Beam looks to accelerated approval for AATD base editing after promising update

For people living with alpha-1 antitrypsin deficiency, the disease is a slow-motion double insult: the lungs erode without protection, and the liver accumulates a misfolded protein it cannot clear. Weekly intravenous infusions of replacement protein have been the standard for decades. There is no cure. Beam Therapeutics thinks it has one — and the FDA apparently agrees enough to talk about accelerated approval.

Beam reported updated Phase 1/2 data on March 25 for BEAM-302, its base editing therapy for AATD, and selected 60 milligrams as the go-forward dose for a pivotal cohort expected to open in the second half of 2026 with approximately 50 additional patients. The data, from 29 patients treated as of a February 10 cutoff, showed mean steady-state total AAT of 16.1 micromolar at the 60 mg dose — comfortably above the 11 micromolar threshold considered protective. At that same dose, corrected M-AAT made up 94 percent of circulating AAT, and the toxic mutant Z-AAT was reduced by 84 percent. No serious adverse events were reported in single-dose cohorts. The FDA has already aligned with Beam on an accelerated approval pathway using 12-month AAT biomarkers as the primary endpoint, according to the company press release published that morning.

The most striking data point does not appear in the headline. Around month eight, a patient in the 60 mg cohort contracted a respiratory infection — the kind of inflammatory stressor that would send an untreated AATD patient spiraling. Their total AAT rose from a steady-state 15.9 micromolar to 29.5 micromolar. The composition held: 95 percent corrected M-AAT throughout. In other words, the edited liver responded like a normal gene, not a protein factory. The current standard of care — weekly plasma-derived AAT — cannot do this. It delivers a fixed dose that does not vary with the body's needs.

"By enabling the liver to produce corrected M-AAT for the first time while reducing the toxic mutant protein, this approach has the potential to fundamentally transform how we as clinicians treat AATD," said Jeffrey Teckman, a professor of pediatrics at Saint Louis University School of Medicine, in the company's announcement. Teckman has studied AATD for decades.

AATD is caused by a single point mutation — the PiZ variant — in the SERPINA1 gene. Patients who inherit two copies (the PiZZ genotype) produce a misfolded protein that accumulates in liver cells rather than secreting into the bloodstream, leaving the lungs undefended against neutrophil elastase. The same protein clogs the liver, sometimes leading to cirrhosis and the need for transplant. Beam's adenine base editor makes a single-letter correction at the mutation site, aiming to restore the normal M-AAT protein while eliminating production of the mutant at its source.

More than 100,000 individuals in the United States carry the PiZZ genotype, though only about 10 percent of all patients are thought to be diagnosed. That diagnostic gap is both a clinical problem and a commercial one: a therapy that requires identifying patients before they develop advanced disease faces a market that is largely unaware it exists.

The competitive picture adds texture. Wave Life Sciences is developing WVE-006, an RNA editing approach to the same mutation, and reported first-in-human data from its RestorAATion-2 trial late last year. Wave expects FDA regulatory feedback on a potential accelerated approval pathway by mid-2026, according to a company announcement. The two programs are pursuing the same indication by different routes — Wave edits the messenger RNA, Beam edits the DNA — and the comparative durability and off-target profiles will matter enormously if both reach review.

Investors did not initially reward the update. Beam shares fell 4.85 percent on March 25 despite the data, StockTitan reported, underperforming the historical average 24-hour move of negative 1.86 percent for Beam clinical updates. The reaction may reflect the usual dilution risk of a pivotal-stage biotech, or skepticism about enrollment speed in a disease where most patients do not know they have it. It may also simply be wrong.

If the pivotal cohort reads out cleanly — and that is the open question — this would be the first base editing therapy to reach approval for any genetic disease. That is not a small thing. It would also mean, for the first time, that the 90 percent of undiagnosed PiZZ patients have a reason to get tested.