BEAM-302 “has set the bar for efficacy in this space,” William Blair analysts wrote in an investor note on Monday.
Beam Therapeutics’ investigational gene editor BEAM-302 can correct the disease-causing genetic mutation in patients with alpha-1 antitrypsin deficiency, according to preliminary findings from a Phase I/II study.
Patients with the deficiency commonly suffer from lung disease and damage, while a few—children in particular—will sustain liver injuries. There is currently no established cure for alpha-1 antitrypsin deficiency (AATD), and symptoms are managed as they arise.
Afflicting around 1 in 2,500 people, AATD is a rare and genetic disease characterized by no or insufficient expression of the AAT protein. AAT is made in the liver but functions in the lungs, working to protect them from damage caused by environmental stressors, such as dust, smoke and other forms of pollution.
Beam’s answer to this disease is BEAM-302, a liver-targeted formulation of base-editing agents designed to target and correct the most common genetic mutation in AATD patients. According to the biotech, a one-time correction of this mutation can both lower the production and accumulation of a mutated form of AAT, while also boosting the expression of the normal, correctly folded protein. In turn, BEAM-302 increases the levels of functional AAT in circulation, thereby addressing the underlying pathway of AATD.
Monday’s readout backs BEAM-302’s mechanism of action. Results showed that in patients treated with a 60-mg dose of the gene therapy, total AAT levels jumped from 4.4 µM at baseline to 12.4 µM at 28 days. According to CEO John Evans, this therapeutic effect was “sustainable” and came “above the therapeutic threshold” for AAT.
Over the same time span, circulating concentrations of the mutant AAT protein dropped by 78% in patients treated at the same dose level.
The Phase I/II study also found BEAM-302 to be well-tolerated with an “acceptable” safety profile. All toxicities were mild or moderate in severity, with no serious side effects documented. As of data cutoff, none of the patients dosed with the gene therapy had experienced dose-limiting toxicities. There were instances of grade 1 elevations in liver enzymes (a “mild” elevation), though these were asymptomatic and did not necessitate treatment, according to Beam.
In a note to investors on Monday, William Blair analysts said these initial data for BEAM-302 “validates the safety and efficacy” of Beam’s lipid nanoparticle and in vivo base editing platform, adding that the gene therapy’s early AAT expression data are highly competitive in this space. “We are inclined to say BEAM-302 has set the bar for efficacy in this space,” the analysts wrote.
Wave Life Sciences is also advancing an editing therapy for AATD, which in October 2024 elicited AAT levels of 10.8 µM. Unlike Beam, however, Wave’s asset is an RNA editor, which would make its effects transient.
