The Medicines Company and Alnylam Advance Development Candidate for ALN-PCSsc, a Subcutaneously Administered RNAi Therapeutic

The Medicines Company and Alnylam Advance Development Candidate for ALN-PCSsc, 
a Subcutaneously Administered RNAi Therapeutic Targeting
PCSK9 Under Investigation for the Treatment of Hypercholesterolemia 
New Pre-Clinical Results Demonstrate That ALN-PCSsc Achieves Up to
90% PCSK9 Knockdown and Up to 68% Lowering of LDLc in Absence of
Statins; Pre-clinical Durability Data Support Every-Two-Weeks Dosing 
NEW YORK, NY -- (Marketwired) -- 10/09/13 --  The Medicines Company
(NASDAQ: MDCO) a leading acute/ intensive hospital care company, and
Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY), a leading RNAi
therapeutics company, announced today that their strategic alliance
has yielded a lead Development Candidate that is a subcutaneously
administered RNAi therapeutic (ALN-PCSsc) targeting PCSK9 for the
potential treatment of hypercholesterolemia.  
New data from non-human primate studies were presented at the
Oligonucleotide Therapeutics Society (OTS) meeting, and show that
ALN-PCSsc leads to an up to a 90% PCSK9 knockdown and an up to 68%
lowering of LDL cholesterol in the absence of statins. PCSK9 is a
protein that regulates low-density lipoprotein (LDL) receptor levels
on hepatocytes.  
The ALN-PCSsc lead Development Candidate utilizes Alnylam's
GalNAc-siRNA conjugate delivery technology that enables subcutaneous
dose administration. Pre-clinical durability data support the
potential for every-two-weeks dosing, with possible every-four-weeks
dosing.  
Additional details of the subcutaneously administered development
candidate, and the data, will be presented by John Maraganore, PhD,
Chief Executive Officer of Alnylam at The Medicines Company's
Investor & Analyst Day in New York (webcast 8:30ET to noon at
www.themedicinescompany.com). 
Dr. Maraganore said, "We have rapidly advanced the ALN-PCS
collaboration to reach our first goal, which was to designate our
Development Candidate by the end of this year. We anticipate
submitting an investigative new drug application for ALN-PCSsc with
the US Food and Drug Administration in late 2014. This is an
important program within our 'Alnylam 5x15' product development and
commercialization strategy focused on RNAi therapeutics directed
toward genetically validated targets." 
"These new data with subcutaneous delivery support our belief that
the unique mechanism of action for ALN-PCS holds great promise for a
differentiated and potentially best-in-class strategy for PCSK9
antagonism," said Clive Meanwell, MD, PhD, Chairman and Chief
Executive Officer of The Medicines Company. "Subcutaneous dosing
holds the potential for administration of a therapeutic in patients
less frequently and less invasively than intravenous dosing." 
The Medicines Company-Alnylam PCSK9 collaboration plan is for Alnylam
to complete certain pre-clinical and additional 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. 
Last week, The Lancet published results from a Phase I trial with
ALN-PCS02, a systemically administered RNAi therapeutic. The data
presented today are for the subcutaneous form ALN-PCSsc. 
About PCSK9
 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.  
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 therapies.  
About ALN-PCS 
 ALN-PCS is an investigational, 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 GalNAc Conjugates
 GalNAc-siRNA conjugates are a proprietary
Alnylam delivery platform and are designed to achieve targeted
delivery of RNAi therapeutics to hepatocytes through uptake by the
asialoglycoprotein receptor. Research findings demonstrate potent and
durable target gene silencing, as well as a wide therapeutic index,
with subcutaneously administered GalNAc-siRNAs from multiple "Alnylam
5x15" programs. 
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's purpose is to
save lives, alleviate suffering and contribute to the economics of
healthcare by focusing on 3000 leading acute/intensive care hospitals
worldwide. Its vision is to be a leading provider of solutions in
three areas: acute cardiovascular care, surgery and perioperative
care, and serious infectious disease care. The company operates in
the Americas, Europe and the Middle East, and Asia Pacific regions
with global centers today in Parsippany, NJ, USA and Zurich,
Switzerland. 
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,
2013, 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 toward
genetically defined targets for the treatment of serious,
life-threatening diseases with limited treatment options for patients
and their caregivers. These include: 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 familial amyloidotic
cardiomyopathy (FAC); ALN-AT3, an RNAi therapeutic targeting
antithrombin (AT) for the treatment of hemophilia and rare bleeding
disorders (RBD); ALN-AS1, an RNAi therapeutic targeting
aminolevulinate synthase-1 (ALAS-1) for the treatment of porphyria
including acute intermittent porphyria (AIP); ALN-PCS, an RNAi
therapeutic targeting PCSK9 for the treatment of
hypercholesterolemia; ALN-TMP, an RNAi therapeutic targeting TMPRSS6
for the treatment of beta-thalassemia and iron-overload disorders;
ALN-AAT, an RNAi therapeutic targeting alpha-1-antitrypsin (AAT) for
the treatment of AAT deficiency liver disease; and ALN-CC5, an RNAi
therapeutic targeting complement component C5 for the treatment of
complement-mediated diseases, amongst other programs. 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 an 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(TM) 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, 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. 
About "Alnylam 5x15(TM)" 
 The "Alnylam 5x15" strategy, launched in
January 2011, establishes a path for development and
commercialization of novel RNAi therapeutics toward genetically
defined targets for the treatment of 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-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 familial amyloidotic
cardiomyopathy (FAC); ALN-AT3, an RNAi therapeutic targeting
antithrombin (AT) for the treatment of hemophilia and rare bleeding
disorders (RBD); ALN-AS1, an RNAi therapeutic targeting
aminolevulinate synthase-1 (ALAS-1) for the treatment of porphyria
including acute intermittent porphyria (AIP); ALN-PCS, an RNAi
therapeutic targeting PCSK9 for the treatment of
hypercholesterolemia; ALN-TMP, an RNAi therapeutic targeting TMPRSS6
for the treatment of beta-thalassemia and iron-overload disorders;
ALN-AAT, an RNAi therapeutic targeting alpha-1-antitrypsin (AAT) for
the treatment of AAT deficiency liver disease; and ALN-CC5, an RNAi
therapeutic targeting complement component C5 for the treatment of
complement-mediated diseases, amongst 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, ALN-AS1, and
ALN-CC5, amongst other programs. 
Alnylam Forward-Looking Statements 
 Various statements in this press
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-PCS and
ALN-PCSsc, its expectations with respect to the timing of filing an
IND for ALN-PCSsc, and its expectations regarding the commercial
opportunity for the ALN-PCSsc program, 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 discover and develop novel
drug candidates and delivery approaches, successfully demonstrate the
efficacy and safety of its drug candidates, including ALN-PCSsc, 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
Quarterly Report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on August 9, 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
explicitly disclaims any obligation to update any forward-looking
statements. 
Contacts: 
Michael Mitchell
The Medicines Company
973-290-6097
michael.mitchell@themedco.com 
Neera Dahiya Ravindran, MD
The Medicines Company
973-290-6044
neera.ravindran@themedco.com 
Cynthia Clayton
Alnylam Pharmaceuticals, Inc.
617-551-8207 
Amanda Sellers (Media)
Spectrum
202-955-6222 x2597 
 
 
Press spacebar to pause and continue. Press esc to stop.