Isis Pharmaceuticals Initiates Phase 1b/2a Study Of ISIS-SMNRx In Patients With Spinal Muscular Atrophy

  Isis Pharmaceuticals Initiates Phase 1b/2a Study Of ISIS-SMNRx In Patients
                         With Spinal Muscular Atrophy

Ongoing Phase 1 Study Shows ISIS-SMNRx Well-Tolerated in Children with SMA

PR Newswire

CARLSBAD, Calif., Nov. 1, 2012

CARLSBAD, Calif., Nov. 1, 2012 /PRNewswire/ -- Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced the initiation of a Phase 1b/2a study evaluating
ISIS-SMNRx in children 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.

"SMA is a devastating disease that leads to the premature loss of nerve cells
in the spinal cord necessary for normal muscle function. Children with SMA
generally appear normal at birth, with muscle wasting and atrophy developing
as early as a few months after birth. In the most severe form of the disease,
children never sit or walk and have a significantly shortened lifespan.
Although the genetic cause of SMA is well understood, the identification of an
effective drug that will halt or improve the disease process has not
occurred," said Richard Finkel, M.D., chief, division of neurology, Nemours
Children's Hospital, Orlando, Florida. "ISIS-SMNRx is specifically designed
to intervene in the nerve cell's RNA machinery by improving splicing
efficiency. This results in an increase in the production of a normal
protein, SMN, which is deficient in children with SMA. This promising new
approach could for the first time have a profound effect in children with

The Phase 1b/2a study of ISIS-SMNRx is a multiple-dose, dose-escalation study
designed to assess the safety, tolerability and pharmacokinetic profile of the
drug in children with SMA between the ages of 2-15 who are medically stable.
In the ongoing Phase 1 study in children with SMA, all patients have completed
dosing and ISIS-SMNRx was well tolerated as a single dose administered
directly into the cerebral spinal fluid. In the Phase 1b/2a study, children
with SMA will receive either two or three doses of ISIS-SMNRx during the
course of the study. Data from this study will also provide information to
aid in identifying the dose for the Phase 2/3 registration-directed program in
patients with SMA.

"SMA represents a serious unmet medical need with no currently available
treatments. Based on its mechanism of action, ISIS-SMNRx could be an effective
treatment for these very sick children. The rapid advancement of this drug
into a multiple-dose Phase 1b/2a study 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-SMNRx is our first drug to intervene in the splicing of RNA to
increase the production of a normal protein, SMN. We believe that antisense
drugs could offer novel new therapeutics for a number of neurodegenerative
diseases where there are limited therapeutic options available. 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 a number of severe
neurodegenerative diseases."

ISIS-SMNRx is designed to treat all types of childhood SMA by altering 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-SMNRx for the treatment
of patients with SMA. Isis is currently in collaboration with Biogen Idec
(NASDAQ:BIIB) to develop and potentially commercialize the investigational
compound ISIS-SMNRx 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 trial.

About SMA
SMA is a severe genetic disease that affects approximately 30,000-35,000
patients in the United States, Europe and Japan. One in 50 people, the
equivalent of about 6 million people in the United States, are carriers of the
SMA gene. 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. 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. The severity of SMA correlates with the amount of SMN protein.
Infants with Type 1 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

Isis acknowledges support from the following organizations for ISIS-SMNRx:
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 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 Isis'
strategic alliance with Biogen Idec, and the discovery, development, activity,
therapeutic and commercial potential and safety of ISIS-SMNRx. 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, +1-760-603-2741, or Amy Blackley, Ph.D., Associate
Director, Corporate Communications, +1-760-603-2772, both of Isis
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