Cambridge, Massachusetts-based Prime Medicine, Inc. (Nasdaq: PRME) received US FDA clearance to begin first-in-human testing of PM647, a one-time in vivo prime editing therapy designed to correct the genetic defect underlying alpha-1 antitrypsin deficiency (AATD). Initial clinical data are expected in 2027.
Why it matters: Current augmentation therapies for AATD require regular lifelong infusions and do not correct the underlying genetic defect or address toxic accumulation of mutant alpha-1 antitrypsin in the liver. PM647 is designed to make a permanent correction to the disease-causing SERPINA1 mutation, potentially addressing both the lung and liver manifestations of the disease with a single treatment.
PM647 uses liver-directed lipid nanoparticles to deliver a prime editor that corrects the E342K, or PiZ, mutation in hepatocytes, restoring production of functional M-type alpha-1 antitrypsin. In humanized mouse models, Prime said a single infusion produced high editing efficiency and restored corrected protein to levels within the healthy human range.
The Phase I/II trial will initially enroll adults with AATD-associated lung disease before expanding to patients with significant liver disease, with or without lung involvement. The study will evaluate ascending doses of a single intravenous infusion of PM647 for safety, tolerability, and preliminary efficacy.