Isis Initates Phase 2/3 Study Of ISIS-TTR Rx And Earns $7.5 Million Milestone Payment From GlaxoSmithKline

Isis Initates Phase 2/3 Study Of ISIS-TTR Rx And Earns $7.5 Million Milestone
                         Payment From GlaxoSmithKline

PR Newswire

CARLSBAD, Calif., Feb. 19, 2013

CARLSBAD, Calif., Feb. 19, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced today that it has earned a $7.5 million milestone
payment from GlaxoSmithKline (GSK) related to the initiation of a Phase 2/3
clinical study for ISIS-TTR[Rx]. ISIS-TTR[Rx ]is an antisense drug in
development with GlaxoSmithKline (GSK) for the treatment of transthyretin
(TTR) amyloidosis, a severe and rare genetic disease characterized by
progressive dysfunction of peripheral nerve and/or heart tissues. Isis and
GSK recently amended the clinical development plan and financial terms
relating to ISIS-TTR[Rx ]to support this registration-directed Phase 2/3
clinical study on ISIS-TTR[Rx].

"TTR amyloidosis is a severe and rare genetic disease that leads to death.
TTR amyloidosis affects approximately 50,000 patients worldwide and current
treatments are limited. Patients with familial amyloid polyneuropathy, or
FAP, experience TTR build up in their peripheral nerves and experience the
loss of motor functions, such as walking," said Merrill D. Benson, M.D.,
Professor of Medical Genetics at Indiana University. "By inhibiting the
production of TTR protein, ISIS-TTR[Rx] could offer an alternative approach to
treating patients with FAP. Furthermore, a drug that can reduce TTR levels
could potentially slow or arrest progression of this terrible disease."

The Phase 2/3 study of ISIS-TTR[Rx] is a randomized, double-blinded,
placebo-controlled, international study designed to support an application for
marketing approval of ISIS-TTR[Rx] in patients with FAP. The fifteen month
study will enroll approximately 200 patients randomized 2:1 to receive 300
mg/week of ISIS-TTR[Rx] or placebo and will measure the effects of
ISIS-TTR[Rx] on neurological dysfunction and on quality-of-life. The United
States Food and Drug administration granted ISIS-TTR[Rx] fast track
designation and orphan drug status for the treatment of FAP.

"The rapid development of ISIS-TTR[Rx] from a research-stage program to a drug
in late-stage clinical development in just over two years represents the
strong commitment of both teams to bring this novel drug to patients who are
in need of new therapeutic options," said B. Lynne Parshall, chief operating
officer at Isis. "The encouraging data from our Phase 1 study, in which our
drug was well tolerated and produced significant reductions in TTR protein,
supported the advancement of ISIS-TTR[Rx] directly into this
registration-directed Phase 2/3 study. While we will continue to manage the
clinical development of ISIS-TTR[Rx], we will benefit from GSK's late-stage
clinical development, regulatory and commercial expertise."

ISIS-TTR[Rx] is part of the Isis-GSK strategic alliance to develop RNA
therapeutics for rare and infectious diseases. For the initiation of the
Phase 2/3 study, Isis will receive a $7.5 million milestone payment and is
eligible to earn an additional $50 million in pre-licensing milestone payments
to support the Phase 2/3 study of ISIS-TTR[Rx. ]In addition, Isis is eligible
to receive regulatory and sales milestone payments and double-digit royalties
on sales of ISIS-TTR[Rx].

]Transthyretin amyloidosis is a genetic disease in which the patient inherits
a mutant gene that produces a misfolded form of TTR, which progressively
accumulates in tissues, impairing their function. In patients with
transthyretin amyloidosis, both the mutant and normal forms of TTR can build
up as fibrils in tissues, including heart, peripheral nerves, and the
gastrointestinal tract. The presence of TTR aggregates interferes with the
normal functions of these tissues, and as the TTR protein aggregates enlarge
more tissue damage occurs and the disease worsens. There are two common types
of transthyretin amyloidosis, familial amyloid cardiomyopathy, or FAC, which
affects more than 40,000 patients worldwide, and FAP, which affects more than
10,000 patients worldwide. Patients with FAC have TTR build up in the heart
muscle and succumb to heart failure five to six years after symptom onset.
Patients with FAP have TTR build up in peripheral nerve tissue leading to the
loss of nerve function and wasting. ISIS-TTR[Rx] is an investigational drug
that is designed to inhibit the production of all forms of TTR, and could
offer an alternative approach to treat all types of transthyretin-related

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,
including Europe. 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'
collaboration with GlaxoSmithKline, the discovery, development and potential
of drugs for severe and rare diseases, and the development, activity,
therapeutic potential and safety of ISIS-TTR[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, 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: Isis Pharmaceuticals,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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