Isis Pharmaceuticals And AstraZeneca Form Strategic Alliance On RNA Therapeutics For Cancer

     Isis Pharmaceuticals And AstraZeneca Form Strategic Alliance On RNA
                           Therapeutics For Cancer

PR Newswire

CARLSBAD, Calif., Dec. 11, 2012

CARLSBAD, Calif., Dec. 11, 2012 /PRNewswire/ --Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) and AstraZeneca announced today a strategic alliance for the
discovery and development of novel generation antisense therapeutics against
five cancer targets, which includes a license to develop and commercialise
ISIS-STAT3[Rx], a drug Isis is currently evaluating in an early clinical trial
in patients with advanced lymphomas. Antisense therapies target the proteins
involved in disease processes by destroying the RNA that is involved in
creating these proteins. The Isis discovery platform develops specific
therapies that bind to messenger RNA (mRNA) and inhibit the production of
disease-causing proteins.

The strategic alliance aims to apply AstraZeneca's experience in developing
personalised medicines to enhance the drug discovery and development process
for four research programs in the oncology area and to aid in the development
of ISIS-STAT3[Rx] for patient populations that could benefit the most from
inhibition of STAT3, a protein that drives cancer growth. The combination of
Isis' antisense technology and its new Generation 2.5 chemistry, which
increases the potency of its therapeutics, provides AstraZeneca the
opportunity to develop drugs that could be much more effective in cancers that
are difficult to address with conventional small molecules or antibodies.

"Isis' antisense technology platform allows AstraZeneca to broaden our
oncology research efforts beyond traditional drug discovery methods, while at
the same time becoming more specific about how we target cancer," said Susan
Galbraith, head of the AstraZeneca Oncology Innovative Medicines Unit.
"AstraZeneca's expertise in oncology translational science and our global
capabilities in development and commercialisation of oncology products and
Isis' innovative approach to discovering novel medicines reflect a common goal
of bringing new medicines to cancer patients."

"We are excited to collaborate with AstraZeneca, a global leader in oncology,
to apply our technology and drug discovery expertise to developing novel
anti-cancer agents.We will benefit from AstraZeneca's extensive oncology
expertise in the use of novel pre-clinical animal models to validate targets
and develop predictive assays to identify which patients would benefit the
most from these new targets," said B. Lynne Parshall, chief operating officer
and chief financial officer at Isis.

"ISIS-STAT3[Rx] is our first cancer drug to incorporate our new technology and
we are encouraged by the early clinical data we have observed," said Brett
Monia, Ph.D., senior vice president, antisense drug discovery at Isis."While
STAT3 is implicated in a number of different cancers, the focus in our ongoing
clinical study is to evaluate the effectiveness of our drug in hematologic
malignancies, such as lymphoma.We have worked closely with AstraZeneca to
design a rapid path to the market for ISIS-STAT3[Rx] in these patient
populations.While working toward this goal, AstraZeneca's resources,
expertise and development capabilities also provide us the opportunity to
evaluate ISIS-STAT3[Rx] as a broad-based anti-tumor agent."

Under the terms of the agreement, Isis will receive from AstraZeneca $31
million in upfront and near term payments, comprising a $25 million payment on
signing followed by a $6 million payment in the second quarter of 2013
assuming the research program is continuing.In exchange, Isis has granted
AstraZeneca an exclusive license to develop and commercialise ISIS-STAT3[Rx]
and a pre-clinical program as well as an option to license products developed
under a separate research program. Once licensed, AstraZeneca will be
responsible for all further development and commercialization. AstraZeneca
will be responsible for all development of ISIS-STAT3[Rx] other than the
conduct of the ongoing clinical trial, which Isis will complete. Isis is
eligible to receive further milestone payments subject to achieving certain
predefined clinical success criteria for the ISIS-STAT3[Rx] program and
pre-clinical milestones for the other programs. Isis is also eligible to
receive downstream development and approval milestone payments, license fees
for research program targets as well as royalties on sales from products that
are successfully commercialized.

Isis will hold a conference call and live audio webcast today, December 11,
2012 at 8:30 am ET to provide detailed information on its new strategic
alliance with AstraZeneca. Interested parties may listen to the call by
dialing 866-713-8567and refer to passcode "ISIS 2012," or access the webcast

]ISIS-STAT3[Rx] is the first drug in Isis' pipeline that incorporates Isis'
Generation 2.5 chemistry, which was developed to increase potency of antisense
drugs thereby creating opportunities for drugs like ISIS-STAT3[Rx] to be more
effective in addressing targets in a broader range of tissues, including
tumors. ISIS-STAT3[Rx] is designed to inhibit the production of signal
transducer and activator of transcription 3 (STAT3), a protein critical for
tumor growth and survival. Because STAT3 is overexpressed in numerous types of
cancers, ISIS-STAT3[Rx] has the potential to be broadly useful for both solid
and hematological tumors. Isis recently reported encouraging data from its
ongoing Phase 1 study showing that ISIS-STAT3[Rx] had an acceptable safety
profile and treatment with ISIS-STAT3[Rx] resulted in clear responses in a
number of patients with advanced cancer who were refractory to multiple prior
chemotherapy treatments. The indication of activity so early in development in
a Phase 1 study prompted Isis to initiate a follow up clinical study to
evaluate the safety and efficacy of ISIS-STAT3[Rx] in focused patient
populations with lymphomas and other advanced hematologic cancers linked to
activation of STAT3 who have failed other treatment options.

AstraZeneca is a global, innovation-driven biopharmaceutical business with a
primary focus on the discovery, development and commercialisation of
prescription medicines for gastrointestinal, cardiovascular, neuroscience,
respiratory and inflammation, oncology and infectious disease. AstraZeneca
operates in over 100 countries and its innovative medicines are used by
millions of patients worldwide. For more information please visit:

Isis is exploiting its leadership position in antisense technology to discover
and develop novel drugs for its product pipeline and for its partners. Isis'
broad pipeline consists of 25 drugs to treat a wide variety of diseases with
an emphasis on cardiovascular, metabolic, severe and rare diseases, and
cancer. Isis' partner, Genzyme, plans to commercialize Isis' lead product,
KYNAMRO™, in the United States and Europe following regulatory approval. Isis'
patents provide strong and extensive protection for its drugs and
technology.Additional information about Isis is available at

This press release includes forward-looking statements, including statements
regarding Isis' strategic alliance with AstraZeneca, Isis' research and
development opportunities in cancer, the development, activity, therapeutic
potential and safety of ISIS-STAT3[Rx], and the therapeutic benefit of
antisense drugs that incorporate Isis' Generation 2.5 chemistry. Any
statement describing Isis' goals, expectations, financial or other
projections, intentions or beliefs, including the planned commercialization of
KYNAMRO, is a forward-looking statement and should be considered an at-risk
statement. Such statements are subject to certain risks and uncertainties,
particularly those inherent in the process of discovering, developing and
commercializing drugs that are safe and effective for use as human
therapeutics, and in the endeavor of building a business around such drugs.
Isis' forward-looking statements also involve assumptions that, if they never
materialize or prove correct, could cause its results to differ materially
from those expressed or implied by such forward-looking statements. Although
Isis' forward-looking statements reflect the good faith judgment of its
management, these statements are based only on facts and factors currently
known by Isis. As a result, you are cautioned not to rely on these
forward-looking statements. These and other risks concerning Isis' programs
are described in additional detail in Isis' annual report on Form 10-K for the
year ended December 31, 2011 and its most recent quarterly report on Form
10-Q, which are on file with the SEC. Copies of these and other documents are
available from the Company.

Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.
KYNAMRO™ is a trademark of Genzyme Corporation.

SOURCE Isis Pharmaceuticals, Inc.

Contact: AstraZeneca's Contacts: Laura Woodin, R&D Media Lead,
+1-302-885-1087, or Isis Pharmaceuticals' Contacts: D. Wade Walke, Ph.D.,
Executive Director, Corporate Communications and Investor Relations,
+1-760-603-2741, or Amy Blackley, Ph.D., Associate Director, Corporate
Communications, +1-760-603-2772
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