ISIS Pharmaceuticals Initiates a Clinical Study of ISIS-SMN Rx in Infants With Spinal Muscular Atrophy

ISIS Pharmaceuticals Initiates a Clinical Study of ISIS-SMN Rx in Infants With
                           Spinal Muscular Atrophy

Isis to Earn $3.5 Million Milestone Payment

PR Newswire

CARLSBAD, Calif., April 23, 2013

CARLSBAD, Calif., April 23, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced the initiation of a Phase 2 study of ISIS-SMN[Rx] in
infants with spinal muscular atrophy (SMA). SMA is a severe and rare genetic
neuromuscular disease characterized by muscle atrophy and weakness and is the
most common genetic cause of infant mortality. The study, which will begin
enrolling patients soon, is a Phase 2 study in eight patients with
infantile-onset SMA. The study, which initiates the Phase 2/3 program for
ISIS-SMN[Rx] in infants, is designed to provide data to allow Isis to define
the optimal dose for the larger planned Phase 2/3 study in infants and to
provide safety and tolerability data. Isis will earn a $3.5 million milestone
payment from Biogen Idec when the first infant is dosed in the study, which is
projected for May 2013.

The Phase 2 study of ISIS-SMN[Rx] is an open-label, multiple-dose,
dose-escalation pilot study, which will include eight infants who have been
diagnosed with SMA. To meet enrollment criteria, infants must be between the
ages of three weeks and seven months, live in close proximity to a study site
and pass screening evaluations conducted at study sites. The study will be
conducted at centers in the United States and Canada. For further study
information, please visit and search for ISIS-SMN[Rx].

"We are very pleased with the progress Isis has made in advancing this new
potential therapeutic agent, which could fill the therapeutic void for SMA and
transform the hopes and futures of patients and families with this devastating
disease. It is a testament to the commitment of Isis that, in just a few
years, this program has moved rapidly from research to late-stage clinical
development. We look forward to continuing to support the SMA community with
the goal of accelerating a treatment for children with SMA," said Karen S.
Chen, Ph.D., chief scientific officer at the SMA Foundation.

"We are very pleased with the achievement of this clinical milestone of
advancing a potentially disease-modifying drug treatment into later-stage
clinical trials. This achievement is a culmination of the close interactions
between basic researchers, families, clinicians and industry. Families of SMA
applauds Isis for investing in and leading drug development efforts for this
devastating, orphan disease," said Jill Jarecki, Ph.D., research director of
Families of SMA.

Isis completed an open-label Phase 1 study evaluating ISIS-SMN[Rx] in children
(age 2 and older) with SMA, in which ISIS-SMN[Rx] was well tolerated at all
dose levels when administered intrathecally as a single dose directly into the
spinal fluid. Although the study was not designed to provide evidence of
functional activity improvements in the Hammersmith Functional Motor
Scale-Expanded, a measure of muscle function, were observed in a number of
these children. In addition to the infant pilot study, Isis is also
completing a multiple-dose, dose-escalation Phase 1b/2a study of ISIS-SMN[Rx]
in children with SMA. Data from the Phase 1b/2a study will provide
information to determine the dose for the Phase 2/3 registration-directed
study in children (age 2 and older) with SMA.

"SMA represents a serious unmet medical need with no currently available
treatments. Based on its mechanism of action and encouraging preclinical and
clinical data, ISIS-SMN[Rx] could be an effective treatment for these very
sick children, though additional work still needs to be done. The rapid
advancement of this drug to this stage in development reflects the support
from the SMA community and the success of the collaboration between Isis and
Biogen Idec. Isis and Biogen Idec are committed to advancing the program for
children with SMA," said C. Frank Bennett, Ph.D., senior vice president of
research at Isis. "ISIS-SMN[Rx] is our first drug designed to intervene in
the splicing of RNA to increase the production of a normal protein, SMN.
Antisense drugs could offer novel new therapeutics for a number of severe
neurodegenerative diseases. The encouraging safety data from this program and
our preclinical and clinical experience in other neurodegenerative diseases
support the broadening of our efforts to develop antisense drugs to treat such

SMA is a severe genetic disease that affects approximately 30,000-35,000
patients in the United States, Europe and Japan. SMA is caused by a loss of,
or defect in, the survival motor neuron 1 (SMN1) gene leading to a decrease in
the survival motor neuron (SMN) protein. SMN is critical to the health and
survival of nerve cells in the spinal cord responsible for neuromuscular
growth and function. One in 50 people, the equivalent of about 6 million
people in the United States, are carriers of a defective SMN1 gene, which is
unable to produce fully functional SMN protein. Carriers experience no
symptoms and do not develop the disease. However, when both parents are
carriers, there is a one in four chance that their child will have SMA. The
severity of SMA correlates with the amount of SMN protein. Infants with Type I
SMA, the most severe form of the disease, produce very little SMN protein and
have a life expectancy of less than two years. Children with Type II have
greater amounts of SMN protein but still have a shortened lifespan and are
never able to stand independently. Children with Type III have a normal
lifespan but accumulate life-long physical disabilities as they grow.

ISIS-SMN[Rx] is designed to alter the splicing of a closely related gene
(SMN2) to increase production of fully functional SMN protein. The United
States Food and Drug Administration granted orphan drug status and fast track
designation to ISIS-SMN[Rx] for the treatment of patients with SMA. Isis is
currently in collaboration with Biogen Idec to develop and potentially
commercialize the investigational compound, ISIS-SMN[Rx], to treat all types
of SMA. Under the terms of the January 2012 agreement, Isis is responsible
for global development and Biogen Idec has the option to license the compound
until completion of the first successful Phase 2/3 study. ISIS-SMN[Rx] is
currently being evaluated in a Phase 1b/2a multiple-dose, dose-escalation
study in children with SMA. In this study, children will either receive two
or three doses of ISIS-SMN[Rx] over the course of the study.

Isis acknowledges support from the following organizations for ISIS-SMN[Rx]:
Muscular Dystrophy Association, SMA Foundation, Families of SMA and
intellectual property licensed from Cold Spring Harbor Laboratory and the
University of Massachusetts Medical School.

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 Biogen Idec, and the discovery, development, activity,
therapeutic and commercial potential and safety of ISIS-SMN[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, +1-760-603-2741, or Amy Blackley, Ph.D., Associate
Director, Corporate Communications, +1-760-603-2772
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