Rona Therapeutics Advances First Bi-valent siRNA for Heart Health

Rona Therapeutics has taken a significant step in cardiovascular medicine by submitting RN5681 to the Australian Human Research Ethics Committee (HREC), marking the entry of the first bi-valent siRNA into clinical development. This innovative therapy aims to reduce cardiovascular risk by targeting two critical factors, PCSK9 and LPA, which are known contributors to atherosclerotic cardiovascular disease. The Phase 1 trial for RN5681 is set to commence in the first quarter of 2026.

RN5681 is designed to simultaneously silence both PCSK9 and LPA, leveraging a GalNAc-conjugated, dual-targeting siRNA approach. This unification of lipid-lowering mechanisms within a single molecule is intended to provide significant and lasting improvements in lipid profiles, addressing the residual risk that current therapies do not fully mitigate.

Alex DePaoli, MD and Chief Medical Officer of Rona Therapeutics, expressed optimism about the bi-valent siRNA strategy. He noted, “As a clinician who has helped bring lipid-lowering therapies to patients, I see exceptional promise in a bi-valent siRNA approach. RN5681 has the potential to expand the treatment paradigm by tackling two of the most important cardiovascular risk factors with unimolecular medicine that could potentially be easily dosed every 6-12 months.”

The visibility of Rona’s advancements was highlighted at the recent 22nd Global Cardiovascular Clinical Trialists Forum (CVCT) held in Washington, D.C. Here, Dr. DePaoli presented the company’s bi- and multi-target siRNA platform, underscoring Rona’s leadership in the field of multi-target siRNA design and development.

Stella Shi, CEO of Rona Therapeutics, remarked on the significance of this submission, stating, “RN5681 is the first bi-valent siRNA therapy emerging from our pioneering plug-and-play technology platform. This filing marks an important step toward bringing the next generation of RNAi therapy to patients globally with transformative cardiovascular benefit.” She expressed excitement about future opportunities in cardiometabolic and obesity areas, aiming to address related health challenges.

Rona Therapeutics, founded in 2021, is dedicated to developing RNAi therapeutics focused on cardiometabolic and degenerative diseases. The company has successfully progressed four programs into clinical stages, utilizing its proprietary platform in delivery, multi-valency, and oligo chemistry. To date, Rona has attracted approximately $200 million from prominent global healthcare investors and strategic partners.

As RN5681 moves toward clinical trials, it represents a promising advancement in the ongoing fight against cardiovascular diseases, potentially reshaping treatment protocols and improving patient outcomes in the future.