Beam Therapeutics Inc. · NASDAQ:BEAM
Beam Therapeutics — 2025 Alpha-1 Foundation 7th Global Research Conference and 10th Patient Congress
20 slides from Beam Therapeutics's conference presentation, May 2025
Slide 1: BEAM-302: A potential base editing therapeutic for alpha-1 antitrypsin deficiency
BEAM-302: A potential base editing therapeutic f or alpha-1 antitrypsin deficiency (Alpha-1) 2025 Alpha-1 Foundation 7th Global Research Conference and 10th Patient Congress Nicolas Currier, MD, PhD Senior Medical Director
Slide 2: Disclosure
DISCLOSURE • I am a Beam employee and shareholder 2
Slide 3: Our vision is to provide life-long cures for individuals suffering from serious diseases
Our vision is to provide life-long cures for individuals suffering from serious diseases To achieve our vision, we have created a strong values-driven organization focused on people, advancing cutting-edge science, and developing a new class of precision genetic medicines Two locations Base editin
Slide 4: Base editing provides a unique opportunity to address serious disease with precision
Base editing provides a unique opportunity to address serious disease with precision “ • DNA is made up of 3 billion bases defined by letters A,T,C,G Many existing gene editing • A single spelling error in your DNA, a point mutation, can approaches are like ‘scissors’ that lead to disease cut the ge
Slide 5: Alpha-1 lung and liver disease are both caused by a single point mutation
Alpha-1 lung and liver disease are both caused by a single point mutation (spelling error) Alpha-1 cause1–3 Liver Lung • PiZ is caused by a single G → A point mutation in the SERPINA1 gene • PiZ AAT causes liver damage and is poorly secreted by the liver into circulation. Decreased Alpha-1 circulati
Slide 6: BEAM-302 has the potential to be the only one-time treatment for lung and liver Alpha-1
BEAM-302 has the potential to be the only one-time treatment for both lung and liver manifestations of Alpha-1 BEAM-302 has potential to address critical aspects of Alpha-1 Increase secreted AAT to prevent lung damage Correct DNA mutation – Restore normal control of Potential durable, the root cause
Slide 7: The Phase 1/2 study aims to evaluate the safety and efficacy of BEAM-302
The Phase 1/2 study aims to evaluate the safety and efficacy of BEAM-302 in people with Alpha-1 Part A: Alpha-1-associated lung disease PART A: KEY ELIGIBILITY CRITERIA Dose exploration Dose expansion • 18–70 years of age • Homozygous for PiZZ mutation DOSING COMPLETE in first three cohorts of Part
Slide 8: Preliminary data support the safety of BEAM-302 at doses up to 60 mg
Preliminary data support the safety of BEAM-302 at doses up to 60 mg 15 mg N=3 30 mg N=3 60 mg N=3 • There were no serious adverse events Patients with n (%) n (%) n (%) (AEs), dose-limiting toxicities or Any TEAEs 3 (100) 3 (100) 2 (66.7) ≥Grade 3 AEs Related to • All treatment-related AEs (TEAEs)
Slide 9: BEAM-302 led to a rapid, dose-responsive increase of total AAT above protective threshold
BEAM-302 treatment led to a rapid, dose-responsive increase of total AAT above the 11µM protective threshold Total AAT by Turbidimetry (Mean ± SE) 16 14 Serum Concentration (μM) Baseline, Total AAT at Day 28, Dose 12 mean mean Protective threshold 10 15 mg 4.4µM 7.0µM 60 mg 8 30 mg 15 mg 6 30 mg 5.3
Slide 10: Dose-dependent increase in fold change in total AAT following BEAM-302
Dose-dependent increase in fold change in total AAT observed following treatment with BEAM-302 Fold Change in Total AAT by Turbidimetry (Mean ± SE) 3 Fold Change in Dose Baseline, mean Total AAT at Fold Change Over Baseline 2.5 Day 28, mean 2 15 mg 4.4µM 1.6× 1.5 1 60 mg 30 mg 5.3µM 1.9× 30 mg 15 mg
Slide 11: Rapid, dose-dependent reductions in circulating mutant Z-AAT
BEAM-302 treatment also led to rapid, dose-dependent reductions in circulating mutant Z-AAT % Change Mutant Z-AAT from Baseline by LC-MS (Mean ± SE) % change in Z-AAT at Dose Day 28, mean 15 mg −11% 30 mg −38% 60 mg −79% Data cutoff February 26, 2025. Baseline for each patient is defined as the aver
Slide 12: Up to 91% M-AAT in circulation; correction durable up to 6 months
BEAM-302 treatment led to up to 91% M-AAT in circulation; correction has been durable up to 6 months Proportion (%) of Corrected M-AAT and Mutant Z-AAT by LC-MS by Cohort (Mean ± SE) MZ genotype profile: 80% M, 20% Z in circulation Corrected M-AAT Mutant Z-AAT Corrected M-AAT is comprised of both Pi
Slide 13: Increased AAT in circulation is functional following BEAM-302
Increased AAT in circulation is functional following BEAM-302 Total AAT (Turbidimetry) and Functional AAT (Inhibition) by Cohort (Mean ± SE) 15 mg 30 mg 60 mg Serum Concentration (µM) 18 15 12 9 6 3 0 N= N= N= 3 3 3 3 3 2 3 3 33 3 3 3 3 3 3 3 3 3 1 1 3 3 3 3 3 2 3 3 33 3 3 3 3 3 3 3 3 3 3 3 Visit Fu
Slide 14: Summary: Initial data demonstrated safety and efficacy in patients with Alpha-1
Summary: Initial data from BEAM-302 clinical study demonstrated safety and efficacy in patients with Alpha-1 Target the liver Decrease mutant Z-AAT Correct DNA Correct mutation –– DNA mutation (where AAT is produced) Increase secreted AAT to to prevent liver and the root the root cause cause of of d
Slide 15: Next steps
Next steps • Continue dose escalation to identify the BEAM-302 dose regimen that has optimal safety and efficacy in patients with Alpha-1 • Expand country and site activation: o Regulatory approvals obtained in Australia, Ireland, Netherlands, New Zealand, UK, and US • Presentation of updated study
Slide 16: Thank you
a ", : Beam THERAPEUTICS THANK YOU
Slide 17: BEAM-302 utilizes LNP delivery to target the liver and correct the A base mutation
BEAM-302 utilizes lipid nanoparticle (LNP) delivery to target the liver and correct the A base mutation back to the typical G Nuclear import Lipid Base editor mRNA T ▲ Target DNA gRNA A Editor + gRNA (PiZ) binding RNP Formulate LNP T Translation of Correction ▲ editor protein editing A PiZ PiM Relea
Slide 18: BEAM-302 is a potential one-time therapy using base editing to correct E342K
BEAM-302 is a potential one-time therapy that uses base editing to directly correct the E342K mutation causing AATD BEAM-302 BASE EDITOR PiZ PiM CRISPR Protein Deaminase Guide RNA E342K mutation Corrected SERPINA1 gene • Presence of an additional “A” within the editing window yields a mixture of cor
Slide 19: Corrected PiM + variant AAT is structurally and functionally comparable to PiM AAT
Corrected PiM + variant AAT is structurally and functionally comparable to PiM AAT Superimposable Equivalent secretion in Equivalent Inhibition of Human genetic structures* cell culture** Neutrophil Elastase in vitro validation Human Neutrophil Elastase • PiM variant is naturally AAT secretion form
Slide 20: Increasing total AAT above protective threshold reduces lifetime risks for lung and/or liver disease
Increasing total AAT levels above protective threshold reduces patients’ lifetime risks for lung and/or liver disease AAT Levels and Disease Manifestations Across Genotypes1–3 The goal of treatment with BEAM-302 is to: • Increase circulating total AAT above the 11µM “protective threshold” • Reduce Z