Prime Medicine said the U.S. Food and Drug Administration cleared its Investigational New Drug application for PM647, an investigational in vivo Prime Editor for Alpha-1 Antitrypsin Deficiency (AATD). The clearance allows a global, single-arm, open-label, first-in-human Phase 1/2 study to begin in the U.S. The trial will evaluate the safety, tolerability and initial clinical efficacy of ascending doses delivered through a one-time intravenous infusion. It will initially enroll adults with lung manifestations of AATD, then add a separate cohort of adults with significant liver disease after tolerability is established. PM647 is designed to correct the E342K (Pi*Z) mutation in the SERPINA1 gene, which causes the PiZZ form of AATD, and restore functional M-AAT production. The PiZZ genotype affects roughly 100,000 people in the U.S. and an estimated 200,000 across the U.S. and Europe. In fully humanized mouse models, a single infusion at clinically relevant doses restored corrected M-AAT protein levels to a healthy human range. Prime Medicine shares were down 6.19% at $2.88 at the time of publication Friday, according to Benzinga Pro data.