RN-0191

Single dose of RN0191 achieved up to 95% individual maximum and 87% mean maximum PCSK9 reduction, and up to 74% individual maximum and 56% mean maximal LDL-C lowering Robust and sustainable treatment effects support at least bi-annual dosing regimen Best-in-class potential of novel PCSK9 siRNA RN0191 supports further development as single agent or combination to further reduce atherosclerosis cardiovascular risk SHANGHAI, Nov. 18, 2024 /PRNewswire/ -- Rona Therapeutics, a leader in innovative RNA-based therapies, today presented positive results from the Phase 1 clinical trial of RN0191 at the American Heart Association's (AHA) Annual Scientific Sessions in Chicago, IL, November 16th, 2024. RN0191 is a proprietary GalNAc conjugated PCSK9 siRNA designed to significantly lower low-density lipoprotein cholesterol (LDL-C) and other lipid parameters. The Ph1 study was a randomized, single-dose ascending, placebo-controlled study to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics in healthy subjects with elevated LDL-C. The demographics included adults aged 18 to 60 years, spanning a BMI range of 19-30 kg/m2. All results are based on data in the database as of Oct. 14, 2024. A total of 32 subjects were randomized and treated with RN0191 from 60mg to 600mg, respectively. The baseline LDL-C mean level was ranging from 110-130 mg/dL. After a single-dose subcutaneous injection, RN0191 showed a favorable safety profile with no serious adverse events and only mild, transient adverse events reported across all dose- levels. Dose-dependent, significant and durable changes in PCSK9, LDL-C and other lipid parameters were observed (see table below). Mean maximum reduction of PCSK9 >85% and LDL-C >55% have been achieved. Significant and durable LDL-C reduction is achieved up to 42% through Day180, supporting a bi-annual dosing regimen for future development Significant lowering of ApoB, Lp(a), non-HDL-C and total cholesterol are also noted Remarkable treatment effects with reduction of PCSK9, LDL-C and the other lipid parameters maintained to 6 months. Stella Shi, CEO of Rona Therapeutics, shared, "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 single agent therapy or as combinatory backbone to improve cardiovascular outcome. " About Rona Therapeutics Rona Therapeutics is a global leader in nucleic acid innovative drug platform company, specializing in the treatment of metabolic diseases and neurological diseases. Rona Therapeutics is always committed to developing the best and first-in-class siRNA drugs with differentiation and innovation to address unmet needs and improve outcome in cardiovascular diseases, obesity, and MASH. In addition, Rona Therapeutics is unlocking potential of extra-hepatic delivery for neurological disorders and adipose/muscle delivery or various metabolic syndromes. For Further information, Please visit: or contact: [email protected] WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

单次给药RN0191可实现PCSK9 （前蛋白转化酶亚型9）87%平均最大降幅和95%个体最大降幅；同时可实现LDL-C（低密度脂蛋白胆固醇）56%平均最大降幅和74%个体最大降幅 该持久且稳固的治疗效果支持至少半年一次的给药方案 RN0191作为新型PCSK9 siRNA疗法，在同类别中展现出最佳潜力，支持其作为单药开发或与其他疗法联合使用，进一步降低动脉粥样硬化心血管风险 上海 2024年11月18日 /美通社/ -- 大睿生物作为创新RNA疗法的领军企业，今日在美国心脏协会（AHA）年度科学会议上，公布了其新型GalNAc结构共轭PCSK9 siRNA药物RN0191的 一 期临床试验的积极结果。该药物旨在显著降低低密度脂蛋白胆固醇（LDL-C）及其他脂质指标。 此 一 期研究为随机、单剂量递增、安慰剂对照试验，旨在评估LDL-C水平升高的健康受试者的安全性、耐受性、药代动力学和药效学。试验受试者年龄在18至60岁之间，体质指数（BMI）在19-30 kg/m 2 之间。数据截止日期为2024年10月14日。共有32名受试者被随机分配接受60mg、200mg、400mg和600mg的治疗。基线时LDL-C的平均水平在110-130 mg/dL之间。 在进行了单次皮下注射后，RN0191表现出良好的安全性，未报告严重不良事件，各剂量组仅报告了轻微的、短暂的不良事件。同时，观察到剂量依赖的、显著而持久的PCSK9、LDL-C及其他脂质参数的变化（见下表）。其中， 达到超过85%的PCSK9平均最大降幅和超过55%的LDL-C平均最大降幅；第180天时，LDL-C的降幅仍高达42%，该结果支持RN0191后续开发半年一次的给药方案 ApoB、Lp(a)、non-HDL-C和总胆固醇水平显著降低 上述PCSK9、LDL-C及其他脂质参数的降低效果可维持到6个月（至试验随访结束）。 表 单次皮下给药 RN019 后 PCSK9 蛋白和 LDL-C 较基线变化的百分比 安慰剂 60mg 200mg 400mg 600mg PCSK9 平均最大变化 (%) （给药后天数） -10% (8) -64% (15) -79% (29) -86% (22) -87% (57) 第 85天平均变化(%) -4 % -33 % -69 % -79 % -83 % 个体最大变化 % -50 % -81 % -87 % -91 % -95 % LDL-C 平均最大变化 (%) （给药后天数） -6% (85) -23% (57) -48% (29) -56% (71) -51% (22) 第 85天平均变化(%) -6 % -20 % -36 % -47 % -45 % 个体最大变化 (%) -20 % -63 % -61 % -71 % -74 % 大睿生物的首席执行官史艺宾女士（Stella Shi）表示："我们非常高兴地宣布，RN0191展现了其作为PCSK9 siRNA疗法中的最佳类别药物的潜力。这些结果突显了RN0191作为一种变革性siRNA疗法，为高胆固醇患者降低其动脉粥样硬化心血管疾病的主要风险因素。无论是作为单一疗法还是联合疗法的核心药物，均可为全球患者改善心血管预后。" 关于大睿生物 大睿生物是全球领先的核酸创新药物平台公司，专注于代谢性疾病和神经系统疾病的治疗。大睿生物始终致力于开发具有差异化和创新性的同类最佳和业内首创siRNA药物，以解决未被满足的临床需求并改善心血管疾病、肥胖症和代谢障碍相关脂肪性肝炎等的治疗预后。此外，大睿生物正全力解锁肝外递送技术用于神经系统疾病及脂肪肌肉递送针对各种代谢综合症治疗的巨大潜力。 更多信息，请访问：www.ronatherapeutics.com 或联系： BD@ronatherapeutics.com