Caribou Biosciences, Inc. · NASDAQ:CRBU

Caribou Biosciences — Investor Presentation (May 2024)

46 slides from Caribou Biosciences's investor presentation, May 7, 2024

  1. Slide 1: Corporate presentation

    May 2024 Corporate presentation Transformative genome-edited therapies for patients

  2. Slide 2: Forward-looking statements

    Forward-looking statements All statements in this presentation, other than statements of historical facts, are forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements speak only as of the date of this presentation and a

  3. Slide 3: Precision genome editing with industry-leading expertise

    Precision genome editing with industry-leading expertise chRDNA precision Armored off-the-shelf Resourced for genome-editing technology cell therapies successful execution Novel, next-generation CRISPR Experienced, mission- Allogeneic CAR-T and CAR-NK technology engineered for driven leadership cell

  4. Slide 4: Advancing pipeline of clinical-stage allogeneic CAR-T cell therapies

    Advancing pipeline of clinical-stage allogeneic CAR-T cell therapies for hematologic malignancies and autoimmune diseases Program Clinical trial Target Indication Preclinical Phase 1 Phase 2 Phase 3 Designations Hematologic malignancies ANTLER RMAT, CB-010 CD19 r/r B-NHL Fast Track, Dose expansion O

  5. Slide 5: 2024 clinical catalysts

    Program Clinical milestone Expected timing 2024 CB-010 Present initial dose expansion data, RP2D, and translational data from the ANTLER ASCO June 2024 clinical Phase 1 clinical trial catalysts CB-011 Present initial dose escalation data from CaMMouflage Phase 1 trial YE 2024 CB-010 Initiate GALLOP

  6. Slide 6: chRDNA technology

    chRDNA technology

  7. Slide 7: chRDNA guides promote on-target and reduce off-target edits

    chRDNA guides promote on-target and reduce off-target edits First-generation chRDNA all-RNA CRISPR-Cas CRISPR hybrid RNA-DNA Corporate Presentation | May 2024 7 ©2024 Caribou Biosciences, Inc.

  8. Slide 8: chRDNA guides significantly improve editing specificity

    chRDNA guides significantly improve editing specificity Knockout Knock-in Cas9 Cas12a 13.1 63.0 Insert 2: 76% all-RNA guide chRDNA chRDNA 100 100 80 80 60 60 40 40 20 20 % editing % editing 6 6 6.9 16.9 4 4 Insert 1: 80% 2 2 0 0 Cas12a chRDNA genome editing + AAV6 ON OFF ON OFF ON OFF ON OFF transdu

  9. Slide 9: Engineering for improved activity against disease is key to unlocking allogeneic cell therapies

    Engineering for improved activity against disease is key to unlocking the full potential of allogeneic cell therapies Caribou is implementing multiple armoring strategies Checkpoint disruption (CB-010) PD-1 knockout (KO) sustains initial activity due to exhaustion resistance Immune cloaking (CB-011)

  10. Slide 10: Caribou is a leader in the allogeneic CAR-T cell space

    Caribou is a leader in the allogeneic CAR-T cell space with a platform of genome-edited cell therapies 3 Edits 4 Edits 5 Edits B2M–HLA-E PD-1 KO B2M–HLA-E PD-1 KO CB-010 CB-011 CB-012 Anti-CD19 Anti-BCMA Anti-CLL-1 B cell non-Hodgkin Multiple Acute myeloid lymphoma CAR myeloma CAR leukemia CAR TCR K

  11. Slide 11: Off-the-shelf CAR-T cell therapy programs

    Update with patient-oriented images Off-the-shelf CAR-T cell therapy programs • CB-010 for r/r B-NHL • CB-010 for lupus • CB-011 for r/r MM • CB-012 for r/r AML

  12. Slide 12: Patients shouldn't have to wait for treatment

    Patients shouldn’t have to wait for treatment Allogeneic therapy Screening Product The future of shipment N=many per batch cell therapy is Days Lymphodepletion off-the-shelf Sample Manufacturing, product shipment failure identification Autologous therapy Screening Queuing, leukapheresis Leukapheresi

  13. Slide 13: CB-010 for r/r B-NHL

    CB-010 Allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout for r/r B cell non-Hodgkin lymphoma (B-NHL) Corporate Presentation | May 2024 13 ©2024 Caribou Biosciences, Inc.

  14. Slide 14: CB-010 has a PD-1 KO designed to reduce CAR-T cell exhaustion

    CB-010 has a PD-1 KO designed to reduce CAR-T cell exhaustion CB-010 Armored with 3 genome edits 1 TRAC gene knockout (KO) PD-1 KO • Eliminates TCR expression, reduces GvHD risk Anti-CD19 3 TCR KO CAR Anti-CD19 CAR site-specific insertion into TRAC locus 2 2 PD-L1 1 • Eliminates random integration,

  15. Slide 15: CB-010 ANTLER Phase 1 trial: dose expansion in 2L LBCL underway

    CB-010 ANTLER Phase 1 trial: dose expansion in 2L LBCL underway Part A: 3+3 dose escalation – completed (N=16) Part B: dose expansion – enrolling • Eligibility: aggressive r/r B-NHL1 with ≥2 prior lines of • Eligibility: 2nd line LBCL2 chemoimmunotherapy or primary refractory • Exclusion: prior CD19

  16. Slide 16: Patients in ANTLER dose escalation all had aggressive r/r B-NHL

    Patients in ANTLER dose escalation all had aggressive r/r B-NHL Patients’ baseline and disease characteristics Characteristics Total (N=16) Median age, years (range) 66 (55-82) Male, n (%) 14 (88) ECOG performance status, n (%) 0 6 (38) 1 10 (62) Time since first diagnosis, years Median (range) 2.4

  17. Slide 17: CB-010 has generally well-tolerated safety profile

    CB-010 has generally well-tolerated safety profile No DLTs at dose level 2 or dose level 3, no Grade 3+ CRS, no GvHD observed (N=16) AEs of special ANTLER dose escalation (N=16) interest CRS ICANS Infections CRS ICANS1 Infections2, 3 Gr 3+ Gr 3+ Gr 3+ Any grade, N (%) 7 (44%) 4 (25%) 7 (44%) CB-010

  18. Slide 18: CB-010 ANTLER dose escalation efficacy assessment

    CB-010 ANTLER dose escalation efficacy assessment Overall depth and duration of response SINGLE CB-010 6-month Prior Best DOSE benchmark Subtype Dose # Rx Resp. Pt # FL1 40M 8 CR 1 DLBCL 40M 4 CR 4 * DLBCL2 80M 1 CR 7 CR: complete response DLBCL2 80M 1 CR 8 PR: partial response PMBCL3 40M 2 CR 5 SD:

  19. Slide 19: CB-010 drives durable CRs that rival autologous CAR-T cell therapies

    CB-010 drives durable CRs that rival autologous CAR-T cell therapies 94% 72% 73% 69% CB-010 CR rate at ≥6 months 54% 50% 51% 44% 36% 35% 32% 30% Overall response rate (ORR) Complete response (CR) rate CR rate at 6 months CB-010 Kymriah Yescarta Breyanzi Phase 1 trial Phase 2 trial Phase 1/2 trial Ph

  20. Slide 20: Subgroup efficacy profile supports 2L LBCL clinical development

    Subgroup efficacy profile supports 2L LBCL clinical development r/r B-NHL r/r LBCL2 2L LBCL3 Endpoints All patients Subgroup Subgroup N, (%) (N=16) (N=10) (N=4) Overall response rate (ORR)1 15 (94%) 9 (90%) 4 (100%) Complete response (CR) rate1 11 (69%) 7 (70%) 2 (50%) ≥6-month CR rate1 7 (44%) 5 (5

  21. Slide 21: Advancing CB-010 to establish new standard of care for 2L LBCL

    Advancing CB-010 to establish new standard of care for 2L LBCL and broaden patient access • Response rates rival approved autologous CAR-T cell therapies 94% overall response rate (ORR)1 • Generally well-tolerated safety profile • Off-the-shelf, readily-available single dose cell therapy 69% • RMAT

  22. Slide 22: CB-010 for lupus

    CB-010 Allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout for lupus Corporate Presentation | May 2024 22 ©2024 Caribou Biosciences, Inc.

  23. Slide 23: Lupus is a chronic, inflammatory autoimmune disease driven by B cells

    Lupus is a chronic, inflammatory autoimmune disease driven by autoantibody-producing B cells Lupus is a chronic disease affecting ~320,000 individuals in the US1 Lupus is caused by B cell production of autoantibodies that drive damage of healthy tissue Lupus can cause widespread organ damage, increa

  24. Slide 24: CB-010 is an allogeneic CAR-T cell therapy that targets autoantibody-producing B cells

    CB-010 is an allogeneic CAR-T cell therapy that targets autoantibody-producing B cells Engineered for improved activity CB-010 is engineered chRDNA genome editing Anti-CD19 CAR targets with a PD-1 KO1 to enables precision autoantibody-producing B cells potentially enhance anti-B engineering and redu

  25. Slide 25: CB-010 GALLOP Phase 1 trial design

    CB-010 GALLOP Phase 1 trial design Eligibility and matching Treatment and objective • Non-responsive to glucocorticoids and have tried • Single dose level of CB-010 following LD and failed at least 2 defined immunosuppressive • Primary endpoint: safety therapies v • Excludes cardiac and CNS involvem

  26. Slide 26: Partial HLA matching to potentially improve patient outcomes

    Partial HLA matching to potentially improve patient outcomes HLA matching and DSA screening for How does HLA matching work? ANTLER and GALLOP Phase 1 trials Self cell Partially matched SINGLE HLA typing/ DOSE Self cell T cell DSA analysis CB-010 lot shipped CB-010 Self cell Screening Lymphodepletion

  27. Slide 27: Advancing CB-010 for autoimmune disease

    Advancing CB-010 for autoimmune disease Allogeneic CAR-T cell therapies are derived from healthy donor T cells and offer readily-available, single dose treatment •Expansion of CB-010 development to include autoimmune disease Encouraging initial safety and efficacy in r/r B-NHL CB-010-driven depletio

  28. Slide 28: CB-011 for r/r multiple myeloma

    CB-011 Allogeneic anti-BCMA CAR-T cell therapy with immune cloaking for r/r multiple myeloma (MM) Corporate Presentation | May 2024 28 ©2024 Caribou Biosciences, Inc.

  29. Slide 29: CB-011: anti-BCMA allogeneic CAR-T with immune cloaking

    CB-011: anti-BCMA allogeneic CAR-T cell therapy with immune cloaking to blunt rejection Armored with 4 genome edits TRAC gene knockout (KO) 1 3 B2M • Eliminates TCR expression, reduces GvHD risk Anti-BCMA KO CAR 4 Humanized anti-BCMA CAR site-specifically inserted into B2M–HLA-E 2 TRAC gene 2 • Elim

  30. Slide 30: CB-011 editing strategy designed to reduce T cell- and NK cell-mediated rejection

    CB-011 editing strategy designed to reduce both T cell- and NK cell-mediated rejection B2M KO removes all endogenous HLA class I presentation to reduce T cell-mediated rejection B2M gene knockout reduces B2M—HLA-E expression reduces T cell-mediated rejection NK cell-mediated rejection B2M—HLA-E-pept

  31. Slide 31: B2M KO and B2M–HLA-E fusion protects CB-011 CAR-T cells

    B2M KO and B2M–HLA-E fusion strategy protects CB-011 CAR-T cells from NK and T cell-mediated lysis B2M–HLA-E fusion enables CB-011 cells to B2M KO enables CB-011 cells to resist resist killing by NK cells killing by T cells CAR-T cell co-incubation with NK-92 cells* CAR-T cell co-incubation with PBM

  32. Slide 32: CB-011 enhanced long-term survival in preclinical studies

    CB-011 enhanced long-term survival in preclinical studies CB-011 led to statistically significant and longer survival of tumor-bearing mice relative to an alternative anti-BCMA CAR-T cell therapy after a single dose CB-011 vs alternative BCMA CAR CB-011 vs vehicle p=0.0006 p=0.0001 100 100 Percent s

  33. Slide 33: CB-011 CaMMouflage Phase 1 trial design

    CB-011 CaMMouflage Phase 1 trial design Patients with r/r MM Part A: 3+3 dose escalation • ≥3 prior lines of therapy, including a PI, an IMiD, and an anti- • Objective: safety, determine MTD, RDE CD38 antibody • Exclusions: prior CAR-T cell therapy and/or BCMA-targeted Part B: dose expansion therapy

  34. Slide 34: CB-012 for r/r AML

    CB-012 Allogeneic anti-CLL-1 CAR-T cell therapy with a PD-1 knockout and immune cloaking for r/r acute myeloid leukemia (AML) Corporate Presentation | May 2024 34 ©2024 Caribou Biosciences, Inc.

  35. Slide 35: CB-012: anti-CLL-1 allogeneic CAR-T with PD-1 knockout and immune cloaking

    CB-012: anti-CLL-1 allogeneic CAR-T cell therapy with a PD-1 knockout and immune cloaking 4 Armored with 5 genome edits B2M KO 1 TRAC gene knockout (KO) • Eliminates TCR expression, reduces GvHD risk Anti- PD-1 KO Human anti-CLL-1 CAR site-specifically inserted into TRAC gene CLL-1 3 2 CAR B2M–HLA-E

  36. Slide 36: CB-012 significantly reduced tumor burden and increased overall survival in preclinical studies

    CB-012 significantly reduced tumor burden and increased overall survival in preclinical studies Overall survival analysis Overall survival analysis 100 vehicle Vehicle Control CB-012 CAR-T survival (4 of 5 CB-012 edits, CB-012 unedited PD-1 unedited) ofSurvival PDCD1 CB-012 Probability of 50 Probabi

  37. Slide 37: CB-012 AMpLify Phase 1 trial design

    CB-012 AMpLify Phase 1 trial design Patients with r/r AML • Relapsed or refractory AML patients should have received at Part A: 3+3 dose escalation – enrolling least 1 but not more 3 prior lines of therapy • Objective: safety, determine MTD/RDE • Patients with prior allo or auto SCT are allowed • Ex

  38. Slide 38: 2024 accomplishments and upcoming milestones

    2024 accomplishments and upcoming milestones Hematologic malignancies Autoimmune disease CB-010 in 2L LBCL Present initial dose CB-010 in LN and ERL expansion data from ASCO June Initiate GALLOP Phase 1 trial YE 2024 ANTLER Phase 1 trial in 2L 2024 LBCL, RP2D CB-011 in r/r MM Present initial dose es

  39. Slide 39: Thank you

    Thank you https://cariboubio.com info@cariboubio.com

  40. Slide 40: Allogeneic CAR-T cell manufacturing process overview for CB-010

    Allogeneic CAR-T cell manufacturing process overview for CB-010 Caribou’s process development team created the manufacturing process and transferred it to a CMO to generate phase 1 cGMP clinical material cGMP starting Genetic modification via Gene-modified In vitro expansion of Removal of residual F

  41. Slide 41: CB-010 ANTLER dose escalation efficacy assessment

    CB-010 ANTLER dose escalation efficacy assessment Overall, r/r, and 2L LBCL subgroups, by dose level r/r B-NHL r/r LBCL2 2L LBCL3 CB-010 dose level Endpoints All patients Subgroup Subgroup 40M 80M 120M (N, %) (N=16) (N=10) (N=4) (N=8) (N=5) (N=3) Overall response rate 15 (94%) 9 (90%) 4 (100%) 8 (10

  42. Slide 42: CB-010's responses rival autologous CAR-T cell therapies

    CB-010’s responses rival autologous CAR-T cell therapies CB-010 Kymriah Yescarta Breyanzi dose escalation Phase 2 Phase 1/2 Phase 1 Phase 1 % (n/N) % (n/N) % (n/N2) % (n/N) Overall response rate (ORR)1 94% (15/16) 50% (34/68) 72% (73/101) 73% (141/192) Complete response (CR) rate1 69% (11/16) 32% (2

  43. Slide 43: CB-010 is generally well tolerated

    CB-010 is generally well tolerated Treatment-emergent adverse events (TEAE) Event Any Grade1 All Grade 3+ Related Grade 3+ (N=16) N (%) N (%) N (%) Total number of TEAEs, N 348 96 28 Subjects with TEAE, n (%) 15 (94) 14 (88) 8 (50) Thrombocytopenia/platelet count decreased 11 (69) 11 (69) 5 (31) Ane

  44. Slide 44: CB-010 demonstrated differentiated, long-term antitumor activity in preclinical studies

    CB-010 demonstrated differentiated, long-term antitumor activity in preclinical studies A single dose of CB-010 resulted in profound tumor regression of metastatic CD19+ tumor xenografts and led to a significantly longer antitumor response and survival vs. conventional CD19-specific allogeneic CAR-T

  45. Slide 45: Potential to address high unmet medical need in 2L LBCL

    Potential to address high unmet medical need in 2L LBCL LBCL patient treatment journey (U.S. incidence 2022) Diagnosed ~32.4K patients 1L ~30.8K patients ANTLER dose 2L ~10.0K patients expansion 3L ~4.4K patients Corporate Presentation | May 2024 45 ©2024 Caribou Biosciences, Inc.

  46. Slide 46: Herd diversity

    Herd diversity Corporate Presentation | May 2024 46 ©2024 Caribou Biosciences, Inc.

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