Rona Therapeutics showcased significant Phase 1 clinical data for its investigational drug, RN0361, during the American Heart Association conference in New Orleans on November 10, 2025. This long-acting siRNA targets Apolipoprotein C3 (ApoC3) and has demonstrated the ability to achieve sustained reductions in both ApoC3 and triglyceride (TG) levels for at least six months following a single dose. The trial results suggest RN0361 could play a crucial role in preventing pancreatitis associated with severe hypertriglyceridemia (HTG) and reducing cardiovascular risk linked to atherogenic lipoproteins.
Dr. Alex DePaoli, Chief Medical Officer of Rona Therapeutics, presented the findings of the randomized, placebo-controlled Single Ascending Dose (SAD) study involving volunteers with baseline triglycerides exceeding 80 mg/dl. The results showed that RN0361 was well tolerated, with no serious adverse events reported. Most side effects were mild and self-limiting, primarily involving injection-site reactions and temporary increases in liver enzymes, which are typical for GalNAc-conjugated siRNAs.
The data revealed a remarkable dose-dependent response, with a maximum reduction of 93% in ApoC3 levels and a 69% decrease in triglycerides by Day 180. Notably, RN0361 also significantly lowered atherogenic lipoproteins, including non-HDL cholesterol, VLDL cholesterol, and remnant cholesterol, while maintaining stable levels of fasting glucose and HbA1c compared to the placebo group.
Elevated ApoC3 is known to exacerbate the accumulation of triglyceride-rich lipoproteins, raising the risk of acute pancreatitis and cardiovascular disease, particularly among individuals with diabetes. Current treatment options often fall short in managing severe cases effectively. The long duration of RN0361’s efficacy from a single administration may address this critical unmet need in the management of lipid-related disorders.
Stella Shi, CEO of Rona Therapeutics, highlighted the importance of these findings. “These data confirm RN0361’s long-acting potency and favorable safety profile, supporting its advancement in Phase 2 studies in patients with hypertriglyceridemia,” she stated. “By profoundly lowering ApoC3, TG, and atherogenic lipids for at least six months after a single dose, RN0361 is an important potential therapeutic for the critical unmet need in severe HTG and CVD risk reduction.”
Rona Therapeutics, founded in 2021, has quickly established itself as a leader in RNAi therapeutics. The company is dedicated to developing innovative treatments for cardiometabolic, obesity, and degenerative diseases using its next-generation RNA technology platform. To date, Rona has successfully advanced four programs into clinical development, backed by approximately $200 million from prominent global healthcare investors and strategic partnerships.
As RN0361 moves towards further clinical trials, the implications for patients suffering from severe hypertriglyceridemia and related cardiovascular risks could be substantial, marking a promising advancement in the field of lipid management.
