ARC-F12

**ARC-F12** is an investigational RNA interference (RNAi) therapeutic developed using Arrowhead Pharmaceuticals' Dynamic Polyconjugate (DPC) delivery platform to silence the F12 gene, which encodes coagulation **factor XII (F12)**, a key initiator of the contact activation pathway in the intrinsic coagulation cascade and the kinin-kallikrein system implicated in bradykinin-mediated angioedema. Preclinical studies in rodents and non-human primates demonstrated potent, durable F12 knockdown (>90-99% reduction in serum levels) following subcutaneous or intravenous dosing, with monthly administration maintaining >80% knockdown; it significantly reduced edema in carrageenan-induced paw models, inhibited thrombus formation in thrombosis models without increasing bleeding risk, and showed good tolerability with no drug-related toxicity. Initially targeted for prophylactic treatment of **hereditary angioedema (HAE)** and thromboembolic diseases, leveraging F12's liver-predominant expression for RNAi targeting.[1][2][3][4][5][9]