Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi
therapeutics company, announced today the presentation of new
pre-clinical data from its hypercholesterolemia program, performed in
collaboration with scientists at the University of Texas Southwestern
Medical Center at Dallas. The data were presented at the PCSK9
Conference: From Gene to Therapeutics held in Nantes, France from March
11-13, 2010. Alnylam has an ongoing development program focused on using
RNAi therapeutics targeting proprotein convertase subtilisin/kexin type
9, or PCSK9, as a novel strategy for reducing LDL (or "bad”)
cholesterol. The new data demonstrated durable reductions of cholesterol
levels in both rodents and non-human primates with an RNAi therapeutic
targeting PCSK9 using second generation lipid nanoparticle (LNP)
formulations. Further, data also showed the ability to utilize siRNA
combination approaches to achieve efficient silencing of separate and
distinct genes to achieve cholesterol lowering.
"We are very encouraged by the progress we have made in our development
efforts for an RNAi therapeutic targeting PCSK9 for the treatment of
hypercholesterolemia. With an RNAi approach, both intracellular and
extracellular PCSK9 levels can be reduced, thereby replicating the human
genetics,” said Kevin Fitzgerald, Ph.D., Director of Research at
Alnylam. "In addition to the markedly improved potency we demonstrated
last year with second generation LNPs, we are now able to show that
PCSK9 silencing effects are durable over a remarkably extended period of
time. Further, these new data highlight our ability to investigate
liver-specific silencing of target combinations in order to develop
novel RNAi therapeutics for the treatment of hypercholesterolemia, as
well as potentially other metabolic disorders.”
The new in vivo research findings presented at this meeting were
performed using a systemically delivered RNAi therapeutic targeting
PCSK9 and formulated in a second generation LNP, developed in
collaboration with Tekmira Pharmaceuticals Corporation, The University
of British Columbia, and AlCana Technologies, Inc. Data from these
studies include:
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in vivo non-human primate data showing durable silencing of
PCSK9 for more than 30 days following a single dose administration,
with reduction in LDL cholesterol levels of approximately 50%;
-
unlike results reported with monoclonal antibody strategies targeting
extracellular PCSK9 (Chan et al., Proc. Natl. Acad. Sci. USA,
106(24): 9820-5, 2009), RNAi-mediated silencing of both intracellular
and extracellular PCSK9 resulting in no lowering of HDL (or "healthy”)
cholesterol;
-
in vivo rodent data demonstrating the ability to utilize a
novel dual-targeting approach to silence PCSK9 and a second
undisclosed gene involved in lipid metabolism with a single RNAi
therapeutic, resulting in a reduction in total cholesterol of greater
than 40%; and,
-
in vivo rodent data showing that injection of multiple siRNAs
packaged in a single LNP formulation results in silencing of as many
as 10 distinct target genes simultaneously.
"These new data continue to support the development of an RNAi
therapeutic strategy of targeting PCSK9 for disease intervention in
hypercholesterolemia,” said Jay Horton, M.D., Professor of Internal
Medicine and Molecular Genetics, University of Texas Southwestern
Medical Center. "Based on its novel mechanism and promising pre-clinical
data observed to date, an RNAi therapeutic targeting PCSK9 has the
potential to lower LDL cholesterol while preserving HDL cholesterol, and
possibly function synergistically with statins for the treatment of
hypercholesterolemia.”
Alnylam is developing ALN-PCS, an RNAi therapeutic targeting PCSK9 for
the treatment of hypercholesterolemia; ALN-PCS is a systemically
delivered RNAi therapeutic comprised of an optimized siRNA encapsulated
in a second generation LNP formulation. Alnylam expects to advance its
ALN-PCS program toward the clinic with a goal of initiating a Phase I
clinical trial in 2011.
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. RNAi
therapeutics target the cause of diseases by potently silencing specific
messenger RNAs (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. In addition, the company is developing RNAi therapeutics for
the treatment of a wide range of disease areas, including liver cancers,
TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntington’s
disease. 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 Kirin, and Cubist. Alnylam and Isis are
joint owners of Regulus Therapeutics Inc., a company focused on the
discovery, development, and commercialization of microRNA-based
therapeutics. Founded in 2002, Alnylam maintains headquarters in
Cambridge, Massachusetts. For more information, please visit www.alnylam.com.
Alnylam Forward-Looking Statement
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-PCS, its plan to initiate a clinical trial ALN-PCS, the
timing of regulatory filings, and its expectations regarding the
continued development of ALN-PCS, 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
discover and develop novel drug candidates, and successfully demonstrate
efficacy and safety of its drug candidates, including ALN-PCS, in human
clinical trials, as well as those risks more fully discussed in the
"Risk Factors” section of its most recent annual report on Form 10-K 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.
