Beam Therapeutics (BEAM) European Respiratory Society Congress presentation summary

Background and rationale

• Alpha-1 antitrypsin deficiency (AATD) is caused by a single G-to-A mutation in the SERPINA1 gene, leading to progressive lung and liver disease due to low and dysfunctional AAT levels and Z-AAT aggregation.

• BEAM-302 is designed as a one-time gene editing treatment to correct the DNA mutation, restore normal AAT production, and address both lung and liver manifestations of AATD.

Study design and methods

• Phase 1/2 study enrolled adults with AATD-associated lung and/or liver disease, divided into Part A (lung disease) and Part B (liver disease with/without lung involvement).

• Doses ranged from 15 mg to 75 mg in Part A and 30 mg to 60 mg in Part B, with key endpoints including safety, AAT levels, and functional outcomes.

• Participants were homozygous for the PIZZ mutation, with a mean baseline blood AAT level of 4.8 μM and clinical diagnosis of emphysema or liver disease.

Safety and tolerability

• Safety profile was consistent with lipid nanoparticle (LNP)-based therapies, with most treatment-emergent adverse events (TEAEs) being mild or moderate.

• No serious TEAEs related to BEAM-302 were observed; transient Grade 1 transaminase elevations and mild-to-moderate infusion-related reactions were most common.