ARC-HIF2

**ARC-HIF2** is an investigational RNAi therapeutic developed by Arrowhead Pharmaceuticals using their extrahepatic Dynamic Polyconjugate (DPC™) delivery system to target tissues outside the liver, specifically tumors. It employs RNA interference to silence the transcription factor **hypoxia-inducible factor 2α (HIF-2α)**, a key driver of tumor progression, metastasis, and angiogenesis in **clear cell renal cell carcinoma (ccRCC)** due to VHL mutations that prevent HIF-2α degradation under hypoxia. Preclinical data showed >80% HIF-2α mRNA knockdown in ccRCC tumor models, leading to significant tumor reduction, cell death, decreased VEGF-A, and vascular destruction; it advanced to IND-enabling studies in 2015.[1]