# RN5681 is a GalNAc-conjugated, dual-targeting siRNA designed to simultaneously silence both PCSK9 and LPA.

*biotech · news · 2025-12-17 · The Manila Times*

## Key points

- Rona Therapeutics submitted RN5681, its first bi-valent siRNA, to Australian HREC for review.
- RN5681 dual-targets PCSK9 and LPA, aiming to address two key cardiovascular disease drivers simultaneously.
- Phase 1 clinical trial dosing for RN5681 is planned to begin in Q1 2026.
- RN5681 is designed for durable lipid improvement with dosing intervals of every 6-12 months.

SHANGHAI and SANTA BARBARA, Calif., Dec. 17, 2025 /PRNewswire/ -- Rona Therapeutics, a global leader in next-generation RNAi medicines, today announced the submission of RN5681 to the Australian Human Research Ethics Committee (HREC), advancing the company's first bi-valent siRNA into clinical development. The Phase 1 trial is expected to begin dosing in Q1 2026. RN5681 is a GalNAc-conjugated, dual-targeting siRNA designed to simultaneously silence both PCSK9 and LPA, two genetically validated and complementary drivers of atherosclerotic cardiovascular disease. By unifying LDL-C lowering and Lp(a) reduction within a single molecule, RN5681 aims to deliver deep, durable lipid improvement and address persistent residual risk not resolved by current therapies. "As a clinician who has helped bring lipid-lowering therapies to patients, I see exceptional promise in a bi-valent siRNA approach," said Alex DePaoli, MD, CMO. "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." Dr. DePaoli recently presented Rona's bi- and multi-target siRNA platform at the 22nd Global Cardiovascular Clinical Trialists Forum (CVCT, Washington, DC). The visibility of Rona's science at a premier global cardiovascular meeting underscores rapid recognition of the company's leadership in multi-target siRNA design and development. "RN5681 is the first bi-valent siRNA therapy emerging from our pioneering plug-and-play technology platform," said Stella Shi, CEO. "This filing marks an important step toward bringing next generation of RNAi therapy to patients globally with transformative cardiovascular benefit. We are excited about future multi-valency siRNA breakthrough opportunities in cardiometabolic and obesity areas to address comorbidities. About Rona Therapeutics

**Companies:** Rona Therapeutics
**Countries:** Australia, United States

[Read the full story on The Manila Times](https://www.manilatimes.net/2025/12/17/tmt-newswire/pr-newswire/rona-therapeutics-unveils-the-global-first-bi-valent-pcsk9-lpa-sirna-into-clinical-development-for-cardiovascular-risk-reduction/2245318)

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