Exelixis Reports Positive Phase 1 Data for XL228 at EORTC-NCI-AACR Symposium

Inhibitor of IGF1R and SRC Shows Early Signs of Clinical Benefit
GENEVA--(Business Wire)--
Exelixis, Inc. (Nasdaq:EXEL) today reported preliminary phase 1
data from a dose-escalation trial of XL228 in patients with advanced
malignancies (solid tumors, lymphoma, or multiple myeloma) for which
standard therapies are no longer effective. XL228 is a potent small
molecule inhibitor of insulin-like growth factor type 1 receptor
(IGF1R) and SRC, which are protein kinases known to promote cancer
cell survival, proliferation, and migration. XL228 also inhibits
BCR-ABL, a protein kinase associated with chronic myelogenous leukemia
(CML). Carolyn Britten, MD, Associate Professor and Director of the
Phase 1 Oncology Program, UCLA Jonsson Comprehensive Cancer Center,
and an investigator on the phase 1 trial, presented the data in a
poster session (Abstract #390) at the EORTC-NCI-AACR Symposium on
Molecular Targets and Cancer Therapeutics, which is being held October
21-24 in Geneva, Switzerland. The poster will be available today on
the Exelixis web site.

"The data presented today show that XL228 has been well tolerated
and exhibits favorable pharmacokinetics and target modulation," said
Michael M. Morrissey, PhD, President of Research and Development at
Exelixis. "The compound shows clear evidence of inhibiting both IGF1R
and SRC, which are promising new targets of interest in solid tumors
and hematological malignancies, and also shows early signs of clinical
benefit. We have recently presented data showing that XL228 inhibits
both wild-type and mutationally-resistant forms of BCR-ABL and thus
has potential utility in the treatment of refractory CML. We are
therefore highly encouraged about the prospects for this compound in
the potential treatment of multiple solid tumors and hematological
malignancies."

XL228 is administered as a one-hour IV infusion once- or
twice-weekly in patients with solid tumors, multiple myeloma, or
lymphoma, for whom standard therapies are no longer effective. Dose
levels tested so far are 0.45, 0.9, 1.8, 3.6, 5.4, and 8.0 mg/kg
once-weekly (Cohorts 1-6) and 2.7 mg/kg twice weekly (Cohort 1T).

Thirty patients have received greater than or equal to 1 dose of
XL228 in this study, and of these, 23 have completed at least 4 weeks
of treatment as of October 10, 2008. Full data are available for 16
subjects. As of October 10, 2008, 7 of 16 evaluable patients have
experienced prolonged stable disease (greater than 3 months), with one
metastatic non-small cell lung cancer patient experiencing a 27%
reduction in all target lesions by RECIST criteria.

"These early signs of clinical benefit with XL228 are
encouraging," said Carolyn Britten, MD, Associate Professor and
Director of the Phase 1 Oncology Program, UCLA Jonsson Comprehensive
Cancer Center. "We look forward to continued studies of this promising
compound."

No drug-related serious adverse events (SAEs) have been reported
as of October 10, 2008. Asymptomatic XL228-related hyperglycemia
(Grade 1 to 3) not requiring medical intervention and lasting up to 4
hours post-infusion has been observed at doses greater than or equal
to 3.6 mg/kg weekly and at 2.7 mg/kg twice-weekly. Other common AEs
(Grade 1 to 2) reported as possibly XL228-related include perioral
numbness, tongue tingling and numbness, dysgeusia, lightheadedness,
euphoria, anxiety, diarrhea, and hypophosphatemia. Dose-limiting
toxicity (DLT) of neutropenia (Grade 3 and 4) has been reported in two
subjects receiving XL228 at the 8.0 mg/kg once-weekly dose. One DLT of
neutropenia (Grade 4) has also been reported in a subject receiving
XL228 at the 2.7 mg/kg twice-weekly dose. Final determination of the
maximum tolerated dose (MTD) is ongoing.

In pharmacodynamic analyses, inhibition of IGF1R and SRC kinase
pathway signaling by XL228 was observed in circulating leukocytes,
hair follicles, and skin biopsy samples. Transient upregulation of
plasma glucose and insulin was also observed, consistent with an
impact on insulin and insulin-like growth factor signaling.

About XL228

XL228 is a small molecule protein kinase inhibitor, with potent
activity against IGF1R, SRC,, fibroblast growth factor receptors 1-3
(FGFR1-3), and the Aurora kinases. IGF1R is commonly activated in
neoplastic growth and contributes to cell proliferation, cell
survival, and resistance to genotoxic agents. SRC is a mediator of
cell migration and invasion, key aspects of the metastatic phenotype.
FGFR1-3 play important roles in tumor growth and angiogenesis. Aurora
kinases control crucial steps in mitotic progression and cytokinesis.
XL228 also inhibits BCR-ABL, including the T315I mutant form which is
resistant to currently approved BCR-ABL inhibitors. XL228 has
exhibited potent pharmacodynamic and anti-tumor activity in a variety
of solid tumor xenograft models.

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 3, phase 2, and phase 1
clinical development. Exelixis has established strategic corporate
alliances with major pharmaceutical and biotechnology companies,
including GlaxoSmithKline, Bristol-Myers Squibb, Genentech, Wyeth
Pharmaceuticals and Daiichi-Sankyo. For more information, please visit
the company's website at http://www.exelixis.com.

Forward-Looking Statements

This press release contains forward-looking statements, including,
without limitation, statements related to the potential utility of
XL228 in the treatment of refractory chronic myelogenous leukemia as
well as multiple solid tumors and hematological malignancies; XL228 as
a potentially effective treatment option for a variety of tumor types;
and continued studies for XL228. Words such as "hope," "potential,"
"look," "continued," and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are based
upon Exelixis' current plans, assumptions, beliefs, and 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 XL228 to demonstrate safety and efficacy in
clinical testing; the therapeutic and commercial value of XL228; and
the ability to conduct XL228 clinical trials sufficient to achieve a
positive completion. These and other risk factors are discussed under
"Risk Factors" and elsewhere in Exelixis' quarterly report on Form
10-Q for the quarter ended June 27, 2008, and 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.

Exelixis and the Exelixis logo are registered U.S. trademarks.

Exelixis, Inc.
Charles Butler, 650-837-7277
Senior Director
Corporate Communications & Investor Relations
cbutler@exelixis.com
Soleil Harrison, 650-837-7012
Senior Manager
Corporate Communications
sharrison@exelixis.com

Copyright Business Wire 2008