– ESC+ Platform Incorporates Novel Design
Features, Including Glycol Nucleic Acid (GNA) Modifications, that
Confer Greater Specificity, Further Improving Already Wide
Therapeutic Index by Over 6-fold –
– First ESC+ Development Candidate, ALN-AAT02,
in Development for Treatment of
Alpha-1 Antitrypsin (AAT) Deficiency-Associated
Liver Disease,
Expected to Enter Clinical Trials in 2018 –
Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading RNAi
therapeutics company, today announced that the Company presented
new pre-clinical data highlighting its next generation “Enhanced
Stabilization Chemistry Plus” (ESC+) GalNAc-siRNA conjugate
platform at the 13th Annual Meeting of the Oligonucleotide
Therapeutics Society (OTS), held September 24 – 27, 2017 in
Bordeaux, France.
ESC+ GalNAc conjugates utilize advanced design features to
further improve specificity, including a glycol nucleic acid (GNA)
modification in the antisense seed region of the siRNA, while
maintaining potency and durability. The data presented at OTS
indicated that incorporation of GNA destabilizes seed-driven
pairing with partially complementary transcripts, thus greatly
reducing potential off-target effects while maintaining on-target
pairing and activity. Additionally, it was shown that GNA
modifications confer enhanced specificity and a greater-than 6-fold
improvement in therapeutic index as observed in pre-clinical
studies in rodents. The ESC+ design is now being applied to all of
Alnylam’s pre-clinical programs and has shown successful
translation of potency from rodents to non-human primates. Alnylam
intends to employ its ESC+ siRNA-conjugate platform in all future
development programs.
“At Alnylam, we’ve been successful in advancing our ESC
GalNAc-siRNA conjugate platform with many potent and generally well
tolerated investigational RNAi therapeutics in clinical
development, including in Phase 3 studies. Nevertheless, we
continue to strive to even further optimize our RNAi therapeutics
platform to achieve improved target specificity and an even greater
therapeutic index. Accordingly, we were pleased to share these new
pre-clinical results at this year's OTS meeting,
highlighting our ESC+ GalNAc conjugate platform,” said Kevin
Fitzgerald, Ph.D., Senior Vice President, Research at Alnylam. “Our
goal is to employ the ESC+ chemistry in all future development
candidates, beginning with ALN-AAT02, which we plan to advance into
clinical development in 2018. We believe that by implementing
platform improvements that preemptively address potential
off-target effects we can further enhance the therapeutic index of
our investigational RNAi therapeutics for all future programs in
our pipeline.”
In addition to new data on the Company’s ESC+ platform, Alnylam
scientists and collaborators presented additional pre-clinical
findings showing continued leadership in RNAi technologies and
delivery. First, Alnylam scientists presented further advances
toward optimizing the Company’s GalNAc-siRNA conjugate platform.
These included studies to further improve the mechanistic
understanding of conjugate duration of activity as well as the
development of advanced ESC designs with significantly improved
metabolic stability and in vivo efficacy. Further, new data on
Alnylam’s Reversir™ platform were presented. Specifically,
optimizations were implemented that enable rapid reversal of
siRNA-mediated mRNA silencing, providing the means to fine-tune the
pharmacology of GalNAc-siRNA conjugates. Finally, pre-clinical data
demonstrating extra-hepatic siRNA delivery, involving Centyrins, a
novel class of highly stable FN3 domain proteins, were also
presented as part of a research collaboration with Janssen Research
& Development, LLC. Centyrin-siRNA conjugates showed excellent
cross-tumor penetration and mediated robust target knockdown in a
mouse xenograft tumor model. Also, the generalizability of this
approach was demonstrated in vitro using Centyrins for a number of
different receptors and gene targets.
These results can be viewed on the Capella section of the
Alnylam website.
About RNAi
RNAi (RNA interference) is a revolution in biology, representing
a breakthrough in understanding protein synthesis 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, with the goal of preventing
disease-causing proteins from being made.
About Reversir™
Alnylam's Reversir platform utilizes GalNAc-conjugated
single-stranded high affinity oligonucleotides complementary to the
guide strand of the siRNA to rapidly reverse RNAi-mediated
silencing of target transcripts. Reversir provides the means to
fine-tune the pharmacology of GalNAc-siRNA conjugates by enabling
control of duration of silencing.
About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is leading the translation of RNA
interference (RNAi) into a whole new class of innovative medicines
with the potential to transform the lives of patients who have
limited or inadequate treatment options. Based on Nobel
Prize-winning science, RNAi therapeutics represent a powerful,
clinically validated approach for the treatment of a wide range of
debilitating diseases. Founded in 2002, Alnylam is delivering on a
bold vision to turn scientific possibility into reality, with a
robust discovery platform and deep pipeline of investigational
medicines, including four product candidates that are in late-stage
development. Looking forward, Alnylam will continue to execute on
its "Alnylam 2020" strategy of building a multi-product,
commercial-stage biopharmaceutical company with a sustainable
pipeline of RNAi-based medicines. For more information about our
people, science and pipeline, please
visit www.alnylam.com and engage with us on Twitter at
@Alnylam or on LinkedIn.
Alnylam Forward Looking Statements
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 its ESC+
GalNAc-siRNA-conjugate platform to address potential off-target
effects and enhance the specificity of its investigational
therapeutics, its plans to employ its ESC+ siRNA-conjugate platform
in all future development programs, expectations regarding the
timing for initiation of a clinical study for ALN-AAT02, and
expectations regarding its "Alnylam 2020" guidance for the
advancement and commercialization of RNAi therapeutics, constitute
forward-looking statements for the purposes of the safe harbor
provisions under The Private Securities Litigation Reform Act of
1995. Actual results and future plans may differ materially from
those indicated by these forward-looking statements as a result of
various important risks, uncertainties and other 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 product candidates, the
pre-clinical and clinical results for its product candidates, which
may not be replicated or continue to occur in other subjects or in
additional studies or otherwise support further development of
product candidates for a specified indication or at all, actions or
advice of regulatory agencies, which may affect the design,
initiation, timing, continuation and/or progress of clinical trials
or result in the need for additional pre-clinical and/or clinical
testing, delays, interruptions or failures in the manufacture and
supply of its product candidates, obtaining, maintaining and
protecting intellectual property, Alnylam's ability to enforce its
intellectual property rights against third parties and defend its
patent portfolio against challenges from third parties, obtaining
and maintaining regulatory approval, pricing and reimbursement for
products, progress in establishing a commercial and ex-United
States infrastructure, competition from others using technology
similar to Alnylam's and others developing products for similar
uses, Alnylam's ability to manage its growth and operating
expenses, 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 and distribution of products, the
outcome of litigation, the risk of government investigations, and
unexpected expenditures, as well as those risks more fully
discussed in the "Risk Factors" filed with Alnylam's most recent
Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) 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, except to the extent required
by law, to update any forward-looking statements.
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Alnylam Pharmaceuticals, Inc.Investors and
Media:Christine Regan Lindenboom, 617-682-4340orInvestors:Josh
Brodsky, 617-551-8276
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