YolTech Therapeutics Receives FDA IND Approval for YOLT-101, a Novel Base Editing Therapy for HeFH

June 5, 2025 /PRNewswire/  YolTech Therapeutics, a clinical-stage biotechnology company pioneering in vivo gene editing therapies, has announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for YOLT-101. This significant milestone paves the way for further clinical development of YOLT-101, an innovative base editing therapy designed to treat heterozygous familial hypercholesterolemia (HeFH) by precisely targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene.

HeFH is a genetic disorder stemming from mutations affecting genes related to LDL metabolism, such as LDLR, Apolipoprotein B (APOB), and PCSK9. Individuals with FH typically experience elevated levels of low-density lipoprotein cholesterol (LDL-C), which significantly increases their risk of developing early-onset atherosclerotic cardiovascular diseases. YOLT-101 aims to address this critical unmet medical need by offering a potential one-time, durable solution for lifelong LDL-C reduction.

Key aspects of YOLT-101 and its development include:

• Mechanism of Action: YOLT-101 leverages YolTech’s proprietary adenine base editor, hpABE5. This advanced editor is composed of a Cas9 nickase (nCas) and a novel deaminase evolved from Hafnia paralvei. Unlike traditional gene editing approaches that can induce DNA double-strand breaks, hpABE5 performs precise A•T to G•C base conversions within the PCSK9 gene. This targeted edit is designed to “turn off” the PCSK9 gene, leading to enhanced uptake of LDL-C by liver cells and a sustained reduction in blood LDL-C levels, while minimizing the risks associated with chromosomal abnormalities and off-target effects.
• Delivery System: The therapeutic agent is delivered via an advanced lipid nanoparticle (LNP) delivery system, administered through intravenous infusion. This system is designed to specifically deliver the therapeutic payload, including the hpABE5 mRNA and guide RNA (gRNA), to hepatocytes in the liver.
• Clinical Trial Status and Promising Results: YOLT-101 is currently under evaluation in an ongoing investigator-initiated trial (IIT). As of March 15, 2025, six subjects with HeFH have been enrolled across three dose cohorts (0.2 mg/kg, 0.4 mg/kg, and 0.6 mg/kg), with all subjects completing at least 24 weeks of safety follow-up, and some reaching 36 weeks.

  • Favorable Safety Profile: YOLT-101 has demonstrated a favorable safety and tolerability profile. The most common treatment-related adverse events reported were transient infusion-related reactions (primarily fever, resolving within 24 hours) and mild, transient elevations in liver enzymes, which improved within a week. Importantly, no serious adverse events, dose-limiting toxicities, or Grade $\ge$3 adverse events have been observed across any dose group.
  • Significant Efficacy: The trial has shown promising and dose-dependent LDL-C-lowering effects. In the 0.6 mg/kg group, mean LDL-C levels decreased by approximately 50% compared to baseline and were sustained through the last follow-up. Consistent with this, plasma PCSK9 protein levels in the 0.6 mg/kg group showed a substantial reduction of over 70% from baseline, beginning as early as Week 4.

Yuxuan Wu, co-founder and CEO of YolTech Therapeutics, emphasized the significance of the FDA IND clearance, stating, “In vivo gene editing represents a new generation of therapeutics — offering one-time, durable solutions for chronic and genetic diseases. We are committed to advancing breakthrough gene editing solutions that offer transformative benefits for patients living with severe genetic and cardiovascular diseases.” The promising interim clinical data for YOLT-101 underscores its potential to revolutionize the treatment landscape for HeFH patients.