Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi
therapeutics company, today announced new pre-clinical data from its
ALN-VSP program presented at the AACR-NCI-EORTC Molecular Targets and
Cancer Therapeutics International conference being held November 15 -
19, 2009 in Boston, Mass. ALN-VSP is an RNAi therapeutic currently in a
Phase I clinical trial for the treatment of liver cancers, including
hepatocellular carcinoma (HCC) and other solid tumors with liver
involvement. The new data demonstrated robust anti-tumor activity in
orthotopic liver tumor models comprised of both HCC- and colorectal
cancer-derived cell lines. ALN-VSP was also shown to act on disseminated
tumors outside of the liver. Further, in addition to anti-proliferative
effects, studies showed that ALN-VSP exerts a potent anti-angiogenic
effect on tumors.
"ALN-VSP is Alnylam’s first systemic RNAi program, as well as our first
clinical program in an oncology indication,” said Dinah Sah, Ph.D., Vice
President Research, CNS and Oncology at Alnylam. "This RNAi therapeutic
targets two well-validated genes critical for tumor cell proliferation
and survival, an attractive strategy supported by these current data for
the advancement of novel anti-cancer medicines. Meanwhile, we are making
continued progress in our Phase I clinical trial with ALN-VSP having now
enrolled a significant portion of the study across multiple dose
cohorts, and look forward to sharing preliminary results in mid-2010.”
ALN-VSP is an RNAi therapeutic comprised of two small interfering RNAs
(siRNAs) formulated in a lipid nanoparticle (LNP) and designed to target
two genes critical in the growth and survival of cancer cells: kinesin
spindle protein, or KSP, required for tumor cell proliferation; and
vascular endothelial growth factor, or VEGF, required for blood vessel
formation to sustain tumor growth. The pre-clinical studies were
performed using ALN-VSP in an orthotopic liver tumor model utilizing
either human HCC cells or human colorectal carcinoma cells. In a poster
titled "Development of ALN-VSP: an RNAi Therapeutic for Liver
Malignancies,” Alnylam scientist Dr. Iva Toudjarska, presented the
following data:
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ALN-VSP-mediated silencing of KSP in both HCC and colorectal carcinoma
models, resulting in the accumulation in tumor cells of aberrant
mitotic figures, also known as monoasters, a hallmark of KSP
inhibition;
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monoaster formation in tumor cells within lymph node metastases
derived from the orthotopic liver tumors, demonstrating the ability of
LNPs in general, and ALN-VSP in particular, to achieve effective
delivery in extra-hepatic tumor sites;
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marked anti-angiogenic effects resulting from ALN-VSP treatment,
including reductions in both tumor microvessel density and
intratumoral hemorrhage; and
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similar anti-angiogenic results with an LNP containing only the VEGF
siRNA, demonstrating that the vascular effects are due to VEGF
silencing.
"We are very encouraged by these new results, as they show anti-tumor
activity for ALN-VSP in both primary and metastatic disease settings,”
said David Bumcrot, Ph.D., Director, Research at Alnylam. "Importantly,
these new studies demonstrate anti-tumor activity in extra-hepatic
tumors, highlighting the potential for effective delivery of siRNAs to
sites beyond the liver. These new results also confirm the
anti-angiogenic effects of ALN-VSP, providing continued support for our
dual-targeting strategy.”
ALN-VSP is currently in a Phase I multicenter, open-label,
dose-escalation trial to evaluate the safety, tolerability,
pharmacokinetics, and pharmacodynamics of ALN-VSP in patients with
advanced solid tumors with liver involvement, including HCC. Alnylam has
enrolled a significant number of patients across multiple dose cohorts
in the Phase I trial, and expects to present preliminary data from the
Phase I trial in mid-2010. ALN-VSP is formulated in an LNP, also known
as SNALP, in collaboration with Tekmira Pharmaceuticals Corporation.
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 Kirin. 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 Kirin, 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 demonstrate efficacy and safety of its drug candidates,
including ALN-VSP, in human clinical trials, 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.
