One-Time AATD Treatment Shows Lasting Results Up to 18 Months

A one-time treatment designed to fix the genetic error behind alpha-1 antitrypsin deficiency (AATD) produced lasting increases in protective protein levels, according to updated clinical trial data presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain.

The investigational therapy, BEAM-302, uses a technology called base editing to correct a single “letter” in a person’s DNA. The new results include up to 18 months of follow-up and suggest the correction holds over time.

A Single Gene Error Behind Lung and Liver Damage

AATD is an inherited condition that can cause early-onset emphysema and liver disease. The most common severe form happens when a person inherits two copies of a mutation called the Z allele, known as the PiZZ genotype.

In people with this genotype, the liver makes a misfolded version of the AAT protein. Instead of being released into the bloodstream, much of it gets stuck inside liver cells. As a result, circulating AAT levels fall to just 10% to 15% of normal.

AAT’s main job is to protect the lungs from neutrophil elastase, an enzyme released during inflammation. Without enough AAT, that enzyme can gradually damage lung tissue, sometimes leading to the need for a lung transplant. Meanwhile, the trapped protein can inflame and scar the liver, which can lead to cirrhosis, liver failure or liver cancer.

More than 100,000 people in the United States are estimated to have the PiZZ genotype, but only about 10% are thought to have been diagnosed. Augmentation therapy, which delivers AAT protein through regular infusions, is approved for AATD-related lung disease. However, there are currently no curative treatments.

Protein Levels Climbed Past the Protective Threshold

The Phase 1/2 trial includes two groups: people with AATD-related lung disease and people with mild to severe liver disease, with or without lung disease. The ERS presentation included 29 patients who received a single dose of the treatment.

At the selected 60-mg dose, average total AAT in the lung disease group rose to 14.4 micromolar, up from 5.0 at baseline. In the liver disease group, it rose to 13.5 micromolar from 4.7. Both results exceed the 11-micromolar level considered protective.

The added protein also appeared to work as intended. Levels of functional AAT rose with higher doses, and activity of neutrophil elastase dropped. More than 80% of patients in the 60-mg lung disease group had at least one elastase measurement too low to detect.

Mutant Protein and Toxic Clumps Dropped

Treatment reduced circulating mutant Z-AAT by 84% in both 60-mg groups. It also lowered Z-polymers, clumps of the mutant protein that have been linked to more severe liver disease and to increased lung inflammation.

After treatment, 93% of the AAT in circulation was the corrected, normal form. That is higher than the roughly 80% seen in people who carry only one Z allele.

“These data reinforce the potential of BEAM-302 to address AATD at its root cause by correcting the disease-causing mutation and restoring production of functional AAT needed to prevent lung and liver damage with a single treatment,” said Amy Simon, M.D., chief medical officer of Beam Therapeutics.

Responding to Infection the Way a Healthy Body Does

In healthy people, the liver ramps up AAT production during infection or inflammation, when the lungs need extra protection. One patient in the 60-mg lung disease group showed this same natural rise during an upper respiratory infection.

This matters because current augmentation therapy delivers a set amount of protein and does not adjust to the body’s changing needs.

Side Effects Were Mostly Mild

The most common treatment-related side effect was a mild to moderate infusion reaction, which occurred in 41% of patients. Some patients had temporary, mostly mild increases in liver enzymes. One patient with existing AATD-related liver disease had a more significant temporary increase in liver enzymes, which resolved without treatment.

Next Steps Toward Possible Approval

Based on feedback from the U.S. Food and Drug Administration, Beam plans to seek accelerated approval based on AAT blood measurements over 12 months. The company began dosing a pivotal group of about 50 additional patients in July.

These results are early. The trial is small and open-label, meaning everyone knew they were receiving the treatment. It also did not include a comparison group, and it has not yet shown effects on lung function or long-term health outcomes. BEAM-302 is not approved, so people living with AATD should continue working with their care team on current treatment options.