Beam Therapeutics Updates Safety and Efficacy Data for BEAM-302

Beam Therapeutics announced updated safety and efficacy data from the ongoing Phase 1/2 trial of BEAM-302 and the selection of 60 mg as the optimal biological dose to advance into pivotal development to support potential accelerated approval. BEAM-302 is a liver-targeting lipid-nanoparticle formulation designed to directly correct the underlying genetic mutation that causes the severe form of alpha-1 antitrypsin deficiency through base editing. BEAM-302 is being evaluated in a Phase 1/2, open-label, dose exploration and dose expansion clinical trial to investigate its safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy. Part A of the trial is designed to evaluate patients with AATD-associated lung disease, while Part B evaluates patients with mild to severe liver disease, with or without lung disease. As of the February 10data cutoff date, 29 patients have been treated with BEAM-302 in Part A and Part B and followed for up to 18 months. Data from 26 patients treated with single-dose BEAM-302 support a well-tolerated safety profile up to 75 mg that is consistent across Part A and Part B. Adverse events were mild to moderate, with no serious AEs reported and no dose-limiting toxicities as of the data cutoff. Transient Grade 1 and Grade 2 infusion-related reactions and Grade 1 asymptomatic alanine transaminase and aspartate aminotransferase elevations were observed. In the multi-dose cohort, following the second dose of BEAM-302, patients experienced Grade 2 IRRs, one patient had Grade 4 ALT and Grade 3 AST elevations, and one patient had a Grade 2 ALT elevation. All ALT/AST elevations were asymptomatic and did not require treatment. No bilirubin increases were observed in any patient. Treatment with BEAM-302 led to rapid and durable increases of total and functional AAT, decreases in mutant Z-AAT, and new production of corrected M-AAT. Key data from 28 efficacy evaluable patients1 include the following: After treatment with a single dose of BEAM-302 in Part A, the steady-state circulating total AAT mean was 16.1 microM in the 60 mg cohort and 14.4 microM in the 75 mg cohort. In the multi-dose cohort, patients achieved a mean of 16.5 microM total AAT at Day 84, 28 days after the second 60 mg dose. These early data suggest a single dose of 60 mg BEAM-302 has achieved near saturation editing. Across all cohorts, increased total AAT in circulation was functional as demonstrated by a neutrophil elastase inhibition assay. Mutant Z-AAT was durably and significantly reduced after treatment with BEAM-302. The steady-state mean reduction in Z-AAT was 84% in the 60 mg cohort and 79% in the 75 mg cohort. In the multi-dose cohort, the mean reduction in Z-AAT was 80% at Day 84. Evidence of dynamic induction of AAT expression was observed during a respiratory infection around Month 8 in a patient in the 60 mg Part A cohort. During the infection, total AAT levels increased from steady-state levels of 15.9 microM to 29.5 microM while maintaining consistent AAT composition of 95% M-AAT. Following treatment with BEAM-302, newly produced corrected M-AAT comprised the majority of AAT in circulation. The steady-state mean proportion of M-AAT was 94% in the 60 mg cohort and 91% in the 75 mg cohort. In the multi-dose cohort, the mean proportion of M-AAT was 93% at Day 84. In Part B patients with AATD-associated liver disease, single doses of 30 mg and 60 mg BEAM-302 demonstrated consistent efficacy comparable to results observed in Part A patients without liver disease. Based on feedback from the FDA, Beam intends to pursue an accelerated approval pathway for BEAM-302 based on a primary endpoint of AAT biomarkers evaluated over 12 months, with 60 mg as the selected dose. To support a future biologics licensing application submission, the company anticipates enrolling approximately 50 additional patients with AATD-associated lung disease, with or without liver disease, in an expansion of the ongoing open-label Phase 1/2 trial. Beam expects to initiate the pivotal cohort in the second half of 2026, leveraging its existing global clinical trial network.