Beam Therapeutics (BEAM) Study result summary

Study design and objectives

• BEAM-302 is a base editing therapy targeting the E342K (PiZ) mutation in AATD, aiming for a one-time, curative treatment addressing both lung and liver manifestations.

• Phase 1/2 open-label trial included dose escalation from 15 mg to 75 mg, with single and multi-dose cohorts in patients with AATD-associated lung and/or liver disease.

• 29 patients were treated with up to 18 months of follow-up.

• Primary goals were to assess safety, efficacy, and identify the optimal dose for pivotal studies.

Key efficacy results

• Single 60 mg dose achieved durable total AAT levels (>11 μM) in all patients, with a mean of 16.1 μM, exceeding the protective threshold for lung health for up to 12 months.

• Mutant Z-AAT reduced by 84%, and newly produced M-AAT comprised 94% of total AAT, indicating effective correction.

• Functional AAT increase confirmed by neutrophil elastase inhibition assay; efficacy trends were consistent in both lung and liver disease patients.

• AAT levels were inducible during inflammation or infection, with one patient reaching up to 29.5–30 μM and maintaining ~95% M-AAT.

Safety profile

• BEAM-302 was well tolerated up to 75 mg, with no serious adverse events or dose-limiting toxicities in 26–29 patients.

• Most adverse events were mild to moderate, including transient Grade 1 transaminase elevations and infusion-related reactions that resolved quickly.

• Multi-dose cohorts experienced higher transaminase increases post-second dose, all asymptomatic and resolved without treatment; no liver dysfunction or bilirubin increases observed.