YolTech's YOLT-202 Gene Editing Therapy Shows Promising Results in Alpha-1 Antitrypsin Deficiency Trial
核心洞察
YolTech Therapeutics (搜索) reported positive interim data from a first-in-human trial of YOLT-202, an in vivo base editing therapy for Alpha-1 Antitrypsin Deficiency (搜索) (AATD (搜索)).
Single doses of YOLT-202 at 35 mg and 45 mg demonstrated rapid, dose-dependent increases in AAT (搜索) levels, with the 45 mg group reaching normal range (>20 μM) by Week 1.
The therapy showed favorable safety and tolerability with only Grade 1 adverse events, primarily infusion-related reactions and mild, reversible liver enzyme elevations.
YolTech Therapeutics (搜索) announced positive interim results from its first-in-human trial of YOLT-202, an investigational in vivo base editing therapy for Alpha-1 Antitrypsin Deficiency (搜索) (AATD (搜索)). The data demonstrated meaningful increases in AAT (搜索) levels and favorable safety profiles in patients treated with 35 mg and 45 mg doses.
Rapid and Robust Efficacy Results
The open-label, single dose escalation study enrolled two participants with genetically confirmed PiZZ genotype, the most severe form of AATD (搜索) affecting over 95% of patients with the condition. Following administration of YOLT-202, both patients showed rapid, robust and dose-dependent increases in AAT (搜索) levels as early as Week 1.
AAT (搜索) levels in both patients reached above the protective threshold of 11 μM, with the 45 mg dose group achieving normal range levels (>20 μM). The newly produced AAT proteins were both structurally corrected (M-AAT) and functional, with the proportion of corrected M-AAT increasing to >95% in the 45 mg dose group.
"The rapid, robust, and dose-dependent increases in functional AAT (搜索) levels observed in this study—particularly among individuals with the PiZZ genotype—underscore the transformative potential of in vivo base editing as a one-time treatment approach," stated Yuxuan Wu, M.D., Founder and CEO of YolTech Therapeutics (搜索).
Favorable Safety Profile
YOLT-202 demonstrated favorable safety and tolerability with manageable adverse events (AEs). No severe AEs or AEs leading to discontinuation were reported, and all AEs were classified as Grade 1. The most common adverse event was infusion-related reaction (IRR). Elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were asymptomatic, mild and recovered without medication.
Clinical Development and Regulatory Path
The ongoing investigator-initiated trial (NCT07193615) is evaluating single doses administered via intravenous infusion at 35 mg, 45 mg and 55 mg dose levels. YolTech is actively preparing to file an Investigational New Drug (IND) application with the FDA to support global clinical development of YOLT-202 in AATD (搜索).
YOLT-202 has previously been granted Orphan Drug Designation by the U.S. FDA. The therapy utilizes YolTech's proprietary adenine base editor and is engineered to achieve on-target editing with minimal bystander activity.
About the Disease and Treatment Approach
AATD (搜索) is an inherited, genetic, autosomal co-dominant disorder caused by mutations in the SERPINA1 (搜索) gene, with the most frequent deficient variants coming from the Z (Glu342Lys) and S alleles (Glu264Val). The presence of Z alleles results in misfolding and polymerization of the AAT (搜索) protein.
YOLT-202 is an in vivo gene-editing therapy that corrects PiZ mutation to PiM for the treatment of AATD (搜索). Built on YolTech's HEPDONE™ Novel Editor Platform and non-viral LNP technologies, the company is pioneering in vivo gene-editing medicines with the potential for one-time treatment that provides lifelong benefit.