Slide 1: ACTengine IMA203 / IMA203CD8 TCR-T Monotherapy Targeting PRAME – Phase 1 Interim Data Update
© Immatics. Not for further reproduction or distribution. Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. ACTengine® IMA203 / IMA203CD8 TCR - T Monotherapy Targeting PRAME – Phase 1 Interim Data Update Martin Wermke , Professor at the Univ
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: Realizing the Full Multi-Cancer Opportunity of PRAME
Realizing the Full Multi - Cancer Opportunity of PRAME ACTengine® IMA203 (TCR Cell Therapy) and TCER® IMA402 (TCR Bispecific) 3 ACTengine® IMA203 (TCR Cell Therapy) 1 PRAME target prevalence is based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expre
Slide 4: Two Assets with Distinct Opportunities and Near-Term Catalysts
ACTengine® IMA203 / IMA203CD8 TCR - T Monotherapy Two Assets with Distinct Opportunities and Near - Term Catalysts 4 GEN1: IMA203 in Melanoma at RP2D GEN2: IMA203CD8 in Solid Tumors Initial Clinical Data • Complete dose escalation • Signal finding in non - melanoma indications, such as ovarian cance
Slide 5: ACTengine IMA203 / IMA203CD8 Trial in Advanced Solid Tumors Overview
ACTengine® IMA203 / IMA203CD8 TCR - T Trial in Advanced Solid Tumors Overview D ose Level 1 - 4 ( total N=27): Patients in DL4 (N=7) treated at RP2D Phase 1b Dose Expansion Phase 1a Dose Escalation Efficacy population shown: patients treated with IMA203 (Cohort A) or IMA203CD8 (Cohort C) and with at
Slide 6: Overview of Patient Characteristics and Responses
Overview of Patient Characteristics and Responses 6 * Patients with at least one available tumor response assessment post infusion; # All patients were PD at data cut - off; Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR ( cORR ): Confirmed obje
Slide 7: ACTengine IMA203 Interim Update
ACTengine® IMA203 TCR - T Interim Update Delivering a Meaningful Benefit to Patients with an Unmet Medical Need 7 IMA203 GEN1 Monotherapy Phase 1a & Cohort A – Focus on Melanoma at RP2D IMA203CD8 GEN2 Monotherapy Cohort C – First Data Set on 2 nd Generation Summary & Next Development Steps
Slide 8: IMA203 GEN1 in All Melanoma Patients at RP2D – Most Frequent Adverse Events
8 Data cut - off Sep 30, 2023 IMA203 GEN1 in All Melanoma Patients at RP2D – Most Frequent Adverse Events • Expected cytopenia (Grade 1 - 4) associated with lymphodepletion in all patients • Mostly mild to moderate cytokine release syndrome (CRS) • 63% (10/16) with Grade 1 CRS • 31% (5/16) with Grad
Slide 9: IMA203 GEN1 in Melanoma Patients at RP2D – BOR and Response over Time
# # # # # # # # # # IMA203 GEN1 in All Melanoma Patients at RP2D (N=13) – BOR and Response over Time Durable Responses 15+ Months after Treatment 9 Data cut - off Sep 30, 2023 Ongoing ORR 62% (8/13) cORR 50% (6/12) Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion sca
Slide 10: High Medical Need in Cutaneous and Uveal Melanoma
10 High Medical Need in Cutaneous and Uveal Melanoma Clinically and Commercially Attractive Features of IMA203 Cutaneous Melanoma Uveal Melanoma Patient Population 2L+ CPI - refractory, BRAF/MEK inhibitor - refractory if BRAF mutation+ 2L+ Kimmtrak - refractory, CPI/chemotherapy - refractory IMA203
Slide 11: ACTengine IMA203 Interim Update
ACTengine® IMA203 TCR - T Interim Update Delivering a Meaningful Benefit to Patients with an Unmet Medical Need 11 IMA203 GEN1 Monotherapy Phase 1a & Cohort A – Focus on Melanoma at RP2D IMA203CD8 GEN2 Monotherapy Cohort C – First Data Set on 2 nd Generation Summary & Next Development Steps
Slide 12: IMA203CD8 GEN2 – Leveraging CD8 and CD4 Cells
IMA203CD8 GEN2 – IMA203 TCR - T Monotherapy Leveraging CD8 and CD4 cells Differentiated Pharmacology Compared to 1 st - Generation TCR - only Approaches • IMA203CD8 GEN2 designed to broaden the clinical potential of IMA203 TCR - T monotherapy by adding functional CD4 T cells via co - transduction of
Slide 13: IMA203CD8 GEN2 in Cohort C – Most Frequent Adverse Events
IMA203CD8 GEN2 in Cohort C (N=12) – Most Frequent Adverse Events Manageable Tolerability in 12 Patients Treated with IMA203CD8 at 3 Escalating Dose Levels 1 • Expected cytopenia (Grade 1 - 4) associated with lymphodepletion in all patients • Cytokine release syndrome (CRS) in 92% (11/12) of patients
Slide 14: IMA203CD8 GEN2 in Cohort C – BOR and Response over Time
IMA203CD8 GEN2 in Cohort C (N=12 # ) – BOR and Response over Time Deepening of Response from SD to PR in 2 Patients, 6 Responses Ongoing 14 • 6 out of 7 responses ongoing • 11/12 patients show tumor shrinkage • Deepening of response from SD to PR in two patients (C - DL4a - 01, C - DL4a - 03) • Ongo
Slide 15: IMA203CD8 GEN2: Translational Data Shows Enhanced Pharmacology
IMA203CD8 GEN2: Translational Data Shows Enhanced Pharmacology Cohort A IMA203 GEN1 (All Patients at RP2D) vs Cohort C IMA203CD8 GEN2 15 Trend towards responses at lower cell dose and higher tumor burden with IMA203CD8 Higher peak expansion ( C max ) of IMA203CD8 T cells when normalized to infused d
Slide 16: ACTengine IMA203 Interim Update
ACTengine® IMA203 TCR - T Interim Update Delivering a Meaningful Benefit to Patients with an Unmet Medical Need 16 IMA203 GEN1 Monotherapy Phase 1a & Cohort A – Focus on Melanoma at RP2D IMA203CD8 GEN2 Monotherapy Cohort C – First Data Set on 2 nd Generation Summary & Next Development Steps
Slide 17: Summary of GEN1 and GEN2 Clinical Data and Planned Next Steps
ACTengine® IMA203 / IMA203CD8 TCR - T Monotherapy Targeting PRAME Summary of GEN1 and GEN2 Clinical Data and Planned Next Steps 17 Next Step Alignment with FDA on patient population, trial design, CMC targeting registration - enabling Phase 2 trial in melanoma • Well tolerated, mostly mild to modera
Slide 18: Potential of IMA203 in Additional Solid Cancer Indications Based on PRAME Expression
PRAME mRNA expression in IMA203 GEN1 Phase 1a and Cohort A responders at RP2D (n=13) PRAME mRNA expression in IMA203CD8 GEN2 Cohort C responders (n=7) Potential of IMA203 in Additional Solid Cancer Indications Based on PRAME Expression in IMA203 GEN1 and IMA203CD8 GEN2 Responders 18 % PRAME - positi
Slide 19: Leveraging the Full Breadth of PRAME in Three Steps
ACTengine® IMA203 / IMA203CD8 TCR - T Monotherapy Targeting PRAME Leveraging the Full Breath of PRAME in Three Steps 19 Development Strategy Step 1 IMA203 GEN1 in cutaneous melanoma (potentially bundled with uveal melanoma) as first tumor type targeted to enter registration - enabling trial Signal f
Slide 20: Upcoming 2024 Catalysts for ACTengine and TCER Clinical Lead Assets
Upcoming 2024 Catalysts for ACTengine® and TCER® Clinical Lead Assets Projected Cash Runway Well into 2026 to Reach Multiple Value Inflections Points 20 IMA203 GEN1 • Update on clinical development plan in 1Q 2024 • Targeted registration - enabling Phase 2 trial for ACTengine® IMA203 GEN1 in melanom
Slide 21: We are Immensely Grateful to the Patients, Their Families and Investigators
University Hospital Dresden University Hospital Bonn University Hospital Würzburg Columbia University University of Pittsburgh MD Anderson Cancer Center University Hospital Hamburg Dr. D . Araujo Dr. A . Tsimberidou Dr. A. Jazaeri Dr. S . Patel Dr. W. Alsdorf Dr. T . Holderried Dr. M . C hatterjee D
Slide 22: Q&A
Delivering s the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. www.immatics.com Q&A
Slide 23: Appendix – Additional Data
Appendix – Additional Data 1. Patient Flow and PRAME Expression in Pre - Treatment Tumor Biopsies 2. Dose Escalation and Cohort A IMA203 GEN1 3. Cohort B IMA203 GEN1 + Nivolumab 4. Cohort C IMA203 GEN2 5. Manufacturing and in vivo Engraftment Data IMA203 GEN1 and IMA203CD8 GEN2
Slide 24: ACTengine IMA203/IMA203CD8 Monotherapy – Patient Flow
ACTengine® IMA203/IMA203CD8 TCR - T Monotherapy – Patient Flow 24 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 Profilin
Slide 25: PRAME Expression in Pre-Treatment Tumor Biopsies
PRAME Expression in Pre - Treatment Tumor Biopsies Comparable PRAME Expression Levels in Patients Treated in Phase 1a Dose Escalation, Cohort A and C 25 Data cut - off Sep 30, 2023 PRAME RNA expression in pre - treatment biopsies relative to threshold Immatics’ mass spectrometry - guided mRNA thresh
Slide 26: PRAME Expression in Pre-Treatment Tumor Biopsies – Responders
PRAME Expression in Pre - Treatment Tumor Biopsies Responders in Cohort A IMA203 GEN1 and Cohort C IMA203CD8 GEN2 26 Indication No significant difference in PRAME expression between Cohort A and C responders Best Overall Response PRAME RNA expression in pre - treatment biopsies relative to threshold
Slide 27: Appendix – Additional Data
Appendix – Additional Data 1. Patient Flow and PRAME Expression in Pre - Treatment Tumor Biopsies 2. Dose Escalation and Cohort A IMA203 GEN1 3. Cohort B IMA203 GEN1 + Nivolumab 4. Cohort C IMA203 GEN2 5. Manufacturing and in vivo Engraftment Data IMA203 GEN1 and IMA203CD8 GEN2
Slide 28: IMA203 GEN1 – Melanoma as First Indication for Pivotal Development
IMA203 GEN1 – Melanoma as First Indication for Pivotal Development 28 * Patients with at least one post treatment tumor response assessment Patient characteristics All comers Cohort A Melanoma pts Ph1a & Cohort A at RP2D Ovarian cancer pts Ph1a & Cohort A at RP2D Efficacy population* 18 13 4 Prior l
Slide 29: IMA203 GEN1 in Phase 1a Dose Escalation – BOR and Response over Time
IMA203 GEN1 in Phase 1a Dose Escalation (N=27 # ) – BOR and Response over Time 29 * Maximum change of target lesions and RECIST 1.1 BOR at different timepoints ; # Synovial sarcoma patient (DL3) PD at week 6 not shown as t arget lesions were not evaluable; PD: Progressive disease; SD: Stable disease
Slide 30: IMA203 GEN1 in Cohort A – BOR and Response over Time
* IMA203 GEN1 in Cohort A (N=18) – BOR and Response over Time Objective Responses across Multiple Solid Cancer T ypes 30 1 Patient received one dose nivolumab erroneously; 2 Progressive disease at month 6 due to unequivocal progression of non - target lesions, target lesions not evaluable due to ext
Slide 31: IMA203 GEN1 in Cohort A – Most Frequent Adverse Events
31 Data cut - off Sep 30, 2023 IMA203 GEN1 in Cohort A – Most Frequent Adverse Events N=21 Patients in Safety Population 1 • Expected cytopenia (Grade 1 - 4) associated with lymphodepletion in all patients • Mild - moderate cytokine release syndrome (CRS) in 90% (19/21) of patients • 43% (9/21) with
Slide 32: Adverse Events ≥ Grade 3
Adverse event ( System organ class , Preferred term ) ≥ Grade 3 No . % Patients with any adverse event 49 100.0 Adverse Events of Special Interest 2 4.1 Cytokine release syndrome 2 4.1 ICANS 2 0 0.0 Blood and lymphatic system disorders 48 98.0 Neutropenia 36 73.5 Lymphopenia 27 55.1 Leukopenia 26 53
Slide 33: Tolerability Data – IMA203 GEN1 at RP2D
Tolerability Data – IMA203 GEN1 at RP2D Phase 1a DL4 and Cohort A – All ≥Grade 3 Adverse Events (N=28) 33 • IMA203 was well tolerated at doses as high as ~10x10 9 TCR - T cells • Most frequent ≥Grade 3 AEs were expected cytopenia associated with lymphodepletion • No IMA203 - related Grade 5 AEs All
Slide 34: Biological Data Consistent with Clinical Data – IMA203 GEN1
Biological Data Consistent with Clinical Data – IMA203 GEN1 IMA203 T cell Levels and Tumor Infiltration across Patients in Phase 1a and Cohort A 34 Data cut - off Sep 30, 2023 Mann - Whitney U test; 1 T cell infiltration for 22 patients (11 non - responder, 11 responder) with 6 - week post infusion
Slide 35: Melanoma Patients – Phase 1a and Cohort A IMA203 GEN1
Melanoma Patients – Phase 1a and Cohort A IMA203 GEN1 (N=13) Cohort 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 Reason for Progression Cohort A A - DL5 - 01 Uveal Melanoma 1 ARRY614 +
Slide 36: Indications beyond Melanoma – Cohort A IMA203 GEN1
Indications beyond Melanoma – Cohort A IMA203 GEN1 (N=10) 36 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 Reason for Progression A - DL4 - 01 Head & Neck Cancer 1 Paclitaxel + Carboplat
Slide 37: Appendix – Additional Data
Appendix – Additional Data 1. Patient Flow and PRAME Expression in Pre - Treatment Tumor Biopsies 2. Dose Escalation and Cohort A IMA203 GEN1 3. Cohort B IMA203 GEN1 + Nivolumab 4. Cohort C IMA203 GEN2 5. Manufacturing and in vivo Engraftment Data IMA203 GEN1 and IMA203CD8 GEN2
Slide 38: Cohort B: ACTengine IMA203 + Nivolumab Summary
Cohort B: ACTengine® IMA203 TCR - T + Nivolumab Summary • IMA203 TCR - T combined with nivolumab was well tolerated with no unexpected adverse events or additive toxicities • The combination therapy showed clinical activity with one durable objective response exceeding 12 months post infusion and tu
Slide 39: Patient Flow – Cohort B IMA203 + Nivolumab
Patient Flow – Cohort B IMA203 + Nivolumab 39 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 IMADetect ® Biopsy
Slide 40: PRAME Expression in Pre-Treatment Tumor Biopsies – Cohorts A and B
PRAME Expression in Pre - Treatment Tumor Biopsies Comparable PRAME Expression Levels in Patients Treated in Cohort A and B 40 Data cut - off Sep 30, 2023 PRAME RNA expression in pre - treatment biopsies relative to threshold Immatics’ mass spectrometry - guided mRNA threshold IMA203 + Nivo Mann - W
Slide 41: Patient Characteristics Dose Escalation vs. Cohort A vs. Cohort B
Patient Characteristics Dose Escalation vs. Cohort A IMA203 vs. Cohort B IMA203 + Nivolumab 41 • Heavily pre - treated, metastatic last - line patients that have exhausted all available SOC treatments • Patients in IMA203+Nivo cohort had more prior lines of treatment and higher tumor burden while re
Slide 42: Most Frequent Adverse Events – Cohort B IMA203 + Nivolumab
Most Frequent Adverse Events – Cohort B IMA203 + Nivolumab (N=7) 1 Manageable Treatment - Emergent Adverse Events (TEAEs) • Expected cytopenia (Grade 1 - 4) associated with lymphodepletion in all patients • Low - moderate (Grade 1 - 2) cytokine release syndrome (CRS) in 100% (7/7) of patients • 57%
Slide 43: Detailed Tolerability Data – Cohort B IMA203 + Nivolumab
Detailed Tolerability Data – Cohort B IMA203 + Nivolumab (N=7) 1 All ≥Grade 3 Adverse Events (N=7) 43 Adverse event ≥ Grade 3 ( System organ class , preferred term) No. % Patients with any adverse event 7 100.0 Adverse events of special interest 0 0.0 Cytokine release syndrome 0 0.0 Immune effector
Slide 44: Best Overall Response & Durability – Cohort B
Best Overall Response & Durability – Cohort B IMA203 + Nivolumab (N=6) Ongoing Durable Response 12+ Months post Treatment 44 1 Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; 2 Confirmed ORR ( cORR ): Confirmed objective response rate according to RECIST 1.1 f
Slide 45: Particularly Hard-to-Treat Patient Population – Cohort B
Particularly Hard - to - Treat Patient Population – Cohort B IMA203 + Nivolumab 45 Patient ID Indication No of prior treatment lines Prior treatments Total infused dose TCR - T cells [x10 9 ] BOR BOR (Max % change of target lesions) Comment Reason for Progression B - DL4 - 06 Uveal Melanoma 0 NA 2.2
Slide 46: IMA203 T cell Levels – Cohort A vs. Cohort B
IMA203 T cell Levels – Molecular Immunomonitoring Cohort A IMA203 vs. Cohort B IMA203 + Nivolumab 46 Statistical test: Mann - Whitney U 2 6 1 0 1 4 1 8 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 4 0 6 0 8 0 1 0 0 2 0 0 4 0 0 6 0 0 8 0 0 Days post infusion V e c t o r c o p i
Slide 47: IMA203 T cell Activation and Differentiation
IMA203 T cell Activation and Differentiation Cohort A IMA203 vs. Cohort B IMA203 + Nivolumab 47 Trend towards increased terminal differentiation of IMA203 T cells and exhaustion surrogate receptor expression in combination with nivolumab Statistical Test: Mann Whitney; *TEMRA (CCR7 - CD45RA+), CD39
Slide 48: Kinetics of PD-1+ Frequency on IMA203 T Cells
Kinetics of PD - 1 + Frequency on IMA203 T Cells 48 Cohort A IMA203 vs. Cohort B IMA203 + Nivolumab Sustained PD - 1 expression on IMA203 T cells after initial activation observed in few patients *Patient B - DL4 - 04 did not have available samples for analysis of week 1 and month 6 Cohort A Cohort
Slide 49: Patient Case B-DL4-04: Tumor Reduction in Multiple Large Metastatic Lesions
Patient Case B - DL4 - 04: Tumor Reduction in Multiple Large Metastatic Lesions Observed Sustained Clinical Benefit in Patient despite PD at Week 11 49 Pre - treatment Post - treatment, week 11 = bladder 1 Per treating physician; CT scans courtesy of treating physician Clinical benefit observed desp
Slide 50: Appendix – Additional Data
Appendix – Additional Data 1. Patient Flow and PRAME Expression in Pre - Treatment Tumor Biopsies 2. Dose Escalation and Cohort A IMA203 GEN1 3. Cohort B IMA203 GEN1 + Nivolumab 4. Cohort C IMA203 GEN2 5. Manufacturing and in vivo Engraftment Data IMA203 GEN1 and IMA203CD8 GEN2
Slide 51: Tolerability Data – Cohort C IMA203CD8 GEN2
Tolerability Data – Cohort C IMA203CD8 GEN2 51 Adverse event ≥ Grade 3 ( System organ class , preferred term) No. % Patients with any adverse event 12 100.0 Adverse events of special interest 3 25.0 Cytokine release syndrome 1 3 25.0 Immune effector cell - associated neurotoxicity syndrome 0 0.0 Blo
Slide 52: Patients Treated in Cohort C IMA203CD8
Patients Treated in Cohort C IMA203CD8 52 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 Reason for Progression C - DL3 - 02 Cut. Melanoma 3 Ipilimumab + Nivolumab Nivolumab Binimetinib 0
Slide 53: Appendix – Additional Data
Appendix – Additional Data 1. Patient Flow and PRAME Expression in Pre - Treatment Tumor Biopsies 2. Dose Escalation and Cohort A IMA203GEN1 3. Cohort B IMA203 GEN1 + Nivolumab 4. Cohort C IMA203 GEN2 5. Manufacturing and in vivo Engraftment Data IMA203 GEN1 and IMA203CD8 GEN2
Slide 54: Favorable Product Characteristics and Manufacturing Improvements
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 54 Increased peak IMA203 T cell levels in patients Robust TCR - T product features DL4 only, normalized to cell dose Data cut - of
Slide 55: Delivering the Power of T cells to Cancer Patients
Delivering s the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. www.immatics.com