Beam Therapeutics expanded its liver-targeted genetic disease technology with a new program, BEAM-304, for the treatment of phenylketonuria (PKU), a disease with significant unmet need that affects approximately 20,000 individuals in the U.S. The company also signed a $500 million strategic financing agreement with Sixth Street to fund the potential launch of ristoglogene autogetemcel (risto-cel) in sickle cell disease (SCD).
Beam’s newest liver-targeted genetic disease program, BEAM-304, leverages Beam’s proprietary and clinically validated base editing technology and lipid nanoparticle (LNP) delivery capabilities to correct mutations in the phenylalanine hydroxylase (PAH) gene that cause PKU, according to company officials. 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 within recommended guidelines while enabling normalization of diet and freedom from medical food.
Multiple base editors
Beam is advancing BEAM-304 using an approach in which multiple mutation-specific base editors are developed within a single clinical program. With this approach, Beam’s platform has the potential to create one-time therapies for the vast majority of patients with PKU, noted a Beam spokesperson.
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. Preclinical data with both base editors demonstrate that BEAM-304 normalized plasma Phe levels in mouse models at clinically relevant doses with on-target editing in the liver, continued the spokesperson.
Beam expects to file an IND application with the FDA for BEAM-304 in 2026 following completion of pre-IND activities. The planned Phase I/II trial will initially evaluate safety, tolerability, and reduction of blood Phe levels in PKU patients with the R408W mutation, followed thereafter by a base editor for a second mutation, with a goal of establishing clinical proof of concept for base editing in PKU and laying the foundation for future expansion to patients with additional PAH mutations.
“In 2025, we established base editing as a best-in-class technology for genetic medicine, with positive proof-of-concept data and regulatory and clinical development paths to approval across multiple high-value programs,” said John Evans, CEO. “The announcement of BEAM-304 for PKU marks an important expansion of our pipeline and exemplifies the power and scalability of our platform. We have the potential to bring forward one-time, durable treatments for the vast majority of PKU patients.
“Moreover, with BEAM-304 we are pursuing an innovative and efficient development approach designed to advance multiple base editors within a single clinical program to address different PKU patient populations, one of the first such programs to reach the clinic.”
