Pre-Clinical Data on ALN-AAT for the Treatment of Alpha-1 Antitrypsin (AAT) Deficiency-Associated Liver Disease

Pre-Clinical Data on ALN-AAT for the Treatment of Alpha-1 Antitrypsin (AAT) Deficiency-Associated Liver Disease

We presented new pre-clinical data supporting the advancement of a Development Candidate (DC) for ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease. Data were presented in a Late-Breaking Abstract Session at Digestive Disease Week (DDW), held May 3 – 6, 2014 in Chicago. As previously presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD, “The Liver Meeting”) in November 2013 and as updated at DDW, studies were performed in transgenic mice overexpressing the human Z-AAT protein. Subcutaneous administration of a GalNAc-siRNA targeting AAT led to rapid, potent, dose-dependent, and durable knockdown of AAT of greater than 95%, as well as a significant reduction in fibrosis and the incidence of liver tumors.



The ALN-AAT DC employs Alnylam’s Enhanced Stabilization Chemistry (ESC) GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency, durability, and a wide therapeutic index. New data presented at DDW showed that in rodents and non-human primates, subcutaneous administration of ALN-AAT led to potent and dose-dependent knockdown of serum AAT, a surrogate for AAT knockdown in the liver. We believe ALN-AAT holds considerable promise as a novel therapeutic approach for the treatment of liver disease associated with AAT deficiency, an increasingly recognized problem where there is significant unmet need.

 



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