Alnylam Receives Positive Opinion for Orphan Drug Designation in the European Union for ALN-TTRsc, a Subcutaneously Delivered

  Alnylam Receives Positive Opinion for Orphan Drug Designation in the
  European Union for ALN-TTRsc, a Subcutaneously Delivered RNAi Therapeutic
  for the Treatment of Transthyretin-Mediated Amyloidosis (ATTR)

Business Wire

CAMBRIDGE, Mass. -- April 2, 2014

Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics
company, announced today that the European Medicines Agency (EMA) Committee
for Orphan Medicinal Products (COMP) has adopted a positive opinion
recommending ALN-TTRsc for designation as an orphan medicinal product for the
treatment of transthyretin (TTR)-mediated amyloidosis (ATTR).

“We are very pleased to have received a positive opinion from the EMA COMP on
our application for Orphan Drug Designation for ALN-TTRsc,” said Saraswathy
(Sara) Nochur, Ph.D., Senior Vice President, Regulatory Affairs and Quality
Assurance at Alnylam. “We believe RNAi therapeutics represent a promising new
approach for the treatment of ATTR, with the potential to make a meaningful
impact for patients with this progressive and debilitating disease. We look
forward to sharing Phase 2 clinical data from our ALN-TTRsc program later in
the year, and, assuming continued positive results, we plan to advance to a
Phase 3 pivotal trial in ATTR patients with TTR cardiac amyloidosis by the end
of the year.”

ALN-TTRsc is currently in a pilot Phase 2 clinical trial for the treatment of
ATTR patients with TTR cardiac amyloidosis; this study is aimed at evaluating
the tolerability of ALN-TTRsc in approximately 15 patients. In addition, the
study will assess preliminary clinical activity as measured by knockdown of
serum TTR levels and additional exploratory tests, such as cardiac imaging
(including echocardiography and cardiac MRI), circulating cardiac biomarkers
(NT-proBNP and troponins T and I), 6-minute walk test, New York Heart
Association (NYHA) classification, and measures of heart failure symptoms and
quality of life (Kansas City Cardiomyopathy Questionnaire and EQ-5D QOL). The
company expects to present data from the Phase 2 trial in late 2014. Patients
completing the Phase 2 trial will be eligible to participate in an open-label
extension (OLE) study for further assessment of general tolerability and
clinical activity with long-term dosing; the ALN-TTRsc Phase 2 OLE study is
expected to be initiated in mid-2014. Assuming positive results, Alnylam
expects to begin a Phase 3 trial in TTR cardiac amyloidosis patients by the
end of 2014.

Orphan Drug Designation by the European Commission provides regulatory and
financial incentives for companies to develop and market therapies that treat
a life-threatening or chronically debilitating condition affecting no more
than five in 10,000 persons in the European Union (EU), and where no
satisfactory treatment is available. In addition to a 10-year period of
marketing exclusivity in the EU after product approval, Orphan Drug
Designation provides incentives for companies seeking protocol assistance from
the EMA during the product development phase, and direct access to centralized
marketing authorization.

In January 2014, Genzyme and Alnylam formed an alliance to accelerate and
expand the development and commercialization of RNAi therapeutics across the
world. The alliance is structured as a multi-product geographic alliance in
the field of rare diseases. Alnylam retains product rights in North America
and Western Europe, while Genzyme obtains the right to access Alnylam’s
current “5x15” and future genetic medicines pipeline in the rest of the world
(ROW), including co-development/co-commercialization and/or global product
rights for certain programs. In the case of ALN-TTRsc, Alnylam and Genzyme are
co-developing and co-commercializing the product in North America and Western
Europe, while Genzyme will advance the product in the ROW.

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. Senile systemic
amyloidosis (SSA) is a non-hereditary form of TTR cardiac amyloidosis caused
by idiopathic deposition of wild-type TTR; its prevalence is generally
unknown, but is associated with advanced age. There is a significant need for
novel therapeutics to treat patients with TTR amyloid polyneuropathy and/or
cardiomyopathy.

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 aminolevulinate 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 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; 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. 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 January
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 expectations
regarding its "Alnylam 5x15" product strategy, Alnylam’s views with respect to
the potential for RNAi therapeutics, including ALN-TTRsc for the treatment TTR
cardiac amyloidosis, its expectations with respect to the timing and success
of its clinical trials, the expected timing of additional clinical trials, and
its plans regarding commercialization of RNAi therapeutics, 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 Annual Report on Form 10-K 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
Media:
Spectrum
Amanda Sellers, 202-955-6222 x2597
 
Press spacebar to pause and continue. Press esc to stop.