Beam Therapeutics reported updated clinical data from its ongoing Phase I/II trial of BEAM-302 in alpha-1 antitrypsin deficiency, showing that a single 60 mg dose produced mean steady-state total AAT levels of 16.1 µM, with all patients in the cohort sustained above the 11 µM protective threshold across follow-up ranging from five to twelve months. The Cambridge, Massachusetts-based company said the data, drawn from 29 treated patients as of a February 10, 2026 cutoff, support its selection of 60 mg as the dose to carry into a pivotal cohort it expects to initiate in the second half of 2026, according to a press release.
Across single-dose cohorts, corrected M-AAT comprised 94% of total circulating AAT in the 60 mg group and 91% in the 75 mg group, with concomitant mean reductions in mutant Z-AAT of 84% and 79%, respectively. A three-patient multi-dose cohort receiving two 60 mg doses reached a mean total AAT of 16.5 µM at Day 84. In one patient from the 60 mg cohort, total AAT rose from a steady-state level of 15.9 µM to 29.5 µM during a respiratory infection at approximately eight months, while maintaining 95% M-AAT composition, which the company characterized as evidence of physiologic inducibility. Safety data from 26 single-dose patients showed adverse events that were mild to moderate, with no serious adverse events or dose-limiting toxicities reported. Transient Grade 1 and Grade 2 infusion-related reactions and Grade 1 asymptomatic ALT and AST elevations were observed. In the multi-dose cohort, one patient experienced Grade 4 ALT and Grade 3 AST elevations, described as asymptomatic and not requiring treatment. No bilirubin increases were reported in any patient.
The Phase I/II trial is an open-label, dose-exploration and dose-expansion study evaluating BEAM-302 at doses from 15 mg to 75 mg in patients with AATD-associated lung disease (Part A) and those with mild to severe liver disease with or without lung involvement (Part B). Cohort sizes were small, ranging from two to nine patients per dose level, and follow-up durations varied from two to eighteen months. No placebo or active comparator arm is included. The company stated that Part B patients treated at 30 mg and 60 mg showed efficacy consistent with Part A, though only five patients were enrolled in Part B at the cutoff. Beam disclosed that the US FDA has provided feedback supporting an accelerated approval pathway based on AAT biomarker endpoints evaluated over twelve months, with approximately 50 additional patients planned for the pivotal expansion. The data remain interim and are based on a small, open-label dataset without a control group, and no clinical outcome endpoints such as lung function or liver histology were reported.
BEAM-302 is a lipid-nanoparticle-delivered base editing therapy designed to correct the PiZ point mutation in the SERPINA1 gene, converting it to the wild-type M allele in hepatocytes. The only currently approved treatment class for AATD-associated lung disease is augmentation therapy, which provides exogenous AAT protein through regular intravenous infusions but does not address the underlying genetic defect or liver pathology. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.
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