The US Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for Beam Therapeutics’ BEAM-304 for the treatment of 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 requires strict, lifelong dietary management.  

BEAM-304 uses an innovative development approach in which multiple mutation-specific base editors are developed efficiently within a single clinical programme using in vivo delivery, in accordance with the FDA’s recent efforts to accelerate development of genome editing therapies. 

“PKU affects approximately 20,000 people in the US, with significant unmet need for therapies that address the underlying cause of disease,” said Giuseppe Ciaramella, President of Beam. “FDA clearance of our IND for BEAM-304 supports our novel approach of developing multiple mutation-specific base editors through a single clinical platform programme, leveraging emerging FDA guidance intended to accelerate development of base editing therapeutics. We look forward to initiating our Phase I/II trial, intending to establish clinical proof of concept for base editing in PKU.” 

BEAM-304 leverages Beam’s proprietary and clinically validated base editing technology and lipid nanoparticle (LNP) delivery capabilities to directly and durably correct mutations in the phenylalanine hydroxylase (PAH) gene that cause PKU.  

By correcting mutations in the PAH gene, BEAM-304 aims to restore PAH enzyme activity in order to reduce toxic Phe to the recommended guideline levels (≤ 360 µmol/L) while enabling diet normalisation and freedom from medical food. 

Preclinical data demonstrate that BEAM-304 normalised plasma Phe levels in PKU mouse models at clinically relevant doses with robust on-target editing in the liver. The planned Phase I/II trial will aim to establish clinical proof of concept for base editing in PKU.