BEAM-302 demonstrated the first-ever clinical genetic correction of a disease-causing mutation, leading to a durable and dose-dependent increase in total and functional AAT. How significant is this breakthrough in the treatment of genetic disorders, and what are the implications for patients with AATD?

At the highest tested dose (60 mg), BEAM-302 achieved a mean total AAT of 12.4µM at Day 28, exceeding the protective therapeutic threshold. How does this compare to the levels achieved with current augmentation therapy, and could this be a functional cure for AATD patients?

BEAM-302 reduced circulating mutant Z-AAT by up to 78%. Given that Z-AAT accumulation is a primary driver of liver toxicity, how important is this reduction in addressing the liver manifestations of AATD, and could it help prevent long-term complications such as cirrhosis?

BEAM-302 was well tolerated with no serious adverse events or dose-limiting toxicities. With genetic therapies, long-term safety is always a concern. What data would you like to see in later-stage trials to further confirm the safety profile of this base editing approach?

Unlike protein augmentation therapy, which requires lifelong treatment, BEAM-302 is designed as a one-time genetic correction. What are the potential advantages and challenges of a single-dose curative approach compared to chronic therapy for AATD?

Part A of the trial focuses on AATD patients with lung disease, while Part B will include those with mild to moderate liver disease. How might BEAM-302 impact patients at different stages of AATD, and do you foresee it being more beneficial for one organ system over the other?

Beam Therapeutics plans to continue dose escalation and present additional data later in 2025. What are the key milestones that regulators and clinicians will be looking for in order to advance BEAM-302 to late-stage clinical trials?"

BEAM-302’s success also demonstrates the viability of in vivo base editing for treating monogenic diseases. What do you see as the broader implications of this trial for the future of genetic medicine, and could this technology extend to other inherited disorders beyond AATD?