ZUG, Switzerland and BOSTON — October 10, 2025 — Leads & Copy — CRISPR Therapeutics (Nasdaq: CRSP) presented new preclinical data at the European Society of Gene and Cell Therapy (ESGCT) 2025 Annual Congress regarding its SyNTase™ gene editing platform for Alpha-1 Antitrypsin Deficiency (AATD). The AATD program, CTX460™, is the first investigational candidate to use SyNTase editing and is expected to enter the clinic in mid-2026.
According to Naimish Patel, M.D., Chief Medical Officer of CRISPR Therapeutics, current treatments for Alpha-1 antitrypsin deficiency do not address the underlying genetic cause, and the goal of therapy should be to normalize alpha-1 antitrypsin levels. Patel added that the preclinical results demonstrate the potential of CTX460 to correct the mutation with precision and efficiency, supporting its potential best-in-class profile in AATD.
CTX460 targets the E342K mutation in SERPINA1 and is encapsulated in a lipid nanoparticle (LNP). Preclinical data evaluated CTX460 in NSG-PiZ mouse model and a humanized PiZ rat model, assessing gene and mRNA correction, serum protein levels, and durability of effect following a single dose. A single dose of CTX460 achieved significant, dose-dependent correction of liver DNA in both rat and mouse AATD models, with near saturating editing in hepatocytes at doses as low as 0.1 mg/kg. Furthermore, a single dose of CTX460 was able to achieve >90% mRNA correction at a clinically relevant dose of 0.5 mg/kg in PiZ mice.
Editing with CTX460 yielded a >5-fold increase in total serum AAT levels with an M-AAT:Z-AAT ratio of over 99% in the serum of PiZ rats. AAT upregulation was linearly correlated with editing efficiency, and durability of editing was maintained in both rat and mouse models for up to 7 weeks and 9 weeks, respectively.
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Source: CRISPR Therapeutics
