On May 31st, 2023, Sanegene Bio Inc. (Sanegene) first subject was dosed with SGB-3403 for the heathy volunteers in Australia, enabling the Phase I clinical study of its self-developed RNAi therapeutic targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) for treatment of hypercholesterolemia. SBG-3403 is Sanegene' s first small RNA interference (siRNA) drug to enter clinical development, marking a milestone step for Sanegene.

On May 10th, 2023, SGB-3403 was approved by the Australian Human Research Ethics Committees for the Phase I clinical trial, by when it only took less than 12 months from SGB-3403 being identified as preclinical candidate compound (PCC) to the FSD, showing Sanegene' s excellent execution efficiency and innovation velocity.

The Phase I, randomized, double-blind, placebo-controlled, single-dose, and multiple-dose escalation study is designed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of SGB-3403 when administered subcutaneously in healthy participants and participants with elevated Low Density Lipoprotein Cholesterol (LDL-C).

Cardiovascular disease has become the "first killer" threatening human health worldwide. In China, for example, cardiovascular disease was the leading cause of death among urban and rural residents in 2018. The prevalence and mortality of cardiovascular diseases will continue to rise with the increasing number of people with hypertension, dyslipidemia, diabetes, and obesity. LDL-C is a pathogenic risk factor for cardiovascular disease and needs to be closely monitored and reduced in clinical practice to prevent and treat cardiovascular disease. Currently, statins are the standard of choice for lowering LDL-C levels, however many high-risk cardiovascular diseases patients cannot achieve ideal LDL-C levels after taking statin drugs in practice. Therefore, there is a huge and urgent unmet medical need for a more effective and innovative treatment choice to better manage the LDL-C levels.

SGB-3403, an siRNA-N-acetylgalactosamine (GalNAc) conjugate targeting PCSK9, is delivered to liver using Sanegene's novel GalNAc platform technology to inhibit the synthesis of PCSK9 in the liver through RNA interference. The advantages of GalNAc platform have been also fully verified, including safety, effectiveness, and stability. SGB-3403 has been shown in preclinical studies with good safety and tolerability, superior efficacy than benchmark products in multiple animal disease models (including the hyperlipidemic cynomolgus monkey model), and it can reduce LDL-C by up to 40% - 70% even with lower dose and less frequency of administration, showing its potential to be the best-in-class siRNA drug targeting PCSK9.

"As the first siRNA drug to enter the clinical development, SBG-3403 is expected to achieve positive results in subsequent clinical trials. We will also do our best to accelerate the clinical development to bring such innovative treatment options to more patients with cardiovascular disease sooner. In the future, Sanegene will leverage the platform advantages and push forward more innovative assets into clinical stage, to address the unmet medical needs, and bringing more effective therapies to prolong and reshape patients' lives." said Dr. Weimin Wang, Founder and Chief Executive Officer of Sanegene.

Sanegene will keep committed to the research and development of innovative siRNA drugs through continuous and focusing investment on the technology breakthroughs. We will also expand our pipeline in cardiovascular and metabolic diseases, immunology-related diseases, and nervous system diseases, to bring more safe, effective, and accessible RNAi drugs to the patients in need as soon as possible.