By Fineline Cube 
Shanghai-based YolTech Therapeutics announced that it has received clearance from the US Food and Drug Administration (FDA) to proceed with clinical trials for its PCSK9-targeted in vivo base editing drug, YOLT-101. The drug is intended for the treatment of heterozygous familial hypercholesterolemia (HeFH).
Innovative Drug Mechanism
YOLT-101 utilizes YolTech’s proprietary adenine base editor (ABE), YolBE (specifically hpABE5), which is created by fusing nCas9 with a novel deaminase derived from Hafnia paralvei. This technology enables single-base precision editing without inducing DNA double-strand breaks, significantly reducing the risks of chromosomal abnormalities and off-target effects.
Therapeutic Approach
YOLT-101 works by precisely editing and silencing the PCSK9 gene at the single-base DNA level, thereby lowering PCSK9 protein levels in the blood. This mechanism inhibits PCSK9-mediated degradation of the low-density lipoprotein receptor (LDLR), enhancing LDLR’s ability to uptake LDL and effectively clear low-density lipoprotein cholesterol (LDL-C) from the bloodstream. The goal is to delay or potentially cure familial hypercholesterolemia.
Regulatory Progress
An Investigational New Drug (IND) filing for YOLT-101 was accepted for review by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) in April of this year.-Fineline Info & Tech