Beam shares positive initial trial data for base editing therapy in rare lung condition

Beam Therapeutics announced initial safety and efficacy data from its phase 1/2 trial of its liver-targeting lipid-nanoparticle formulation of base editing reagents, BEAM-302, establishing clinical proof-of-concept as a potential treatment for alpha-1 antitrypsin deficiency (AATD) and for in vivo base editing.

According to Beam, preliminary results from the first three single-ascending dose cohorts demonstrated that BEAM-302 was well tolerated, with single doses of BEAM-302 leading to durable dose-dependent correction of the disease-causing mutation.

AATD is an inherited genetic disorder — with no approved curative treatments — that affects the lungs and/or liver, leading to early onset emphysema and liver disease. A number of genetic mutations cause AATD, but it’s estimated that approximately 100,000 individuals in the U.S. have the PiZZ genotype.

Patients with the PiZZ genotype have very low circulating levels of functional alpha-1 antitrypsin (AAT) protein, all of which is the mutant form, known as Z-AAT, which accumulates and causes liver toxicity. By correcting the PiZ mutation at the DNA level, BEAM-302 has the potential to be a one-time therapy that simultaneously reduces the amount of Z-AAT in circulation, generates therapeutic levels of corrected protein (M-AAT), and increases total and functional AAT in circulation above the 11µM protective threshold, thereby addressing the underlying pathophysiology of both the liver and lung disease.

Beam plans to continue the dose-escalation portion of part A of the ongoing phase 1/2 trial, including enrolling and dosing a fourth dose cohort, and expects to report further data at a medical conference in the second half of 2025. In addition, the company plans to dose the first patient in part B, which will include AATD patients with mild to moderate liver disease, in the second half of 2025.

Beam recently shared new safety and efficacy data from a phase 1/2 trial of its base-editing therapy, BEAM-101, in patients with sickle cell disease with severe vaso-occlusive crises. The therapy continued to demonstrate robust and durable increases in fetal hemoglobin and reductions in sickle hemoglobin, rapid neutrophil and platelet engraftment, and normalized or improved markers of hemolysis.