Beam Therapeutics Inc. Q3 FY2024 earnings call

• Beam's base editing technology allows precise single base changes, enabling potential one-time treatments for serious diseases.
• In hematology, the BEACON trial for BEAM-101 in sickle cell disease has 35 patients enrolled, with initial clinical data showing potential differentiation. Non-human primate data for ESCAPE technology validate gene editing and stem cell transplant without chemotherapy.
• In liver genetic diseases, BEAM-302 in AATD has completed dosing in the first cohort, with first clinical data expected in 2025. BEAM-301 received U.S. IND clearance and is set to commence dosing in early 2025.
• Four abstracts accepted for presentation at ASH 2024, including oral presentations on BEACON trial data and ESCAPE technology, and poster presentations on BEAM-101 and BEAM-201.
• Financial highlights: Exceeded enrollment expectations in BEACON trial, completed dosing in first cohort of BEAM-302 trial, and received U.S. IND clearance for BEAM-301.

Beam operates in two core franchises: hematology and liver genetic diseases. In hematology, the BEACON trial for BEAM-101 in sickle cell disease has exceeded enrollment expectations with 35 patients enrolled, and initial clinical data from the BEACON Phase 1/2 trial supports potential clinical differentiation. For liver genetic diseases, BEAM-302 in alpha-1 antitrypsin deficiency (AATD) has completed dosing in the first cohort of its Phase 1/2 trial, with first clinical data expected in 2025. Additionally, BEAM-301 received U.S. IND clearance for glycogen storage disease 1a and is expected to commence patient dosing in early 2025.

• Expect to report first clinical data from BEAM-302 in AATD in 2025.
• BEAM-301 patient dosing expected to commence in early 2025.
• Continue dose escalation in BEAM-302 trial and aim to release data in 2025 showcasing proof-of-concept for the program.
• Accelerate development of ESCAPE technology towards the clinic, with plans to initiate Phase I enabling studies by the end of 2024.

• Safety risk associated with busulfan used in transplant conditioning, including rare instances of lung injury and death, as seen in one patient in the BEACON trial.
• Potential off-target editing risks, though none have been observed in preclinical or early clinical studies to date.
• Regulatory and clinical trial risks related to demonstrating efficacy and safety for new gene editing therapies in different disease indications.

Q: Concern about the patient's death due to busulfan toxicity and its impact on safety?

A: John Evans noted it's a real risk of transplant and chemotherapy, but the team uses standard dosing and the event was determined unrelated to BEAM-101. Amy Simon explained busulfan is associated with dose-dependent pulmonary toxicity, a known complication of myeloablative conditioning.

Q: How does higher HbF induction translate to clinical benefit compared to approved products?

A: Giuseppe Ciaramella stated the 60-40 HbF to S ratio seen with BEAM-101 is similar to sickle cell trait, leading to normalized hemolysis, decreased RBC sickling, and improved blood function, potentially offering better clinical benefit than approved products.

Q: Concerns about high total hemoglobin counts in early patients and long-term follow-up?

A: Amy Simon noted mild elevations are laboratory abnormalities with no clinical symptoms, and patients' blood health and function have improved to levels similar to sickle cell trait, with no concerns from investigators.

Q: Safety concerns for BEAM-103 targeting CD117?

A: Giuseppe Ciaramella mentioned antibodies against CD117 have been studied, showing transient mild neutropenia, but no myeloblative effects, opening the possibility of outpatient treatment.

Q: Expansion to beta thalassemia with ESCAPE technology and trial locations?

A: Giuseppe Ciaramella said ESCAPE alters risk-benefit for beta thalassemia, potentially treating beyond transfusion-dependent patients. Trial locations for Phase 1 studies will be determined based on efficiency and rapid exploration.