Isis Pharmaceuticals Reports Encouraging Data on ISIS-STAT3rx in Patients With Cancer

Isis Pharmaceuticals Reports Encouraging Data on ISIS-STAT3rx in Patients With

Data presented today at the American Society of Clinical Oncology

PR Newswire

CARLSBAD, Calif., June 3, 2013

CARLSBAD, Calif., June 3, 2013 /PRNewswire/ --Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced that data from the Phase 1 study of ISIS-STAT3[Rx] in
patients with cancer were presented today at the American Society of Clinical
Oncology in Chicago. Results of the initial dose escalation study in patients
with metastatic cancer showed that ISIS-STAT3[Rx] treatment resulted in
partial responses that were durable and prolonged in two out of three patients
with diffuse large B-cell lymphoma (DLBCL) who were refractory to prior
chemotherapy treatments. Isis and AstraZeneca are currently evaluating
ISIS-STAT3[Rx], in two clinical studies in patients with advanced lymphoma and
metastatic liver cancer.

"STAT3 activation has been shown to be associated with the growth,
invasiveness and metastases of many types of cancer making it an attractive
anti-cancer target. However, STAT3 has proven to be a difficult target to
inhibit. ISIS-STAT3[Rx] is one of the new molecules in development that
inhibit STAT3," 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 often have failed multiple
therapies and have few 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 cancer patients. The early
clinical data on ISIS-STAT3[Rx ]is impressive because it suggests that this
drug can produce durable responses in patients with advanced cancer who have
failed to respond to other therapies."

ISIS-STAT3[Rx], also referred to as AZD9150, is the first drug in Isis'
pipeline that incorporates Isis' Generation 2.5 chemistry, which Isis
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, like DLBCL. The open-label, dose-escalation Phase
1 study evaluated ISIS-STAT3[Rx] in 15 patients with advanced solid tumors and
lymphoma who had relapsed or were refractory to multiple chemotherapy
regimens. Signals of tumor responses were observed in four patients, including
objective partial responses in two of three patients with DLBCL. One patient
with a partial response with DLBCL, who had previously failed ten different
chemotherapy regimens, experienced a 50 percent reduction in tumor burden and
has maintained a partial response for longer than one year and continues to
receive weekly ISIS-STAT3[Rx] therapy. Another patient with DLBCL
experienced a partial response with a 65 percent reduction in tumor burden
and, as a result, was well enough to receive an autologous stem cell
transplant. This patient successfully completed a bone marrow transplant and
remains disease free. Isis and AstraZeneca are currently evaluating
ISIS-STAT3[Rx] in two other clinical studies, including a study in patients
with advanced lymphomas, like DLBCL, and a study in patients with advanced
metastatic hepatocellular carcinoma.

"AstraZeneca's considerable expertise in developing anti-cancer drugs has
enabled us to rapidly advance the clinical development of ISIS-STAT3[Rx]. We
believe that ISIS-STAT3[Rx] may be applicable to many different types of
cancer. As such, together with AstraZeneca, we plan to evaluate
ISIS-STAT3[Rx] in a broad Phase 2 program," 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 initial clinical study
of ISIS-STAT3[Rx] and look forward to the results from the two ongoing
clinical studies in patients, which we plan to report next year."

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. In addition, STAT3 is an important mediator of signaling in the
JAK2/STAT3 pathway, which has been previously shown to be an important target
for drug development. Because STAT3 is activated in numerous types of cancer,
ISIS-STAT3[Rx] has the potential to be broadly useful for both solid and
hematologic 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, TGF, and IL-10,
which could serve as important biomarkers in clinical studies.

Conference Call

At 2:00 p.m. Eastern Time today, June 3, 2013, Isis will conduct a live
webcast conference call to discuss recent highlights from its cancer
franchise, including the addition of ISIS-AR[Rx] to its cancer franchise and
data from the Phase 1 study of ISIS-STAT3[Rx] that was presented today at the
American Society of Clinical Oncology. Interested parties may listen to the
call by dialing 866-652-5200, or access the webcast at A
webcast replay will be available for a limited time at the same address.


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 28 drugs to treat a wide variety of diseases with
an emphasis on cardiovascular, metabolic, severe and rare diseases, and
cancer. Isis' partner, Genzyme, is commercializing Isis' lead product,
KYNAMRO™, in the United States for the treatment of patients with HoFH.
Genzyme is also pursuing marketing approval of KYNAMRO in other markets.
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 Isis'
strategic alliance with AstraZeneca, 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 commercial potential 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, 2012, 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.

Isis Pharmaceuticals' Contacts:

D. Wade Walke, Ph.D.                             Amy Blackley, Ph.D.

Executive Director, Corporate Communications and Associate Director, Corporate
Investor Relations                               Communications

760-603-2741                                     760-603-2772

SOURCE Isis Pharmaceuticals, Inc.

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