Slide 1: Immatics Corporate Presentation May 2, 2023
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation May 2, 2023
Slide 2: Forward-Looking Statement
Forward - Looking Statement 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 resp
Slide 3: Building a Leading TCR Therapeutics Company
Therapeutic O pp o rtun i t y Potential for addressing large patient populations with high prevalence targets in solid tumors Two Clinical - Stage Modalities Pipeline of TCR - T and TCR Bispecific product candidates in clinical & preclinical development Building a Leading TCR Therapeutics Company 3
Slide 4: Our Near-Term Focus – Clinical Development of Our Lead Assets
4 • IMA203 monotherapy • Checkpoint combo • IMA203CD8 monotherapy Next update on all three IMA203 cohorts and clinical development path for PRAME TCR - T monotherapy towards registration - directed trials is planned for 4Q 2023 ACTengine® IMA203 (PRAME) Three IMA203 Ph1b cohorts Establish clinical P
Slide 5: Our TCR-based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface
Our TCR - based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface 5 I n t r o
Slide 6: Two Distinct TCR-based Therapeutic Modalities in Clinical Development
Two Distinct TCR - based Therapeutic Modalities in Clinical Development 6 Differentiated positioning of ACTengine® vs. TCER® based on patient population and medical need I n t r o 1 Interim data update from the ACTengine® IMA203 TCR - T Phase 1 trial with a 50% (6/12) confirmed ORR target dose or ab
Slide 7: Our Pipeline of TCR-based Adoptive Cell Therapies and Bispecifics
Our Pipeline of TCR - based Adoptive Cell Therapies and Bispecifics 7 I n t r o 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion; 2 Opdivo® (nivolumab): programmed death - 1 (PD - 1) immune checkpoint inhibitor; * Immatics proprietary ACTallo® platform utilizing Editas’ CRISPR gene editing tech
Slide 8: Strategic Collaborations
Strategic Collaborations Synergistic Expertise that Can Foster Transformative Innovations for ACT and Bispecifics Research collaboration to develop bispecific immunotherapies 2 Immatics targets $54 M upfront Co - promotion option Broadening the clinical framework beyond our pipeline Research collabo
Slide 9: Potential for Large Patient Populations across Multiple Solid Cancers
Potential for Large Patient Populations across Multiple Solid Cancers 9 Uterine Carcinoma – 100% Sarcoma Subtypes – up to 100% Cut. Melanoma – 95% Uveal Melanoma 1 – 90% Ovarian Carcinoma – 80% Squamous NSCLC – 65% TNBC – 60% Small Cell Lung Cancel – 55% Kidney Carcinoma – up to 45% Cholangiocarcino
Slide 10: Realizing the Full Multi-Cancer Opportunity of PRAME
Realizing the Full Multi - Cancer Opportunity of PRAME ACTengine® IMA203 (TCR - T) and TCER® IMA402 (TCR Bispecific) 10 Indication % PRAME positive patients 1 Uterine Carcinoma Uterine Carcinosarcoma Sarcoma Subtypes Cut. Melanoma Uveal Melanoma 2 Ovarian Carcinoma Squamous NSCLC T N BC Small Cell L
Slide 11: ACTengine IMA203 – Targeting PRAME
ACTengine® IMA203 – TCR - T Targeting PRAME 11
Slide 12: ACTengine IMA203 Targeting PRAME – Mechanism of Action
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ Leading TCR - T Approach 12 I M A 203
Slide 13: Key Pillars of Developing a Successful Product Candidate
Key Pillars of Developing a Successful TCR - T Product Candidate Summary of Interim Update on IMA203 TCR - T Phase 1b Cohort A as of April 2023 S a f e ty Anti - Tumor Activity Durability Product Quality Broad Reach Manageable tolerability at doses as high as ~9x10 9 TCR - T cells High rate of objec
Slide 14: The Multi-Cancer Opportunity of PRAME
The Multi - Cancer Opportunity of PRAME One of the Most Promising Solid Tumor Targets for TCR - based Therapies Known To Date 14 High prevalence High target density Homogeneous expression “Clean” expression profile Clinical proof - of - concept s q N S C L C Ovarian Cancer PRAME fulfills all propert
Slide 15: ACTengine IMA203 Monotherapy – Patient Flow
ACTengine® IMA203 TCR - T Monotherapy – Patient Flow 15 HLA - A*02 Testing Blood sample; Central lab Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase Manufacturing by Immatics Infusion of ACTengine® IMA203 TCR - T Product Lymphodepletion * Target Profiling Fresh Tu
Slide 16: ACTengine IMA203 Phase 1b Design
ACTengine® IMA203 TCR - T Phase 1 Design Focus on IMA203 TCR - T Monotherapy Investigated in Cohort A 16 Phase 1b Cohort A Interim Update on 11 patients 1 Updated target dose (provisional recommended Phase 2 dose, RP2D) determined at DL4+DL5 for Cohort A and B, for Cohort C treatment of n=3 patients
Slide 17: Phase 1b Cohort A Patient and Product Characteristics
N =11 ACTengine® IMA203 TCR - T Monotherapy – Phase 1b Cohort A Patient and Product Characteristics Data cut - off Apr 04, 2023 17 Heavily pre - treated, metastatic last - line patients that have exhausted all available standard of care treatments 1 Including ovarian cancer patient A - DL5 - 04 who
Slide 18: Most Frequent Adverse Events – Phase 1b Cohort A
Most Frequent Adverse Events – Phase 1b Cohort A (N=11) Manageable Treatment - emergent Adverse Events (TEAEs) CRS and ICANS graded by CARTOX criteria (Neelapu et al ., 2018); 1 ICANS: Immune Effector Cell - Associated Neurotoxicity Syndrome • Expected cytopenia (Grade 1 - 4) associated with lymphod
Slide 19: Best Overall Response – Phase 1b Cohort A
Best Overall Response – Phase 1b Cohort A Deep Objective Responses Independent of Tumor Type 1 Ovarian cancer patient A - DL5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population; 2 Initial ORR: Objective respons
Slide 20: Response over Time – Phase 1b Cohort A
Response over Time – Phase 1b Cohort A Durable Partial Responses 9+ Months after IMA203 TCR - T Treatment **Ovarian cancer patient A - DL 5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population ; 1 Duration of res
Slide 21: Biological Data Consistent with Clinical Data
Biological Data Consistent with Clinical Data IMA203 TCR - T Levels and Tumor Infiltration across Patients in Phase 1a and Phase 1b Cohort A IMA203 T cells found in all evaluable tumor tissues, level of infiltration associated with objective responses 1 Increased levels of IMA203 T cells in the bloo
Slide 22: Favorable Product Characteristics and High Levels in Patients
0 2 î 10 5 4 î 10 5 6 î 10 5 8 î 10 5 0. 0025 Favorable TCR - T Product Characteristics and High TCR - T Levels in Patients Manufacturing Improvements Implemented in Phase 1b Enhance Key Features of the Cell Product Manufacturing success rate of 94% to reach provisional RP2D ** Mean cell dose infuse
Slide 23: Responses above PRAME RNA Threshold Independent of Tumor Type
Responses above Immatics’ PRAME RNA Threshold Independent of Tumor Type Highlighting Tumor Types (left) and Type of Best Overall Response (right) – Phase 1b Cohort A PRAME RNA expression in pre - treatment biopsies relative to threshold IMA203 achieved objective responses at all expression levels ab
Slide 24: Potential of IMA203 in Additional Solid Cancer Indications
Potential of IMA203 in Additional Solid Cancer Indications Based on PRAME Expression in IMA203 TCR - T Responders – Phase 1b Cohort A 24 Immatics’ proprietary mass spectrometry - guided mRNA threshold 100% 100% 95% 100% 50% (90% 2 ) 80% 60% 65% 25% % PRAME - positive patients 1 PRAME target expressi
Slide 25: IMA203 Monotherapy Summary of Phase 1b Cohort A Interim Data
ACTengine® IMA203 TCR - T Monotherapy Targeting PRAME Summary of Phase 1b Cohort A Interim Data Update • Manageable tolerability with no high - grade CRS, no ICANS in 11 patients in Cohort A 1 • Objective responses observed in heavily pre - treated last - line solid cancer patients including checkpo
Slide 26: ACTengine IMA203 Development Strategy
Immatics’ ACTengine® IMA203 TCR - T Development Strategy Two Pillared Strategy 26 Objective: Deliver best - in - class therapy in 1 - 2 last - line solid cancer types as fast as possible • Focus on indications with PRAME prevalence above 80% with available clinical PoC, such as cut. melanoma (potent
Slide 27: IMA203 Product Manufacturing
ACTengine® IMA203 TCR - T Product Manufacturing Enhancing Manufacturing Process and Capabilities Leukapheresis Rapid Manufacturing Process 1 week Expedited QC Release Testing 1 week I nf usio n - r e a d y Manufacturing of ACTengine® IMA203 TCR - T & other future autologous /allogeneic candidates Ea
Slide 28: IMA203 Has the Potential to Reach a Large Patient Population
Selected Indications Incidence R/R Incidence PRAME Positive Patient Population Based on R/R Incidence; PRAME and HLA - A*02:01+ Cut. Melanoma 99,800 7,700 95% 2,999 Uveal Melanoma 1,500 800 90% 295 Ovarian Carcinoma 19,900 12,800 80% 4,198 Uterine Carcinoma 62,700 10,700 100% 4,387 Uterine Carcinosa
Slide 29: ACTengine IMA203CD8 – Next-generation
ACTengine® IMA203CD8 – Next - generation TCR - T Building on First - Gen IMA203 Success to Further Improve Anti - Tumor Activity • Engagement of CD4 T cells by CD8 co - transduction reported to boost anti - tumor activity in TCR - T trials • Recent data from leukaemia patients treated with CAR - T s
Slide 30: IMA203CD8 – Preclinical Assessment of Anti-Tumor Efficacy
ACTengine® IMA203CD8 – Preclinical Assessment of Anti - Tumor Efficacy Functional CD4 T cells Mediate Longer Anti - Tumor Activity than CD8 T cells in vitro 30 0 .0 0 .5 1 .0 1 .5 2 .0 CD8 0 50 100 150 200 250 300 350 400 450 Hours after Coculture Tumor fold growth 0 .0 0 .5 1.0 1 .5 2 .0 CD4 0 50 1
Slide 31: ACTengine IMA204 – Targeting COL6A3 Exon 6
ACTengine® IMA204 – TCR - T Targeting COL6A3 Exon 6 31
Slide 32: ACTengine IMA204 First-in-Class Targeting Tumor Stroma
ACTengine® IMA204 First - in - Class TCR - T Targeting Tumor Stroma Key Features 32 HLA - A*02 - presented peptide derived from COL6A3 exon 6 Naturally and specifically presented on tumors at high target density 1 : 100 - 700 copies/cell Novel tumor stroma target identified and validated by XPRESIDE
Slide 33: IMA204 – High Affinity, CD8-independent TCR
ACTengine® IMA204 – High Affinity, CD8 - independent TCR Complete Tumor Eradication in vitro & in vivo 1 by Affinity - enhanced IMA204 TCR CD8 - independent TCR leads to tumor eradication in all mice treated 33 W Si Do ild t ngl ub l ype e e m muta n u t a n t t T u N mo o n - t r c ra n ells o s du
Slide 34: ACTallo – Our Next-generation Off-the-shelf Platform
ACTallo® – Our Next - generation Off - the - shelf TCR - T 34
Slide 35: ACTallo – Immatics' Allogeneic Cell Therapy Approach
ACTallo® – Immatics’ Allogeneic Cell Therapy Approach • Off - the - shelf cell therapy , no need for personalized manufacturing reduced logistics and time to application • Potential for hundreds of doses from one single donor leukapheresis lower cost of goods • Use of healthy donor material prov
Slide 36: Why γδ T cells?
Why γδ T cells? γδ T cells Are Well Suited for an Off - the - shelf Cell Therapy Approach 36 γδ T cells x are abundant in the peripheral blood x show intrinsic anti - tumor activity x naturally infiltrate solid tumors & correlate with favorable prognosis x are HLA - independent, thus do not cause gr
Slide 37: TCER – TCR Bispecifics
ooe@ immatics TCER® — TCR Bispecifics
Slide 38: TCER – Next-generation, Half-Life Extended Bispecifics
TCER® – Immatics’ Next - generation, Half - Life Extended Bispecifics Proprietary TCER® Format Consisting of Three Distinct Elements 38 High - affinity TCR domains targeting XPRESIDENT® - selected tumor - specific peptide - HLA molecules L o w - a ff i n i t y T cell recruiter against CD3/TCR Fc par
Slide 39: TCER – Half-Life Extended Bispecifics Features
TCER® – Immatics’ Next - generation, Half - Life Extended Bispecifics 39 pHLA targeting TCR x High - affinity (single digit nM) TCR targeting XPRESIDENT® - selected tumor - specific peptide - HLA molecules x Broad therapeutic window through XPRESIDENT® - guided affinity maturation (>1000x) 1 x Compl
Slide 40: Potency of Our Proprietary TCR Bispecific Format TCER
Potency of Our Proprietary TCR Bispecific Format TCER® 40 • Seven different TCR Bispecific formats were evaluated with a pHLA targeting TCR and the identical T cell recruiting antibody • TCER® format had higher combination of potency and specificity 1 than six alternative TCR Bispecific format desig
Slide 41: TCER Format Designed for Optimized Efficacy and Safety – Tumor Control
TCER® Format Is Designed for Optimized Efficacy and Safety Superior Tumor Control Using a Novel, Low - Affinity Recruiter 41 n = 6 mice/treatment group, n = 10 mice in vehicle group, 2 donors/group Dose : 0 . 025 mg/kg Proprietary, low - affinity T cell recruiting region demonstrates superior tumor
Slide 42: TCER Format – Reduced Cytokine Release
TCER® Format Is Designed for Optimized Efficacy and Safety Reduced Target - Unrelated Recruiter - Mediated Cytokine Release using a Low - Affinity Recruiter 42 T CE R ® Whole blood cytokine release assay N=3 HLA - A*02 - positive donors N=16 cytokines tested, 4 exemplary cytokines shown
Slide 43: Our TCER Portfolio
Our TCER® Portfolio Broad Pipeline of Next - Gen Half - Life Extended TCR Bispecifics 43 T CE R ® • PRAME peptide presented by HLA - A*02:01 • Start of clinical trial planned for 2H 2023, first clinical data in 2024 IM A 402 • Undisclosed peptide presented by HLA - A*02:01 • Preclinical PoC studies
Slide 44: TCER IMA402 Targeting PRAME – Efficacy Assessment in vitro
TCER® IMA402 Targeting PRAME – Efficacy Assessment in vitro Tumor Cell Killing at Low Physiological PRAME Peptide Levels 44 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] ~50 PRAME CpCs 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] Cytotoxic
Slide 45: TCER IMA402 Achieves Durable Tumor Control in vivo
TCER® IMA402 Achieves Durable Tumor Control of Large Tumors in vivo 45 - 2 9 0 50 0 100 0 150 0 200 0 250 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 Study day Median tumor volume [mm 3 ] Vehicle IMA402 [0.01 mg/kg] IMA402 [0.05 mg/kg] IMA402 [0.25 mg/kg] • Dose - dependent efficacy of IMA402 in cell line - der
Slide 46: Half-life Extended Format of IMA402
Half - life Extended Format of IMA402 Confers Terminal Half - life of >1 Week 46 pHLA – aFc Assay pHLA – aV L Assay • IMA402 shows a terminal serum half - life of ≈ 8 days in mice • IMA402 will be initially dosed weekly in the clinical trial • Dosing frequency may be adapted based on clinical data I
Slide 47: Advancing TCER IMA402 Towards Clinical Development
Upcoming activities • Start of patient treatment planned for 2H 2023 • First clinical data planned in 2024 Advancing TCER® IMA402 Towards Clinical Development Recent and Upcoming Activities 47 IMA402 TCER® Ph1/2 clinical trial in patients with solid tumors Recent activities x Completion of IND - ena
Slide 48: TCER IMA402 Phase 1/2 Clinical Trial to Start in 2023
TCER® IMA402 Phase 1/2 Clinical Trial to Start in 2023 48 MABEL: minimum anticipated biological effect level Phase 1: Dose Escalation Phase 2a: Dose Expansion Basket trial with focus indications Adaptive design aimed at accelerating dose escalation • Specific indications plus ongoing basket • Combin
Slide 49: Accelerated Development of TCER IMA402
Accelerated Development of TCER® IMA402 TCER® IMA402 Phase 1/2 Clinical Trial Design Targeting enhanced treatment convenience • Initially weekly i.v. infusions, potential for early optimization of scheduling based on half - life extended TCER® format • Exploring s.c. application 49 I M A 402 MABEL:
Slide 50: Immatics' Proprietary Target and TCR Discovery Platforms
Immatics’ Proprietary Target and TCR Discovery Platforms 50
Slide 51: True Cancer Targets & Matching Right TCRs
True Cancer Targets & Matching Right TCRs Goal to Maximize Anti - Tumor Activity and Minimize Safety Risks of TCR - based Immunotherapies 51 True Targets via XPRESIDENT® technology platform • are naturally presented on tumor tissues as identified by mass - spec • are absent or presented at only low
Slide 52: Pool of Prioritized Targets as Foundation for Future Value Generation
T e chn olo g y Pool of 200 Prioritized Targets as Foundation for Future Value Generation 52 200 Prioritized Targets Grouped in 3 Target Classes: 1. Well known and characterized parent protein (20%) e.g. MAGE family cancer testis antigens 2. Unknown or poorly characterized parent protein (60%) e.g.
Slide 53: Identification of the Most Relevant Target – MAGEA4/8 Peptide
Immatics’ Unique Capability – Identification of the most Relevant Target Example of MAGEA4/8 Peptide Target 53 1 Copy number per tumor cell (CpC) measured on a paired - sample basis by AbsQuant®, i.e. comparing MAGEA4 vs. MAGEA4/A8 peptide presentation on same sample, 2 Students paired T test p<0.00
Slide 54: Development of the Right TCR – XCEPTOR Technology
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics 54 TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy A C T e n g i n e® ACTallo® • Fast, efficient and highly sensitive discovery of highly specific, natural TCRs • Prote
Slide 55: Optimal Target Selection & TCR Specificity for Minimizing Safety Risks
Optimal Target Selection & TCR Specificity for Minimizing Safety Risks Unique Interplay between Technology Platforms Allows Early De - risking for Clinical Development 55 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Of f - t a r ge
Slide 56: Robust IP Portfolio
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 56 Cancer targets, TCRs and technology protected by: • 5 , 800 applications and patents filed in all major countries and regions • >115 patent families • >2,400 granted patents, thereof >550 granted patents in the US T e chn olo g y
Slide 57: Corporate Information & Milestones
Corporate Information & Milestones 57
Slide 58: Experienced Global Leaders
Harpreet Singh Chief Executive Officer Co - Founder >20 yrs biotech experience Arnd Christ Chief Financial Officer >20 yrs biotech experience (InflaRx, Medigene, NovImmune, Probiodrug) Carsten Reinhardt Chief Development Officer >20 yrs pharma & biotech experience (Micromet, Roche, Fresenius) Cedrik
Slide 59: Strong, Focused and Highly Integrated Trans-Atlantic Organization
Strong, Focused and Highly Integrated Trans - Atlantic Organization 59 Houston, Texas ~150 FTEs Cell therapy development & manufacturing Munich, Germany ~65 FTEs Various operating functions Tübingen, Germany ~215 FTEs Target & TCR discovery and TCR Bispecifics d ev e l o p me nt Corporate FTE status
Slide 60: Appendix
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. ww w .i mm a ti c s . c o m Appendix
Slide 61: IMA203 Monotherapy Tolerability Data – Phase 1b Cohort A
ACTengine® IMA203 TCR - T 1 st Gen Monotherapy Tolerability Data Focus on IMA203 Phase 1b Cohort A – All ≥Grade 3 Adverse Events (N=11) • IMA203 was well tolerated • No Adverse Event ≥Grade 3 was observed with a frequency ≥10% when excluding expected cytopenias associated with lymphodepletion • No I
Slide 62: Deep & Durable Responses in Heavily Pre-Treated Patients
Deep & Durable Responses in Heavily Pre - Treated Patients – Phase 1b Cohort A Patient ID Indication No of prior treatment lines Prior treatments Total infused dose TCR - T cells 1 [x10 9 ] BOR BOR (Max % change of target lesions) Comment A - DL5 - 01 Uveal Melanoma 1 ARRY614/Nivolumab 4.16 cPR - 60
Slide 63: IMA203 Monotherapy Tolerability Data
ACTengine® IMA203 TCR - T 1 st Gen Monotherapy Tolerability Data • IMA203 was well tolerated • No Adverse Event ≥Grade 3 was observed with a frequency ≥10% when excluding expected cytopenias associated with lymphodepletion • No IMA203 - related Grade 5 Adverse Events All treatment - emergent adverse
Slide 64: Phase 1a and Phase 1b Cohort A – Best Overall Response
Phase 1a and Phase 1b Cohort A – Best Overall Response 64 Confirmed objective responses across a broad spectrum of different tumor types such as cutaneous melanoma, uveal melanoma, head and neck cancer, ovarian cancer, synovial sarcoma * Maximum change of target lesions and RECIST 1.1 BOR at differe
Slide 65: Phase 1a and Phase 1b Cohort A – Responses over Time
Phase 1a and Phase 1b Cohort A – Responses over Time Improved Durability at Higher Dose and in Phase 1b Patients 65 Phase 1a (Dose Escalation) N=27 # Phase 1b (Cohort A) N=5 Best overall resp o nse (RE C I S T 1.1) I M A 203 # Synovial sarcoma patient (DL3) PD at week 6 not shown as target lesions w
Slide 66: Focus on Melanoma Patients
Focus on Melanoma Patients Phase 1a (DL4 only) and Phase 1b Cohort A Patient Characteristics (n=10) Prior lines of treatment Mean (min, max) 4.5 (1, 7) Previous lines of CPI Mean (Min, Max) 2.6 (1, 4) LDH at baseline >1 x ULN [% of patients] 60.0 Baseline tumor burden Mean target lesion sum of diame
Slide 67: Delivering the Power of T cells to Cancer Patients
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. ww w .i mm a ti c s . c o m