Beam Therapeutics (BEAM) Study result summary

Study design and objectives

• Phase 1/2 trial of BEAM-302 included 29 patients with AATD-associated lung and/or liver disease, evaluating single and multi-dose cohorts from 15 mg to 75 mg, with up to 18 months of follow-up.

• The study aimed to assess safety, efficacy, and dose selection, focusing on achieving protective AAT levels and reducing mutant Z-AAT.

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

• The trial included both patients with lung disease and those with mild to moderate liver disease.

• The optimal biological dose was determined for pivotal development.

Key efficacy results

• Single 60 mg dose led to 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 84%, and corrected M-AAT comprised 94% of total AAT at 60 mg, exceeding levels seen in MZ carriers.

• Functional AAT increase was confirmed by neutrophil elastase inhibition assay; efficacy was consistent across patients with and without liver disease.

• AAT production was inducible during inflammation, with one patient reaching up to 30 μM and maintaining ~95% M-AAT.

• Multi-dose cohorts showed similar efficacy to single-dose cohorts.

Safety profile

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

• Most adverse events were mild to moderate, including transient Grade 1 ALT/AST elevations and infusion reactions, all resolving without intervention.

• Multi-dose cohorts showed higher rates of transient liver enzyme elevations after the second dose, all asymptomatic and not requiring treatment.

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

• Safety and efficacy were consistent across patient subgroups.