CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented multiple posters and presentations at the 53rd American Society of Hematology (ASH) Annual Meeting and Exposition held in San Diego, CA between December 10 – 13, 2011. At the meeting, research was presented from programs in the company’s “Alnylam 5x15” product pipeline, including pre-clinical data from ALN-APC, an RNAi therapeutic targeting protein C for the treatment of hemophilia, and ALN-HPN, an RNAi therapeutic targeting the hepcidin pathway for the treatment of refractory anemia. In addition, pre-clinical research was also presented from candidate programs in beta-thalassemia and erythropoiesis.
“The research we presented at this meeting highlights the significant progress we are making in translating RNAi therapeutics toward an innovative class of medicines for a broad range of human disease,” said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Alnylam. “Specifically, we were pleased to present additional updates from some of our ‘Alnylam 5x15’ programs, including ALN-APC for the treatment of hemophilia and ALN-HPN for the treatment of refractory anemia in addition to candidate programs in beta-thalassemia and erythropoiesis. Importantly, all four programs are focused on genetically defined targets expressed in the liver, where we have recently proven safe and effective delivery in man, with target and/or disease biomarkers measureable in early clinical studies. We remain on track to nominate our fifth ‘Alnylam 5x15’ program at or around year’s end from these and other candidate programs.”
Presentations and posters from Alnylam scientists at the ASH Meeting included a poster titled “RNAi-Mediated Inhibition of Activated Protein C. A New Approach for Hemophilia Treatment,” where Alnylam scientists presented pre-clinical data from its ALN-APC program. These data demonstrate dose-dependent silencing of protein C mRNA with silencing of greater than 90% and an ED50 of approximately 0.02 mg/kg. When administered as a single dose of 0.3 mg/kg, the lipid nanoparticle (LNP)-formulated siRNA achieved greater than 75% silencing of protein C mRNA with effects lasting for over two weeks. Based on Western blot analysis, the reduction of protein C mRNA led to virtually undetectable levels of circulating protein C protein levels in plasma. By reducing levels of protein C, ALN-APC is expected to increase thrombin generation in hemophilia.
A presentation titled “Targeting the Hepcidin Pathway with RNAi Therapeutics for the Treatment of Anemia,” showed new pre-clinical data from the company’s ALN-HPN program for the treatment of refractory anemia. New data was shown highlighting the ability of an RNAi therapeutic to silence the hepcidin pathway in pre-clinical models, resulting in associated dose-dependent increases in serum iron and transferrin saturation, a measure of effective iron mobilization in vivo. New data also revealed transferrin receptor type 2 (TFR2) as the optimal target in the hepcidin pathway, as TFR2 silencing was associated with marked decreases in hepcidin expression and greater levels of transferrin saturation as compared with direct targeting of the hepcidin mRNA itself. TFR2 silencing was also found to be more effective than direct silencing of hepcidin in animal models, including correction of hemoglobin levels in a model of inflammatory anemia. TFR2 is a genetically validated target as loss of function human mutations are associated with a hereditary form of hemochromatosis. Further efforts on ALN-HPN will focus on TFR2 as the molecular target.
In a poster titled “RNAi-Mediated Inhibition of Tmprss6 Elevates Hamp1 [Hepcidin] Expression and Reduces Serum Iron Levels in Mice,” Alnylam scientists and collaborators from Children’s Hospital Boston showed that the systemic administration of an LNP-formulated siRNA targeting Transmembrane protease, serine 6 (Tmprss6) represents a potential novel approach to treat congenital iron overload disorders. In a pre-clinical model of iron overload in beta-thalassemia, potent and dose dependent silencing of Tmprss6 was achieved, resulting in a concomitant induction of hepcidin mRNA. As a result of increased hepcidin levels, treatment with the Tmprss6 siRNA resulted in significant decreases in serum iron concentration and transferrin saturation. Moreover, Tmprss6 silencing with a single dose of the RNAi therapeutic was associated with a dramatic normalization of multiple hematological parameters including hemoglobin, normalization of splenic iron levels and tissue histology, and reductions in splenomegaly. These findings suggest that iron restriction via Tmprss6 silencing can correct the disease phenotype of beta-thalassemia intermedia in a pre-clinical model.
Lastly, in a poster titled “Liver Specific Delivery of siRNA Targeting EGLN Prolyl Hydroxylases Activates Hepatic Erythropoietin Production and Stimulates Erythropoiesis,” Alnylam scientists and collaborators at the Dana-Farber Cancer Institute and the Massachusetts Institute of Technology (MIT) highlighted the potential of RNAi therapeutics targeting liver-expressed egl nine homolog (EGLN) prolyl hydroxlase genes to promote effective and durable erythropoiesis. Pre-clinical data demonstrated that LNP-formulated EGLN siRNA induced hepatic erythropoietin (EPO) mRNA activation leading to increased serum EPO levels and stimulation of erythropoiesis. Following a single dose, increases in serum EPO and hematocrit were durable for approximately two weeks and one month, respectively. Treatment with EGLN siRNAs corrected anemia in both renal failure and inflammatory anemia pre-clinical disease models.
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’s VaxiRNA™ platform applies RNAi technology to improve the manufacturing processes for vaccines; GlaxoSmithKline is a collaborator in this effort. 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 the potential for RNAi therapeutics, including ALN-APC and ALN-HPN, its expectations regarding the potential of identifying RNAi therapeutics for beta-thalassemia and erythropoiesis, its expectations with respect to the timing and success of its pre-clinical studies, the expected timing for nominating the fifth ‘Alnylam 5x15’ program, 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 drug candidates, successfully demonstrate the efficacy and safety of its drug candidates, including ALN-APC, ALN-HPN, and potential candidates for beta-thalassemia and erythropoiesis , the pre-clinical and clinical results for its product candidates, which may not 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, obtaining regulatory approval for products, competition from others using technology similar to Alnylam’s and others developing products for similar uses, and Alnylam’s ability to 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 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.