Isis Initiates Phase 1 Study of ISIS-APOA Rx to Treat Atherosclerosis

    Isis Initiates Phase 1 Study of ISIS-APOA Rx to Treat Atherosclerosis

PR Newswire

CARLSBAD, Calif., April 3, 2013

CARLSBAD, Calif., April 3, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced today that it has initiated a Phase 1 clinical study
for ISIS-APOA[Rx], an antisense drug targeting apolipoprotein(a) for the
treatment of atherosclerosis. Apolipoprotein(a) contributes to the formation
of plaque in arteries through its attachment to an LDL-C particle in a complex
termed lipoprotein(a), or Lp(a). High levels of Lp(a) are associated with an
increased risk of atherosclerosis, coronary heart disease, heart attack and
stroke. ISIS-APOA[Rx] is designed to reduce Lp(a) by inhibiting the
production of apolipoprotein(a). Isis plans to develop ISIS-APOA[Rx] to treat
patients with high Lp(a) levels who are at high risk of experiencing
cardiovascular events.

"Lp(a) is an independent risk factor for coronary heart disease. Although
Lp(a) can be measured during a routine lipid blood panel, the lack of drugs
that effectively lower Lp(a) have made treating patients with high Lp(a)
levels difficult. Because elevated Lp(a) is an inherited genetic condition,
patients are unable to adequately control their Lp(a) levels through diet or
lifestyle changes. By inhibiting the production of apolipoprotein(a),
ISIS-APOA[Rx] is designed to reduce the levels of Lp(a), thereby offering a
unique and specific approach to treating patients who have high cardiovascular
risk due to high Lp(a) levels," said Walter Singleton, M.D., vice president
of development and chief medical officer at Isis. "ISIS-APOA[Rx] is part of
Isis' strategy to create a cardiovascular disease franchise comprised of drugs
that target all the key components of cardiovascular disease, including
various atherogenic lipids, inflammation and thrombosis."

The Phase 1 study of ISIS-APOA[Rx] is a blinded, placebo-controlled,
dose-escalation study in approximately 56 healthy volunteers. The study is
designed to assess the safety, tolerability and pharmacokinetics of both
single and multiple doses of ISIS-APOA[Rx].


Lp(a) is considered an independent risk factor for cardiovascular disease due
to its association with an increased risk of coronary heart disease and
atherosclerotic plaque formation. Lp(a) is a lipoprotein particle that is
assembled in the liver that consists of an LDL-C-like particle and
apolipoprotein(a). Lp(a) levels in blood can vary greatly between individuals
due primarily to genetic variations in the gene that encodes for
apolipoprotein(a). As a result, Lp(a) levels are genetically determined,
reached by the age of two and remain constant throughout the life of the
individual. Diet and lifestyle changes have little impact on Lp(a) levels and
currently therapies are not able to adequately reduce elevated levels of Lp(a)
to acceptable levels in patients who have severely elevated Lp(a). As a
general guideline for ideal Lp(a) levels, the European Atherosclerosis Society
recommends that Lp(a) levels be less than or equal to 50 mg/dL. ISIS-APOA[Rx]
is designed to selectively reduce levels of Lp(a) by inhibiting the production
of apolipoprotein(a).


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 the
discovery, development, activity, therapeutic potential and safety of
ISIS-APOA[Rx]. 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, which is on file with the SEC.
Copies of this 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, 760-603-2741, Amy Blackley, Ph.D., Associate Director,
Corporate Communications, 760-603-2772
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