– New Research Presented at 6th International Conference on Complement Therapeutics Demonstrates Potent, Dose-Dependent, and Durable Silencing of Serum C5 and Inhibition of Complement Hemolytic Activity by Approximately 90% –
– ALN-CC5 Advanced as New “Alnylam 5×15” Program Using Company’s GalNAc-Conjugate Delivery Technology Enabling Subcutaneous Dose Administration –
– Company Expands Pipeline Guidance and Expects to Nominate Development Candidate by Late 2013 –
CAMBRIDGE, MA, USA I June 20, 2013 I Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today that it has presented new pre-clinical data with ALN-CC5, an RNAi therapeutic targeting complement component C5. These data were presented at the 6th International Conference on Complement Therapeutics being held June 18 – 23, 2013 in Kos, Greece. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in serious, life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, amongst others. C5 is a genetically and clinically validated target; loss of function human mutations are associated with an attenuated immune defense against certain infections and intravenously administered anti-C5 monoclonal antibody therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. In a presentation titled “Development of an RNAi Therapeutic Silencing the C5 Component of Complement,” Alnylam scientists presented pre-clinical results showing potent, dose-dependent, and durable RNAi-mediated knockdown of serum C5 and inhibition of complement-mediated hemolytic activity of approximately 90% with a subcutaneously administered RNAi therapeutic. Alnylam believes that ALN-CC5 – part of the company’s “Alnylam 5×15” product strategy – represents a novel approach for the treatment of complement-mediated diseases; the company expects to nominate a development candidate for clinical advancement in late 2013.
“C5 is a genetically and clinically validated target that exemplifies the potential of Alnylam’s ‘5×15’ product strategy for innovative new medicines. First, C5 is predominantly expressed in liver, where we have established clinical activity and tolerability for RNAi therapeutics. In addition, our clinical development plan for an RNAi therapeutic targeting C5 will be facilitated by serum biomarkers in Phase I trials and a relatively streamlined and focused path for advanced development,” said Rachel Meyers, Ph.D., Vice President, Research and RNAi Lead Development at Alnylam. “Indeed, we believe that a subcutaneously administered RNAi therapeutic targeting C5 could represent an important advance for the treatment of a broad range of complement-mediated diseases.”
New data presented at the scientific meeting showed that a GalNAc-siRNA conjugate targeting the C5 mRNA resulted in potent, dose-dependent, and durable silencing of C5 liver mRNA, knockdown of C5 serum protein levels, and inhibition of complement-mediated hemolysis activity. Specifically, a prototype GalNAc-siRNA conjugate targeting C5 showed a single dose ED50 for C5 knockdown of approximately 0.6 mg/kg in rodent models. In multi-dose experiments, subcutaneous administration of the GalNAc-siRNA conjugate resulted in approximately 90% knockdown of serum C5 levels at doses of ≥1.25 mg/kg. Additional multi-dose experiments showed that the current lead candidate siRNA could achieve an approximately 90% inhibition of complement-mediated hemolytic activity in the rat at subcutaneous doses of 5 mg/kg; these effects were rapid, dose-dependent, and durable for weeks after cessation of treatment. The company is performing additional optimization of the GalNAc-siRNA conjugate lead molecule and expects to nominate its ALN-CC5 development candidate in late 2013.
“The complement system plays a central role in immunity as part of host defense. However, dysregulation of this pathway can lead to life-threatening complications in a wide range of human diseases including PNH, aHUS, myasthenia gravis, neuromyelitis optica, amongst others,” said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Alnylam. “We are excited about these pre-clinical data showing potent, dose-dependent, and durable knockdown of serum C5 with about 90% inhibition of hemolysis activity using a subcutaneously administered RNAi therapeutic. We believe that if these results can extend in the clinical setting, they could represent a very promising therapeutic strategy and new treatment option for patients with complement-mediated diseases.”
About ALN-CC5
ALN-CC5 is an RNAi therapeutic targeting the C5 component of the complement pathway for the treatment of complement-mediated diseases. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, amongst others. Complement component C5, which is predominantly expressed in liver cells, is a genetically and clinically validated target; loss of function human mutations are associated with an attenuated immune response against certain infections and intravenous anti-C5 monoclonal antibody therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. A subcutaneously administered RNAi therapeutic that silences C5 represents a novel approach to the treatment of complement-mediated diseases. ALN-CC5 utilizes Alnylam’s proprietary GalNAc conjugate delivery platform enabling subcutaneous dose administration.
About GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Research findings demonstrate potent and durable target gene silencing, as well as a wide therapeutic index, with subcutaneously administered GalNAc-siRNAs from multiple “Alnylam 5×15” programs.
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 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 with a core focus on RNAi therapeutics toward genetically defined targets for the treatment of serious, life-threatening diseases with limited treatment options for patients and their caregivers. These include: ALN-TTR02, an intravenously delivered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR for the treatment of ATTR in patients with familial amyloidotic cardiomyopathy (FAC); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-AS1, an RNAi therapeutic targeting aminolevulinate synthase-1 (ALAS-1) for the treatment of acute intermittent porphyria (AIP); ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of beta-thalassemia and iron-overload disorders; ALN-AAT, an RNAi therapeutic targeting alpha-1-antitrypsin (AAT) for the treatment of AAT deficiency liver disease; and ALN-CC5, an RNAi therapeutic targeting the C5 component of the complement pathway for the treatment of complement-mediated diseases, amongst other programs. As part of its “Alnylam 5×15TM” strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in clinical development, including programs in advanced stages, on its own or with a partner by the end of 2015. Alnylam has additional partnered programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection and ALN-VSP for the treatment of liver cancers. 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, Cubist, Ascletis, Monsanto, Genzyme, and The Medicines Company. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for applications 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.
SOURCE: Alnylam Pharmaceuticals
Post Views: 152
– New Research Presented at 6th International Conference on Complement Therapeutics Demonstrates Potent, Dose-Dependent, and Durable Silencing of Serum C5 and Inhibition of Complement Hemolytic Activity by Approximately 90% –
– ALN-CC5 Advanced as New “Alnylam 5×15” Program Using Company’s GalNAc-Conjugate Delivery Technology Enabling Subcutaneous Dose Administration –
– Company Expands Pipeline Guidance and Expects to Nominate Development Candidate by Late 2013 –
CAMBRIDGE, MA, USA I June 20, 2013 I Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today that it has presented new pre-clinical data with ALN-CC5, an RNAi therapeutic targeting complement component C5. These data were presented at the 6th International Conference on Complement Therapeutics being held June 18 – 23, 2013 in Kos, Greece. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in serious, life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, amongst others. C5 is a genetically and clinically validated target; loss of function human mutations are associated with an attenuated immune defense against certain infections and intravenously administered anti-C5 monoclonal antibody therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. In a presentation titled “Development of an RNAi Therapeutic Silencing the C5 Component of Complement,” Alnylam scientists presented pre-clinical results showing potent, dose-dependent, and durable RNAi-mediated knockdown of serum C5 and inhibition of complement-mediated hemolytic activity of approximately 90% with a subcutaneously administered RNAi therapeutic. Alnylam believes that ALN-CC5 – part of the company’s “Alnylam 5×15” product strategy – represents a novel approach for the treatment of complement-mediated diseases; the company expects to nominate a development candidate for clinical advancement in late 2013.
“C5 is a genetically and clinically validated target that exemplifies the potential of Alnylam’s ‘5×15’ product strategy for innovative new medicines. First, C5 is predominantly expressed in liver, where we have established clinical activity and tolerability for RNAi therapeutics. In addition, our clinical development plan for an RNAi therapeutic targeting C5 will be facilitated by serum biomarkers in Phase I trials and a relatively streamlined and focused path for advanced development,” said Rachel Meyers, Ph.D., Vice President, Research and RNAi Lead Development at Alnylam. “Indeed, we believe that a subcutaneously administered RNAi therapeutic targeting C5 could represent an important advance for the treatment of a broad range of complement-mediated diseases.”
New data presented at the scientific meeting showed that a GalNAc-siRNA conjugate targeting the C5 mRNA resulted in potent, dose-dependent, and durable silencing of C5 liver mRNA, knockdown of C5 serum protein levels, and inhibition of complement-mediated hemolysis activity. Specifically, a prototype GalNAc-siRNA conjugate targeting C5 showed a single dose ED50 for C5 knockdown of approximately 0.6 mg/kg in rodent models. In multi-dose experiments, subcutaneous administration of the GalNAc-siRNA conjugate resulted in approximately 90% knockdown of serum C5 levels at doses of ≥1.25 mg/kg. Additional multi-dose experiments showed that the current lead candidate siRNA could achieve an approximately 90% inhibition of complement-mediated hemolytic activity in the rat at subcutaneous doses of 5 mg/kg; these effects were rapid, dose-dependent, and durable for weeks after cessation of treatment. The company is performing additional optimization of the GalNAc-siRNA conjugate lead molecule and expects to nominate its ALN-CC5 development candidate in late 2013.
“The complement system plays a central role in immunity as part of host defense. However, dysregulation of this pathway can lead to life-threatening complications in a wide range of human diseases including PNH, aHUS, myasthenia gravis, neuromyelitis optica, amongst others,” said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Alnylam. “We are excited about these pre-clinical data showing potent, dose-dependent, and durable knockdown of serum C5 with about 90% inhibition of hemolysis activity using a subcutaneously administered RNAi therapeutic. We believe that if these results can extend in the clinical setting, they could represent a very promising therapeutic strategy and new treatment option for patients with complement-mediated diseases.”
About ALN-CC5
ALN-CC5 is an RNAi therapeutic targeting the C5 component of the complement pathway for the treatment of complement-mediated diseases. The complement system plays a central role in immunity as a protective mechanism for host defense, but its dysregulation results in life-threatening complications in a broad range of human diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic-uremic syndrome (aHUS), myasthenia gravis, neuromyelitis optica, amongst others. Complement component C5, which is predominantly expressed in liver cells, is a genetically and clinically validated target; loss of function human mutations are associated with an attenuated immune response against certain infections and intravenous anti-C5 monoclonal antibody therapy has demonstrated clinical activity and tolerability in a number of complement-mediated diseases. A subcutaneously administered RNAi therapeutic that silences C5 represents a novel approach to the treatment of complement-mediated diseases. ALN-CC5 utilizes Alnylam’s proprietary GalNAc conjugate delivery platform enabling subcutaneous dose administration.
About GalNAc Conjugates
GalNAc-siRNA conjugates are a proprietary Alnylam delivery platform and are designed to achieve targeted delivery of RNAi therapeutics to hepatocytes through uptake by the asialoglycoprotein receptor. Research findings demonstrate potent and durable target gene silencing, as well as a wide therapeutic index, with subcutaneously administered GalNAc-siRNAs from multiple “Alnylam 5×15” programs.
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 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 with a core focus on RNAi therapeutics toward genetically defined targets for the treatment of serious, life-threatening diseases with limited treatment options for patients and their caregivers. These include: ALN-TTR02, an intravenously delivered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR for the treatment of ATTR in patients with familial amyloidotic cardiomyopathy (FAC); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-AS1, an RNAi therapeutic targeting aminolevulinate synthase-1 (ALAS-1) for the treatment of acute intermittent porphyria (AIP); ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of beta-thalassemia and iron-overload disorders; ALN-AAT, an RNAi therapeutic targeting alpha-1-antitrypsin (AAT) for the treatment of AAT deficiency liver disease; and ALN-CC5, an RNAi therapeutic targeting the C5 component of the complement pathway for the treatment of complement-mediated diseases, amongst other programs. As part of its “Alnylam 5×15TM” strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in clinical development, including programs in advanced stages, on its own or with a partner by the end of 2015. Alnylam has additional partnered programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection and ALN-VSP for the treatment of liver cancers. 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, Cubist, Ascletis, Monsanto, Genzyme, and The Medicines Company. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for applications 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.
SOURCE: Alnylam Pharmaceuticals
Post Views: 152
