Roche and Isis Pharmaceuticals form alliance for Huntington's disease

    Roche and Isis Pharmaceuticals form alliance for Huntington's disease

PR Newswire

BASEL, Switzerland, and CARLSBAD, Calif., April 8, 2013

BASEL, Switzerland, and CARLSBAD, Calif., April 8, 2013 /PRNewswire/ -- Roche
(SIX: RO, ROG; OTCQX: RHHBY) and Isis Pharmaceuticals, Inc (NASDAQ: ISIS)
today announced that they have formed an alliance to develop treatments for
Huntington's disease (HD) based on Isis' antisense oligonucleotide (ASO)
technology. This alliance combines Isis' antisense expertise with Roche's
scientific expertise in developing neurodegenerative therapeutics. In
addition, Isis and Roche will be collaborating to combine Isis' ASOs and
Roche's proprietary "brain shuttle" program with the objective of increasing
the brain penetration of ASOs with systemic administration.

Huntington's disease is an inherited genetic brain disorder that results in
the progressive loss of both mental faculties and physical control. Symptoms
usually appear between the ages of 30 to 50, and worsen over a 10 to 25 year
period. Ultimately, the weakened individual succumbs to pneumonia, heart
failure or other complications. Presently, there is no effective treatment or
cure for the disease, and current treatments focus on reducing the severity of
some disease symptoms.

Initially, research will focus on Isis' lead drug candidate that blocks
production of all forms of the huntingtin (HTT) protein, the protein
responsible for HD and thus has the potential to treat all HD patients. Isis
is also conducting research into treatments that specifically block production
of the disease-causing forms of the HTT protein which has the potential to
treat subsets of HD patients. In parallel, Roche will combine its proprietary
brain shuttle technology with Isis ASO technology that, if successful, will
also allow systemic administration of antisense drugs to treat asymptomatic

Under the terms of the agreement, Roche will make an upfront payment of $30
million to Isis, with total payments related to license fee and pre- and
post-licensing milestone payments reaching potentially $362 million, including
up to $80 million in potential commercial milestone payments. In addition,
Isis will receive tiered royalties on sales of the drugs. Roche has the option
to license the drugs from Isis through the completion of the first Phase 1
trial. Prior to option exercise, Isis is responsible for the discovery and
development of an antisense drug targeting HTT protein. Roche and Isis will
work collaboratively on the discovery of an antisense drug utilizing Roche's
"brain shuttle" program. If Roche exercises its option, it will be responsible
for global development, regulatory and commercialization activities for all
drugs arising out of the collaboration.

Commenting on the deal, Luca Santarelli, Head of Neuroscience and Small
Molecules Research at Roche, said: "Huntington's is a severely debilitating
neurodegenerative disease and a large unmet medical need. Patients experience
gradually worsening motor function and psychological disturbances, with a
significant shortening of life expectancy after the disease is diagnosed.
Treatments are urgently needed, and we believe that the Isis approach in
combination with Roche's brain shuttle represent one of the most advanced
programs targeting the cause of HD with the aim of slowing down or halting the
progression of this disease."

Shafique Virani, Global Head Neuroscience, Cardiovascular & Metabolism at
Roche Partnering, added: "Central to the partnership is Roche's brain shuttle
program, which we see as highly complementary to Isis' drug development work.
This dual track development program ensures whichever candidate compound
proves to be most promising -- Isis' lead target or Roche's brain shuttle
version -- can be taken forward to pivotal clinical trials."

"We are pleased to be working with Roche, a global leader in drug development
with significant experience in developing and commercializing drugs to treat
neurological diseases. We believe that Roche's expertise in developing CNS
drugs, along with their clinical development experience, will greatly enhance
our development efforts for this program and allow us to move forward more
rapidly. In addition, by utilizing Roche's brain shuttle technology with our
antisense drug discovery capabilities, we have the potential to significantly
improve the therapeutic potential for this program," said B. Lynne Parshall,
Chief Operating Officer of Isis. "By partnering our more complex and nuanced
research and development programs earlier in development, like our
Huntington's disease CNS program, we add value and resources with partners
that bring unique benefits."

"We are excited to be working with Roche," said Frank Bennett, Senior Vice
President of Research at Isis. "We believe our mature antisense drug discovery
platform is a perfect fit for Roche's neuroscience franchise, and we
anticipate a fruitful collaboration to advance our pre-clinical compounds."

CHDI Foundation, a non-profit foundation exclusively dedicated to the
development of therapies that slow the progression of HD, provided financial
and scientific support to Isis' HD drug discovery program through a
development collaboration with Isis. CHDI's support has enabled Isis to make
significant progress in discovering a drug to treat HD. Together Isis and CHDI
demonstrated that antisense compounds can be used to inhibit the production of
HTT protein in both brain and peripheral tissues, and that the inhibition of
normal HTT protein was well tolerated. Over time, CHDI will be reimbursed for
its support of Isis' program out of the milestone payments received by Isis.
CHDI will receive $1.5 million associated with the signing of the Roche
agreement. CHDI will continue to provide advice to Isis and Roche on the
development of antisense drugs to treat patients with HD.

Isis also recognizes the tremendous benefit provided to its HD program by its
academic collaborators, Drs. Don Cleveland at the Ludwig Institute, University
of California San Diego and David Corey at University of Texas Southwestern.
These collaborators have been instrumental in Isis' early preclinical work
demonstrating that antisense drugs can inhibit the HTT protein and produce
activity in animal models of disease.

Conference Call

At 9:45 a.m. Eastern Time today, April 08, 2013, Isis will conduct a live
webcast conference call to discuss the alliance with Roche. Interested parties
may listen to the call by dialing 866-323-2841 and provide the conference
identification number "34237203", or access the webcast at
A webcast replay will be available for a limited time at the same address.

About Isis Pharmaceuticals, Inc.

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

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused
healthcare with combined strengths in pharmaceuticals and diagnostics. Roche
is the world's largest biotech company with truly differentiated medicines in
oncology, infectious diseases, inflammation, metabolism and neuroscience.
Roche is also the world leader in in-vitro diagnostics and tissue-based cancer
diagnostics,and a frontrunner in diabetes management. Roche's personalised
healthcare strategy aims at providing medicines and diagnostic tools that
enable tangible improvements in the health, quality of life and survival of
patients. In 2012, Roche had over 82,000 employees worldwide and invested over
8 billion Swiss francs in R&D. The Group posted sales of 45.5 billion Swiss
francs. Genentech, in the United States, is a wholly owned member of the Roche
Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For
more information: All trademarks used or mentioned in this
release are protected by law.

About Roche Neurosciences

Roche is working on new molecular entities in neuroscience that could become
the next generation of medicines for a range of diseases including
schizophrenia, multiple sclerosis, depression, neurodevelopmental disorders,
Parkinson's disease and Alzheimer's disease. With one of the strongest
neuroscience pipelines in the industry, and by working closely with academic
institutions, biotech companies, and forming public-private partnerships,
Roche's focus is on expanding its neuroscience franchise to better serve

Isis Pharmaceuticals' Forward-Looking Statement

This press release includes forward-looking statements regarding Isis'
strategic alliance with Roche, Isis' research and development opportunities in
neurological diseases, the development, activity and therapeutic potential of
an antisense drug targeting the huntingtin gene to treat Huntington's disease.
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.

Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.
KYNAMRO™ is a trademark of Genzyme Corporation.

SOURCE Isis Pharmaceuticals Inc.

Contact: Isis, Isis Media Relations, Amy Blackley, Ph.D., 760-603-2772
(Media),, or Isis Investor Relations, D. Wade Walke,
Ph.D., 760-603-2741 (Investors),; or Roche Partnering,
Emilie Vincent, Head of Roche Partnering Communications,
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