Immatics N.V 6-K, filed Oct 18, 2022
Immatics N.V. (IMTX)
About this 6-K
Immatics N.V filed this 6-K on October 18, 2022.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR 15d-16 UNDER THE SECURITIES EXCHANGE ACT OF 1934
October 18, 2022
Commission File Number: 001-39363
IMMATICS N.V.
Paul-Ehrlich-Straße 15
72076 Tübingen, Federal Republic of Germany
(Address of principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F:
| Form 20-F | ☒ | Form 40-F | ☐ |
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K
On October 18, 2022, Immatics N.V. (the “Company”) made available an updated investor presentation on its website, a copy of which is attached hereto as Exhibit 99.1. The fact that this presentation is being made available and filed herewith is not an admission as to the materiality of any information contained in the presentation. The information contained in the presentation is being provided as of October 18, 2022 and the Company does not undertake any obligation to update the presentation in the future or to update forward-looking statements to reflect subsequent actual results.
EXHIBIT INDEX
| Exhibit No. | Description |
| 99.1 | Presentation dated October 18, 2022 |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| IMMATICS N.V. | ||
| Date: October 18, 2022 | ||
| By: | /s/ Harpreet Singh | |
| Name: | Harpreet Singh | |
| Title: | Chief Executive Officer | |
Exhibit 99.1
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation October 18, 2022
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 control persons, officers, directors, employees or representatives makes any representation or warranty, express or implied, as to the accuracy, completeness or reliability of the information contained in this Presentation . Forward - Looking Statements . Certain statements in this presentation may be considered forward - looking statements . Forward - looking statements generally relate to future events or the Company’s future financial or operating performance . For example, statements concerning timing of data read - outs for product candidates, the timing of IND or CTA filing for pre - clinical stage product candidates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward - looking statements . In some cases, you can identify forward - looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology . Such forward - looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements . These forward - looking statements are based upon estimates and assumptions that, while considered reasonable, Immatics and its management, are inherently uncertain . New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties . Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual report on Form 20 - F and other filings with the Securities and Exchange Commission (SEC) . Nothing in this presentation should be regarded as a representation by any person that the forward - looking statements set forth herein will be achieved or that any of the contemplated results of such forward - looking statements will be achieved . You should not place undue reliance on forward - looking statements, which speak only as of the date they are made . The Company undertakes no duty to update these forward - looking statements . No Offer or Solicitation . This communication is for informational purposes only and does not constitute, or form a part of, an offer to sell or the solicitation of an offer to sell or an offer to buy or the solicitation of an offer to buy any securities, and there shall be no sale of securities, in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction . No offer of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933 , as amended, or in an offering exempt from registration . Certain information contained in this Presentation relates to or is based on studies, publications, surveys and the Company’s own internal estimates and research . In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions . Finally, while the Company believes its internal research is reliable, such research has not been verified by any independent source . All the scientific and clinical data presented within this presentation are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification . 2
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 I n t r o Clinical PoC for Cell Therapy High rate of confirmed objective responses across multiple solid tumors in early TCR - T clinical development Di f f e r e n t i a t ed Platforms Unique technologies to identify true cancer targets and right TCRs Strategic P a rtn e r sh i p s World - leading industry players with synergistic expertise Solid Cash Runway To reach multiple value inflections points across our portfolio
Our TCR - based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface 4 I n t r o
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 ORR target dose or above with at least 1 billion infused TCR - T cells across several solid tumor indications, 80% (4/5) confirmed ORR in Phase 1b patients only; 2 Repeat dosing without re - manufacturing possible TCR Bispecifics (TCER®) • Off - the - shelf biologic for immediate treatment • Repeat dosing • All hospitals and out - patient, opportunity for larger patient reach • Favorable commercial characteristics • Target requirements: strong tumor association, median to high copy numbers Autologous TCR - T (ACTengine®) • Strong clinical activity in patients with high tumor burden 1 • Single dose 2 • Proprietary manufacturing process for enhanced potency of T cells • Specialized medical centers • Target requirements: stringent tumor selectivity, low, medium, high copy numbers
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 technology Modality Product Candidate Target Preclinical Phase 1a 1 Phase 1b 1 Phase 2/3 ACTengine® Autologous ACT IMA203 PRAME + Ch eckpoint Inhibitor 2 IMA203CD8 PRAME IMA201 MAGEA4/8 IMA204 COL6A3 Autologous ACT 4 programs Undisclosed 2 programs Undisclosed ACTallo® Allogeneic ACT γδ T cells IMA30x Undisclosed * 2 programs Undisclosed TCER® Bispecifics IMA401 MAGEA4/8 IMA402 PRAME IMA40x Undisclosed Bispecifics 3 programs Undisclosed
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 collaboration to develop TCR - T therapies 4 Immatics targets (3 in 2019 + 1 in 2022) $75 M (2019) + $20 M (2022) upfront; Opt - in rights for BMS Co - development/Co - fund option Research collaboration to develop TCR - T therapies 2 Immatics targets $50 M upfront Co - development option Clinical co - development collaboration to develop Immatics’ TCR Bispecific program TCER® IMA401 $150 M upfront Co - promotion option in the US Research collaboration to develop off - the - shelf allogeneic γδ - based TCR - T/ CAR - T programs $60 M upfront 2022 2018 2019 2020 2021 Each of our 12 partnered programs may be eligible for • >$500 million aggregated milestone payments • Tiered royalties I n t r o
ACTengine® IMA203 – TCR - T Targeting PRAME 8
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ Leading TCR - T Approach 9 I M A 203
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 toxicity screening against normal tissue peptides selected from our immunopeptidome database to retain specificity Indication % PRAME positive patients 1 Uterine Carcinoma Uterine Carcinosarcoma Sarcoma Subtypes Cut. Melanoma Uveal Melanoma 2 Ovarian Carcinoma Squamous NSCLC T N B C Small Cell Lung Cancer Kidney Carcinoma C ho l an g io c ar c ino m a Adeno NSCLC Breast Carcinoma H N SCC Esophageal Carcinoma H CC Bladder Carcinoma 100% 100% up to 100% 95% 50% 80% 65% 60% 55% up to 45% 35% 25% 25% 25% 20% 20% 20% TUMOR CELL T CELL HLA - A*02:01 PRAME TCR PRAME Pep ೦ de SqNSCLC Ovarian Cancer PRAME RNA detection in tumor samples (ISH) 1 PRAME target prevalence is based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; 2 TCGA: early & late - stage primary tumor samples, Immatics clinical trials: late - stage/metastatic tumor samples, Role of PRAME in metastasis of uveal melanoma: Field et al. 2016 Clinical Cancer Research; NSCLC: Non - small cell lung cancer, TNBC: Triple - negative breast cancer, HNSCC: Head and neck squamous cell carcinoma; HCC: Hepatocellular carcinoma Uterine Carcinoma Cut . Melanoma Uveal Melanoma 2 Ovarian Carcinoma 90% 95% 90% 70% • 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 - specific, not expressed in normal tissue at relevant levels • Highly prevalent across many solid cancers • Patient screening data from Immatics’ clinical trials support high prevalence of PRAME: I M A 203
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 2 Cyclophosphamide for 4 days Target Profiling Fresh Tumor Biopsy; IMADetect® Low dose IL - 2 1m IU daily days 1 - 5 and twice daily days 6 - 10 * Safety and efficacy monitoring for 12 months I M A 203 * IL - 2 dose reduction from twice daily to daily for the first 5 days and dosing duration from 14 to 10 days introduced prior to treatment of first patients on dose level 3; 1 Dose reduction of Fludarabine (from 40mg/m 2 to 30mg/m 2 ) was introduced prior to treatment of the first patient on dose level 3 Leuka - ph e r e s is I M A 203 x x E xpr e ss i on Antigen 1 2 3
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 for registration trials 12 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 Checkpoint Inhibitor 3 Blocking PD - 1/PD - L1 pathway Cohort C IMA203 Monotherapy in Basket Trial Completed & provisional RP2D 1 determined in March 2022 First pt treated March 2022 First pt treated May 2022 I M A 203 Interim Update Oct 10, 2022 Phase 1a: all 27 patients Phase 1b cohort A: 5 patients 1 RP2D (target dose) determined at DL4, exploration of higher dose (DL5) ongoing; 2 Demonstrated to be associated with durable response: Locke et al. 2020 Blood Advances; 3 Opdivo® (nivolumab): programmed death - 1 (PD - 1) immune checkpoint inhibitor; * Treatment of n=3 patients ongoing in DL3 prior to patient treatment at Target Dose (DL4), exploration of higher dose (DL5) planned; 4 Demonstrated to be important for long - term remission: Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances IMA203CD8 2nd Gen at Target Dose (plus DL5) * Adding functional CD4 T cells 4
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 registration trials We continue to improve key determinants as we move from Phase 1a into Phase 1b 1. Higher T cell dose: Only RP2D or exploratory DL5 2. Enhanced cell product: Implementation of manufacturing enhancements (e.g. monocyte depletion, see appendix) focusing on robustness, quality, and speed of product release 3. “Real life” patients: Working with more disease area experts to reduce the fraction of very heavily pre - treated patients with extreme disease burden who have exhausted standard of care and have undergone multiple clinical trials I M A 203
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 confirmed ORR: Confirmed objective response rate (confirmed partial responses) according to RECIST 1.1 at second scan post infusion (~12 weeks), 14 1 patient with SD at ~ 6 - week scan with pending ~12 - week scan considered as non - responder for confirmed ORR; * Total transduced viable CD8 T cells, all patients in Phase 1a DL4 and Phase 1b DL4/DL5; RPD2: Recommended Phase 2 dose; DL: Dose level • Acceptable & manageable treatment - emergent adverse events (TEAEs) • DL4 defined as provisional RP2D • 48% (13/27) initial ORR 1 across all doses and multiple solid cancers • Limited number of confirmed responses • Acceptable & manageable TEAEs • Patients treated at RP2D (DL4) and exploratory DL5 • 80 % ( 4 / 5 ) initial ORR 1 in patients with 4 different solid tumors • 80% (4/5) confirmed ORR 2 : Confirmation of all objective responses after ~3 months; all responses ongoing • Favorable tolerability profile • Confirmed responses in multiple heavily pre - treated solid tumor types (cut. melanoma, uveal melanoma, head and neck cancer, ovarian cancer, synovial sarcoma) • Positively evolving durability profile for IMA203 » above 1 bn TCR - T cells (DL4/5) * in phase 1a and phase 1b: 50% (6/12) confirmed ORR 2 » in phase 1b patients only : 80% (4/5) confirmed ORR 2 Data cut - off – 06 - Sept - 2022 I M A 203
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 ULN [% of patients] 66.7 85.7 40.0 Baseline tumor burden Mean target lesion sum of diameter [mm] (min, max) 130.3 (29.0, 219.7) 115.8 (37.0, 197.6) 55.2 (21.0, 102.9) Dose Mean transduced viable CD8 T cells infused [x10 9 ] (min, max) 0.65 (0.08, 2.09) 1.48 (1.07, 2.09) 2.22 (1.30, 4.16) Manufacturing Process Prior versions 1 Current version IMA203 Dose Levels 1 Except for 1 product for patient at DL3 generated with current manufacturing process; * DL4: 200m to 1.2bn transduced viable CD8 T cells per m 2 BSA, all patients in DL4 received cell doses in the upper tier of DL4, above DL3; ** DL5: up to 4.7bn transduced viable CD8 T cells per m 2 BSA; ULN: Upper limit of normal; BSA: Body surface area; RP2D: Recommended Phase 2 dose; LHD: Lactate dehydrogenase 32 heavily pre - treated patients, thereof 12 patients at target dose or above , were infused with IMA203 TCR - T cells targeting PRAME DL4 was defined as provisional RP2D for Phase 1b, exploration of higher DL5 ongoing * ** Data cut - off – 06 - Sept - 2022 Phase 1a Phase 1b I M A 203
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 CRS of any Grade ▪ 29 patients had Grade 1 or 2 CRS ▪ 2 patients had Grade 3 CRS (both in phase 1a); recovered to Grade ≤2 after 3 and 4 days, respectively • Low - moderate ICANS 1 : 5 of 32 (16%) patients infused with IMA203 experienced Grade 1 or 2 ICANS (all in phase 1a) • No dose - dependent increase of CRS and ICANS • No additional DLT 2 16 One patient that started lymphodepletion in Phase 1a died from sepsis of unknown origin and did not receive IMA203 T cells, patient reported earlier and not shown; CRS and ICANS graded by CARTOX criteria (Neelapu et al ., 2018); 1 ICANS: Immune effector cell - associated neurotoxicity syndrome; 2 DLT: dose - limiting toxicity, one DLT in phase 1a at DL2 reported on March 17, 2021 Data cut - off – 06 - Sept - 2022 I M A 203
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); 3 Confirmed ORR (cORR): Confirmed objective response rate (confirmed partial responses) according to RECIST 1.1 at second scan post infusion (~12 weeks); * 1 patient with SD at ~ 6 - week scan with pending ~12 - week scan considered as non - responder for cORR. • Higher ORR and confirmed ORR observed at doses above 1 billion TCR - T cells (DL4, DL5) • Early trends towards higher ORR and confirmed ORR observed in Phase 1b vs. Phase 1a patients Phase 1a Phase 1a + Phase 1b Phase 1b only All pts (DL1 - 4) DL4 pts only 1 DL4/DL5 pts only 1 All pts (DL4/DL5) 1 Patients Treated 27 7 12 5 ORR (~6 weeks) 2 48% (13/27) 57% (4/7) 67% (8/12) 80% (4/5) cORR (~12 weeks) 3 19% (5/27) 29% (2/7) 50% (6/12) * 80% (4/5) * Data cut - off – 06 - Sept - 2022 I M A 203
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 target lesions and RECIST 1.1 BOR at different timepoints; # 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 response; BL: Baseline Data cut - off – 06 - Sept - 2022 Phase 1a (Dose Escalation) N=27 # Phase 1b (Cohort A) N=5 I M A 203
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 response; BL: Baseline Phase 1a (Dose Escalation) N=27 # Phase 1b (Cohort A) N=5 Best overall resp o nse (RE C I S T 1.1) Data cut - off – 06 - Sept - 2022 I M A 203
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) IMA203 T cell infiltration into tumor correlates with objective responses 1 1 î 10 1 1 î 10 2 1 î 10 3 1 î 10 4 1 î 10 5 1 î 10 6 A N gD ] 6 g k μ W es/ y i p op s o C i r B o [ ect V 0 .0010 IMA203 T cell infiltration [vector copies/µg gDNA] Data cut - off – 06 - Sept - 2022 p =0 . 001 Vector copies/µg gDNA N =19 N =32 1 î 10 7 1 î 10 6 1 î 10 5 1 î 10 4 1 î 10 3 1 î 10 2 1 î 10 1 1 î 10 0 1 î 10 - 1 Days post infusion 0 5 î 10 5 1 î 10 6 1.5 î 10 6 cy e n N A] u D eq g r f g ea k e s/ μ p i l p l c e c o r T o 20 3 v e ct A [ M I Phase 1a Phase 1b Cohort A p=0.0003 P D /SD PR cPR High IMA203 T cell engraftment and persistence in peripheral blood Persistence over time Peak frequency P D /SD PR cPR Vector copies/µg gDNA N =32 I M A 203
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, Faster Turn Around Time Accelerated Product Release ACTengine® clinical programs: ~3 weeks Implementation planned All Phase 1b cell products were manufactured with the current, optimized process including manufacturing improvements such as x Monocyte depletion x Serum - free transduction Manufacturing Improvements Implemented in Phase 1b Enhance Key Features of the Cell Product C urren t P ri o r process versions (n=6) 1 (n=27) 0 Manufacturing process (infused products) 20 40 60 80 % CD8+ Cells p = 0.0232 0 20 40 60 100 80 % Transduction p = 0.0025 Significantly higher peak frequencies in Phase 1b patients infused with current, optimized product version p=0.0232* p=0.0025* C urren t P ri o r process versions (n=6) 1 (n=27) 0 5 î 10 5 1 î 10 6 1.5 î 10 6 D N A] c y g en μ g u e q es / i r p f a k co e r o P t ec V [ Phase 1a Phase 1b Cohort A p = 0.0003 p=0.0003 # Current process Prior versions 1 Includes 5 IMA203 products infused into Phase 1b cohort A patients, and 1 product infused into Phase 1a patient at DL3; * Unpaired t test; # Mann - Whitney U test, 1 patient in Phase 1a at DL3 received ~0.5 x 10 9 total transduced viable CD8 T cells manufactured with current process IMA203 T cell peak frequency [vector copies/µg gDNA] I M A 203
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 clinical benefit for all PRAME biomarker - positive cancer patients Data cut - off – 06 - Sept - 2022 p= 0.076 IMA203 achieved objective responses at all expression levels above Immatics’ mass spectrometry - guided RNA threshold p= 0.076 p= 0.076 I M A 203
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 RNAseq data combined with a proprietary mass spectrometry - guided RNA expression threshold; * PRAME target prevalence in uveal melanoma based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=21) demonstrates substantial higher prevalence of 90%, TCGA: early & late - stage primary tumor samples, Immatics clinical trials: late - stage/metastatic tumor samples, Role of PRAME in metastasis of uveal melanoma: Field et al. 2016 Clinical Cancer Research I M A 203
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 positive population in the US; PRAME target prevalence is based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=21) Multiple opportunities to broaden patient reach and patient benefit: » Expand beyond US population » Expand into other indications such as kidney, esophageal, bladder, liver cancer, other sarcoma subtypes through indication - specific or indication - agonistic label expansion » Move into earlier lines of therapy (R/R Incidence Incidence) » Inclusion of patients with lower PRAME - threshold TOTAL ~39,000 annually in the US Selected Indications Incidence R/R Incidence PRAME Positive Patient Population Based on R/R Incidence; PRAME and HLA - A*02:01+ Cut. Melanoma rest 99,800 7,700 95% 2,999 Uveal Melanoma nce, 1,500 800 90% 295 Ovarian Carcinoma and 19,900 12,800 80% 4,198 Uterine Carcinoma ses 62,700 10,700 100% 4,387 Uterine Carcinosarcoma 3,300 1,900 100% 779 Synovial Sarcoma 1,000 400 100% 164 Squamous NSCLC 57,000 34,600 65% 9,221 Small Cell Lung Cancer 31,900 19,400 55% 4,375 Cho l a n g io c a r c i no m a 8,000 7,000 35% 1,005 Adeno NSCLC 91,200 55,300 25% 5,668 Breast Carcinoma 290,600 43,800 25% TNBC: 60% 4,490 H N S CC 66,500 15,100 25% 1,548 Initial indications of inte based on PRAME prevale patient population size observed clinical respon I M A 203
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 of different solid tumor types in heavily pre - treated patients • Positively evolving durability profile for patients treated with higher doses and in phase 1b • Clinical validation of PRAME biomarker threshold and associated prevalences » We have clinically validated PRAME as one of the largest known T cell targets for solid cancers to date IMA203 development strategy: • Transition to indication - specific development strategy • Three Phase 1b expansion cohorts ongoing each designed to establish safety, evaluate the observed objective response rate, demonstrate durability & provide the trigger for registration trials Data highlight the clinical potential of IMA203 TCR - T to achieve meaningful benefit for a large patient population I M A 203
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 suggest a relevant role of engineered CD4 T cells in maintaining durable tumor responses over a long period of time 1 • Functional superiority of the CD8αβ construct over multiple other CD8 constructs in preclinical experiments • Proprietary 4 - in - 1 lentiviral vector to engineer CD4 and CD8 T cells with the PRAME - specific IMA203 TCR and CD8αβ construct (IMA203CD8) TUMOR CELL DEATH CD4 T CELL Cy t o t o x ic Activity CD8 T CELL T cell Help Cy t o t o x ic Activity 26 1 Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances IMA203CD8
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 50 100 150 200 250 300 350 400 450 Hours after Coculture Tumor fold growth 2 nd addition of tumor cells 3 rd 4 th 5 th 6 th 2 nd addition of tumor cells 3 rd 4 th 5 th 6 th IMA203CD8 Engagement of CD4 T cells may enhance depth and durability of anti - tumor response and clinical outcome of TCR - T in solid cancer patients
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 Checkpoint Inhibitor 3 Blocking PD - 1/PD - L1 pathway Cohort C IMA203CD8 2nd Gen at Target Dose (plus DL5) * Adding functional CD4 T cells 4 IMA203 Monotherapy in Basket Trial Completed & provisional RP2D 1 determined in March 2022 ACTengine® IMA203: Next data read - outs with meaningful data across all cohorts in 2023 TCER® IMA402: Entering clinical development in 2023 Upcoming Value Inflection Points for Our PRAME Programs First pt treated March 2022 First pt treated May 2022 1 RP2D (target dose) determined at DL4, exploration of higher dose (DL5) ongoing; 2 Demonstrated to be associated with durable response: Locke et al. 2020 Blood Advances; 3 Opdivo® (nivolumab): programmed death - 1 (PD - 1) immune checkpoint inhibitor; * Treatment of n=3 patients ongoing in DL3 prior to patient treatment at Target Dose (DL4), exploration of higher dose (DL5) planned; 4 Demonstrated to be important for long - term remission: Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances First pt treated Aug 2022; First 3 pts on DL3 *
ACTengine® IMA201 and IMA204 – TCR - T Targeting MAGEA4/8 and COL6A3 29
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/cell Identified and validated by XPRESIDENT® quant . mass spectrometry platform High - affinity, specific TCR targeting MAGE4/8 High functional avidity 2 : EC50 ~10 ng/ml Identified and characterized by XCEPTOR® TCR discovery and engineering platform Dose escalation ongoing, target dose level to commence Too early for assessment of safety or anti - tumor activity Sarcoma Subtypes – up to 80% Squamous NSCLC – 50% HNSCC – 35% Bladder Carcinoma – 30% Esophageal Carcinoma – 25% Uterine Carcinosarcoma – 25% Ovarian Carcinoma – 20% Melanoma – 20% 1 Target density: peptide copy number per tumor cell, approximate range representing the majority of tumor samples analyzed; 2 Functional avidity: EC50 half maximal effective concentration; 3 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data) T A R GET T CR CLINICAL DATA PATIENT POPULATION 3 I M A 201 Status – 02 - June - 2022
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 XPRESIDENT® quant. mass spectrometry platform High - affinity, specific TCR targeting COL6A3 exon 6 Affinity - maturated, CD8 - independent TCR High functional avidity 2 : ~0.01ng/ml Identified and characterized by XCEPTOR® TCR discovery and engineering platform CD8 - independent, next - generation TCR engages both, CD8 and CD4 T cells In vitro anti - tumor activity against target - positive cell lines in CD8 and CD4 T cells Complete tumor eradication in in vivo mouse models Pancreatic Carcinoma – 80% Breast Carcinoma – 75% Stomach Carcinoma – 65% Sarcoma – 65% Esophageal Carcinoma – 60% Squamous NSCLC – 55% Adeno NSCLC – 55% HNSCC – 55% Uterine Carcinosarcoma – 55% Colorectal Carcinoma – 45% Mesothelioma – 45% Cholangiocarcinoma – 40% Ovarian Carcinoma – 40% Melanoma – 35% Bladder Carcinoma – 35% 1 Target density: peptide copy number per tumor cell, approximate range representing the majority of tumor samples analyzed; 2 Functional avidity: EC50 half maximal effective concentration; 3 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data) T A R GET T CR PRECLINICAL DATA PATIENT POPULATION 3 IMA204 provides a promising therapeutic opportunity for a broad patient population as monotherapy or in combination with TCR - T cells directed against tumor targets I M A 204
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 duc nl y ed Control IMA204 TCR D7 D 16 D 22 D 29 Affinity maturated CD8 - independent, next - generation TCR engages both CD4 and CD8 T cells without the need of CD8 co - transduction S tr o ma cells T u m or cells Stroma Target (COL6A3 exon 6) in Ovarian Cancer sample Example of a Tumor Target in same Ovarian Cancer sample 1 In vivo data in collaboration with Jim Riley, University of Pennsylvania, control: non - transduced T cells. TCR avidity and specificity data not shown, available in IMA204 presentation on Immatics website. COL6A3 exon 6 prevalently expressed at high target density in tumor stroma across many solid cancers I M A 204
ACTallo® – Our Next - generation Off - the - shelf TCR - T 33
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 provides standardized quality and quantity of starting material 34 γδ T cell Cell Engineering (gene editing & enhancements) γδ T cell Collection from Healthy Donor Expansion O f f - t he - she l f Products Patient T r e a t me n t A C T a llo® 1 Immatics proprietary ACTallo® platform utilizing Editas’ CRISPR gene editing technology 1
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 graft - vs - host disease in allogeneic setting x can be expanded to high numbers in a cGMP - compatible manner x can be effectively redirected using αβ TCR or CAR constructs In vitro anti - tumor activity 0 48 14 4 19 2 0 5 10 15 96 H o u rs ) P + F R - 2 0 S U ( h t o w r G d o l F T u m o r c e lls o n ly T ce lls ( N T ) T c e lls ( N T ) T c e lls IM A 2 0 3 TC R + T ce lls IM A 2 0 3 T C R + γδ T cells (control) + tumor cells tumor cells only αβ T cells (control) + tumor cells γδ T cells TCR + + tumor cells αβ T cells TCR + + tumor cells A C T a llo® 0 . 00 1 0 . 0 1 0 . 1 1 1 0 100 100 0 1000 0 100000 100000 0 0 5 10 15 20 25 Day Fold expansion of T cells Expansion Fold - growth (target - positive tumor cells)
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: Clinical development and c omme r c i a li z a ti o n Innovative γδ - derived allogeneic cell therapy platform ACTallo® Activities for initial 2 BMS programs: Preclinical development Expertise in oncology drug development and c omme r c i a li z a ti o n Complementary next - gen technologies to potentiate anti - tumor activity Bristol Myers Squibb Immatics • Initial 2 BMS programs • Up to 4 additional BMS programs (TCRs developed in the context of the autologous TCR - T collaboration 2 might feed into allogeneic TCR - T programs) • Up to 4 Immatics programs State of the art manufacturing & gene editing via collaboration with Editas 1 1 Immatics proprietary ACTallo® platform utilizing Editas’ CRISPR gene editing technology; 2 Exclusive options to 3 Immatics TCR - T targets in 2019, expansion in 2022 by exclusive option to 1 additional Immatics TCR - T target A C T a llo®
TCER® – TCR Bispecifics 37
TCER® – Mechanism of Action Immatics’ Off - the - Shelf TCR Bispecifics Approach 38 T CE R ®
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 doses T cell recruiting antibody x Low - affinity T cell recruiter against both TCR & CD3 x Optimized biodistribution aiming for enrichment at tumor site and prevention of CRS 2 x Superior anti - tumor activity in mouse models as compared to widely used CD3 recruiters Next - generation TCER® format x Off - the - shelf biologic with antibody - like manufacturability 3 and low cost of goods x Superior anti - tumor activity 4 compared to six alternative bispecific formats x Half - life of several days expected in humans T C E R ® T cell r ec r ui t ing antibody pHLA t a r g e t ing TCR Fc domain (silenced) with KiH technology Our TCER® format is designed to maximize efficacy while minimizing toxicities in patients 1 As compared to natural TCR; 2 Based on literature data for other low - affinity recruiters (e.g. Harber et al ., 2021, Nature; Trinklein et al ., 2019, mAbs); 3 Production in mammalian cells (CHO cells); 4 Based on preclinical testing T CE R ®
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 designs evaluated Flexible Plug - and - play platform: TCER® format successfully validated for different TCRs & different T cell recruiting antibodies T CE R ® T CE R® 2+1 TCR bispecific format: High potency was linked to a significantly reduced specificity profile Killing of target - positive cells by different TCR Bispecifics 1 Preclinical data on specificty not shown
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 control compared to analogous TCER® molecules designed with higher - affinity variants of a widely used recruiter 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) T CE R ® Tumor Model in Mice 1 1 Hs695T xenograft model in NOG mice, tumor volume of group means shown
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
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 testing ongoing Preclincial P r oof - of - c o n ce pt – Efficacy / Safety » Complete remission of estab. tumors in xenograft mouse models at low doses » Very broad therapeutic window (reactivity tumor compared to normal cells) n/a Half - life Half - life extended to several days via effector function silenced Fc part Clinical D e v elop m e n t Strategy » First - in - human basket trial » Adaptive design aiming at fast dose escalation » Development strategy includes TCER® as add on to checkpoint inhibitor - based standard of care in early lines of treatment T CE R ®
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 opportunity to optimize scheduling to a less frequent regimen. 2 Conducted in collaboration with BMS Phase 1a: Dose Escalation Phase 1b: Dose Expansion • Weekly i.v. infusions 1 • Dose escalation decisions based on cohorts of 1 - 6 patients in adaptive design (BLRM model) • Up to N=50 in phase 1 M TD/ RP2D Adaptive design aimed at accelerating dose escalation • Focus on specific indications planned Potential development option for checkpoint inhibitor combination or other combination therapies 2 Monotherapy expansion cohort Primary Objective • Determine MTD and/or RP2D Secondary Objectives • Safety and tolerability • Initial anti - tumor activity • Pharmacokinetics I M A 401
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 animals even at low IMA401 dose of 0.05 mg/kg • No detectable outgrowth of tumors during prolonged observation period of 70 days Study day N=6 mice per group, two PBMC donors Dose: two dose levels 1 Hs695T xenograft model in MHC I/II ko NSG mice, tumor volume of individual mice shown I M A 401
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] Cytotoxicity [%] Target - negative 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] ~110 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] ~250 PRAME CpCs 0 • 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 – 1000 CpCs I M A 402
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 - 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 effect I M A 402
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 M A 402
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 optimize scheduling. Phase 1: Dose Escalation Phase 2a: Dose Expansion • Basket trial in focus indications for accelerated signal finding • Initially weekly i.v. infusions # • MABEL - based starting dose • Dose escalation decisions based on cohorts of 1 - 6 patients in adaptive design (BLRM model) Adaptive design aimed at accelerating dose escalation • Specific indications plus ongoing basket • Combination therapies • Optional dose/application optimization Expansion cohort Expansion cohort Expansion cohort Trial Overview Phase 1/2 clinical trial to evaluate safety, tolerability and anti - tumor activity of IMA402 HLA - A*02:01 - positive patients with PRAME - expressing recurrent and/or refractory solid tumors M TD/ RP2D 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 I M A 402
Immatics’ Proprietary Target and TCR Discovery Platforms 50
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 levels on normal tissues • are presented at high copy numbers to trigger a pharmacological response + T e chn olo g y Right TCRs via XCEPTOR® technology platform • recognize the target peptide with high affinity and specificity • show selective killing of tumor cells • are developed to be suitable for two different therapeutic modalities, Cell Therapies and TCR Bispecifics
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<0.001 2 T e chn olo g y MAGEA4/8 target is presented at >5 - fold higher target density 1 than a commonly used MAGEA4 target peptide XPRESIDENT® quantitative information on target density 1 between peptides originating from the same source protein Ranking of pHLA targets
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. stroma target COL6A3 exon 6 3. Crypto - targets/Neoantigens (20%) Novel target class which includes RNA - edited peptides & non - classical neoantigens ~50% of our prioritized targets are non - HLA - A*02 restricted, substantially broadening the potential patient reach >2,500 cancer & normal tissues analyzed by Quantitative, Ultra - Sensitive Mass Spectrometry pHLA Database based on primary tissues >200 p ri o ri t i z e d targets
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 • Protein engineering capabilities to design and maturate TCRs with increased affinity while retaining specificity • Early de - selection of cross - reactive TCRs by the unique interplay between Immatics’ target and TCR discovery platforms XPRESIDENT® and XCEPTOR® during TCR discovery 1 and TCR maturation 2 Micromolar affinity Nanomolar affinity T e chn olo g y 1 XPRESIDENT® - guided off - target toxicity screening; 2 XPRESIDENT® - guided similar peptide counterselection
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 t toxicity On - target (off - tumor) toxicity A different HLA is recognized on normal cells Alloreactivity Similar peptide presented on normal cells 1 XPRESIDENT® - guided screening for on - and off - target toxicities of TCRs based on the extensive database of peptides presented on normal tissues T e chn olo g y 1 Clinical fatalities have occurred in TCR - T trials using a titin cross - reactive TCR (Cameron et al ., Sci Transl Med)
Corporate Information & Milestones 56
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 Britten Chief Medical Officer >14 yrs pharma & biotech (GSK, BioNTech) Rainer Kramer Chief Business Officer 25 yrs pharma & biotech experience (Amgen, MorphoSys, Jerini, Shire, Signature Dx) Steffen Walter Chief Technology Officer Co - Founder Immatics US >15 yrs biotech experience Edward Sturchio General Counsel >15 yrs pharma & biotech experience (Abeona Therapeutics, AAA, Novartis, Merck, Schering Jordan Silverstein Head of Strategy >10 yrs biotech experience (InflaRx, AAA) Toni Weinschenk Chief Innovation Officer Co - Founder >15 yrs biotech experience Experienced Global Leadership Team Across Europe and the US Corporate
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 as of June 2022
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
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 across all cohorts in 2023 • Additional ACTengine® programs in clinical and preclinical development Further clinical development of TCER® candidates • Ongoing Ph1 trial for IMA401 (MAGEA4/8) (start in May 2022) • IMA402 Ph 1/2 clinical trial on track to start in 2023; submission of CTA/IND application 2Q 2023 • Innovative TCER® program(s) IMA40X in preclinical development Corporate Solid cash runway into 2025 to reach multiple value inflections points across our portfolio
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