Trial launches of gene editing therapy for primary hyperoxaluria type 1

The first patients have been dosed in the early phase 1 YOLT-203-101 trial (NCT06511349), which is assessing the safety and tolerability of the in vivo gene editing therapy YOLT-203 in patients with primary hyperoxaluria type 1 (PH1), YolTech Therapeutics, the developer of the therapy, announced in a news release.¹

Final completion of the phase 1 study is expected for January 2026.

"PH1 is a devastating disease that can lead to life-threatening kidney damage and systemic complications," said Yuxuan Wu, PhD, founder and CEO of YolTech Therapeutics, in the news release.¹ "As the first in vivo gene editing therapy for PH1, YOLT-203, using our proprietary YolCas12 editor, has the potential to transform treatment options for patients suffering from this debilitating disease. We believe YOLT-203 is expected to bring significant clinical benefits to both children and adults affected by this condition, and we look forward to sharing and reporting more data from this program in the future."

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.”¹

Overall, the early phase 1, open-label, dose escalation study is assessing the safety and tolerability of YOLT-203 in patients with PH1. The study will also assess the effects of a single administration of the gene editing therapy on plasma oxalate levels.

In total, the trial plans to enroll 7 patients with PH1 through a single center in China. The first adult patient in the study was dosed on August 5, 2024, and the first pediatric patient was dosed on August 20, 2024.

To be eligible for enrollment, patients need 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.²

The dose escalation phase of the trial will involve 3 dose level groups that will be dosed using an accelerated titration approach. Patients will be followed for 52 weeks.

The primary end point for the trial is safety and tolerability, measured by the incidence and severity of adverse events (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 eGFR at various time points.

Final completion of the phase 1 study is expected 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.

References

1. 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 August 24, 2024. https://www.prnewswire.com/news-releases/yoltech-therapeutics-administers-first-patient-dose-in-iit-of-yolt-203-the-worlds-first-in-vivo-gene-editing-therapy-for-ph1-302228388.html

2. Clinical exploration study of YOLT-203 in the treatment of type 1 primary hyperoxaluria (PH1). ClinicalTrials.gov. Last updated August 21, 2024. Accessed August 24, 2024. https://clinicaltrials.gov/study/NCT06511349