Carisma Therapeutics : Corporate Presentation May 2024

HARNESSING THE POWER OF MACROPHAGES

May 2024

Cautionary Note Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Carisma's business, strategy, future operations, cash runway, the advancement of Carisma's product candidates and product pipeline, and clinical development of Carisma's product candidates, including expectations regarding timing of initiation and results of clinical trials. The words "anticipate," "believe," "contemplate," "continue," "could," "estimate," "expect," "goals," "intend," "may," "might," "outlook," "plan," "project," "potential," "predict," "target," "possible," "will," "would," "could," "should," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, (i) Carisma's ability to realize the anticipated benefits of its pipeline reprioritization and corporate restructuring, (ii) Carisma's ability to obtain, maintain and protect its intellectual property rights related to its product candidates; (iii) Carisma's ability to advance the development of its product candidates under the timelines it anticipates in planned and future clinical trials and with its current financial and human resources; (iv) Carisma's ability to replicate in later clinical trials positive results found in preclinical studies and early-stage clinical trials of its product candidates; (v) Carisma's ability to realize the anticipated benefits of its research and development programs, strategic partnerships, research and licensing programs and academic and other collaborations; (vi) regulatory requirements or developments and Carisma's ability to obtain and maintain necessary approvals from the U.S. Food and Drug Administration and other regulatory authorities related to its product candidates; (vii) changes to clinical trial designs and regulatory pathways; (viii) risks associated with Carisma's ability to manage expenses; (ix) changes in capital resource requirements; (x) risks related to the inability of Carisma to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; and (xi) legislative, regulatory, political and economic developments. For a discussion of these risks and uncertainties, and other important factors, any of which could cause Carisma's actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" set forth in the Company's Annual Report on Form 10-K for the year ended December 31, 2023, as well as discussions of potential risks, uncertainties, and other important factors in Carisma's other recent filings with the Securities and Exchange Commission. Any forward-looking statements that are made in this press release speak as of the date of this press release. Carisma undertakes no obligation to revise the forward-looking statements or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.

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Pioneering engineered macrophages in oncology and beyond

Harnessing the Power of Macrophages

Developing unique and transformative cell therapies for patients with devastating diseases

+

HER2

Program

• Focused development of CT-0525(CAR-Monocyte), which we believe is best suited to deliver benefit to patients with HER2 over-expressing solid tumors refractory to available treatments
• CT-0525initial data is expected end of 2024
• CT-0508trial to conclude post Regimen Level 2 of sub-study in combination with pembrolizumab

+	Beyond
HER2*

+

Corporate

• In Vivo Oncology: Advancing multiple targets in our in vivo CAR-M program in collaboration with Moderna
• Fibrosis: Advancing an engineered macrophage in liver fibrosis, with development candidate nomination expected in the first quarter of 2025
• Cash runway into 3Q 2025, funding multiple clinical and preclinical catalysts
• Strong IP position
• Potential for collaborations (except in vivo oncology)

• In late March 2024, Carisma made the decision to pause further development of CT-1119, pending additional financing MOA: Mechanism of Action

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CAR-M: Differentiated from CAR-T and CAR-NK

CAR-M has the potential for key solid tumor advantages over both

	CAR-T	CAR-NK	CAR-M
Mechanism of Action
Effector Cell	CD4/CD8 T cells	Natural Killer Cells	Macrophages or Monocytes
Persistence
High	Low	Intermediate
Trafficking Potential
Low	Low	High
TME Activation
Low	Low	High
Antigen Presentation
None	None	High
Epitope Spreading
Low	Low	High
Safety
Chemotherapy Conditioning	Yes	Yes	No
CRS / ICANS
High / High	Low / Low	Low / Low
Manufacturing
Manufacturing Time	Days to weeks	Days to weeks	Monocyte: 1 day

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First-in-Class Pipeline

Multiple value inflection points across therapeutic areas and modalities

THERAPEUTIC	PRODUCT	PLATFORM	DISCOVERY PRE-CLINICAL	PHASE 1	PHASE 2	PHASE 3	COLLABORATOR
AREA	CANDIDATE
Ex Vivo Oncology
		CT-0525	CAR-Monocyte		4Q 2024: Initial data1
HER2+			(1st Gen CAR)
solid tumors	CT-0508*	CAR-Macrophage		2Q 2024: Combination data`1
		(1st Gen CAR)
Mesothelin+	CT-1119**	CAR-Monocyte
solid tumors	(Next-Gen CAR2)

In Vivo Oncology

Solid Tumor Antigen3	CAR-Macrophage +
mRNA/LNP
Oncology
CAR-Macrophage +
4 Additional Targets4
mRNA/LNP

Fibrosis and Immunology

Liver Fibrosis	TBD	Engineered	1Q 2025: Development candidate nomination1
macrophage

• In late March 2024, Carisma made the decision to cease further development of CT-0508, including monotherapy and in combination with pembrolizumab
• In late March 2024, Carisma made the decision to pause further development of CT-1119, pending additional financing

1. Anticipated milestones; 2. Includes SIRPα knockdown technology; 3. Target undisclosed

4. Moderna collaboration has identified 5 total oncology targets, with the option to identify an additional 7 oncology targets; First lead candidate was nominated in 4Q 2023

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Drive to 2025

Leverage world-leading macrophage engineering platform to deliver three product opportunities

Program

2024 Tactical Plan

2025 Objectives

HER2 CAR-M

In vivo CAR-M

(Collaboration with Moderna)

Liver Fibrosis

CT-05251 Safety Study Cohort 1: 3 Billion Cells

CT-05251 Safety Study Cohort 2: 10 Billion Cells

IND-enabling activities for lead candidate Pre-clinical studies for additional identified targets

Preclinical studies for development candidate nomination

Phase II/III Regimen Identified2

Undisclosed Development &

Regulatory Milestones

Development Candidate Nominated

& IND-enabling Activities

1. CAR-Monocyte; 2. In late March 2024, the Company selected CAR-Monocyte approach for the Phase II/III Regimen Identified

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Targeting HER2:

CT-0525 and CT-0508

HER2 Development Strategy

CT-0525 selected as HER2 product candidate, with additional considerations to be informed by ongoing studies

Demonstrate Safety, Tolerability,

Feasibility & MOA:

CAR-Macrophage(CT-0508*)

Phase 1: No Further Data Expected

Overcome T Cell Exhaustion:

CAR-Macrophage(CT-0508*) +

Pembrolizumab

Phase 1: Data Expected 2Q'24

Increase Dose:

CAR-Monocyte(CT-0525)

Phase 1: Initial Data Expected 4Q'24

Potential Registrational Profile

Cell		Monotherapy		Line of		Tumor
Dose	vs. Combo
Type		Therapy		Type
	Therapy

MOA: Mechanism of Action

* In late March 2024, Carisma made the decision to cease further development of CT-0508, including monotherapy and in combination with pembrolizumab

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CT-0525

CT-0525: HER2 Targeted CAR-Monocyte(Macrophage Precursor)

Potential to significantly improve upon the observed biological activity of CT-0508

Highlights

Key Manufacturing Advantages Over CAR-Macrophage

• Higher cell numbers
• Faster manufacturing (1 day)
• Reduced COGS

Potential Biological Advantages Over CAR-Macrophage

• 2,000-foldincreased exposure
• • Cell count, trafficking, and persistence
• Increased potency
• • Killing, cytokine release, and antigen presentation
• Dosing flexibility

Development Plan & Timeline

• IND cleared

• First patient expected to be treated in 2Q 2024

• Initial data expected in 4Q 2024

CT-0525		CAR COMPONENTS

Humanized anti-HER2 scFv

CD8 Hinge

CD8 TM

CD3-zeta

TECHNICALS: CT-0508	CT-0525 Product Description
	Cells		Autologous monocytes
	Vector		Ad5f35
	Phenotype		M1
	CAR		1st Generation

* Compared to CAR-Macrophage

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