclinical models has demonstrated potent inhibition of both MET and

VEGFR2. XL184 has also exhibited potent inhibition of other important receptor

tyrosine kinases (RTKs) that have been implicated in various forms of cancer

including RET, KIT, FLT3, and TIE2. 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 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 www.exelixis.com.

Forward-Looking Statements

This press release contains forward-looking statements, including, without

limitation, statements related to the future development and potential

efficacy of XL184, the future conduct of the phase 1/2 trial of XL184 and the

expected timing of the initiation of a pivotal trial of XL184. Words such as

"expected," "will," "planning", "suggest" 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 XL184 and the potential failure of XL184 to demonstrate safety and

efficacy in clinical testing. These and other risk factors are discussed under

"Risk Factors" and elsewhere in Exelixis' quarterly report on Form 10-Q for

the quarter ended September 30, 2007 and Exelixis' other filings with the

Securities and Exchange Commission. Exelixis expressly disclaims any duty,

obligation or undertaking to release publicly any updates or revisions to any

forward-looking statements contained herein to reflect any change in Exelixis'

expectations with regard thereto or any change in events, conditions or

circumstances on which any such statements are based.

SOURCE Exelixis, Inc.

Investors, Charles Butler, Senior Director, Corporate Communications,

+1-650-837-7277, cbutler@exelixis.com; or Media, Soleil Maxwell Harrison,

Senior Manager, Corporate Communications, +1-650-837-7012,

sharrison@exelixis.com, both of Exelixis, Inc.

© Reuters 2008 All rights reserved

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