Immatics N.v. · NASDAQ:IMTX
Immatics — Investor Presentation (January 2023)
59 slides from Immatics's investor presentation, Jan 9, 2023
Slide 1: Immatics Corporate Presentation
© Immatics. Not for further reproduction or distribution. Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation January 09, 2023
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: 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 3 Intro
Slide 4: Our Near-Term Focus – Clinical Development of Our Lead Assets
4 Three IMA203 Ph1b cohorts: • Monotherapy • Checkpoint combo • 2nd - gen IMA203CD8 Data read - outs across all cohorts in 2023 ACTengine ® IMA203 (PRAME) Advance ongoing Phase 1 clinical trial Establish clinical PoC TCER® IMA401 (MAGEA4/8) Submission of CTA/IND application planned 2Q 2023 Start of
Slide 5: Our TCR-based Approaches Leverage the Full Target Space
Our TCR - based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface 5 Intro
Slide 6: Two Distinct TCR-based Therapeutic Modalities in Clinical Development
Two Distinct TCR - based Therapeutic Modalities in Clinical Development 6 Differentiated positioning of ACTengine® vs. TCER® based on patient population, medical need and geographical reach Intro 1 Interim data update from the ACTengine® IMA203 TCR - T Phase 1 trial with a 50% (6/12) confirmed ORR t
Slide 7: Our Pipeline of TCR-based Adoptive Cell Therapies and Bispecifics
Modality Product Candidate Target Preclinical Phase 1a 1 Phase 1b 1 Phase 2 Phase 3 Autologous ACT ACTengine ® IMA203 PRAME ACTengine® IMA203CD8 PRAME ACTengine® IMA201 MAGEA4/8 ACTengine® IMA204 COL6A3 Multiple programs Undisclosed Allogeneic ACT γδ T cells ACTallo® IMA30x Undisclosed Multiple prog
Slide 8: ACTengine IMA203 – TCR-T Targeting PRAME
ACTengine® IMA203 – TCR - T Targeting PRAME 8
Slide 9: ACTengine IMA203 Targeting PRAME – Mechanism of Action
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ Leading TCR - T Approach 9 IMA203
Slide 10: Multi-Tumor Target PRAME Promising Opportunity for TCR-based Therapies
Multi - Tumor Target PRAME Promising Opportunity for TCR - based Therapies 10 PRAME Peptide Target • HLA - A*02:01 presented peptide identified by XPRESIDENT® quant. mass spectrometry • Presented at high target density in tumor tissue (100 - 1000 copies/cell) • Homogenously expressed • Highly cancer
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® Manufacturing by Immatics Infusion of ACTengine® T cell Product Lymphodepletion 30 mg/m 2 Flu darabine 1 and 500 mg/m 2 Cy c
Slide 12: IMA203 Phase 1 Design – Three Phase 1b Expansion Cohorts
First pt treated Aug 20 22; DL3 completed, DL4 ongoing * IMA203 TCR - T Phase 1 Design Three Phase 1b Expansion Cohorts to Establish Durable Objective Responses 12 E ach expansion cohort is designed to establish safety, evaluate the observed objective response rate, demonstrate durability & provide
Slide 13: Moving from Phase 1a to Phase 1b
Moving from Phase 1a to Phase 1b Continuous Improvement of Key Aspects that May Influence Clinical Outcome 13 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 r
Slide 14: ACTengine IMA203 – Interim Monotherapy Update
14 ACTengine ® IMA203 – Interim Monotherapy Update Phase 1b Cohort A Initial Data from 5 Patients Key Take Aways IMA203 Monotherapy Phase 1a Dose Escalation Data from 27 Patients 1 ORR: O bjective response rate (partial responses) according to RECIST 1.1 at first scan post infusion (~6 weeks) ; 2 co
Slide 15: IMA203 Monotherapy – Patient and Product Characteristics
ACTengine® IMA203 Monotherapy – Patient and Product Characteristics 15 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
Slide 16: 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 17: Frequency of Observed Objective Responses
Frequency of Observed Objective Responses Improved ORR and Confirmed ORR at Higher Dose and in Phase 1b Cohort A 17 1 All patients received >1 x 10 9 total transduced viable CD8 T cells ; 2 ORR: O bjective response rate (partial responses) according to RECIST 1.1 at first scan post infusion (~6 week
Slide 18: Best Overall Response
Best Overall Response IMA203 Continues to Deliver Objective Responses in Major Solid Tumor Types 18 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 19: Responses over Time
Responses over Time Encouraging Early Signs for Improved Durability at Higher Dose and in Phase 1b Patients 19 # Synovial sarcoma patient (DL3) PD at week 6 not shown as t arget lesions were not evaluable; PD: Progressive disease; SD: Stable disease; PR: Partial response; cPR : Confirmed partial res
Slide 20: Translational Data Consistent with Clinical Outcomes
Translational Data Consistent with Clinical Outcomes Supporting Proposed Mechanism of Action for IMA203 20 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 21: ACTengine IMA203 Product Manufacturing
ACTengine® IMA203 Product Manufacturing Targeting Higher Robustness, Favorable Product Attributes, Faster Turn Around Time 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 ACTengine®
Slide 22: PRAME Expression – RNAseq Data with Mass Spectrometry-guided Threshold
PRAME Expression – RNAseq Data Combined with Immatics’ Mass Spectrometry - guided RNA Threshold for Prevalence Prediction 22 Immatics’ proprietary mass spectrometry - guided RNA threshold 100% 100% 100% 95% 50%* 80% 65% 60% 25% % PRAME positive patients 1 1 PRAME target prevalence is based on TCGA R
Slide 23: PRAME Expression in Tumors from Screened Patients
PRAME Expression in Tumors from Screened Patients (N=32) Highlighting Tumor Types (left), Type of Best Overall Response (middle) and Study Cohort (right) 23 Mann - Whitney U test, p=0.076 PRAME RNA expression in pre - treatment biopsies relative to threshold IMA203 has the p otential to provide clin
Slide 24: 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 90% 295 Ovarian Carcinoma 19,900 12,800 80% 4,198 Uterine Carcinoma 62,700 10,700 100% 4,387 Uterine Carcinosa
Slide 25: IMA203 Monotherapy – Conclusions
IMA203 Monotherapy – Conclusions ACTengine® IMA203 Targeting PRAME Offers a Unique Opportunity for Solid Cancer Patients 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 of
Slide 26: ACTengine IMA203CD8 – Next-generation TCR-T
ACTengine® IMA203CD8 – Next - 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 • Recent data from leukaemia patients treated with CAR - T s
Slide 27: IMA203CD8 – Preclinical Assessment of Anti-Tumor Efficacy
ACTengine® IMA203CD8 – Preclinical Assessment of Anti - Tumor Efficacy Functional CD4 T cells Mediate Longer Anti - Tumor Activity than CD8 T cells in vitro 27 0 50 100 150 200 250 300 350 400 450 0.0 0.5 1.0 1.5 2.0 CD8 Hours after Coculture T u m o r f o l d g r o w t h 0 50 100 150 200 250 300 35
Slide 28: Comprehensive PRAME Strategy
Comprehensive PRAME Strategy To Deliver Meaningful Clinical Benefit to Patients with PRAME - positive Cancers 28 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 29: ACTengine IMA201 and IMA204 – TCR-T Targeting MAGEA4/8 and COL6A3
ACTengine® IMA201 and IMA204 – TCR - T Targeting MAGEA4/8 and COL6A3 29
Slide 30: ACTengine IMA201 Targeting MAGEA4/8 Key Features
ACTengine® IMA201 Targeting MAGEA4/8 Key Features 30 HLA - A*02 - presented peptide derived from MAGEA4 and/or MAGEA/8 >5 - fold higher peptide copy number per tumor cell than a commonly used MAGEA4 target Naturally and specifically presented on tumors at high target density 1 : 100 - 1,000 copies/c
Slide 31: ACTengine IMA204 First-in-Class TCR-T Targeting Tumor Stroma
ACTengine® IMA204 First - in - Class TCR - T Targeting Tumor Stroma Key Features 31 HLA - A*02 - presented peptide derived from COL6A3 exon 6 Naturally and specifically presented on tumors at high target density 1 : 100 - 700 copies/cell Novel tumor stroma target identified and validated by XPRESIDE
Slide 32: IMA204 – High Affinity, CD8-independent TCR
ACTengine® IMA204 – High Affinity, CD8 - independent TCR Complete Tumor Eradication in vitro & in vivo 1 by Affinity - enhanced IMA204 TCR CD8 - independent TCR leads to tumor eradication in all mice treated 32 Control IMA204 TCR D7 D16 D22 D29 Affinity maturated CD8 - independent, next - generation
Slide 33: ACTallo – Our Next-generation Off-the-shelf TCR-T
ACTallo® – Our Next - generation Off - the - shelf TCR - T 33
Slide 34: ACTallo – Immatics' Allogeneic Cell Therapy Approach
ACTallo® – Immatics’ Allogeneic Cell Therapy Approach • Off - the - shelf cell therapy , no need for personalized manufacturing reduced logistics and time to application • Potential for hundreds of doses from one single donor leukapheresis lower cost of goods • Use of healthy donor material prov
Slide 35: Why γδ T cells?
Why γδ T cells? γδ T cells Are Well Suited for an Off - the - shelf Cell Therapy Approach 35 γδ T cells x are abundant in the peripheral blood x show intrinsic anti - tumor activity x naturally infiltrate solid tumors & correlate with favorable prognosis x are HLA - independent, thus do not cause gr
Slide 36: TCER — TCR Bispecifics
eoe@ Immatics TCER® — TCR Bispecifics 36
Slide 37: TCER – Next-generation, Half-Life Extended Bispecifics
TCER® – Immatics’ Next - generation, Half - Life Extended Bispecifics Proprietary TCER® Format Consisting of Three Distinct Elements 37 High affinity TCR domains targeting tumor - specific peptide HLA molecules Low affinity T cell recruiter against CD3/TCR Fc part for half - life extension, favorabl
Slide 38: TCER – Next-generation, Half-Life Extended Bispecifics Features
TCER® – Immatics’ Next - generation, Half - Life Extended Bispecifics 38 pHLA targeting TCR x High - affinity (single digit nM ) TCR targeting HLA - restricted tumor - specific peptides x Broad therapeutic window through XPRESIDENT® - guided affinity maturation (>1000x) 1 x Complete tumor eradicatio
Slide 39: Potency of Our Proprietary TCR Bispecific Format TCER
Potency of Our Proprietary TCR Bispecific Format TCER® 39 • 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 specificity 1 than six alternative TCR Bispecific format desig
Slide 40: 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 40 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 Dos
Slide 41: TCER Format Designed for Optimized Efficacy and Safety – Cytokine Release
TCER® Format Is Designed for Optimized Efficacy and Safety Reduced Target - Unrelated Recruiter - Mediated Cytokine Release using a Low - Affinity Recruiter 41 TCER® Whole blood cytokine release assay N= 3 HLA - A*02 - positive donors N=16 cytokines tested, 4 exemplary cytokines shown
Slide 42: Our TCER Portfolio
Our TCER® Portfolio Broad Pipeline of Next - Gen Half - Life Extended TCR Bispecifics 42 TCER® • PRAME peptide presented by HLA - A*02:01 • Start of clinical trial planned for 2023 IMA402 • Undisclosed peptide presented by HLA - A*02:01 • Preclinical PoC studies ongoing IMA403 Potential for addressi
Slide 43: 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 43 0 20 40 60 80 100 120 140 10 -1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] Cytotoxicity [%] ~50 PRAME CpCs 0 0 20 40 60 80 100 120 140 10 -1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402
Slide 44: TCER IMA402 Achieves Durable Tumor Control of Large Tumors in vivo
TCER® IMA402 Achieves Durable Tumor Control of Large Tumors in vivo 44 -29 0 500 1000 1500 2000 2500 0 10 20 30 40 50 60 70 Study day M e d i a n t u m o r v o l u m e [ m m 3 ] Vehicle IMA402 [0.01 mg/kg] IMA402 [0.05 mg/kg] IMA402 [0.25 mg/kg] • Dose - dependent efficacy of IMA402 in cell line - d
Slide 45: Half-life Extended Format of IMA402 Confers Terminal Half-life of >1 Week
Half - life Extended Format of IMA402 Confers Terminal Half - life of >1 Week 45 pHLA – aV L 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 I
Slide 46: Advancing TCER IMA402 Towards Clinical Development
Upcoming activities • CTA/IND submission planned for 2Q 2023 • Start of patient treatment planned in 2023 Advancing TCER® IMA402 Towards Clinical Development Recent and Upcoming Activities 46 IMA402 TCER® Ph1/2 clinical trial in patients with solid tumors Recent activities x Completion of IND - enab
Slide 47: TCER IMA402 Phase 1/2 Clinical Trial to Start in 2023
TCER® IMA402 Phase 1/2 Clinical Trial to Start in 2023 47 MABEL: minimum anticipated biological effect level Phase 1: Dose Escalation Phase 2a: Dose Expansion Basket trial with focus indications Adaptive design aimed at accelerating dose escalation • Specific indications plus ongoing basket • Combin
Slide 48: Accelerated Development of TCER IMA402
Accelerated Development of TCER® IMA402 TCER® IMA402 Phase 1/2 Clinical Trial Design Targeting enhanced treatment convenience • Initially weekly i.v. infusions, potential for early optimization of scheduling based on half - life extended TCER® format • Exploring s.c. application 48 IMA402 MABEL: min
Slide 49: Immatics' Proprietary Target and TCR Discovery Platforms
Immatics’ Proprietary Target and TCR Discovery Platforms 49
Slide 50: 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 50 True Targets via XPRESIDENT® technology platform • are naturally presented on tumor tissues as identified by mass - spec • are absent or presented at only low
Slide 51: Pool of Prioritized Targets as Foundation for Future Value Generation
Technology Pool of 200 Prioritized Targets as Foundation for Future Value Generation 51 200 Prioritized Targets Grouped in 3 Target Classes: 1. Well known and characterized parent protein (20%) e.g. MAGE family cancer testis antigens 2. Unknown or poorly characterized parent protein (60%) e.g. strom
Slide 52: Identification of the Most Relevant Target – MAGEA4/8 Example
Immatics ’ Unique Capability – Identification of the most Relevant Target Example of MAGEA4/8 Peptide Target 52 1 Copy number per tumor cell (CpC) measured on a paired - sample basis by AbsQuant®, i.e. comparing MAGEA4 vs. MAGEA4/A8 peptide pre sentation on same sample, 2 Students paired T test p<0.
Slide 53: Development of the Right TCR – XCEPTOR Technology
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics 53 TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy ACTengine® ACTallo ® • Fast, efficient and highly sensitive discovery of highly specific, natural TCRs • Protein engi
Slide 54: 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 54 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Off - target to
Slide 55: Robust IP Portfolio
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 55 Cancer targets, TCRs and technology protected by: • 5,800 applications and patents filed in all major countries and regions • >115 patent families • >2,000 granted patents, thereof >550 granted patents in the US Technology
Slide 56: Corporate Information & Milestones
Corporate Information & Milestones 56
Slide 57: 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 De
Slide 58: Strong, Focused and Highly Integrated Trans-Atlantic Organization
Strong, Focused and Highly Integrated Trans - Atlantic Organization 58 Houston, Texas ~ 140 FTEs Cell therapy development & manufacturing Munich, Germany ~55 FTEs Various operating functions Tübingen, Germany ~195 FTEs Target & TCR discovery and TCR Bispecifics developme nt Corporate FTE status as o
Slide 59: 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