Isis Pharmaceuticals Reports Encouraging Interim Phase 1 Data On ISIS-STAT3Rx In Patients With Cancer

Isis Pharmaceuticals Reports Encouraging Interim Phase 1 Data On ISIS-STAT3Rx
                           In Patients With Cancer

Isis Initiates Phase 2 Study of ISIS-STAT3Rx in Patients with Advanced Cancer

PR Newswire

CARLSBAD, Calif., Oct. 31, 2012

CARLSBAD, Calif., Oct. 31, 2012 /PRNewswire/ -- Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced that preliminary data from the Phase 1 study of
ISIS-STAT3[Rx] in patients with cancer were presented today at the
Oligonucleotide Therapeutics Society in Boston. Interim results of the
initial dose escalation study in patients with cancer showed that
ISIS-STAT3[Rx] treatment resulted in clear responses in patients with advanced
cancer who were refractory to prior chemotherapy treatment, with an acceptable
safety profile. Based on these results, Isis has initiated a Phase 2 study in
focused patient populations with advanced cancer.

"STAT3 expression has been shown to be associated with the growth,
invasiveness and metastases of many types of cancer making it an attractive
target. However, STAT3 has proven to be a difficult target to inhibit safely
with small molecule drugs, making ISIS-STAT3[Rx] even more interesting," said
David S. Hong, M.D., associate professor, department of investigational cancer
therapeutics at the University of Texas MD Anderson Cancer Center. "Patients
with advanced cancer have often failed multiple therapies and have no other
chemotherapeutic options. For these patients there is a desperate need for
new therapies that can halt their disease progression. The clinical responses
observed to date suggest that inhibition of STAT3 could provide benefit to
some of these patients. The early data on ISIS-STAT3[Rx] is impressive
because it suggests that this drug can produce responses in patients with
advanced cancer who have failed to respond to other therapies."

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
effective in more difficult to treat cancers. The Phase 1 study evaluated
ISIS-STAT3[Rx] in patients with solid tumors and lymphoma who have relapsed or
were refractory to multiple chemotherapy regimens. The Phase 2 study will
evaluate the safety and efficacy of ISIS-STAT3[Rx] in focused patient
populations with advanced cancers that have been linked to STAT3 who have
failed all other treatment options. The endpoints for the study include
measurements of anti-tumor activity, STAT3 protein levels in tumor biopsies,
STAT3-related biomarkers, and safety. Efficacy will be evaluated across
different types of cancer and correlated with genetic sequencing from patient
tumor biopsies.

"We believe that the significant improvements in potency we have observed in
our preclinical cancer studies with our Generation 2.5 chemistry should
translate into an effective anti-tumor agent that is broadly applicable to
many different types of cancer. The important role that STAT3 plays in tumor
survival and growth made it a great target to evaluate our Generation 2.5
platform in patients," said Brett Monia, Ph.D., senior vice president,
antisense drug discovery at Isis. "We are very pleased and encouraged with
the safety and efficacy observed in our Phase 1 study of ISIS-STAT3[Rx]. The
promising data generated in our Phase 1 study has enabled us to accelerate our
development plans and move into a Phase 2 study earlier than originally

ISIS-STAT3[Rx] is designed to inhibit the production of signal transducer and
activator of transcription 3 (STAT3), a protein critical for tumor cell growth
and survival. Because STAT3 is overexpressed in numerous types of cancer,
ISIS-STAT3[Rx] has the potential to be broadly useful for both solid and
liquid tumors. ISIS-STAT3[Rx] has been shown to reduce STAT3 levels in
preclinical tumor models and produce anti-tumor activity. Inhibition of STAT3
has also been shown to block the induction of tumor-associated cytokines
involved in the progression of cancer, such as IL-6, IL-1, TGFb, and IL-10,
which could serve as important biomarkers in clinical studies.


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 regarding the
discovery, 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.

In this press release, unless the context requires otherwise, "Isis,"
"Company," "we," "our," and "us" refers to Isis Pharmaceuticals and its

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

SOURCE Isis Pharmaceuticals, Inc.

Contact: D. Wade Walke, Ph.D., Executive Director, Corporate Communications
and Investor Relations, Isis Pharmaceuticals, +1-760-603-2741; Amy Blackley,
Ph.D., Associate Director, Corporate Communications, Isis Pharmaceuticals,
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