Immatics N : ACTengine Combined Data Readout presentation March2021

ACTengine® IMA200 Clinical Trial Series Phase 1a Data Update

Cedrik Britten, Chief Medical Officer Harpreet Singh, Chief Executive Officer March 17, 2021

© Immatics. Not for further reproduction or distribution.

Forward-Looking Statements

This presentation ("Presentation") is provided by Immatics N.V. ("Immatics" or the "Company") for informational purposes only. The information contained herein does not purport to be all-inclusive and none of Immatics, any of its affiliates, any of its or their respective control persons, officers, directors, employees or representatives makes any representation or warranty, express or implied, as to the accuracy, completeness or reliability of the information contained in this Presentation.

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Certain information contained in this Presentation relates to or is based on studies, publications, surveys and the Company's own internal estimates and research. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while the Company believes its internal research is reliable, such research has not been verified by any independent source. All the scientific and clinical data presented within this presentation are - by definition prior to completion of the clinical trial and a clinical study report - preliminary in nature and subject to further quality checks including customary source data verification.

Key Takeaways from ACTengine® Phase 1a Data Update

Clinical Overview

Key Findings

Clinical ACTengine® (TCR-T) Programs: IMA201, IMA202, IMA203

3 14 <1bn

Patients infused as of data cut-off on Feb 16, 2021*

T cells infused per patient at dose levels 1 and 2 - presumed to be sub-therapeutic

Transient and manageable treatment-

emergent adverse events as expected for

cell therapies

Robust T cell engraftment and persistence post infusion and tumor infiltration in all evaluable patients

Tumor shrinkage observed in 8/10 evaluable patients including one unconfirmed partial response (RECIST1.1)

First anti-tumor activity observed consistent with robust biological activity during early phases of dose escalation

* Thereof 10 patients evaluable for biological activity and clinical efficacy analysis at data cut-off

ACTengine® IMA200 Series - Key Features

Differentiated Targets, TCRs and Cellular Manufacturing Designed to Enhance Safety and Activity

IMA201

IMA202

IMA203

Peptide Target

MAGEA4/8

HLA-A*02-presented peptide derived from

MAGEA1

PRAME

shown to be naturally and specifically presented on native tumor tissues at differentiated high peptide target density1

100-1,000 copies/cell

50-900 copies/cell

100-1,000 copies/cell

T cell Receptor

(TCR)

Natural TCR ~10 ng/ml

High-affinity specific TCRs with high functional avidity2

Natural TCR ~15 ng/ml

Pairing-enhanced TCR ~5 ng/ml

T cell Product

Autologous T cells gene-engineered with lentiviral vector expressing TCR and applying proprietary short-term manufacturing process designed to achieve better T cell engraftment and persistence

7-10 days

7-10 days

6-7 days

• 1 Applying XPRESIDENT® quantitative mass spectrometry engine; target density: peptide copy number per tumor cell, approximate range representing the majority of tumor samples analyzed

• 2 Applying XCEPTOR® TCR discovery and engineering platform incl. XPRESIDENT®-guided off-target toxicity and similar peptide screening to minimize off-target reactivity; functional avidity: EC50 half maximal effective concentration

ACTengine® Trial Design and Key Study Objectives

Each IMA200 Series Clinical Trial Includes Dose Escalation and Dose Expansion Cohorts

Phase 1a: Dose Escalation

Phase 1b: Dose Expansion

Trial Design: IMA201 and IMA202: 2+2 Design; IMA203 3+3 Design

Dose Level 1*	Dose Level 2*	Dose Level 3*	Dose Level 4*
IMA201/202	~50m /m2	~300m /m2	~1000m /m2	NA
IMA203	40-60m /m2	120-180m /m2	200-480m /m2	up to 1200m /m2

Key Objectives	Dose Level 1 & 2	Dose Level 3 & 4
Primary: Safety
Secondary: Biological Activity Secondary: Clinical Activity

* Dose is shown as transduced viable CD8 T cells per m2 total body surface area; NA: not available

ACTengine® Patient Flow

High Enrollment Efficiency through Combined Screening for Three Targets

Screening & Manufacturing Phase

Treatment & Observation Phase

Safety and efficacy monitoring for 12 months

Target Profiling	Lymphodepletion
Fresh Tumor Biopsy;	40 mg/m2 Fludarabine and
IMADetect®	500 mg/m2 Cyclophosphamide
for 4 days*

Long Term Follow-up

* Dose modifications of lymphodepletion regimen for certain risk groups (e.g. patients with HCC & patients with reduced renal-clearance)

Patient Characteristics

Heavily Pre-treated Patients Suffering from Diverse Solid Cancers Enrolled in ACTengine® Trials

Patient Distribution (N=16)

NumberCharacteristics in Efficacy Pop. (N=10)Median (range)

Patients lymphodepleted 16

Thereof patients infused1 14

Patients in Safety Population2 16

Patients in Efficacy Population3 10

Patients with serial biopsies 6

Patients in IMA201 study 1

Patients in IMA202 study 7

Patients in IMA203 study 8

Age [years]

61 (33 - 68)

Number of prior lines of systemic therapies

5 (2 - 7)

Years from diagnosis4

4 (1 - 12)

Total transduced T cells5 [x109]

0.11 (0.08 - 0.65)

• • At data cut-off, 10 patients across multiple tumor indications (including NSCLC, head & neck cancer, melanoma, synovial sarcoma and others) received ACTengine® T cell products and had at least one tumor response assessment

• • All patients infused were heavily pre-treated, failed all previous therapies and entered the study with recurrent and/or refractory solid tumors

1 Infusion of one patient pending; 2 Patients that started lymphodepletion; 3 Patients with at least one tumor response assessment post baseline; 4 Until start of lymphodepletion; 5 viable CD8 T cells

Safety Profile

Treatment-emergent Adverse Events Are Manageable, Transient and Expected for Cell Therapies

Adverse Events:

• • Most frequent adverse events were transient cytopenias associated with lymphodepletion

• • Transient CRS3 (Grade 1-2) in 13/14 infused patients.

• • Transient Grade 1 or 2 ICANS in 3/14 infused patients, resolved within 48h in all cases

Dose-limiting toxicities:

• • IMA201 and IMA202: No DLT5 observed

• • IMA203: One transient, Grade 3 atrial fibrillation with onset on day 5 post infusion that resolved within 48h after onset. DLT triggered expansion of dose level 2 from three to six patients

All treatment-emergent adverse events (TEAEs) with grade 1-2 occurring in at least 5 patients (incidence ≥31.3%) and additionally all events with grade 3-5 regardless of relatedness to study treatment are presented. Data source: clinical and safety database; hematological adverse events were derived from lab values. Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events, version 5.0. Grades for CRS and ICANS were determined according to CARTOX criteria (Neelapu et al, 2018). Patients are counted only once per adverse event and severity classification.

TEAEs by maximum severity (N=16)

All Grades

≥ Grade 3

Adverse event

Patients with any adverse event Lymphopenia

Leukopenia Neutropenia Anaemia Thrombocytopenia Nausea

Pyrexia Vomiting Fatigue Hypoxia Hyponatraemia Dyspnoea1 Atrial fibrillation Hypertension Muscular weakness Pleural effusion Tumor pain

Blood alkaline phosphatase increased Candida infection

Corona virus infection Febrile neutropenia Infection Pneumonia1 Sepsis2

No. 16

% 100.0

No. 16

16

100.0

16 100.0

16

100.0

16 100.0

16

100.0

15 93.8

16

100.0

10 62.5

15

93.8

6 37.5

11

68.8

0 0

8

50.0

0 0

6

37.5

1 6.3

5

31.3

1 6.3

5

31.3

1 6.3

5

31.3

0 0

3

18.8

1 6.3

2

12.5

1 6.3

2

12.5

1 6.3

2

12.5

1 6.3

2

12.5

1 6.3

2

12.5

1 6.3

1

6.3

1 6.3

1

6.3

1 6.3

1

6.3

1 6.3

1

6.3

1 6.3

1

6.3

1 6.3

1

6.3

1 6.3

1

6.3

1 6.3

Adverse Events of Special InterestCytokine release syndrome3 ICANS4

13 3

81.3 18.8

0 0

0 0

1 Patient died from tumor progression and pneumonia 69 days after IMA202 T cell infusion (determined not related to any study medication), 2 Patient died from sepsis of unknown origin and did not receive IMA203 T cells, 3 CRS: Cytokine release syndrome, 4ICANS: Immune effector cell associated neurotoxicity syndrome, 5DLT: Dose limiting toxicities

% 100.0

Biological Activity

T cells Robustly Engraft, Persist and Infiltrate into Tumor after Infusion of Low Doses of ACTengine®

Engraftment & T cell Persistence in the Blood

Detection of T cells in the Tumor

201-DL1-01

202-DL1-01

202-DL1-02

202-EC1-01

202-DL2-01

202-DL2-02

203-DL1-01

203-DL1-02

203-DL1-03

203-DL2-01

202-DL1-02

202-EC1-01

202-DL2-02

203-DL1-01

203-DL1-03

203-DL2-01

• • Robust T cell engraftment and persistence post infusion until the end of the observation period as assessed by qPCR*

• • Engineered T cells are detectable in serial tumor biopsies post T cell infusion in all evaluable patients by qPCR

* Up to 9 months (data not shown), UD: Undetected, NA: Not available, DL: Dose level, EC1: Enrichment cohort with intermediate dose level between DL1 and DL2 , TBD: To be determined

Clinical Activity - Best Overall Response (BOR) Assessment

Disease Control in 9 out of 10 Patients at Dose Level 1 and 2 (below 1 Billion Transduced CD8 T cells)

Diagnosis

Prior lines of systemic therapy

RECIST1.1

Prior lines of ICI2 treatment Disease status at infusion Best response

Patients with recurrent and/or refractory solid tumors

SD

SD

SD

SD

PD

10

1 Total infused dose of transduced viable CD8 T cells; 2 Immune checkpoint inhibitor; 3 Unconfirmed as of data cut-off; DL: Dose level, EC1: Enrichment cohort with intermediate dose level between DL1 and DL2 ,

SD: stable disease, PD, progressive disease, PR: partial response

Clinical Activity - Change of Sum of Diameters in Target Lesions

Tumor Shrinkage Observed in 8 of 10 Patients at Low Dose Levels

203-DL1-03

Diagnosis

202-DL1-02

Best Overall Response (RECIST1.1) :

SD

PRPD

)

202-DL2-022

)

SCC

Melanoma

)

203-DL1-01

)

201-DL1-01

)

202-DL2-01

)

203-DL1-02

)

202-DL1-01

202-EC1-013

203-DL2-014

Ovarian Cancer

Head & Neck

NSCLC

SCC

Head & Neck

HNSCCMelanoma SSayrncoovmiaal

1 Shortest diameter for nodal lesions; 2 Stable target lesions with parallel growth of a CNS non-target lesion;

3 RECIST1.1 response at timepoint of maximum in change of target lesions (week 12): PD due to growth of non-target lesion; 4 PR unconfirmed as of data cut-off

Case Study - Melanoma Patient 202-EC1-01

Tumor Shrinkage Associated with T cell Persistence in Blood and Tumor Infiltration

• • 64-year-old female; Stage 4 melanoma

• • Infused at progressive disease after failing 4 prior systemic lines of treatment including immune checkpoint inhibitors

• • Patient received total dose of 189m transduced CD8 IMA202 T cells following lymphodepletion

T cell Detection in the Tumor

Baseline Week6 LastVisit

IMA202

IMA203

• • T cells persisted until end of observation and were detected in the tumor

• • 20% and 35% decrease in target lesions (RECIST1.1) at week 6 and 12, respectively

• • Best Response: SD (week 6), Patient off-study (week 12) due to growth of an existing non-target lung lesion

Change in Target Lesions

Scans by courtesy of Dr. Wermke 12

Case Study - Synovial Sarcoma Patient 203-DL2-01

RECIST Response in Patient with High Tumor Burden Observed at Dose Level 2

• • 57-year-old male; Stage 4 synovial sarcoma

• • Infused at refractory disease after failing previous lines of therapy

• • Patient received total dose of 350m transduced CD8 IMA203 T cells (DL2) following lymphodepletion

T cell Detection in the Tumor

Baseline Week6 LastVisit

IMA202

IMA203

• • T cells persisted at high levels until end of observation and were detected in the tumor

• • All 14 lesions (22-62 mm longest diameter) decreased at week 6 with 40% decrease in target lesions (RECIST1.1)

• • Best Response: PR (unconfirmed, week 6)

Size Changes across 14 Lesions

T2: Left soleus muscle

T1: Right vastus lateralis muscle

Target Lesion T2: Left soleus muscle

Scans by courtesy of Dr. Araujo

Summary and Future Directions

Key Findings

Next Steps

Transient and manageable treatment-

emergent adverse events as expected for

cell therapies

• • Complete Dose Escalation for IMA201,

  IMA202, IMA203 clinical trials

Robust T cell engraftment and persistence post infusion and tumor infiltration in all evaluable patients

• • Initiate Dose Expansion and treat patients at target dose

  Tumor shrinkage observed in 8/10 evaluable patients including one unconfirmed partial response (RECIST1.1)

• • Update on patients treated at target dose expected for 2H2021

First anti-tumor activity observed consistent with robust biological activity during early phases of dose escalation

Upcoming R&D Milestones in 2021

1H 2021

2H 2021

ACTengine®

IMA201, 202, 203: Initial Ph1a dose escalation read-out

IMA201, 203: Additional Ph1a read-out

IMA202: Initial Ph1b dose expansion read-out

IMA204 IND* submission

TCER®

IMA401 IND* submission

IMA402 Preclinical PoC & start GMP mf. activities

* IND: May be investigational drug application with FDA or analogous clinical trial application (CTA) to a European regulatory agency

Special Thanks to Our Patients, Their Families … and Our Investigators at the Clinical Sites

United States

Columbia University

Dr. M. Bishop

University of Chicago	Dr. R. Reshef
University of

Pittsburgh

MD Anderson Cancer

Center

Dr. D. Araujo Dr. G. Blumenschein

Dr. A. Kaseb

Dr. A. Jazaeri Dr. Van Morris Dr. A. Tsimberidou

Dr. J. Luke

Dr. T. Holderried

Germany

University Hospital

Hamburg

Dr. C. Bokemeyer

University Hospital Bonn

Dr. M. Wermke

Dr. C. List

University Hospital

DresdenUniversity Hospital Würzburg

Dr. M. Chatterjee

www.immatics.com

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