Immatics N.v. · NASDAQ:IMTX
Immatics — Investor Presentation (May 2024)
65 slides from Immatics's investor presentation, May 14, 2024
Slide 1: Immatics Corporate Presentation
Immatics Corporate Presentation May 14, 2024 Exhibit 99.3
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 respective c
Slide 3: Building a Leading TCR Therapeutics Company
Therapeutic Opportunity Potential for addressing large patient populations with high prevalence targets in solid tumors Two Clinical-Stage Modalities Pipeline of TCR-T and TCR Bispecific product candidates in clinical & preclinical development Building a Leading TCR Therapeutics Company Intro Differ
Slide 4: Upcoming 2024 Catalysts for ACTengine and TCER Clinical Lead Assets
Upcoming 2024 Catalysts for ACTengine® and TCER® Clinical Lead Assets Projected Cash Runway into 2027 to Reach Multiple Value Inflections Points Targeted randomized Phase 2/3 trial1 for ACTengine® IMA203 in 2L+ melanoma in 2024 Next data updates for IMA203 & IMA203CD8 (GEN2) planned in 2H 2024 ACTen
Slide 5: Two Distinct TCR-based Therapeutic Modalities in Clinical Development
Two Distinct TCR-based Therapeutic Modalities in Clinical Development Differentiated positioning of ACTengine® vs. TCER® based on patient population and medical need Intro 1 Interim data update from the ACTengine® IMA203 (published May 14, 2024) and IMA203CD8 monotherapies (published November 08, 20
Slide 6: Our Pipeline of TCR-based Adoptive Cell Therapies and Bispecifics
Modality Product Candidate Target Preclinical Phase 1a1 Phase 1b1 Phase 2 Phase 3 Autologous ACT ACTengine® IMA203 PRAME ACTengine® IMA203CD8 PRAME ACTengine® IMA204 COL6A3 Autologous ACT Multiple programs Undisclosed Allogeneic ACT γδ T cells ACTallo® IMA30x Undisclosed Multiple programs Undisclose
Slide 7: Realizing the Full Multi-Cancer Opportunity of PRAME
Realizing the Full Multi-Cancer Opportunity of PRAME ACTengine® IMA203 (TCR-T) and TCER® IMA402 (TCR Bispecific) ACTengine® IMA203 (TCR-T) Cancer Cell Death PRAME is one of the most promising and most prevalent, clinically validated solid tumor targets known to date Leverage the full potential of ta
Slide 8: ACTengine IMA203 – TCR-T Targeting PRAME
ACTengine® IMA203 – TCR-T Targeting PRAME
Slide 9: The Multi-Cancer Opportunity of PRAME
The Multi-Cancer Opportunity of PRAME One of the Most Promising Solid Tumor Targets for TCR-based Therapies Known To Date High prevalence High target density Homogeneous expression “Clean” expression profile Clinical proof-of-concept sqNSCLC Ovarian Cancer PRAME fulfills all properties of an ideal t
Slide 10: ACTengine IMA203 Targeting PRAME – Mechanism of Action
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ Leading TCR-T Approach IMA203 LEUKAPHARESIS
Slide 11: ACTengine IMA203 TCR-T Product Manufacturing
ACTengine® IMA203 TCR-T Product Manufacturing Differentiated Manufacturing Process and Setup 1-week manufacturing process followed by 1-week QC release testing High manufacturing success rate of >95% to reach IMA203 target dose* Lean and cost-efficient process Proprietary Manufacturing Process IMA
Slide 12: IMA203/IMA203CD8 TCR-T Monotherapy – Patient Flow
ACTengine® IMA203/IMA203CD8 TCR-T Monotherapy – Patient Flow 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®
Slide 13: ACTengine IMA203 TCR-T Trial in Advanced Solid Tumors
Melanoma Efficacy Population3 (N=30) ACTengine® IMA203 TCR-T Trial in Advanced Solid Tumors Data cut-off Apr 25, 2024 Heavily Pretreated Patient Population IMA203 Phase 1a Dose Escalation Dose Level 1-4 (total Safety Pop. N=281) Total Safety Population (N=651,2) Phase 1b Dose Expansion Dose Level 4/
Slide 14: IMA203 Adverse Events
Adverse event (System organ class, Preferred term) ≥ Grade 3 No. % table continued… Nervous system disorders 2 3.1 Headache 1 1.5 Posterior reversible encephalopathy syndrome 1 1.5 Endocrine disorders 1 1.5 Inappropriate antidiuretic hormone secretion 1 1.5 Hepatobiliary disorders 1 1.5 Cholangitis
Slide 15: Best Overall Response for IMA203
Best Overall Response for IMA203 Objective Responses in Heavily Pretreated Melanoma Patients at RP2D Data cut-off Apr 25, 2024 IMA203 cORR 55% (16/29) median DOR 13.5 months min, max DOR 1.2+, 21.5+ months 11/16 confirmed responses ongoing ORR 67% (20/30) Tumor shrinkage* 87% (26/30) DCR (at week 6)
Slide 16: Response over Time of IMA203
Response over Time of IMA203 Durable Responses 20+ Months after Treatment in Heavily Pretreated Melanoma Patients at RP2D Data cut-off Apr 25, 2024 IMA203 Scans at approximately week 6, month 3 and then every 3 months Ongoing cORR 55% (16/29) median DOR 13.5 months min, max DOR 1.2+, 21.5+ months 11
Slide 17: IMA203 Summary of Clinical Data and Planned Next Steps
ACTengine® IMA203 TCR-T Monotherapy Targeting PRAME in Melanoma Summary of Clinical Data and Planned Next Steps Next Steps Ongoing alignment with FDA on trial design of the randomized Phase 2/3 trial in 2L+ melanoma to start in 2024 Safety Anti-Tumor Activity Durability RP2D Broad Reach Favorable sa
Slide 18: High Unmet Medical Need in Cutaneous and Uveal Melanoma
High Unmet 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 Oppor
Slide 19: IMA203CD8 GEN2 – Leveraging CD8 and CD4 cells
IMA203CD8 GEN2 – IMA203 TCR-T Monotherapy Leveraging CD8 and CD4 cells Differentiated Pharmacology Compared to 1st-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 CD8αβ alon
Slide 20: IMA203CD8 (GEN2) – Preclinical Assessment of Anti-Tumor Efficacy
IMA203CD8 (GEN2) – Preclinical Assessment of Anti-Tumor Efficacy Functional CD4 T cells Mediate Longer Anti-Tumor Activity than CD8 T cells in vitro 2nd addition of tumor cells 3rd 4th 5th 6th 2nd addition of tumor cells 3rd 4th 5th 6th IMA203CD8
Slide 21: IMA203CD8 (GEN2) – Overview of Patient Characteristics
IMA203CD8 (GEN2) – Overview of Patient Characteristics * Patients with at least one available tumor response assessment post infusion; IMA203CD8 DL3: 0.2-0.48x109 TCR-T cells/m2 BSA, IMA203CD8 DL4a: 0.481-0.8x109 TCR-T cells/m2 BSA, IMA203CD8 DL4b: 0.801-1.2x109 TCR-T cells/m2; 1 DL4a cleared in Dec
Slide 22: Tolerability Data – IMA203CD8 (GEN2)
Tolerability Data – IMA203CD8 (GEN2) 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 Blood and lymphat
Slide 23: IMA203CD8 (GEN2) – BOR and Response over Time
IMA203CD8 (GEN2) (N=12#) – BOR and Response over Time Data cut-off Sep 30, 2023 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) Ongoing durable response 12+ months after infusion Median DOR, min, max DOR Not
Slide 24: IMA203CD8 (GEN2): Translational Data Shows Enhanced Pharmacology
IMA203CD8 (GEN2): Translational Data Shows Enhanced Pharmacology IMA203 Phase 1b vs IMA203CD8 (GEN2) Trend towards responses at lower cell dose and higher tumor burden with IMA203CD8 Higher peak expansion (Cmax) of IMA203CD8 T cells when normalized to infused dose Higher activation levels in IMA203C
Slide 25: IMA203CD8 Summary of Clinical Data and Planned Next Steps
ACTengine® IMA203CD8 (GEN2) TCR-T Monotherapy Targeting PRAME Summary of IMA203CD8 Clinical Data and Planned Next Steps Enhanced primary and secondary pharmacology when compared to IMA203 Manageable tolerability (2 DLTs at DL4b, dose escalation ongoing) Initial clinical activity observed with differ
Slide 26: Potential of IMA203 in Additional Solid Cancer Indications
PRAME mRNA expression in IMA203 Phase 1a and Phase 1b responders at RP2D (n=13) PRAME mRNA expression in IMA203CD8 (GEN2) responders (n=7) Potential of IMA203 in Additional Solid Cancer Indications Based on PRAME Expression in IMA203 and IMA203CD8 (GEN2) Responders % PRAME-positive patients1 PRAME t
Slide 27: 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 Development Strategy Step 1 IMA203 in cutaneous melanoma (potentially bundled with uveal melanoma) as first tumor type targeted to enter registration-enabling trial Further dose escalat
Slide 28: IMA203 TCR-T Has the Potential to Reach a Large Patient Population
Selected Indications Incidence R/R Incidence PRAME Positive Patient Population Based on R/R Incidence; PRAME and HLA-A*02:01+ Cut. Melanoma 99,800 7,700 95% 2,999 Uveal Melanoma 1,500 800 91% 298 Ovarian Carcinoma 19,900 12,800 84% 4,408 Uterine Carcinoma 62,700 10,700 97% 4,255 Uterine Carcinosarco
Slide 29: TCER — TCR Bispecifics
8oe@ Immatics TCER® — TCR Bispecifics
Slide 30: TCER – Next-generation, Half-Life Extended Bispecifics
TCER® – Immatics’ Next-generation, Half-Life Extended Bispecifics Proprietary TCER® Format Consisting of Three Distinct Elements High-affinity TCR domains targeting XPRESIDENT®-selected tumor-specific peptide-HLA molecules Low-affinity T cell recruiter against CD3/TCR Fc part for half-life extension
Slide 31: TCER – Next-generation, Half-Life Extended Bispecifics
TCER® – Immatics’ Next-generation, Half-Life Extended Bispecifics pHLA targeting TCR High-affinity (single digit nM) TCR targeting XPRESIDENT®-selected tumor-specific peptide-HLA molecules Broad therapeutic window through XPRESIDENT®-guided affinity maturation (>1000x)1 Complete tumor eradication in
Slide 32: Potency of Our Proprietary TCR Bispecific Format TCER
Potency of Our Proprietary TCR Bispecific Format TCER® 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 specificity1 than six alternative TCR Bispecific format designs evalu
Slide 33: TCER Format Designed for Optimized Efficacy and Safety: Tumor Control
TCER® Format Is Designed for Optimized Efficacy and Safety Superior Tumor Control Using a Novel, Low-Affinity Recruiter Widely used T cell recruiting Ab (3 variants) medium to high affinity (single to double digit nM) n = 6 mice/treatment group, n = 10 mice in vehicle group, 2 donors/group Dose: 0.0
Slide 34: TCER Format: Reduced Recruiter-Mediated Cytokine Release
TCER® Format Is Designed for Optimized Efficacy and Safety Reduced Target-Unrelated Recruiter-Mediated Cytokine Release using a Low-Affinity Recruiter TCER® Whole blood cytokine release assay N=3 HLA-A*02-positive donors N=16 cytokines tested, 4 exemplary cytokines shown
Slide 35: Our TCER Portfolio
Our TCER® Portfolio Broad Pipeline of Next-Gen Half-Life Extended TCR Bispecifics TCER® PRAME peptide presented by HLA-A*02:01 Start of clinical trial in Aug 2023, first clinical data expected 2H 2024 IMA402 Potential for addressing different indications and large patient populations with novel, off
Slide 36: TCER IMA401 Targeting MAGEA4/8
TCER® IMA401 Targeting MAGEA4/8 Homogeneous Expression, Broad Prevalence and High Copy Number Target MAGEA4 RNA detection in tumor samples (ISH) Indications Target prevalence [%] Squamous non-small cell lung carcinoma 52% Head and neck squamous cell carcinoma 36% Bladder carcinoma 29% Uterine carcin
Slide 37: TCER IMA401 – Anti-Tumor Activity in vitro
TCER® IMA401 (MAGEA4/8) – Assessment of Anti-Tumor Activity in vitro Patient-Derived Tumor Model NSCLC adenocarcinoma: Male, Caucasian, age 58, no therapy prior to surgery Site of origin: lung, differentiation poor Date of surgery: 1987, Freiburg Medical Center Volume doubling time: 7.3 day Histolog
Slide 38: TCER IMA401 – Pharmacokinetics
TCER® IMA401 (MAGEA4/8) – Pharmacokinetics PK Analysis in NOG Mice Two different PK assays established to ensure functional integrity of protein domains Terminal half-life in mice: 10-11 days pHLA – VL Assay Fc – VL Assay IMA401
Slide 39: Phase 1 Clinical Trial to Evaluate TCER IMA401
Phase 1 Clinical Trial to Evaluate TCER® IMA401 Targeting MAGEA4/8 MTD: maximum tolerated dose, RP2D: recommended phase 2 dose; BLRM: Bayesian logistic regression model; 1 Pharmacokinetics data assessed throughout the trial might provide an opportunity to optimize scheduling to a less frequent regim
Slide 40: TCER IMA402 Targeting PRAME – Efficacy Assessment in vitro
TCER® IMA402 Targeting PRAME – Efficacy Assessment in vitro Tumor Cell Killing at Low Physiological PRAME Peptide Levels TCER® IMA402 induces killing of tumor cells with PRAME target copies as low as 50 CpCs Physiological PRAME levels detected in majority of cancer tissues from patients are 100 – 10
Slide 41: TCER IMA402 Achieves Durable Tumor Control in vivo
TCER® IMA402 Achieves Durable Tumor Control of Large Tumors in vivo Dose-dependent efficacy of IMA402 in cell line-derived in vivo mouse model Durable shrinkage of large tumors including complete responses over prolonged period Sufficiently high drug doses are key to achieving desired anti-tumor eff
Slide 42: Half-life Extended Format of IMA402
Half-life Extended Format of IMA402 Confers Terminal Half-life of >1 Week pHLA – aVL Assay pHLA – aFc Assay IMA402 shows a terminal serum half-life of ≈ 8 days in mice IMA402 will be initially dosed weekly in the clinical trial Dosing frequency may be adapted based on clinical data IMA402
Slide 43: Phase 1/2 Clinical Trial to Evaluate TCER IMA402
Phase 1/2 Clinical Trial to Evaluate TCER® IMA402 Targeting PRAME First Clinical Data Planned in 2H 2024 Phase 1: Dose Escalation Phase 2a: Dose Expansion Adaptive design aimed at accelerating dose escalation Specific indications plus ongoing basket Combination therapies Optional dose/application op
Slide 44: In Vivo Expressed TCER Molecules with Moderna
In Vivo Expressed TCER® Molecules Targeting Cancer-specific pHLA Targets Combining Immatics’ Target and TCR Platforms with Moderna’s mRNA Technology Immatics Moderna Delivery of TCER® biologics through mRNA Proprietary cancer targets & TCR Bispecifics format mRNA-encoded TCER® molecule XPRESIDENT® t
Slide 45: Immatics' Proprietary Target and TCR Discovery Platforms
Immatics’ Proprietary Target and TCR Discovery Platforms
Slide 46: Our TCR-based Approaches Leverage the Full Target Space
Our TCR-based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface Technology
Slide 47: 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 True Targets via XPRESIDENT® technology platform are naturally presented on tumor tissues as identified by mass-spec are absent or presented at only low levels on nor
Slide 48: Pool of Prioritized Targets: XPRESIDENT Target Platform
Technology Pool of 200 Prioritized Targets as Foundation for Future Value Generation XPRESIDENT® Target Platform 200 Prioritized Targets Grouped in 3 Target Classes: Well known and characterized parent protein (20%) e.g. MAGE family cancer testis antigens Unknown or poorly characterized parent prote
Slide 49: Potential for Large Patient Populations across Multiple Solid Cancers
Potential for Large Patient Populations across Multiple Solid Cancers Uterine Carcinoma – 97% Uterine Carcinosarcoma – 100% Sarcoma Subtypes – up to 100% Cut. Melanoma ≥ 95% Uveal Melanoma1 ≥ 91% Ovarian Carcinoma – 84% Squamous NSCLC – 68% TNBC – 63% Small Cell Lung Cancer – 45% Kidney Carcinoma –
Slide 50: Identification of the most Relevant Target
Immatics’ Unique Capability – Identification of the most Relevant Target Example of MAGEA4/8 Peptide Target 1 Copy number per tumor cell (CpC) measured on a paired-sample basis by AbsQuant®, i.e. comparing MAGEA4 vs. MAGEA4/A8 peptide presentation on same sample, 2 Students paired T test p<0.0012 Te
Slide 51: Development of the Right TCR – XCEPTOR Technology
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy ACTengine® ACTallo® Fast, efficient and highly sensitive discovery of highly specific, natural TCRs Protein engineering
Slide 52: 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 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Off-target toxicity
Slide 53: Bioinformatics and AI-Platform XCUBE
“AI Is Where the Data Is®” Bioinformatics and AI-Platform XCUBE™ Data Engineering Development of data warehouses & user interfaces Data Science Development of statistical & machine learning models Data Processing Processing of mass-spec & next-gen sequencing data 1 THERAPEUTIC KNOWLEDGE XPRESIDENT®/
Slide 54: Immatics' Robust Intellectual Property Portfolio
Immatics’ Robust Intellectual Property Portfolio Protection Strategy of Key Assets in Major Markets and Beyond Technologies Targets TCRs TCER® Therapeutic Uses Cell Therapy TCRs with high affinity and specificity profile Differentiated technologies, platforms and assays for Target Research, TCR and
Slide 55: ACTengine IMA204 – TCR-T Targeting COL6A3 Exon 6
ACTengine® IMA204 – TCR-T Targeting COL6A3 Exon 6
Slide 56: ACTengine IMA204 First-in-Class TCR-T Targeting Tumor Stroma
ACTengine® IMA204 First-in-Class TCR-T Targeting Tumor Stroma Key Features HLA-A*02-presented peptide derived from COL6A3 exon 6 Naturally and specifically presented on tumors at high target density1: 100-700 copies/cell Novel tumor stroma target identified and validated by XPRESIDENT® quant. mass s
Slide 57: IMA204 – High Affinity, CD8-independent TCR
ACTengine® IMA204 – High Affinity, CD8-independent TCR Complete Tumor Eradication in vitro & in vivo1 by Affinity-enhanced IMA204 TCR CD8-independent TCR leads to tumor eradication in all mice treated Control IMA204 TCR D7 D16 D22 D29 Affinity maturated CD8-independent, next-generation TCR engages b
Slide 58: ACTallo – Our Next-generation Off-the-shelf TCR-T
ACTallo® – Our Next-generation Off-the-shelf TCR-T
Slide 59: ACTallo – Immatics' Allogeneic Cell Therapy Approach
ACTallo® – Immatics’ Allogeneic Cell Therapy Approach Off-the-shelf cell therapy, no need for personalized manufacturing à reduced logistics and time to application Potential for hundreds of doses from one single donor leukapheresis à lower cost of goods Use of healthy donor material provides standa
Slide 60: Why γδ T cells?
Why γδ T cells? γδ T cells Are Well Suited for an Off-the-shelf Cell Therapy Approach γδ T cells are abundant in the peripheral blood show intrinsic anti-tumor activity naturally infiltrate solid tumors & correlate with favorable prognosis are HLA-independent, thus do not cause graft-vs-host disease
Slide 61: Corporate Information & Milestones
Corporate Information & Milestones
Slide 62: Management Team
David Leitner Schuldirektor David Leitner Schuldirektor David Leitner Schuldirektor Harpreet Singh Chief Executive Officer Co-Founder >20 yrs biotech experience Arnd Christ Chief Financial Officer >20 yrs biotech experience (InflaRx, Medigene, NovImmune, Probiodrug) Carsten Reinhardt Chief Developme
Slide 63: Strong, Focused and Highly Integrated Trans-Atlantic Organization
Strong, Focused and Highly Integrated Trans-Atlantic Organization Houston, Texas ~190 FTEs Cell therapy development & manufacturing Munich, Germany ~70 FTEs Various operating functions Tübingen, Germany ~225 FTEs Target & TCR discovery and TCR Bispecifics development Corporate
Slide 64: Delivering the Power of T cells to Cancer Patients
Delivering the Power of T cells to Cancer Patients Appendix www.immatics.com 028 immatics
Slide 65: IMA203 Phase 1 Patient Population Flow Chart
IMA203 Phase 1 Patient Population Flow Chart Total Safety Population N=65* enrolled patients N=1 patient in Phase 1a started lymphodepletion but did not receive IMA203 N=64 patients treated with IMA203 N=27 patients in Phase 1a Dose Escalation (DL1-4) Melanoma Efficacy Population N=5 melanoma patien