– Company Expects to Initiate Trial in First Half of 2012 with Data
in Third Quarter of 2012 –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 6, 2012--
Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics
company, announced today that it has filed a Clinical Trial Application
(CTA) with the U.K. Medicines and Healthcare products Regulatory Agency
(MHRA) to initiate a Phase I clinical trial with ALN-TTR02, an RNAi
therapeutic targeting transthyretin (TTR) for the treatment of
TTR-mediated amyloidosis (ATTR). ALN-TTR02 is a systemically delivered
RNAi therapeutic, targeting the TTR gene, that comprises an siRNA
formulated in a second-generation lipid nanoparticle (LNP). Following
clearance of the CTA, Alnylam expects to initiate the ALN-TTR02 Phase I
study in the first half of 2012 with data expected to be reported in the
third quarter of 2012.
“We are very committed to the continued advancement of our ALN-TTR
program, which we believe has the potential to emerge as the leading
innovative medicine for the treatment of ATTR. Indeed, our
preliminary ALN-TTR01 trial results showed rapid and durable lowering of
TTR serum levels in ATTR patients with just a single dose; we can
confidently expect even more robust results with ALN-TTR02 which
utilizes our second-generation lipid nanoparticle delivery platform,”
said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President and Chief
Medical Officer of Alnylam. “To put this new program into context,
pre-clinical studies have shown that administration of ALN-TTR02 results
in a greater than 10-fold improvement in TTR silencing as compared with
ALN-TTR01. Moreover, our recent preliminary clinical results with
ALN-PCS, utilizing the same second-generation LNP formulation as
ALN-TTR02, demonstrated initial safety and robust potency with greater
than 65% silencing of the protein target, PCSK9, at the current dose
level. Accordingly, we very much look forward to the continued
advancement of ALN-TTR02, including the start of this Phase I clinical
trial in healthy volunteers in the first half of this year and data in
the third quarter. We also expect to initiate a Phase II study with
ALN-TTR02 in familial amyloidotic polyneuropathy, or FAP, patients in
the second half of this year with the start of pivotal trials with
ALN-TTR02 in 2013.”
ATTR is an autosomal dominant inherited disease caused by mutations in
the TTR gene, which is expressed predominantly in the liver and results
in the accumulation of pathogenic deposits of mutant and wild-type TTR
protein in multiple extra-hepatic tissues, including the peripheral
nervous system, gastrointestinal tract, and heart. Alnylam recently
presented preliminary results from its Phase I study of ALN-TTR01, which
utilizes the identical siRNA as in ALN-TTR02 but formulated in a
first-generation LNP. Preliminary data from this study showed that
administration of ALN-TTR01 resulted in statistically significant
reductions in serum TTR protein levels in ATTR patients with a mean
reduction of 41% relative to placebo (p=0.02). Lowering of TTR was
demonstrated to be dose dependent, rapid, and durable after just a
single dose. ALN-TTR01 was found to be generally safe and well
tolerated. Pre-clinical studies have shown that administration of
ALN-TTR02 results in a greater than 10-fold improvement in TTR lowering
compared with ALN-TTR01. Moreover, recent preliminary clinical results
with ALN-PCS, which utilizes the identical second-generation LNP
delivery platform as ALN-TTR02, demonstrated initial safety and the
expected improvements in potency.
“RNAi therapeutics represent a novel and compelling approach for the
treatment of ATTR. Based on our understanding of the pathogenesis of
this disease, TTR lowering defines an encouraging therapeutic strategy,”
said Philip Hawkins, FMedSci., Professor of Medicine, University College
London Medical School. “The recent preliminary clinical data for
ALN-TTR01 in patients are very promising and I am excited about the
translation of this second-generation agent in clinical trials, as there
are currently few options for patients suffering from this disease.”
As per the filed CTA, the Phase I trial of ALN-TTR02 is planned to be
conducted in the U.K. as a randomized, single-blind, single-ascending
dose study, enrolling up to 32 healthy volunteer subjects. The primary
objective of the study is to evaluate the safety and tolerability of a
single dose of ALN-TTR02. Secondary objectives include characterization
of pharmacokinetics of ALN-TTR02 and assessment of clinical activity of
the drug as measured by serum TTR levels.
About Transthyretin (TTR)-Mediated Amyloidosis
Transthyretin (TTR)-mediated amyloidosis (ATTR) is a hereditary,
systemic disease caused by mutations in the TTR gene. TTR protein is
produced primarily in the liver and is normally a carrier for thyroid
hormones and retinol binding proteins. 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. In its
severest form, ATTR represents a major unmet medical need with
significant morbidity and mortality as an orphan disease; FAP (familial
amyloidotic polyneuropathy) affects approximately 10,000 people
worldwide and FAC (familial amyloidotic cardiomyopathy) affects
approximately 40,000 people worldwide. ATTR patients with FAP have a
mean life expectancy of five to 15 years from symptom onset and the only
treatment option is liver transplantation; as a result there is a
significant need for novel therapeutics to treat patients who have
inherited mutations in the TTR gene.
About “Alnylam 5x15™”
The “Alnylam 5x15” strategy, launched in January 2011, establishes a
path for development and commercialization of novel RNAi therapeutics to
address genetically defined 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. This strategy
leverages Alnylam’s clinical progress on siRNA delivery, including
definitive human proof-of-concept data for systemic delivery. By the end
of 2015, the company expects to have five such RNAi therapeutic programs
in advanced clinical development. These include ALN-TTR for the
treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the
treatment of severe hypercholesterolemia, ALN-HPN for the treatment of
refractory anemia, ALN-APC for the treatment of hemophilia, and one
additional program from the company’s ongoing discovery efforts that
will be designated at or around the end of 2011. Alnylam intends to
focus on developing and commercializing certain products arising under
the “Alnylam 5x15” strategy itself in the United States and potentially
certain other countries; the company will seek development and
commercial partners for other core products both in the United States
and in other global territories.
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 RNAs (siRNAs), 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 for the treatment of genetically defined
diseases, including ALN-TTR for the treatment of transthyretin-mediated
amyloidosis (ATTR), ALN-PCS for the treatment of severe
hypercholesterolemia, ALN-HPN for the treatment of refractory anemia,
and ALN-APC for the treatment of hemophilia. As part of its “Alnylam 5x15TM”
strategy, the company expects to have five RNAi therapeutic products for
genetically defined diseases in advanced stages of clinical development
by the end of 2015. Alnylam has additional partner-based programs in
clinical or development stages, including ALN-RSV01 for the treatment of
respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment
of liver cancers, and ALN-HTT for the treatment of Huntington’s disease.
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, and Cubist. In addition, Alnylam and Isis co-founded
Regulus Therapeutics Inc., a company focused on discovery, development,
and commercialization of microRNA therapeutics; Regulus has formed
partnerships with GlaxoSmithKline and Sanofi. Alnylam has also formed
Alnylam Biotherapeutics, a division of the company focused on the
development of RNAi technologies for application 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 www.alnylam.com.
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 ALN-TTR01, ALN-TTR02, and ALN-PCS, the
therapeutic potential for its second-generation lipid nanoparticle
delivery technology, the filing of a CTA with the MHRA to initiate a
Phase I clinical trial with ALN-TTR02 and the expected timing of
regulatory clearance and clinical trial initiation for ALN-TTR02, its
expectations with respect to the timing and success of its clinical and
pre-clinical trials, including for ALN-TTR01, ALN-TTR02 and ALN-PCS, the
expected timing for initiation of a Phase II study in FAP with ALN-TTR02
and the potential start of pivotal trials with ALN-TTR02 in 2013, its
expectations regarding the reporting of data from its ALN-TTR02 clinical
trial, 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 discover
and develop novel drug candidates, successfully demonstrate the efficacy
and safety of its drug candidates, including those formulated in its
second-generation lipid nanoparticle delivery technology, including
ALN-TTR02, and ALN-PCS, 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, 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
and new business initiatives, as well as those risks more fully
discussed in the “Risk Factors” section of its most recent quarterly
report on Form 10-Q on file with the Securities and Exchange Commission.
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.

Source: Alnylam Pharmaceuticals
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice
President, Investor Relations and
Corporate Communications
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Media
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Sellers, 202-955-6222 x2597