Beam Therapeutics Reports Positive Phase 1/2 Data for BEAM-302 Base Editing Therapy in Alpha-1 Antitrypsin Deficiency

Mar 25, 2026-

Beam Therapeutics has reported updated Phase 1/2 clinical data for BEAM-302, its investigational in vivo base editing therapy designed to treat alpha-1 antitrypsin deficiency (AATD). The company also announced that 60 mg has been selected as the optimal biological dose, with plans to initiate a global pivotal cohort in the second half of 2026 as part of a potential accelerated approval pathway.

BEAM-302 is delivered using a liver-targeting lipid nanoparticle (LNP) system, which transports base editing components directly to liver cells. The therapy is designed to correct the PiZ mutation in the SERPINA1 gene, the most common genetic cause of severe AATD. By correcting this mutation, BEAM-302 enables the liver to produce functional M-type alpha-1 antitrypsin (M-AAT) while reducing the toxic accumulation of Z-AAT, which contributes to both lung and liver disease.

Data from the ongoing Phase 1/2 trial demonstrated strong biological activity following treatment. Patients receiving the 60 mg dose achieved a mean steady-state total AAT level of 16.1 µM, exceeding the 11 µM protective threshold considered necessary to prevent lung damage. Importantly, all treated patients maintained AAT levels above this threshold for up to 12 months of follow-up.

The therapy also produced substantial molecular correction of the disease. After treatment with BEAM-302 at the 60 mg dose, corrected M-AAT accounted for approximately 94% of circulating AAT, while mutant Z-AAT levels were reduced by 84%. These findings indicate effective editing of the underlying mutation and restoration of functional protein production.

Researchers also observed that AAT expression remained physiologically responsive after treatment. During a respiratory infection in one patient, total AAT levels increased from approximately 15.9 µM to 29.5 µM, while maintaining 95% corrected M-AAT composition, demonstrating that the corrected gene retained its natural regulatory behavior.

Safety results were also encouraging. Across 26 patients receiving single doses of BEAM-302, the therapy was generally well tolerated up to 75 mg, with no serious adverse events or dose-limiting toxicities reported as of the February 2026 data cutoff. Observed side effects were primarily mild to moderate infusion-related reactions and transient liver enzyme elevations.

The Phase 1/2 trial is evaluating BEAM-302 in patients with AATD-associated lung disease and liver disease, with 29 patients treated across multiple dose cohorts. Based on the strong efficacy and safety profile observed so far, the 60 mg dose has been selected for further development.

Following discussions with the U.S. Food and Drug Administration, Beam plans to pursue an accelerated approval pathway, using AAT biomarker levels measured over 12 months as the primary endpoint. The company intends to enroll approximately 50 additional patients in the pivotal expansion cohort.

Alpha-1 antitrypsin deficiency is a genetic disorder caused by mutations in the SERPINA1 gene, leading to reduced levels of functional AAT protein. This deficiency can result in progressive lung disease such as emphysema and serious liver disease, often requiring lifelong management or organ transplantation. Current treatments primarily rely on protein augmentation therapy, which does not address the underlying genetic defect.

BEAM-302 represents a different therapeutic strategy by directly correcting the disease-causing mutation in the patient’s DNA. Unlike many gene therapies that rely on viral vectors such as AAV to deliver therapeutic genes, BEAM-302 uses LNP-mediated delivery of base editing machinery to repair the gene in its natural genomic location.

If successful in later-stage trials, BEAM-302 could become a first-in-class one-time genetic medicine for AATD, offering the potential to correct the root cause of the disease and restore long-term physiological production of functional AAT.