After GSK’s return of Wave Life Sciences’ WVE-006 as well as the mid-stage failure of Korro Bio’s candidate, the alpha-1 antitrypsin deficiency landscape is coming into focus, with Wave and Beam Therapeutics leading the way.
A burst of bad news in the alpha-1 antitrypsin deficiency space belies a still-competitive clinical race. While Korro Bio’s lead asset flopped in AATD in November, sending the young biotech back to the drawing board, and GSK handed back an AATD asset to Wave Life Sciences, the first approval for the genetic disease could still come as early as next year.
Currently worth $2.6 billion, the AATD treatment market is expected to reach $6.2 billion by 2032. There are no FDA-approved drugs for the disease, which is caused by a duplicate copy of the SERPINA1 gene that makes an abnormal type of the alpha-1 protein, leading to low levels of alpha-1 antitrypsin (AAT) and ultimately lung and liver damage. Intravenous augmentation therapies aim to slow the destruction of the lungs.
Despite the somewhat niche indication, there are several companies—including Wave, Korro and Beam Therapeutics—vying to bring the first disease-modifying drug to the market for AATD.
AATD Contenders
The Phase I/IIa failure of Korro’s KRRO-110 in AATD was catastrophic for the company. Shares fell by just under 80% after the asset, an RNA-editing oligonucleotide, failed to produce adequate levels of functional M-AAT protein.
Korro’s misfortune may be Wave’s gain.
“We like the AATD program where WVE-006’s profile continues to look strong in a relatively white space given [the] recent setback by Korro,” Truist analysts wrote in a Monday note to investors.
Indeed, GSK may have walked away from WVE-006, also an RNA-editing oligonucleotide, but Wave will continue on alone. On Monday, the biotech stated that it plans to engage with the agency on an accelerated pathway for the asset, with feedback expected in mid-2026.
Although a mid-stage readout in September underwhelmed analysts, Truist Securities analysts said Monday that “there should not be any read-through [of GSK’s exit] to forthcoming AATD data.” Data from a 400-mg multidose cohort are expected this quarter, with results from a 600-mg single dose and from multidose cohorts coming later this year.
A key competitor for Wave is Beam, which Truist noted is in late-stage development with its base editing treatment BEAM-302. Using total serum AAT as an endpoint, the biotech is on a path to FDA accelerated approval, Beam revealed in a Jan. 11 business update.
H.C. Wainwright was positive regarding Beam’s path to the market. “We believe this defined regulatory path for BEAM-302 significantly de-risks development,” they wrote on Jan 14.
In March 2025 in a Phase I/II study, BEAM-302 achieved the “first ever” genetic correction in AATD. William Blair said at the time that the asset “has set the bar for efficacy in this space.”
Also developing a gene editor for AATD is Tessera Therapeutics, which in December announced an up to $275 million global pact with Regeneron to advance the program.
The asset, TSRA-196, which is designed to be a one-time therapy that restores the production of functional AAT, has just begun Phase I trials, according to Truist. Under the Regeneron partnership, Tessera is taking the lead on this first-human-trial, while the larger company will be responsible for subsequent global development and collaboration.
The Truist group said there is room in the AATD market for multiple victors. “Given very different modality, we think there’s room for both genome editing and RNA editing,” the analysts wrote Monday. “However, we think RNA editing may offer a more ‘drug-like’ profile,” giving it more commercial traction.
And Wave, Beam and Tessera are not the only biotechs in the broader AATD space. With Takeda as a partner, Arrowhead Pharmaceuticals is currently ensconced in a Phase III trial is fazirsiran, an RNA interference (RNAi) therapy for AATD-associated liver disease. The trial, which began in 2023, is expected to wrap up in February 2028.
The implications for success in AATD go beyond the unmet need. Last May, William Blair analyst Sami Corwin told BioSpace the disease is one of three indications in which base editing has been derisked; the others, she said, are sickle cell disease (SCD) and familial hypercholesterolemia.
Beam, which owns the intellectual property behind base editing, also has programs in development for SCD and beta-thalassemia. With Beam coming to terms with the FDA on a path to accelerated approval, could an approval in AATD pave the way for more base-editing therapies to come?
