CAMBRIDGE, Mass., March 10, 2025 (GLOBE NEWSWIRE) — Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today announced initial safety and efficacy data from its Phase 1/2 trial of BEAM-302, establishing clinical proof-of-concept as a potential treatment for alpha-1 antitrypsin deficiency (AATD) and for in vivo base editing. Preliminary results from the first three single-ascending dose cohorts demonstrated that BEAM-302 was well tolerated, with single doses of BEAM-302 leading to durable dose-dependent correction of the disease-causing mutation.
AATD is an inherited genetic disorder that affects the lungs and/or liver, leading to early onset emphysema and liver disease, and for which there are no currently approved curative treatments. BEAM-302 is a liver-targeting lipid-nanoparticle (LNP) formulation of a guide RNA and an mRNA encoding a base editor designed to correct the disease-causing PiZ mutation. Patients homozygous for this mutation, known as the PiZZ genotype, have very low circulating levels of functional alpha-1 antitrypsin (AAT) protein, all of which is the mutant form, known as Z-AAT, which accumulates and causes liver toxicity. By correcting the PiZ mutation at the DNA level, BEAM-302 has the potential to be a one-time therapy that simultaneously reduces the amount of Z-AAT in circulation, generates therapeutic levels of corrected protein (M-AAT), and increases total and functional AAT in circulation above the 11µM protective threshold, thereby addressing the underlying pathophysiology of both the liver and lung disease. It is estimated that approximately 100,000 individuals in the U.S. have the PiZZ genotype.
“AATD is a serious genetic disorder that impacts the lungs and liver, often leading to emphysema and significant liver disease. Despite its severity, AATD remains underdiagnosed, and effective treatment options remain limited,” said Noel “Gerry” McElvaney, M.D., professor of medicine, Royal College of Surgeons, Dublin, Ireland. “The initial data for BEAM-302 demonstrate that the direct correction of the PiZ mutation both increased levels of functional AAT in the blood and reduced the harmful mutant protein which directly contributes to the liver and lung disease in this condition. These data represent a major breakthrough in the area of AATD, offering, for the first time ever, an opportunity to simultaneously treat the lung and liver disease associated with the condition by targeting the root cause and the potential for a cure from a single therapeutic administration, something which we have never seen before in a genetic lung disease.”
BEAM-302 is being evaluated in a Phase 1/2, open-label, dose exploration and dose expansion clinical trial to investigate its safety, tolerability, pharmacodynamics, pharmacokinetics and efficacy. Part A of the trial is designed to evaluate AATD patients with lung disease, and Part B will evaluate AATD patients with mild to moderate liver disease with or without lung disease. The dose expansion portions of the trial will identify the optimal dose to take forward in development. To date, single-ascending fixed doses of 15 mg (n=3), 30 mg (n=3) and 60 mg (n=3) of BEAM-302 have been administered via intravenous infusion in patients in Part A. Initial safety and efficacy data reported are from all nine patients as of a data cut-off date of February 26, 2025.
Treatment with BEAM-302 was well tolerated with an acceptable safety profile at all dose levels explored to date. All adverse events (AEs) were mild to moderate, with no serious AEs reported and no dose-limiting toxicities as of the data cutoff. Grade 1 asymptomatic alanine transaminase (ALT) and aspartate aminotransferase (AST) elevations and transient Grade 1 infusion-related reactions were observed in some patients and did not require treatment.
Following a single infusion of BEAM-302, rapid, durable, and dose-dependent increases in total AAT, new production of corrected M-AAT, and decreases in mutant Z-AAT were observed in circulation. Changes in total AAT were observed by turbidimetry assays as early as Day 7, plateaued around Day 21 and were maintained for the duration of follow-up (up to Month 6 in the 15 mg cohort, Month 2 in the 30 mg cohort, and Day 28 in the 60 mg cohort). Increased total AAT was functional as determined by both neutrophil elastase inhibition and neutrophil elastase binding assays.
“This landmark result in medicine represents the first clinical evidence of precise correction of a disease-causing mutation by rewriting the genetic code. The correction of the PiZ mutation in AATD is a potentially optimal application of base editing to precisely and potently repair mutations in DNA,” said John Evans, chief executive officer of Beam. “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 and accelerating the development of BEAM-302 for patients with AATD who urgently need more effective therapeutic options. Importantly, these data are also a demonstration of Beam’s state-of-the-art LNP in vivo delivery capabilities and open the door for the further expansion of our liver genetic disease franchise.”
Beam plans to continue the dose-escalation portion of Part A of the ongoing Phase 1/2 trial, including enrolling and dosing a fourth dose cohort, and expects to report further data at a medical conference in the second half of 2025. In addition, the company plans to dose the first patient in Part B, which will include AATD patients with mild to moderate liver disease, in the second half of 2025.
Source – Beam Therapeutics
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