Today, Salubris announced that the clinical trial application for its innovative gene-editing drug YOLT-101 injection, licensed from YOLT Therapeutics (Shanghai) Co., Ltd. ("YOLT Therapeutics"), has been officially accepted by China's National Medical Products Administration (NMPA). YOLT-101 is being developed for indications including familial hypercholesterolemia (FH) [1].
YOLT-101 consists of a base editor（YolBE ）and a guide RNA (gRNA) encapsulated in lipid nanoparticles (LNPs). The drug achieves liver-targeted delivery via LNP-mediated transport. Upon entering hepatocytes through LDL receptor (LDLR)-mediated endocytosis, the LNPs release the base editor and gRNA. These components form a YolBE-gRNA complex that targets specific sequences of the PCSK9 gene, performing precise base editing at defined sites. This process silences gene expression, inhibits PCSK9-mediated degradation of LDLR, enhances LDLR's binding to low-density lipoprotein cholesterol (LDL-C), and ultimately promotes effective clearance of circulating LDL-C. The mechanism aims to address the underlying pathology of familial hypercholesterolemia.
Current clinical approaches for cholesterol management primarily include statins, cholesterol absorption inhibitors, PCSK9 inhibitors, and other lipid-lowering therapies. The PCSK9 target is a well-established gene involved in cholesterol metabolism, a small subset of individuals naturally harbor loss-of-function mutations in the PCSK9 gene. Population studies reveal that individuals carrying loss-of-function mutations in PCSK9 exhibit significantly reduced LDL-C levels, conferring robust cardiovascular protection. Recent clinical trials demonstrate that PCSK9 monoclonal antibodies, whether used as monotherapy or in combination with statins, substantially lower serum LDL-C levels, improve other lipid parameters, and enhance cardiovascular outcomes. Supported by extensive clinical evidence, PCSK9 inhibitors have been recommended in multiple domestic and international lipid management guidelines, including those from China, Europe, and the United States.
Compared to existing PCSK9-targeted therapies such as monoclonal antibodies and siRNA drugs, YOLT-101 represents a novel approach as a DNA-level base-editing therapeutic. By permanently modifying a single nucleotide in the PCSK9 gene, it reduces target protein expression. If successfully developed, YOLT-101 could significantly improve medication adherence for FH patients and offer a more convenient, groundbreaking treatment option for this condition [1].
About Familial Hypercholesterolemia (FH)
Classic familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder caused by pathogenic mutations in genes involved in low-density lipoprotein (LDL) metabolism mediated by the LDL receptor (LDLR). Its primary clinical manifestations include markedly elevated serum LDL cholesterol (LDL-C) levels and cutaneous/tendon xanthomas. FH patients face a significantly increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Early screening and prompt pharmacological intervention can improve survival rates in this population [2].
About YOLT Therapeutics
YOLT Therapeutics, founded in 2021, is an innovation-driven biotechnology company focused on developing in vivo gene-editing therapeutics utilizing mRNA-LNP delivery platforms. Leveraging multiple proprietary technology platforms, the company has successfully developed and optimized next-generation gene editors, including YolCas and the base editor YolBE, as well as novel lipid nanoparticles (YOL-LNPs) with independent intellectual property rights. These advancements enable more efficient in vivo delivery and have led to the development of China’s first LNP-mRNA-delivered in vivo gene-editing drug to enter registration-stage clinical trials. In August 2024, Salubris announced a licensing agreement with YOLT Therapeutics, securing exclusive rights in Mainland China to the drug substance, finished product, and related intellectual property and technical data for YOLT-101, a PCSK9-targeted base-editing drug. These rights encompass R&D, regulatory approval, manufacturing, and commercialization.
References:
[1] Shenzhen Salubris Pharmaceuticals Co., Ltd. Announcement on the Acceptance of YOLT-101 Clinical Trial Application.
[2] Chinese Expert Consensus on the Screening, Diagnosis, and Treatment of Familial Hypercholesterolemia.
Disclaimer:
1. This document aims to enhance disease-related knowledge and awareness and is not intended for advertising purposes.
2. The information provided herein is for reference only. Always follow the advice of physicians or qualified healthcare professionals.
About Salubris
Shenzhen Salubris Pharmaceutical Co., LTD., founded in 1998 and listed in Shenzhen Stock Exchange in 2009 (Stock code: 002294), is an innovation-driven pharmaceutical enterprise based in China, facing the world and integrating research, production and marketing. The company has the entire chain of innovative drug research and development capabilities, focusing on cardiovascular and cerebrovascular diseases, diabetes, cancer, osteoporosis and chronic kidney disease and other chronic diseases; There are five innovative drug research and development centers in the world, which form an innovation platform mainly for small molecules, biologics, siRNA small nucleic acid and gene editing therapy, and medical devices, and develop innovative products with clinical value. The company continues to improve the accessibility of medicines, and its products cover many countries and regions in Europe, Asia, Africa, North America and South America, benefiting patients around the world.
