BEAM-304

BEAM-304

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BEAM-304 is a liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents designed to correct mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU). PKU is a rare, inherited metabolic disorder that results in toxic accumulation of phenylalanine (Phe), leading to serious neurologic and neurocognitive impairments and lifelong dietary management. By correcting mutations in the PAH gene, BEAM-304 aims to reduce toxic Phe to within recommended guidelines while enabling normalization of diet and freedom from medical food. BEAM-304 is delivered via an intravenous infusion.

BEAM-304 will be evaluated in a Phase 1/2, open-label, dose exploration and dose expansion clinical trial to investigate its safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy in PKU patients. Beam is advancing BEAM-304 using an innovative development approach in which multiple mutation-specific base editors are developed efficiently within a single clinical program. Initial clinical development will focus on base editors addressing the two most prevalent variants found in nearly half of patients with PKU in the U.S., with ongoing research effort to address additional pathogenic mutations.

BEAM-302

BEAM-302

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BEAM-302 is a liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents designed to correct the most common severe form of alpha-1 antitrypsin deficiency (AATD), which results from mutations in the Z allele, known as PiZ, caused by a single G to A point mutation in the SERPINA1 gene. A one-time A-to-G correction of the PiZ mutation with Beam’s adenine base editor has the potential to simultaneously reduce the aggregation of mutant, misfolded AAT protein that causes toxicity to the liver (Z-AAT), generate therapeutic levels of corrected protein (M-AAT), and increase total and functional AAT in circulation, thereby addressing the underlying pathophysiology of both the liver and lung disease. BEAM-302 is delivered via an intravenous infusion.

BEAM-302 is being evaluated in a Phase 1/2, open-label, dose exploration and dose expansion clinical trial to investigate its safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy in AATD patients. Part A of the trial is designed to evaluate AATD patients with lung disease, and Part B will evaluate AATD patients with mild to moderate liver disease with or without lung disease. The dose expansion portions of the trial will identify the optimal dose to take forward in development.

BEAM-302 was granted orphan drug designation and Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. Food and Drug Administration.

BEAM-301

BEAM-301

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BEAM-301 is a liver-targeting LNP formulation of base editing reagents designed to correct the R83C mutation, the most prevalent disease-causing mutation for, and the mutation which results in the most severe form of glycogen storage disease Ia (GSDIa). GSDIa is an autosomal recessive disorder caused by mutations in the G6PC gene that disrupts a key enzyme, G6Pase, critical for maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can result in seizures and be fatal. Patients with this mutation typically require ongoing corn starch administration, without which they may enter into hypoglycemic shock within one to three hours.

BEAM-301 is being evaluated in a Phase 1/2, open-label, dose exploration and dose expansion clinical trial to investigate its safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy in GSDIa patients.