Rona Therapeutics announced the submission of its RN5681 bi-valent small interfering RNA (siRNA) candidate to the Australian Human Research Ethics Committee, advancing it into Phase 1 clinical development for cardiovascular risk reduction. The move marks what the company describes as the first bi-valent siRNA therapy designed to simultaneously target PCSK9 and LPA, two established genetic drivers of atherosclerotic cardiovascular disease.
RN5681 is a GalNAc-conjugated, dual-targeting siRNA that aims to unify low-density lipoprotein cholesterol (LDL-C) lowering and lipoprotein(a) [Lp(a)] reduction in a single molecule—addressing residual cardiovascular risk that persists despite existing treatments. The investigational therapy is expected to begin dosing in its first human study in Q1 2026, pending the ethics committee review.
According to Rona, this “bi-valent” approach could expand current lipid-lowering paradigms by making dual modulation of key risk factors possible with a once-every-6-to-12-month dosing regimen, potentially enhancing patient adherence and long-term outcomes. The company highlighted that RN5681’s development builds on its proprietary RNAi platform, designed to enable multi-target siRNA therapies across cardiometabolic and related diseases.
Rona Therapeutics has progressed multiple RNAi programmes into the clinic and aims to leverage its multi-valent design technology to pursue additional siRNA constructs for complex disease targets, including cardiometabolic and obesity-related indications.
