YolTech Therapeutics Doses First Patient with YOLT-203 in PH1 Gene Editing Therapy Trial

YolTech Therapeutics has reached a significant milestone by administering the first dose of YOLT-203, an innovative in vivo genome editing therapy, to a patient. This groundbreaking event marks the launch of an Investigator-Initiated Trial (IIT) and is a global first in using in vivo gene editing therapies to treat Primary Hyperoxaluria Type 1 (PH1). The therapy, designed to be a single-dose, potentially curative treatment, leverages YolTech’s proprietary YolCas12™ editor. This development sets a new benchmark in the field of gene editing, expanding the possibilities for treating severe genetic disorders.

Primary hyperoxaluria (PH) is a genetic condition characterized by excessive hepatic oxalate production, leading to high levels of renal oxalate excretion. PH1, the most prevalent form of the disease, manifests in childhood due to mutations in the AGXT gene. This mutation results in the lack or malfunction of the enzyme alanine-glyoxylate aminotransferase, eventually causing renal failure and necessitating a liver and kidney transplant for metabolic correction and kidney replacement.

YOLT-203, an independent creation of YolTech, incorporates the YolCas12™ editor. This editor is a novel CRISPR/Cas gene-editing tool developed via YolTech's HEPDONE® (High-Throughput Evolution Platform for Discovery and Optimization of Novel Editors) system. The YolCas12™ editor has shown extraordinary gene editing efficiency in both prokaryotic and eukaryotic systems. It has been effective in vivo through LNP-mRNA delivery in animal models, including mice and non-human primates. YOLT-203 targets the HAO1 gene, aiming to inhibit the production of pathogenic proteins as demonstrated in pre-clinical trials, thereby offering an effective therapeutic option for both child and adult PH1 patients.

The clinical trial of YOLT-203, initiated by investigators, is a single-arm, open-label, dose-escalation study designed to evaluate the safety and tolerability of YOLT-203 in Chinese patients with PH1. The trial plans to enroll seven subjects. The first adult patient was dosed on August 5, 2024, followed by the first child patient on August 20, 2024. This study signals a pioneering effort as the inaugural global clinical trial of an in vivo gene editing therapy for PH1.

Dr. Yuxuan Wu, Founder, and CEO of YolTech, expressed optimism about the potential impact of YOLT-203. He acknowledged the devastating nature of PH1, which can lead to severe kidney damage and other systemic issues. He emphasized that YOLT-203, utilizing the YolCas12™ editor, could revolutionize treatment options for those affected by PH1. Dr. Wu anticipates that YOLT-203 will offer substantial clinical benefits to both children and adults suffering from this debilitating disease. He looks forward to sharing more data from the ongoing program.

YolTech remains dedicated to advancing the clinical development of YOLT-203. The company plans to collaborate closely with regulatory bodies, healthcare professionals, and patient advocacy groups to further the progress of gene editing therapies.

YOLT-203 is an avant-garde in vivo gene-editing treatment created using YolTech’s YolCas12™ system. This therapy is delivered through lipid nanoparticles (LNPs) that target the liver, addressing the genetic mutations causing PH1. Upon intravenous administration, the LNPs are absorbed by liver cells. The YolCas12™ editor, guided by the corresponding gRNA, then targets and corrects the AGXT gene mutations, aiming to lower harmful oxalate levels in the blood, offering a potential one-time curative solution for PH1.

The YOLT-203-101 clinical trial is a single-arm, open-label, dose-escalation study to assess the safety and tolerability of YOLT-203 in Chinese PH1 patients. It will also preliminarily evaluate the effect of a single dose of YOLT-203 on plasma oxalate levels, a key efficacy marker in PH1. The dose-escalation phase will involve three dose groups, with an accelerated titration approach to determine the highest dose. After the main study's one-year duration, participants will enter a fifteen-year follow-up period to monitor long-term effects and safety.

YolTech Therapeutics is a groundbreaking gene editing firm focused on developing treatments that offer lifelong cures for severe diseases. The company has established a leading high-throughput evolution platform and an innovative LNP delivery system, excelling in novel Cas and base editor discovery and in-house LNP production for GMP manufacturing. With independent intellectual property rights and global core patent protection, YolTech's primary pipeline, YOLT-201, was the first LNP-mediated in vivo gene editing drug in China to enter registered clinical development in 2024. The firm is also advancing gene editing therapies for familial hypercholesterolemia (FH) and PH1, showing promising early clinical results.