New clinical trial results indicate that Beam Therapeutics’ innovative base editing treatment shows promise in treating alpha-1 antitrypsin deficiency (AATD), a rare genetic disorder affecting the lungs and liver. The preliminary data, derived from nine patients in an early-stage study, demonstrates the therapy’s ability to correct the underlying genetic mutation responsible for the condition.
The experimental treatment, BEAM-302, employs a refined CRISPR gene editing approach that precisely modifies individual DNA letters. In this case, the therapy targets the SERPINA1 gene variant by replacing a “G” with an “A,” addressing the root cause of severe AATD. The treatment is administered intravenously using lipid nanoparticles that deliver the editing machinery to the liver.
Initial findings reveal encouraging outcomes across three ascending dose levels. One month post-treatment, researchers observed total AAT protein increases ranging from 1.6 to 2.8 times above baseline levels. Notably, patients showed decreased levels of misfolded protein circulation, suggesting successful production of properly formed AAT protein.
Particularly promising results emerged from the highest dose group, where one patient exhibited a 78% reduction in circulating misfolded protein after one month. The three patients receiving this dose achieved average AAT protein levels of 12.4 micromolars, surpassing the protective threshold typically seen in AATD carriers.
AATD’s harmful effects stem from a misfolded AAT protein produced by the mutated SERPINA1 gene. Under normal circumstances, this protein travels from liver cells to the lungs, protecting tissue from neutrophil elastase, an enzyme released during immune responses. The misfolded protein, however, accumulates in liver cells, leading to inflammation and cirrhosis, while leaving lung tissue vulnerable to enzyme damage.
Safety data from the trial appears favorable, with no concerning adverse events reported – a crucial consideration for novel genetic therapies. Beam Therapeutics CEO John Evans expressed optimism about BEAM-302’s potential to transform AATD treatment across all disease manifestations in severely affected patients.
The company plans to expand its testing program by exploring higher doses and initiating a second study phase focusing on AATD patients with mild-to-moderate liver disease. Additional data from the current trial is expected to be presented at an upcoming medical conference.
Concurrent with the data release, Beam announced a stock offering anticipated to generate $500 million in gross proceeds. The company, which reported $850 million in cash and equivalents at 2024’s end, expects these new funds to extend its operational runway through 2028.
The AATD treatment landscape is increasingly competitive, with several companies pursuing different therapeutic approaches. Wave Life Sciences is developing RNA editing solutions, while Arrowhead Pharmaceuticals and Takeda are investigating RNA interference treatments. However, one potential competitor, Intellia Therapeutics, recently discontinued its AATD program.
The market responded cautiously to the announcement, with Beam’s shares declining approximately 15% in Monday morning trading, reflecting the current challenging environment for genetic medicine developers despite the promising clinical results.