Beam Therapeutics (BEAM) Status update summary

Clinical Data and Efficacy

• Updated phase I/II data for BEAM-302 show durable restoration of normal AAT physiology, with follow-up out to two years and functional M-AAT production under physiologic control in response to inflammation.

• A single 60 mg dose led to total AAT levels above the protective threshold, substantial reductions in mutant Z-AAT and Z-polymers, and a favorable safety profile consistent with LNP therapies.

• In both lung and liver disease cohorts, BEAM-302 achieved sustained increases in total and functional AAT, with 84% reduction in circulating Z-AAT and significant decrease in Z-polymers, moving patients toward a carrier-like state with lower disease risk.

• Restored predominant production of M-AAT isoform (>93%), exceeding levels seen in MZ genotype.

• Demonstrated normal physiologic control of AAT during inflammation, with increased AAT levels in response to acute infection.

Regulatory and Operational Status

• Alignment reached with FDA on accelerated approval pathway, with ongoing discussions about confirmatory trial design and endpoints, including total AAT, M/Z ratio, Z reduction, and Z-polymers.

• The pivotal global cohort is enrolling across multiple countries, with high enthusiasm and strong patient demand, aiming for accelerated approval based on AAT biomarkers over 12 months.

• Enrollment momentum is strong, with high interest from patients and clinics, and site expansion underway to support both pivotal and confirmatory trials.

• Safety profile remains favorable, with mostly mild, transient liver enzyme elevations and infusion reactions; one Grade 3 event resolved without intervention.

• Accepted to FDA CMC Development and Readiness Pilot program.

Scientific and Clinical Implications

• BEAM-302 is the first and only genetic medicine in pivotal development for AATD, targeting both lung and liver manifestations by correcting the E342K mutation in SERPINA1.

• The therapy aims to move patients from severe PiZZ phenotype to a carrier-like state, reducing disease risk and addressing both toxic protein accumulation and functional deficiency.

• Reduction in Z-polymers is linked to decreased inflammation and improved clinical outcomes, with BEAM-302 achieving polymer levels at or below those seen in MZ carriers.

• The base editing platform and LNP delivery technology are being leveraged across multiple programs, including sickle cell disease and phenylketonuria, demonstrating scalability and value creation.

• Ongoing collaborations with patient organizations and regulatory bodies aim to refine clinical endpoints and improve detection and diagnosis in AATD.