Beam Therapeutics Inc. reported new preclinical data demonstrating the ability of its in vivo drug candidate, BEAM-302, to directly correct the PiZ mutation, the primary disease-causing mutation associated with severe alpha-1 antitrypsin deficiency (AATD). The data are featured in an oral presentation titled "BEAM-302: Targeting AATD Liver and Lung Disease with Base editing" at the Alpha-1 Antitrypsin Deficiency 2023 Meeting in Naples, Italy. BEAM-302 was evaluated in two preclinical species: an NSG-PiZ mouse model of AATD carrying multiple copies of the human PiZ allele and a novel humanized PiZ rat model developed by Beam scientists in which the normal rat AAT is replaced with human mutated PiZ AAT.

Treatment with a single dose of BEAM-302 induced dose-dependent correction of the PiZ mutation. Clinically relevant doses up to 1mpk resulted in correction of up to 39% and 49% of liver DNA in rats and mice, respectively. These findings support the potential of BEAM-302 to efficiently correct the disease-causal PiZ mutation after a single dose and potentially address both the liver and lung disease associated with AATD.

Beam plans to submit a regulatory application for authorization to initiate clinical trials of BEAM-302 in the first quarter of 2024.