YOLT-203 shows promise in early phase 1 trial for primary hyperoxaluria 1

Data from the early phase 1 YOLT-203-101 trial (NCT06511349) show encouraging safety, tolerability, and efficacy of the investigational in vivo gene editing therapy YOLT-203 for the treatment of patients with primary hyperoxaluria type 1 (PH1).¹

The YOLT-203-101 trial enrolled 7 patients with PH1.

The data, shared by YolTech Therapeutics, encompass 7 patients with PH1 who were enrolled in the study. Patients received YOLT-203 intravenously at 1 of 3 dose levels: 0.3 mg/kg, 0.45 mg/kg, and 0.6 mg/kg.²

In the highest dose cohort, patients achieved a nearly 70% reduction in 24-urinary oxalate levels, which were sustained through 16-week follow-up. Treatment was well tolerated across all dose levels. No serious adverse events (AEs), treatment discontinuations, or patient withdrawals have been observed to date.

"The clinical results of YOLT-203 represents a breakthrough in the field of in vivo gene-editing therapies,” said Yuxuan Wu, founder and CEO of YolTech Therapeutics, in the news release.¹“In this clinical trial, we have proven the potential efficacy of our proprietary gene-editing system YolCas12HF, a system with enhanced editing precision and efficiency compared to conventional platforms and the ability to avoid legal complexities of the ongoing CRISPR/Cas9 patent disputes. Most importantly, it marks the first full-cycle innovation by a Chinese team, spanning from discovery, optimization to clinical translation of next-generation in vivo gene-editing drugs. We fully understand the urgent need for patients with rare diseases to have a treatment addressing the root of their diseases. Exemplified by YOLT-203, we believe one-time treatments for lifelong cure will redefine the standard of care for rare diseases globally."

In total, the single-arm, open-label YOLT-203-101 trial enrolled 7 patients with PH1 through a single center in China.²

To be eligible for enrollment, patients needed to be 2 years of age or older, have a diagnosis of PH1, harbor AGXT gene mutations, and have at least 2 instances of 24-hour urinary oxalate levels of 0.7 mmol/1.73m² or greater per day or the ratio of urinary oxalate to creatinine in a single urine collection must be higher than the upper limit of normal for the patients’ age group. Additionally, if patients are treated with vitamin B6, the treatment must be stable for 90 days before enrollment and remain stable for the duration of the study.

The primary end point for the trial is safety and tolerability, measured by the incidence and severity of AEs and serious AEs through week 52. Secondary end points include various pharmacokinetic measures, such as the peak plasma concentration through day 14, as well as various pharmacodynamic measures, such as changes in estimated glomerular filtration rate at various time points.

Patients in the study will continue to be followed through week 52 in the trial, with final completion planned for January 2026. Following the 1-year main study, the sustained safety and efficacy of the treatment will continue to be monitored in patients for up to 15 years.²

According to YolTech, YOLT-203 is encapsulated within lipid nanoparticles, which are recognized and internalized by liver cells upon intravenous administration. The company explained, “Once inside, the YolCas12 editor protein, guided by the corresponding guide RNA (gRNA), targets and corrects mutations in the AGXT gene, aiming to reduce harmful oxalate levels in the blood, thereby offering a potential one-time, curative treatment for PH1.”³

YOLT-203 was granted an Orphan Drug Designation and a Rare Pediatric Disease Designation for this indication in September 2024. According to the news release, YOLT-203 is the first in vivo gene editing therapy to show positive clinical data for the treatment of patients with PH1.

References

1. YolTech Therapeutics Announces Positive Clinical Data for YOLT-203, an In Vivo Gene Editing Therapy for Primary Hyperoxaluria Type 1 (PH1). News release. YolTech Therapeutics. Published online and accessed February 25, 2025. https://www.yoltx.com/news/press-release/74

2. Clinical exploration study of YOLT-203 in the treatment of type 1 primary hyperoxaluria (PH1). ClinicalTrials.gov. Last updated December 19, 2024. Accessed February 25, 2025. https://clinicaltrials.gov/study/NCT06511349

3. YolTech Therapeutics administers first patient dose in IIT of YOLT-203, the world's first in vivo gene editing therapy for PH1. News release. YolTech Therapeutics. August 22, 2024. Accessed February 25, 2025. https://www.yoltx.com/news/press-release/67