Abstract 4775: Optimizing the potency and dosing design for ARO-HIF2: An RNAi therapeutic for clear cell renal cell carcinoma

Antitumoral RNA‐targeted oligonucleotide therapeutics: The third pillar after small molecule inhibitors and antibodies

“…ARO‐HIF2 is composed of HIF2 siRNA targeting HIF2α and uses a proprietary targeted‐RNAi molecule (TRiM) delivery platform, which comprises targeting ligands, such as RGD motifs designed to transport siRNA to cancer cells. ARO‐HIF2 use resulted in HIF2α mRNA knockdown, tumor growth inhibition, and OS improvement in a xenograft model of clear cell renal cell carcinoma, frequently involving the inactivation of the von Hippel–Lindau tumor suppressor, leading to the accumulation of HIFs 31 . Arrowhead Pharmaceuticals reported that seven of nine tumor samples had a low HIF2α level, and one patient achieved partial response with tumor shrinkage of approximately 65% in a phase 1 study 32…”

“…ARO-HIF2 use resulted in HIF2α mRNA knockdown, tumor growth inhibition, and OS improvement in a xenograft model of clear cell renal cell carcinoma, frequently involving the inactivation of the von Hippel-Lindau tumor suppressor, leading to the accumulation of HIFs. 31 Arrowhead Pharmaceuticals reported that seven of nine tumor samples had a low HIF2α level, and one patient achieved partial response with tumor shrinkage of approximately 65% in a phase 1 study. 32 Atu027 is a liposomal siRNA formulation targeting human PKN3, which acts as a Rho effector downstream of phosphoinositide 3-kinase signaling, with AtuPLEX comprising three types of lipids.…”