17 May, 2015 Pre-Clinical Data on ALN-AAT at Digestive Disease Week
We presented pre-clinical data on ALN-AAT, an investigational RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease. New data, presented at the Digestive Disease Week (DDW) meeting, held May 16 – 19, 2015, showed a robust knockdown of serum AAT of up to 93% in non-human primates (NHPs) with monthly subcutaneous dosing. This level of knockdown was highly durable, lasting for greater than 30 days following the final dose. Further, ALN-AAT was found to have a wide therapeutic index based on results from GLP toxicology studies. In addition, study results were reported from a transgenic mouse model of alpha-1 liver disease, where mice overexpress the human Z-AAT protein.
In addition, as previously presented, sustained reduction of Z-AAT in aged transgenic mice with established liver disease led to improvement in tissue pathology, decrease in fibrosis, decrease in number of proliferating hepatocytes, and reduction in tumor burden as measured by both number and size of tumors.
If these results extend in clinical studies, we believe that this investigational RNAi therapeutic has the potential to become an important treatment option for the management of alpha-1 liver disease, an increasingly recognized clinical manifestation of alpha-1 antitrypsin deficiency where there is a significant unmet need and where liver transplantation is the only available treatment option.