Data From ISIS-SMN Rx Phase 1 Study in Children With Spinal Muscular Atrophy Presented at the American Academy of Neurology

 Data From ISIS-SMN Rx Phase 1 Study in Children With Spinal Muscular Atrophy
            Presented at the American Academy of Neurology Meeting

Isis to host an investor event and live webcast at 7:30 am PT on Thursday,
March 21 in San Diego

PR Newswire

CARLSBAD, Calif., March 20, 2013

CARLSBAD, Calif., March 20, 2013 /PRNewswire/ --Isis Pharmaceuticals, Inc.
(NASDAQ: ISIS) announced that data from the Phase 1 study of ISIS-SMN[Rx] in
children with spinal muscular atrophy (SMA) were presented today at the 65^th
American Academy of Neurology (AAN) Annual Meeting by Dr. Claudia Chiriboga,
from Columbia University Medical Center. In the presentation, Dr. Chiriboga
reported that, in this single-dose, open-label study, ISIS-SMN[Rx] was well
tolerated in children with SMA at all dose levels tested and that improvements
were observed in Hammersmith scores, a measure of muscle function, in a number
of the children. 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. ISIS-SMN[Rx] is an antisense drug designed to
treat all types of SMA.

"SMA is a devastating disease that results in severe muscle weakness and
respiratory failure in infants and children. Current treatments are
supportive and do not address the underlying genetic cause of SMA, the loss of
SMN protein, which is critical to the health and survival of nerve cells
responsible for neuromuscular growth and function. ISIS-SMN[Rx] is designed
to address the underlying genetic problem for patients with SMA by increasing
the production of functional SMN protein," said Claudia Chiriboga, M.D.,
associate professor of clinical neurology and pediatrics at Columbia
University Medical Center. "I am pleased to report that ISIS-SMN[Rx]
administration was very well tolerated in these young children with a safety
profile that supports additional development of the drug. The improvements in
muscle function observed in this study following a single dose of the drug
were encouraging. For these reasons, I am very excited about the potential
benefit of ISIS-SMN[Rx] for children with this terrible disease."

In the presentation titled, 'Results of an Open-Label, Escalating Dose Study
To Assess the Safety, Tolerability, and Dose Range Finding of a Single
Intrathecal Dose of ISIS-SMN[Rx] in Patients with Spinal Muscular Atrophy', Dr
Chiriboga reported that ISIS-SMN[Rx] was well tolerated when administered
intrathecally as a single dose directly into the spinal fluid and that no
safety concerns related to the drug were identified. In addition, the
intrathecal injection procedure was well tolerated in children with SMA.
Concentrations of ISIS-SMN[Rx] measured in cerebral spinal fluid were
consistent with levels predicted from preclinical studies, indicating that the
drug half-life in nervous system tissues is very long and that dosing once
every six to nine months is feasible. Although the study was not designed to
provide evidence of functional activity, clinically significant,
dose-dependent improvements in the Hammersmith Functional Motor Scale-Expanded
(HFMSE), a measure of muscle function, were observed in these children. The
mean increase in the HFMSE scores observed in the highest dose cohort (9 mg)
at 3 months was 3.1 points or a 17.6% increase from baseline, with six of ten
patients experiencing an increase of 4 to 7 points. Observed improvements in
HFMSE scores equal to or greater than a 4 point increase were distributed by
age with half (3) in children under the age of five and half in children five
and older. Children who participated in this study are allowed to either
enter the ongoing multiple-dose Phase 1b/2a study or a separate re-dosing
study. Please click here to access Dr. Chiriboga's AAN slide presentation.

"SMA is a heartbreaking disease. Children with SMA are bright and engaging,
but often never achieve the simplest motor milestones like walking, crawling,
or sitting up. In its most severe form, children do not live beyond 2 years
of age. Even in milder cases, SMA patients inexorably grow weaker and
experience the loss of the few abilities they did acquire. In addition to
motor losses, SMA patients young and old are at constant risk of tragic
consequences from simple respiratory infections that you and I take in
stride," said Karen S. Chen, Ph.D., chief scientific officer at the SMA
Foundation. "The landmark science behind ISIS-SMN[Rx] is compelling and it has
a chance to fill the therapeutic void for SMA and transform the hopes and
futures of thousands of patients and families."

The Phase 1 study of ISIS-SMN[Rx] was an open-label, single-dose,
dose-escalation study designed to assess the safety, tolerability and
pharmacokinetic profile of ISIS-SMN[Rx] in medically stable children from age
2-14. In this study, 28 children, including 15 with TypeII SMA and 13 with
TypeIII SMA, received ISIS-SMN[Rx] as a single dose of 1, 3, 6, or 9 mg
administered intrathecally. ISIS-SMN[Rx] concentrations in plasma and
cerebral spinal fluid were measured to provide information on the dose
concentration and frequency for future studies. In addition, exploratory
analyses of changes in motor function were conducted. Gross motor movements
were measured in all children throughout the study using the Hammersmith Motor
Function Scale-Expanded (HFMSE), a modified version of the Hammersmith
Functional Motor Scale. The HFMSE is used to assess responses on 33 motor
function tasks, each scored on a scale from 0 to 2 and allows for assessment
of any SMA patient aged 2 or older. HFMSE has demonstrated good test-retest
reliability in other studies.

"ISIS-SMN[Rx] is our first drug to modify the splicing of RNA to increase the
production of a functional SMN protein. This Phase 1 study is the first time
that we have administered an antisense drug to patients as young as 2 years of
age. We are very encouraged that the drug was safe and that intrathecal
dosing was tolerated well by these children even at the highest dose level,"
said C. Frank Bennett, Ph.D., senior vice president of research at Isis.

"Early evidence of activity in these children is encouraging, but it is
important to note that this was an open-label study without a control arm,"
said Stanley T.Crooke, M.D., Ph.D., chairman of the board and chief executive
officer at Isis. "We are cautiously optimistic with the observed improvements
in muscle function in the higher dose cohort, however, we will need further
clinical data from a controlled study to assess the safety and activity of
this drug in patients with SMA. We plan to have additional clinical data from
our ongoing multiple-dose study in children with SMA by late 2013 or early
2014. We also plan to initiate a Phase 2/3 program in infants this year and a
Phase 2/3 study in children in the first half of 2014."

]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 Idecto 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.

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 TypeI
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 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.

At 7:30 a.m. Pacific Time Thursday, March 21, Isis will host an investor event
and live webcast to discuss ISIS-SMN[Rx] data presented at the AAN. A live
audio webcast of the presentation will be available on the "Investors & Media"
section of the Company's Web site, A replay will be
available for a limited time. The slides presented at the AAN meeting are
available on Isis' Web site at

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'
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
Press spacebar to pause and continue. Press esc to stop.