Alnylam Receives Orphan Drug Designations in the European Union for ALN-AT3, an RNAi Therapeutic in Development for the

  Alnylam Receives Orphan Drug Designations in the European Union for ALN-AT3,
  an RNAi Therapeutic in Development for the Treatment of Hemophilia

Business Wire

CAMBRIDGE, Mass. -- August 7, 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 granted Orphan Drug Designations for
ALN-AT3 as an orphan medicinal product for the treatment of hemophilia A and
hemophilia B. Alnylam is developing ALN-AT3, a subcutaneously administered
RNAi therapeutic targeting antithrombin (AT), for the treatment of hemophilia
and other Rare Bleeding Disorders (RBD).

“We are very pleased to have received Orphan Drug Designations from the EMA
COMP for ALN-AT3, a key program in our ‘Alnylam 5x15’ product development and
commercialization strategy. We believe that our subcutaneously delivered RNAi
therapeutic represents an innovative approach for the management of hemophilia
and has great potential to make a meaningful impact in the treatment of this
often debilitating bleeding disorder,” said Saraswathy (Sara) Nochur, Ph.D.,
Senior Vice President, Regulatory Affairs and Quality Assurance at Alnylam.
“Having announced positive top-line results in adult healthy volunteers
earlier this year, we look forward to presenting initial Phase 1 results,
including data in hemophilia subjects, later in the year.”

ALN-AT3 is currently being investigated in a multinational Phase 1 trial. At
the World Federation of Hemophilia 2014 World Congress held in May, Alnylam
presented positive top-line data from Part A of the study performed in adult
healthy volunteers. Initial results from the sole dose cohort enrolled (n=4;
3:1, drug:placebo) showed that a single, low subcutaneous ALN-AT3 dose of 0.03
mg/kg resulted in an up to 28-32% knockdown of AT at nadir (p < 0.01 by ANOVA,
relative to placebo). This resulted in a statistically significant (p < 0.01)
increase in peak thrombin generation, that was temporally associated and
consistent with the degree of AT knockdown. ALN-AT3 was found to be well
tolerated with no significant adverse events reported. With these data and in
light of a dose escalation stopping rule at a 40% level of AT knockdown, the
company has transitioned to Part B of the study – an open-label, multi-dose,
dose-escalation study enrolling up to 18 people with moderate to severe
hemophilia A or B. The primary objective of this part of the study is to
evaluate the safety and tolerability of multiple doses, specifically three
weekly doses, of subcutaneously administered ALN-AT3 in hemophilia subjects.
Secondary objectives include assessment of clinical activity as determined by
knockdown of circulating AT levels and increase in thrombin generation at
pharmacologic doses of ALN-AT3. In this part of the study, dose escalation
will be allowed to proceed beyond the 40% AT knockdown level. The company
plans to present initial clinical results, including results in hemophilia
subjects from Part B of the study, by the end of the year.

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.

Alnylam will be discussing its progress with the ALN-AT3 program in an RNAi
Roundtable webinar to be held at 9:30 a.m. ET today, and can be accessed by
clicking here.

About Hemophilia and Rare Bleeding Disorders

Hemophilias are hereditary disorders caused by genetic deficiencies of various
blood clotting factors, resulting in recurrent bleeds into joints, muscles,
and other major internal organs. Hemophilia A is defined by loss-of-function
mutations in Factor VIII, and there are greater than 40,000 registered
patients in the U.S. and E.U. Hemophilia B, defined by loss-of-function
mutations in Factor IX, affects greater than 9,500 registered patients in the
U.S. and E.U. Other Rare Bleeding Disorders (RBD) are defined by congenital
deficiencies of other blood coagulation factors, including Factors II, V, VII,
X, and XI, and there are about 1,000 patients worldwide with a severe bleeding
phenotype. Standard treatment for hemophilia patients involves replacement of
the missing clotting factor either as prophylaxis or on-demand therapy.
However, as many as one third of people with severe hemophilia A will develop
an antibody to their replacement factor - a very serious complication; these
'inhibitor' patients become refractory to standard replacement therapy. There
exists a small subset of hemophilia patients who have co-inherited a
prothrombotic mutation, such as Factor V Leiden, antithrombin deficiency,
protein C deficiency, and prothrombin G20210A. Hemophilia patients that have
co-inherited these prothrombotic mutations are characterized as having a later
onset of disease, lower risk of bleeding, and reduced requirements for Factor
VIII or Factor IX treatment as part of their disease management. There exists
a significant need for novel therapeutics to treat hemophilia patients.

About Antithrombin (AT)

Antithrombin (AT, also known as “antithrombin III” and "SERPINC1") is a liver
expressed plasma protein and member of the "serpin" family of proteins that
acts as an important endogenous anticoagulant by inactivating Factor Xa and
thrombin. AT plays a key role in normal hemostasis, which has evolved to
balance the need to control blood loss through clotting with the need to
prevent pathologic thrombosis through anticoagulation. In hemophilia, the loss
of certain procoagulant factors (Factor VIII and Factor IX, in the case of
hemophilia A and B, respectively) results in an imbalance of the hemostatic
system toward a bleeding phenotype. In contrast, in thrombophilia (e.g.,
Factor V Leiden, protein C deficiency, antithrombin deficiency, amongst
others), certain mutations result in an imbalance in the hemostatic system
toward a thrombotic phenotype. Since co-inheritance of prothrombotic mutations
may ameliorate the clinical phenotype in hemophilia, inhibition of AT defines
a novel strategy for improving hemostasis.

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

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-AT3 for the
treatment of hemophilia and rare bleeding disorders, its expectations with
respect to the design, timing, and success of its clinical trials, including
with ALN-AT3, its expectations regarding the presentation of data from
clinical trials with ALN-AT3, its expectations regarding the potential market
opportunity for ALN-AT3, its expectations regarding its “Alnylam 5x15” product
strategy, 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 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.


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