Beam Therapeutics reports new preclinical data from BEAM-301 studies

Beam Therapeutics reported new preclinical data demonstrating the ability of its in vivo drug candidate, BEAM-301, to directly correct the R83C mutation, one of the primary disease-causing mutations of glycogen storage disease type Ia, or GSDIa. The data were presented in an oral presentation titled “A Single, Systemic Administration of BEAM-301 Mitigated Fasting Hypoglycemia One Year after Dosing in a Transgenic Mouse Model of Glycogen Storage Disease Type-Ia” at the 30th Annual European Society of Gene & Cell Therapy, or ESGCT, Congress in Brussels. GSDIa is a genetic disease caused by mutations in the G6PC gene encoding glucose-6-phosphatase, or G6Pase, a predominantly liver-expressed enzyme vital to glucose metabolism. The prevalent pathogenic variant, G6PC-p.R83C, completely abolishes G6Pase activity and is associated with life-threatening fasting hypoglycemia as well as long-term complications impacting the liver and kidney. BEAM-301 is a liver-targeting lipid-nanoparticle, or LNP, formulation containing base editing reagents optimized to correct the R83C mutation. Beam previously demonstrated that treatment with a single dose of BEAM-301 yielded up to ~60% base-editing efficiency to correct the R83C mutation and was associated with restored G6Pase activity in the livers of young huR83C mice. Today’s data build on those findings and show that a single dose of BEAM-301 yielded: Long-term survival of treated mice out to at least one year post treatment, compared to untreated GSDIa mice that exhibit poor survival of only a few weeks; Sustained editing of G6PC in liver, confirmed by the normalization of glucose homeostasis and glycogen accumulation at one year; Normal growth and liver size throughout one year post treatment relative to untreated homozygous mutant mice that developed three-fold larger liver size by three weeks of age; Normalization of circulating glucose and metabolites, including cholesterol, triglycerides, lactic and uric acid; and, Prevention of hypoglycemia during several, intermittent 24-hour fasts up through one year post dosing.