Bolt Biotherapeutics : Boltbody™ISAC Platform

Bolt Biotherapeutics

Nasdaq: BOLT

Boltbody™ ISAC Platform

October 2023

Disclaimer

This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding Bolt Biotherapeutics, Inc. (the "Company," "we," "us," or "our")'s future financial condition, ability to achieve upcoming milestones for our product candidates, the timing of our clinical trials, and the success and results of our pipeline programs and partnerships, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potentially" "predict," "should," "will" or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy, and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the success, cost and timing of our product development activities and clinical trials; our expectations about the timing of achieving regulatory approval and the cost of our development programs; our ability to obtain funding for our operations, including funding necessary to complete further development and commercialization of our product candidates; our ability to fund our clinical programs and the sufficiency of our cash, cash equivalents, and marketable securities to fund operations through 2025 and the achievement of key milestones; the commercialization of our product candidates, if approved; our plans to research, develop, and commercialize our product candidates; our ability to attract collaborators with development, regulatory and commercialization expertise; future agreements with third parties in connection with the commercialization of our product candidates; the success of our current collaborations with third parties, including our collaborations with Bristol-Myers Squibb Company, Roche, Innovent Biologics, Inc., Genmab A/S, and Toray Industries, Inc.; the achievement of milestone payments or any tiered royalties related to our collaborations; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; the rate and degree of market acceptance of our product candidates; and regulatory developments in the United States and foreign countries. These risks are not exhaustive. For a detailed discussion of the risk factors that could affect our actual results, please refer to the risk factors identified in our SEC reports, including, but not limited to our Annual Report on Form 10-K for the year ended December 31, 2022. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward- looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation.

In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.

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Bolt Bio: Dedicated to Generating Breakthroughs for Patients

BDC-1001: Monotherapy Activity, Efficient Plan

Promising Phase 1 Results

• Monotherapy ORR1 of 29% at RP2D of 20 mg/kg q2w
• Well tolerated

Phase 2 Program

• Option-baseddevelopment
• 4 tumor types
• Upcoming data readouts

Focused Pipeline,

Proven Platform Technology

Pipeline

• BDC-1001in Phase 2
• BDC-3042in Phase 1

Collaborations validate Boltbody™ ISAC platform

Well-Capitalized,

Significant Upside Potential

Nasdaq: BOLT

• 6 covering research analysts
• Consensus price target: $5.002

$157M cash & equivalents3

Simple Corporate Structure

• 37.95 million shares of common stock oustanding4
• No debt
• No warrants

	1 Objective Response Rate in evaluable patients with HER2+ tumors	RP2D = Recommended Phase 2 Dose
3	2	$5.00 is consensus price target of 6 covering analysts as of 8/31/23	q2w = every other week dosing schedule
3	$157.1 million cash & cash equivalents
	4 37,950,986 shares outstanding as of 6/30/23	ISAC = Immune-Stimulating Antibody Conjugate

Boltbody™ ISAC Platform

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Boltbody™ ISAC Platform

Best-in-class ISAC Platform with Emerging Clinical Validation

Antibody

Payload

Conjugation

Linker

Proven Ability to Achieve:

 Target-dependent activity

 Low systemic cytokine production  Low immunogenicity

Antibody	Payload
• Targets tumor antigen	• 100s of payloads evaluated
• Active Fc essential for	• TLR7, TLR8, dual TLR7/8 &
phagocytosis	STING payloads available
• Impacts ISAC PK, activity &
safety

Linker	Conjugation
•	Non-cleavable for better safety	•	Suite of modern & classical
•	Optimize physicochemical		methods available
	properties	•	Conjugation site impacts
			activity & safety

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Innate Immune Response

Myeloid Cells Kill Tumor Cells via ADCP

TUMOR MICROENVIRONMENT

Adaptive Immune Response

Engages T Cell-driven Tumor Killing

TUMOR-DRAINING	TUMOR MICROENVIRONMENT
LYMPH NODES

Tumor

1 Antigen

Recognition

FcR-

1. Dependent Phagocytosis (ADCP)
   TLR-
2. Mediated
   Activation TLR

Antigen Expression

• High, medium, & low

Myeloid Antigen-presenting Cells

• Monocytes
• Macrophages
• pDCs and cDCs

Activated Myeloid Cells

• Chemokine & cytokine secretion
• Enhanced antigen presentation

4	5
T cell Priming &	T Cell Killing of Tumor Cells
Expansion

Result: An Immune "Hot" Tumor

• Chemokines attract immune effector cells
• Cytokines lower immune activation threshold
• Increases myeloid APC phagocytosis
• Activated T cells migrate to tumor

Boltbody™	Tumor	Tumor	Dying	Myeloid	T Cell	Activated	MHC-Tumor	Granzymes,
ISAC			Tumor Cell			T Cell	Peptide	IFN , TNF	α
	Antigen	Cell		APC			Complex	γ

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Adapted from Creative Biolabs

ISACs Deliver Powerful Synergies

Covalent Attachment of TLR7/8 Agonist Dramatically Improves Anti-tumor Efficacy

HCC1954 Tumor Xenograft Model

HUMAN HCC1954		SUBCUTANEOUS INJECTION
TUMOR CELL LINE		OF CULTURED CELLS

• SCID/Beige lack T, B and functional NK cells, but retain a myeloid compartment
• Enables assessment of myeloid-mediatedanti-tumor activity

Single ISAC Dose Mediates Tumor Regression

Trastuzumab T785-ISAC (Systemic)

Trastuzumab (Systemic) + T785 (intratumoral)

Trastuzumab (Systemic)

Tx

7 Ackerman SE, et al. Nature Cancer. 2021.

Preclinical Boltbody™ ISAC Data Shows Advantage to Combining TLR7 and TLR8

TLR7/8 Dual Agonist Provides an Amplification of Immune Response

cDC

α TLR7/8

pDC IFN

TLR7

IFNα receptor

Tumor

Cell

CD8+ T Cell

TLR7/8 Dual Agonist Results in Enhanced Myeloid Activation

TLR7/8 ISAC vs. TLR8 ISAC (CD86)

TLR7/8 ISAC

TLR8 ISAC

TLR7/8 ISAC vs. TLR7 ISAC (CD86)

TLR7/8 ISAC

TLR7 ISAC

8 Human myeloid APCs were co-cultured with CD20+ tumor cells and rituximab ISACs or rituximab for 18 hours.

Boltbody™ ISAC Induces Immune Memory that Extends to Tumors Lacking HER2

Immunity Extends to Tumor Neoantigens through Epitope Spreading

Heterogenous HER2+ Tumors

10% of Tumor Cells Lack HER2 Expression

In Vivo rHER2 Expression

rHER2+

91.4%

rHER2-

8.57%

Epitope Spreading with ISAC

Clearance of Heterogenous Tumors in Mice

	HER2 ISAC	0/8 CRs
		HER2 mAb

6/8 CRs

Rechallenge with HER2neg CT26

Epitope Spreading Dependent on T Cells

CR Mice (from prior HER2 ISAC)

CR Mice + CD4/CD8 Depletion

Tumor Naive Mice

CT26-rHER2+ or CT26-rHER2neg Syngeneic Colorectal Cancer Models

9 Ackerman SE, et al. Nature Cancer. 2021.

Strategic Collaborations Provide External Validation for Boltbody™ Platform

Fully integrated biopharma	•	Innovent funds up to 3 Boltbody™ ISACs through early clinical development
with large antibody library	•	Bolt has option to co-develop & commercialize 2 candidates in certain regions
and strong presence in
Greater China		- Bolt received $5M upfront; eligible for future milestones & royalties

Innovative leader in antibody & bispecific development for oncology

• Genmab funds 3 bispecific Boltbody ISACs through early clinical development
• Bolt has option to co-develop & commercialize 1 candidate in certain regions
• • Bolt received $25M upfront; eligible for up to $285M in milestones plus tiered royalties per program exclusively developed & commercialized by Genmab

Global leader in innovative technologies, conducting research in cancer immunotherapeutics

• Toray funds Boltbody ISAC for specific & novel target through end of Phase 1
• Global co-development/co-commercialization

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