Slide 1: CB-010 ANTLER Phase 1 trial update and KOL discussion
CB-010 ANTLER Phase 1 trial update and KOL discussion Transformative genome-edited therapies for patients June 2, 2024
Slide 2: Forward-looking statements
2 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. 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 199
Slide 3: The future of CAR-T cell therapies is off-the-shelf
The future of CAR-T cell therapies is off-the-shelf CB-010 ANTLER Phase 1 trial Rachel Haurwitz, PhD President & CEO Caribou Biosciences, Inc.
Slide 4: Today's guests
4 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Today’s guests Assistant professor, director of lymphoma and CLL in the division of hematology and hematologic malignancies Huntsman Cancer Institute University of Utah Professor of medicine and section chief of
Slide 5: Patients shouldn't have to wait for treatment
5 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Patients shouldn’t have to wait for treatment 1 Mikhael, J. et al. JCO Oncology Practice 2022 18:12, 800-807 The future of cell therapy is off-the-shelf Allogeneic therapy N=many per batch Autologous therapy N=1
Slide 6: Allogeneic anti-CD19 CAR-T with a PD-1 knockout for r/r B-NHL
6 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout for r/r B cell non-Hodgkin lymphoma (B-NHL) CB-010
Slide 7: CB-010 has a PD-1 KO designed to reduce CAR-T cell exhaustion
7 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 has a PD-1 KO designed to reduce CAR-T cell exhaustion CB-010 NHL cell 1 2 3 TCR KO MHC I Anti-CD19 CAR CD19 PD-L1 PD-1 KO Armored with 3 genome edits 1 2 3 TRAC gene knockout (KO) • Eliminates TCR express
Slide 8: CB-010 ANTLER Phase 1 trial in 2L LBCL
8 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER Phase 1 trial in 2L LBCL Part A: 3+3 dose escalation – completed (N=16) • Eligibility: aggressive r/r B-NHL1 with ≥2 prior lines of chemoimmunotherapy or primary refractory • Exclusion: prior CD19-t
Slide 9: Foundational data: durable responses in dose escalation
9 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010’s foundational data: durable responses in dose escalation 4 of 4 DLBCL patients remain in CR since last data cutoff June 20, 2023 DLBCL: diffuse large B cell lymphoma; FL: follicular lymphoma; HGBL: high-g
Slide 10: Partial HLA matching shows safety, efficacy, and durability
10 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 with partial HLA matching shows safety, efficacy, and durability can potentially rival autologous CAR-T cell therapies 2L: second-line; 3L: third-line; B-NH: B cell non-Hodgkin’s lymphoma; CI: confidence
Slide 11: Improved PFS with partial HLA matching
11 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Improved PFS for all patients treated with CB-010 from a donor with partial (≥4) HLA matching PFS by level of HLA matching All patients N=46*, median PFS (95% CI) PFS by level of HLA matching LBCL patients N=40*
Slide 12: Preliminary PFS on par with approved autologous CAR-T
12 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Preliminary PFS with partial HLA matching has potential to be on par with an approved autologous CAR-T cell therapy Source: ZUMA-7, Locke et al, NEJM, 2022 PFS: progression free survival; 2L: second-line; 3L: th
Slide 13: ANTLER Phase 1 trial initial dose expansion data
ANTLER Phase 1 trial initial dose expansion data Boyu Hu, MD Director of Lymphoma and CLL Division of Hematology and Hematologic Malignancies Huntsman Cancer Institute
Slide 14: Disclosures
14 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Disclosures Consulting: Novartis, Bristol Meyers Squibb, Eli Lilly, GenMab, ADC Therapeutics, ImmPACT Bio, Seattle Genetics, Regeneron, Caribou Biosciences, Abbvie Research Funding: Genentech, Celgene, CRISPR Th
Slide 15: Patients in ANTLER all had aggressive r/r B-NHL
15 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Patients in ANTLER all had aggressive r/r B-NHL DLBCL: diffuse large B cell lymphoma; FL: follicular lymphoma; HGBL: high-grade B cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; PMBCL: pri
Slide 16: Rapid timeline to treatment key to patients choosing CB-010
16 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Rapid timeline to treatment key to patients choosing CB-010 over approved autologous CAR-T cell therapies Rapid disease progression prohibited waiting for autologous CAR-T Insurance rejection of autologous CAR-T
Slide 17: CB-010 is generally well tolerated
17 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 is generally well tolerated Treatment-emergent adverse events (TEAE1) in ≥20% of all patients CRS: cytokine release syndrome; ICANS: immune effector cell-associated neurotoxicity syndrome 1 TEAEs are defi
Slide 18: Generally well-tolerated safety profile
18 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 has generally well-tolerated safety profile No Grade ≥3 CRS, no GvHD observed (N=46) CRS: cytokine release syndrome; GvHD: graft-versus-host disease; ICANS: immune effector cell–associated neurotoxicity s
Slide 19: ANTLER efficacy assessment all patients
19 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER efficacy assessment all patients ≥4 HLAPLoTSubtype ✓8FL 4DLBCL ✓2MCL 2PMBCL 2FL 4MCL ✓1DLBCL ✓1DLBCL 2DLBCL 1tFL 1HGBL 1DLBCL 1HGBL 1DLBCL 1DLBCL 1DLBCL ✓2DLBCL ✓1DLBCL 4MZL 1DLBCL 1HGBL ✓1HGBL 1DL
Slide 20: Efficacy assessment by all patients and LBCL subgroups
20 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER efficacy assessment by all patients and LBCL subgroups As of April 1, 2024 cutoff date. 2L LBCL 80M (N=20) LBCL (N=40) All patients (N=46) Endpoints (N, %) 15 (75%)29 (73%)35 (76%)Overall response
Slide 21: Efficacy with and without partial HLA matching
21 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER efficacy assessment with and without partial HLA matching HLA: human leukocyte antigen; partial HLA matching: patient has ≥4 HLA alleles that match donor T cells used for CB-010 manufacturing; NR:
Slide 22: Improved PFS with partial HLA matching
22 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Improved PFS for all patients treated with CB-010 from a donor with partial HLA matching PFS by level of HLA matching All patients N=46*, median PFS (95% CI) PFS by level of HLA matching LBCL patients N=40*, med
Slide 23: CB-010 translational research data
CB-010 translational research data Kike Zudaire, PhD SVP of translational sciences and therapeutic discovery Caribou Biosciences
Slide 24: Partial HLA matching improves exposure of CB-010
24 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Partial HLA matching improves exposure of CB-010 • Peak expansion (Cmax) occurred 7 to 10 days post infusion • Persistence was observed up to ~30 days • PK consistent for three dose levels evaluated LLOQ: lower
Slide 25: Single dose results in extended B cell aplasia and rapid immune recovery
25 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Single dose of CB-010 results in extended B cell aplasia and rapid recovery of immune cells • CB-010 specifically targets B cells, resulting in extended B cell aplasia for ~114 days • B cells recover to normal l
Slide 26: Duration of B cell aplasia similar to lupus case studies
26 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 duration of B cell aplasia is similar to lupus case studies Duration of B cell aplasia Days 114 Mean (IQR 42-150) CB-010 N=44 112 Mean (IQR 72-153) Müller et al N=141 FOR ILLUSTRATIVE PURPOSES ONLY: The r
Slide 27: Partial HLA matching does not impact time to treatment
27 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Partial HLA matching does not impact time to treatment DSA: donor-specific antibodies 1 Based on data from the ongoing ANTLER Phase 1 trial in r/r B-NHL and to be confirmed in the ANTLER and GALLOP Phase 1 trial
Slide 28: Off-the-shelf CAR-T easily matched to 2L LBCL patients
28 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. HLA: human leukocyte antigen; partial HLA match: patient has ≥4 HLA alleles that match donor T cells used for CB-010 manufacturing 1 Planned pivotal Phase 3 intends to enroll CD19 naïve 2L LBCL patients who will
Slide 29: Advancing CB-010 development
Advancing CB-010 development Tonia Nesheiwat, PharmD VP of medical affairs and project leadership Caribou Biosciences
Slide 30: Broadening patient access through outpatient administration
30 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Broadening patient access through outpatient administration and expanding into an additional population of unmet need New protocol amendment enables outpatient administration Sites have the option to provide out
Slide 31: Advancing CB-010 for 2L LBCL patients
31 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Advancing CB-010 for 2L LBCL patients Phase 1 trial dose escalation r/r B-NHL1 N=16 Generally well tolerated Responses rivaling autologous CAR-T cell therapies NCT04637763 DSA: donor-specific antibodies; HLA: hu
Slide 32: Fireside chat
Fireside chat CARIBOU p> BIOSCIENCES’
Slide 33: Fireside chat with leaders in hematologic malignancies
33 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Fireside chat with leaders in hematologic malignancies President and CEO Caribou Biosciences Professor of medicine and section chief of hematologic malignancies Medical College of Wisconsin Assistant professor,
Slide 34: CARIBOU
CARIBOU p> BIOSCIENCES’
Slide 35: Open to your questions
35 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Open to your questions Rachel Haurwitz, PhD Jason O’Byrne President and CEO CFOCSO VP, medical affairs and project leadership Steve Kanner, PhD Tonia Nesheiwat, PharmD SVP, translational sciences and therapeutic
Slide 36: Advancing CB-010 to establish new standard of care for 2L LBCL
36 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Advancing CB-010 to establish new standard of care for 2L LBCL and broaden patient access 2L: second-line; LBCL: large B cell lymphoma; PFS: progression free survival; HLA: human leukocyte antigen 1To be confirm
Slide 37: Potential to address high unmet medical need in 2L LBCL
37 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Potential to address high unmet medical need in 2L LBCL ~32.4K patientsDiagnosed 1L ~30.8K patients 2L ~10.0K patients 3L ~4.4K patients LBCL patient treatment journey (U.S. incidence 2022) ANTLER dose expansion
Slide 38: Upcoming clinical catalysts
38 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. Upcoming clinical catalysts Expected timingClinical milestoneProgram H1 2025 H2 2025 Present initial data on partial HLA matching (~20 patients, some outpatient), CD19 relapsed (~10 patients) from the ANTLER Pha
Slide 39: With gratitude for patients, caregivers, investigators
39 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. With gratitude for patients, caregivers, investigators contributing to CB-010’s clinical development ANTLER Phase 1 trial: 29 active sites in US, Australia, and Israel Alabama University of Alabama Birmingham (M
Slide 40: Thank you
Thank you https://cariboubio.com info@cariboubio.com
Slide 41: CARIBOU
CARIBOU p> BIOSCIENCES’
Slide 42: Efficacy assessment in 2L LBCL at RP2D
42 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER efficacy assessment in 2L LBCL at RP2D Overall depth and duration of response in 2L LBCL at 80x106 CAR-T cells (N=20) Months from CB-010 infusion ≥4 HLA matchesPLoTSubtype 1DLBCL 1DLBCL ✓1DLBCL 1DL
Slide 43: Efficacy assessment for patients with ≥4 HLA matching
43 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER efficacy assessment for patients with ≥4 HLA matching (N=13) Months from CB-010 infusion As of April 1, 2024, data collection ongoing, efficacy based on Lugano criteria CR: complete response PR: pa
Slide 44: Efficacy assessment all patients
44 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER efficacy assessment all patients Months from CB-010 infusion ≥4 HLAPLoTSubtype? ✓8FL 4DLBCL 1DLBCL 1DLBCL ✓2DLBCL ✓2MCL ✓1tFL ✓1DLBCL ✓1DLBCL 2PMBCL 4MZL 1DLBCL 1HGBL 2FL 4MCL ✓1HGBL ✓1DLBCL 1DLBCL
Slide 45: Efficacy assessment by dose level
45 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 ANTLER efficacy assessment by dose level 80x106 selected as RP2D M: million cells per dose; NR: not reached; PFS: progression free survival; RP2D: recommended Phase 2 dose ANTLER Phase 1 clinical trial as
Slide 46: Allogeneic CAR-T cell manufacturing process overview for CB-010
46 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. chRDNA Cas9 AAV Healthy donor leukapheresis Anti-CD19 CARTCR PD1 TRAC PDCD1 Anti-CD19 CAR Chr 14 Chr 2 Allogeneic CAR-T cell manufacturing process overview for CB-010 Caribou’s process development team created t
Slide 47: Differentiated, long-term antitumor activity in preclinical studies
47 KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc. CB-010 demonstrated differentiated, long-term antitumor activity in preclinical studies Lau E, et al. Cytotherapy. 2023;25(7):750 • NALM-6/PD-L1+ B-ALL tumors were established by IV engraftment for 23 days (Day