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CB-010 ANTLER Phase 1 trial update and KOL discussion Transformative genome-edited therapies for patients June 2, 2024

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 1995. These forward-looking statements speak only as of the date of this presentation and are subject to a number of known and unknown risks, assumptions, uncertainties, and other factors that may cause the actual results, levels of activity, performance, or achievements of Caribou Biosciences, Inc. (the “Company,” “Caribou,” “we,” or “our”) to be materially different from those expressed or implied by any forward-looking statements. The words “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” or “continue” or the negative of these terms or other similar expressions are intended to identify forward- looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements of historical facts contained in this presentation, are forward-looking statements, including but not limited to any statements regarding the initiation, timing, progress, strategy, plans, objectives, expectations (including as to the results) with respect to our product candidate preclinical studies, clinical trials, and research programs, including our expectations and timing regarding the release of dose expansion clinical data, and emerging translational data from our ongoing ANTLER phase 1 clinical trial for our CB-010 product candidate, disclosure of the recommended Phase 2 dose for CB-010, and an updated timeline for our planned phase 3 pivotal trial for CB-010 in second-line large B cell lymphoma patients (and the conditions to meet that timeline); the status, progress, and expectations relating to the timing of release of clinical data from our ongoing CaMMouflage phase 1 clinical trial for our CB-011 product candidate in patients with multiple myeloma; the status, progress, and expectations relating to the timing of release of clinical data from our ongoing AMpLify phase 1 clinical trial for our CB-012 product candidate in patients with acute myeloid leukemia; the timing for the initiation of our GALLOP phase 1 clinical trial for adults with lupus nephritis and extrarenal lupus; our ability to successfully develop our product candidates and to obtain and maintain regulatory approval for our product candidates; the number and type of diseases, indications, or applications we intend to pursue for our product candidates; the beneficial characteristics, safety, efficacy, therapeutic effects, and potential advantages of our product candidates; the expected timing or likelihood of regulatory filings and approval for our product candidates; our expected cash runway; and the sufficiency and anticipated use of our existing capital resources to fund our future operating expenses and capital expenditure requirements and needs for additional financing. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this presentation is given. This presentation discusses product candidates that are or will be under clinical investigation and that have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the therapeutic uses for which such product candidates are being or will be studied. As a result of many factors, including risks related to our limited operating history, history of net operating losses, financial position and our ability to raise additional capital as needed to fund our operations and product candidate development; uncertainties related to the initiation, cost, timing, and progress, and results of our current and future research and development programs, preclinical studies, and clinical trials; risks that initial or interim clinical trial data will not ultimately be predictive of the safety and efficacy of our product candidates or that clinical outcomes may differ as more clinical data becomes available; the risk that preclinical study results we observed will not be borne out in human patients; our ability to obtain and maintain regulatory approval for our product candidates; risks that our product candidates, if approved, may not gain market acceptance due to negative public opinion and increased regulatory scrutiny of cell therapies involving genome editing; our ability to meet future regulatory standards with respect to our products; our ability to obtain key regulatory input and approvals, our ability to establish and/or maintain intellectual property rights covering our product candidates and genome-editing technology; risks of third parties asserting that our product candidates infringe their patents; developments related to our competitors and our industry; our reliance on third parties to conduct our clinical trials and manufacture our product candidates; the impact of public health crises and geopolitical events on our business and operations; and other risks described in greater detail in our filings with the Securities and Exchange Commission (the “SEC”), including the section titled “Risk Factors” of our Annual Report on Form 10-K for the year ended December 31, 2023, and other filings we make with the SEC; the events and circumstances reflected in our forward-looking statements may not be achieved or may not occur, and actual results could differ materially from those described in or implied by the forward-looking statements contained in this presentation. Caution should be exercised when interpreting results from separate trials involving other CAR-T cell therapies. The results of other CAR-T cell therapies presented or referenced in these slides have been derived from publicly available reports of clinical trials not conducted by us, and we have not performed any head-to-head trials comparing any of these other CAR-T cell therapies with CB-010. As such, the results of these other clinical trials may not be comparable to clinical results for CB-010. The design of these other trials vary in material ways from the design of the clinical trials for CB-010, including with respect to patient populations, follow-up times, the clinical trial phase, and subject characteristics. As a result, cross-trial comparisons may have no interpretive value on our existing or future results. For further information and to understand these material differences, you should read the reports for the other CAR-T cell therapies’ clinical trials and the sources included in this presentation. In light of the foregoing, you are urged not to rely on any forward-looking statement in reaching any conclusion or making any investment decision about our securities. The forward-looking statements in this presentation are made only as of the date hereof. Except to the extent required by law, the Company assumes no obligation and does not intend to update any of these forward-looking statements after the date of this presentation or to conform these statements to actual results or revised expectations. From time to time, we may release additional clinical data from our ongoing ANTLER phase 1 clinical trial, our CaMMouflage phase 1 clinical trial, our AMpLify phase 1 clinical trial, and our GALLOP phase 1 clinical trial. We make no representations regarding such additional clinical data or the timing of its release, or whether any such data will support or contradict the findings of the clinical data reported earlier. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities.

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.

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 hematologic malignancies Medical College of Wisconsin

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 per batch Weeks to months1 Screening Queuing, leukapheresis scheduling Leukapheresis Bridging therapy Sample shipment Manufacturing, product failure identification Product shipment Lymphodepletion Product shipment Screening LymphodepletionDays

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 expression, reduces GvHD risk Anti-CD19 CAR site-specific insertion into TRAC locus • Eliminates random integration, targets tumor antigen PD-1 KO for enhanced antitumor activity • Reduces CAR-T cell exhaustion • Potentially contributes to initial tumor debulking CAR: chimeric antigen receptor; KO: knockout; CD: cluster of differentiation; chRDNA: CRISPR hybrid RNA-DNA; CRISPR: clustered regularly interspaced short palindromic repeats; PD-1: programmed cell death protein 1; TCR: T cell receptor; TRAC: T cell receptor alpha constant; scFv: single-chain variable fragment 1 To Caribou’s knowledge. 1st CAR-T in the clinic with checkpoint disruption via PD-1 KO1 Cas9 chRDNA editing for reduced off-target editing and enhanced genomic integrity Anti-CD19 scFv FMC63 with a 4-1BB costimulatory domain

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-targeted therapy -9 to -3 DAYS DAY 0 28 DAYS 3 MONTHS 6 MONTHS 9 MONTHS 12 MONTHS r/r B-NHL Lymphodepletion Part B: dose expansion – enrolling • Eligibility: 2nd line LBCL2 • Exclusion: prior CD19-targeted therapy • Objective: tumor response, RP2D CB-010 Safety and tolerability Response assessmentCyclophosphamide (60 mg/kg/d for 2 days) followed by Fludarabine (25 mg/m2/d for 5 days)3 SINGLE DOSE Dose level 1: 40x106 CAR-T cells Dose level 2: 80x106 CAR-T cells Dose level 3: 120x106 CAR-T cells Dose expansion: 30th patient dosed; 80x106 CAR-T cells selected as RP2D Will enroll ~20 patients at RP2D to prospectively evaluate partial (≥4) HLA matching, DSA screening NCT04637763 DSA: donor-specific antibodies; HLA: human leukocyte antigen 1 Subtypes include: DLBCL (diffuse large B cell lymphoma ), HGBL (high-grade B cell lymphoma), tFL (transformed DLBCL from follicular lymphoma, PMBCL (primary mediastinal large B cell lymphoma), FL (follicular lymphoma, aggressively behaving with POD24 (high risk)), MZL (marginal zone lymphoma). 2 LBCL subtypes include: DLBCL NOS (DLBCL not otherwise specified), HGBL, transformed DLBLC from FL or MZL, and PMBCL. 3 Clin Cancer Res. 2011 July 1; 17(13): 4550–4557. doi:10.1158/1078-0432.CCR-11-0116.

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-grade B cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; PLoT: prior lines of therapy (#); PMBCL: primary mediastinal large B cell lymphoma ✓ = patients with ≥4 HLA (human leukocyte antigen) matches (all other patients have ≤3 HLA matches). 1 Aggressively behaving, with POD24 (high risk). 2 Patient 5’s 3-month scan conducted on day 63 post CB-010 as per investigator’s discretion. ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing. 1 2 3 Months from CB-010 infusion 4 12 ≥4 HLAPt #PLoTDoseSubtype ✓1840MFL1 4440MDLBCL 7180MDLBCL 8180MDLBCL 5240MPMBCL2 ✓13240MMCL ✓9280MDLBCL 15480MMZL 2440MMCL 3240MFL1 6240MDLBCL 102120MDLBCL 14140MHGBL 16280MMCL 121120MHGBL 112120MDLBCL 9 15 24 CR: complete response PR: partial response SD: stable disease PD: progressive disease 5 18 216 ////////// // Overall r/r B-NHL dose escalation 5 of 6 patients with CR as of June 20, 2023 data cutoff remain in CR as of April 1, 2024 2 patients completed 24-month follow-up in CR Data collection ongoing, efficacy based on Lugano criteria SINGLE CB-010 DOSE Denotes patients with continued CRs since June 20, 2023 June 20, 2023 data

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 interval; CR: complete response; HLA: human leukocyte antigen; LBCL: large B cell lymphoma; NE: not estimable; NR: not reached; PFS: progression free survival; partial HLA matching: patient has ≥4 HLA alleles that match donor T cells used for CB-010 manufacturing; RP2D: recommended Phase 2 dose; CR: complete response; NR: not reached 1Retrospective analysis in 13 patients with ≥4 HLA allele matching; subset includes: 2L LBCL (N=10), 3L LBCL (N=1), and 3L+ B-NHL (N=2). ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing. 1 dose per patient, 3 dose levels evaluated, all generally well tolerated 2L LBCL at RP2D CR rate: 50% Median duration of CR: NR Advancing CB-010 with partial HLA matching in 2L LBCL and lupus Phase 1 clinical trials Median PFS 14.4 months (95% CI: 1.7-NE) observed in 13 patients with partial (≥4) HLA matching1 RP2D selected 80x106 CAR-T cells

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*, median PFS (95% CI) CI: confidence interval; HLA: human leukocyte antigen; NE: not estimable; partial HLA matching: patient has ≥4 HLA alleles that match donor T cells used for CB-010 manufacturing * Retrospective analysis of HLA allele matching for class I and class II antigens. ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing.

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: third-line; LBCL: large B cell lymphoma; HLA: human leukocyte antigen; NE: not estimable; partial HLA matching: patient has ≥4 HLA alleles that match donor T cells used for CB-010 manufacturing 1 N=11 ≥4 HLA matching subset includes: 2L LBCL patients (N=10) and 3L LBCL patient (N=1). ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing. FOR ILLUSTRATIVE PURPOSES ONLY: The results of other CAR-T cell therapies presented on this slide have been derived from publicly available reports of clinical trials run independently of Caribou and the data has been digitally recreated from publicly available original sources to compare approximations of the findings. The Company has not performed any head-to-head trials comparing any of these other CAR-T cell therapies with CB-010. As such, the results of these other clinical trials may not be comparable to clinical results for CB-010. The design of these other trials vary in material ways from the design of the clinical trials for CB-010, including with respect to patient populations, follow-up times, the clinical trial phase, and subject characteristics. As a result, cross-trial comparisons may have no interpretive value on the Company’s existing or future results. For further information and to understand these material differences, you should read the reports for the other trials at the sources included below. ANTLER 1st assessment at 28 days after CB-010 infusion ZUMA-7 1st assessment at 50 days after randomization ANTLER Day 0 = CB-010 infusion ZUMA-7 Day 0 = randomization + censored

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

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 Therapeutics, Morphosys AG, Caribou Biosciences, Repare Therapeutics, Artiva Biotherapeutics, Newave, AstraZeneca, ImmPACT Bio

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: primary mediastinal large B cell lymphoma; IPI: International Prognostic Index; LDH: lactate dehydrogenase; ULN: upper limit of normal 1 Aggressively behaving, with POD24 (high risk). 2 Patients are CD19 CAR-T naïve. 3 IPI scores were not recorded for all patients. As of April 1, 2024 cutoff date. Screening Dose expansion (N=30) Dose escalation (N=16) All treated (N=46)Patient and disease characteristics 63.0 (21-78)66.0 (55-82)65.0 (21-82)Age, years, median (range) 22 (73.3)14 (87.5)36 (78.3)Men, n (%) ECOG performance status, n (%) 15 (50.0)6 (37.5)21 (45.7)0 15 (50.0)10 (62.5)25 (54.3)1 9.5 (4.9-79.6)29.0 (2.9-196.4)10.6 (2.9-196.4)Time since diagnosis, months, median (range) NHL subtype, n (%) LBCL 19 (63.3)7 (43.8)26 (56.5)DLBCL 6 (20.0)2 (12.5)8 (17.4)HGBL 4 (13.3)04 (8.7)tFL 1 (3.3)1 (6.3)2 (4.3)PMBCL Other B-NHL 03 (18.8)3 (6.5)MCL 02 (12.5)2 (4.3)FL1 01 (6.3)1 (2.2)MZL 1 (1-1)2 (1-8)1 (1-8)Prior systemic therapies, median (range)2 IPI score at screening, n (%)3 7 (23.3)4 (25.0)11 (23.9)0 or 1 6 (20.0)2 (12.5)8 (17.4)2 15 (50.0)3 (18.8)18 (39.1)≥3 7 (23.3)3 (18.8)10 (21.7)Maximum lesion diameter ≥7.5 cm, n (%) 233.5 (140-1799)202 (126-710)216 (126-1799)LDH at screening, U/L, median (range) 18 (60.0)5 (31.3)23 (50.0)Baseline LDH > ULN, n (%) 6 (20.0)1 (6.3)7 (15.2)LDH >2 x ULN, n (%)

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 Patient not wanting to go through apheresis Preference for an off-the-shelf therapy Preference for no bridging therapy during autologous CAR-T cell manufacturing LD: lymphodepletion 1 Based on survey answers from ANTLER investigators asking why patients were dosed with CB-010 versus autologous CAR-T cell therapy; 86% of ANTLER sites offer one of the approved auto CAR-Ts in 2L LBCL. 2 days (median, range 0-12) from confirmation of eligibility to LD Rest (2 days) CB-010 Lymphodepletion (7 days)

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 defined as adverse events (AEs) with a start date on or after the CB-010 infusion date. 2 One death possibly related to CB-010 per investigator due to complications of a bladder perforation in the context of BK virus hemorrhagic cystitis. As of April 1, 2024 cutoff date. 2L LBCL RP2D subgroup (N=20) LBCL subgroup (N=40) All treated (N = 46)System organ class, n (%) Preferred term, n (%) Related grade ≥3 Grade ≥3Any grade Related grade ≥3 Grade ≥3Any grade Related grade ≥3 Grade ≥3Any grade 10 (50)18 (90)20 (100)20 (50)35 (88)40 (100)23 (50)41 (89)46 (100)Any TEAE 6 (30)11 (55)12 (60)13 (33)25 (63)26 (65)15 (33)29 (63)30 (65)Thrombocytopenia 6 (30)11 (55)13 (65)10 (25)22 (55)24 (60)10 (22)24 (52)27 (59)Anemia 4 (20)8 (40)10 (50)6 (15)15 (38)18 (45)7 (15)19 (41)22 (48)Neutropenia 2 (10)8 (40)9 (45)5 (13)13 (33)14 (35)6 (13)14 (30)15 (33) White blood cell count decreased 0013 (65)0023 (58)0026 (57)CRS 3 (15)6 (30)9 (45)4 (10)8 (20)19 (48)4 (9)10 (22)22 (48)Infections 004 (20)009 (23)0011 (24)Hypokalemia 002 (10)0010 (25)0011 (24)Pyrexia 1 (5)1 (5)5 (25)2 (5)2 (5)8 (20)3 (7)3 (7)10 (22)ICANS 003 (15)007 (18)0010 (22)Diarrhea Five patients died due to adverse events following CB-010 infusion (4 unrelated, 1 possibly related2 to CB-010)

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 syndrome; NR: not reported 1 Prolonged cytopenias are defined as grade 3 or higher events lasting beyond 30 days following CB-010 infusion; 37/46 (80%) recovered from cytopenias to grade ≤2 by day 35 post CB-010 treatment. 2 Prolonged cytopenias of grade 3 or higher that were present at or after 30 days from Yescarta infusion. 3 Median time of onset was 3 days (range 0-22) and median duration was 3 days (range 1-19). 4 Infection events reported were on or after CB-010 infusion, with highest grade reported per patient; median onset 8 days (range 0-279) and media duration is 14 days (range 1-239). 5 Median time of onset was 7.5 days (range 6-34) and median duration was 2 days (range 1-27). 6 2 Grade 3 and 1 Grade 4; all resolved with supportive care. Median time of onset was 8 days and median duration 2 days. ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing. Source: ZUMA-7, Locke et al, NEJM, 2022 (prolonged cytopenia at 30 days), Westin et al, NEJM, 2023 (CRS, infections, ICANs/neurological events) Yescarta (N=170) All CB-010 treated (N=46) Grade ≥3 (n, %) Any grade (n, %) Grade ≥3 (n, %) Any grade (n, %) 49 (29)249 (29)29 (20)19 (20)1Prolonged cytopenias 11 (6)157 (92)0 (0)26 (57)3CRS 28 (17)76 (45)10 (22)422 (47)4Infections 36 (21)102 (60)3 (7)610 (22)5ICANS NRNR01 (2)Hemophagocytic lymphohistiocytosis (HLH) NRNR00GvHD FOR ILLUSTRATIVE PURPOSES ONLY: The results of other CAR-T cell therapies presented on this slide have been derived from publicly available reports of clinical trials run independently of Caribou. The Company has not performed any head-to-head trials comparing any of these other CAR-T cell therapies with CB-010. As such, the results of these other clinical trials may not be comparable to clinical results for CB-010. The design of these other trials vary in material ways from the design of the clinical trials for CB-010, including with respect to patient populations, follow-up times, the clinical trial phase, and subject characteristics. As a result, cross-trial comparisons may have no interpretive value on the Company’s existing or future results. For further information and to understand these material differences, you should read the reports for the other trials at the sources included below.

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 1DLBCL 1tFL 1HGBL 1HGBL ✓1DLBCL 1DLBCL ✓1DLBCL 1DLBCL 2MCL ✓1DLBCL 1DLBCL 1DLBCL 1DLBCL 1DLBCL 1PMBCL ✓1tFL ✓1DLBCL 1DLBCL 2DLBCL 1tFL ✓1DLBCL 1HGBL 2DLBCL 1HGBL PLoT: prior lines of therapy (#) ✓ = patients with ≥4 HLA (human leukocyte antigen) matches (all other patients have ≤3 HLA matches); *Denotes patient that did not have Day 28 efficacy scan. ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing, efficacy based on Lugano criteria. CR: complete response PR: partial response SD: no response/stable disease PD: progressive disease Death SINGLE CB-010 DOSE Months from CB-010 infusion

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 rate (ORR)1 5 (1-20+)2 (1-23+)5 (1-23+)DoR, median months (range) 10 (50%)17 (43%)21 (46%)Complete response (CR) rate1 NR (1-12+)7 (1-23+)7 (1-23+) Duration of CR, Median months (range) 38%28%35%6-month PFS 3.5 (1-21+)3 (1-24+)3 (1-24+)PFS, median months (range) + censored observation

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: not reached ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing. LBCL ≥4 HLA matches (N=11) All patients ≥4 HLA matches (N=13) All patients ≤3 HLA matches (N=33) Endpoints (N, %) 10 (91%)12 (92%)23 (69%)Overall response rate (ORR) NR (1-15+)13.5 (1-23+)2.0 (1-23+)Duration of response (DoR), median months (range) 4 (36%)6 (46%)15 (45%)Complete response (CR) rate NR (5-15+)NR (5-23+)5.0 (1-23+)Duration of CR, median months (range) 53%62%25%6-month PFS NR (2-16+)14.4 (2-24+)2.8 (1-24+)PFS, median months (range) + censored observation

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*, median PFS (95% CI) CI: confidence interval; HLA: human leukocyte antigen; NE: not estimable; partial HLA matching: patient has ≥4 HLA alleles that match donor T cells used for CB-010 manufacturing * Retrospective analysis of HLA allele matching for class I and class II antigens. ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing.

CB-010 translational research data Kike Zudaire, PhD SVP of translational sciences and therapeutic discovery Caribou Biosciences

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 limit of quantification Mean values represented by dots with standard error shown; values below LLOQ converted to 0; Includes all available data from the V2 ddPCR assay; visits up to D28 shown; D0 values represent pre-infusion level set to 0. N=35 total number of patients included in PK analysis based on samples analyzed as of data cutoff of April 1, 2024. • Higher numbers of HLA matched alleles demonstrate more expansion and persistence vs. lower numbers

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 levels by ~268 days • T cells and NK cells recovered ~3 weeks after LD regimen LD: lymphodepletion; LLOQ: lower limit of quantification Baseline B cells absolute levels calculated with samples of 10 cells/µl or above.

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 results of other CAR-T cell therapies presented on this slide have been derived from publicly available reports of clinical trials run independently of Caribou. The Company has not performed any head-to-head trials comparing any of these other CAR-T cell therapies with CB-010. As such, the results of these other clinical trials may not be comparable to clinical results for CB-010. The design of these other trials vary in material ways from the design of the clinical trials for CB-010, including with respect to patient populations, follow-up times, the clinical trial phase, and subject characteristics. As a result, cross-trial comparisons may have no interpretive value on the Company’s existing or future results. For further information and to understand these material differences, you should read the reports for the other trials at the sources included below.

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 trials. How does HLA matching work? Partial HLA matching and DSA screening for ANTLER and GALLOP Phase 1 trials • Human leukocyte antigens (HLAs) help the immune system identify “self” from “non-self” • Patient’s immune cells recognize allogeneic CAR-T cells as “non-self” and initiate rejection HLA typing and DSA analysis occur within screening timeline and does not impact time to receive treatment Partial HLA matching could result in enhanced outcomes for patients1 Partially matched CB-010 dose shipped HLA typing DSA analysis SINGLE DOSE CB-010 LymphodepletionScreening

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 be dosed with best matched CB-010 Only a small number of manufacturing batches are needed to provide partially HLA matched CB-010 to ~90% of patients CB-010 is an off-the shelf CAR-T cell therapy that is easily matched to 2L LBCL patients

Advancing CB-010 development Tonia Nesheiwat, PharmD VP of medical affairs and project leadership Caribou Biosciences

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 outpatient administration of both lymphodepletion and CB-010 treatment Proof-of-concept cohort to evaluate CB-010 for patients who have relapsed following prior CD19-targeted therapy Assess safety, efficacy, durability in patients who relapsed following any prior CD19-directed therapy (N=10)

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: human leukocyte antigen 1 Subtypes include: DLBCL (diffuse large B cell lymphoma ), HGBL (high-grade B cell lymphoma), tFL (transformed DLBCL from follicular lymphoma, PMBCL (primary mediastinal large B cell lymphoma), FL (follicular lymphoma, aggressively behaving with POD24 (high risk)), MZL (marginal zone lymphoma). 2 LBCL subtypes include: DLBCL NOS (DLBCL not otherwise specified), HGBL, transformed DLBCL from FL or MZL, and PMBCL. Pivotal Phase 3 trial CB-010 2L LBCL2 regardless of HLA type Initiation in H2 2025, upon CB-010 partial HLA matched data confirmation Phase 1 trial dose expansion 2L LBCL2 N=30 RP2D (80M) selected Improved outcomes with ≥4 HLA matching observed retrospectively Phase 1 trial partial (≥4) HLA matching 2L LBCL2 N=~20 at RP2D and CD19 relapsed LBCL N=~10 at RP2D Outpatient administration Initial data in H1 2025

Fireside chat

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, director of lymphoma and CLL in the division of hematology and hematologic malignancies Huntsman Cancer Institute University of Utah

Q&A

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 discovery Kike Zudaire, PhD 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 hematologic malignancies Medical College of Wisconsin

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 confirmed with additional clinical data. ANTLER Phase 1 clinical trial as of April 1, 2024 cutoff date, data collection ongoing. • With partial HLA matching, safety, efficacy, durability has the potential to rival approved autologous CAR-T cell therapies1 • Generally well-tolerated safety profile • Off-the-shelf, readily-available single dose cell therapy • RMAT and Fast Track designations enable FDA interactions • Safety and efficacy profile supports clinical development for 2L LBCL and lupus patients and in outpatient setting

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 Future: planned pivotal Phase 3 trial

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 Phase 1 clinical trial Initiate pivotal Phase 3 trial CB-010 2L LBCL YE 2024Present initial dose escalation data from CaMMouflage Phase 1 trial CB-011 r/r MM YE 2024Initiate GALLOP Phase 1 trial CB-010 LN/ERL

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 (Mehta) Arizona HonorHealth Cancer Institute (Kanate) University of Arizona (Husnain) Banner MD Anderson (Nath) California University of California Irvine (O'Brien) University of California San Diego (Hamdan) Florida Advent Health (Patel) Georgia Augusta (Kota) BMT of Georgia (Sohl) Iowa University of Iowa (Farooq) Kentucky University of Kentucky (Yalniz) Norton Cancer Institute (Stevens) New Jersey Morristown Memorial Hospital (Cherry) Hackensack (Feldman) New York Montefiore (Kornblum) NYU Langone (Diefenbach) Ohio Oncology Hematology Care (Essell) Pennsylvania University of Pennsylvania (Nasta) Tennessee Vanderbilt University (Oluwole) Texas Baylor Charles A. Sammons (Holmes) MD Anderson Cancer Center (Nastoupil) Utah Huntsman Cancer Institute (Hu) Washington Swedish Cancer Institute (Patel) Wisconsin Medical College of Wisconsin (Hamadani) UC Irvine UC San Diego HonorHealth Huntsman Baylor MD Anderson OHC MorristownIowa University of AZ Augusta UAB Kentucky MCW BMTGA Montefiore Advent Health Norton Hackensack Swedish Israel Hadassah University Hospital Rabin Medical Center Tel Aviv Sourasky Medical Center Univ of Penn NYU Langone Australia Westmead Hospital Epworth Hospital Banner MD Anderson Vanderbilt

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

Appendix

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 1DLBCL 1HGBL ✓1HGBL 1DLBCL 1tFL 1HGBL 1HGBL ✓1DLBCL 1DLBCL ✓1DLBCL 1DLBCL ✓1DLBCL 1DLBCL 1DLBCL 1DLBCL 1DLBCL 1PBMCL DLBCL: diffuse large B cell lymphoma; CR: complete response; HGBL: high-grade B cell lymphoma; PMBCL: primary mediastinal large B cell lymphoma; tFL: transformed DLBCL from follicular lymphoma; PLoT: prior lines of therapy; HLA: human leukocyte antigen 1 50% CR rate measures the number of patients (10 of 20) achieving a CR at any time point after treatment with CB-010. As of April 1, 2024, data collection ongoing, efficacy based on Lugano criteria. CR: complete response PR: partial response SD: no response/stable disease PD: progressive disease Death SINGLE CB-010 DOSE Median duration of CR Not reached CR1 rate 50% KOL discussion CB-010 ANTLER Phase

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: partial response SD: no response/stable disease PD: progressive disease Death SINGLE CB-010 DOSE DosePLoTSubtype 408FL 802DLBCL 402MCL 1201tFL 1201DLBCL 801DLBCL 801HGBL 401DLBCL 401DLBCL 801DLBCL 801DLBCL 801DLBCL 1201DLBCL Median duration of CR Not reached Median PFS 14.4 months KOL discussion CB-010 ANTLER Phase DLBCL: diffuse large B cell lymphoma; CR: complete response; HGBL: high-grade B cell lymphoma; PFS: progression free survival; PMBCL: primary mediastinal large B cell lymphoma; tFL: transformed DLBCL from follicular lymphoma; PLoT: prior lines of therapy 1 46% CR rate measures the number of patients (6 of 13) achieving a CR at any time point after treatment with CB-010. As of April 1, 2024, data collection ongoing, efficacy based on Lugano criteria. CR1 rate 46%

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 1tFL 1HGBL 2DLBCL 2DLBCL 1DLBCL 1tFL ✓1DLBCL 1HGBL ✓1DLBCL ✓1DLBCL 1DLBCL 1DLBCL 1HGBL ✓1DLBCL 1HGBL ✓1DLBCL 1DLBCL 2MCL 1HGBL 2DLBCL 1tFL 1HGBL 1DLBCL 1DLBCL 1DLBCL 1DLBCL 1PMBCL 1DLBCL As of April 1, 2024, data collection ongoing, efficacy based on Lugano criteria. *Denotes patient that did not have Day 28 efficacy scan. CR: complete response PR: partial response SD: no response/stable disease PD: progressive disease Death SINGLE CB-010 DOSE

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 of April 1, 2024 cutoff date, data collection ongoing. CB-010 dose levelr/r B-NHL 120M (N=9) 80M (N=23) 40M (N=14) All patients (N=46) Endpoints (N, %) 8 (89%)18 (78%)9 (64%)35 (76%)Overall response rate (ORR) 1.9 (1-8+)7.4 (1-20+)7.9 (1-23+)5 (1-23+) Duration of response (DoR), median months (range) 3 (33%)11 (48%)7 (50%)21 (46%)Complete response (CR) rate 1.8 (1-3+)NR (1-15+)6.7 (2-23+)7 (1-23+)Duration of CR, median months (range) 22%43%33%35%6-month PFS + censored observation

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 the manufacturing process and transferred it to a CMO to generate phase 1 cGMP clinical material cGMP starting material Genetic modification via chRDNA and AAV Gene-modified CAR-T cells In vitro expansion of edited donor T cells Removal of residual TCR+ cells Final formulation & cryopreservation Treatment Anti-TCR microbeads Anti-CD19 CAR

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 -1) • A single dose treatment was administered by IV on Day 24 (PBS or 107 cells where indicated) 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 cells (expressing PD-1) Overall survival analysis Data to 160 days Days post CAR-T Pe rc en t s ur vi va l 100 50 0 p<0.0001 0 20 40 60 80 10 0 12 0 14 0 16 0 CB-010 Conventional allo CAR-T PBS PBS (negative control) CB-010 (PD-1 negative) D-1 D14 (post CAR-T) D65 D108 CD19 CAR-T (PD-1 positive)