Beam Therapeutics Inc. · NASDAQ:BEAM
Beam Therapeutics — Investor Presentation (January 2021)
34 slides from Beam Therapeutics's investor presentation, Jan 12, 2021
Slide 1: Precision Genetic Medicines Through Base Editing
PRECISION GENETIC MEDICINES THROUGH BASE EDITING Beam Therapeutics NASDAQ: BEAM Exhibit 99.1
Slide 2: Forward-looking statements
This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements reflect, among other things, our current expectations and anticipated results of operations, all of which are subject to known and unknown
Slide 3: Coming era of one-time, curative therapies
Coming era of one-time, curative therapies Gene editing for rare and common diseases Platform for rapidly-programmable precision medicines Our vision is to provide life-long cures for patients suffering from serious diseases 3
Slide 4: Base editing is a new approach to gene editing
Base editing is a new approach to gene editing Nuclease editing CRISPR, Zinc Fingers, TALEs Base editing 4
Slide 5: Base editing is a highly-differentiated, potentially best-in-class gene editing technology
Base editing is a highly-differentiated, potentially best-in-class gene editing technology
Slide 6: Diversified portfolio of wholly-owned base editing programs
Diversified portfolio of wholly-owned base editing programs LNP = Lipid Nanoparticle; AAV = Adeno Associated Virus; CNS = Central Nervous System 6
Slide 7: Key progress and milestones
Key progress and milestones 7 ELECTRO- PORATION NON-VIRAL (LNP) ✓ ✓ 2020 achievements VIRAL (AAV) ✓ ✓ In vivo proof of concept and development candidate nomination for BEAM-101 Initiate IND-enabling studies for BEAM-101 >80% direct correction of sickle mutation and development candidate nomination f
Slide 8: We are establishing the leading platform for precision genetic medicine
We are establishing the leading platform for precision genetic medicine Full suite of gene editing technologies Base editing Nuclease editing RNA editing Prime editing Full suite of delivery technologies Auto / allo cell products mRNA LNP vectors Viral vectors Wholly-owned manufacturing capability 1
Slide 9: Electroporation
Electroporation Ex vivo delivery of base editors using clinically validated electroporation technology Target cell Electroporation of program-specific gRNA and base editor mRNA Base editor performs gRNA-dependent editing 9
Slide 10: Autologous ex vivo cell process for editing hematopoietic stem cells
Autologous ex vivo cell process for editing hematopoietic stem cells Collect cells Electroporate Infuse cell product Condition patient Sickle Cell Disease Patient Sickle Cell Disease Patient 3 4 1 2 10
Slide 11: Sickle cell disease (SCD)
Sickle cell disease (SCD) T-to-A mutation causes sickling Adult β-globin gene β-globin gene Glutamic acid at 6th amino acid (HbA) Normal red blood cells Sickle β-globin gene Valine at 6th amino acid (HbS) Sickling red blood cells 11 Approximately 100,000 sickle cell disease patients in the US
Slide 12: BEAM-101: Recreating HPFH with base editing
BEAM-101: Recreating hereditary persistence of fetal hemoglobin (HPFH) with base editing Reactivating fetal hemoglobin genes Sickle cell disease patient Naturally-occurring base changes cause Hereditary Persistence of Fetal Hemoglobin (HPFH), which protects patients from SCD/B-Thal Base editors can
Slide 13: BEAM-101: Robust base editing at HBG1/2 gene promoters in SCD patient cells
BEAM-101: Robust base editing at HBG1/2 gene promoters in sickle cell disease patient cells 13 Experiments shown are in vitro-derived erythroid cells
Slide 14: BEAM-101: High levels of editing and robust HbF induction after engraftment
BEAM-101: High levels of editing and robust HbF induction after long-term in vivo engraftment >90% human chimerism in bone marrow 16 weeks post-transplanta >90% base editing at HBG1/2 promoters in multilineage cellsb >65% gamma globin protein levels in sorted erythroid cellsc 14 Unedited Edited Bulk
Slide 15: BEAM-102: Direct correction of the sickle causing mutation
BEAM-102: Direct correction of the sickle causing mutation Base editing recreates naturally-occurring human variant Hb-G Makassar which has alanine (E6A) instead of sickle-causing valine (E6V)1 Hb-G Makassar is a normal β-globin variant and does not cause sickle disease, e.g., blood smear shows nega
Slide 16: BEAM-102: Efficient direct correction of sickle mutation in patient cells
BEAM-102: Highly efficient, novel direct correction of sickle mutation in sickle patient cells Allelic editing of 100 individual erythroid colonies post-electroporation was assessed for the Makassar edit by NGS using cells from HbSS donor. ~93% of cells have at least one sickle allele converted to M
Slide 17: BEAM-102: High editing leads to elimination of HbS globin
BEAM-102: High editing of sickle mutation leads to significant elimination of HbS globin in patient donor cells Sickle (HbS) and Makassar variant globin protein, at varying bulk levels of Makassar editing assessed by NGS, was measured by UPLC and expressed as a fraction of total beta globin in 18 da
Slide 18: Two base editing approaches to silence genes
Two base editing approaches to silence genes Expanding list of targets for CAR-T editing1 Two strategies for silencing with base editors Splice disruption with CBE CONFIDENTIAL 18 1. Adapted from Jung & Lee. 2018. Molecules and Cells.
Slide 19: Allogeneic multiplex edited CAR-T cell process
Allogeneic multiplex edited CAR-T cell process Collect T-cells Electroporate and transduce Lymphodeplete and infuse Expand and freeze Editor mRNA gRNA #1 gRNA #2 gRNA #3 gRNA #4 Lentiviral CAR 3 4 1 2 19
Slide 20: BEAM-201: Multiplex editing across four genomic loci
BEAM-201: Multiplex editing across four genomic loci with base editing 20 Single electroporation of base editor mRNA and 4 gRNAs With few options to induce a second remission, post-relapse survival for T-cell acute lymphoblastic leukemia (T-ALL) is low TRAC: Prevent graft-vs-host disease CD52: Enabl
Slide 21: Clinical scale BEAM-201 process produces 96-99% individual gene knock-out
Clinical scale BEAM-201 process produces 96-99% individual gene knock-out & potent in vivo activity 21 Clinical-scale process produces individually 96-99% editing, estimated 91% quad edited Potent in vivo tumor clearance or control across a 25-fold dose Treatment Randomization
Slide 22: Multiplex base editing with no detectable translocations
Multiplex base editing with no detectable translocations and maintained cell expansion 22 1. Lower limit of detection for rearrangements of 0.1%; 2. B2M-B only measurable if translocation includes local rearrangement in B2M; 3. Extensive guide screen across three targets, with both BE4 and spCas9 sg
Slide 23: Clinically validated technology for in vivo delivery to the liver
Clinically validated technology for transient, in vivo delivery to the liver Scalable LNP manufacturing Beam has developed several proprietary LNP formulations Non-viral delivery for in vivo base editing 23 Infuse Formulate LNP 1 2
Slide 24: Alpha-1 Antitrypsin (A1AT) Deficiency
Alpha-1 Antitrypsin (A1AT) Deficiency Normal A1AT Function Genetics Liver Respiratory A1AT Deficiency Wild type SERPINA1 gene A1AT protein is secreted, protecting lungs E342K (PiZ) mutation Direct correction of the PiZ mutation through base editing can: Restore circulation of functional A1AT to prot
Slide 25: Direct correction of PiZ mutation in primary PiZZ fibroblasts
Direct correction of PiZ mutation by base editing in primary PiZZ fibroblasts Alpha-1 Antitrypsin Deficiency base editing products ~45% correction of PiZ mutation in primary PiZZ fibroblasts ABE edits Resulting A1AT Variant Target Target + Bystander Bystander only Beneficial alleles are secreted and
Slide 26: PiZ correction may confer a proliferative advantage to edited hepatocytes
PiZ correction may confer a proliferative advantage to edited hepatocytes LNP-mediated in vivo correction of the PiZ mutation increases over time 26 P value assessed by T-test
Slide 27: In vivo direct correction of A1AT mutation – addressing liver and lung
In vivo direct correction of A1AT mutation with base editing – addressing both liver and lung 27 4.9-fold increase in functional A1AT secretion Reduction in toxic liver aggregates
Slide 28: Glycogen Storage Disease Type 1a
Glycogen Storage Disease Type 1a Genetic liver disease caused by mutations in G6PC gene encoding G6Pase R83C and Q347X mutations affect 900 and 500 patients in US, respectively G6PC activity reaching >11% of wildtype activity may be enough to improve liver histology and survival2 1. Rake, et al. 200
Slide 29: Precise correction of G6PC may provide life-long genetic change
Unlike AAV gene therapy that can wane, precise correction of G6PC may provide life-long genetic change, passed through cell division, and may enable treatment in children Precise correction at native locus would restore the endogenous regulation of tightly coordinated glucose metabolism ABE achieves
Slide 30: Clinically validated technology for in vivo delivery to a variety of tissue types
Clinically validated technology for in vivo delivery to a variety of tissue types Split intein technology designed to deliver base editor and guide RNA by co-infection with two viruses DNA base editors are larger than the ~4.5kb limit of AAV vectors Viral delivery for in vivo base editing 30 Co-infe
Slide 31: ABCA4 mutations cause central vision loss and death of photoreceptor cells
ABCA4 mutations cause central vision loss and death of photoreceptor cells Most prevalent G1961E mutation accounts for 5,500 patients in US No approved therapies today ABCA4 gene cannot be packaged into a single AAV vector due to size Stargardt Macular Dystrophy ABE achieves ~75% correction delivere
Slide 32: Strategic collaborations and investment in future capabilities
Strategic collaborations and investment in future capabilities 32 Base editing for the prevention of cardiovascular disease Non-ablative conditioning for improved hematology transplant in combination with BEAM-101 and BEAM-102 Clinical and research activities for sickle cell disease, leukemias, and
Slide 33: Meet the Beam Team
Meet the Beam Team John Evans Chief Executive Officer Giuseppe Ciaramella, PhD President, Chief Scientific Officer Courtney Wallace Chief Business Officer Susan O’Connor Chief Human Resources Officer Christine Bellon PhD, JD SVP, Chief Legal Officer Suzanne Fleming SVP, Finance Terry-Ann Burrell Chi
Slide 34: Thank you
Thank you 34
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