Immatics N.v. · NASDAQ:IMTX
Immatics — Investor Presentation (November 2022)
60 slides from Immatics's investor presentation, Nov 17, 2022
Slide 1: Immatics Corporate Presentation
Immatics Corporate Presentation November 17, 2022 Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution.
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
Slide 3: Building a Leading TCR Therapeutics Company
Building a Leading TCR Therapeutics Company Two Clinical-Stage Clinical PoC for Differentiated Therapeutic Strategic Solid Modalities Cell Therapy Platforms Opportunity Partnerships Cash Runway Pipeline of TCR-T and High rate of confirmed Unique technologies Potential for addressing World-leading To
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 Intro 4
Slide 5: Two Distinct TCR-based Therapeutic Modalities in Clinical Development
Two Distinct TCR-based Therapeutic Modalities in Clinical Development Autologous TCR-T (ACTengine®) TCR Bispecifics (TCER®) • Strong clinical activity in patients • Off-the-shelf biologic for with high tumor burden1 immediate treatment • Single dose2 • Repeat dosing • Proprietary manufacturing proce
Slide 6: Our Pipeline of TCR-based Adoptive Cell Therapies and Bispecifics
Our Pipeline of TCR-based Adoptive Cell Therapies and Bispecifics Modality Product Candidate Target Preclinical Phase1a1 Phase1b1 Phase 2 Phase 3 ACTengine ® IMA203 PRAME + Checkpoint Inhibitor2 ACTengine® IMA203CD8 PRAME Autologous ACT ACTengine® IMA201 MAGEA4/8 ACTengine® IMA204 COL6A3 Multiple pr
Slide 7: ACTengine IMA203 – TCR-T Targeting PRAME
ACTengine® IMA203 – TCR-T Targeting PRAME 7
Slide 8: ACTengine IMA203 Targeting PRAME – Mechanism of Action
ACTengine® IMA203TargetingPRAME – Mechanism of Action Immatics’ Leading TCR-T Approach IMA203 8
Slide 9: Multi-Tumor Target PRAME Promising Opportunity for TCR-based Therapies
Multi-Tumor Target PRAME Promising Opportunity for TCR-based Therapies PRAME RNA detection in tumor samples (ISH) PRAME Peptide Target SqNSCLC Ovarian Cancer • HLA-A*02:01 presented peptide identified by XPRESIDENT® quant. mass spectrometry TUMOR CELL • Presented at high target density in tumor tiss
Slide 10: ACTengine IMA203 – Patient Flow
ACTengine® IMA203–Patient Flow Treatment & Observation Phase Long Term Screening & Manufacturing Phase Follow-up Safety and efficacy monitoring for 12 months Infusion of ACTengine® HLA-A*02 Testing Leuka- T cell Product Blood sample; Central lab pheresis LowdoseIL-2 1m IU daily days 1-5 and x x ACTe
Slide 11: IMA203 TCR-T Phase 1 Design
IMA203 TCR-T Phase1Design Three Phase 1b Expansion Cohorts to Establish Durable Objective Responses Phase 1b Dose Expansion Interim Update Oct 10, 2022 IMA203 Monotherapy at Target Dose (plus DL5)1 First pt treated Phase 1a: all 27 patients CohortA 2 March 2022 Phase 1b cohort A: 5 patients Increasi
Slide 12: Moving from Phase 1a to Phase 1b
Moving from Phase1atoPhase1b Continuous Improvement of Key Aspects that May Influence Clinical Outcome Our Focus in Phase 1b Our Focus in Phase 1a • Safety • Safety • Durability of response at 6 • Biological activity months and beyond to pave the • Initial signs of clinical activity way for registra
Slide 13: ACTengine IMA203 – Interim Monotherapy Update
ACTengine® IMA203–Interim Monotherapy Update Phase 1a Phase 1b Cohort A Key Take Aways Dose Escalation Data Initial Data IMA203 Monotherapy from 27 Patients from 5 Patients • Acceptable & manageable • Acceptable & manageable • Favorable tolerability profile treatment-emergent TEAEs • Confirmed respo
Slide 14: IMA203 Monotherapy – Patient and Product Characteristics
ACTengine® IMA203Monotherapy –Patient and Product Characteristics Phase 1a Phase1b(CohortA) IMA203 Dose Levels Dose Escalation Dose Expansion All pts(DL1 4) DL4pts only Allpts (DL4/DL5) Phase 1b Phase 1a Patients treated 27 7 5 Prior lines of treatment 4.2 4.6 4.0 Mean (min, max) (1, 8) (1, 7) (1, 1
Slide 15: 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 experienced CR
Slide 16: Frequency of Observed Objective Responses
Frequency of Observed Objective Responses Improved ORR and Confirmed ORR at Higher Dose and in Phase 1b Cohort A Phase 1a Phase 1a + Phase 1b Phase 1b only 1 1 1 All pts (DL1-4) DL4 pts only DL4/DL5 pts only All pts (DL4/DL5) Patients Treated 27 7 12 5 ORR (~6 weeks)2 48% (13/27) 57% (4/7) 67% (8/12
Slide 17: Best Overall Response
Best Overall Response IMA203 Continues to Deliver Objective Responses in Major Solid Tumor Types Phase 1a (Dose Escalation) Phase 1b (Cohort A) N=27# N=5 Confirmed objective responses across a broad spectrum of different tumor types such as cutaneous melanoma, uveal melanoma, head and neck cancer, o
Slide 18: Responses over Time
Responses over Time Encouraging Early Signs for Improved Durability at Higher Dose and in Phase 1b Patients Phase 1a (Dose Escalation) Phase 1b (Cohort A) N=27# N=5 Best overall response (RECIST1.1) Data cut-off – 06-Sept-2022 IMA203 # Synovial sarcoma patient (DL3) PD at week 6 not shown as target
Slide 19: Translational Data Consistent with Clinical Outcomes
Translational Data Consistent with Clinical Outcomes Supporting Proposed Mechanism of Action for IMA203 High IMA203 T cell engraftment and IMA203 T cell infiltration into tumor persistence in peripheral blood correlates with objective responses1 Persistence over time Peak frequency 7 1×106 1×10 1.5×
Slide 20: ACTengine IMA203 Product Manufacturing
ACTengine® IMA203Product Manufacturing Targeting Higher Robustness, Favorable Product Attributes, Faster Turn Around Time Accelerated Product Release ACTengine® clinical programs: ~3weeks Manufacturing time QC testing (~1 week) (Full sterility, 2 weeks) FasterACTengine®:expected ~2weeks Manufacturin
Slide 21: PRAME Expression in Tumors from Screened Patients
PRAME Expressionin Tumors from Screened Patients(N=32) Highlighting Tumor Types (left), Type of Best Overall Response (middle) and Study Cohort (right) p=0.076 p=0.076 in p=0.076 threshold to expression RNA relative IMA203 achieved PRAME biopsies objective responses at all expression levels above Im
Slide 22: PRAME Expression – RNA seq Data and Mass Spectrometry-guided Threshold
PRAME Expression – RNA seq Data Combined with Immatics’ Mass Spectrometry-guided RNA Threshold for Prevalence Prediction Immatics’ proprietary mass spectrometry- % PRAME guidedRNA threshold positive patients1 100% 100% 100% 95% 50%* 80% 65% 60% 25% 1 PRAME target prevalence is based on TCGA RNA seq
Slide 23: IMA203 TCR-T Has the Potential to Reach a Large Patient Population
IMA203 TCR-T Has the Potentialto Reacha Large Patient Population ~39,000 Patients per Year in the US only Patient Population Selected Indications Incidence R/R Incidence PRAME Positive Based on R/R Incidence; PRAME and HLA-A*02:01+ Cut. Melanoma 99,800 7,700 95% 2,999 st Initial indications of in te
Slide 24: 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 di
Slide 25: ACTengine IMA203CD8 – Next-generation TCR-T
ACTengine® IMA203CD8–Next-generationTCR-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 T cell anti-tumor activity in TCR-T trials Help CD4TCELL • Recent data from leukaemia patients treated with CAR-T
Slide 26: ACTengine 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 CD8 CD4 2.0 6th 2.0 5th 1.5 1.5 2nd addition 4th 5th 6th of tumor cells nd 4th growth 2 addition growth 3rd of tumor cells 1.0 1.0 fold 3rd fold Tumo
Slide 27: Comprehensive PRAME Strategy
Comprehensive PRAME Strategy To Deliver Meaningful Clinical Benefit to Patients with PRAME-positive Cancers Phase 1b Dose Expansion Upcoming Value Inflection Points for Our PRAME Programs IMA203 Monotherapy 1 First pt treated CohortA at Target Dose (plus DL5) March 2022 Increasing Tcell:TumorcellRat
Slide 28: ACTengine IMA201 and IMA204 – TCR-T Targeting MAGEA4/8 and COL6A3
ACTengine® IMA201 and IMA204 – TCR-T Targeting MAGEA4/8 and COL6A3 28
Slide 29: ACTengine IMA201 Targeting MAGEA4/8
ACTengine® IMA201TargetingMAGEA4/8 Key Features TARGET TCR CLINICALDATA PATIENT POPULATION3 HLA-A*02-presented peptide High-affinity, specific TCR Doseescalation on going, Sarcoma Subtypes – up to 80% derived from MAGEA4 and/or targeting MAGE4/8 target dose level to commence Squamous NSCLC – 50% MAG
Slide 30: ACTengine IMA204 First in Class TCR-T Targeting Tumor Stroma
ACTengine® IMA204 First in Class TCR T Targeting Tumor Stroma Key Features TARGET TCR PRECLINICALDATA PATIENT POPULATION3 HLA A*02 presented peptide High affinity,specific TCR CD8 independent, next Pancreatic Carcinoma – 80% derived from COL6A3 exon 6 targeting COL6A3 exon 6 generation TCR engages b
Slide 31: ACTengine IMA204 – High Affinity, CD8-independent TCR
ACTengine® IMA204–HighAffinity, CD8-independentTCR Complete Tumor Eradication in vitro & in vivo1 by Affinity-enhanced IMA204 TCR Stroma Target (COL6A3 exon 6) Example of a Tumor Target IMA204 TCR in Ovarian Cancer sample in same Ovarian Cancer sample Control D7 Stroma D16 cells D22 Tumor cells D29
Slide 32: ACTallo – Our Next-generation Off-the-shelf TCR-T
ACTallo® – Our Next-generation Off-the-shelf TCR-T 32
Slide 33: ACTallo – Immatics' Allogeneic Cell Therapy Approach
ACTallo® – Immatics ’Allogeneic Cell Therapy Approach Tcell 1 T cell Collection Cell Engineering Expansion Off the shelf Patient from Healthy Donor (gene editing & enhancements) Products Treatment • Off the shelf cell therapy, no need for personalized manufacturing reduced logistics and time to appl
Slide 34: 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 Expansion Invitro anti-tumor activity  show intrinsic anti-tumor activity 1000000 15  naturally infiltrate solid tumors & tumor cells only 100000 cell
Slide 35: 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 Off-the-shelf allogeneic TCR-T/CAR-T therapies Immatics for patients with solid cancers Bristol Myers Squibb Innovative γδ-derived Comp
Slide 36: TCER – TCR Bispecifics
TCER® – TCR Bispecifics 36
Slide 37: TCER – Mechanism of Action
TCER® – Mechanism of Action Immatics’ Off-the-Shelf TCR Bispecifics Approach TCER® 37
Slide 38: TCER – Immatics' Half-Life Extended Bispecifics
TCER® – Immatics ’Half-Life Extended Bispecifics pHLA targeting TCR  High-affinity TCR targeting HLA-restricted tumor-specific peptides TCER®  Broad therapeutic window through XPRESIDENT® -guided affinity maturation (>1000x)1 ƒ¼ Complete tumor eradication in mouse xenograft models at low doses
Slide 39: Potency of Our Proprietary TCR Bispecific Format TCER
Potency of Our Proprietary TCRBi specific Format TCER® Killing of target-positive cells by different TCR Bispecifics TCER® 2+1 TCR bispecific format: High potency was linked to a significantly reduced specificity profile • Seven different TCR Bispecific formats were evaluated with a pHLA targeting T
Slide 40: TCER Format Designed for Optimized Efficacy and Safety: Tumor Control
TCER® Format Is Designedfor Optimized EfficacyandSafety Superior Tumor Control Using a Novel, Low-Affinity Recruiter Tumor Model in Mice1 Widely used T cell recruiting Ab (3 variants) medium to high affinity (single to double digit nM) Immatics’ T cell recruiting Ab low affinity (triple digit nM) n
Slide 41: TCER Format: Reduced Recruiter-Mediated Cytokine Release
TCER® Format Is Designedfor Optimized EfficacyandSafety Reduced Target-Unrelated Recruiter-Mediated Cytokine Release using a Low-Affinity Recruiter Whole blood cytokine release assay N=3 HLA-A*02-positive donors N=16 cytokines tested, 4 exemplary cytokines shown TCER® 41
Slide 42: TCER Portfolio
TCER® Portfolio Building a Pipeline of Next-Gen Half-Life Extended TCR Bispecifics IMA401 IMA402 IMA40X MAGEA4/8 PRAME Undisclosed targets Start of Phase 1 trial Submission of CTA/IND application TCER® engineering and Status in May 2022 2Q 2023, Phase 1/2 trial in 2023 preclinical testing ongoing Pr
Slide 43: Phase 1 Clinical Trial to Evaluate TCER IMA401 Targeting MAGEA4/8
Phase 1 Clinical Trialto Evaluate TCER® IMA401TargetingMAGEA4/8 Phase 1a: Dose Escalation Phase 1b: Dose Expansion Primary Objective • Determine MTD and/or RP2D Monotherapy expansion cohort Adaptive design MTD/ aimed at accelerating RP2D dose escalation Potential development option for Secondary Obj
Slide 44: TCER IMA401 Targeting MAGEA4/8
TCER® IMA401 TargetingMAGEA4/8 Product Candidate in Clinical Development with Bristol Myers Squibb Treatment schedule Tumor Model in Mice1 Transplantation Tumor Transplantation Human PBMC IMA401 TCER® -22 -12 1 8 15 22 Study day N=6 mice per group, two PBMC donors Dose: two dose levels • Complete re
Slide 45: TCER IMA402 Targeting PRAME – Efficacy Assessment in vitro
TCER® IMA402 Targeting PRAME–Efficacy Assessmentinvitro Tumor Cell Killing at Low Physiological PRAME Peptide Levels 140 140 Target-negative 120 ~50 PRAME CpCs 120 [%] 100 • TCER® IMA402 induces killing of tumor cells 100 80 80 target copies as50 CpCs with PRAME aslow 60 60 40 40 Cytotoxicity 20 20
Slide 46: TCER IMA402 Achieves Durable Tumor Control of Large Tumors in vivo
TCER® IMA402 Achieves Durable Tumor Control of Large Tumorsinvivo ] 2500 3 • Dose-dependent efficacy of IMA402 in cell [mm 2000 line-derived in vivo mouse model 1500 volume • Durable shrinkage of large tumors including Vehicle 1000 IMA402 [0.01 mg/kg] tumor IMA402 [0.05 mg/kg] complete responses ove
Slide 47: Half-life Extended Format of IMA402 Confers Terminal Half-life >1 Week
Half-life ExtendedFormatofIMA402ConfersTerminalHalf-lifeof>1 Week pHLA – aVL Assay • IMA402 shows a terminal serum half-life of â‰^ 8 days in mice pHLA – aFc Assay • IMA402 will be initially dosed weekly in the clinical trial • Dosing frequency may be adapted based on clinical data IMA402 47
Slide 48: TCER IMA402 Phase 1/2 Clinical Trial to Start in 2023
TCER® IMA402 Phase1/2ClinicalTrial to Startin2023 CMC and supply activities on track for clinical trial • Manufacturing process development completed • High titer (>3.5 g/L) and good stability allowing liquid formulation Trial Overview Phase 1: Dose Escalation Phase 2a: Dose Expansion Expansion coho
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 + True Targets via XPRESIDENT® technology platform Right TCRs via XCEPTOR® technology platform • are naturally presented on tumor tissues as identified by mass-spec •
Slide 51: Immatics' Unique Capability – Identification of the most Relevant Target
Immatics’ Unique Capability–Identification of the most Relevant Target Example of MAGEA4/8 Peptide Target Ranking of p<0.0012 pHLA targets XPRESIDENT® quantitative information on MAGEA4/8 target is presented at target density1 between peptides originating >5-fold higher target density1 than a from t
Slide 52: Pool of Prioritized Targets as Foundation for Future Value Generation
Pool of 200 Prioritized Targets as Foundation for Future Value Generation 200 Prioritized Targets pHLA Database based on primary tissues Grouped in 3 Target Classes: 1. Well known and characterized parent protein (20%) e.g. MAGE family cancer testis antigens >2,500 cancer & normal tissues analyzed b
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 Adoptive Cell Therapy TCR Bispecifics ACTengine® T cell engaging ACTallo® receptor (TCER®) Micromolar affinity Nanomolar affinity • Fast, efficient and highly sensitive discovery of highly spec
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 Target peptide Target peptide Similar peptide A different HLA is presented presented presented recognized on tumor cells on normal cel
Slide 55: Corporate Information & Milestones
Corporate Information & Milestones 55
Slide 56: Experienced Global Leadership Team Across Europe and the US
Experienced Global Leadership Team Across Europe and theUS Harpreet Singh Arnd Christ Carsten Reinhardt Chief Executive Officer Chief Financial Officer Chief Development Officer Co-Founder >20 yrs biotech experience >20 yrs pharma & biotech experience >20 yrs biotech experience (InflaRx, Medigene, N
Slide 57: Strong, Focused and Highly Integrated Trans-Atlantic Organization
Strong, Focused and Highly Integrated Trans-Atlantic Organization Tübingen, Germany, ~195 FTEs Target & TCR discovery and TCR Bispecifics development Houston, Texas, ~140 FTEs Cell therapy development and manufacturing Munich, Germany, ~55 FTEs Various operating functions Corporate FTE status as of
Slide 58: Robust IP Portfolio
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 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 58
Slide 59: Near-Term Value Drivers
Near-Term Value Drivers Clinical Development of TCR-T and TCR Bispecifics 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 across all cohor
Slide 60: Delivering the Power of T cells to Cancer Patients
Delivering the Power of T cells to Cancer Patients www.immatics.com © Immatics. Not for further reproduction or distribution.