Alnylam Pharmaceuticals Inc (ALNY)

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Alnylam Scientists & Collaborators Report Significant New Advances in Delivery of RNAi Therapeutics at 2011 Oligonucleotides ...

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Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented multiple posters and presentations at the 7th Annual Meeting of Oligonucleotide Therapeutics Society (OTS) held in Copenhagen, Denmark between September 8-10, 2011. Newly presented data include significant advances in the company’s efforts in systemic delivery of RNAi therapeutics.

“We and our collaborators continue to achieve major breakthroughs in systemic delivery of RNAi therapeutics. Some key highlights from the OTS meeting include the discovery of a novel class of third generation LNPs, so-called ‘reLNPs,’ that show dramatic improvements in therapeutic index based on our current analysis. Further, we are excited about the MD1 lipid discovered in our MIT collaboration resulting in LNPs with gene silencing potency of approximately 0.002 mg/kg, approaching picogram/kilogram levels and setting a new benchmark,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “Moreover, we have now achieved a robust performance level for our conjugate platform that enables clear translation into the clinic. Specifically, our GalNAc-siRNA conjugates demonstrate potent, dose-dependent, and durable target gene silencing with subcutaneous administration at single digit milligram/kilogram dose levels. We now fully expect this platform to deliver clinical candidates for the future.”

In a poster titled “Mechanistic Insights Into Lipid Nanoparticle (LNP)-Mediated Delivery of siRNA,” Alnylam scientists and collaborators at AlCana Technologies, Inc., The University of British Columbia, the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), and The Massachusetts Institute of Technology (MIT) described recent progress with lipid nanoparticle (LNP)-based delivery of RNAi therapeutics, including further delineation of in vivo cellular and physiologic mechanisms and also the discovery of novel lipids which drive the development of yet a new generation of LNPs. Specifically, a novel class of third generation LNPs, designated “reLNPs,” was described that demonstrate promising improvement in therapeutic index. reLNPs demonstrate potent target gene silencing in vivo, with an ED50 (the dose that provides a 50% silencing effect) at doses of less than 0.05 mg/kg while demonstrating tolerability (defined as no adverse effect level, or “NOAEL”) at doses exceeding 10 mg/kg. Based on an ongoing assessment, the performance of reLNPs appears to represent an approximately 10-fold improvement compared with Alnylam second generation “MC3” LNP technology and an approximately 100-fold improvement as compared with first generation LNPs. Further, in collaboration with Professor Daniel Anderson’s laboratory at MIT, continued progress has been made in the discovery of novel “lipidoid” formulations based on a combinatorial synthesis approach. In particular, in vivo data demonstrated improved efficacy for the novel “MD1” lipidoid formulation with an ED50 of approximately 0.002 mg/kg following a single intravenous injection, setting a new potency benchmark for systemically administered RNAi therapeutics.

In addition, Alnylam scientists also presented new data in a poster titled “Hepatocyte-Specific Targeting and Delivery of siRNA-Carbohydrate Conjugates” demonstrating significant advances related to the stability, potency, and efficacy of novel GalNAc-conjugated siRNAs for systemic delivery of RNAi therapeutics. The new research findings showed that improvements in chemistry lead to markedly increased potency for in vivo target gene silencing with GalNAc-conjugated siRNAs administered by subcutaneous injection at low, clinically relevant doses. Administration of novel GalNAc-conjugated siRNAs targeting transthyretin (GalNAc-TTR) resulted in robust gene silencing in vivo with an ED50 of approximately 5 mg/kg after a single subcutaneous injection in multiple pre-clinical models. Moreover, dose regimen optimization enabled yet further improvements in TTR target gene silencing with subcutaneous doses of 1 mg/kg. The achievement of robust target gene silencing with siRNA-conjugates delivered by subcutaneous dosing broadens the range of clinical opportunities for RNAi therapeutics. Alnylam believes that its’ advancements in this effort now warrant translation into development efforts for future pipeline programs.

About ‘Alnylam 5x15’

The “Alnylam 5x15” strategy, launched in January 2011, establishes a path for development and commercialization of novel RNAi therapeutics to address genetically defined diseases with high unmet medical need. Products arising from this initiative share several key characteristics including: a genetically defined target and disease; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam RNAi delivery platform; the opportunity to monitor an early biomarker in Phase I clinical trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. This strategy leverages Alnylam’s clinical progress on siRNA delivery, including definitive human proof-of-concept data for systemic delivery. By the end of 2015, the company expects to have five such RNAi therapeutic programs in advanced clinical development. These include ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, ALN-APC for the treatment of hemophilia, and one additional program from the company’s ongoing discovery efforts that will be designated and advanced into development later in 2011. Alnylam intends to commercialize the products arising under the “Alnylam 5x15” strategy itself in the United States and potentially certain other countries; the company will seek development and commercial partners in other global territories.

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 leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and ALN-APC for the treatment of hemophilia. As part of its “Alnylam 5x15TM” strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in advanced stages of clinical development by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT for the treatment of Huntington’s disease. The company’s leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has formed partnerships with GlaxoSmithKline and Sanofi. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world’s top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including without limitation, statements regarding Alnylam’s views with respect to its advances in certain systemic delivery approaches, including a novel class of third generation LNPs, designated “reLNPs,” the novel “MD1” lipidoid formulation, and novel GalNAc-conjugated siRNAs, the potential of such novel approaches for RNAi therapeutic development, and Alnylam’s expectations regarding its “Alnylam 5x15” product strategy, 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, without limitation, Alnylam’s ability to discover and develop novel delivery approaches, such as reLNPs, the MD1 lipidoid and GalNAc-conjugated siRNAs, and novel drug candidates, successfully demonstrate the efficacy and safety of its delivery approaches, such as reLNPs, the MD1 lipidoid and GalNAc-conjugated siRNAs, and its drug candidates in pre-clinical and human clinical trials, and establish and maintain strategic business alliances and new business initiatives, as well as those risks more fully discussed in the “Risk Factors” section of its most recent annual 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.