Alnylam Continues Leadership in RNAi Technologies and Delivery with New Pre-Clinical Data Presented on "Enhanced Stabilization Chemistry Plus" (ESC+) GalNAc-siRNA Conjugate Platform at 13th Annual Meeting of the Oligonucleotide Therapeutics Society
– 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 –
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
“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,”
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
These results can be viewed on the Capella section of the Alnylam website.
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.
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.
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
Alnylam Pharmaceuticals, Inc.
Investors and Media:
Christine Regan Lindenboom, 617-682-4340
Josh Brodsky, 617-551-8276