Slide 1: Immatics Corporate Presentation May 18, 2022
© Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation May 18, 2022
Slide 2: Forward-Looking Statements
Forward - Looking Statements 2 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 Immatics nor any of its affiliates nor any of its or their con
Slide 3: Building a Leading TCR Therapeutics Company
Building a Leading TCR Therapeutics Company 3 Intro Clinical PoC for Cell Therapy Objective responses across multiple solid tumors in early TCR - T clinical development Differentiated Approach Unique technologies to identify true cancer targets and right TCRs Strategic Partnerships World - leading i
Slide 4: 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 4 Intro
Slide 5: Two TCR-based Therapeutic Modalities
Two TCR - based Therapeutic Modalities 5 Distinct mechanisms of actions and therapeutic application to address the needs of a broad patient population at different stages of disease and with different types of tumors Intro
Slide 6: Our Pipeline of TCR-based Adoptive Cell Therapies and Bispecifics
Our Pipeline of TCR - based Adoptive Cell Therapies and Bispecifics 6 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion; 2 Opdivo ® (nivolumab): programmed death - 1 (PD - 1) immune checkpoint inhibitor Modality Product Candidate Target Preclinical Phase 1a 1 Phase 1b 1 Phase 2/3 ACTengine® Auto
Slide 7: Strategic Collaborations
Strategic Collaborations Synergistic Expertise that Can Foster Transformative Innovations for ACT and Bispecifics 7 2019 2021 2020 2018 Each of our 9 partnered programs may be eligible for • >$500 million aggregated milestone payments • Tiered royalties Broadening the clinical framework beyond our p
Slide 8: Selected solid cancer indications with significant target prevalence
IMA201 / IMA401 IMA202 IMA203 / IMA402 IMA204 MAGEA4/8 MAGEA1 PRAME COL6A3 exon 6 Selected solid cancer indications with significant target prevalence 1 Sarcoma Subtypes – up to 80% Squamous NSCLC – 50% HNSCC – 35% Bladder Carcinoma – 30% Esophageal Carcinoma – 25% Uterine Carcinosarcoma – 25% Ovari
Slide 9: Key Features of Our Clinical ACTengine Programs
IMA201 IMA202 IMA203 Peptide Target HLA - A*02 - presented peptide derived from MAGEA4/8 MAGEA1 PRAME shown to be naturally and specifically presented on native tumor tissues at d ifferentiated high peptide target density 1 100 - 1,000 copies/cell 50 - 900 copies/cell 100 - 1,000 copies/cell T cell
Slide 10: ACTengine IMA203 – TCR-T Targeting PRAME
ACTengine® IMA203 – TCR - T Targeting PRAME 10
Slide 11: ACTengine IMA203 – TCR-T Targeting PRAME
ACTengine® IMA203 – TCR - T Targeting PRAME Broadly Expressed Target on Multiple Solid Cancers Combined with Highly Specific TCR 11 HLA - A*02 - presented peptide derived from PRAME Naturally and specifically presented on tumors at high target density 1 : 100 - 1,000 copies/cell Identified and valid
Slide 12: ACTengine IMA203 Targeting PRAME – Mechanism of Action
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ Leading TCR - T Approach 12 IMA203
Slide 13: Optimized Cell Therapy Products to Enhance T cell Persistence & Efficacy
Optimized Cell Therapy Products to Enhance T cell Persistence & Efficacy Current Proprietary Manufacturing P rotocol for ACTengine® Product Candidates 13 Proprietary Manufacturing Process, designed to x reduce manufacturing process to approx. 1 week x shorten vein - to - vein time x generate younger
Slide 14: ACTengine IMA203 – Patient Flow
ACTengine® IMA203 – Patient Flow 14 HLA - A*02 Testing Blood sample; Central lab Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase ACTengine® Manufacturing by Immatics Infusion of ACTengine® T cell Product Lymphodepletion 30 mg/m 2 Flu darabine 1 and 500 mg/m 2 Cy c
Slide 15: ACTengine IMA203 – Key Objectives & Trial Design
ACTengine® IMA203 – Key Objectives & Trial Design Presented at SITC Conference as Late - Breaking Presentation (Cut - off October 05, 2021) Trial Design & Recruitment Status 1 Enrichment cohorts EC1 & EC2: patients infused with intermediate doses enabling infusion of patients with medical need durin
Slide 16: ACTengine IMA203 – Safety Profile
ACTengine® IMA203 – Safety Profile Manageable & Transient Treatment - emergent Adverse Event s – No ≥ Grade 3 CRS or ICANS Adverse event All grades ≥ Grade 3 No . % No . % Patients with any adverse event 19 100.0 19 100.0 Adverse Events of Special interest Cytokine release syndrome 1 7 8 9.5 0 0.0 I
Slide 17: ACTengine IMA203 – Change in Target Lesions
ACTengine® IMA203 – Change in Target Lesions Objective Responses across Multiple Tumor Types at Doses below 1 billion Transduced Cells 1 RECIST1.1 response at the timepoint of maximum change of target lesions (week 12): PD due to new lesions ( leptomeningeal disease) at week 12 2 Patients dosed with
Slide 18: ACTengine IMA203 – Response Over Time
Patient ID Indication Dose 203 - DL1 - 01 Head & Neck Cancer DL1 203 - DL1 - 02 Head & Neck Cancer DL1 203 - DL1 - 03 Ovarian Cancer DL1 203 - EC1 - 01 Melanoma EC1 203 - EC1 - 02 Melanoma EC1 203 - EC1 - 03 Uveal Melanoma EC1 203 - DL2 - 01 Synovial Sarcoma DL2 203 - DL2 - 02 Synovial Sarcoma DL2 2
Slide 19: ACTengine IMA203 – Engraftment, Persistence & Tumor Infiltration
ACTengine® IMA203 – Engraftment, Persistence & Tumor Infiltration Clinical Responses Consistent with Biological Data T cell Engraftment & Persistence Tumor Infiltration post I nfusion 2 1 Mann - Whitney U test, p=0.065 ; 2 Post infusion biopsies at week 6 (except one patient with SD at week 3); 3 Ma
Slide 20: ACTengine IMA203 – Case Study Patient IMA203-DL3
ACTengine® IMA203 – Case Study Patient IMA203 - DL3 - 01 Confirmed Partial Response with Deepening Tumor Regression in Multiple Lesions Liver metastasis Lung metastasis Sub cut . metastasis 0 5 10 15 -100 -50 0 50 Weeks from T Cell Infusion C h a n g e i n D i a m e t e r f r o m B a s e l i n e [ %
Slide 21: Preliminary Findings after Completion of Dose Level 3
Preliminary Findings after Completion of Dose Level 3 ACTengine® IMA203 PRAME – Phase 1a Dose Escalation Interim Update 1 DLT: dose - limiting toxicity, since March 17, 2021 (reported DLT at DL2); 2 CRS: cytokine release syndrome, I CANS: Immune effector cell - associated neurotoxicity syndrome, bot
Slide 22: Our Plans to Achieve Long-Lasting Responses with TCR-T cells against PRAME
Our Plans to Achieve Long - Lasting Responses with TCR - T cells against PRAME Phase 1b Cohort A: IMA203 Monotherapy at Target Dose 1 Phase 1b Cohort B: IMA203 at Target Dose plus Checkpoint Inhibitor 3 Phase 1b Cohort C: IMA203CD8 2nd Gen Phase 1a: IMA203 Monotherapy Dose Escalation in Basket Trial
Slide 23: ACTengine IMA203CD8 – Next-generation TCR-T
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 a
Slide 24: ACTengine IMA203CD8 – Preclinical Assessment of Anti-Tumor Efficacy
ACTengine® IMA203CD8 – Preclinical Assessment of Anti - Tumor Efficacy Co - Transduction of CD8 Enhances Anti - Tumor Activity in Vitro 18 36 56 74 94 114134 152 172192 0.0 0.5 1.0 1.5 2.0 IMA203CD8 TCR IMA203 TCR Non - Transduced Control S erial Killing Assay – CD8 & CD4 T cells Engagement of CD4 T
Slide 25: ACTengine IMA201 Targeting MAGEA4/8
ACTengine® IMA201 Targeting MAGEA4/8 Key Features 25 HLA - A*02 - presented peptide derived from MAGEA4 and/or MAGEA/8 >5 - fold higher peptide copy number per tumor cell than a commonly used MAGEA4 target Naturally and specifically presented on tumors at high target density 1 : 100 - 1,000 copies/c
Slide 26: ACTengine IMA202 Targeting MAGEA1
ACTengine® IMA202 Targeting MAGEA1 Key Features 26 HLA - A*02 - presented peptide derived from MAGEA1 Naturally and specifically presented on tumors at high target density 1 : 50 - 900 copies/cell Identified and validated by XPRESIDENT® quant. mass spectrometry platform High - affinity, specific TCR
Slide 27: ACTengine IMA204 First-in-Class TCR-T Targeting Tumor Stroma
ACTengine® IMA204 First - in - Class TCR - T Targeting Tumor Stroma Key Features 27 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 28: ACTengine 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 Control IMA204 TCR D7 D16 D22 D29 28 • Affinity maturated CD8 - independent, next - generati
Slide 29: ACTallo IMA30X – Immatics' Allogeneic Cell Therapy Approach
ACTallo® IMA30X – Immatics’ Allogeneic Cell Therapy Approach Effective Redirection of γδ T cells Using αβ TCR 29 • Proprietary manufacturing protocol delivering robust expansion of γδ T cells with the potential for hundreds of doses from one single donor leukapheresis • Off - the - shelf cell therap
Slide 30: TCER — TCR Bispecifics
008 immiatics TCER® — TCR Bispecifics
Slide 31: TCER – Mechanism of Action
TCER® – Mechanism of Action Immatics’ Off - the - Shelf TCR Bispecifics Approach 31 TCER®
Slide 32: TCER – Immatics' Half-Life Extended Bispecifics
TCER® – Immatics’ Half - Life Extended Bispecifics 32 pHLA targeting TCR x High - affinity TCR targeting HLA - restricted tumor - specific peptides x Broad therapeutic window through XPRESIDENT® - guided affinity maturation (>1000x) 1 x Complete tumor eradication in mouse xenograft models at low dos
Slide 33: TCER – Development of a Proprietary TCR Bispecific Format
TCER® – Development of a Proprietary TCR Bispecific Format Flexible Plug - and - play Platform Designed to Efficiently Generate New TCR Bispecifics 33 • Immatics developed a proprietary TCR Bispecific format for specific targeting of tumor - specific pHLA at low copy numbers • TCER® format successfu
Slide 34: Potency of Our Proprietary TCR Bispecific Format TCER
Potency of Our Proprietary TCR Bispecific Format TCER® 34 • 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 35: TCER Portfolio
TCER® Portfolio Building a Pipeline of Next - Gen Half - Life Extended TCR Bispecifics 35 IMA401 IMA402 IMA40X MAGEA4/8 PRAME Undisclosed Status Start of Phase 1 trial in May 2022 Clinical GMP batch targeted in 2022 Phase 1 trial in 2023 TCER ® engineering and preclinical testing ongoing Preclincial
Slide 36: Phase 1 Clinical Trial to Evaluate TCER IMA401 Targeting MAGEA4/8
Phase 1 Clinical Trial to Evaluate TCER® IMA401 Targeting MAGEA4/8 36 Trial Overview Primary Objective Biomarker positive patients with recurrent and/or refractory solid tumors • HLA - A*02:01 • MAGEA4/8 (Immatics’ IMADetect® test) Basket trial in indications with high MAGEA4/8 prevalence, e.g. sqNS
Slide 37: Phase 1 Clinical Trial to Evaluate TCER IMA401 Targeting MAGEA4/8
Phase 1 Clinical Trial to Evaluate TCER® IMA401 Targeting MAGEA4/8 37 MTD: maximum tolerated dose, RP2D: recommended phase 2 dose; MABEL: minimum anticipated biological effect level; BLRM: Bayesian logistic regression model; 1 P harmacokinetics data assessed throughout the trial might provide an opp
Slide 38: TCER IMA401 Targeting MAGEA4/8
TCER® IMA401 Targeting MAGEA4/8 Product Candidate in Clinical Development with Bristol Myers Squibb 38 Treatment schedule Tumor Model in Mice 1 1 8 15 22 Study day Transplantation Human PBMC IMA401 TCER ® Transplantation Tumor -22-12 • Complete remissions observed in all animals even at low IMA401 d
Slide 39: TCER IMA402 Targeting PRAME
TCER ® IMA402 Targeting PRAME Preclinical - stage Product Candidate Fully Owned by Immatics PRAME Target Peptide • HLA - A*02 - restricted PRAME peptide targeted by TCER® IMA402 is one of the most frequently expressed intracellular cancer targets for TCR - based therapies » Homogenously expressed at
Slide 40: TCER IMA402 – Efficacy Assessment in Tumor Model in Mice
TCER® IMA402 – Efficacy Assessment in Tumor Model in Mice Superior Tumor Control Using a Proprietary, Low - Affinity Recruiter 40 Widely used T cell recruiting Ab (3 variants) medium to high affinity Treatment schedule N=6 mice per group, two PBMC donors Dose: 0.025 mg/kg Proprietary, low - affinity
Slide 41: TCER IMA402 – In vitro Safety Assessment with Normal Tissue Cells
TCER® IMA402 – In vitro Safety Assessment with Normal Tissue Cells 41 • Cytotoxicity against N≥9 different human normal tissue cell types • TCER® IMA402 shows a minimum of 1,000 - fold therapeutic window between normal tissue cell reactivity and tumor cell reactivity Normal Tissue Type Therapeutic W
Slide 42: Immatics' Proprietary Target and TCR Discovery Platforms
Immatics’ Proprietary Target and TCR Discovery Platforms 42
Slide 43: 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 43 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 44: Immatics' Unique Capability – Identification of the most Relevant Target
Immatics ’ Unique Capability – Identification of the most Relevant Target Example of MAGEA4/8 Peptide Target 44 1 Copy number per tumor cell (CpC) measured on a paired - sample basis by AbsQuant®, i.e. comparing MAGEA4 vs. MAGEA4/A8 peptide pre sentation on same sample, 2 Students paired T test p<0.
Slide 45: Pool of Prioritized Targets as Foundation for Future Value Generation
Technology Pool of 200 Prioritized Targets as Foundation for Future Value Generation 45 200 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. strom
Slide 46: Development of the Right TCR – XCEPTOR Technology
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics 46 TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy ACTengine® ACTallo ® • Fast, efficient and highly sensitive discovery of highly specific, natural TCRs • Protein engi
Slide 47: 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 47 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Off - target to
Slide 48: Corporate Information & Milestones
Corporate Information & Milestones 48
Slide 49: Experienced Global Leadership Team Across Europe and the US
Experienced Global Leadership Team Across Europe and the US 49 Harpreet Singh Chief Executive Officer Co - Founder >20 yrs biotech experience Carsten Reinhardt Chief Development Officer >20 yrs pharma & biotech experience ( Micromet , Roche, Fresenius) Rainer Kramer Chief Business Officer 25 yrs pha
Slide 50: Strong, Focused and Highly Integrated Trans-Atlantic Organization
Strong, Focused and Highly Integrated Trans - Atlantic Organization 50 Senior Leadership, Business Development, Clinical Operations, Intellectual Property, Regulatory Affairs, Communications Senior Leadership, Research and Development (Adoptive Cell Therapy), CMC, Clinical Operations, Regulatory Aff
Slide 51: Robust IP Portfolio
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 51 Cancer targets, TCRs and technology protected by: • 5,800 applications and patents filed in all major countries and regions • >120 patent families • >2,000 granted patents, thereof >490 granted patents in the US Corporate
Slide 52: Near-Term Value Drivers and Development Milestones
Near - Term Value Drivers and Development Milestones Clinical Expansion of TCR Bispecifics and the Next - generation of TCR - T 52 Leverage full potential of targeting PRAME • Focused & accelerated development of IMA203 expansion cohorts • Develop IMA402, an off - the - shelf TCER® Advance clinical
Slide 53: Thank you!
www.immatics.com Thank you!