Rona Therapeutics Presented Positive Phase 1 Results of RN0191, a Novel siRNA Therapy Targeting PCSK9, at the 2024 American Heart Association (AHA) Scientific Sessions

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.

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 %

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: www.ronatherapeutics.com or contact: [email protected]