Alnylam Earns $7 Million Milestone Payment from Genzyme for Phase II Success with Patisiran (ALN-TTR02), an RNAi Therapeutic

  Alnylam Earns $7 Million Milestone Payment from Genzyme for Phase II Success
  with Patisiran (ALN-TTR02), an RNAi Therapeutic Targeting Transthyretin
  (TTR) for the Treatment of TTR-Mediated Amyloidosis (ATTR)

  – Recent Phase II Clinical Results Showed up to 96% Knockdown of TTR with
               Activity toward Both Wild-Type and Mutant TTR –

 – Alnylam Recently Initiated APOLLO Phase III Trial to Evaluate Efficacy and
Safety of Patisiran in ATTR Patients with Familial Amyloidotic Polyneuropathy
                                   (FAP) –

Business Wire

CAMBRIDGE, Mass. -- November 25, 2013

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics
company, announced today that it has earned a $7 million milestone from its
partner Genzyme, a Sanofi company, for achieving Phase II success with
patisiran (ALN-TTR02). Alnylam recently presented positive Phase II results at
the IXth International Symposium on Familial Amyloidotic Polyneuropathy
(ISFAP) held in Rio de Janeiro, Brazil, November 10 – 13. Results showed that
multiple doses of patisiran led to robust and statistically significant
knockdown of serum TTR protein levels of up to 96%, with mean levels of TTR
knockdown exceeding 85%. Knockdown of TTR, the disease-causing protein in
ATTR, was found to be rapid, dose dependent, and durable, and similar activity
was observed toward both wild-type and mutant protein. In addition, patisiran
was found to be generally safe and well tolerated in this study. Alnylam has
also recently initiated its APOLLO Phase III trial of patisiran in ATTR
patients with FAP, with the study now open for enrollment.

“We believe patisiran holds considerable promise to become a breakthrough
therapy for the treatment of ATTR, a progressive and debilitating orphan
disease. As the lead program in our ‘Alnylam 5x15’ product strategy, this
program is also a key part of building Alnylam for the future and driving
towards commercialization,” said John Maraganore, Ph.D., Chief Executive
Officer of Alnylam. “We have made tremendous progress with this program in
recent months, including reporting positive Phase II results, and initiating
both an open-label Phase II extension study as well as our Phase III APOLLO
study. We look forward to continued progress with Genzyme as our collaborator
for the development and commercialization of our TTR program in the Japanese
and Asian markets, and we are pleased to achieve this milestone based on
successful completion of our Phase II study.”

“We continue to be very encouraged by Alnylam’s progress with their ATTR
program and are excited by the potential for this innovative drug candidate to
make a difference in the lives of patients,” said David Meeker, M.D.,
President and Chief Executive Officer of Genzyme. “The results to date
demonstrate impressive clinical activity and support advancement of this
promising therapeutic into pivotal studies and toward the market. We very much
look forward to working with Alnylam on this important program.”

In 2012, Alnylam entered into an exclusive alliance with Genzyme, a Sanofi
company, to develop and commercialize RNAi therapeutics, including patisiran
and ALN-TTRsc, for the treatment of ATTR in Japan and the broader
Asian-Pacific region. Alnylam plans to develop and commercialize the ALN-TTR
program in North and South America, Europe, and rest of the world.

About Transthyretin-Mediated Amyloidosis

Transthyretin (TTR)-mediated amyloidosis (ATTR) is an inherited, progressively
debilitating, and fatal disease caused by mutations in the TTR gene. TTR
protein is produced primarily in the liver and is normally a carrier for
retinol binding protein. Mutations in TTR cause abnormal amyloid proteins to
accumulate and damage body organs and tissue, such as the peripheral nerves
and heart, resulting in intractable peripheral sensory neuropathy, autonomic
neuropathy, and/or cardiomyopathy. ATTR represents a major unmet medical need
with significant morbidity and mortality; familial amyloidotic polyneuropathy
(FAP) affects approximately 10,000 people worldwide and familial amyloidotic
cardiomyopathy (FAC) affects at least 40,000 people worldwide. FAP patients
have a life expectancy of five to 15 years from symptom onset, and the only
approved treatment options for early stage disease are liver transplantation,
and tafamidis (approved in Europe). The mean survival for FAC patients is
approximately 2.5 years, and there are no approved therapies. There is a
significant need for novel therapeutics to treat patients who have inherited
mutations in the TTR gene.

About LNP Technology

Alnylam has licenses to Tekmira LNP intellectual property for use in RNAi
therapeutic products using LNP technology.

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a
breakthrough in understanding how genes are turned on and off in cells, and a
completely new approach to drug discovery and development. Its discovery has
been heralded as “a major scientific breakthrough that happens once every
decade or so,” and represents one of the most promising and rapidly advancing
frontiers in biology and drug discovery today which was awarded the 2006 Nobel
Prize for Physiology or Medicine. RNAi is a natural process of gene silencing
that occurs in organisms ranging from plants to mammals. By harnessing the
natural biological process of RNAi occurring in our cells, the creation of a
major new class of medicines, known as RNAi therapeutics, is on the horizon.
Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise
Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently
silencing specific mRNAs, thereby preventing disease-causing proteins from
being made. RNAi therapeutics have the potential to treat disease and help
patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on
RNA interference, or RNAi. The company is leading the translation of RNAi as a
new class of innovative medicines with a core focus on RNAi therapeutics
toward genetically defined targets for the treatment of serious,
life-threatening diseases with limited treatment options for patients and
their caregivers. These include: patisiran (ALN-TTR02), an intravenously
delivered RNAi therapeutic targeting transthyretin (TTR) for the treatment of
TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic
polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic
targeting TTR for the treatment of ATTR in patients with familial amyloidotic
cardiomyopathy (FAC); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT)
for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-AS1, an
RNAi therapeutic targeting aminolevulinate synthase-1 (ALAS-1) for the
treatment of porphyria including acute intermittent porphyria (AIP); ALN-CC5,
an RNAi therapeutic targeting complement component C5 for the treatment of
complement-mediated diseases; ALN-PCS, an RNAi therapeutic targeting PCSK9 for
the treatment of hypercholesterolemia; ALN-TMP, an RNAi therapeutic targeting
TMPRSS6 for the treatment of beta-thalassemia and iron-overload disorders;
ALN-AAT, an RNAi therapeutic targeting alpha-1-antitrypsin (AAT) for the
treatment of AAT deficiency liver disease; and ALN-ANG, an RNAi therapeutic
for the treatment of genetic forms of mixed hyperlipidemia and severe
hypertriglyceridemia, amongst other programs. As part of its “Alnylam 5x15”
strategy, the company expects to have five RNAi therapeutic products for
genetically defined diseases in clinical development, including programs in
advanced stages, on its own or with a partner by the end of 2015. Alnylam has
additional partnered programs in clinical or development stages, including
ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection and
ALN-VSP for the treatment of liver cancers. The company’s leadership position
on RNAi therapeutics and intellectual property have enabled it to form major
alliances with leading companies including Merck, Medtronic, Novartis, Biogen
Idec, Roche, Takeda, Kyowa Hakko Kirin, Cubist, Ascletis, Monsanto, Genzyme,
and The Medicines Company. In addition, Alnylam holds an equity position in
Regulus Therapeutics Inc., a company focused on discovery, development, and
commercialization of microRNA therapeutics. Alnylam has also formed Alnylam
Biotherapeutics, a division of the company focused on the development of RNAi
technologies for applications in biologics manufacturing, including
recombinant proteins and monoclonal antibodies. Alnylam’s VaxiRNA™ platform
applies RNAi technology to improve the manufacturing processes for vaccines;
GlaxoSmithKline is a collaborator in this effort. Alnylam scientists and
collaborators have published their research on RNAi therapeutics in over 100
peer-reviewed papers, including many in the world’s top scientific journals
such as Nature, Nature Medicine, Nature Biotechnology, Cell, the New England
Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains
headquarters in Cambridge, Massachusetts. For more information, please visit
www.alnylam.com.

About “Alnylam 5x15™”

The “Alnylam 5x15” strategy, launched in January 2011, establishes a path for
development and commercialization of novel RNAi therapeutics toward
genetically defined targets for the treatment of diseases with high unmet
medical need. Products arising from this initiative share several key
characteristics including: a genetically defined target and disease; the
potential to have a major impact in a high unmet need population; the ability
to leverage the existing Alnylam RNAi delivery platform; the opportunity to
monitor an early biomarker in Phase I clinical trials for human proof of
concept; and the existence of clinically relevant endpoints for the filing of
a new drug application (NDA) with a focused patient database and possible
accelerated paths for commercialization. By the end of 2015, the company
expects to have five such RNAi therapeutic programs in clinical development,
including programs in advanced stages, on its own or with a partner. The
“Alnylam 5x15” programs include: patisiran (ALN-TTR02), an intravenously
delivered RNAi therapeutic targeting transthyretin (TTR) in development for
the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial
amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi
therapeutic targeting TTR in development for the treatment of ATTR in patients
with familial amyloidotic cardiomyopathy (FAC); ALN-AT3, an RNAi therapeutic
targeting antithrombin (AT) in development for the treatment of hemophilia and
rare bleeding disorders (RBD); ALN-AS1, an RNAi therapeutic targeting
aminolevulinate synthase-1 (ALAS-1) in development for the treatment of
porphyria including acute intermittent porphyria (AIP); ALN-CC5, an RNAi
therapeutic targeting complement component C5 in development for the treatment
of complement-mediated diseases; ALN-PCS, an RNAi therapeutic targeting PCSK9
in development for the treatment of hypercholesterolemia; ALN-TMP, an RNAi
therapeutic targeting TMPRSS6 in development for the treatment of
beta-thalassemia and iron-overload disorders; ALN-AAT, an RNAi therapeutic
targeting alpha-1-antitrypsin (AAT) for the treatment of AAT deficiency liver
disease; and ALN-ANG, an RNAi therapeutic for the treatment of genetic forms
of mixed hyperlipidemia and severe hypertriglyceridemia, amongst other
programs. Alnylam intends to focus on developing and commercializing certain
programs from this product strategy itself in North and South America, Europe,
and other parts of the world.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations,
plans and prospects, including without limitation, Alnylam’s expectations
regarding its “Alnylam 5x15” product strategy, Alnylam’s views with respect to
the potential for RNAi therapeutics, including patisiran (ALN-TTR02), its
expectations with respect to the timing, execution, and success of its
clinical trials for patisiran, and its expectations regarding the potential
market opportunity for patisiran, constitute forward-looking statements for
the purposes of the safe harbor provisions under The Private Securities
Litigation Reform Act of 1995. Actual results may differ materially from those
indicated by these forward-looking statements as a result of various important
factors, including, without limitation, Alnylam’s ability to manage operating
expenses, Alnylam’s ability to discover and develop novel drug candidates and
delivery approaches, successfully demonstrate the efficacy and safety of its
drug candidates, the pre-clinical and clinical results for its product
candidates, which may not support further development of product candidates,
actions of regulatory agencies, which may affect the initiation, timing and
progress of clinical trials, obtaining, maintaining and protecting
intellectual property, Alnylam’s ability to enforce its patents against
infringers and defend its patent portfolio against challenges from third
parties, obtaining regulatory approval for products, competition from others
using technology similar to Alnylam’s and others developing products for
similar uses, Alnylam’s ability to obtain additional funding to support its
business activities and establish and maintain strategic business alliances
and new business initiatives, Alnylam’s dependence on third parties for
development, manufacture, marketing, sales and distribution of products, the
outcome of litigation, and unexpected expenditures, as well as those risks
more fully discussed in the “Risk Factors” filed with Alnylam’s most recent
Quarterly Report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) and in other filings that Alnylam makes with the SEC. In
addition, any forward-looking statements represent Alnylam’s views only as of
today and should not be relied upon as representing its views as of any
subsequent date. Alnylam explicitly disclaims any obligation to update any
forward-looking statements.

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Contact:

Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice President, Investor Relations and Corporate Communications
or
Spectrum
Amanda Sellers (Media), 202-955-6222 x2597
 
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