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Immatics. Not for further reproduction or distribution. ACTengine IMA200 TCR - T Programs Interim Phase 1a Update Cedrik Britten, Chief Medical Officer Harpreet Singh, Chief Executive Officer

Key Takeaway: Immatics. Not for further reproduction or distribution. ACTengine IMA200 TCR - T Programs Interim Phase 1a Update Cedrik Britten, Chief Medical Officer Harpreet Singh, Chief Executive Officer November 09, 2021 Additional late - breaking oral presentation at SITC Annual Meeting on

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Immatics. Not for further reproduction or distribution. ACTengine IMA200 TCR - T Programs Interim Phase 1a Update Cedrik Britten, Chief Medical Officer Harpreet Singh, Chief Executive Officer November 09, 2021 Additional late - breaking oral presentation at SITC Annual Meeting on November 13 , 2021 , by Martin Wermke MD, Coordinating Investigator of Immatics ACTengine trials in Germany
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 . Forward - Looking Statements . Certain statements in this presentation may be considered forward - looking statements . Forward - looking statements generally relate to future events or the Company's future financial or operating performance . For example, statements concerning timing of data read - outs for product candidates, the timing of IND or CTA filing for pre - clinical stage product candidates, the Company's focus on partnerships to advance its strategy, and other metrics are forward - looking statements . In some cases, you can identify forward - looking statements by terminology such as "may", "should", "expect", "intend", "will", "estimate", "anticipate", "believe", "predict", "potential" or "continue", or the negatives of these terms or variations of them or similar terminology . Such forward - looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements . These forward - looking statements are based upon estimates and assumptions that, while considered reasonable, Immatics and its management, are inherently uncertain . New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties . Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company's filings with the Securities and Exchange Commission (SEC) . Nothing in this presentation should be regarded as a representation by any person that the forward - looking statements set forth herein will be achieved or that any of the contemplated results of such forward - looking statements will be achieved . You should not place undue reliance on forward - looking statements, which speak only as of the date they are made . The Company undertakes no duty to update these forward - looking statements . No Offer or Solicitation . This communication is for informational purposes only and does not constitute, or form a part of, an offer to sell or the solicitation of an offer to sell or an offer to buy or the solicitation of an offer to buy any securities, and there shall be no sale of securities, in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction . No offer of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933 , as amended, and otherwise in accordance with applicable law . 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 . 2
Agenda Introduction & Summary IMA203 Phase 1a Interim Update Comprehensive Strategy to Target PRAME ACTengine IMA 200 Programs Update Summary Q&A 3
Introduction & Summary 4
Immatics' Proprietary PRAME Peptide - HLA/TCR Pair Broadly Expressed Target on Multiple Solid Cancers Combined with Highly Specific TCR Uterine carcinoma SqNSCLC Melanoma Ovarian carcinoma HNSCC Uveal melanoma 2 Peptide Target PRAME: HLA - A*02 - restricted peptide identified by XPRESIDENT quant. mass spec Naturally and specifically presented at high levels (100 - 1000 copies/cell) Homogenously expressed at high prevalence across multiple solid tumors 1 PRAME T cell Receptor (TCR): Engineered to avoid mispairing Selected for high specificity guided by XPRESIDENT H igh functional avidity : EC50 5ng/ml 1 Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data); 2 Based on metastatic uveal melanoma patients screened in IMA203 study (N=12) Breast carcinoma 5 SqNSCLC Ovarian Cancer PRAME RNA expression in native tumor samples (ISH analysis) Synovial sarcoma
ACTengine IMA203 PRAME - Phase 1a Dose Escalation Interim Update 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, I CANS: Immune effector cell - associated neurotoxicity syndrome, both graded by CARTOX criteria ( Neelapu et al ., 2018); 3 Objective response rate according to RECIST 1.1 including confirmed and unconfirmed partial responses; * Includes patients treated at enrichment cohorts EC1 and EC2 Additional DLTs 1 ORR 3 at DL2 * & DL3 (8/13 patients) - all still dosed below 1 bn cells SAFETY CLINICAL ACTIVITY BIOLOGICAL ACTIVITY 3 0 Dose levels completed, all below 1 bn cells 0 Grade 3 CRS or ICANS 2 50% 62% ORR 3 across all doses and multiple solid cancers (8/16 patients) Blood Tumor High T cell engraftment and persistence High T cell infiltration associated with clinical response Dose level (target dose) commenced, first DL >1 bn cells 4 th 6 Preliminary Findings after Completion of Dose Level 3 Data cut - off - 05 - Oct - 2021
Comprehensive Strategy to Target PRAME Focused and broad approach targeting PRAME: Aiming to maximize clinical benefit through ACT programs and TCR Bispecifics Complete IMA203 Ph1a Dose Escalation with doses above 1 bn cells (DL4) D etermine Recommended Phase 2 Dose (RP2D) in 1Q2022 Initiate IMA203 Ph1b Dose Expansion in 1H2022 Maximize therapeutic potential through multiple Ph1b cohorts Monotherapy at RP2D Checkpoint Inhibitor Combination 2 nd gen IMA203CD8 Focused development of half - life - extended Bispecific (TCER IMA402) following promising preclinical data Complete GMP run in 2022 & advance IMA402 to phase 1 trial PRAME TCR - T (IMA203 Ph1a) PRAME TCR - T (IMA203 Ph1b) PRAME BISPECIFIC (IMA402) 7
IMA203 Phase 1a Interim Update 8
ACTengine IMA203 - Patient Flow 9 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 clophosphamide for 4 days Target Profiling Fresh Tumor Biopsy; IMADetect Low dose IL - 2 1m IU daily days 1 - 5 and twice daily days 6 - 10 * Safety and efficacy monitoring for 12 months IMA201 IMA202 IMA203 * IL - 2 dose reduction from twice daily to daily for the first 5 days and dosing duration from 14 to 10 days introduced prior to treatment of first patients on dose level 3 ; 1 Dose reduction of Fludarabine (from 40 mg/m 2 to 30 mg/m 2 ) was introduced prior to treatment of the first patient on dose level 3 Leuka - pheresis
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 do se escalation observation periods, or in case of lower production yields; * One patient infused at the same dose level as part of the enrichment cohort; ** Dose is shown as transduced viable CD8 T cells per m 2 total body surface area Key Study Objectives Primary: Safety Investigation of Adverse Events, Determination of a recommended Phase 2 dose Secondary: Biological and Clinical Activity T cell engraftment and persistence Objective responses as per RECIST1.1 Duration of response Exploratory Tumor Infiltration 10 Data cut - off - 05 - Oct - 2021 18 patients 1 infused with PRAME - directed T cells at 5 clinical sites - Highest Dose Level 4 has commenced N=3 ** N=3 Ongoing N=1 N=4 patients treated at intermediate dose levels 1 N=7 *
ACTengine IMA203 - Patient Characteristics & Manufacturing Heavily Pre - Treated Patients Across Multiple Solid Cancers Were Infused Data cut - off - 05 - Oct - 2021 Efficacy Population (N=16) Median (range) Age [years] 53 (18 - 65) Prior lines of systemic therapies 4 (2 - 8) Years from diagnosis 4 (1 - 25) Transduced T cells infused [x10 9 ] 0.33 (0.08 - 0.81) 1 Patients that started lymphodepletion, one patient died from sepsis of unknown origin and did not receive IMA203 T cells; 2 Patients with at least one tumor assessment post treatment, 2 patients infused but pending first tumor assessment; 3 Plus currently 14d release testing, expected to be reduced to 7d in 2022 16 patients (all dosed below 1 bn transduced cells) evaluable for clinical and biological activity assessment For remaining 2 treated patients first tumor assessment pending as of data cut - off 11 Manufacturing Manufacturing duration 3 6 - 7d Overall manufacturing success rate 92% Patient Distribution Number Patients in Safety Population 1 19 Thereof patients infused 18 Patients in Efficacy Population 2 16 Synovial Sarcoma 5 Head & Neck Cancer 3 Cutaneous Malignant Melanoma 3 Uveal Melanoma 2 Other (NSCLC, Ovarian, Squamous Cell Carcinoma) 3 Patients with evaluable paired tumor biopsies 1 0
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 ICANS 2 4 21.1 0 0.0 Blood and lymphatic system disorders Neutropenia* 16 84.2 15 78.9 Anaemia 1 6 84.2 9 47.4 Thrombocytopenia 15 78.9 7 36.8 Lymphopenia* 14 73.7 14 73.7 Leukopenia* 12 63.2 1 1 57.9 Cytopenia 1 5.3 1 5.3 Infections and infestations Enterococcal infection 1 5.3 1 5.3 COVID - 19 1 5.3 1 5.3 Appendicitis 1 5.3 1 5.3 Sepsis 3 1 5.3 1 5.3 Respiratory, thoracic and mediastinal disorders Hypoxia 2 10.5 1 5.3 Pleural effusion 2 10.5 1 5.3 Bronchial obstruction 1 5.3 1 5.3 Metabolism and nutrition disorders Hyponatraemia 7 36.8 1 5.3 Hypokalaemia 5 26.3 1 5.3 Decreased appetite 3 15.8 0 0.0 Adverse event All grades Grade 3 No . % No . % table continued Cardiac or vascular disorders Hypertension 3 15.8 2 10.5 Atrial fibrillation 2 10.5 1 4 5.3 General disorders and administration site conditions Fatigue 7 36.8 1 5.3 Pyrexia 5 26.3 0 0.0 Oedema peripheral 3 15.8 0 0.0 Gastrointestinal disorders Nausea 12 63.2 0 0.0 Vomiting 7 36.8 0 0.0 Diarrhoea 7 36.8 0 0.0 Constipation 6 31.6 0 0.0 Investigations Aspartate aminotransferase increased 5 26.3 0 0.0 Alanine aminotransferase increased 4 21.1 0 0.0 Blood creatinine increased 4 21.1 0 0.0 Other Rash 5 26.3 0 0.0 Myalgia 4 21.1 0 0.0 Arthralgia 3 15.8 0 0.0 Alopecia 3 15.8 0 0.0 Rash maculo - papular 2 10.5 1 5.3 Orchitis 1 5.3 1 5.3 Contrast media allergy 1 5.3 1 5.3 TEAEs by maximum severity ( N=19) 1 1 All treatment - emergent adverse events (TEAEs) with grade 1 - 2 occurring in at least 3 patients (incidence 15 . 8 % ) and additionally all events with grade 3 - 5 regardless of relatedness to study treatment are presented . Data source : clinical database . Adverse events were coded using the Medical Dictionary for Regulatory Activities . Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE), version 5 . 0 . Grades for Cytokine release syndrome and ICANS were determined according to CARTOX criteria ( Neelapu et al . , 2018 ) . Patients are counted only once per adverse event and severity classification ; 2 ICANS : Immune effector cell - associated neurotoxicity syndrome ; 3 Patient died from sepsis of unknown origin and did not receive IMA 203 T cells ; 4 DLT : Dose limiting toxicity ; * 100 % of patients experienced transient cytopenias Grade 3 (CTCAE v 5 . 0 ) DLT: Transient, Grade 3 atrial fibrillation Onset on day 5 post infusion that resolved within 48h DLT triggered expansion of DL2 CRS/ICANS: No Grade 3 CRS or ICANS observed so far Most Adverse Events were associated with lymphodepletion 12 Data cut - off - 05 - Oct - 2021
ACTengine IMA203 - Best Overall Response Assessment (RECIST 1.1) Multiple Objective Responses in Various Solid Cancer Indications During Dose Escalation 203 - DL1 - 01 203 - DL1 - 02 203 - DL1 - 03 203 - EC1 - 01 203 - EC1 - 02 203 - EC1 - 03 203 - DL2 - 01 203 - DL2 - 02 203 - DL2 - 03 203 - DL2 - 04 203 - DL2 - 05 203 - DL2 - 06 203 - EC2 - 01 203 - DL3 - 01 203 - DL3 - 02 203 - DL3 - 03 Patient ID 203 - 60 - 010 203 - 60 - 032 203 - 60 - 041 203 - 10 - 004 203 - 11 - 001 203 - 10 - 009 203 - 65 - 003 203 - 65 - 004 203 - 65 - 005 203 - 65 - 007 203 - 10 - 010 203 - 73 - 001 203 - 10 - 016 203 - 10 - 012 203 - 10 - 014 203 - 65 - 008 Median total transduced cells (10 9 ) 1 0.11 0.20 0.36 0.36 0.59 Age (gender) 40 (F) 63 (M) 61 (F) 18 (F) 65 (M) 42 (M) 57 (M) 40 (M) 20 (M) 49 (M) 50 (F) 55 (F) 65 (M) 62 (F) 50 (M) 59 (F) Diagnosis Head and Neck Cancer Ovarian Cancer Malig . Melanoma Uveal Melanoma Synovial Sarcoma Head & Neck Cancer NSCLC SCC Uveal Melanoma Malig . Melanoma Synovial Sarcoma Prior lines of systemic therapy 6 4 7 4 7 2 2 3 2 2 3 8 4 4 3 5 Prior lines of ICI 2 treatment 2 - 1 2 4 1 - - - - - 4 1 2 2 - Disease status at infusion Patients with recurrent and/or refractory solid tumors failing all prior lines of treatment Best response RECIST1.1 SD SD SD PR PR SD PR SD PR 3 PR 3 PR SD PD PR 3 PR 4 SD Objective Response Rate per Dose Level 0/3 Objective Responses (0% ORR) 6/10 Objective Responses (60% ORR) 2/3 Objective Responses (67% ORR) 13 DL: Dose level; EC1: Enrichment cohort with intermediate dose level between DL1 and DL2; EC2: Enrichment cohort with intermed iat e dose level between DL2 and DL3; SD: Stable disease; PR: Partial response. 1 Total infused dose of transduced viable CD8 T cells; 2 Immune checkpoint inhibitor; 3 PR confirmed at subsequent scan; 4 Pending confirmation 13 Data cut - off - 05 - Oct - 2021
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 DL2, EC1 and EC2; * Confirmed at subsequent scan; ** Confirmation pending as of data cut - off Preliminary Objective Response Rates (RECIST1.1., confirmed and unconfirmed) All doses Dosed above DL1 All comers 8/16 (50%) 8/13 (62%) Melanoma 3/3 (100%) 3/3 (100%) Head & Neck Cancer 1/3 (33%) 1/1 (100%) Synovial Sarcoma 3/5 (60%) 3/5 (60%) Uveal Melanoma 1/2 (50%) 1/2 (50%) 14 Best Overall Response (RECIST1.1) 2 0 3 - E C 2 - 0 1 2 0 3 - D L 2 - 0 2 2 0 3 - E C 1 - 0 3 2 0 3 - D L 3 - 0 3 2 0 3 - D L 2 - 0 6 2 0 3 - D L 1 - 0 3 2 0 3 - D L 1 - 0 1 2 0 3 - D L 1 - 0 2 2 0 3 - D L 2 - 0 4 2 0 3 - D L 3 - 0 2 2 0 3 - D L 2 - 0 1 2 0 3 - E C 1 - 0 2 2 0 3 - E C 1 - 0 1 2 0 3 - D L 2 - 0 5 2 0 3 - D L 2 - 0 3 2 0 3 - D L 3 - 0 1 -50 0 50 -63.3 -61.0 -51.7 -50.5 -47.7 -39.9 -37.9 -33.8 -13.1 -9.7 -6.9 -4.2 -2.0 -0.5 5.2 8.8 B e s t c h a n g e i n s u m o f d i a m e t e r [ % ] a n d B O R ( R E C I S T 1 . 1 ) Dose Level: DL2 2 DL1 DL3 PD SD SD SD SD SD SD PR* PR* PR PR PR PR PR PR* + + S C C S y n o v i a l S a r c o m a U v e a l M e l a n o m a N S C L C O v a r i a n C a n c e r H e a d & N e c k C a n c e r H e a d & N e c k C a n c e r S y n o v i a l S a r c o m a M e l a n o m a S y n o v i a l S a r c o m a S y n o v i a l S a r c o m a U v e a l M e l a n o m a M e l a n o m a M e l a n o m a 1 H e a d & N e c k C a n c e r S y n o v i a l S a r c o m a SD ** Data cut - off - 05 - Oct - 2021
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 203 - DL2 - 03 Synovial Sarcoma DL2 203 - DL2 - 04 Synovial Sarcoma DL2 203 - DL2 - 05 Head & Neck Cancer DL2 203 - DL2 - 06 NSCLC DL2 203 - EC2 - 01 SCC EC2 203 - DL3 - 01 Uveal Melanoma DL3 203 - DL3 - 02 Melanoma DL3 203 - DL3 - 03 Synovial Sarcoma DL3 ACTengine IMA203 - Response Over Time Objective Responses across Multiple Tumor Types at Doses below 1 billion Transduced Cells x x x x x Alive (time from infusion to data cut - off or death) PD Deceased x x SD PR Week Month x x x x 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 x PR ongoing at data cut - off According to RECIST1.1 First tumor response assessment x Data cut - off - 05 - Oct - 2021 15
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 Mann - Whitney U test, p=0.0159 2 4 1 10 -1 1 10 0 1 10 1 1 10 2 1 10 3 1 10 4 1 10 5 1 10 6 1 10 7 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 2 5 0 4 0 0 5 5 0 7 0 0 V e c t o r c o p i e s / g g D N A PD SD PR B a s e l i n e Days post-infusion SD PR 1 10 1 1 10 2 1 10 3 1 10 4 1 10 5 V e c t o r c o p i e s / g g D N A 0.0159 Case study High T cell engraftment and persistence with trend for association of peak vector copies with clinical response 1 High T cell infiltration observed through serial biopsies associated with clinical response 3 Data cut - off - 05 - Oct - 2021 16 p=0.0159
ACTengine IMA203 - Case Study Patient IMA203 - DL3 - 01 Confirmed Partial Response with Deepening Tumor Regression in Multiple Lesions BL D42 D84 Liver metastasis Lung metastasis s.c. metastasis Data cut - off - 05 - Oct - 2021 62 - year - old female patient Metastatic uveal melanoma with h igh tumor burden in multiple organs Infused at refractory disease after failing 4 prior lines of therapy incl. 2 lines of checkpoint inhibitors R eceived total dose of 0.59 bn ( 0.36 bn/m 2 ) transduced cells directed against PRAME target peptide/HLA 17 Tumor Response Best response (RECIST1.1) : PR (confirmed; ongoing as of data cut - off) Target Lesions decreased at week 6 post treatment to - 40%, response deepened at week 12 to - 63% CT scans courtesy of Dr. Wermke
ACTengine IMA203 - Case Study Patient IMA203 - DL3 - 01 Partial Response Consistent with Biological Data 0 10 20 30 0 10000 20000 30000 40000 50000 0 50 100 150 50 70 90 Patient IMA203-DL3-01 Day I L - 6 p g / m l L D H m o l / ( s * L ) S - 1 0 0 m g / l LDH IL6 S-100 T cell Engraftment, Persistence & Tumor Infiltration Change in Size of Target Lesions Serum Biomarkers in Blood 1 Initial LDH level reflecting high tumor burden prior to infusion Steep increase in IL - 6 , LDH and increase in S - 100 indicative of tumor cell killing Target Lesions decreased at week 6 post treatment to - 40% Response deepened at week 12 to - 63% (RECIST1.1) High T cell engraftment and persistence until end of observation. At peak 32% of CD8 T cells express IMA203 TCR High T cell infiltration into tumor at week 6 post treatment (data on slide 16) 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 [ % ] SUM T1: Lymph Node T2: Lymph Node T3: Lung T4: Liver T5: Liver Data cut - off - 05 - Oct - 2021 18 1 Serum biomarker data courtesy of Dr. Wermke
Comprehensive Strategy to Target PRAME 19
Targeted 2022 Comprehensive Strategy to Target PRAME 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: PRAME TCR Bispecific Maximizing PRAME Mediated Clinical Benefit Through ACT and TCR Bispecifics IND - enabling studies Ph1a C ompletion & Determination RP2D early 2022 Ph1b Expansion starting 2022 Ph2b Pivotal Trial(s) Phase 1 TCER IMA402 GMP Run TCER IMA402 Targeted 2023 20
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 CD8 IMA203 construct (IMA203CD8) over multiple other CD8 constructs in preclinical experiments - Poster presentation at SITC, Nov 12, 2021 Secured access to CD8 technology through exclusive license from Baylor College of Medicine IND filing for IMA203CD8 lead candidate targeted in 1H2022 TUMOR CELL DEATH CD4 T CELL Cytotoxi c Activity CD8 T CELL T cell Help Cytotoxi c Activity 21
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 cells may enhance depth and durability of anti - tumor response and clinical outcome of TCR - T in solid cancer patients 2 nd addition of tumor cells 3 rd addition of tumor cells Tumor Growth Hours after co - culture F ull Data Presentation at SITC 2021: Improved anti - tumor activity of next - generation TCR - engineered T cells through CD8 co - expressio n Day 0 D ay 3 N o CD4 T cells IMA203 TCR D ay 6 IMA203CD8 TCR 3D Spheroid Killing - CD4 T cells 22
TCER IMA402 - A Novel Half - Life Extended Bispecific for PRAME 23 pHLA targeting TCR x High - affinity TCR with broad therapeutic window through XPRESIDENT - guided affinity maturation (>1000x) 2 x Targets HLA - A*02 - restricted PRAME peptide with unusually high t arget density 3 x Complete tumor eradication in mouse xenograft models at low doses Fc domain (silenced) with knob - into - hole technology Optimized Design of TCR and T cell Recruiter for Maximizing Efficacy while Minimizing Toxicities Next - generation TCER format x Off - the - shelf b iologic with antibody - like manufacturability 4 and low cost of goods x Superior anti - tumor activity 5 compared to six alternative bispecific formats x Half - life of several days expected in humans T cell recruiting antibody x Low - affinity T cell recruiter against both TCR & CD3 x Optimized biodistribution aiming for enrichment at tumor site and prevention of CRS 1 x Superior anti - tumor activity in mouse models as compared to widely used CD3 recruiters 1 Based on literature data for other low - affinity recruiters (e.g. Harber et al ., 2021, Nature); 2 As compared to natural TCR; 3 Compared to other HLA - restricted epitopes; 4 Production in mammalian cells (CHO cells); 5 Based on preclinical testing
ACTengine IMA 200 TCR - T Programs Update 24
IMA201 IMA202 IMA203 IMA204 Cancer Target Peptide HLA - A*02 - presented peptide derived from MAGEA4/8 MAGEA1 PRAME COL6A3 exon 6 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 100 - 700 copies/cell T cell Receptor (TCR) High - affinity specific TCRs with high functional avidity 2 Natural TCR ~10 ng /ml Natural TCR ~15 ng /ml Pairing - enhanced TCR ~5 ng /ml Affinity - maturated , CD8 - independent TCR ~0.01ng/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 7 days 7 days ACTengine Programs - Key Features 25 1 Applying XPRESIDENT quantitative mass spectrometry platform; target density: p eptide 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 scree ning to minimize off - target reactivity; functional a vidity : EC50 half maximal effective concentration
IMA201 IMA202 IMA203 IMA204 MAGEA4/8 MAGEA1 PRAME COL6A3 exon 6 Status Dose escalation ongoing Enrollment at target dose level (DL3) ongoing Enrollment at target dose level (DL4) ongoing IND - enabling studies close to completion Recruitment DL2 commenced N=2 pts treated DL3 commenced N=10 pts treated DL4 commenced N=18 pts treated NA Safety Too early Manageable safety profile; no DLTs or CRS/ICANS grade 3 Manageable safety profile; no additional DLTs 1 & no CRS/ICANS grade 3 NA Clinical Activity Too early Disease control in 7/10 patients (9 pts in DL1 & 2) , no objective responses Objective responses in 8/16 patients, thereof 8/13 responses above DL1 NA Next milestone Complete Ph1a dose escalation including target dose (DL3) Complete Ph1a dose esca - lation incl. target dose (DL4). Initiate expansion cohorts incl. monotherapy, checkpoint inhibitor combination & IMA203CD8 2 nd gen IND in 2022 due to acceleration of PRAME expansion cohorts ACTengine Programs - Status Update 26 1 One DLT in DL2 previously reported in March 2021, fully resolved
IMA201 IMA202 IMA203 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% Ovarian Carcinoma - 20% Melanoma - 20% HCC - 40% Squamous NSCLC - 35% Sarcoma Subtypes - up to 30% Melanoma - 30% Bladder Carcinoma - 20% Esophageal Carcinoma - 20% Uterine Carcinoma - 100% Sarcoma Subtypes - up to 100% Melanoma - 95% Uveal Melanoma - 80% 2 Ovarian Carcinoma - 80% Squamous NSCLC - 65% Kidney Carcinoma - up to 45% Cholangiocarcinoma - 35% Adeno NSCLC - 25% Breast Carcinoma - 25% HNSCC - 25% Esophageal Carcinoma - 20% HCC - 20% Bladder Carcinoma - 20% Pancreatic Carcinoma - 80% Breast Carcinoma - 75% Stomach Carcinoma - 65% Sarcoma - 65% Esophageal Carcinoma - 60% Squamous NSCLC - 55% Adeno NSCLC - 55% HNSCC - 55% Uterine Carcinosarcoma - 55% Colorectal Carcinoma - 45% Mesothelioma - 45% Cholangiocarcinoma - 40% Ovarian Carcinoma - 40% Melanoma - 35% Bladder Carcinoma - 35% ACTengine Programs - Target Prevalence 27 IMA200 targets show relevant expression in m ultiple s olid cancers 1 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data); 2 Based on metastatic uveal melanoma patients screened in IMA203 study (N=12)
ACTengine IMA201 & IMA202 - Patient Characteristics Heavily Pre - Treated Patients Were Infused during Dose Escalation Data cut - off - 17 - Sep - 2021 Characteristics in Efficacy Population Median (range) Age [years] 60 (27 - 68) Prior lines of systemic therapies 5 (3 - 7) Years from diagnosis 4 (1 - 8) Transduced T cells infused [x10 9 ] 0.46 (0.09 - 1.90) 1 Patients that started lymphodepletion; 2 Patients with at least one tumor assessment post treatment 28 Patient Distribution Number Patients in Safety Population 1 12 Patients in Efficacy Population 2 12 Thereof IMA201 infused 2 Thereof at target dose 0 Thereof IMA202 infused 10 Thereof at target dose 1 I MA201 study currently enrolls patients at dose level 2 (0.3 x 10 9 /m 2 ) IMA202 study is infusing patients at target dose (1 x 10 9 /m 2 )
Data cut - off - 17 - Sep - 2021 ACTengine IMA201 & IMA202 - Safety Profile Treatment - emergent Adverse Event s Are Manageable, Transient and Expected for Cell Therapies Adverse event All grades Grade 3 No . % No . % Patients with any adverse event 1 2 100.0 1 2 100.0 Adverse Events of Special interest Cytokine release syndrome 11 91.7 0 0.0 ICANS 2 1 8.3 0 0.0 Blood and lymphatic system disorders Lymphopenia* 10 83.3 10 83.3 Neutropenia** 10 83.3 10 83.3 Anaemia 8 66.7 6 50.0 Thrombocytopenia 8 66.7 6 50.0 Leukopenia* 6 50.0 5 41.7 Febrile Neutropenia 1 8.3 1 8.3 Infections and infestations Candida infection 1 8.3 1 8.3 Infection 1 8.3 1 8.3 Pneumonia 3 1 8.3 1 8.3 Urinary tract infection 1 8.3 1 8.3 Respiratory, thoracic and mediastinal disorders Hypoxia 2 16.7 0 0.0 Dyspnoea 3 1 8.3 1 8.3 Metabolism and nutrition disorders Hypocalcaemia 3 25.0 0 0.0 Decreased appetite 2 16.7 1 8.3 Adverse event All grades Grade 3 No . % No . % table continued Cardiac or vascular disorders Hypotension 4 33.3 0 0.0 Hypertension 1 8.3 1 8.3 General disorders and administration site conditions Pyrexia 6 50.0 0 0.0 Chills 4 33.3 0 0.0 Fatigue 3 25.0 1 8.3 Oedema peripheral 2 16.7 0 0.0 Gastrointestinal disorders Nausea 5 41.7 0 0.0 Vomiting 2 16.7 0 0.0 Constipation 2 16.7 0 0.0 Diarrhoea 2 16.7 0 0.0 Investigations Alanine aminotransferase increased 2 16.7 0 0.0 International normalised ratio increased 2 16.7 0 0.0 Aspartate aminotransferase increased 2 16.7 0 0.0 Blood alkaline phosphatase increased 1 8.3 1 8.3 Other Rash 3 25 0 0.0 Insomnia 2 16.7 0 0.0 Muscular weakness 1 8.3 1 8.3 Tumour pain 1 8.3 1 8.3 TEAEs by maximum severity ( N=12) 1 1 All treatment - emergent adverse events (TEAEs) with grade 1 - 2 occurring in at least 2 patients (incidence 16 . 7 % ) and additionally all events with grade 3 - 5 regardless of relatedness to study treatment are presented . Data source : clinical database . Adverse events were coded using the Medical Dictionary for Regulatory Activities . Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE), version 5 . 0 . Grades for Cytokine release syndrome and ICANS were determined according to CARTOX criteria ( Neelapu et al . , 2018 ) . Patients are counted only once per adverse event and severity classification .; 2 ICANS : Immune effector cell - associated neurotoxicity syndrome ; 3 Patient died from tumor progression and pneumonia 69 days after IMA 202 T cell infusion (determined not related to any study medication) ; * 100 % of patients experienced transient lymphopenia and leukopenia Grade 3 (CTCAE v 5 . 0 ) ; ** 91 . 7 % of patients experienced transient neutropenia Grade 3 (CTCAE v 5 . 0 ) CRS/ICANS: No Grade 3 CRS or ICANS observed so far Most Adverse Events were associated with lymphodepletion 29
ACTengine IMA201, IMA202, IMA203 - Change in Target Lesions Disease Control in 23 of 28 Patients Across 3 TCR - T Trials and Multiple Solid Cancers IMA201 & IMA202: Data cut - off - 17 - Sep - 2021 and IMA203: Data cut - off - 5 Oct - 2021 30 1 RECIST1.1 response at the timepoint of maximum change of target lesions (week 12): PD due to growth of non - target lesion; 2 RECIST1.1 response at the timepoint of maximum change of target lesions (week 12): PD due to new lesions ( leptomeningeal disease) at week 12; * Confirmed at subsequent scan; Confirmation pending as of data cut - off + + PD 2 0 1 - D L 1 - 0 2 2 0 2 - E C 2 - 0 2 2 0 2 - E C 2 - 0 1 2 0 2 - D L 1 - 0 2 2 0 2 - E C 1 - 0 2 2 0 3 - E C 2 - 0 1 2 0 3 - D L 2 - 0 2 2 0 2 - D L 2 - 0 2 2 0 2 - E C 2 - 0 3 2 0 3 - E C 1 - 0 3 2 0 3 - D L 3 - 0 3 2 0 3 - D L 2 - 0 6 2 0 2 - D L 3 - 0 1 2 0 3 - D L 1 - 0 3 2 0 3 - D L 1 - 0 1 2 0 1 - D L 1 - 0 1 2 0 2 - D L 2 - 0 1 2 0 3 - D L 1 - 0 2 2 0 2 - D L 1 - 0 1 2 0 3 - D L 2 - 0 4 2 0 2 - E C 1 - 0 1 2 0 3 - D L 3 - 0 2 2 0 3 - D L 2 - 0 1 2 0 3 - E C 1 - 0 2 2 0 3 - E C 1 - 0 1 2 0 3 - D L 2 - 0 5 2 0 3 - D L 2 - 0 3 2 0 3 - D L 3 - 0 1 -100 -50 0 50 100 -63.3 -61.0 -51.7 -50.5 -47.7 -39.9 -37.9 -35.4 -33.8 -16.2 -13.1 -11.1 -10.8 -9.7 -6.9 -5.0 -4.2 -2.0 -0.5-0.4 1.9 5.2 8.8 10.8 12.8 33.8 39.2 48.3 B e s t c h a n g e i n s u m o f d i a m e t e r [ % ] a n d B O R ( R E C I S T 1 . 1 ) Study: SD PR PR PR PR PR PR PR PR* S C C S y n o v i a l S a r c o m a U v e a l M e l a n o m a N S C L C O v a r i a n C a n c e r H e a d & N e c k C a n c e r H e a d & N e c k C a n c e r S y n o v i a l S a r c o m a M e l a n o m a S y n o v i a l S a r c o m a S y n o v i a l S a r c o m a U v e a l M e l a n o m a M e l a n o m a M e l a n o m a 2 H e a d & N e c k C a n c e r SD SDSD SD SD PD SD SD SD PD PD PD G a s t r i c C a n c e r M e l a n o m a M e l a n o m a B r o n c h i a l C a r c i n o m a S C C M e l a n o m a M e l a n o m a M e l a n o m a N S C L C S C C H N S C C M e l a n o m a 1 + + + + + + IMA201 IMA202 IMA203 SD SD SD SD SD SD S y n o v i a l S a r c o m a ** 1
University Hospital Dresden University Hospital Bonn University Hospital W rzburg Columbia University University of Pittsburgh MD Anderson Cancer Center University Hospital Hamburg Dr. D . Araujo Dr. A . Tsimberidou Dr. G . Blumenschein Dr. A . Kaseb Dr. Van Morris Dr. C . Bokemeyer Dr. W. Alsdorf Dr. T . Holderried Dr. M . C hatterjee Dr. J . Luke Germany United States Dr. M . Wermke Dr. C. List and the Investigators at the Clinical Sites Dr. R. Carvajal Dr. R . Reshef University of Chicago Dr. M . Bishop We are Immensely Grateful to the Patients, Their Families 31
Unlocking Immunotherapies for Solid Cancer Patients IMA203 - PRAME Objective responses observed across multiple tumor types 33 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 at DL2 * & DL3 (8/13 patients) - all still dosed below 1 bn cells 50% 62% ORR 2 across all doses and multiple solid cancers (8/16 patients) Multiple Ph1b cohorts Monotherapy at RP2D Checkpoint Inhibitor Combo 2 nd gen IMA203CD8 Focused development of half - life - extended Bispecific (TCER IMA402) TCR - T TCER IMA201, IMA202, IMA203 Interim Data from ongoing Dose Escalation 1 CRS: cytokine release syndrome, I CANS: Immune effector cell - associated neurotoxicity syndrome, both graded by CARTOX criteria ( Neelapu et al ., 2018); 2 Objective response rate according to RECIST 1.1 including confirmed and unconfirmed partial responses; * Includes patients treated at enrichment cohorts EC1 and EC2
Updated Immatics Pipeline 34 Modality Product Candidate Status Preclinical Phase 1a 1 Phase 1b 1 Phase 2/3 Next Milestone ACTengine Autologous ACT IMA201 (MAGEA4/8) Proprietary Complete dose escalation 2022 IMA202 (MAGEA1) Proprietary Complete dose escalation 1Q2022 IMA203 (PRAME) Proprietary Complete dose escalation 1Q2022 IMA203 (PRAME) + Checkpoint Inhibitor Proprietary Start Ph1 in 2022 IMA203CD8 (PRAME) Proprietary IND 1H2022 IMA204 (COL6A3) Proprietary IND 2022 Autologous ACT 3 ACT programs (Undisclosed) 2 ACT programs (Undisclosed) Allogeneic ACT ACTallo IMA30x (Undisclosed) Proprietary TCER Bispecifics IMA401 (MAGEA4/8) Proprietary IND YE2021; Start Ph1 1H2022 IMA402 (PRAME) Proprietary GMP run 2H2022, Start Ph1 2023 IMA40x (Undisclosed) Proprietary Bispecifics 3 Bispecific programs (Undisclosed) 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion
Last updated: Nov 9, 2021