March 7, 2016
We’re announcing the addition of a new program to our genetic medicines pipeline, ALN-F12, an investigational RNAi therapeutic targeting F12 for the treatment of Hereditary Angioedema (HAE). Pre-clinical data for ALN-F12 were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual meeting, held March 4-7, 2016.
HAE is a genetic disorder characterized by episodes of severe swelling in various parts of the body, including the face, hands, feet, gastrointestinal tract, and airways. It is caused by a defect in the C1-inhibitor gene that results in poor control of contact pathway activation and excessive bradykinin generation. Elevated levels of bradykinin increase vascular permeability, ultimately causing the episodic swelling attacks that are characteristic of HAE. The F12 gene encodes Factor XII (FXII), which is at the top of the contact pathway cascade. Pre-clinical data showed that administration of ALN-F12 resulted in dose-dependent reduction of vascular permeability in two different mouse models of bradykinin-driven vascular leakage, demonstrating that suppression of F12 mRNA has the potential to mitigate excess bradykinin stimulation. Further, in non-human primates, a single subcutaneous dose of ALN-F12 at 3 mg/kg resulted in potent and durable knockdown of serum FXII of greater than 85 percent, with knockdown of over 50 percent sustained out to three months following administration.