Caribou Biosciences : KOL discussion of CB-010 ANTLER Phase 1 final trial data at ASCO

June 2, 2024

CB-010 ANTLER Phase 1 trial update and KOL discussion

Transformative genome-edited therapies for patients

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.

KOL discussion CB-010 ANTLER Phase 1 data | June 2024

2

©2024 Caribou Biosciences, Inc.

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.

Today's guests

Boyu Hu, MD

Assistant professor, director of

lymphoma and CLL in the division of

hematology and hematologic

malignancies

Huntsman Cancer Institute

University of Utah

Mehdi Hamadani, MD

Professor of medicine and section chief of

hematologic malignancies

Medical College of Wisconsin

KOL discussion CB-010 ANTLER Phase 1 data | June 2024

4

©2024 Caribou Biosciences, Inc.

Patients shouldn't have to wait for treatment

Allogeneic therapy

N=many per batch

Autologous therapy

N=1

per batch

ScreeningProduct

shipment

Days Lymphodepletion

Sample

shipment

Queuing,

Screening leukapheresis Leukapheresis scheduling

Weeks to months1

The future of cell therapy is off-the-shelf

Manufacturing, product

failure identification

Bridging therapy	Product
shipment

Lymphodepletion

5	1 Mikhael, J. et al. JCO Oncology Practice 2022 18:12, 800-807	KOL discussion CB-010 ANTLER Phase 1 data | June 2024
©2024 Caribou Biosciences, Inc.

CB-010

Allogeneic anti-CD19CAR-T cell therapy with a PD-1 knockout for r/r B cell non-Hodgkin lymphoma (B-NHL)

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

Armored with 3 genome edits

PD-1 KO

1

TRAC gene knockout (KO)

Anti-CD193

TCR KO	CAR	2
	2
1	PD-L1
CD19
MHC I		3

NHL cell

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

1st CAR-T in the clinic with checkpoint disruption via PD-1 KO1

Cas9 chRDNA editing for reduced off-targetediting and enhanced genomic integrity

Anti-CD19 scFv FMC63 with a 4-1BB costimulatory domain

	CAR: chimeric antigen receptor; KO: knockout; CD: cluster of differentiation; chRDNA: CRISPR hybrid RNA-DNA; CRISPR: clustered	KOL discussion CB-010 ANTLER Phase 1 data | June 2024
7	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	©2024 Caribou Biosciences, Inc.

1 To Caribou's knowledge.

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

Part B: dose expansion - enrolling

• Eligibility: 2nd line LBCL2
• Exclusion: prior CD19-targeted therapy
• Objective: tumor response, RP2D

r/r B-NHL

Lymphodepletion

-9 to -3DAYS

Cyclophosphamide

(60 mg/kg/d for 2 days)

followed by Fludarabine

(25 mg/m2/d for 5 days)3

CB-010

DAY 0

28 DAYS

3 MONTHS

6 MONTHS

9 MONTHS

12 MONTHS

Safety and tolerability

Response assessment

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)),

8 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.

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

Subtype	Dose PLoT	Pt #
FL1	40M	8	1
DLBCL	40M	4	4
DLBCL	80M	1	7
DLBCL	80M	1	8
PMBCL2	40M	2	5
MCL	40M	2	13
DLBCL	80M	2	9
MZL	80M	4	15
MCL	40M	4	2
FL1	40M	2	3
DLBCL	40M	2	6
DLBCL	120M	2	10
HGBL	40M	1	14
MCL	80M	2	16
HGBL	120M	1	12
DLBCL	120M	2	11

≥4

HLA

✓

✓

✓

SINGLE	1	2	3
CB-010
DOSE

*

*

CR: complete response

PR: partial response

*

SD: stable disease

*

PD: progressive disease

Denotes patients with

continued CRs since

June 20, 2023

June 20, 2023 data

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-monthfollow-up in CR

Data collection ongoing, efficacy based on Lugano criteria

4

5

6

//

9

//

12

//

15

//

18

//

21

//

24

*

*

			Months from CB-010 infusion
	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
9	✓ = patients with ≥4 HLA (human leukocyte antigen) matches (all other patients have ≤3 HLA matches).	KOL discussion CB-010 ANTLER Phase 1 data | June 2024
1	Aggressively behaving, with POD24 (high risk).	©2024 Caribou Biosciences, Inc.
	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.

CB-010 with partial HLA matching shows safety, efficacy, and durability can potentially rival autologous CAR-T cell therapies

1 dose per patient,	RP2D selected	2L LBCL at RP2D
3 dose levels evaluated,
CR rate: 50%
80x106 CAR-T cells
all generally well tolerated
Median duration of CR: NR

Median PFS

14.4 months

(95% CI: 1.7-NE)

observed in 13 patients with partial (≥4) HLA matching1

Advancing CB-010 with

partial HLA matching

in 2L LBCL and lupus Phase 1 clinical trials

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

10 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.

KOL discussion CB-010 ANTLER Phase 1 data | June 2024 ©2024 Caribou Biosciences, Inc.