Promising early results from a clinical trial suggest Beam
Therapeutics’ novel genetic treatment can successfully repair the DNA mutation responsible for a rare condition affecting the liver and lungs.
The company released data from nine patients treated with their base editing therapy, BEAM-302, designed to correct alpha-1 antitrypsin deficiency (AATD). This marks the first time Beam has demonstrated its precision gene editing technology can directly fix a disease-causing genetic mutation.
BEAM-302 works by utilizing specialized machinery delivered to the liver via lipid nanoparticles to exchange a single DNA letter – replacing a “G” with an “A” in the SERPINA1 gene variant associated with severe AATD. This genetic condition causes problems when a misfolded protein called AAT accumulates in liver cells rather than traveling to protect lung tissue as intended.
Initial findings indicate the treatment is achieving its intended effects without concerning safety issues. The nine lung disease patients received one of three escalating doses intravenously. After one month, researchers observed total AAT protein levels increased 1.6 to 2.8 times above baseline, along with decreases in circulating misfolded protein – suggesting successful production of properly formed AAT.
Notably, one patient on the highest dose showed a 78% reduction in misfolded protein levels compared to pre-treatment. The three patients at this dose reached average AAT protein levels of 12.4 micromolars, exceeding what’s considered a protective threshold seen in AATD carriers.
“BEAM-302 could potentially transform treatment for AATD patients across the full spectrum of disease manifestations,” said John Evans, Beam’s CEO.
Safety data has been encouraging, according to Jefferies analyst Michael Yee – a critical consideration for novel genetic medicines where side effects have previously hindered development programs.
Beam plans to test higher doses in more patients while expanding the trial to include those with mild-to-moderate liver disease. Additional data is expected to be presented at an upcoming medical conference this year.
Alongside the clinical results, Beam announced a stock offering anticipated to raise $500 million. The company had $850 million in cash and equivalents at 2024’s end, projected to fund operations into 2027. The new capital should extend their runway through 2028, Leerink Partners analysts noted.
Several other companies are also pursuing AATD treatments through different approaches. Wave Life Sciences is investigating RNA editing, while Arrowhead Pharmaceuticals and Takeda are studying RNA
interference methods. However, competitor Intellia Therapeutics recently discontinued its AATD program.
The disease occurs when the mutated SERPINA1 gene produces misfolded AAT protein that builds up in liver cells instead of being properly secreted. This accumulation can lead to liver inflammation and cirrhosis. Additionally, without functional AAT protein reaching the lungs, tissue becomes vulnerable to damage from neutrophil elastase, an enzyme released by white blood cells during immune responses.
By directly correcting the genetic mutation, BEAM-302 aims to restore normal AAT protein production and address both the liver and lung manifestations of the disease. The early trial results suggest this approach may successfully target the root cause of AATD, though further testing is needed to fully evaluate the therapy’s potential.