YolTech Reports Positive Clinical Results for YOLT-203 Gene Therapy for PH1

YolTech Therapeutics, a clinical-stage company specializing in in vivo gene editing, has announced promising outcomes from their ongoing trial of YOLT-203 for primary hyperoxaluria type 1 (PH1). The trial, which is investigator-initiated, has demonstrated YOLT-203's excellent safety and pharmacodynamics profiles, as well as its potential to significantly lower urinary oxalate levels in PH1 patients. Notably, YOLT-203 represents a pioneering achievement as the first in vivo gene-editing treatment to yield positive clinical results for this condition.

YOLT-203 is an experimental gene-editing therapy designed to be a one-time, lifelong solution for PH1, a rare genetic disorder that can lead to kidney stones and potentially kidney failure. The therapy aims to reduce oxalate overproduction in PH1 patients by deactivating the enzyme glycolate oxidase (GO), which is encoded by the HAO1 gene. This is achieved using YolTech's proprietary CRISPR/Cas system, YolCas12HF, delivered through innovative lipid nanoparticles (LNPs).

In August 2024, YOLT-203 became the first investigational in vivo gene-editing therapy for PH1 to enter clinical trials. The trial's objectives were to assess the safety, efficacy, and pharmacodynamics of YOLT-203. By January 2025, seven patients had been enrolled and treated with YOLT-203 via intravenous infusion. Remarkably, those receiving high doses experienced a nearly 70% reduction in 24-hour urinary oxalate levels, with these effects persisting throughout the 16-week observation period. Across all dosage levels, YOLT-203 was well-tolerated, with no serious adverse events, treatment discontinuations, or patient withdrawals reported.

In September 2024, YOLT-203 received both Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) from the FDA, underscoring its potential importance in treating this rare condition.

Dr. Yuxuan Wu, the Founder and CEO of YolTech Therapeutics, highlighted the significance of YOLT-203's clinical results as a major breakthrough in in vivo gene-editing therapies. He emphasized that the trial confirmed the potential effectiveness of YolCas12HF, a system noted for its enhanced editing precision and efficiency over existing platforms. Importantly, this success marks the first full-cycle innovation by a Chinese team, covering discovery through to clinical application of next-generation gene-editing drugs. Dr. Wu expressed the company's commitment to addressing the urgent needs of patients with rare diseases by offering treatments that tackle the root causes, with YOLT-203 exemplifying the potential for one-time treatments to offer lifelong cures.

Primary Hyperoxaluria (PH) is a rare genetic disorder characterized by the excessive production of oxalate due to enzyme deficiencies in hepatic metabolism. PH1, the most prevalent form, is caused by mutations in the AGXT gene and generally appears in early childhood. Patients with PH often suffer from kidney stones, nephrocalcinosis, and renal insufficiency, with severe cases progressing to end-stage renal disease (ESRD), necessitating dialysis or transplantation. The disorder primarily affects children, with symptoms typically emerging between ages 0–3. Without effective intervention, most patients face ESRD during adolescence, posing significant health risks. PH has a prevalence of approximately 1 in 58,000, affecting around 10,000 individuals in the U.S. and EU.

YolTech Therapeutics is dedicated to advancing the next generation of precision genetic medicines through innovative gene editing technologies and advanced LNP delivery systems. Their approach aims to transform treatment possibilities for serious diseases, with YOLT-203 being a significant milestone as China's first LNP-mediated in vivo gene editing therapy to enter clinical development. The company is also working on therapies for familial hypercholesterolemia and PH1, continually pushing the boundaries in gene editing.