FDA Grants YolTech Orphan and Rare Pediatric Status for YOLT-203 in Treating Type 1 Primary Hyperoxaluria

SHANGHAI, Sept. 4, 2024 – YolTech Therapeutics, a company at the forefront of clinical-stage in vivo gene editing, recently announced a significant achievement as the U.S. Food and Drug Administration (FDA) awarded Orphan Drug Designation (ODD) to its innovative gene therapy, YOLT-203, for addressing primary hyperoxaluria type 1 (PH1). Earlier in the month, YOLT-203 also received Rare Pediatric Disease Designation (RPDD) from the FDA. These accolades highlight the potential of YOLT-203 to be a transformative treatment for PH1 and possibly broader primary hyperoxaluria (PH).

Primary hyperoxaluria (PH) is characterized by an overproduction of oxalate in the liver, leading to the formation of kidney stones, progressive kidney damage, and systemic oxalosis. The most prevalent form, primary hyperoxaluria type 1 (PH1), is caused by defects in alanine-glyoxylate aminotransferase (AGT) due to mutations in the AGXT gene. Without effective treatment, many patients progress to end-stage renal disease (ESRD), necessitating dialysis and potentially liver-kidney transplants to address metabolic defects and organ failure.

YOLT-203 presents an innovative and potentially groundbreaking approach to treating PH1. This investigational in vivo gene editing therapy is designed as a one-time treatment aimed at permanently reducing excessive oxalate production. It accomplishes this by targeting and deactivating the HAO1 gene using YolTech's proprietary YolCas12™ system, a novel CRISPR/Cas enzyme. Administered via intravenous infusion, YOLT-203 delivers liver-targeted lipid nanoparticles (LNPs) encapsulating YolCas12 mRNA and guide RNA (gRNA) to target the HAO1 gene effectively.

A historic milestone for YolTech, YOLT-203 is the first in vivo gene editing therapy to undergo a clinical trial for a pediatric rare disease globally. The clinical study began on August 5, 2024, with the first adult patient receiving treatment, followed by the initial pediatric patient on August 20, 2024. Both preclinical and early clinical data have shown promising results, with over 90% reduction in blood oxalate levels and no significant side effects or dose-limiting toxicities reported so far.

The FDA's designations play a crucial role in encouraging the development of treatments for rare diseases. The RPDD program incentivizes the creation of therapies for rare pediatric conditions, offering YolTech the potential to receive a priority review voucher (PRV) should YOLT-203 achieve FDA approval. The ODD program provides further advantages, such as tax credits, exemption from specific FDA fees, and seven years of market exclusivity upon approval.

YolTech Therapeutics is dedicated to pioneering cutting-edge precision genetic medicines. The company's approach combines advanced gene editing technologies with a sophisticated lipid nanoparticle delivery system, creating a platform capable of addressing various serious diseases. YolTech's commitment to excellence is reflected in its development of internal manufacturing capabilities to ensure top-tier quality and scalability. With its lead candidate targeting ATTR, YolTech has achieved a milestone as China's first LNP-mediated in vivo gene editing therapy to enter clinical development. Alongside YOLT-203, the company is also advancing therapies for familial hypercholesterolemia (FH) and PH1, continually pushing the boundaries of what is possible in gene editing.