Beam Therapeutics to Present New Preclinical Data from Base Editing Pipeline at ASGCT 25th Annual Meeting

CAMBRIDGE, Mass., May 02, 2022 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today announced that the company will present new preclinical data from several programs across its base editing portfolio at the American Society of Gene and Cell Therapy (ASGCT) 25th Annual Meeting. The meeting is being held May 16-19, 2022, in Washington, DC.

Beam’s presentations showcase a key component of the company’s long-term strategy: making early and deliberate investments in preclinical assessments to better understand levels of editing required to generate therapeutic responses and to potentially restore physiological function. Updated findings to be presented at the meeting include data from two of the company’s in vivo, liver-targeted programs – BEAM-301, its base editing program in development for the treatment of glycogen storage disease type Ia (GSDIa), and its base editing program in development for the treatment of alpha-1 antitrypsin deficiency (Alpha-1). In addition, Beam will present research highlighting its proprietary lipid nanoparticle (LNP) delivery capabilities for potential in vivo delivery to both T cells and natural killer (NK) cells, which could have broad applications in both immunology and oncology.

“Beam research continues to advance on many fronts in parallel, including both ex vivo and in vivo programs as well as novel delivery technologies, and we are excited to present new preclinical findings at ASGCT,” said Giuseppe Ciaramella, Ph.D., president and chief scientific officer of Beam. “Updated data from our BEAM-301 in vivo candidate for GSDIa continue to show potent and durable liver editing that translated into improved metabolic parameters and survival in a mouse model of homozygous GSDIa, combined with a favorable off-target profile, providing further support for its advancement toward IND-enabling studies this year. In addition, updated data from our Alpha-1 program demonstrate Beam’s capabilities to optimize base editing for a challenging target site, achieving significantly improved editing potency and therapeutically relevant levels of gene correction in a clinically relevant dose range.”

Dr. Ciaramella added, “Lastly, we’ve leveraged our proprietary LNP capabilities to deliver mRNA to immune cells both ex vivo and in vivo. In vivo delivery of mRNA encoding therapeutic transgenes such as CARs to T and NK cells could circumvent certain critical challenges associated with current-generation autologous CAR-T therapies, potentially complementing our existing platform for multiplex-edited allogeneic ex vivo CAR-T therapies. Collectively, this research is exciting for Beam and the entire gene editing field, bringing us closer to delivering important new disease-modifying therapies to patients suffering from a wide range of severe diseases.”

Details of the presentations are as follows:

Title: Single, systemic administration of BEAM-301 mitigates fasting hypoglycemia and restores metabolic function in a transgenic mouse model of glycogen storage disease type IaDate & Time: Monday, May 16, 2022, from 4:15-4:30 p.m. ETData Summary: GSDIa is an autosomal recessive disorder caused by mutations in the G6PC gene that disrupt a key enzyme, glucose-6-phosphatase (G6Pase), involved in maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can be fatal. Beam is advancing BEAM-301, composed of a guide RNA and an mRNA encoding an adenine base editor (ABE) delivered via LNP, which aims to directly correct the R83C mutation, one of the primary disease-causing mutations of GSDIa. Beam has previously shown editing efficiencies of approximately 60% in liver extracts, with survival of a GSDIa mouse model to three weeks of age without hypoglycemia-induced seizures. Today’s data build on those findings, showing that in a GSDIa mouse model, treated mice, which otherwise have poor survival outcomes if left untreated, grew normally to at least 35 weeks following administration of BEAM-301, with survival ongoing in the study. Notably, as low as single digit percentage base-editing rates were sufficient to restore physiologically relevant levels of hepatic G6Pase activity, normalize serum metabolites, and most importantly, prevent hypoglycemia during a 24-hour fast. In addition, preliminary off-target assessments have suggested a favorable profile of BEAM-301.

Title: Optimized base editing reagents yield more potent genetic correction in a mouse model of alpha-1 antitrypsin deficiency (poster M-123)Date & Time: Monday May 16, 2022, from 5:30-6:30 p.m. ETData Summary: Alpha-1 is a rare, inherited genetic disorder that can cause progressive lung and liver disease. It is most commonly caused by a G-to-A point mutation – referred to as the PiZ mutation – within the SERPINA1 gene, which produces alpha-1 antitrypsin (AAT) protein. In healthy individuals, the AAT protein is secreted from the liver and, in circulation, protects the lungs from damage. In individuals with the PiZ mutation, AAT is misfolded, preventing secretion and resulting in damaging build-up in the liver, as well as loss of its protective function in the lungs. Previous studies conducted by Beam, have shown the ability of LNP-delivered base editing reagents to correct the PiZ mutation in the livers of mouse models, suggesting the potential of Beam’s base editors to treat both lung and liver manifestations of the disease. In updated research to be presented at ASGCT, Beam scientists sought to optimize both the ABE and the guide RNA used to correct the disease-causing PiZ mutation, with the improvements over the original reagents leading to a greater than two-fold increase in editing potency and therapeutically relevant increases in circulating AAT in mice treated at clinically relevant doses (