Alnylam Advances New Innovations in RNAi Therapeutics

- Bis-RNAiTM Platform Enables Potent and Durable Knockdown of Two Distinct Disease Genes with Single, Subcutaneously Administered Molecular Entity -

- ReversirTM Platform Enables Rapid Reversal of Target Gene Silencing for Tailored Control of RNAi Pharmacology -

- Both Innovations have Broad Applicability across Alnylam Pipeline and Expand Universe of Opportunities for RNAi Therapeutics -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today advancement of innovations in RNAi therapeutics with presentation of scientific data on two new platform technologies. The research was presented at the 11th Annual Meeting of theOligonucleotide Therapeutics Society (OTS), held October 11 - 14, 2015, in Leiden, Netherlands. First, the company presented data on its Bis-RNAiTM platform that enables simultaneous knockdown of two distinct disease genes with a single, subcutaneously administered molecular entity. Further, the company presented data on its ReversirTM platform. Reversir molecules enable tailored control of RNAi pharmacology with rapid reversal of target gene silencing effects. The company believes that these new platform technologies greatly expand the universe of opportunities for RNAi therapeutics.

"At Alnylam we strive to pioneer new breakthroughs in RNAi. Today, we're announcing development of two new platform technologies that we believe broaden the opportunities for RNAi therapeutics as a whole new class of medicines. With Bis-RNAi, we've developed an approach for the simultaneous knockdown of two distinct target genes with a single, subcutaneously administered molecular entity. We can imagine meaningful applications of Bis-RNAi in many clinical indications, including those in our Cardio-Metabolic and Hepatic Infectious Disease Strategic Therapeutic Areas," said Rachel Meyers, Senior Vice President of Research at Alnylam. "With our Reversir platform, we now have a tool for control of RNAi pharmacology that enables rapid reversal of target gene silencing. We believe that tailored pharmacology is a highly desired attribute for precision medicines. We look forward to the advancement of new pipeline programs based on these platforms as early as next year."

In a poster presentation entitled "Bis-RNAiTM Conjugates for Simultaneous Silencing of Two Transcripts," Alnylam scientists described a novel approach whereby a single molecular entity consisting of two linked siRNAs conjugated to a GalNAc moiety can simultaneously achieve robust silencing of two different mRNA transcripts. Multiple Bis-RNAi designs were evaluated to determine the effects of linker structure and GalNAc ligand placement on in vivo activity. In rodent and non-human primate studies, a Bis-RNAi tool compound targeting transthyretin (TTR) and Factor VII (FVII) achieved similar levels of target gene knockdown as that observed with a "parent" mixture consisting of the individual siRNAs at a 1:1 ratio. In addition, the duration of silencing effects for the Bis-RNAi compound was found to be similar to that of the individual siRNAs in the parent mixture. Furthermore, the Bis-RNAi constructs were found to lack immune activity as measured in both an in vitro human whole blood assay and in an in vivo mouse model, with cytokine profiles comparable to the parent mixture and untreated controls. Alnylam believes that there are many potential clinical applications for the Bis-RNAi platform, including in the company's Cardio-Metabolic and Hepatic Infectious Disease STArs, and expects to advance its first Development Candidate from this platform in 2016.

In a second presentation entitled "Reversirs for Rapid and Potent Reversal of siRNA Silencing Activity," the company shared key scientific data characterizing the development of its Reversir platform. Reversir molecules are GalNAc-conjugated, single-stranded oligonucleotide constructs that are designed to recognize and bind to the complimentary RISC-bound antisense strand of an siRNA, leading to rapid and complete reversal of RNAi-mediated target gene silencing activity in vivo. Studies were performed in mice using a GalNAc-siRNA targeting Factor IX (FIX) and Reversir constructs designed to specifically reverse the FIX siRNA silencing activity. Specifically, a single subcutaneous dose of the FIX siRNA led to robust FIX knockdown of approximately 80% that was sustained for over 4 weeks. When a single subcutaneous dose of the Reversir molecule was administered on day 8, FIX knockdown was rapidly reversed, with levels returning to baseline within one week. A preliminary rat toxicology study showed that Reversir constructs are generally well tolerated with no significant findings to date, including lack of changes in body weight gain or serum chemistry. Alnylam believes that its Reversir platform can be deployed across existing and future pipeline programs to enable tailored control of RNAi pharmacology for precision medicines, and expects to advance initial Development Candidates from this platform in 2016.

About 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 RNA (siRNA), 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. Alnylam's pipeline of investigational RNAi therapeutics is focused in 3 Strategic Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline of RNAi therapeutics for the treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics toward genetically validated, liver-expressed disease targets for unmet needs in cardiovascular and metabolic diseases; and Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that address the major global health challenges of hepatic infectious diseases. In early 2015, Alnylam launched its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics as a whole new class of innovative medicines. Specifically, by the end of 2020, Alnylam expects to achieve a company profile with 3 marketed products, 10 RNAi therapeutic clinical programs - including 4 in late stages of development - across its 3 STArs. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, Cell, New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information about Alnylam's pipeline of investigational RNAi therapeutics, please visit

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 RNAi therapeutics, including the Bis-RNAiTM and ReversirTM platforms, its expectations regarding development timelines for products based on these platforms, its expectations regarding its STAr pipeline growth strategy, and its plans regarding 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 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 drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its drug 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, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage operating expenses, Alnylam's ability to 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, marketing, sales and distribution of products, the outcome of litigation, 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 to update any forward-looking statements.

Alnylam Pharmaceuticals, Inc.
Michael Mason, 617-551-8327
Vice President, Finance and Treasurer


Liz Bryan (Media), 202-955-6222 x2526


Source: Alnylam Pharmaceuticals, Inc.

News Provided by Acquire Media