Beam advances AATD base-editing therapy toward accelerated approval on strong trial data

Beam Therapeutics announced updated safety and efficacy data from the ongoing phase 1/2 trial of BEAM-302 and the selection of an optimal dose to advance into pivotal development to support potential accelerated approval.

BEAM-302 is a liver-targeting lipid-nanoparticle (LNP) formulation designed to directly correct the underlying genetic mutation that causes the severe form of alpha-1 antitrypsin deficiency (AATD) through base editing.

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 this 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.

In the phase 1/2 trial, treatment with BEAM-302 led to rapid and durable increases of total and functional AAT, decreases in mutant Z-AAT, and new production of corrected protein M-AAT. Corrected M-AAT comprised 94% of total AAT with a concomitant 84% reduction in mutant Z-AAT following BEAM-302 60 mg treatment, which was selected as the optimal biological dose.

“These updated results, now with a robust clinical dataset from 29 patients, reinforce the potential for BEAM-302 to become a first- and best-in-class one-time treatment for patients with AATD,” said John Evans, CEO, Beam Therapeutics.

Based on feedback from the U.S. FDA, Beam says it will pursue an accelerated approval pathway for BEAM-302 based on a primary endpoint of AAT biomarkers evaluated over 12 months, with 60 mg as the selected dose. To support a future BLA submission, the company anticipates enrolling approximately 50 additional patients with AATD-associated lung disease, with or without liver disease, in an expansion of the ongoing open-label phase 1/2 trial.