YolTech Therapeutics has announced positive clinical data from its ongoing investigator-initiated trial (IIT) of YOLT-203 in patients with primary hyperoxaluria type 1 (PH1), showcasing promising safety and efficacy results. The data indicates that YOLT-203 has the potential to normalize urinary oxalate levels in PH1 patients effectively.
The IIT of YOLT-203 (ClinicalTrials.gov ID: NCT06511349) aimed to evaluate the efficacy, safety, and pharmacodynamics of the therapy. As of January 2025, seven PH1 patients were enrolled and dosed with YOLT-203 via intravenous infusion. Patients receiving the high dose (0.45 mg/kg) experienced nearly a 70% reduction in 24-hour urinary oxalate levels, which was sustained throughout the 16-week primary observation period. The therapy was well-tolerated across all dose levels, with no serious adverse events (SAEs), treatment discontinuations, or patient withdrawals reported.
Mechanism of Action
YOLT-203 is designed as a one-time, potentially curative treatment for PH1. It works by deactivating glycolate oxidase (GO), an enzyme encoded by the HAO1 gene, thereby reducing the overproduction of oxalate. The therapy utilizes YolTech's proprietary CRISPR/Cas gene-editing system, YolCas12HF, delivered via lipid nanoparticles (LNPs) to edit the HAO1 gene in hepatocytes.
Significance of the Results
Dr. Yuxuan Wu, Founder and CEO of YolTech Therapeutics, emphasized the breakthrough nature of these clinical results, stating that they prove the potential efficacy of their proprietary gene-editing system, YolCas12HF. This system offers enhanced editing precision and efficiency compared to conventional platforms and avoids the legal complexities of ongoing CRISPR/Cas9 patent disputes. The success of YOLT-203 marks the first full-cycle innovation by a Chinese team, from discovery and optimization to clinical translation of next-generation in vivo gene-editing drugs.
Regulatory Designations
In September 2024, YOLT-203 received both Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) from the FDA. These designations provide several benefits, including tax credits, exemption from certain FDA fees, and seven years of market exclusivity upon regulatory approval, further supporting the development and potential commercialization of YOLT-203.
About Primary Hyperoxaluria Type 1
Primary hyperoxaluria (PH) is a rare autosomal recessive genetic disorder characterized by enzyme deficiencies in hepatic oxalate metabolism, leading to excessive oxalate production and systemic oxalate deposition. PH1, the most common subtype, results from mutations in the AGXT gene. This leads to kidney stone formation, progressive renal damage, and systemic oxalosis. Without intervention, most patients progress to end-stage renal disease (ESRD), often requiring intensive hemodialysis and a dual liver-kidney transplant.
Competitive Landscape
YolTech's YOLT-203 is not the only gene-editing therapy in development for PH1. Arbor Biotechnologies' ABO-101, another LNP-delivered CRISPR-Cas12i2 therapeutic targeting HAO1, received similar designations from the FDA earlier this month. The Phase 1/2 redePHine trial of ABO-101 is anticipated to begin in the first half of 2025.
YolTech's Broader Pipeline
YolTech Therapeutics is also advancing therapies for familial hypercholesterolemia (FH) and transthyretin amyloidosis (ATTR), demonstrating its commitment to pioneering precision genetic medicines. The company's lead candidate targeting ATTR is China’s first LNP-mediated in vivo gene editing therapy to enter clinical development.
