Core Insights - CRISPR Therapeutics presented promising preclinical data for CTX460, a novel gene editing candidate for Alpha-1 Antitrypsin Deficiency (AATD), at the ESGCT 2025 Annual Congress, indicating a potential best-in-class profile [1][2][6] - The company plans to initiate clinical trials for CTX460 in mid-2026, marking a significant advancement in gene-based therapies for AATD [1][2] Preclinical Data Highlights - CTX460 demonstrated over 90% mRNA correction and a 5-fold increase in total AAT levels in AATD disease models, with a serum M-AAT:Z-AAT ratio exceeding 99% [1][5] - A single dose of CTX460 achieved significant liver DNA correction in both rat and mouse models, with effective editing observed at doses as low as 0.1 mg/kg [5] - The durability of the editing effect was maintained for up to 7 weeks in rats and 9 weeks in mice, supporting the long-term efficacy of the treatment [5] AATD Background - AATD is primarily caused by a mutation in the SERPINA1 gene, leading to insufficient functional AAT levels, which increases the risk of lung diseases such as emphysema [2][3] - Current treatments do not address the genetic cause of AATD, highlighting the need for innovative therapies that can normalize AAT levels [3][4] SyNTase Editing Platform - CTX460 utilizes the SyNTase editing platform, encapsulated in a proprietary lipid nanoparticle, targeting the E342K mutation in SERPINA1 [4][6] - The preclinical models used for evaluation included the NSG-PiZ mouse model and a humanized PiZ rat model, demonstrating the platform's potential for gene correction [4][6] Company Overview - CRISPR Therapeutics has evolved into a leader in gene editing, with a diverse portfolio across various disease areas, including hemoglobinopathies and rare diseases [7] - The company has made significant strides in advancing CRISPR technology, including the approval of the first CRISPR-based therapy, CASGEVY, for sickle cell disease and beta thalassemia [7]