Slide 1: ACTengine IMA203 TCR-T Targeting PRAME – Monotherapy Interim Data Update
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. ACTengine® IMA203 TCR - T Targeting PRAME Cedrik Britten, Chief Medical Officer Harpreet Singh, Chief Executive Officer October 10, 2022 – Monotherapy Interim Data Update
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: Multi-Tumor Target PRAME: Promising Opportunity for TCR-based Therapies
Multi - Tumor Target PRAME Promising Opportunity for TCR - based Therapies 3 PRAME Peptide Target Potential to reach a large cancer patient population IMA203 T cell Receptor (TCR): • Affinity - improved TCR by enhanced TCR chain pairing • High functional avidity: EC50 ~5 ng/ml • Off - target toxicit
Slide 4: IMA203 TCR-T Phase Design: Three Phase 1b Expansion Cohorts
IMA203 TCR - T Phase 1 Design Three Phase 1b Expansion Cohorts to Establish Durable Objective Responses 4 Each expansion cohort is designed to establish safety, evaluate the observed objective response rate, demonstrate durability & provide the trigger for registration trials 1 RP2D (target dose) de
Slide 5: IMA203 TCR-T Phase Design: Interim Clinical Data Update
IMA203 TCR - T Phase 1 Design Interim Clinical Data Update Focused on Phase 1a and Expansion Cohort A 5 Phase 1b Dose Expansion Phase 1a Dose Escalation Cohort A IMA203 Monotherapy at Target Dose (plus DL5) 1 Increasing T cell:Tumor cell Ratio 2 First pt treated March 2022 Cohort B IMA203 at Target
Slide 6: Moving from Phase 1a to Phase 1b
Moving from Phase 1a to Phase 1b Continuous Improvement of Key Aspects that May Influence Clinical Outcome 6 Our Focus in Phase 1a • Safety • Biological activity • Initial signs of clinical activity Our Focus in Phase 1b • Safety • Durability of response at 6 months and beyond to pave the way for re
Slide 7: ACTengine IMA203 – Interim Monotherapy Update: Key Take Aways
7 ACTengine® IMA203 – Interim Monotherapy Update Initial Data from 5 Patients Key Take Aways IMA203 Monotherapy Phase 1a Phase 1b Cohort A Dose Escalation Data from 27 Patients 1 ORR: Objective response rate (partial responses) according to RECIST 1.1 at first scan post infusion (~6 weeks); 2 confir
Slide 8: IMA203 Monotherapy – Patient and Product Characteristics
ACTengine® IMA203 Monotherapy – Patient and Product Characteristics 8 Phase 1a Dose Escalation Phase 1b (Cohort A) Dose Expansion All pts (DL1 - 4) DL4 pts only All pts (DL4/DL5) Patients treated 27 7 5 Prior lines of treatment Mean (min, max) 4.2 (1, 8) 4.6 (1, 7) 4.0 (1, 10) LDH at baseline >1 x U
Slide 9: IMA203 Tolerability Profile – Most Frequent Adverse Events
IMA203 Tolerability Profile – Most Frequent Adverse Events Acceptable and Manageable Treatment - emergent Adverse Events (TEAEs) • Expected cytopenia (Grade 1 - 4) associated with lymphodepletion in all patients • Cytokine release syndrome (CRS) : 31 of 32 (97%) patients infused with IMA203 experien
Slide 10: Frequency of Observed Objective Responses
Frequency of Observed Objective Responses Improved ORR and Confirmed ORR at Higher Dose and in Phase 1b Cohort A 10 1 All patients received >1 x 10 9 total transduced viable CD8 T cells; 2 ORR: Objective response rate (partial responses) according to RECIST 1.1 at first scan post infusion (~6 weeks)
Slide 11: Best Overall Response
Best Overall Response IMA203 Continues to Deliver Objective Responses in Major Solid Tumor Types 11 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 ta
Slide 12: Responses over Time
Responses over Time Encouraging Early Signs for Improved Durability at Higher Dose and in Phase 1b Patients 12 # Synovial sarcoma patient (DL3) PD at week 6 not shown as target lesions were not evaluable; PD: Progressive disease; SD: Stable disease; PR: Partial response; cPR: Confirmed partial respo
Slide 13: Translational Data Consistent with Clinical Outcomes
Translational Data Consistent with Clinical Outcomes Supporting Proposed Mechanism of Action for IMA203 13 Mann - Whitney U test; 1 T cell infiltration for 19 patients (9 non - responder, 10 responder) with 6 - week post infusion biopsy available (1 patient with ~5 - week post infusion biopsy) IMA20
Slide 14: PRAME Expression in Tumors from Screened Patients
PRAME Expression in Tumors from Screened Patients Clinical Validation of Immatics’ Mass Spectrometry - guided RNA Threshold for PRAME 14 Mann - Whitney U test, p=0.076 IMA203 achieved objective responses at all expression levels above threshold PRAME RNA expression in pre - treatment biopsies relati
Slide 15: Moving from Phase 1a to Phase 1b
Moving from Phase 1a to Phase 1b 15 Our Focus in Phase 1a • Safety • Biological activity • Initial signs of clinical activity Our Focus in Phase 1b • Safety • Durability of response at 6 months and beyond to pave the way for registration trials We continue to improve key determinants as we move from
Slide 16: IMA203 TCR-T Has the Potential to Reach a Large Patient Population
IMA203 TCR - T Has the Potential to Reach a Large Patient Population ~39,000 Patients per Year in the US only 16 Incidences based on public estimates and Immatics internal model; Relapsed/refractory (R/R) or last - line patient population approximated by annual mortality; Estimated 41% HLA - A*02:01
Slide 17: IMA203 Monotherapy – Conclusions
IMA203 Monotherapy – Conclusions ACTengine® IMA203 Targeting PRAME Offers a Unique Opportunity for Solid Cancer Patients 17 IMA203 monotherapy Phase 1a and Phase 1b cohort A summary: • IMA203 continues to be well tolerated with manageable safety profile • Confirmed responses across a broad spectrum
Slide 18: Comprehensive PRAME Strategy
Comprehensive PRAME Strategy To Deliver Meaningful Clinical Benefit to Patients with PRAME - positive Cancers 18 Phase 1b Dose Expansion Phase 1a Dose Escalation Cohort A IMA203 Monotherapy at Target Dose (plus DL5) 1 Increasing T cell:Tumor cell Ratio 2 Cohort B IMA203 at Target Dose plus Checkpoin
Slide 19: 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. W. Alsdorf Dr. T. Holderried Dr. M. Chatterjee Dr. J. Luke Ge rma n y United State
Slide 20: 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
Slide 21: ACTengine IMA203 Product Manufacturing
ACTengine® IMA203 Product Manufacturing 21 Expedited QC testing (~1 week) Manufacturing time (~1 week) QC testing (Full sterility, 2 weeks) Manufacturing time (~1 week) Faster ACTengine®: expected ~2 weeks Leukapheresis Infusion - Ready Targeting Higher Robustness, Favorable Product Attributes, Fast
Slide 22: IMA203 Tolerability Profile – All ≥Grade Adverse Events
IMA203 Tolerability Profile – All ≥Grade 3 Adverse Events Adverse event ≥ Grade 3 No. % TEAEs by maximum severity (N=33) 1* ≥ Grade 3 No. % Adverse event Patients with any adverse event 33 100.0 table continued… Adverse Events of Special Interest Investigations Cytokine release syndrome 2 6.1 ICANS
Slide 23: Focus on Melanoma Patients
Focus on Melanoma Patients High ORR and cORR in Heavily Pre - Treated Patients with High Tumor Burden 23 Melanoma Subtype ORR (~6 weeks) 1 cORR (~12 weeks) 2 Melanoma (DL4/DL5) 3 6/8 (75%) 4/8 (50%) # Melanoma (all DL) 10/13 (77%) 5/13 (38%) # Cutaneous Melanoma 7/8 (88%) 2/8 (25%) Uveal Melanoma 2/
Slide 24: PRAME Expression in Tumors from Screened Patients
PRAME Expression in Tumors from Screened Patients Highlighting Type of Best Overall Response (left) and Study Cohort (right) 24 Mann - Whitney U test, p=0.076 PRAME RNA expression in pre - treatment biopsies relative to threshold IMA203 has the potential to provide clinical benefit for all PRAME bio
Slide 25: PRAME Expression – RNAseq Data with Mass Spectrometry-guided RNA Threshold
PRAME Expression – RNAseq Data Combined with Immatics’ Mass Spectrometry - guided RNA Threshold for Prevalence Prediction 25 Immatics’ proprietary mass spectrometry - guided RNA threshold 100% 100% 95% 50 %* 80% 65% 60% 25% % PRAME positive patients 1 100% 1 PRAME target prevalence is based on TCGA