adenine base editor based non-viral lipid nanoparticle therapeutic / Beam Therap - LARVOL DELTA

BEAM‐302 decreases hepatic aggregates of mutant AAT and increases circulating functional AAT in rodent models of Alpha‐1 Antitrypsin Deficiency (ESGCT 2023) - "The PiZ mutation is an ideal target for correction to wildtype (PiM) by an adenine base editor (ABE) which converts an A to G in genomic DNA...Furthermore, repeat administration of BEAM-302 resulted in further increases in editing rates. Taken together these data support the hypothesis that base-editing by BEAM-302 has the potential to mitigate both the liver and lung pathology of AATD."

Preclinical • Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Pulmonary Disease • Respiratory Diseases • ELANE • SERPINA1

Optimized Base Editing Reagents Yield More Potent Genetic Correction in a Mouse Model of Alpha-1 Antitrypsin Deficiency (ASGCT 2022) - "The p.Glu342Lys variant is caused by a G-to-A single nucleotide polymorphism and is amenable to correction by an adenine base editor (ABE), a gene editing construct capable of performing RNA-programmable A-to-G base conversions in genomic DNA...Furthermore, similar efficacy and durability was observed in NSG-PiZ mice dosed at >37 weeks of age despite liver fibrosis analogous to what might be encountered in a clinical setting. These results go beyond previous proof-of-concept studies in demonstrating both therapeutic relevance and technical feasibility of base editing as a potential treatment for alpha-1 antitrypsin deficiency."

Preclinical • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Pulmonary Disease • Pulmonary Emphysema • Rare Diseases • Respiratory Diseases • ELANE • SERPINA1

[VIRTUAL] Using Base Editing and LNP Delivery to Correct Disease-Causing Mutations Underlying Genetic Liver Diseases (ASGCT 2021) - "To treat Alpha-1 Antitrypsin (A1AT) Deficiency, we engineered novel adenine base editor (ABE) variants and chemically modified guide RNAs to efficiently correct the PiZ mutation in patient-derived cells...These results indicate that base editors in combination with LNP delivery have the potential to treat genetic liver diseases. Further efforts including optimization of the delivery system are ongoing."

Hepatology • Metabolic Disorders • Pulmonary Disease • AAT

[VIRTUAL] EVALUATION OF ADENINE BASE EDITING AS A POTENTIAL TREATMENT FOR ALPHA-1 ANTITRYPSIN DEFICIENCY (AASLD 2020) - "Taken together, these results indicate that base editing has the potential to address both lung and liver disease in Alpha-1 Antitrypsin Deficiency."

Alpha-1 Antitrypsin Deficiency • Genetic Disorders • Hepatology • Respiratory Diseases • AAT • ELANE

BEAM THERAPEUTICS : Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - "An important next step for the liver disease programs is finalizing our LNP formulation, and we are making progress on developing a formulation using proof of concept targets. To date, with this formulation, we have shown high levels of editing in mice at doses consistent with clinical use. We are currently conducting non-human primate studies to evaluate our LNP formulation and anticipate initial data in early 2021. We believe we are on track to nominate our first development candidate from our liver portfolio in 2021."

Preclinical • Alpha-1 Antitrypsin Deficiency

Beam Therapeutics Announces Business and Pipeline Progress and Reports Third Quarter 2020 Financial Results (Streetinsider.com) - "Beam will also report data during an oral presentation at AASLD from its Alpha-1 Antitrypsin Deficiency (Alpha-1) program."

Preclinical • Alpha-1 Antitrypsin Deficiency

Beam Therapeutics Reports Additional Data at ASGCT Annual Meeting and First Quarter 2020 Financial Results (GlobeNewswire, Beam Therapeutics) - "Alpha-1 Antitrypsin Deficiency Program Demonstrates Proof-of-Concept in a Mouse Model: Beam reported additional data from its direct editing program for Alpha-1 in a poster at ASGCT titled 'Use of Adenine Base Editors to Precisely Correct the Disease-Causing PiZ Mutation in Alpha-1 Antitrypsin Deficiency'. Updated data demonstrate that using Beam's adenine base editors (ABEs) to directly correct the PiZ mutation resulted in an average of 16.9% correction of beneficial alleles at seven days and 28.8% at three months....Treated mice demonstrate decreased alpha-1 antitrypsin (A1AT) globule burden within the liver and a durable increase in serum A1AT, roughly 4.9-fold higher than in controls, was observed at three months."

Preclinical • Alpha-1 Antitrypsin Deficiency • Anemia • Infectious Disease

Beam Therapeutics to Present First Data Highlighting Base Editing Program for Alpha-1 Antitrypsin Deficiency at 23rd ASGCT Annual Meeting (GlobeNewswire, Beam Therapeutics) - "CAMBRIDGE, Mass., April 28, 2020 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today announced preclinical data showcasing the potential of its novel base editing approach for the treatment of alpha-1 antitrypsin deficiency (Alpha-1) liver and lung diseases. The data will be presented in oral and poster sessions during the 23rd American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, which will be hosted virtually May 12-15, 2020."

New molecule • Preclinical • Alpha-1 Antitrypsin Deficiency • Gastroenterology