Beam Therapeutics (BEAM) Study result summary

Study design and objectives

• Phase I/II trial of BEAM-302 in AATD included 29 patients across dose cohorts and disease spectrums, with single and multi-dose regimens and up to 18 months of follow-up.

• The study aimed to assess safety, efficacy, and dose selection, focusing on durable correction of the PiZ (E342K) mutation and restoring functional AAT above the protective threshold.

• Both patients with lung disease and those with mild to moderate liver disease were included.

• Primary goals included identifying the optimal dose for pivotal studies and evaluating efficacy endpoints such as total and functional AAT, reduction in mutant Z-AAT, and restoration of M-AAT production.

• Doses ranged from 15 mg to 75 mg, with dose escalation in both Part A (lung) and Part B (liver) cohorts.

Key efficacy results

• Single 60 mg dose achieved mean steady-state total AAT of 16.1 μM, with all patients above the 11 μM protective threshold for up to 12 months.

• Mutant Z-AAT was reduced by 80-86%, and newly produced M-AAT comprised 91-95% of total AAT, indicating effective correction.

• Efficacy was consistent in patients with and without liver disease, and multi-dose cohorts showed similar results to single-dose cohorts.

• AAT levels were inducible during inflammation, with one patient reaching up to 30 μM and maintaining 94-95% M-AAT during infection.

• Functional AAT increase was confirmed by neutrophil elastase inhibition assay.

Safety profile

• BEAM-302 was well-tolerated at single doses up to 75 mg, with no serious adverse events or dose-limiting toxicities in up to 29 patients.

• Most adverse events were mild to moderate, including transient elevations in liver enzymes and infusion-related reactions that resolved quickly.

• Multi-dose cohorts experienced higher rates of transient liver enzyme elevations after the second dose, all resolving without intervention or treatment.

• No clinical signs of liver dysfunction or bilirubin increases were observed.

• Safety and efficacy were consistent across patient subgroups.