Beam Therapeutics Announces Groundbreaking Positive Initial Data from BEAM-302 Phase 1/2 Trial for Alpha-1 Antitrypsin Deficiency

CAMBRIDGE, Mass., March 10, 2025 (GLOBE NEWSWIRE) – Beam Therapeutics Inc. (Nasdaq: BEAM), a pioneering biotechnology company at the forefront of precision genetic medicines through base editing, today announced transformative positive initial safety and efficacy data from its ongoing Phase 1/2 clinical trial evaluating BEAM-302. These landmark results mark the first-ever clinical genetic correction of a disease-causing mutation, establishing an unprecedented proof-of-concept for in vivo base editing and signaling a potential paradigm shift in the treatment of alpha-1 antitrypsin deficiency (AATD).

The trial demonstrated that a single intravenous dose of BEAM-302 resulted in durable, dose-dependent increases in total and functional alpha-1 antitrypsin (AAT) levels, robust production of corrected M-AAT protein, and significant reductions in circulating mutant Z-AAT across the initial three single-ascending dose cohorts. These findings underscore the potential of BEAM-302 to address the root cause of AATD and offer a one-time, potentially curative therapeutic approach.

Key Efficacy and Safety Highlights:

• • Clinically Meaningful Therapeutic AAT Levels Achieved: At the highest dose level (60 mg, N=3), BEAM-302 successfully achieved a mean total AAT level of 12.4µM at Day 28, surpassing the established protective therapeutic threshold of 11µM. This achievement is crucial for long-term protection against lung and liver damage.
  • Substantial and Sustained Reduction in Mutant Z-AAT: A remarkable 78% reduction in circulating mutant Z-AAT was observed at the 60mg dose level, demonstrating the direct impact of BEAM-302 on the disease’s underlying pathophysiology and potentially halting the progression of liver damage.
  • Confirmation of Corrected M-AAT Protein Production and Functional Restoration: The trial provided definitive evidence of the new and sustained production of corrected M-AAT protein, confirming successful base editing and the restoration of physiologically functional AAT. This is a critical step towards addressing both the systemic deficiency and the toxic accumulation of Z-AAT, which are the dual hallmarks of AATD.
  • Exceptional Safety and Tolerability Profile: BEAM-302 exhibited an exceptional safety and tolerability profile across all dose levels investigated, with no serious adverse events or dose-limiting toxicities reported to date. This robust safety profile is essential for the potential widespread application of BEAM-302.
  • Durable and Dose-Dependent Response: Clear evidence of durable, dose-dependent increases in total and functional AAT levels, and corresponding decreases in mutant Z-AAT, was observed across the initial three dose cohorts, indicating a promising therapeutic profile.

“This landmark result in medicine represents the first clinical evidence of precise correction of a disease-causing mutation by rewriting the genetic code within the human body, a monumental achievement in the field of gene therapy,” stated John Evans, chief executive officer of Beam Therapeutics. “The correction of the PiZ mutation in AATD is a potentially optimal application of base editing to precisely and potently repair mutations in DNA, offering the promise of a one-time, potentially curative treatment. With a simple intravenous infusion, promising safety profile, sustainable increase of total AAT above the therapeutic threshold, and rapid reduction in toxic mutant Z-AAT, we believe BEAM-302 has the potential to be a transformative therapy that could treat the entire spectrum of disease manifestations in severely deficient AATD patients. We look forward to continuing dose escalation, exploring the potential of combination therapies, and accelerating the development of BEAM-302 for patients with AATD who urgently need more effective therapeutic options.”

Trial Design and Detailed Results:

BEAM-302, a pioneering liver-targeting lipid nanoparticle (LNP) formulation, is meticulously engineered to precisely correct the PiZ mutation in the SERPINA1 gene—the fundamental genetic defect underlying AATD. The Phase 1/2 trial is an open-label, dose exploration and dose expansion study designed to evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics, and efficacy of BEAM-302. Part A of the trial is focused on evaluating AATD patients with lung disease, while Part B will assess patients with mild to moderate liver disease, with or without lung involvement.

Data from the first three single-ascending dose cohorts (15 mg, 30 mg, and 60 mg) demonstrated:

• • Rapid, durable increases in total AAT levels, observed as early as Day 7, plateauing around Day 21, and sustained throughout the follow-up period.
  • New and sustained production of corrected M-AAT protein, confirming successful base editing and functional restoration.
  • Significant, dose-dependent reductions in circulating mutant Z-AAT, with the highest dose achieving a 78% reduction.
  • A favorable safety profile, characterized by mild, transient adverse events, including Grade 1 asymptomatic alanine transaminase (ALT) and aspartate aminotransferase (AST) elevations and transient Grade 1 infusion-related reactions.

Clinical Significance and Therapeutic Potential:

AATD, an inherited genetic disorder affecting approximately 100,000 individuals in the U.S. with the PiZZ genotype, leads to severe lung and liver disease due to the accumulation of misfolded Z-AAT protein. BEAM-302’s ability to correct the PiZ mutation at the DNA level offers the potential for a one-time, potentially curative therapy that addresses the underlying pathophysiology of both lung and liver disease manifestations. This targeted approach represents a significant advancement over current therapies, which primarily focus on protein replacement and do not address the root cause of the disease.

Next Steps and Future Outlook:

Beam Therapeutics plans to continue the dose-escalation phase of Part A of the ongoing Phase 1/2 trial, including the enrollment and dosing of a fourth dose cohort. The company anticipates presenting more detailed data, including long-term follow-up results, at a prominent medical conference in the second half of 2025 and will pursue further studies to explore the long-term effects of BEAM-302 and its potential to halt disease progression. The company also intends to dose the first patient in Part B of the trial in the second half of 2025.

About BEAM-302:

BEAM-302 is a pioneering liver-targeting lipid nanoparticle (LNP) formulation of base editing reagents, meticulously engineered to precisely correct the PiZ mutation in the SERPINA1 gene—the fundamental genetic defect underlying AATD.

About Alpha-1 Antitrypsin Deficiency (AATD):

AATD is an inherited genetic disorder caused by a mutation in the SERPINA1 gene, leading to severe lung and liver disease due to the accumulation of misfolded Z-AAT protein.

Source:
https://investors.beamtx.com/news-releases/news-release-details/beam-therapeutics-announces-positive-initial-data-beam-302-phase

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