Promising early results from a clinical trial suggest that an innovative genetic therapy developed by Beam Therapeutics may effectively repair genetic mutations causing a rare disorder affecting both liver and lung function.
The preliminary findings, which involved nine patients, represent a significant milestone for Beam’s base editing technology – a refined version of CRISPR gene editing that can make precise single-letter changes in DNA sequences. While the company has previously shared results from other experimental treatments, this marks their first demonstration of directly correcting a disease-causing genetic mutation.
The therapy targets alpha-1 antitrypsin deficiency (AATD), a genetic condition where a single DNA letter mistake in the SERPINA1 gene leads to the production of misfolded proteins. Beam’s treatment, BEAM-302, works by replacing a “G” with an “A” in the gene variant responsible for severe cases of AATD. The editing machinery is delivered to the liver through lipid nanoparticles.
AATD typically manifests in two ways: misfolded proteins accumulate in liver cells, eventually causing inflammation and cirrhosis, while the lungs become vulnerable to damage from an enzyme called neutrophil elastase due to lack of protection from properly functioning AAT protein.
Initial data from the trial shows encouraging signs of efficacy. The nine treated patients, all with AATD-related lung disease, received one of three ascending doses of BEAM-302 intravenously. One month post-treatment, patients showed increases in total AAT protein levels ranging from 1.6 to 2.8 times their baseline measurements, along with decreases in misfolded protein circulation.
Particularly noteworthy was one patient on the highest dose, who experienced a 78% reduction in circulating misfolded protein after one month. The three patients receiving the highest dose achieved average AAT protein levels of 12.4 micromolars – reaching a threshold considered protective, similar to levels seen in AATD carriers.
Safety data has also been reassuring, with no concerning adverse events reported – a crucial consideration for novel genetic therapies where unexpected side effects have previously complicated development efforts.
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 this year.
The company has simultaneously announced a stock offering expected to raise $500 million in gross proceeds. This funding, combined with their existing cash reserves of $850 million, should extend their operational runway into 2028.
Several other companies are also pursuing treatments for AATD, including Wave Life Sciences working on RNA editing approaches and Arrowhead Pharmaceuticals and Takeda investigating RNA interference methods. However, one competitor in the gene editing space, Intellia Therapeutics, recently discontinued its AATD program.
Despite the positive clinical results, Beam’s stock experienced a nearly 15% decline in Monday morning trading, reflecting current market challenges facing genetic medicine developers.
The development of BEAM-302 represents a potential breakthrough in treating AATD, with CEO John Evans stating it could become “a transformative therapy” addressing all manifestations of severe AATD. The initial results demonstrate successful genetic correction and protein production restoration, offering hope for patients affected by this rare genetic disorder.