Alnylam Receives Notice of Allowance from United States Patent and Trademark Office (USPTO) for New Patent Broadly Covering

  Alnylam Receives Notice of Allowance from United States Patent and Trademark
  Office (USPTO) for New Patent Broadly Covering Conjugate-Based Delivery of
  RNA Therapeutics

    – Allowed Claims of Manoharan ’478 Application Cover GalNAc-Conjugates
            Independent of Length, Sequence, and Disease Target –

Business Wire

CAMBRIDGE, Mass. -- July 22, 2014

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics
company, announced today that the United States Patent and Trademark Office
(USPTO) has issued a Notice of Allowance for claims in the Manoharan et al.
patent application 13/693,478. The ’478 patent application includes newly
allowed claims directed to compositions including those comprising a modified
RNA agent linked to a biantennary or triantennary ligand. Specifically, the
allowed application includes claims that broadly cover single-stranded or
double-stranded, chemically modified RNA therapeutics conjugated with an
N-acetylgalactosamine (GalNAc) ligand independent of length, sequence, or
disease target. The allowance of this patent application represents a major
advance in Alnylam’s intellectual property (IP) estate, since GalNAc-siRNA
conjugates enable potent and durable silencing of liver-expressed disease
genes with subcutaneous dose administration and a wide therapeutic index.
Importantly, this delivery approach is a key component of the company’s
execution on its “Alnylam 5x15” and broader genetic medicine product strategy.

“These newly allowed claims from the Manoharan ’478 patent recognize the
pioneering work of Alnylam scientists in the advancement of conjugates as a
delivery platform for RNA therapeutics. We are gratified that the USPTO has
acknowledged these innovations by allowance of broad claims from this patent
application,” said Laurence Reid, Ph.D., Senior Vice President and Chief
Business Officer of Alnylam. “Our conjugate delivery platform - specifically
utilizing GalNAc-siRNA conjugates - enables subcutaneous dosing of RNAi
therapeutics with potent and durable effects and a wide therapeutic index.
With our Enhanced Stabilization Chemistry (ESC) conjugates, we believe that
once-monthly and possibly once-quarterly subcutaneous dosing regimens can be
achieved in our clinical pipeline programs. Based on this progress, we believe
that GalNAc-conjugates are now the industry-leading delivery approach for RNA
therapeutics targeting liver-expressed genes, and this patent allowance will
reinforce Alnylam’s central role in value creation based on therapeutics
linked to this technology.”

The allowed claims of the Manoharan ’478 patent application, as well as other
granted, Alnylam-owned or -licensed patents, are provided on the company’s
website, and in aggregate broadly cover delivery of RNAi therapeutics,
including those that employ GalNAc-siRNA conjugate technology; additional
claims from this and other patent families are pending. In addition, Alnylam’s
owned or licensed patents broadly cover siRNAs and their use in a wide range
of lengths from 15 to 49 nucleotides, and chemical modifications with
naturally or non-naturally occurring nucleotides, including, for example,
acyclic nucleotides such as “unlocked nucleoside analogs.” Alnylam’s IP estate
also includes patents that broadly cover siRNAs toward a wide range of disease
targets.

Alnylam will be providing an update on advances in the delivery of RNAi
therapeutics with ESC-GalNAc-siRNA conjugates in an RNAi Roundtable webinar to
be held at 11:00 a.m. ET today, and can be accessed by clicking here.

About 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 as
genetic medicines, including programs as part of the company's "Alnylam
5x15TM" product strategy. Alnylam's genetic medicine programs are RNAi
therapeutics directed 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 TTR cardiac
amyloidosis, including familial amyloidotic cardiomyopathy (FAC) and senile
systemic amyloidosis (SSA); ALN-AT3, an RNAi therapeutic targeting
antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders
(RBD); ALN-CC5, an RNAi therapeutic targeting complement component C5 for the
treatment of complement-mediated diseases; ALN-AS1, an RNAi therapeutic
targeting aminolevulinic acid synthase-1 (ALAS-1) for the treatment of hepatic
porphyrias including acute intermittent porphyria (AIP); ALN-PCS, an RNAi
therapeutic targeting PCSK9 for the treatment of hypercholesterolemia;
ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the
treatment of AAT deficiency-associated liver disease; ALN-TMP, an RNAi
therapeutic targeting TMPRSS6 for the treatment of beta-thalassemia and
iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting
angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed
hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, an RNAi therapeutic
targeting apolipoprotein C-III (apoCIII) for the treatment of
hypertriglyceridemia; and other programs yet to be disclosed. As part of its
"Alnylam 5x15" strategy, as updated in early 2014, the company expects to have
six to seven genetic medicine product candidates in clinical development -
including at least two programs in Phase 3 and five to six programs with human
proof of concept - by the end of 2015. Alnylam is also developing ALN-HBV, an
RNAi therapeutic targeting the hepatitis B virus (HBV) genome for the
treatment of HBV infection. The company's demonstrated commitment to RNAi
therapeutics has enabled it to form major alliances with leading companies
including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko
Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and
Genzyme, a Sanofi company. In March 2014, Alnylam acquired Sirna Therapeutics,
a wholly owned subsidiary of Merck. In addition, Alnylam holds an equity
position in Regulus Therapeutics Inc., a company focused on discovery,
development, and commercialization of microRNA therapeutics. Alnylam
scientists and collaborators have published their research on RNAi
therapeutics in over 200 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.

Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam’s future expectations,
plans and prospects, including without limitation, Alnylam’s views with
respect to the potential for RNAi therapeutics, its expectations regarding its
“Alnylam 5x15” product strategy, its plans regarding commercialization of RNAi
therapeutics, and its views with regard to the scope of its IP estate,
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.

Contact:

Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice President, Investor Relations and Corporate Communications
or
For Media:
Spectrum
Liz Bryan, 202-955-6222 x2526
 
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