Preclinical in vivo data support the ability of BEAM-302 to correct the primary disease-causing PiZ mutation linked with severe alpha-1 antitrypsin deficiency (AATD), Beam Therapeutics announced.

The data were presented at the AATD 2023 Meeting that took place in early September in Naples, Italy.

“In today’s presentation, we shared—for the first time—a full summary of preclinical in vivo data for BEAM-302, our lead candidate for the potential treatment of AATD. In two rodent models of AATD, one-time treatment at clinically relevant dose levels of BEAM-302 led to significant increases in circulating total corrected AAT and corresponding reductions in circulating mutant PiZ AAT,” Giuseppe Ciaramella, PhD, president of Beam, noted.

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The researchers evaluated the experimental drug in a NOD-SCID-gamma chain knockout-PiZ mouse model of AATD carrying multiple copies of the human PiZ allele and a novel humanized PiZ rat model developed by Beam scientists in which the normal rat AAT is replaced with human mutated PiZ AAT.

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According to the results, clinically relevant doses of up to 1 mg per kilogram of BEAM-302 resulted in the correction of up to 39% and 49% of liver DNA in rats and mice, respectively. The experimental drug yielded 2 and 4 times higher functional AAT levels in rats and mice, respectively, as evidenced by the increased capacity of serum samples to inhibit human neutrophil elastase.

Moreover, the rats expressed 2 times higher levels of total serum AAT and a 70% decrease in serum Z-AAT, while the mice expressed 4 times higher levels of total serum AAT, and a 90% decrease in serum Z-AAT in mice.

The experimental drug also demonstrated a reduction in toxic liver aggregates, also known as liver polymers. The obtained correction is expected to be durable based on the existing preclinical evidence.

“Importantly, because the native AAT gene would be corrected in its normal genetic location, AAT levels would be anticipated to increase in response to inflammation or infection, an important aspect of normal AAT function, which does not occur with currently approved protein replacement therapies,” the authors emphasized.

“These data support the continued advancement of BEAM-302 as a potential treatment option for AATD-related lung and liver disease, and we remain focused on the planned submission of our regulatory application in the first quarter of next year.”

 AATD is most often associated with homozygous PiZZ mutations in the SERPINA1 gene. BEAM-302 is a liver-targeting experimental medication that is designed to correct the PiZ mutation.


Beam Therapeutics presents preclinical data highlighting utility of BEAM-302 to correct an alpha-1 antitrypsin (AAT) deficiency disease-causing mutation. News release. Beam Therapeutics Inc.; September 7, 2023.