Breaking News! Base Editing Therapy YOLT-101 Clinical Trial Approved for Familial Hypercholesterolemia

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Recently, Salubris announced that its in-licensed innovative gene-editing drug YOLT-101 Injection (hereinafter referred to as "YOLT-101") has obtained the Clinical Trial Implied Permission from the NMPA. The intended indication is for the treatment of Heterozygous Familial Hypercholesterolemia (HeFH) [1].

 

YOLT-101 consists of YolBE (a base editor) and guide RNA (gRNA) encapsulated within lipid nanoparticles (LNPs). YOLT-101 utilizes LNP-mediated delivery to target the liver and enter hepatocytes through low-density lipoprotein receptor (LDLR)-mediated endocytosis on the liver cell surface. Following cellular entry, the base editor and gRNA are released and form the YolBE-gRNA complex. This complex targets a specific sequence of the PCSK9 gene, performing precise base editing at the designated site. This editing silences PCSK9 gene expression, thereby inhibits PCSK9-mediated degradation of the LDLR. The resulting increase in functional LDLR enhances binding to low-density lipoprotein cholesterol (LDL-C) and promotes effective clearance of LDL-C from the bloodstream. This mechanism aims to achieve the therapeutic goal of treating Familial Hypercholesterolemia.


In current clinical practice, the primary cholesterol-lowering medications include statins, cholesterol absorption inhibitors, PCSK9 inhibitors, and other lipid-lowering agents. The PCSK9 target represents a classic gene involved in cholesterol metabolism. A small subset of the population naturally carries loss-of-function mutations in the PCSK9 gene. Extensive human genetic research data demonstrate that individuals harboring these PCSK9 loss-of-function mutations exhibit significantly reduced blood LDL-C levels and experience a pronounced protective effect against cardiovascular disease. In recent years, clinical studies have found that PCSK9 monoclonal antibodies, whether used alone or in combination with statins, substantially lower serum LDL-C levels, while also improving other lipid profiles and substantially increasing cardiovascular benefits. Based on multiple evidences from medical studies, numerous lipid management guidelines or consensus statements from China, Europe, and the United States recommend the use of PCSK9 inhibitors.


Compared to existing treatments such as PCSK9 antibodies and siRNA drugs, YOLT-101, as a PCSK9 base-editing drug, can edit a single base of the PCSK9 gene at the DNA level, thereby reducing the expression of the target protein. If successfully developed and approved for market, it is expected to significantly improve medication adherence among patients with familial hypercholesterolemia, provide them with a more convenient and innovative treatment option.

 

About Familial hypercholesterolemia (FH)

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder caused by pathogenic mutations in key genes involved in LDL-C metabolism. Patients with FH are exposed to high serum LDL-C levels from birth, significantly increasing their risk of atherosclerotic cardiovascular diseases. The awareness and diagnosis rates of FH are very low, with diagnostic rates being less than 1% in most countries, and the treatment situation is even worse[2]. Currently, treatment options for FH include lifestyle interventions, lipid-lowering drug therapy, lipoprotein apheresis, and liver transplantation. Among these, the primary treatment method is the use of lipid-lowering medications. Clinically, a common approach for FH patients is a combination therapy of statins, ezetimibe, and PCSK9 inhibitors. However, based on existing treatment options, patients often face numerous challenges during treatment, including suboptimal efficacy, intolerable drug side effects, and poor adherence due to the need for lifelong medication.


References:

[1] Announcement by Shenzhen Salubris Pharmaceutical Co., Ltd. regarding the implied approval for clinical trials of YOLT-101.

[2] Expert Consensus on Screening and Diagnosis of Familial Hypercholesterolemia in China.


Statement:

1. The purpose of this material is to provide relevant knowledge in the field of disease and to enhance awareness of the condition; it is not intended for advertising purposes.

2. The information contained in this material is for reference only and should be followed according to the advice or guidance of a doctor or other healthcare professionals.

3. The medications and related indications mentioned in this document have not yet been approved in China.


About Salubris

Shenzhen Salubris Pharmaceutical Co., Ltd. was established in 1998 and is an innovation-driven pharmaceutical company that integrates research, production, and sales, with a focus on China and a global outlook (stock code: 002294). With the mission of "providing outstanding pharmaceutical products for human health," Salubris specializes in the treatment of chronic diseases, primarily in the cardiovascular and cerebrovascular fields. The company has launched monotherapy, combination, and co-crystal drugs of Alisartan, addressing various complex hypertension issues and forming a unique family of original antihypertensive drugs based on Alisartan.


Salubris has established five major innovative drug R&D centers and three medical device R&D bases globally, creating an innovative platform centered on small molecule drugs, biopharmaceuticals, siRNA small nucleic acids, gene-editing drugs, and medical devices. The company is dedicated to developing innovative products that meet unmet clinical needs, enhancing people's quality of life and extending healthy lifespans.