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 maximalLDL-C lowering
Robust and sustainable treatment effects support at leastbi-annual dosing regimen
Best-in-class potential of novel PCSK9siRNA RN0191 supports further development as single agent or combination to further reduce atherosclerosis cardiovascular risk
SHANGHAI,Nov. 18,2024 -- 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. Allresultsare 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.
Table. Percentage change from baseline of PCSK9 and LDL-C level after single dose of RN0191
Placebo
60mg
200mg
400mg
600mg
PCSK9
Mean Maximum Change (%)
-10%
-64%
-79%
-86%
-87%
(Days post injection)
(8)
(15)
(29)
(22)
(57)
Mean Change (%),Day 85
-4%
-33%
-69%
-79%
-83%
Individual Maximum Change (%)
-50%
-81%
-87%
-91%
-95%
LDL-C
Mean Maximum Change (%)
-6%
-23%
-48%
-56%
-51%
(Days post injection)
(85)
(57)
(29)
(71)
(22)
Mean Change (%),Day 85
-6%
-20%
-36%
-47%
-45%
Individual Maximum Change (%)
-20%
-63%
-61%
-71%
-74%
StellaShi,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:www.ronatherapeutics.comor contact:BD@ronatherapeutics.com