YolTech Therapeutics Administers First Patient Dose in IIT of YOLT-203, the World's First In Vivo Gene Editing Therapy for PH1

SHANGHAI, Aug. 22, 2024 /PRNewswire/ -- YolTech Therapeutics, a pioneering clinical-stage gene editing company dedicated to delivering lifelong cures, today announced a major milestone: the first patient has been dosed with YOLT-203, the company's cutting-edge in vivo genome editing candidate. This marks the commencement of an Investigator-Initiated Trial (IIT) and represents a global first in the application of in vivo gene editing therapies for Primary Hyperoxaluria Type 1 (PH1). YOLT-203 is designed as a single-dose, potentially curative therapy, harnessing the power of YolTech's proprietary YolCas12™ editor. This trial sets a new standard in the field, pushing the boundaries of what gene editing can achieve in treating life-threatening genetic diseases.

Primary hyperoxaluria is a genetic disorder associated with hepatic oxalate overproduction, leading to increased renal oxalate excretion. PH1 as the most commonly diagnosed subtype, is a childhood-onset autosomal recessive disease form caused by AGXT gene mutations and absence or dysfunction of alanine-glyoxylate aminotransferase. Most patients ultimately progress to renal failure and require intensive hemodialysis as a bridge to a dual liver/kidney transplant to resolve the metabolic defect in the liver and replace the terminally damaged kidneys.

YOLT-203, independently developed by YolTech, is powered by YolTech's proprietary YolCas12™ editor, a novel CRISPR/Cas gene editing tool developed through YolTech's metagenomics discovery and protein engineering platform named HEPDONE® (High-Throughput Evolution Platform for Discovery and Optimization of Novel Editors) system. YolCas12™ has demonstrated significantly high gene editing activity in both prokaryotic and eukaryotic systems and has been proven to achieve high-efficiency in vivo editing via LNP-mRNA delivery in mice and non-human primates. YoLT-203 is utilizing YolCas12™ editor to target HAO1 gene, significantly preventing pathogenic protein expression in pre-clinical study, promising to provide effective treatment options for PH1 child and adult patients.

The clinical study of YOLT-203, initiated by investigators, is a single-arm, open-label, dose-escalation clinical trial, aiming to evaluate the safety and tolerability of YOLT-203 in the Chinese population with PH1. 7 subjects are estimated to be enrolled. The first adult subject received the dose on 5th Aug 2024 and the first child patient were treated on 20th Aug 2024. This trial represents a pioneering effort as the first global clinical trial of an in vivo gene editing therapy targeting PH1.

"PH1 is a devastating disease that can lead to life-threatening kidney damage and systemic complications," said Dr. Yuxuan Wu, Founder and CEO of YolTech. "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."

YolTech remains committed to progressing the clinical development of YOLT-203 and working closely with regulatory authorities, healthcare professionals, and patient advocacy groups to further the advancement of gene editing therapies.

About YOLT-203

YOLT-203 is an innovative in vivo gene editing therapy designed using YolTech's proprietary YolCas12™ system, a novel CRISPR/Cas tool developed through the High-Throughput Evolution Platform (HEPDONE®). This therapy is encapsulated within lipid nanoparticles (LNPs) that facilitate targeted delivery to the liver, where it addresses the underlying genetic mutations responsible for primary hyperoxaluria type 1 (PH1). Upon intravenous administration, the LNPs are recognized and internalized by liver cells. 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.

About YOLT-203-101 Study

The YOLT-203-101 trial is a single-arm, open-label, single-dose, dose-escalation clinical study designed to evaluate the safety and tolerability of YOLT-203 in Chinese patients diagnosed with primary hyperoxaluria type 1 (PH1). The study will also preliminarily assess the impact of a single administration of YOLT-203 on plasma oxalate levels, a critical biomarker of therapeutic efficacy in PH1. The trial's dose-escalation phase will involve three dose groups, employing an accelerated titration approach to escalate doses from the starting level to the highest planned dose. Following the one-year main study, participants will enter a long-term follow-up period of fifteen years to monitor the sustained effects and safety of the treatment.

About YolTech

YolTech Therapeutics is a pioneering gene editing company dedicated to developing medicines delivering lifelong cures with serious diseases. YolTech has built a leading high-throughput evolution platform and innovative LNP delivery system. It possesses strong capabilities in novel Cas and base editor discovery and exceptional in-house LNP production capacity for GMP manufacturing, with independent intellectual property rights and core patent protection globally. YolTech's lead pipeline, YOLT-201, became the first LNP-mediated in vivo gene editing drug in China to enter registered clinical development in 2024. The company is also advancing gene editing therapies for familial hypercholesterolemia (FH) and primary hyperoxaluria type 1 (PH1) with promising early clinical results.