Slide 1: Unlocking Immunotherapies for Solid Cancer Patients
© Immatics. Not for further reproduction or distribution. Unlocking Immunotherapies for Solid Cancer Patients Immatics Corporate Presentation, December 2021
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 with a Pipeline in Cell Therapies and Bispecifics
Building a leading TCR Therapeutics Company with a Pipeline in Cell Therapies and Bispecifics 3 Highly Differentiated Technologies to Identify True Cancer Targets and the Right TCRs Unlocking Immunotherapies for Solid Cancer Patients Strategic Collaborations with World - leading Industry Players
Slide 4: Global Licensing Agreement With Bristol Myers Squibb – December 2021
Global Licensing Agreement With Bristol Myers Squibb – December 2021 Exclusive License to TCR Bispecific Candidate IMA401 Targeting MAGEA4/8 $150 million up to $770 million Upfront payment Development, regulatory & commercial milestones plus tiered double - digit royalties on net product sales Compa
Slide 5: Limitations of Current Immunotherapies in Solid Cancer Patients
Limitations of Current Immunotherapies in Solid Cancer Patients … Driven by a Lack of Known Cancer - specific Targets 5 1 Chalmers et al. , 2017; 2 SEER Cancer Statistics Review, 1975 - 2017, Estimated New Cancer Cases for 2020 Most cancer patients do not benefit from current immuno - oncology appro
Slide 6: Immatics Pipeline
Immatics Pipeline 6 Modality Product Candidate Status Preclinical Phase 1a 1 Phase 1b 1 Phase 2/3 IMA201 (MAGEA4/8) Proprietary IMA202 (MAGEA1) Proprietary A C T e n g i n e® Au t o l o g ous ACT IMA203 (PRAME) Proprietary IMA203 (PRAME) + Checkpoint Inhibitor Proprietary IMA203CD8 (PRAME) Proprieta
Slide 7: 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 p r e v alence 1 Sarcoma Subtypes – up to 80% Squamous NSCLC – 50% HNSCC – 35% Bladder Carcinoma – 30% Esophageal Carcinoma – 25% Uterine Carcinosarcoma – 25% O
Slide 8: ACTengine Programs – Key Features
ACTengine® Programs – Key Features 8 1 Applying XPRESIDENT® quantitative mass spectrometry platform; 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®
Slide 9: ACTengine IMA203 – TCR-T to PRAME
ACTengine® IMA203 – TCR - T to PRAME 9
Slide 10: ACTengine IMA203 to PRAME – Mechanism of Action
ACTengine® IMA203 to PRAME – Mechanism of Action Immatics’ Leading TCR - T Approach 10
Slide 11: ACTengine IMA203 – Patient Flow
ACTengine® IMA203 – Patient Flow 11 HLA - A*02 Testing Blood sample; Central lab Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase ACTengine® M a nu f ac tur i ng by Immatics Infusion of ACTengine® T cell Product Lymphodepletion 30 mg/m 2 Fludarabine 1 and 500 mg/m
Slide 12: ACTengine IMA203 – Key Objectives & Trial Design
ACTengine® IMA203 – Key Objectives & Trial Design Trial Design & Recruitment Status 1 Enrichment cohorts EC1 & EC2: patients infused with intermediate doses enabling infusion of patients with medical need during dose escalation observation periods, or in case of lower production yields; * One patien
Slide 13: ACTengine IMA203 – Safety Profile
ACTengine® IMA203 – Safety Profile Cytokine release syndrome ICANS 2 17 4 89.5 21.1 0 0 0.0 0.0 Blood and lymphatic system disorders Neutropenia* Anaemia T hr o m b o cy t o peni a Lymphopenia* Leukopenia* Cytopenia 16 16 15 14 12 1 84.2 84.2 78.9 73.7 63.2 5.3 15 9 7 14 11 1 78.9 47.4 36.8 73.7 57.
Slide 14: 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 15: 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 16: 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 Infusion 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 Mann
Slide 17: ACTengine IMA203 – Case Study
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 - 1 0 0 - 50 0 50 5 1 0 15 Weeks from T Cell Infusion Change in Diameter from Baseline [%] SUM T1: Lymph Node
Slide 18: Objective responses observed across multiple tumor types below 1 billion T cells
Objective responses observed across multiple tumor types at dose levels below 1 billion T cells originally presumed to be subtherapeutic 1 DLT: dose - limiting toxicity, since March 17, 2021 (reported DLT at DL2); 2 CRS: cytokine release syndrome, ICANS: Immune effector cell - associated neurotoxici
Slide 19: Comprehensive Strategy to Target PRAME
Comprehensive Strategy to Target PRAME 19
Slide 20: Immatics' Proprietary PRAME Peptide-HLA/TCR Pair
Immatics’ Proprietary PRAME Peptide - HLA/TCR Pair Broadly Expressed Target on Multiple Solid Cancers Combined with Highly Specific TCR Uterine carcinoma M e l an om a Ovarian carcinoma Peptide Target PRAME: • HLA - A*02 - restricted peptide identified by XPRESIDENT® quant. mass spec • Naturally and
Slide 21: Maximizing PRAME Mediated Clinical Benefit Through ACT and TCR Bispecifics
Targeted 2022 Phase 1b Cohort A: IMA203 Monotherapy in Focus Indications Phase 1b Cohort B: IMA203/Checkpoint Inhibitor Combination Therapy Phase 1b Cohort C: IMA203CD8 2nd gen Monotherapy Phase 1a: IMA203 Monotherapy Dose Escalation in Basket Trial TCR - T Track: PRAME TCR - T Bispecifics Track: PR
Slide 22: ACTengine IMA203CD8 – Second-generation TCR-T
ACTengine® IMA203CD8 – Second - 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 • Functional superiority of a CD8αβ IMA203 construct (IMA2
Slide 23: 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 0 .0 1 .0 0 .5 1 .5 2 .0 IMA203CD8 TCR IMA203 TCR Non - Transduced Control Engagement of CD4 T cells may enhance depth and durability of anti - tumor response and c
Slide 24: Comprehensive Strategy to Target PRAME
Comprehensive Strategy to Target PRAME Focused and broad approach targeting PRAME: Aiming to maximize clinical benefit through ACT programs and TCR Bispecifics • Maximize therapeutic potential through multiple Ph1b cohorts • Monotherapy at RP2D • Checkpoint Inhibitor Combination • 2 nd gen IMA203CD8
Slide 25: ACTengine IMA200 TCR-T Programs Update
ACTengine® IMA200 TCR - T Programs Update 25
Slide 26: ACTengine Programs – Status Update
ACTengine® Programs – Status Update 26 1 One DLT in DL2 previously reported in March 2021, fully resolved A C T IMA201 IMA202 IMA203 IMA204 M A G E A 4/ 8 M A G E A 1 PRA ME COL6A3 exon 6 S ta t us Dose escalation ongoing Enrollment at target dose level (DL3) ongoing Enrollment at target dose level
Slide 27: IMA203 - PRAME: Objective responses observed across multiple tumor types
Unlocking Immunotherapies for Solid Cancer Patients IMA203 - PRAME Objective responses observed across multiple tumor types 27 82% Disease Control Rate 0 Grade ≥3 CRS or ICANS 1 < 1bn T cells infused in almost all patients PRAME STRATEGY Maximizing the therapeutic potential of targeting PRAME ORR 2
Slide 28: ACTengine IMA204 – A Novel TCR-T Program Targeting Tumor Stroma
ACTengine® IMA204 – A Novel TCR - T Program Targeting Tumor Stroma Complete Tumor Eradication in vitro & in vivo 1 by Affinity - enhanced IMA204 TCR CD8 - independent TCR leads to tumor eradication in all mice treated 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
Slide 29: Outlook: ACTallo IMA301 – Allogeneic Cell Therapy Approach
Outlook: ACTallo® IMA301 – 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 ce
Slide 30: TCER — TCR Bispecifics
ooe immatics TCER® — TCR Bispecifics
Slide 31: TCER – Mechanism of Action
TCER® – Mechanism of Action Immatics Dz Off - the - Shelf TCR Bispecifics Approach 31 T CE R ®
Slide 32: TCER – Immatics' Innovative Half-Life Extended Bispecifics
TCER® – Immatics’ Innovative Half - Life Extended Bispecifics 32 pHLA targeting TCR x High - affinity TCR with broad therapeutic window through XPRESIDENT® - guided affinity maturation (>1000x) 2 x Targets HLA - A*02 - restricted MAGEA4/8 (IMA401) or PRAME (IMA402) peptide with high target density x
Slide 33: TCER Portfolio
TCER® Portfolio TCER Pipeline Strengthened by a Third Program IMA40X 33 IMA401 I M A 402 IMA40X MAGEA4/8 PR A ME Undisclosed Status CTA * filed with German Regulatory Authority in November 2021; Phase 1 trial in 2022 Clinical GMP batch targeted in 2022 Phase 1 trial in 2023 TCER® engineering and pre
Slide 34: TCER IMA401 Targeting MAGEA4/8
34 Treatment schedule Tumor Model in Mice 1 8 1 5 22 T r a n s p l a n t a t i o n Tumor T r a n s p l a n t a t i o n Human PBMC IMA401 TCER ® - 22 - 12 1 TCER® IMA401 Targeting MAGEA4/8 IND - stage Product Candidate in Development with Bristol Myers Squibb • Complete remissions observed in all ani
Slide 35: TCER IMA402 Targeting PRAME
35 TCER® IMA402 Targeting PRAME Preclinical - stage Product Candidate Fully Owned by Immatics 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 T cell recruiting region demonstr
Slide 36: Immatics' Proprietary Target and TCR Discovery Platforms
Immatics‘ Proprietary Target and TCR Dicovery Platforms 36
Slide 37: Accessing Intracellular Cancer Targets with TCR-based Therapeutics
Accessing Intracellular Cancer Targets with TCR - based Therapeutics To Unlock Immunotherapies for Solid Cancer Patients 37 T e chn olo g y
Slide 38: True Cancer Targets & Matching Right TCRs
True Cancer Targets & Matching Right TCRs 38 True Targets - expressed on cancer but not or to far lower extent on normal tissue Minimizing risk for on - target toxicity Right TCRs - highly specific and high affinity as outcome of stringent development process Minimizing risk for off - target toxicit
Slide 39: XPRESIDENT – Discovery of True Cancer Targets
XPRESIDENT® – Discovery of True Cancer Targets Pool of 200 Targets as Foundation for our Future Pipeline >2,500 cancer & normal tissues analyzed by Quantitative, Ultra - Sensitive Mass Spectrometry pHLA Database based on primary tissues >200 p ri o ri t i z e d targets T e chn olo g y 39 200 Priorit
Slide 40: Development of the Right TCR – XCEPTOR
Development of the Right TCR – XCEPTOR® Unique Cross - Talk between Target and TCR Discovery 40 TCR Bispecifics T cell engaging receptor (TCER®) Affinity - maturated natural TCR variable domains with nanomolar affinity and favorable specificity profile XPRESIDENT® - guided similar peptide countersel
Slide 41: Corporate Information & Milestones
Corporate Information & Milestones 41
Slide 42: Robust IP Portfolio
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 42 • > 8 , 000 cancer targets, TCRs and technology protected by • 5 , 500 applications and patents filed in all major countries and regions • >120 patent families • >1,550 granted patents, thereof >450 granted patents in the US Corpo
Slide 43: Strong, Focused and Highly Integrated Trans-Atlantic Organization
Strong, Focused and Highly Integrated Trans - Atlantic Organization 43 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 44: Experienced Global Leadership Team Across Europe and the US
Experienced Global Leadership Team Across Europe and the US 44 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 pharm
Slide 45: Upcoming R&D Milestones
Upcoming R&D Milestones 45 Modality Product Candidate Status Preclinical Phase 1a 1 Phase 1b 1 Phase 2/3 Next Milestone IMA201 (MAGEA4/8) Proprietary Complete dose escalation 2022 IMA202 (MAGEA1) Proprietary Complete dose escalation 1Q2022 A C T e n g i n e® Au t o l o g ous ACT IMA203 (PRAME) Propr
Slide 46: Immatics Key Take-Aways
Immatics Key Take - Aways Broadly Positioned in the TCR Therapeutics Space with ACT & TCR Bispecifics ACTengine® (TCR - T) – High Objective Response Rate during ongoing dose escalation in TCR - T Ph1a trial IMA203 to PRAME • IMA203 (PRAME): Objective responses across multiple tumor types at dose lev
Slide 47: Thank you
ooe Immiatics | DELIVERING THE POWER y OF T CELLS TO CANCER PATIENTS {7 Thank you >< Jin | 9