YolTech Therapeutics Receives FDA Clearance for Phase 2/3 Study of YOLT-202 in AATD

YolTech Therapeutics announced that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application for YOLT-202, the company's investigational in vivo base-editing therapy for the treatment of Alpha-1 Antitrypsin Deficiency (AATD). The FDA approval enables the initiation of an open-label, single-dose expansion Phase 2/3 clinical study to evaluate the efficacy and safety of YOLT-202 in adult patients with AATD.

The study is designed as a multiregional clinical trial (MRCT) to be conducted at clinical sites in the U.S. and other countries. YolTech Therapeutics is a late clinical-stage biotechnology company developing in vivo gene-editing therapies.

YOLT-202 is currently being investigated in a first-in-human investigator-initiated trial (IIT) (NCT07193615) designed to evaluate the safety, tolerability, and preliminary efficacy of YOLT-202 in patients with AATD. As of the date of the announcement, two patients had been enrolled and completed dose. Following administration of YOLT-202, both patients showed rapid, robust and dose-dependent increases in AAT level as early as in Week 1.

AAT levels in both patients reached above the protective threshold of 11 μM. Additionally, AAT levels increased to normal range (>20 μM) in the 45 mg dose group. These 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.

As of February 6th, two participants genetically confirmed as PiZZ genotype were enrolled and dosed with YOLT-202 in both the 35 mg and 45 mg dose groups. YOLT-202 demonstrated favorable safety and tolerability with manageable adverse events (AEs). No severe AEs or AEs leading to discontinuation of YOLT-202 were reported, and all AEs were classified as Grade 1. The most common AE was infusion-related reaction (IRR). Elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were asymptomatic, mild and soon recovered without medication.

The ongoing IIT study is evaluating single doses administered via intravenous infusion of YOLT-202 at 35 mg, 45 mg and 55 mg dose levels.

YOLT-202 is an in vivo gene-editing therapy that corrects PiZ mutation to PiM for the treatment of AATD. Utilizing YolTech's proprietary adenine base editor, YOLT-202 is engineered to achieve on-target editing with minimal bystander activity. YOLT-202 has previously been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA).

AATD is an inherited, genetic, autosomal co-dominant disorder caused by mutations in the SERPINA1 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, leading to over 95% of severe AATD patients being PIZZ.

Built on HEPDONE™ Novel Editor Platform and non-viral LNP technologies, YolTech Therapeutics is advancing in vivo gene-editing medicines with the potential for a one-time treatment that provides lifelong benefit. The company's expanding clinical pipeline addresses genetic, metabolic, cardiovascular, and autoimmune diseases.