Updated Phase I/II data from Beam Therapeutics' (Nasdaq: BEAM) BEAM-302 program, presented at the European Respiratory Society Congress in Barcelona, show that a single 60 mg dose sustains alpha-1 antitrypsin (AAT) levels above the 11 µM protective threshold for up to 18 months. With a global pivotal cohort now enrolling, the Cambridge, Massachusetts-based company is on a defined path toward a US biologics license application (BLA) under an FDA-aligned accelerated approval pathway.
BEAM-302 is a lipid nanoparticle (LNP)-delivered adenine base editor that makes a single A-to-G correction of the PiZ (E342K) mutation in the SERPINA1 gene in hepatocytes, converting the disease-causing Z allele to the normal M allele. Unlike approved augmentation therapies — which provide exogenous AAT protein weekly by infusion but have no effect on liver pathology — BEAM-302 restores endogenous production of functional M-type AAT while simultaneously reducing the toxic mutant Z-AAT that accumulates in the liver and drives hepatic injury. No approved therapy currently addresses AATD-associated liver disease.
Data presented at the BTX-302-001 Phase I/II trial covered 29 patients from the dose-escalation cohorts as of a June 24, 2026 cutoff. In the 60 mg Part A cohort (lung disease patients), steady-state total AAT reached a mean of 14.4 µM and median of 15.2 µM, up from a baseline mean of 5.0 µM. Part B patients (liver disease, with or without lung involvement) treated at 60 mg achieved a mean of 13.5 µM and median of 13.8 µM from a baseline of 4.7 µM. Both cohorts sustained levels above the protective threshold. Corrected M-AAT comprised 93% of circulating AAT at steady state in both groups, exceeding the approximately 80% M-AAT proportion associated with the MZ carrier genotype — individuals who generally do not develop lung or liver disease in the absence of additional risk factors. Mutant Z-AAT fell by 84% in both the 60 mg Part A and Part B cohorts, with a corresponding reduction in circulating Z-polymers, which have been associated with liver disease severity and amplified lung inflammation. In one patient from the Part A 60 mg cohort, total AAT rose during an upper respiratory tract infection while retaining 95% M-AAT composition — a finding Beam characterized as evidence that corrected AAT remains under normal physiologic inductive control, a property absent from protein replacement therapy.
These data are consistent with topline results announced in March 2026 and presented at the American Thoracic Society conference in May, with the ERS dataset extending follow-up and adding Part B liver disease patients. The safety profile was consistent with LNP-based therapies: infusion-related reactions occurred in 41% of patients and were mild to moderate; ALT/AST elevations were predominantly transient and Grade 1. One Part B patient with underlying AATD-related liver disease experienced transient Grade 3 ALT/AST elevations that resolved without treatment and were not accompanied by bilirubin increases.