Caribou Biosciences : Corporate Presentation May 2024

May 2024

Corporate presentation

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, emerging translational data, and follow up dose escalation 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 the possibility of improved clinical outcomes by utilizing partial human leukocyte antigen matching; 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; 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; 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 separate product candidates. 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 companies' 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 its ongoing ANTLER phase 1 clinical trial, its CaMMouflage phase 1 clinical trial, its AMpLify phase 1 clinical trial, and its 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.

Corporate Presentation | May 2024

2

©2024 Caribou Biosciences, Inc.

Precision genome editing with industry-leading expertise

chRDNA precision genome-editing technology

Novel, next-generation CRISPR technology engineered for superior specificity and precision

Multiplex editing designed to maintain genomic integrity

Armored off-the-shelf cell therapies

Allogeneic CAR-T and CAR-NK cell therapies armored for enhanced activity

• Checkpoint disruption
• Immune cloaking
• Cytokine support

4 clinical-stage trials targeting hematologic malignancies and autoimmune diseases

Resourced for successful execution

Experienced, mission- driven leadership

Strong in-house process development capabilities

Robust IP portfolio

$346M1 in cash, runway into Q1 2026

3 chRDNA: CRISPR hybrid RNA-DNA

1 $345.9M in cash, cash equivalents, and marketable securities as of March 31, 2024.

Corporate Presentation | May 2024 ©2024 Caribou Biosciences, Inc.

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
CB-010	ANTLER	CD19	r/r B-NHL
Dose expansion
CB-011	CaMMouflage	BCMA	r/r MM
Dose escalation
CB-012	AMpLify	CLL-1*	r/r AML
Dose escalation
				Autoimmune diseases
CB-010	GALLOP	CD19	LN and ERL
Site activation

RMAT,

Fast Track,

Orphan Drug

Fast Track,

Orphan Drug

4	ERL: extrarenal lupus; LN: lupus nephritis, RMAT: Regenerative Medicine Advanced Therapy	Corporate Presentation | May 2024
* Also known as CD371	©2024 Caribou Biosciences, Inc.

2024 clinical catalysts

Program	Clinical milestone	Expected timing

CB-010	Present initial dose expansion data, RP2D,	ASCO
and translational data from the ANTLER
June 2024
	Phase 1 clinical trial

CB-011	Present initial dose escalation data from	YE 2024
CaMMouflage Phase 1 trial

CB-010	Initiate GALLOP Phase 1 trial	YE 2024

Corporate Presentation | May 2024

©2024 Caribou Biosciences, Inc.

chRDNA technology

chRDNA guides promote on-target and reduce off-target edits

First-generation	chRDNA
all-RNACRISPR-Cas	CRISPR hybrid RNA-DNA

7

chRDNA guides significantly improve editing specificity

				Knockout
		Cas9					Cas12a
		all-RNA guide		chRDNA				chRDNA
	100					100
	80					80
	60					60
	40					40
editing%	20				editing%	20
6				6
	4					4
	2					2
	0					0
	ON	OFF	ON	OFF		ON	OFF	ON	OFF
		PDCD1			TRAC		B2M
		All-RNA guide on target		chRDNA guide on target		All-RNA guide off target	chRDNA guide off target

8 Editing assayed in primary human T cells.

		Knock-in
Insert 2: 76%	13.1	63.0

6.916.9

Insert 1: 80%

Cas12a chRDNA genome editing + AAV6

transduction leads to >60% of

manufacturing-scale engineered T cells

with all 4 intended edits

Corporate Presentation | May 2024

©2024 Caribou Biosciences, Inc.

Engineering for improved activity against disease is key to unlocking the full potential of allogeneic cell therapies

Caribou is implementing multiple armoring strategies

CAR-T cell cytotoxic activity

Pretreatment lymphodepletion

Checkpoint disruption

Combination

"Standard"	Immune cloaking
allo CAR-T

Time

Checkpoint disruption (CB-010)

PD-1 knockout (KO) sustains initial activity due to exhaustion resistance

Immune cloaking (CB-011)

B2M KO plus B2M-HLA-E fusion knock-in may delay host immune rejection

Combination strategies (CB-012)Checkpoint disruption AND immune cloaking

Corporate Presentation | May 2024

9

©2024 Caribou Biosciences, Inc.

Caribou is a leader in the allogeneic CAR-T cell space with a platform of genome-edited cell therapies

3 Edits

	PD-1 KO
CB-010	Anti-CD19
B cell non-Hodgkin
CAR
lymphoma
	TCR KO

1st allogeneic anti-CD19CAR-T cell therapy in the clinic with checkpoint disruption via PD-1 knockout (KO)1 to reduce CAR-T cell exhaustion

4 Edits

B2M-HLA-E

CB-011Anti-BCMA

Multiple

myelomaCAR

TCR KO

B2M KO

1st allogeneic anti-BCMACAR-T

cell therapy with immune cloaking via B2M KO and insertion of B2M-HLA-E fusion protein1

5 Edits

	B2M-HLA-E
	PD-1 KO
CB-012	Anti-CLL-1
Acute myeloid
CAR
leukemia
	TCR KO
	B2M KO

1st allogeneic CAR-T cell therapy with both checkpoint disruption and immune cloaking1

10	1 To Caribou's knowledge	Corporate Presentation | May 2024
©2024 Caribou Biosciences, Inc.