#China #Shanghai #YolTech #YOL-101 #Familial Hypercholesterolemia

YolTech's Pioneering Therapy for Familial Hypercholesterolemia

YolTech Therapeutics Co., Ltd., a leader in the field of gene editing, has made headlines with the announcement of promising interim clinical data for their investigational therapy, YOLT-101, aimed at treating patients with heterozygous familial hypercholesterolemia (HeFH). This groundbreaking approach marks a significant advancement in lipid-lowering treatments, providing hope for individuals who struggle with the lifelong challenges of managing elevated cholesterol levels.

Recently published on medRxiv, the interim results from an investigator-initiated trial showcase YOLT-101's ability to safely and effectively lower low-density lipoprotein cholesterol (LDL-C) levels in patients after just one administration. This innovation could revolutionize treatment protocols that traditionally rely on daily medication regimens, shifting towards a more efficient single-treatment model, effectively addressing a long-standing medical need.

What is YOLT-101?

YOLT-101 represents a next-generation in vivo base editing therapy. Distinct from conventional CRISPR/Cas9 approaches, which typically induce double-strand breaks in DNA, YOLT-101 employs a proprietary adenine base editor that enables precise single-base edits without the potential for harmful chromosomal abnormalities. This innovative technology uses a novel lipid nanoparticle formulation for the delivery of its therapeutic components.

Proven through extensive preclinical studies, the safety profile of YOLT-101 is robust, suggesting a minimal risk of off-target effects. Once administered through intravenous infusion, it selectively targets hepatocytes, where it induces a specific edit in the PCSK9 gene, leading to reduced cholesterol levels by enhancing the liver's ability to clear LDL-C from the bloodstream.

Study Design and Results

The open-label study aimed to assess the safety and tolerability of YOLT-101, while also gathering initial data on efficacy and pharmacodynamics. As of March 15, 2025, six participants were enrolled across three dosing cohorts (0.2 mg/kg, 0.4 mg/kg, and 0.6 mg/kg). All subjects completed at least 24 weeks of safety follow-up, with observations extending to 36 weeks for some.

Notably, the results indicate that YOLT-101 is well tolerated, with no serious adverse events reported across any dosing group. The most common side effect was a mild and transient infusion-related reaction, primarily mild fever, which resolved within 24 hours. Further, while some mild elevations in liver enzymes were noted, these changes did not translate into relevant clinical issues.

Efficacy Measures

As for efficacy, results revealed a dose-dependent reduction in LDL-C levels, with significant drops observed in the 0.4 mg/kg and 0.6 mg/kg cohorts as soon as one week post-administration. Remarkably, subjects receiving the highest dose experienced an average decline of 50% in LDL-C from baseline, with one patient showcasing an impressive LDL-C level decrease of over 74%. These reductions have demonstrated durability, persisting for more than six months following just one dose.

In the realm of pharmacodynamics, PCSK9 levels—a known regulator of LDL-C—showed reductions of greater than 70% starting at week four for those receiving the 0.6 mg/kg dose. This suggests that YOLT-101 could provide even more substantial benefits in broader hypercholesterolemic populations, given its preliminary results in HeFH patients, who often demonstrate suboptimal responses to existing therapies.

A Patient-Centric Approach

Dr. Yuxuan Wu, CEO and co-founder of YolTech, spoke passionately about the implications of these findings. He emphasized that the groundbreaking nature of YOLT-101 lies not only in its technology but also in its potential to redefine patient engagement with lipid-lowering therapies.