Rona Therapeutics Shares Positive Phase 1 Results of RN0191 siRNA Therapy at 2024 AHA Sessions

Rona Therapeutics, a prominent innovator in RNA-based therapies, has announced encouraging results from their Phase 1 clinical trial of RN0191. The data was presented at the American Heart Association's Annual Scientific Sessions in Chicago on November 16, 2024. RN0191 is a proprietary GalNAc-conjugated PCSK9 siRNA, designed to significantly lower low-density lipoprotein cholesterol (LDL-C) and other lipid parameters.

The Phase 1 study was aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RN0191 in healthy individuals with elevated LDL-C. The trial was randomized, single-dose ascending, and placebo-controlled, including participants aged 18 to 60 years with a body mass index (BMI) ranging from 19 to 30 kg/m2. Data from October 14, 2024, were analyzed, involving 32 subjects who received varying doses of RN0191, from 60mg to 600mg. The baseline LDL-C levels of these participants ranged from 110-130 mg/dL.

The results demonstrated that RN0191, administered through a single subcutaneous injection, exhibited a favorable safety profile with no serious adverse effects. Only mild and transient adverse events were reported across all dosage levels. The study observed dose-dependent and significant changes in PCSK9, LDL-C, and other lipid parameters. Remarkable reductions were noted, with the mean maximum PCSK9 reduction exceeding 85% and LDL-C reduction surpassing 55%. Sustained LDL-C reduction was observed up to 42% through Day 180, supporting the feasibility of a bi-annual dosing regimen.

In addition to LDL-C, significant reductions in ApoB, Lp(a), non-HDL-C, and total cholesterol were also observed. These effects were maintained for up to six months, indicating the potential for long-lasting benefits.

Stella Shi, CEO of Rona Therapeutics, expressed excitement about the findings, stating, "We are thrilled to report that RN0191 has demonstrated best-in-class PCSK9 siRNA potential. These results highlight RN0191's potential as a transformative siRNA therapy for global patients with elevated LDL-C, a major risk factor for atherosclerotic cardiovascular disease, either as a single-agent therapy or as a combinatory backbone to improve cardiovascular outcomes."

Rona Therapeutics continues to position itself as a leader in nucleic acid innovative drug platforms, focusing on treating metabolic and neurological diseases. Their commitment to developing siRNA drugs with differentiation and innovation aims to address unmet needs and improve outcomes in cardiovascular diseases, obesity, and MASH. Additionally, the company is exploring the potential of extra-hepatic delivery for neurological disorders and adipose/muscle delivery for various metabolic syndromes.

The promising results from the Phase 1 trial of RN0191 underscore its potential as a best-in-class therapeutic option for reducing cardiovascular risk associated with high LDL-C levels. As the company moves forward with its development, RN0191 may offer a significant advancement in the management of atherosclerotic cardiovascular disease and related conditions.