PM647

Sept. 24, 2026: Prime Medicine, Inc. (NASDAQ: PRME) said the FDA cleared the IND for PM647, an investigational in vivo Prime Editor for Alpha-1 Antitrypsin Deficiency (AATD), enabling a Phase 1/2 clinical study to begin initially in the U.S.

PM647 is designed to correct the E342K (Pi*Z) mutation in the SERPINA1 gene, the most common cause of AATD, with the goal of restoring functional M-AAT and addressing both lung and liver disease manifestations. The planned Phase 1/2 trial is a global, single-arm, open-label, first-in-human dose-escalation study of a one-time intravenous infusion in adults with AATD. It will first enroll patients with lung-only manifestations, then expand to a separate cohort with significant liver disease, with or without lung involvement, after tolerability is shown.

The company said initial clinical data are expected in 2027. Preclinically, in fully humanized mouse models, PM647 reportedly achieved high editing efficiency and restored corrected M-AAT protein into the healthy human range at clinically relevant doses after a single infusion.

The release also notes PM647 uses the same liver-directed LNP as PM577a, Prime Medicine’s investigational Wilson disease program, and follows recent regulatory clearances for PM577a.