Immatics N.v. · NASDAQ:IMTX
Immatics — Investor Presentation (October 2022)
61 slides from Immatics's investor presentation, Oct 18, 2022
Slide 1: Immatics Corporate Presentation
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation October 18, 2022
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 O pp o rtun i t y 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
Slide 4: Our TCR-based Approaches Leverage the Full Target Space
Our TCR - based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface 4 I n t r o
Slide 5: Two Distinct TCR-based Therapeutic Modalities in Clinical Development
Two Distinct TCR - based Therapeutic Modalities in Clinical Development 5 Differentiated positioning of ACTengine® vs. TCER® based on patient population, medical need and geographical reach I n t r o 1 Interim data update from the ACTengine® IMA203 TCR - T Phase 1 trial with a 50% (6/12) confirmed O
Slide 6: Our Pipeline of TCR-based Adoptive Cell Therapies and Bispecifics
Our Pipeline of TCR - based Adoptive Cell Therapies and Bispecifics 6 I n t r o 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion; 2 Opdivo® (nivolumab): programmed death - 1 (PD - 1) immune checkpoint inhibitor; * Immatics proprietary ACTallo® platform utilizing Editas’ CRISPR gene editing tech
Slide 7: Strategic Collaborations
Strategic Collaborations Synergistic Expertise that Can Foster Transformative Innovations for ACT and Bispecifics 7 Research collaboration to develop bispecific immunotherapies 3 Immatics targets $54 M upfront Co - promotion option Broadening the clinical framework beyond our pipeline Research colla
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 I M A 203
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 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 toxici
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® M a nu f ac tur i ng by Immatics Infusion of ACTengine® T cell Product Lymphodepletion 30 mg/m 2 Fludarabine 1 and 500 mg/m
Slide 12: IMA203 TCR-T Phase 1 Design
First pt treated Aug 2022; First 3 pts on DL3 * IMA203 TCR - T Phase 1 Design Three Phase 1b Expansion Cohorts to Establish Durable Objective Responses Each expansion cohort is designed to establish safety, evaluate the observed objective response rate, demonstrate durability & provide the trigger f
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
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 confirme
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: Objective response rate (partial responses) according to RECIST 1.1 at first scan post infusion (~6 weeks)
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 target lesions were not evaluable; PD: Progressive disease; SD: Stable disease; PR: Partial response; cPR: Confirmed partial respo
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 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: 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) 22 Mann - Whitney U test, p=0.076 PRAME RNA expression in pre - treatment biopsies relative to threshold IMA203 has the potential to provide clini
Slide 23: PRAME Expression – RNAseq Data and Mass Spectrometry-guided Threshold
PRAME Expression – RNAseq Data Combined with Immatics’ Mass Spectrometry - guided RNA Threshold for Prevalence Prediction 23 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
Slide 24: 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 24 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 25: IMA203 Monotherapy – Conclusions
IMA203 Monotherapy – Conclusions ACTengine® IMA203 Targeting PRAME Offers a Unique Opportunity for Solid Cancer Patients 25 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 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 .0 0 .5 1 .0 1 .5 2 .0 CD8 0 50 100 150 200 250 300 350 400 450 Hours after Coculture Tumor fold growth 0 .0 0 .5 1.0 1 .5 2 .0 CD4 0 50 1
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 W Si Do ild t ngl ub l ype e e m muta n u t a n t t T u N mo o n - t r c ra n ells o s du
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: Immatics and Bristol Myers Squibb – Allogeneic Collaboration
Immatics and Bristol Myers Squibb – Allogeneic Multi - program Collaboration Leveraging Complementary Technologies & Capabilities for the Benefit of Cancer Patients 36 Off - the - shelf allogeneic TCR - T/CAR - T therapies for patients with solid cancers Activities for initial 2 BMS programs: Clinic
Slide 37: TCER – TCR Bispecifics
aoe immatics TCER® — TCR Bispecifics
Slide 38: TCER – Mechanism of Action
TCER® – Mechanism of Action Immatics’ Off - the - Shelf TCR Bispecifics Approach 38 T CE R ®
Slide 39: TCER – Immatics' Half-Life Extended Bispecifics
TCER® – Immatics’ Half - Life Extended Bispecifics 39 pHLA targeting TCR x High - affinity TCR targeting HLA - restricted tumor - specific peptides x Broad therapeutic window through XPRESIDENT® - guided affinity maturation (>1000x) 1 x Complete tumor eradication in mouse xenograft models at low dos
Slide 40: Potency of Our Proprietary TCR Bispecific Format TCER
Potency of Our Proprietary TCR Bispecific Format TCER® 40 • 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 41: TCER Format Designed for Optimized Efficacy and Safety
TCER® Format Is Designed for Optimized Efficacy and Safety Superior Tumor Control Using a Novel, Low - Affinity Recruiter 41 n = 6 mice/treatment group, n = 10 mice in vehicle group, 2 donors/group Dose : 0 . 025 mg/kg Proprietary, low - affinity T cell recruiting region demonstrates superior tumor
Slide 42: TCER 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 42 T CE R ® Whole blood cytokine release assay N=3 HLA - A*02 - positive donors N=16 cytokines tested, 4 exemplary cytokines shown
Slide 43: TCER Portfolio
TCER® Portfolio Building a Pipeline of Next - Gen Half - Life Extended TCR Bispecifics 43 IMA401 I M A 402 IMA40X MAGEA4/8 PR A ME Undisclosed targets Status Start of Phase 1 trial in May 2022 Submission of CTA/IND application 2Q 2023, Phase 1/2 trial in 2023 TCER® engineering and preclinical testin
Slide 44: Phase 1 Clinical Trial to Evaluate TCER IMA401
Phase 1 Clinical Trial to Evaluate TCER® IMA401 Targeting MAGEA4/8 44 MTD: maximum tolerated dose, RP2D: recommended phase 2 dose; MABEL: minimum anticipated biological effect level; BLRM: Bayesian logistic regression model; 1 Pharmacokinetics data assessed throughout the trial might provide an oppo
Slide 45: TCER IMA401 Targeting MAGEA4/8
TCER® IMA401 Targeting MAGEA4/8 Product Candidate in Clinical Development with Bristol Myers Squibb 45 Treatment schedule Tumor Model in Mice 1 8 1 5 22 T r a n s p l a n t a t i o n Tumor T r a n s p l a n t a t i o n Human PBMC IMA401 TCER ® - 22 - 12 1 • Complete remissions observed in all animal
Slide 46: 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 46 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] ~50 PRAME CpCs 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] Cytotoxic
Slide 47: TCER IMA402 Achieves Durable Tumor Control in vivo
TCER® IMA402 Achieves Durable Tumor Control of Large Tumors in vivo 47 - 2 9 0 50 0 100 0 150 0 200 0 250 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 Study day Median tumor volume [mm 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 - der
Slide 48: Half-life Extended Format of IMA402
Half - life Extended Format of IMA402 Confers Terminal Half - life of >1 Week 48 pHLA – aFc Assay pHLA – aV L 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 49: TCER IMA402 Phase 1/2 Clinical Trial to Start in 2023
TCER® IMA402 Phase 1/2 Clinical Trial to Start in 2023 49 MABEL: minimum anticipated biological effect level; BLRM: Bayesian logistic regression model; MTD: maximum tolerated dose, RP2D: recommended phase 2 dose; # Pharmacokinetics data assessed throughout the trial might provide an opportunity to o
Slide 50: Immatics' Proprietary Target and TCR Discovery Platforms
Immatics’ Proprietary Target and TCR Discovery Platforms 50
Slide 51: 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 51 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 52: Immatics' Unique Capability – Identification of the most Relevant Target
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 presentation on same sample, 2 Students paired T test p<0.00
Slide 53: Pool of Prioritized Targets as Foundation for Future Value Generation
T e chn olo g y Pool of 200 Prioritized Targets as Foundation for Future Value Generation 53 200 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.
Slide 54: Development of the Right TCR – XCEPTOR Technology
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics 54 TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy A C T e n g i n e® ACTallo® • Fast, efficient and highly sensitive discovery of highly specific, natural TCRs • Prote
Slide 55: 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 55 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Of f - t a r ge
Slide 56: Corporate Information & Milestones
Corporate Information & Milestones 56
Slide 57: Experienced Global Leadership Team
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 Development Officer >20 yrs pharma & biotech experience (Micromet, Roche, Fresenius) Cedrik
Slide 58: Strong, Focused and Highly Integrated Trans-Atlantic Organization
Strong, Focused and Highly Integrated Trans - Atlantic Organization 58 Munich, Germany, ~55 FTEs Various operating functions Tübingen, Germany, ~195 FTEs Target & TCR discovery and TCR Bispecifics developme nt Houston, Texas, ~140 FTEs Cell therapy development and manufacturing Corporate FTE status
Slide 59: Robust IP Portfolio
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 59 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 >500 granted patents in the US Corporate
Slide 60: Near-Term Value Drivers
Near - Term Value Drivers Clinical Development of TCR - T and TCR Bispecifics 60 Advance clinical development of ACTengine® IMA203 candidates • Multiple IMA203 Ph1b expansion cohorts: Monotherapy, checkpoint combination, 2nd - gen approach IMA203CD8 • Next data read - outs with meaningful data acros
Slide 61: 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