Comprehensive Report on the Investigational siRNA Therapeutic RN-0191

Executive Summary

[RN-0191 is an investigational small interfering RNA (siRNA) therapeutic agent currently under development by Rona Therapeutics.][1][ This agent is engineered to target proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein central to cholesterol metabolism. By inhibiting PCSK9, RN-0191 aims to lower low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipoproteins, thereby addressing a significant risk factor for atherosclerotic cardiovascular disease (ASCVD).][1][ A key feature of RN-0191 is its GalNAc-conjugation, a strategy designed to facilitate liver-specific delivery and enhance therapeutic efficacy.][1]

[Phase 1 clinical trial data for RN-0191 (study NCT06132360), presented at the American Heart Association (AHA) Scientific Sessions in November 2024, have indicated promising results. These findings demonstrated significant, dose-dependent reductions in both PCSK9 and LDL-C levels following a single subcutaneous injection. The therapy was reported to have a favorable safety profile, with only mild and transient adverse events observed across all tested dose levels.][1][ Notably, the duration of LDL-C reduction observed in this early-stage trial suggests the potential for a bi-annual dosing regimen, a feature that could offer substantial patient convenience.][1]