Prime Medicine, Inc. (Nasdaq: PRME) has announced a preclinical program for alpha-1 antitrypsin deficiency (AATD), expanding its liver-focused gene editing pipeline. The company anticipates filing an investigational new drug (IND) or clinical trial application (CTA) by mid-2026.
“Our AATD program, the second high-value initiative in our liver franchise, demonstrates our strategy of leveraging our universal liver lipid nanoparticle (LNP) and Prime Editing platform for rapid development,” stated Keith Gottesdiener, M.D., President and CEO of Prime Medicine. “We aim to demonstrate Prime Editing’s potential in addressing major genetic liver diseases with our AATD and Wilson’s Disease programs, targeting clinical data in 2027.”
Preclinical in vivo data shows Prime Editing’s potential to correct the E342K (Pi*Z) mutation in the SERPINA1 gene, the primary cause of AATD, restoring wild-type protein and addressing both lung and liver manifestations without off-target edits.
Prime Medicine’s Approach to AATD
The program utilizes a GalNAc-targeted LNP to deliver Prime Editors, correcting the Pi*Z mutation in hepatocytes. In humanized mice, this achieved up to 72% SERPINA1 gene correction, restoring over 95% of serum AAT to the corrected isoform, with M-AAT levels exceeding 20µM, indicating normalization.
Preclinical studies with GalNAc-LNP showed improved potency, safety, and biodistribution compared to other LNPs. Non-human primate studies with surrogate Prime Editors demonstrated over 50% editing with excellent safety and no detectable off-target edits.
Prime Medicine is finalizing lead optimization and plans to file an IND/CTA by mid-2026.
About AATD
AATD is a genetic disorder caused by SERPINA1 gene mutations, leading to low circulating AAT and toxic protein buildup in the liver. This results in lung and liver complications, with no curative treatments available for the approximately 200,000 affected individuals in the U.S. and EU.
About Prime Medicine
Prime Medicine is developing gene editing therapies using its Prime Editing platform. This technology aims to precisely correct genetic mutations across various tissues and diseases. The company’s pipeline focuses on hematology, immunology, oncology, liver, and lung diseases, with plans to expand into other areas.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
