Pre-Clinical Results with ALN-AT3 Published in “Nature Medicine”

We have published pre-clinical results with ALN-AT3, an investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia, in Nature Medicine. The paper documents a broad set of pre-clinical data supporting the clinical advancement of ALN-AT3. Among the many findings reported, subcutaneous administration of ALN-AT3 led to potent, dose-dependent, and durable knockdown of AT in wild-type mice, hemophilia A mice, and non-human primates (NHPs). In addition, ALN-AT3 treatment improved hemostasis in hemophilia mice and normalized thrombin generation in a non-human primate “inhibitor” model of hemophilia A (HA). Furthermore, long-term ALN-AT3 administration – even at highly exaggerated doses – was shown to be well tolerated in hemophilia mice, supporting a wide therapeutic index in the disease setting.


ALN-AT3 is a key investigational program in our RNAi therapeutics pipeline, and is aimed at re-balancing the coagulation cascade as a potential disease modifying therapy for people with hemophilia and rare bleeding disorders. New therapeutic options are needed to manage bleeding in these patients, particularly those who experience multiple annual bleeds when receiving replacement factor ‘on demand’ and patients who have developed inhibitory antibodies. We believe that once-monthly subcutaneous administration of ALN-AT3 could provide a functional correction of the bleeding phenotype in hemophilia, which could represent a significant advance in the field. The availability of a safe and effective, subcutaneously administered therapeutic with a long duration of action has the potential to provide significant benefits over currently available approaches for prophylaxis. We look forward to the continued advancement of ALN-AT3, including in the ongoing Phase 1 clinical trial in subjects with hemophilia.