Beam Therapeutics Announces Clearance of Investigational New Drug Application for BEAM-302 for the Treatment of Alpha-1 Antitrypsin Deficiency (AATD) by the United States (U.S.) Food and Drug Administration

Rhea-AI Summary

Beam Therapeutics (Nasdaq: BEAM) announced FDA clearance of its investigational new drug (IND) application for BEAM-302, targeting alpha-1 antitrypsin deficiency (AATD) treatment. This marks the company's second in vivo base editing program with an open IND in the U.S.

BEAM-302, a liver-targeting lipid-nanoparticle formulation, is designed to correct the PiZ mutation in AATD patients. The ongoing Phase 1/2 trial includes Part A for patients with lung disease and Part B for those with mild to moderate liver disease. Initial safety and efficacy data reported in March 2025 demonstrated proof of concept as a potential one-time treatment.

The treatment has received clinical trial authorization across six countries. Beam plans to continue dose-escalation in Part A, including a fourth dose cohort, and expects to begin dosing Part B patients in H2 2025, with updated data presentation scheduled for the same period.

Positive

• FDA clearance expands BEAM-302's clinical trial authorization to six countries
• Initial trial data showed proof of concept for one-time AATD treatment
• First ever clinical genetic correction of disease-causing mutation demonstrated
• Trial expansion with fourth dose cohort and new patient group planned

Negative

• None.

Insights

Biotechnology Regulatory Analyst

The FDA clearance of Beam Therapeutics' IND for BEAM-302 represents a significant regulatory milestone for the company's base editing platform. This is particularly noteworthy as it marks Beam's second in vivo base editing program to receive FDA clearance and expands their regulatory approvals to six countries globally.

What makes this development especially impactful is the timing - it follows Beam's recent announcement of groundbreaking initial clinical data demonstrating the first-ever clinical genetic correction of a disease-causing mutation. This proof-of-concept validation substantially de-risks their technology platform and positions BEAM-302 as a potential first-in-class therapy for AATD.

For context, alpha-1 antitrypsin deficiency affects approximately 1 in 2,500 individuals and currently has no approved curative treatments. The disease leads to progressive lung damage and liver disease, creating a significant unmet medical need. Base editing technology aims to precisely correct the PiZ mutation, potentially offering a one-time treatment that addresses the root cause rather than just managing symptoms.

The company's clinical development strategy appears robust, with plans to continue dose escalation in Part A while expanding into patients with liver manifestations in Part B during H2 2025. This regulatory clearance removes a significant hurdle for U.S. trial expansion and accelerates their development timeline.

Genetic Medicine Specialist

Beam's FDA clearance for BEAM-302 marks a pivotal advancement in genetic medicine. The technology's mechanism - a liver-targeting lipid nanoparticle carrying both guide RNA and mRNA encoding a base editor - represents cutting-edge precision genetic medicine designed to correct the specific PiZ mutation responsible for AATD.

What distinguishes this approach is its potential one-time treatment paradigm versus lifetime management strategies. Their claim of achieving the "first ever clinical genetic correction of a disease-causing mutation" suggests they've demonstrated actual genetic modification in humans with corresponding protein production improvements - a watershed moment for base editing technology.

AATD pathophysiology involves both toxic protein accumulation in the liver and protein deficiency affecting the lungs. The trial design intelligently addresses both disease manifestations separately, with Part A targeting lung-predominant disease and Part B expanding to liver-involved patients. This strategy maximizes safety while comprehensively evaluating efficacy across the disease spectrum.

The global regulatory clearances across six countries will accelerate patient recruitment and diversify the trial population, strengthening eventual results. While early-stage, their plan to present additional data in H2 2025 suggests confidence in their findings thus far. If successful, BEAM-302 could fundamentally transform AATD treatment from symptom management to genetic correction, establishing base editing as a viable therapeutic modality for many genetic disorders.

U.S. IND Represents Regulatory Clearance For BEAM-302 Spanning Six Countries and Second Open IND for a Beam In Vivo Base Editing Program in the U.S.

CAMBRIDGE, Mass., March 27, 2025 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today announced that the United States (U.S.) Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for BEAM-302 for the treatment of alpha-1 antitrypsin deficiency (AATD). 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.

“The FDA’s clearance of our IND for BEAM-302 is a significant step toward advancing the development of this potential breakthrough treatment for patients living with AATD in the U.S.,” said Giuseppe Ciaramella, Ph.D., president of Beam. “Earlier this month, we shared groundbreaking initial safety and efficacy data from our global Phase 1/2 study of BEAM-302, showcasing the first ever clinical genetic correction of a disease-causing mutation. As we move forward, we’re laser focused on progressing this trial to enroll and dose more patients, activating more sites in new geographies, and preparing to present updated data in the second half of the year.”

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 in patients with AATD. BEAM-302 is being evaluated in an ongoing 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. Initial safety and efficacy results from the trial were reported in March 2025 and established proof of concept for BEAM-302 as a potential one-time treatment for AATD. In addition to the U.S., BEAM-302 has received clinical trial authorization from the United Kingdom, New Zealand, Australia, the Netherlands and Ireland.

Beam plans to continue the dose-escalation portion of Part A, 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.

About BEAM-302
BEAM-302 is a liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents designed to convert the mutant PiZ to corrected PiM isoform. Patients homozygous for this mutation (PiZZ) represent the majority of patients living with severe AATD disease. A one-time A-to-G correction of the PiZ mutation with Beam’s adenine base editor has the potential to simultaneously reduce the aggregation of mutant, misfolded AAT protein that causes toxicity to the liver (Z-AAT), generate therapeutic levels of corrected protein (M-AAT), and increase total and functional AAT in circulation, thereby addressing the underlying pathophysiology of both the liver and lung disease. In addition, the reduction in circulating PiZ aggregates (i.e., polymers) has the potential to further minimize lung inflammation and dysfunction. Importantly, because the native AAT gene would be corrected in its normal genetic location, AAT levels are anticipated to increase physiologically in response to inflammation or infection. This is a critical aspect of AAT’s normal function to regulate the body’s inflammatory response, which does not occur with currently approved protein replacement therapies. Correction of the PiZ mutation is expected to be durable based on preclinical and clinical evidence.

About Alpha-1 Antitrypsin Deficiency (AATD)
AATD is an inherited genetic disorder that can cause early onset emphysema and liver disease. The most severe form of AATD arises when a patient has a point mutation in both copies of the SERPINA1 gene at amino acid 342 position (E342K, also known as the PiZ mutation or the “Z” allele). This point mutation causes alpha-1 antitrypsin, or AAT, to misfold, accumulating inside liver cells rather than being secreted, resulting in very low levels (10%-15%) of circulating AAT. In addition to resulting in lower levels, the PiZ AAT protein variant is also less enzymatically effective compared to wildtype AAT protein. As a consequence, the lung is left unprotected from neutrophil elastase, resulting in progressive, destructive changes in the lung, such as emphysema, which can result in the need for lung transplants. The mutant AAT protein also accumulates in the liver, causing liver inflammation and cirrhosis, which can ultimately cause liver failure, requiring patients to undergo a liver transplant, or cancer.

It is estimated that approximately 100,000 individuals in the U.S. have two copies of the Z allele, known as the PiZZ genotype, although only about 10% of all patients are thought to have been diagnosed. There are currently no curative treatments approved for patients with AATD, and the only approved therapy in the U.S., intravenous AAT protein replacement, has not been shown to prevent ongoing lung function decline and destruction in patients.

About Beam Therapeutics
Beam Therapeutics (Nasdaq: BEAM) is a biotechnology company committed to establishing the leading, fully integrated platform for precision genetic medicines. To achieve this vision, Beam has assembled a platform with integrated gene editing, delivery and internal manufacturing capabilities. Beam’s suite of gene editing technologies is anchored by base editing, a proprietary technology that is designed to enable precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This has the potential to enable a wide range of 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.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements related to: the therapeutic applications and potential of our technology, including our potential to develop life-long, curative, precision genetic medicines for patients through base editing; our plans, and anticipated timing, to advance our BEAM-302 program; and the clinical trial designs and expectations for BEAM-302. Each forward-looking statement is subject to important risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including, without limitation, risks and uncertainties related to: our ability to develop, obtain regulatory approval for, and commercialize our product candidates, which may take longer or cost more than planned; our ability to raise additional funding, which may not be available; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the uncertainty that our product candidates will receive regulatory approval necessary to advance human clinical trials; that preclinical testing of our product candidates and preliminary or interim data from preclinical studies and clinical trials may not be predictive of the results or success of ongoing or later clinical trials; that initiation and enrollment of, and anticipated timing to advance, our clinical trials may take longer than expected; that our product candidates or the delivery modalities we rely on to administer them may cause serious adverse events; that our product candidates may experience manufacturing or supply interruptions or failures; risks related to competitive products; and the other risks and uncertainties identified under the headings “Risk Factors Summary” and “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024, and in any subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law.

Contacts:

Investors:
Holly Manning
Beam Therapeutics
hmanning@beamtx.com

Media:
Josie Butler
1AB
josie@1abmedia.com

FAQ

What is the significance of FDA's IND clearance for BEAM-302?

The clearance allows Beam Therapeutics to advance BEAM-302's development in the U.S., representing their second in vivo base editing program with an open IND and expanding their clinical trial authorization to six countries.

How is BEAM-302 designed to treat AATD patients?

BEAM-302 is a liver-targeting lipid-nanoparticle formulation that uses base editing to correct the disease-causing PiZ mutation in AATD patients.

What are the two parts of BEAM-302's Phase 1/2 clinical trial?

Part A evaluates AATD patients with lung disease, while Part B focuses on AATD patients with mild to moderate liver disease with or without lung disease.

When will Beam Therapeutics release new BEAM-302 clinical trial data?

Beam plans to report updated trial data at a medical conference in the second half of 2025, including results from the fourth dose cohort and initial Part B patient dosing.