Beam Therapeutics Presents First Data Highlighting Base Editing Program for Glycogen Storage Disease Type Ia

Beam Therapeutics Inc. recently announced the company will present preclinical data from its liver-focused programs, including the first data highlighting its novel base-editing strategy for correcting disease-causing mutations underlying Glycogen Storage Disease Type Ia (GSDIa), during the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting Digital Experience being held virtually November 13-16, 2020.

GSDIa, also known as Von Gierke disease, is an inborn disorder of glucose metabolism caused by mutations in the G6PC gene that disrupt a key enzyme, Glucose-6- Phosphatase (G6Pase), which is involved in glucose homeostasis. This disruption results in low blood glucose levels that can be fatal if patients do not adhere to a strict regimen of slow-release forms of glucose, administered every one to four hours (including overnight). There are currently no pharmacological therapies approved for patients with GSDIa. Beam has engineered novel adenine base editors (ABE) that, in preclinical models, have achieved high levels of precise correction of the two most prevalent GSD1a mutations, R83C and Q347X, in both in vitro and in vivo settings.

“Base editing represents an exciting new opportunity for the treatment of serious diseases, including GSDIa, where patients are in need of a disease-modifying, life-long treatment,” said Giuseppe Ciaramella, PhD, President and Chief Scientific Officer of Beam. “These first preclinical data from our GSDIa program demonstrate significant levels of precise correction of the disease-causing R83C and Q347X point mutations, well above the level that we believe is needed to have a clinically relevant treatment effect for patients with GSD1a. We look forward to presenting these data, as well as our encore presentation of our Alpha-1 data from ASGCT, as we continue to advance our liver base editing programs toward the clinic.”

Beam’s approach to treating patients with GSDIa is to deliver an ABE via lipid nanoparticle (LNP) to the liver to repair either the R83C or the Q347X mutations in G6PC. It is estimated that these two-point mutations account for 900 and 500 patients, respectively, in the United States, representing approximately 60% of all GSDIa patients. Animal studies suggest that a critical therapeutic threshold of approximately 11% of normal G6Pase activity in liver cells is sufficient to restore fasting glucose; however, this level must be maintained in order to preserve glucose control and alleviate other serious, and potentially fatal, GSDIa symptoms. In vivo correction of both mutations by ABEs was observed in the livers of two strains of transgenic mice, each carrying one of the two G6PC mutations. Next-generation sequencing data from whole liver extracts reveal significant correction for both R83C and Q347X, with nearly 40% and approximately 70% A-to-G conversion efficiency, respectively, of each mutation back to the normal gene sequence. These significant levels of mutation correction greatly surpass those expected to restore glucose homeostasis, and functional studies are ongoing to correlate pathophysiology to extent of mutation correction by base-editing. Further, these levels of in vivo correction for GSDIa by base-editing are achieved without creation of double-stranded breaks. In total, these data support base-editing technology as a promising approach for precise correction of causative mutations in GSDIa.

Beam will also report data during an oral presentation at AASLD from its Alpha-1 Antitrypsin Deficiency (Alpha-1) program, which were previously presented at American Society of Gene & Cell Therapy 2020 Annual Meeting.

Beam Therapeutics (Nasdaq: BEAM) is a biotechnology company developing precision genetic medicines through the use of base editing. Beam’s proprietary base editors create precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This enables a wide range of potential therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs. Beam is a values-driven organization committed to its people, cutting-edge science, and a vision of providing life-long cures to patients suffering from serious diseases. For more information, visit