SHANGHAI, April 28, 2025 /PRNewswire/ — YolTech Therapeutics Co.,Ltd, a clinical-stage in vivo gene editing company committed to pioneering the next generation of precision genetic medicines, announced promising interim clinical data from an investigator-initiated trial (IIT) of YOLT-101 (NCT06458010), and the data has been published on medRxiv. YOLT-101 is an investigational in vivo base editing therapy for the treatment of heterozygous familial hypercholesterolemia (HeFH). Clinical data demonstrate that YOLT-101 can safely and effectively reduce low-density lipoprotein cholesterol (LDL-C) levels in HeFH patients with a single administration. As a next-generation gene-editing therapy, YOLT-101 represents a breakthrough in lipid-lowering treatment – moving beyond daily pills and regular injections, and opening a new era of “one-time treatment for lifelong LDL-C reduction.”
YOLT-101 is a next-generation in vivo base-editing therapeutic independently developed by YolTech. It features the novel, proprietary adenine base editor, YolBE—specifically hpABE5—which consists of nCas9 and a newly discovered deaminase derived from Hafnia paralvei. For delivery, it utilizes a new lipid nanoparticle (LNP) formulation. Unlike traditional CRISPR/Cas9 systems that rely on inducing DNA double-strand breaks (DSBs), hpABE5 enables precise single-base editing without generating DSBs, thereby significantly reducing the risks of chromosomal abnormalities and off-target effects. Extensive preclinical studies have demonstrated its excellent genome editing safety profile.
The in vivo base-editing therapy is delivered via intravenous infusion and selectively internalized by hepatocytes, where it induces a precise nucleotide conversion within the PCSK9 gene. This targeted edit disrupts PCSK9 protein expression, leading to enhanced uptake of LDL-C by LDL receptor on hepatocyte surfaces and finally resulting in a marked reduction in plasma LDL-C levels.
Study Design of the IIT
This is an open-label clinical trial conducted in patients with HeFH. The primary objective is to evaluate the safety and tolerability of YOLT-101, while also aiming to explore preliminary efficacy and pharmacodynamics. As of March 15, 2025, a total of 6 subjects have been enrolled: 1 in the 0.2 mg/kg cohort, 2 in the 0.4 mg/kg cohort, and 3 in the 0.6 mg/kg cohort. All subjects have completed at least 24 weeks of safety follow-up, with the longest reaching 36 weeks.
Safety and Tolerability
YOLT-101 has shown good safety and tolerability. As of March 15, 2025, no serious adverse events (SAEs), dose-limiting toxicity (DLT) events, or Grade ≥3 adverse events (according to CTCAE v5.0) were observed in any dose group. All enrolled subjects are under follow-up as scheduled.
The most common treatment-related adverse event was transient infusion-related reactions (5/6, 83.3%), with a manifestation of fever that resolved within 24 hours. Mild elevations in liver enzymes (3/6, 50.0%) were reported, which emerged on Day 4-7 following administration and rapidly alleviated usually after 7 days. All these patients did not show any relevant symptoms, and their plasma bilirubin levels (important indices for liver function) remained within normal limits throughout. No clinically significant changes were observed in other laboratory parameters.
Efficacy and Pharmacodynamics
LDL-C levels demonstrated a dose-dependent reduction following administration. Baseline LDL-C was 4.9 ± 0.6 mmol/L. In the 0.4 mg/kg and 0.6 mg/kg cohorts, sustained reductions in LDL-C were observed as early as Week 1 post-administration, reaching a maximal effect by Week 4. In the 0.6 mg/kg group, mean LDL-C level decreased by around 50% through the last follow-up with acquired data compared to baseline. The subject with the greatest response showed an LDL-C level of approximately 1 mmol/L (maximal percent change from baseline over 74%), and the efficacy has sustained for over 6 months following single-dose infusion. Pharmacodynamic data showed consistent trends, with plasma PCSK9 protein levels decreasing by over 70% from baseline starting at Week 4 in the 0.6 mg/kg group (maximal individual reduction reached 87%).
Notably, all enrolled subjects in this study were HeFH patients. PCSK9-targeting therapies typically show reduced efficacy in this population compared to with general hypercholesterolemic population. This suggests that YOLT-101 may demonstrate even greater lipid-lowering potential in the general hypercholesterolemic population.
In summary, YOLT-101 exhibits favorable safety and tolerability in HeFH patients, with adverse events being mild and transient. Both pharmacodynamic (PCSK9) and efficacy (LDL-C) outcomes in the 0.4 mg/kg and 0.6 mg/kg groups showed durable, dose-dependent reductions. These results support the potential of YOLT-101 to achieve “single-dose, lifelong lipid lowering.”
“We are dedicated to revolutionizing traditional approaches to cardiovascular disease through next-generation base editing technology and groundbreaking single-dose treatment,” said Dr. Yuxuan Wu, co-founder and CEO of YolTech Therapeutics. ” Patients with heterozygous familial hypercholesterolemia (HeFH) suffer from a lifelong, genetically driven impairment in LDL-C metabolism, resulting in markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. This population is at exceptionally high risk for premature atherosclerotic cardiovascular diseases. Current lipid-lowering therapies rely heavily on long-term, continuous administration. However, once treatment is discontinued, LDL-C levels rebound. These regimens are frequently hindered by poor patient adherence and drug intolerance—highlighting a critical unmet need for more durable, patient-friendly therapeutic solutions. Current clinical data of YOLT-101 demonstrates a single YOLT-101 administration can lead to significant and durable reductions in LDL-C levels. By precisely editing key genes regulating LDL-C levels in the liver, YOLT-101 has the potential to be a transformative ‘one-time treatment, lifelong cure’ therapy. We look forward to further confirming its safety and efficacy in larger-scale clinical studies and conferring benefits to patients worldwide.”
About Familial Hypercholesterolemia (FH)
Familial hypercholesterolemia (FH) is caused by mutations in LDL metabolism-related genes (LDLR, APOB, PCSK9). As a result, patients with FH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). The global prevalence of FH is 1:200-1:250, affecting a total of ~34 million people worldwide.
Current FH management strategies include lifestyle modifications, lipid-lowering medications, lipoprotein apheresis, and liver transplantation. The standard of treatment involves pharmacotherapy, with most patients receiving a triple regimen of statins, ezetimibe, and PCSK9 inhibitors. However, current therapies have significant limitations including suboptimal efficacy, intolerable side effects, and poor long-term adherence. These challenges underscore the urgent need for novel, durable therapies to address the lifelong treatment burden of FH.
About YolTech
YolTech Therapeutics is a clinical-stage in vivo gene editing company committed to pioneering the next generation of precision genetic medicines. Our approach combines innovative gene editing technologies with an advanced lipid nanoparticle (LNP) delivery system, creating a versatile platform designed to address a wide range of serious diseases. Central to our mission is the development of internal capabilities, including end-to-end manufacturing, to ensure the highest standards of quality and scalability. Our lead candidate, targeting ATTR, marks a significant milestone as China’s first LNP-mediated in vivo gene editing therapy to enter clinical development. With promising early clinical outcomes, YolTech is also advancing therapies for familial hypercholesterolemia (FH) and primary hyperoxaluria type 1 (PH1). As a company dedicated to transforming the treatment landscape, YolTech continues to push the boundaries of what is possible in gene editing.
For more information, please visit: www.yoltx.com
