Beam Therapeutics Inc. · NASDAQ:BEAM
Beam Therapeutics — Alpha-1 National Conference 2024
21 slides from Beam Therapeutics's conference presentation, Jun 8, 2024
Slide 1: BEAM-302 Base editing for alpha-1 antitrypsin deficiency
BEAM-302 Base editing as a potential therapeutic approach for alpha-1 antitrypsin deficiency (Alpha-1) Alpha-1 National Conference Nicolas Currier MD, PhD Senior Medical Director June 8, 2024
Slide 2: Disclosure
DISCLOSURE • I am a Beam employee and shareholder 2
Slide 3: Our purpose is patients
OUR PURPOSE IS PATIENTS OUR VISION IS TO PROVIDE LIFE -LONG CURES for patients suffering from serious diseases O U R VA L U E S D R I V E U S A community of RIGOROUS AND Listening with COMMITTED FEARLESS HONEST in our OPEN MINDS to each other INNOVATORS research 3
Slide 4: Founded in 2017
Beam is breaking new ground to advance science with the potential to change lives through precision genetic medicines Founded in 2017 Base editing 3 Programs 1 Program 2 Locations has potential in clinic coming to Cambridge, MA, and to treat • Alpha-1 clinic soon Research Triangle, NC disease • Sick
Slide 5: Base editing
Base editing 5
Slide 6: In our genetic code, spelling matters
In our genetic code, spelling matters, and a single base change can result in disease The genetic information A single spelling error in the code—known as a point mutation— that makes you you is can lead to serious illness just as a single misspelled letter in a word stored as a unique code in can l
Slide 7: Base editing provides a unique opportunity to address serious disease with precision
Base editing provides a unique opportunity to address serious disease with precision “ Base editing • We use a new tool called base editing, which works like a “pencil and eraser” Many existing on the genome; it changes a gene editing approaches are cytosine (C) to thymine (T) like ‘scissors’ that c
Slide 8: What are the components of a Base Editor?
What are the components of a Base Editor? Base editors have two principal components: CRISPR protein Base-editing • 1) a CRISPR protein, bound to a guide enzyme RNA, that uses the established DNA- (deaminase) targeting ability of CRISPR to get to the Guide RNA right location on the gene but is modif
Slide 9: Base editing in Alpha-1
Base editing in Alpha-1 9
Slide 10: BEAM-302: Aims to restore expression of functional AAT
BEAM-302: Aims to restore expression of functional AAT to address Alpha-1-related lung and liver disease Liver Lung Alpha-1 Cause • PiZ is caused by a single G > A point mutation in the SERPINA1 gene • PiZ AAT is poorly secreted by the liver into circulation and has decreased function Alpha-1 Unmet
Slide 11: BEAM-302 utilizes LNP delivery to target the liver
BEAM-302: Utilizes lipid nanoparticle (LNP) delivery to target the liver (“in vivo”) 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 Pi
Slide 12: BEAM-302 corrects PiZ to PiM in an Alpha-1 mouse model
BEAM-302 corrects the PiZ variant to PiM in a dose dependent manner in an Alpha-1 mouse model Liver Editing Corrected SERPINA1 gene* 80 Additional base-edits in SERPINA1 PiZ Editing efficiency (%) Indels (insertions and deletions of bases) i.v. delivery 60 48.7 49.2 PiZ mouse 40 BEAM-302 37.3 28.0 2
Slide 13: Editing decreases Z-AAT and increases total blood AAT
Editing decreases Z-AAT and increases total blood AAT protein, which correlates to increased functional AAT BloodAAT Serum AAT(LC-MS) Levels Functional AAT vs. Blood AAT Levels 80 80 200 Functional AAT (micromolar) Total AAT (micromolar) PiZ AAT (micromolar) 60 60 150 (NE inhibition) 40 40 100 20 20
Slide 14: Base editing by BEAM-302 at the target site
Base editing by BEAM-302 at the target site • BEAM-302 is designed to correct the CRISPR protein mutation that causes PiZ AAT Base-editing enzyme (deaminase) • The corrected functional AAT protein Guide RNA produced is either PiM or PiM with an additional, naturally occurring, bystander edit at a ne
Slide 15: PiM + bystander AAT functionally comparable to PiM AAT
The PiM + bystander AAT protein is functionally comparable to PiM AAT protein Equivalent AAT Equivalent AAT function by binding and inhibition of secretion in cell culture* neutrophil elastase in vitro Human Neutrophil Elastase AAT secretion form Human Neutrophil Elastase Inhibition Assay Transfecte
Slide 16: BEAM-302 correction also addresses liver disease in mouse model
BEAM-302 correction of the PiZ variant also addresses liver disease in an Alpha-1 mouse model Reduction in toxic Day 7 i.v. delivery No Beam-302 liver aggregates ("Control") 50 PAS-D Stained Area (%) PiZ Mouse 40 30 1-week 20 10 Day 7 BEAM-302 0 Control Correction ("Correction") (0.25mpk) Stain for
Slide 17: Single dose of BEAM-302 leads to durable correction
Single dose of BEAM-302 leads to durable correction of the PiZ variant Liver editing 80 Corrected SERPINA1 gene* Additional base-edits in SERPINA1 To date, SERPINA1 gene editing and AAT Indels levels are either stable or increasing after a Editing Efficiency % single dose 60 • Gene editing and AAT l
Slide 18: Next Steps
Next Steps 18
Slide 19: Phase 1/2 trial designed to achieve clinical proof-of-concept
Phase 1/2 trial designed to achieve clinical proof-of- concept across the spectrum of Alpha-1 → now open in the UK* Clinicaltrials.gov NCT06389877 Part A: Alpha-1-associated Lung Disease Opportunity to achieve Dose Exploration Dose Expansion first ever clinical proof- Assess of-concept of in vivo •
Slide 20: Working with the Alpha-1 Community
Working with the Alpha-1 Community Beam worked with individuals with PiZZ to: • Optimize BEAM-302 trial design • Develop trial educational materials that are relevant and understandable 20
Slide 21: Thank You
THANK YOU 21