Promising early results from a clinical trial suggest that an innovative genetic treatment developed by Beam Therapeutics can successfully repair mutated DNA responsible for a rare genetic disorder affecting the liver and lungs.
The preliminary data, derived from nine initial patients, represents a significant milestone for Beam, which specializes in a precise form of CRISPR gene editing capable of correcting individual DNA nucleotides. While the company has previously shared results from other
experimental treatments, these findings mark the first instance of demonstrating direct mutation correction in patients.
The treatment targets alpha-1 antitrypsin deficiency (AATD), a genetic condition where the SERPINA1 gene contains an error. Beam’s approach involves delivering editing machinery to the liver using lipid nanoparticles, which then replace a “G” with an “A” in the specific gene variant associated with severe AATD.
The initial results indicate the treatment is functioning as intended without concerning safety issues, though Beam’s stock declined by approximately 15% following the announcement. AATD causes damage by producing misfolded AAT protein that accumulates in liver cells rather than traveling to protect lung tissue from harmful enzymes. BEAM-302 aims to address both liver and lung complications by correcting the underlying genetic mutation.
All nine trial participants had AATD-related lung disease and received varying doses of BEAM-302 intravenously. One month post-treatment, researchers observed increases in total AAT protein levels ranging from 1.6 to 2.8 times above baseline, accompanied by decreases in misfolded protein circulation.
Notably, one patient receiving the highest dose showed a 78% reduction in circulating misfolded protein after one month. The three patients at this dose level achieved average AAT protein levels of 12.4 micromolars, exceeding the protective threshold typically seen in AATD carriers.
Safety data has been encouraging, with no significant adverse events reported – a crucial consideration for novel genetic therapies where side effects have previously hindered development. Beam plans to evaluate higher doses and expand testing to include patients with mild-to-moderate liver disease, with additional data expected later this year.
Concurrent with the results, Beam announced a stock offering anticipated to raise $500 million. The company, which reported $850 million in cash and equivalents at 2024’s end, expects these new funds to extend their operational timeline through 2028.
The field of AATD treatment is increasingly competitive, with several other companies pursuing different therapeutic approaches. Wave Life Sciences is developing RNA editing treatments, while Arrowhead Pharmaceuticals and Takeda are investigating RNA interference methods. However, one potential competitor, Intellia Therapeutics, recently discontinued its AATD program.
Beam’s CEO John Evans expressed optimism about BEAM-302’s potential, stating it could transform treatment across the spectrum of AATD manifestations in severely affected patients. The therapy’s ability to restore proper protein production while reducing misfolded protein accumulation suggests it could address both the liver and lung aspects of the disease.
The results represent an important validation of base editing technology’s potential in treating genetic diseases. Through precise DNA correction at the molecular level, this approach offers the possibility of addressing conditions at their source rather than merely managing symptoms.