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.

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