The Medicines Company and Alnylam Form Strategic Alliance to Develop and Commercialize RNAi Therapeutics Targeting PCSK9 for the

  The Medicines Company and Alnylam Form Strategic Alliance to Develop and
  Commercialize RNAi Therapeutics Targeting PCSK9 for the Treatment of

 - The Medicines Company Obtains Exclusive Global License to Advance ALN-PCS
                          RNAi Therapeutic Program -

 - Alnylam to Receive $25 Million in Upfront Payment in Addition to Milestone
                  Payments and Royalties on Product Sales -

     - Companies to Host Conference Call Today at 8:30 a.m. ET to Discuss
                               Collaboration -

Business Wire

PARSIPPANY, N.J. & CAMBRIDGE, Mass. -- February 4, 2013

The Medicines Company (Nasdaq: MDCO) and Alnylam Pharmaceuticals, Inc.
(Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that they
have formed an exclusive global alliance for the development and
commercialization of Alnylam’s ALN-PCS RNAi therapeutic program for the
treatment of hypercholesterolemia.

“This new alliance unites two organizations with a shared culture and
commitment to innovation. In my view and past experience, there could be no
stronger partner for our ALN-PCS program than The Medicines Company, which has
demonstrated industry-wide leadership in the advancement of cardiovascular
medicines to patients and remarkable success in its strategy of in-licensing,
developing, and commercializing breakthrough products,” said John Maraganore,
Ph.D., Chief Executive Officer of Alnylam. “For Alnylam, this new partnership
enables the advancement of ALN-PCS, an important program within our ‘Alnylam
5x15’ product development and commercialization strategy focused on RNAi
therapeutics directed toward genetically validated targets. We believe that
the ALN-PCS program holds great promise for the development of a significant
therapeutic option for patients with hypercholesterolemia, and that the unique
mechanism of action for ALN-PCS could provide a differentiated and potentially
best-in-class strategy for PCSK9 antagonism.”

“Our focus on acute and intensive care medicine has led us to a leadership
position with Angiomax® (bivalirudin) and potentially with cangrelor in the
management of patients in extreme risk as a consequence of the rupture of
their vulnerable coronary artery plaque at and around the time of acute
coronary syndromes. Meantime, we have made progress with MDCO-216 (ApoA-1
Milano), a turbocharged form of HDL-C (‘good cholesterol’) which has the
potential to modify disease through reverse cholesterol transport,” said Clive
Meanwell, M.D., Ph.D., Chairman and Chief Executive Officer of The Medicines
Company. “Now,this exciting collaboration with Alnylam - leaders in their
field of RNAi - adds a second potentially disease modifying approach and more
cutting edge technology to our portfolio. We have seen that PCSK9 gene
silencing can substantially reduce LDL-cholesterol in patients and has
epidemiological and disease mechanisms studies suggest this can further reduce
the risks of the world’s number one killer, coronary artery disease. Clearly
we see the complementarity of approaches which increase ‘good cholesterol’
(HDL-C) and decrease ‘bad cholesterol’ (LDL-C). We look forward to working
with our colleagues at Alnylam for whom we have the greatest respect and
admiration based upon earlier collaborations particularly around Angiomax,
which was invented by John Maraganore.”

PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that
regulates low-density lipoprotein (LDL) receptor levels on hepatocytes;
gain-of-function human mutations in PCSK9 are associated with
hypercholesterolemia while loss-of-function mutations are associated with
lower levels of LDL cholesterol and a reduced risk of cardiovascular disease.
ALN-PCS is a PCSK9 synthesis inhibitor that reduces intracellular and
extracellular levels of PCSK9 resulting in lowered plasma levels of LDL-C.
MDCO-216 is a naturally occurring variant of a protein found in high-density
lipoprotein, or HDL. It is a reverse cholesterol transport agent designed to
reduce atherosclerotic plaque burden development and thereby reduce the risk
of adverse thrombotic events.

Under this alliance, The Medicines Company and Alnylam intend to collaborate
on the advancement of the ALN-PCS program. Alnylam’s ALN-PCS program includes
ALN-PCS02 - an intravenously administered RNAi therapeutic which has completed
a Phase I trial, and ALN-PCSsc - a subcutaneously administered RNAi
therapeutic currently in pre-clinical development. Alnylam will continue the
program for an estimated one to two years to complete certain pre-clinical and
Phase I clinical studies. The Medicines Company is responsible for leading and
funding development from Phase II forward and commercializing the ALN-PCS
program if successful. Under the terms of the agreement, The Medicines Company
will make an upfront cash payment of $25 million to Alnylam. Alnylam may also
receive potential development and commercial milestone payments of up to $180
million. Alnylam will be eligible to receive scaled double-digit royalties on
global products sales of ALN-PCS products.

Alnylam has completed a Phase I trial of ALN-PCS02 in healthy volunteer
subjects with elevated baseline LDL-C. Results showed that administration of a
single intravenous dose of drug, in the absence of concomitant lipid-lowering
agents such as statins, resulted in statistically significant and durable
reductions of PCSK9 plasma levels of up to 84% and lowering of LDL-C of up to
50%. ALN-PCS02 was shown to be generally safe and well tolerated in this study
and there were no serious adverse events related to study drug administration.
Alnylam has also presented pre-clinical data from its ALN-PCSsc program
demonstrating potent knockdown of the PCSK9 target gene with an ED[50] of less
than 0.3 mg/kg after a single subcutaneous dose.

“Cardiovascular disease remains the leading cause of mortality worldwide, with
elevated LDL-C a major modifiable risk factor. New strategies are needed to
dramatically and rapidly reduce LDL-C and prevent acute cardiovascular events
that result from the rupture of cholesterol rich plaque when patients are at
their most vulnerable,” said Daniel J. Rader, M.D., professor of Medicine and
chief, Division of Translational Medicine and Human Genetics, at the Perelman
School of Medicine at the University of Pennsylvania. “As a key regulator of
the LDL receptor, liver-expressed PCSK9 is one of the most important and best
validated new targets in molecular medicine for the treatment of
hypercholesterolemia. The ALN-PCS data generated to date are very encouraging
and I look forward to continued clinical studies that highlight the unique
mechanistic approach of PCSK9 synthesis inhibitors.”

Dr. Rader serves as a member of Alnylam’s Scientific Advisory Board and as a
consultant on Alnylam’s ALN-PCS program, and Alnylam and Dr. Rader collaborate
on research for which Alnylam provides materials.

Conference Call Information

The Medicines Company and Alnylam will host a conference call today at 8:30
a.m. ET to discuss this new collaboration. To access the call, please dial
877-312-7507 (domestic) or 631-813-4828 (international) five minutes prior to
the start time and refer to conference ID 96998933. A replay of the call will
be available beginning at 11:30 a.m. ET. To access the replay, please dial
855-859-2056 (domestic) or 404-537-3406 (international) and refer to
conference ID 96998933. A live audio webcast of the presentation will be
available on The Medicines Company website at, and
on the News & Investors section of the Alnylam’s website,

About Hypercholesterolemia

Hypercholesterolemia is a condition characterized by very high levels of
cholesterol in the blood which is known to increase the risk of coronary
artery disease, the leading cause of death in the U.S. Some forms of
hypercholesterolemia can be treated through dietary restrictions, lifestyle
modifications (e.g., exercise and smoking cessation) and medicines such as
statins. However, a large proportion of patients with hypercholesterolemia are
not achieving target LDL-C goals with statin therapy, including genetic
familial hypercholesterolemia patients, acute coronary syndrome patients,
high-risk patient populations (e.g., patients with coronary artery disease,
diabetics, symptomatic carotid artery disease, etc.) and other patients that
are statin intolerant. Severe forms of hypercholesterolemia are estimated to
affect more than 500,000 patients worldwide, and as a result, there is a
significant need for novel therapeutics to treat patients with
hypercholesterolemia whose disease is inadequately managed by existing


ALN-PCS is a systemically delivered RNAi therapeutic targeting the gene
proprotein convertase subtilisin/kexin type 9 (PCSK9), a target validated by
human genetics that is involved in the metabolism of low-density lipoprotein
cholesterol (LDL-C, or “bad” cholesterol). ALN-PCS therapies are PCSK9
synthesis inhibitors that lower levels of both intracellular and extracellular
PCSK9, thereby phenocopying the human genetics observed in loss of function or
null human PCSK9 mutations (N. Engl. J. Med. (2006) 354:1264-1272; Am. J. Hum.
Genet. (2006) 79: 514-523). PCSK9 synthesis inhibition through an RNAi
mechanism has the potential to lower tissue and circulating plasma PCSK9
protein levels resulting in higher LDL receptor levels in the liver, and
subsequently lower LDL-C levels in the blood stream. Lower LDL-C is associated
with a decreased risk of cardiovascular disease, including myocardial
infarction and stroke.

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 The Medicines Company

The Medicines Company (Nasdaq: MDCO) provides medical solutions to improve
health outcomes for patients in acute and intensive care hospitals worldwide.
These solutions comprise medicines and knowledge that directly impact the
survival and well being of critically ill patients.

The Medicines Company Forward-Looking Statement

Statements contained in this press release about The Medicines Company that
are not purely historical, and all other statements that are not purely
historical, may be deemed to be forward-looking statements for purposes of the
safe harbor provisions under The Private Securities Litigation Reform Act of
1995. Without limiting the foregoing, the words “believes,” “anticipates” and
“expects” and similar expressions are intended to identify forward-looking
statements. These forward-looking statements involve known and unknown risks
and uncertainties that may cause the Company’s actual results, levels of
activity, performance or achievements to be materially different from those
expressed or implied by these forward-looking statements. Important factors
that may cause or contribute to such differences include whether the Company’s
products will advance in the clinical trials process on a timely basis or at
all, whether the Company will make regulatory submissions for product
candidates on a timely basis, whether its regulatory submissions will receive
approvals from regulatory agencies on a timely basis or at all, whether
physicians, patients and other key decision makers will accept clinical trial
results, and such other factors as are set forth in the risk factors detailed
from time to time in the Company’s periodic reports and registration
statements filed with the Securities and Exchange Commission including,
without limitation, the risk factors detailed in the Company's Quarterly
Report on Form 10-Q filed on November 9, 2012, which are incorporated herein
by reference. The Company specifically disclaims any obligation to update
these forward-looking statements.

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 for
the treatment of genetically defined diseases, including ALN-TTR for the
treatment of transthyretin-mediated amyloidosis (ATTR), ALN-AT3 for the
treatment of hemophilia and rare bleeding disorders (RBD), ALN-AS1 for the
treatment of acute intermittent porphyria (AIP), ALN-PCS for the treatment of
hypercholesterolemia, and ALN-TMP for the treatment of hemoglobinopathies. As
part of its “Alnylam 5x15^TM” 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 a significant 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, and Cell. Founded in 2002, Alnylam maintains headquarters in
Cambridge, Massachusetts. For more information, please visit

About “Alnylam 5x15™”

The “Alnylam 5x15” strategy, launched in January 2011, establishes a path for
development and commercialization of novel RNAi therapeutics directed toward
genetically defined targets for 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 ALN-TTR for the treatment of transthyretin-mediated
amyloidosis (ATTR), ALN-AT3 for the treatment of hemophilia and rare bleeding
disorders (RBD), ALN-AS1 for the treatment of acute intermittent porphyria
(AIP), ALN-PCS for the treatment of hypercholesterolemia, ALN-TMP for the
treatment of hemoglobinopathies, and 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; these
include ALN-TTR, ALN-AT3, and ALN-AS1; the company will seek global
development and commercial alliances for other programs.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations,
plans and prospects, including without limitation, statements regarding
Alnylam’s views with respect to the potential for RNAi therapeutics, including
the potential for the ALN-PCS program, including ALN-PCS02 and ALN-PCSsc, its
expectations regarding the receipt of upfront and potential development and
commercialization milestones and royalty payments on worldwide net sales, if
any, under The Medicines Company agreement, and Alnylam’s expectations
regarding its “Alnylam 5x15” product strategy, 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
successfully demonstrate the efficacy and safety of its drug candidates and
the pre-clinical and clinical results for these product candidates, including
ALN-PCS02 and ALN-PCSsc, which may not support further development of such
product candidates, both our and The Medicines Company’s ability to
successfully advance ALN-PCS02 and/or ALN-PCSsc resulting in the potential
payment of milestones and royalties to us, actions of regulatory agencies,
which may affect the initiation, timing and progress of clinical trials for
such product candidates, obtaining, maintaining and protecting intellectual
property, obtaining regulatory approval for products, competition from others
using technology similar to Alnylam’s and others developing products for
similar uses, and Alnylam’s ability to establish and maintain strategic
business alliances, including its collaboration with The Medicines Company,
and new business initiatives, as well as those risks more fully discussed in
the “Risk Factors” filed with Alnylam’s current report on Form 8-K filed with
the Securities and Exchange Commission (SEC) on January 14, 2013 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 does not
assume any obligation to update any forward-looking statements.

Photos/Multimedia Gallery Available:



The Medicines Company
Michael Mitchell, 973-290-6097
Head of Global Communications
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice President, Investor Relations and
Corporate Communications
Amanda Sellers (Media), 202-955-6222 x2597
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