Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi
therapeutics company, announced today that it presented new pre-clinical
research findings from its transthyretin (TTR)-mediated amyloidosis
(ATTR) program at the 60th Annual Meeting of the American
Association for the Study of Liver Diseases ("The Liver Meeting”).
Alnylam is developing ALN-TTR, a systemically delivered RNAi therapeutic
targeting the TTR gene for the treatment of ATTR, including familial
amyloidotic cardiomyopathy (FAC) and familial amyloidotic polyneuropathy
(FAP). There are more than 100 mutations that have been identified in
the TTR gene. ALN-TTR targets a region of the gene common to wild-type
and all known mutant forms of TTR, and therefore, has potential as a
therapeutic for all patients with FAC and FAP.
"We are very encouraged by these significant and important pre-clinical
findings, which continue to validate the potential benefit of an RNAi
therapeutic targeting TTR for the treatment of ATTR,” said Dinah Sah,
Ph.D., Vice President, Research, CNS and Oncology at Alnylam. "Our new in
vivo studies represent a significant step forward as they
demonstrate the ability of ALN-TTR to silence the TTR gene for a period
of weeks after a single dose administration. These data provide
continued validation of our RNAi therapeutics strategy, and we are
looking forward to advancing this program towards the clinic.”
The new pre-clinical research findings presented at the meeting
demonstrated dose-dependent ALN-TTR reduction of liver TTR messenger
(mRNA) and serum TTR protein levels by greater than 80% in transgenic
mice and non-human primates, with gene silencing effects found to be
durable for more than three weeks following a single dose administration.
"I am quite excited by these new data, which strongly support the
advancement of this program towards patients who have extremely limited
therapeutic options,” said Maria Joao Saraiva, Ph.D., Professor of
Biochemistry, Molecular Neurobiology Group, Institute for Molecular and
Cellular Biology in Portugal. "ATTR, which presents severe
manifestations in both FAP and FAC, is estimated to affect approximately
50,000 people worldwide and is associated with significant morbidity,
including intractable peripheral sensory neuropathy, disabling
dysfunction of the autonomic nervous system that leads to severe
intestinal dysfunction, and in many cases severe cardiomyopathy.”
Alnylam expects to file regulatory applications for ALN-TTR by the end
of 2009 with a goal of initiating a Phase I clinical trial in early
2010. ALN-TTR is being advanced using stable nucleic acid-lipid
particles (SNALP) delivery technology in collaboration with Tekmira
Pharmaceuticals Corporation.
About TTR-mediated Amyloidosis
TTR-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused
by a mutation in the transthyretin (TTR) gene. TTR protein is produced
primarily in the liver and is normally a carrier for thyroid hormones
and retinol binding proteins. The mutation causes abnormal amyloid
proteins to accumulate in and damage body organs and tissue such as the
peripheral nerves and heart, resulting in intractable peripheral sensory
neuropathy, autonomic neuropathy, and cardiomyopathy. In its severest
form, ATTR represents a tremendous unmet medical need with significant
morbidity and mortality as an orphan disease; FAP (familial amyloidotic
polyneuropathy) affects approximately 10,000 people worldwide with
additional patients affected by FAC (familial amyloidotic
cardiomyopathy). ATTR patients with FAP have a mean life expectancy of
five to fifteen 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 a mutation in the TTR gene.
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 applying its
therapeutic expertise in RNAi to address significant medical needs, many
of which cannot effectively be addressed with small molecules or
antibodies, the current major classes of drugs. Alnylam is leading the
translation of RNAi as a new class of innovative medicines with
peer-reviewed research efforts published in the world’s top scientific
journals including Nature, Nature Medicine, and Cell.
The company is leveraging these capabilities to build a broad pipeline
of RNAi therapeutics; its most advanced program is in Phase II human
clinical trials for the treatment of respiratory syncytial virus (RSV)
infection and is partnered with Cubist and Kyowa Hakko. In addition, the
company is developing RNAi therapeutics for the treatment of a wide
range of disease areas, including liver cancers, hypercholesterolemia,
Huntington’s disease, and TTR amyloidosis. The company’s leadership
position in fundamental patents, technology, and know-how relating to
RNAi has enabled it to form major alliances with leading companies
including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko,
and Cubist. To reflect its outlook for key scientific, clinical, and
business initiatives, Alnylam established "RNAi 2010” in January
2008 which includes the company’s plan to significantly expand the scope
of delivery solutions for RNAi therapeutics, have four or more programs
in clinical development, and to form four or more new major business
collaborations, all by the end of 2010. Alnylam is a joint owner of
Regulus Therapeutics, a joint venture focused on the discovery,
development, and commercialization of microRNA therapeutics. Founded in
2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For
more information, please visit http://www.alnylam.com.
Alnylam Forward-Looking Statement
Various statements in this release concerning Alnylam’s future
expectations, plans and prospects, 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 the company's ability to
successfully research and develop products and to successfully prosecute
and enforce its patents around the world, 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.
