Promising early results from a clinical trial suggest that an innovative genetic therapy developed by Beam Therapeutics could effectively repair mutated DNA responsible for a rare condition affecting both liver and lung function.
Initial data from nine patients demonstrates the potential of Beam’s specialized CRISPR-based technology, which can make precise
single-nucleotide changes to DNA sequences. This represents the first clinical evidence showing the company’s ability to directly correct a disease-causing genetic mutation.
The treatment targets alpha-1 antitrypsin deficiency (AATD), a genetic disorder, by correcting the underlying DNA error. The therapy, BEAM-302, uses lipid nanoparticles to deliver editing machinery to the liver, where it performs a specific nucleotide swap – changing a “G” to an “A” in the SERPINA1 gene variant associated with severe AATD.
While preliminary, the results indicate the treatment is achieving its intended effects without concerning safety issues, though Beam’s stock declined nearly 15% following the announcement.
AATD’s pathology stems from a misfolded AAT protein produced by the mutant SERPINA1 gene. This protein typically protects lung tissue from neutrophil elastase, an enzyme released during immune responses. When misfolded, the protein accumulates in liver cells, leading to inflammation and cirrhosis, while leaving lungs vulnerable to damage.
The trial included nine patients with AATD-related lung disease who received one of three escalating doses of BEAM-302 intravenously. After one month, researchers observed total AAT protein increases of 1.6 to 2.8 times baseline levels, accompanied by decreases in misfolded protein circulation, suggesting successful production of properly formed AAT protein.
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 seen in AATD carriers.
CEO John Evans expressed optimism about BEAM-302’s potential to comprehensively address AATD’s various manifestations in severely affected patients. The therapy’s safety profile has been encouraging, with no concerning adverse events reported – a crucial consideration for novel genetic treatments.
Beam plans to continue testing higher doses and expand the trial to include patients with mild-to-moderate liver disease. Additional data is expected to be presented at an upcoming medical conference.
The company also announced a stock offering anticipated to raise $500 million in gross proceeds. Combined with existing funds of $850 million at 2024’s end, which were projected to last until 2027, the new capital should extend Beam’s operational runway through 2028.
The AATD treatment landscape is increasingly competitive, with several companies pursuing different approaches. Wave Life Sciences is developing RNA editing therapies, while Arrowhead Pharmaceuticals and Takeda are investigating RNA interference treatments. However, one competitor in the gene editing space, Intellia Therapeutics, recently discontinued its AATD program.
The positive results mark an important milestone for Beam’s base editing platform, demonstrating its potential to correct genetic mutations underlying serious diseases. While more extensive testing is needed to confirm these early findings, the data provides encouraging evidence for the therapeutic potential of precise genetic correction in treating inherited disorders.