Alnylam Announces United States Patent and Trademark Office (USPTO) Issues Patent Covering RNAi Therapeutics for the Treatment

  Alnylam Announces United States Patent and Trademark Office (USPTO) Issues
  Patent Covering RNAi Therapeutics for the Treatment of Hepatitis B Virus
  (HBV) Infection

 – New ’277 McSwiggen Patent Includes Broad, Sequence-Independent Claims for
            Chemically Modified siRNAs Targeting the HBV Genome –

Business Wire

CAMBRIDGE, Mass. -- June 12, 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 new patent (U.S. patent no. 8,618,277, or “’277 patent”)
in the company’s McSwiggen patent estate. The McSwiggen patent estate broadly
describes chemical modifications of RNAi therapeutics needed to achieve
“drug-like” properties in siRNA, the molecules that mediate RNAi.
Specifically, the ’277 patent includes claims that the company believes are
critical for the development of RNAi therapeutics for the treatment of
hepatitis B virus (HBV) infection. This patent is held exclusively by Alnylam
and is not licensed to any third parties. The McSwiggen patent estate
comprises a core component of Alnylam’s overall intellectual property (IP)
estate for the advancement of RNAi therapeutics, and was recently obtained
through the company’s acquisition of Sirna Therapeutics from Merck.

“We are pleased with the USPTO’s decision to issue the ’277 patent from our
McSwiggen patent family, a key component of the IP estate we recently obtained
through our acquisition of Sirna Therapeutics from Merck. Our ’277 patent has
broad, sequence-independent claims on chemically modified siRNAs which we
believe are critical for the development and commercialization of RNAi
therapeutics for the treatment of HBV infection,” said Laurence Reid, Ph.D.,
Senior Vice President and Chief Business Officer of Alnylam. “Our IP estate
remains a cornerstone in our efforts to advance RNAi therapeutics to patients
in need. In the case of the ’277 patent, we intend to maximize the value of
this newly issued IP solely through the advancement of ALN-HBV – our
GalNAc-conjugated siRNA targeting the HBV genome for the treatment of HBV
infection – where we expect to select our Development Candidate by this year’s
end and to file an investigational new drug application at or around year-end
2015.”

The McSwiggen patent family includes 23  granted patents around the world,
including patents in the U.S.^1 and the EU^2, and generally describes chemical
modifications of siRNA. The ’277 patent includes broad, sequence-independent
issued claims on compositions of chemically modified siRNA targeting HBV,
including:

  *siRNA that mediates RNAi against a hepatitis B virus target mRNA wherein
    each strand is between 18 to 24 nucleotides; and
  *sense and antisense strand each comprising 10 or more 2’-deoxy, 2-O-Me,
    2’-F or universal base modified nucleotides and 10 or more pyrimidines of
    the sense and/or antisense strand are 2’-deoxy, 2-O-Me, 2’-F.

Such chemical modifications of siRNA are generally required to achieve in vivo
potency and durability for RNAi therapeutics. Additional HBV-directed claims
for the McSwiggen patent family are pending in filed patent applications.

Granted claims of the ’277 patent, as well as other granted Alnylam owned or
licensed patents, are provided on the company’s website, and in aggregate
broadly cover siRNA 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
those termed “unlocked nucleobase analogs.” In addition, Alnylam’s owned or
licensed patents broadly cover delivery of RNAi therapeutics, including those
that employ GalNAc-siRNA conjugate technology. Finally, Alnylam’s IP estate
also includes patents that broadly cover siRNA toward a wide range of disease
targets.

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
5x15^TM” 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, including ALN-HBV for the
treatment of HBV infection, its expectations with respect to the selection of
a Development Candidate and the timing of regulatory filings to initiate a
clinical trial for ALN-HBV, its expectations regarding its “Alnylam 5x15”
product strategy, its plans regarding commercialization of RNAi therapeutics,
including ALN-HBV, 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.

^1 Issued U.S. patents in the McSwiggen patent family include U.S. Patent Nos:
7,923,547; 7,956,176; 7,989,612; 8,202,979; 8,232,383; 8,236,944; 8,242,257;
8,268,986; 8,273,866; 8,507,661; 8,618,277.

^2 Granted EU patents in the McSwiggen patent family include EU Patent Nos:
1423406; 1458741; 1627061; 2278004; 2287306.

Contact:

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