SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR 15d-16 UNDER THE SECURITIES EXCHANGE ACT OF 1934
May 10, 2022
Commission File Number: 001-39363
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 May 10, 2022, Immatics N.V. (the “Company”) announced the initiation of a Phase 1 clinical trial with its T cell engaging receptor (TCER®) IMA401 for patients with recurrent and/or refractory solid tumors. IMA401 is the most advanced product candidate from Immatics’ TCR Bispecific pipeline targeting an HLA-A*02-presented peptide derived from both MAGEA4 and MAGEA8. TCER® IMA401 will be developed in collaboration with Bristol Myers Squibb. Immatics is responsible for conducting the Phase 1 clinical trial. The primary objectives of the clinical trial (NCT#05359445) are to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) for IMA401 in biomarker-positive (HLA-A*02:01 and MAGEA4/8) patients with recurrent and/or refractory solid tumors. Secondary objectives are to characterize safety and tolerability, evaluate initial anti-tumor activity and assess pharmacokinetics of IMA401. The Phase 1 trial consists of a dose-escalation (Phase 1a) portion that will be followed by a dose-expansion (Phase 1b) portion to treat patients at the recommended dose level. The trial is planned to be conducted at up to 15 centers in Germany, with the first site already being initiated. The Phase 1 trial is designed to enroll approximately 50 patients.
In connection with the initiation of the Phase 1 clinical trial, the Company issued a press release, a copy of which is attached hereto as Exhibit 99.1, and made available an updated investor presentation on its website, a copy of which is attached hereto as Exhibit 99.2. 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 May 10, 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.
INCORPORATION BY REFERENCE
This Report on Form 6-K (other than Exhibits 99.1 and 99.2) shall be deemed to be incorporated by reference into the registration statements on Form F-3 (Registration Nos. 333-258351 and 333-240260) of Immatics N.V. and to be a part thereof from the date on which this report is filed, to the extent not superseded by documents or reports subsequently filed or furnished.
|99.1||Press release dated May 10, 2022|
|99.2||Presentation dated May 10, 2022|
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.
|Date: May 10, 2022|
|By:||/s/ Harpreet Singh|
|Title:||Chief Executive Officer|
Initiates Phase 1 Clinical Trial to Evaluate
Lead TCR Bispecific IMA401 in Patients with Advanced Solid Tumors
|·||Patient enrollment for IMA401 Phase 1 trial started at first clinical site in Germany|
|·||The study will evaluate safety, tolerability, and initial anti-tumor activity of IMA401 in patients with recurrent and/or refractory solid tumors|
|·||TCER® IMA401 targets MAGEA4/8 and will be developed in collaboration with Bristol Myers Squibb|
Tuebingen, Germany and Houston, Texas, May 10, 2022 – Immatics N.V. (NASDAQ: IMTX, “Immatics”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today announced the initiation of a Phase 1 clinical trial with its T cell engaging receptor (TCER®) IMA401 for patients with recurrent and/or refractory solid tumors. IMA401 is the most advanced product candidate from Immatics’ TCR Bispecific pipeline targeting an HLA-A*02-presented peptide derived from both MAGEA4 and MAGEA8. TCER® IMA401 will be developed in collaboration with Bristol Myers Squibb. Immatics is responsible for conducting the Phase 1 clinical trial.
The primary objectives of the clinical trial (NCT#05359445) are to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) for IMA401 in biomarker-positive (HLA-A*02:01 and MAGEA4/8) patients with recurrent and/or refractory solid tumors. Secondary objectives are to characterize safety and tolerability, evaluate initial anti-tumor activity and assess pharmacokinetics of IMA401. The Phase 1 trial consists of a dose-escalation (Phase 1a) portion that will be followed by a dose-expansion (Phase 1b) portion to treat patients at the recommended dose level. The trial is planned to be conducted at up to 15 centers in Germany, with the first site already being initiated. The Phase 1 trial is designed to enroll approximately 50 patients.
“IMA401 is the first TCER® candidate from our TCR Bispecifics pipeline entering clinical development, and expands our clinical portfolio with an exciting new TCR-based immunotherapy approach that can be supplied off-the-shelf compared to autologous cell therapies,” said Cedrik Britten, Chief Medical Officer at Immatics. “Our innovative TCER® format leads to an extended-half-life and incorporates novel binding-moieties that are designed to maximize efficacy while
minimizing toxicities in patients. Our TCER® IMA401 could treat a range of solid tumors and therefore meet currently unmet needs of a broad patient population. This is best achieved with a strong pharma partner which we have found in Bristol Myers Squibb.”
Immatics entered into a global exclusive license agreement with Bristol Myers Squibb in December 2021 for the IMA401 program under which both companies will collaborate to advance the program through clinical development.
Immatics’ TCR Bispecific pipeline includes a second TCER® product candidate, IMA402, which targets PRAME. Manufacturing of the clinical IMA402 batch is planned for the second half of 2022 and initiation of the Phase 1 trial is planned in 2023. Immatics’ TCER® pipeline is further strengthened by additional innovative TCER® program(s), IMA40X, in preclinical development.
IMA401 is Immatics’ most advanced TCER® molecule that targets an HLA-A*02-presented (human leukocyte antigen) peptide derived from two different cancer-associated proteins, melanoma-associated antigen 4 and/or 8 (“MAGEA4/8”). The MAGEA4/8 peptide has been identified and validated by Immatics’ proprietary mass spectrometry-based target discovery platform XPRESIDENT® and is presented at a 5-fold higher copy number per tumor cell than a MAGEA4 peptide targeted in other clinical trials. Following preclinical proof-of-concept data, including complete remissions of transplanted human-derived tumors in xenograft mouse models, the Phase 1 trial investigates IMA401 in patients with tumors of high MAGEA4/8 prevalence, such as squamous non-small cell lung carcinoma (sqNSCLC), small cell lung cancer (SCLC), head and neck squamous cell carcinoma (HNSCC), bladder, uterine, esophageal and ovarian carcinomas, as well as melanoma, sarcoma subtypes and other solid cancer types.
Immatics’ half-life extended TCER® molecules are antibody-like “off-the-shelf” biologics that leverage the body’s immune system by redirecting and activating T cells towards cancer cells expressing a specific tumor target. The design of the TCER® molecules enables the activation of any T cell in the body to attack the tumor, regardless of the T cells’ intrinsic specificity. Immatics proprietary biologics are engineered with two binding regions: a TCR domain and a T cell recruiter domain. The TCER® format is designed to maximize efficacy while minimizing toxicities in patients. It contains a high-affinity TCR domain that is designed to bind specifically to the cancer target peptide on the cell surface presented by an HLA molecule. The antibody-derived, low-affinity T cell recruiter domain is directed against the TCR/CD3 complex and recruits a patient’s T cells to the tumor to attack the cancer cells. With a low-affinity recruiter aiming for optimized biodistribution and enrichment of the molecule at the tumor site instead of the periphery, TCER® are engineered to reduce the occurrence of immune-related adverse events, such as cytokine release syndrome. In addition, the TCER® format consists of an Fc-part conferring half-life
extension, stability, and manufacturability. TCER® are “off-the-shelf” biologics and thus immediately available for patient treatment. They can be distributed through standard pharmaceutical supply chains and provide the opportunity to reach a large patient population without the need of specialized medical centers.
- END -
Immatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer.
For regular updates about Immatics, visit www.immatics.com. You can also follow us on Twitter, Instagram and LinkedIn.
Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events or Immatics’ future financial or operating performance. For example, statements concerning the timing of product candidates and Immatics’ focus on partnerships to advance its strategy 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 by 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 filings with the 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.
Immatics undertakes no duty to update these forward-looking statements. All the scientific and clinical data presented within this press release 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.
For more information, please contact:
|Media and Investor Relations Contact|
|Jacob Verghese or Stephanie May|
|Phone: +49 89 2070 89831|
|Anja Heuer||Jordan Silverstein|
|Director, Corporate Communications||Head of Strategy|
|Phone: +49 89 540415-606||Phone: +1 281 810 7545|
© Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation May 10, 2022
Forward - Looking Statements 2 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 Immatics nor any of its affiliates nor any of its or their 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 . You should consult your own counsel and tax and financial advisors as to legal and related matters concerning the matters described herein, and, by accepting this presentation, you confirm that you are not relying upon the information contained herein to make any decision . 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 clinical trial application for IMA 204 , IMA 301 , IMA 401 , the Company’s focus on partnerships to advance its strategy, projections of future cash on hand 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 filings with the Securities and Exchange Commission (the “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 . 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, and otherwise in accordance with applicable law . 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 . Clinical study results and associated biomarker studies presented within this presentation are by definition prior to completion of the clinical trial and a clinical study report and, are therefore, preliminary in nature and subject to further quality checks including customary source data verification . This meeting and any information communicated at this meeting are strictly confidential and should not be discussed outside your organization .
Building a Leading TCR Therapeutics Company 3 Intro Clinical PoC for Cell Therapy Objective responses across multiple solid tumors in early TCR - T clinical development Differentiated Approach Unique technologies to identify true cancer targets and right TCRs Strategic Partnerships World - leading industry players with synergistic expertise Solid Cash Runway To reach next value inflections points across our portfolio Therapeutic Opportunity Addressing relevant patient populations across multiple solid cancer indications Comprehensive TCR Approach Building a TCR - T Cell Therapy and TCR Bispecifics Pipeline
Our TCR - based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface 4 Intro
Two TCR - based Therapeutic Modalities 5 Distinct mechanisms of actions and therapeutic application to address the needs of a broad patient population at different stages of disease and with different types of tumors Intro
Our Pipeline of TCR - based Adoptive Cell Therapies and Bispecifics 6 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion Modality Product Candidate Target Preclinical Phase 1a 1 Phase 1b 1 Phase 2/3 ACTengine® Autologous ACT IMA203 PRAME IMA203CD8 PRAME IMA201 MAGEA4/8 IMA202 MAGEA1 IMA204 COL6A3 Autologous ACT 3 programs Undisclosed 2 programs Undisclosed ACTallo® Allogeneic ACT IMA30x Undisclosed TCER® Bispecifics IMA401 MAGEA4/8 IMA402 PRAME IMA40x Undisclosed Bispecifics 3 programs Undisclosed + Checkpoint Inhibitor Intro
Strategic Collaborations Synergistic Expertise that Can Foster Transformative Innovations for ACT and Bispecifics 7 2019 2021 2020 2018 Each of our 9 partnered programs may be eligible for • >$500 million aggregated milestone payments • Tiered royalties Broadening the clinical framework beyond our proprietary pipeline Research collaboration to develop bispecific immunotherapies 3 Immatics targets $54 M upfront Co - promotion option Research collaboration to develop TCR - T therapies 3 Immatics targets $75 M 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 possibility Licensing agreement to develop Immatics’ TCR Bispecific program TCER® IMA401 $150 M upfront Co - fund/Co - promotion option in the US Intro
IMA201 / IMA401 IMA202 IMA203 / IMA402 IMA204 MAGEA4/8 MAGEA1 PRAME COL6A3 exon 6 Selected solid cancer indications with significant target prevalence 1 Sarcoma Subtypes – up to 80% Squamous NSCLC – 50% HNSCC – 35% Bladder Carcinoma – 30% Esophageal Carcinoma – 25% Uterine Carcinosarcoma – 25% Ovarian Carcinoma – 20% Melanoma – 20% HCC – 40% Squamous NSCLC – 35% Sarcoma Subtypes – up to 30% Melanoma – 30% Bladder Carcinoma – 20% Esophageal Carcinoma – 20% Uterine Carcinoma – 100% Sarcoma Subtypes – up to 100% Melanoma – 95% Uveal Melanoma – 80% 2 Ovarian Carcinoma – 80% Squamous NSCLC – 65% Kidney Carcinoma – up to 45% Cholangiocarcinoma – 35% Adeno NSCLC – 25% Breast Carcinoma – 25% HNSCC – 25% Esophageal Carcinoma – 20% HCC – 20% Bladder Carcinoma – 20% 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% Addressing Relevant Patient Populations across Multiple Solid Cancers 8 1 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data); 2 Based on metastatic uveal melanoma patients screened in IMA203 study (N=12) Intro IMA200 & IMA400 programs demonstrate relevant expression in m ultiple s olid cancers
IMA201 IMA202 IMA203 Peptide Target HLA - A*02 - presented peptide derived from MAGEA4/8 MAGEA1 PRAME shown to be naturally and specifically presented on native tumor tissues at d ifferentiated high peptide target density 1 100 - 1,000 copies/cell 50 - 900 copies/cell 100 - 1,000 copies/cell T cell Receptor (TCR) High - affinity specific TCRs with high functional avidity 2 Natural TCR ~10 ng/ml Natural TCR ~15 ng/ml Pairing - enhanced TCR ~5 ng/ml T cell Product Autologous T cells gene - engineered with lentiviral vector expressing TCR and applying proprietary short - term manufacturing process designed to achieve better T cell engraftment and persistence 7 - 10 days 3 7 - 10 days 3 7 days 3 Key Features of Our Clinical ACTengine® Programs 9 1 Applying XPRESIDENT® quantitative mass spectrometry engine; target density: p eptide copy number per tumor cell, approximate range representing the majority of tumor samples analyzed (25 - 75% percentiles); 2 Applying XCEPTOR® TCR discovery and engineering platform; functional a vidity : EC50 half maximal effective concentration, 3 Manufacturing time (activation, transduction and expansion) without release testing Differentiated Targets, TCRs and Cellular M anufacturing D esigne d to Enhance Safety and Activity Intro
ACTengine® IMA203 – TCR - T Targeting PRAME 10
ACTengine® IMA203 – TCR - T Targeting PRAME Broadly Expressed Target on Multiple Solid Cancers Combined with Highly Specific TCR 11 HLA - A*02 - presented peptide derived from PRAME 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 PRAME Pairing - enhanced, engineered TCR to avoid mispairing High functional avidity 2 : EC50 ~5 ng/ml Identified and characterized by XCEPTOR® TCR discovery and engineering platform TARGET TCR C LINICAL DATA N=18 pts treated in phase 1 dose escalation cohort Manageable tolerability profile; no additional DLTs 3 & no CRS/ICANS ≥ grade 3 16 patients with at least one post treatment tumor assessment Objective responses in 50% (8/16) of patients, thereof 62% (8/13) of responses above DL1; all doses still below 1 bn cells PATIENT POPULATION 4 Uterine Carcinoma – 100% Sarcoma Subtypes – up to 100% Melanoma – 95% Uveal Melanoma – 80% 5 Ovarian Carcinoma – 80% Squamous NSCLC – 65% Kidney Carcinoma – up to 45% Cholangiocarcinoma – 35% Adeno NSCLC – 25% Breast Carcinoma – 25% HNSCC – 25% Esophageal Carcinoma – 20% HCC – 20% Bladder Carcinoma – 20% Data cut - off – 05 - Oct - 2021 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 One DLT in DL2 previously reported in March 2021, fully resolved; 4 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data); 5 Based on metastatic uveal melanoma patients screened in IMA203 study (N=12) IMA203
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ Leading TCR - T Approach 12 IMA203
Optimized Cell Therapy Products to Enhance T cell Persistence & Efficacy Current Proprietary Manufacturing P rotocol for ACTengine® Product Candidates 13 Proprietary Manufacturing Process, designed to x reduce manufacturing process to approx. 1 week x shorten vein - to - vein time x generate younger T cells with increased proliferative capacity x improve engraftment and persistence in patients while utilizing smaller doses In - house state - of - the - art cGMP Facility 1 x Manufacturing by Immatics personnel x Maximum capacity: 48 manufacturing runs/month x Substantial in - house process development expertise 1 Exclusive access through collaboration with UT Health, Houston, TX Expedited QC testing (~1 week) Manufacturing time (~1 week) QC testing (Full sterility, 2 weeks ) Manufacturing time (~1 week) Commercial ACTengine® expected ~2 weeks ACTengine® IMA200 programs : ~3 weeks Leukapheresis Infusion - Ready A CTengine ®
ACTengine® IMA203 – Patient Flow 14 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 clophosphamide 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 IMA201 IMA202 IMA203 * 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 40 mg/m 2 to 30 mg/m 2 ) was introduced prior to treatment of the first patient on dose level 3 Leuka - pheresis IMA203
ACTengine® IMA203 – Key Objectives & Trial Design Presented at SITC Conference as Late - Breaking Presentation (Cut - off October 05, 2021) Trial Design & Recruitment Status 1 Enrichment cohorts EC1 & EC2: patients infused with intermediate doses enabling infusion of patients with medical need during do se escalation observation periods, or in case of lower production yields; * One patient infused at the same dose level as part of the enrichment cohort; ** Dose is shown as transduced viable CD8 T cells per m 2 total body surface area Key Study Objectives • Primary: Safety Investigation of Adverse Events, Determination of a recommended Phase 2 dose • Secondary: Biological and Clinical Activity T cell engraftment and persistence Objective responses as per RECIST1.1 Duration of response • Exploratory Tumor Infiltration 15 Data cut - off – 05 - Oct - 2021 18 patients 1 infused with PRAME - directed T cells at 5 clinical sites N=3 ** N=3 Ongoing N=1 N=4 patients treated at intermediate dose levels 1 N=7 * IMA203
ACTengine® IMA203 – Safety Profile Manageable & Transient Treatment - emergent Adverse Event s – No ≥ Grade 3 CRS or ICANS Adverse event All grades ≥ Grade 3 No . % No . % Patients with any adverse event 19 100.0 19 100.0 Adverse Events of Special interest Cytokine release syndrome 1 7 8 9.5 0 0.0 ICANS 2 4 21.1 0 0.0 Blood and lymphatic system disorders Neutropenia* 16 84.2 15 78.9 Anaemia 1 6 84.2 9 47.4 Thrombocytopenia 15 78.9 7 36.8 Lymphopenia* 14 73.7 14 73.7 Leukopenia* 12 63.2 1 1 57.9 Cytopenia 1 5.3 1 5.3 Infections and infestations Enterococcal infection 1 5.3 1 5.3 COVID - 19 1 5.3 1 5.3 Appendicitis 1 5.3 1 5.3 Sepsis 3 1 5.3 1 5.3 Respiratory, thoracic and mediastinal disorders Hypoxia 2 10.5 1 5.3 Pleural effusion 2 10.5 1 5.3 Bronchial obstruction 1 5.3 1 5.3 Metabolism and nutrition disorders Hyponatraemia 7 36.8 1 5.3 Hypokalaemia 5 26.3 1 5.3 Decreased appetite 3 15.8 0 0.0 Adverse event All grades ≥ Grade 3 No . % No . % table continued… Cardiac or vascular disorders Hypertension 3 15.8 2 10.5 Atrial fibrillation 2 10.5 1 4 5.3 General disorders and administration site conditions Fatigue 7 36.8 1 5.3 Pyrexia 5 26.3 0 0.0 Oedema peripheral 3 15.8 0 0.0 Gastrointestinal disorders Nausea 12 63.2 0 0.0 Vomiting 7 36.8 0 0.0 Diarrhoea 7 36.8 0 0.0 Constipation 6 31.6 0 0.0 Investigations Aspartate aminotransferase increased 5 26.3 0 0.0 Alanine aminotransferase increased 4 21.1 0 0.0 Blood creatinine increased 4 21.1 0 0.0 Other Rash 5 26.3 0 0.0 Myalgia 4 21.1 0 0.0 Arthralgia 3 15.8 0 0.0 Alopecia 3 15.8 0 0.0 Rash maculo - papular 2 10.5 1 5.3 Orchitis 1 5.3 1 5.3 Contrast media allergy 1 5.3 1 5.3 TEAEs by maximum severity ( N=19) 1 1 All treatment - emergent adverse events (TEAEs) with grade 1 - 2 occurring in at least 3 patients (incidence ≥ 15 . 8 % ) and additionally all events with grade 3 - 5 regardless of relatedness to study treatment are presented . Data source : clinical database . Adverse events were coded using the Medical Dictionary for Regulatory Activities . Grades were determined according to National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE), version 5 . 0 . Grades for Cytokine release syndrome and ICANS were determined according to CARTOX criteria ( Neelapu et al . , 2018 ) . Patients are counted only once per adverse event and severity classification ; 2 ICANS : Immune effector cell - associated neurotoxicity syndrome ; 3 Patient died from sepsis of unknown origin and did not receive IMA 203 T cells ; 4 DLT : Dose limiting toxicity ; * 100 % of patients experienced transient cytopenias ≥ Grade 3 (CTCAE v 5 . 0 ) DLT: Transient, Grade 3 atrial fibrillation Onset on day 5 post infusion that resolved within 48h DLT triggered expansion of DL2 CRS/ICANS: No ≥ Grade 3 CRS or ICANS observed so far Most Adverse Events were associated with lymphodepletion 16 Data cut - off – 05 - Oct - 2021 IMA203
ACTengine® IMA203 – Change in Target Lesions Objective Responses across Multiple Tumor Types at Doses below 1 billion Transduced Cells 1 RECIST1.1 response at the timepoint of maximum change of target lesions (week 12): PD due to new lesions ( leptomeningeal disease) at week 12 2 Patients dosed with DL2, EC1 and EC2; * Confirmed at subsequent scan; ** Confirmation pending as of data cut - off Preliminary Objective Response Rates (RECIST1.1., confirmed and unconfirmed) All doses Dosed above DL1 All comers 8/16 (50%) 8/13 (62%) Melanoma 3/3 (100%) 3/3 (100%) Head & Neck Cancer 1/3 (33%) 1/1 (100%) Synovial Sarcoma 3/5 (60%) 3/5 (60%) Uveal Melanoma 1/2 (50%) 1/2 (50%) 17 Best Overall Response (RECIST1.1) 2 0 3 - E C 2 - 0 1 2 0 3 - D L 2 - 0 2 2 0 3 - E C 1 - 0 3 2 0 3 - D L 3 - 0 3 2 0 3 - D L 2 - 0 6 2 0 3 - D L 1 - 0 3 2 0 3 - D L 1 - 0 1 2 0 3 - D L 1 - 0 2 2 0 3 - D L 2 - 0 4 2 0 3 - D L 3 - 0 2 2 0 3 - D L 2 - 0 1 2 0 3 - E C 1 - 0 2 2 0 3 - E C 1 - 0 1 2 0 3 - D L 2 - 0 5 2 0 3 - D L 2 - 0 3 2 0 3 - D L 3 - 0 1 -50 0 50 -63.3 -61.0 -51.7 -50.5 -47.7 -39.9 -37.9 -33.8 -13.1 -9.7 -6.9 -4.2 -2.0 -0.5 5.2 8.8 B e s t c h a n g e i n s u m o f d i a m e t e r [ % ] a n d B O R ( R E C I S T 1 . 1 ) Dose Level: DL2 2 DL1 DL3 PD SD SD SD SD SD SD PR* PR* PR PR PR PR PR PR* + + S C C S y n o v i a l S a r c o m a U v e a l M e l a n o m a N S C L C O v a r i a n C a n c e r H e a d & N e c k C a n c e r H e a d & N e c k C a n c e r S y n o v i a l S a r c o m a M e l a n o m a S y n o v i a l S a r c o m a S y n o v i a l S a r c o m a U v e a l M e l a n o m a M e l a n o m a M e l a n o m a 1 H e a d & N e c k C a n c e r S y n o v i a l S a r c o m a SD ** Data cut - off – 05 - Oct - 2021 IMA203
Patient ID Indication Dose 203 - DL1 - 01 Head & Neck Cancer DL1 203 - DL1 - 02 Head & Neck Cancer DL1 203 - DL1 - 03 Ovarian Cancer DL1 203 - EC1 - 01 Melanoma EC1 203 - EC1 - 02 Melanoma EC1 203 - EC1 - 03 Uveal Melanoma EC1 203 - DL2 - 01 Synovial Sarcoma DL2 203 - DL2 - 02 Synovial Sarcoma DL2 203 - DL2 - 03 Synovial Sarcoma DL2 203 - DL2 - 04 Synovial Sarcoma DL2 203 - DL2 - 05 Head & Neck Cancer DL2 203 - DL2 - 06 NSCLC DL2 203 - EC2 - 01 SCC EC2 203 - DL3 - 01 Uveal Melanoma DL3 203 - DL3 - 02 Melanoma DL3 203 - DL3 - 03 Synovial Sarcoma DL3 ACTengine® IMA203 – Response Over Time Objective Responses across Multiple Tumor Types at Doses below 1 billion Transduced Cells x x x x x Alive (time from infusion to data cut - off or death) PD Deceased x x SD PR Week Month x x x x 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 x PR ongoing at data cut - off According to RECIST1.1 First tumor response assessment x Data cut - off – 05 - Oct - 2021 18 IMA203
ACTengine® IMA203 – Engraftment, Persistence & Tumor Infiltration Clinical Responses Consistent with Biological Data T cell Engraftment & Persistence Tumor Infiltration post I nfusion 2 1 Mann - Whitney U test, p=0.065 ; 2 Post infusion biopsies at week 6 (except one patient with SD at week 3); 3 Mann - Whitney U test, p=0.0159 2 4 1×10 -1 1×10 0 1×10 1 1×10 2 1×10 3 1×10 4 1×10 5 1×10 6 1×10 7 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 2 5 0 4 0 0 5 5 0 7 0 0 V e c t o r c o p i e s / μ g g D N A PD SD PR B a s e l i n e Days post-infusion SD PR 1×10 1 1×10 2 1×10 3 1×10 4 1×10 5 V e c t o r c o p i e s / g g D N A 0.0159 Case study High T cell engraftment and persistence with trend for association of peak vector copies with clinical response 1 High T cell infiltration observed through serial biopsies associated with clinical response 3 Data cut - off – 05 - Oct - 2021 19 p=0.0159 IMA203
ACTengine® IMA203 – Case Study Patient IMA203 - DL3 - 01 Confirmed Partial Response with Deepening Tumor Regression in Multiple Lesions Liver metastasis Lung metastasis Sub cut . metastasis 0 5 10 15 -100 -50 0 50 Weeks from T Cell Infusion C h a n g e i n D i a m e t e r f r o m B a s e l i n e [ % ] SUM T1: Lymph Node T2: Lymph Node T3: Lung T4: Liver T5: Liver * C hange in Target Lesions T cell Persistence & Peak Response in the Blood • 62 - year - old female; m etastatic uveal melanoma • High tumor burden in multiple organs • Infused at refractory disease after failing 4 prior lines of therapy including 2 lines of CPI 1 • Patient received total dose of 0.59 billion transduced T cells following lymphodepletion • T cell persistence until end of observation & detection in the tumor • All lesions decreased at week 6 - 40% decrease in target lesions response deepened at week 12 to 63% decrease • Best Response (RECIST1.1): PR (confirmed & ongoing) Baseline Week 12 2 4 1×10 -1 1×10 0 1×10 1 1×10 2 1×10 3 1×10 4 1×10 5 1×10 6 1×10 7 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 2 5 0 5 0 0 V e c t o r c o p i e s / μ g g D N A B a s e l i n e Days post-infusion IMA203 1 Immune checkpoint inhibitor Data cut - off – 05 - Oct - 2021 20
Preliminary Findings after Completion of Dose Level 3 ACTengine® IMA203 PRAME – Phase 1a Dose Escalation Interim Update 1 DLT: dose - limiting toxicity, since March 17, 2021 (reported DLT at DL2); 2 CRS: cytokine release syndrome, I CANS: Immune effector cell - associated neurotoxicity syndrome, both graded by CARTOX criteria ( Neelapu et al ., 2018); 3 Objective response rate according to RECIST 1.1 including confirmed and unconfirmed partial responses; * Includes patients treated at enrichment cohorts EC1 and EC2 Additional DLTs 1 ORR 3 at DL2 * & DL3 (8/13 patients) – all still dosed below 1 bn cells SAFETY CLINICAL ACTIVITY BIOLOGICAL ACTIVITY 3 0 Dose levels completed, all below 1 bn cells 0 Grade ≥3 CRS or ICANS 2 50% 62% ORR 3 across all doses and multiple solid cancers (8/16 patients) Blood Tumor High T cell engraftment and persistence High T cell infiltration associated with clinical response 21 Data cut - off – 05 - Oct - 2021 IMA203 Objective responses observed across multiple tumor types at dose levels below 1 billion T cells originally presumed to be subtherapeutic
Our Plans to Achieve Long - Lasting Responses with TCR - T cells against PRAME Phase 1b Cohort A: IMA203 Monotherapy at Target Dose 1 Phase 1b Cohort B: IMA203 at Target Dose plus Checkpoint Inhibitor Phase 1b Cohort C: IMA203CD8 2nd Gen Phase 1a: IMA203 Monotherapy Dose Escalation in Basket Trial Addressing Relevant Secondary Resistance Mechanisms to Increase Durability of Response Patient treatment in Ph1a completed & provisional RP2D 1 determined early 2022 Ph1b Expansion starting 2022 Ph2b Pivotal Trial(s) 22 1 2 3 E ach expansion cohort is designed to evaluate the observed objective response rate, demonstrate durability of response & provide the basis for entering registration trials 22 Enrollment starting in Q2 Enrolling patients Enrollment planned for Q2 Increasing T cell:Tumor cell Ratio Blocking PD - 1/PD - L1 pathway Adding functional CD4 T cells 3 IMA203 1 Exploration of higher dose (DL5) planned; 2 Demonstrated to be associated with durable response: Locke et al. 2020 Blood advances; 2 Demonstrated to be important for long - term remission: M elenhorst et al. 2022 Nature
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 achieving decade - long remissions show that CD4 T cells d ominat e at the later t ime p oints of response 1 • Functional superiority of the CD8 αβ 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 CD8 αβ construct (IMA203CD8) IND filing for IMA203CD8 lead candidate targeted in 1H 2022 TUMOR CELL DEATH CD4 T CELL Cytotoxi c Activity CD8 T CELL T cell Help Cytotoxi c Activity 23 IMA203CD8 1 Melenhorst et al. 2022 Nature
ACTengine® IMA203CD8 – Preclinical Assessment of Anti - Tumor Efficacy Co - Transduction of CD8 Enhances Anti - Tumor Activity in Vitro 18 36 56 74 94 114134 152 172192 0.0 0.5 1.0 1.5 2.0 IMA203CD8 TCR IMA203 TCR Non - Transduced Control S erial Killing Assay – CD8 & CD4 T cells Engagement of CD4 T cells may enhance depth and durability of anti - tumor response and clinical outcome of TCR - T in solid cancer patients 2 nd addition of tumor cells 3 rd addition of tumor cells Tumor Growth Hours after co - culture F ull Data Presentation at SITC 2021: Improved anti - tumor activity of next - generation TCR - engineered T cells through CD8 co - expressio n Day 0 D ay 3 N o CD4 T cells IMA203 TCR D ay 6 IMA203CD8 TCR 3D Spheroid Killing – CD4 T cells 24 IMA203CD8
ACTengine® IMA201 Targeting MAGEA4/8 Key Features 25 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 N=2 pts treated in phase 1 dose escalation cohort DL2 commenced 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% Data cut - off – 17 - Sep - 2021 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) TARGET TCR C LINICAL DATA PATIENT POPULATION 3 IMA201
ACTengine® IMA202 Targeting MAGEA1 Key Features 26 HLA - A*02 - presented peptide derived from MAGEA1 Naturally and specifically presented on tumors at high target density 1 : 50 - 900 copies/cell Identified and validated by XPRESIDENT® quant. mass spectrometry platform High - affinity, specific TCR targeting MAGE1 High functional avidity 2 : EC50 ~15 ng/ml Identified and characterized by XCEPTOR® TCR discovery and engineering platform N=10 pts treated in phase 1 dose escalation cohort Target dose level DL3 ongoing Manageable tolerability profile; no DLTs or CRS/ICANS ≥ grade 3 Disease control in 7/10 patients (9 pts in DL1 & DL2) Maximum change of target lesion - 35.4% in melanoma pt 3 HCC – 40% Squamous NSCLC – 35% Sarcoma Subtypes – up to 30% Melanoma – 30% Bladder Carcinoma – 20% Esophageal Carcinoma – 20% Data cut - off – 17 - Sep - 2021 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 Timepoint of maximum change of target lesion (week 12): PD due to growth of non - target lesion; 4 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data) TARGET TCR C LINICAL DATA PATIENT POPULATION 4 IMA202
ACTengine® IMA204 First - in - Class TCR - T Targeting Tumor Stroma Key Features 27 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) TARGET TCR PREC LINICAL 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 IMA204
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 Control IMA204 TCR D7 D16 D22 D29 28 • Affinity maturated CD8 - independent, next - generation TCR engages both CD4 and CD8 T cells without the need of CD8 co - transduction • IND - enabling studies are nearing completion Stroma cells Tumor 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 d ata 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 IMA204
ACTallo® IMA30X – Immatics’ Allogeneic Cell Therapy Approach Effective Redirection of γδ T cells Using αβ TCR 29 • Proprietary manufacturing protocol delivering robust expansion of γδ T cells with the potential for hundreds of doses from one single donor leukapheresis • Off - the - shelf cell therapy , applicable without need for personalized manufacturing and not reliant on potentially encumbered immune system of patient • High potency: TCR transduced γδ T cells show similar anti - tumor activity to αβ T cells • Proprietary single lentiviral vector system (4 - in - 1 construct) including TCR and CD8 alpha & beta chains • γδ T cells are abundant, show intrinsic anti - tumor activity, naturally infiltrate solid tumors and do not cause graft - vs - host disease γδ T cell collection from healthy donor Off - the - shelf product Transduction Expansion ACTallo ® Immatics’ Allogeneic ACT Approach ACTallo®
TCER® – TCR Bispecifics 30
TCER® – Mechanism of Action Immatics’ Off - the - Shelf TCR Bispecifics Approach 31 TCER®
TCER® – Immatics’ Half - Life Extended Bispecifics 32 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 b iologic 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 TCER® T cell recruiting antibody pHLA targeting 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); 3 Production in mammalian cells (CHO cells); 4 Based on preclinical testing TCER®
TCER® – Development of a Proprietary TCR Bispecific Format Flexible Plug - and - play Platform Designed to Efficiently Generate New TCR Bispecifics 33 • Immatics developed a proprietary TCR Bispecific format for specific targeting of tumor - specific pHLA at low copy numbers • TCER® format successfully validated for different TCRs and different T cell recruiting antibodies Fc - domain (silenced IgG1, heterodimerization via KiH S - S ) anti - pHLA TCR high affinity T cell - recruiting Ab low affinity NH 2 NH 2 COOH COOH C H 3 C H 2 Hinge CH3 KiH VL V β VH V α TCER®
Potency of Our Proprietary TCR Bispecific Format TCER® 34 • 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 TCER® TCER® 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® Portfolio Building a Pipeline of Next - Gen Half - Life Extended TCR Bispecifics 35 IMA401 IMA402 IMA40X MAGEA4/8 PRAME Undisclosed Status Start of Phase 1 trial in May 2022 Clinical GMP batch targeted in 2022 Phase 1 trial in 2023 TCER ® engineering and preclinical testing ongoing Preclincial Proof - of - concept – 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 Development 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 TCER® 1 Clinical trial application – the European equivalent of an Investigational New Drug (IND) application
Phase 1 Clinical Trial to Evaluate TCER® IMA401 Targeting MAGEA4/8 36 Trial Overview Primary Objective Biomarker positive patients with recurrent and/or refractory solid tumors • HLA - A*02:01 • MAGEA4/8 (Immatics’ IMADetect® test) Basket trial in indications with high MAGEA4/8 prevalence, e.g. sqNSCLC , SCLC, HNSCC, bladder carcinoma , esophageal carcinoma , ovarian carcinoma, melanoma, uterine carcinosarcoma , sarcoma subtypes Phase 1a: Dose escalation cohort Phase 1b: Dose expansion cohort (s) Up to N=50 patients Up to 15 centers • Determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) Secondary Objectives • Safety and tolerability • Initial anti - tumor activity • Pharmacokinetics MTD: maximum tolerated dose, RP2D: recommended phase 2 dose TCER®
Phase 1 Clinical Trial to Evaluate TCER® IMA401 Targeting MAGEA4/8 37 MTD: maximum tolerated dose, RP2D: recommended phase 2 dose; MABEL: minimum anticipated biological effect level; BLRM: Bayesian logistic regression model; 1 P harmacokinetics 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 • MABEL - based starting dose • Weekly i.v. infusions 1 • 2 - week DLT evaluation period • Dose escalation decisions based on cohorts of 1 - 6 patients in adaptive design (BLRM model) MTD/ 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 TCER®
TCER® IMA401 Targeting MAGEA4/8 Product Candidate in Clinical Development with Bristol Myers Squibb 38 Treatment schedule Tumor Model in Mice 1 1 8 15 22 Study day Transplantation Human PBMC IMA401 TCER ® Transplantation Tumor -22-12 • 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 N=6 mice per group, two PBMC donors Dose: two dose levels TCER® 1 Hs695T xenograft model in MHC I/II ko NSG mice, tumor volume of individual mice shown
TCER ® IMA402 Targeting PRAME Preclinical - stage Product Candidate Fully Owned by Immatics PRAME Target Peptide • HLA - A*02 - restricted PRAME peptide targeted by TCER® IMA402 is one of the most frequently expressed intracellular cancer targets for TCR - based therapies » Homogenously expressed at high prevalence across multiple solid tumors including melanoma, lung cancer, gynecological cancers (ovarian, breast, uterine) and others Preclinical Proof - of - Concept Data • High in vitro potency in killing of tumor cells with physiological PRAME peptide levels • Favorable safety profile with broad therapeutic window between tumor and normal cell reactivity in vitro • Consistent tumor regression including complete responses in NOG mice treated at low doses • Extended serum half - life of several days 1 expected in humans driven by the TCER® Fc part Well Progressing CMC Development • Current data support antibody - like manufacturability and developability • GMP process development and IND - enabling activities ongoing • Manufacturing of the clinical batch for the Phase 1 trial expected in 2H 2022 39 1 Based on preclinical testing TCER®
TCER® IMA402 – Efficacy Assessment in Tumor Model in Mice Superior Tumor Control Using a Proprietary, Low - Affinity Recruiter 40 Widely used T cell recruiting Ab (3 variants) medium to high affinity Treatment schedule N=6 mice per group, two PBMC donors 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 Immatics’ T cell recruiting Ab low affinity IMA402 Treatment start Administration of IMA402 in defined dosage interval TCER® Tumor Model in Mice 1 1 Hs695T xenograft model in NOG m ice , tumor volume of group means shown Bunk at al ; PEGS2021
TCER® IMA402 – In vitro Safety Assessment with Normal Tissue Cells 41 • Cytotoxicity against N≥9 different human normal tissue cell types • TCER® IMA402 shows a minimum of 1,000 - fold therapeutic window between normal tissue cell reactivity and tumor cell reactivity Normal Tissue Type Therapeutic Window (x - fold) IPSC - derived astrocytes ≥1 , 000 IPSC - derived GABA neurons ≥1 , 000 IPSC - derived cardiomyocytes ≥1 , 000 Human Pulmonary Fibroblasts ≥1 , 000 Human Cardiac Microvascular Endothelial Cells ≥1 , 000 Human Dermal Microvascular Endothelial Cells ≥1 , 000 Human Aortic Endothelial Cells ≥1 , 000 Human Coronary Artery Smooth Muscle Cells ≥1 , 000 Human Tracheal Smooth Muscle Cells ≥1 , 000 IPSC - derived Cardiomyocytes 0 50 100 150 10 -1 10 0 10 1 10 2 10 3 10 4 10 5 iAstrocytes and Hs695T TCER [pM] C y t o t o x i c i t y [ % ] w/o PRAME - positive tumor cell line normal tissue cell type TCER®
Immatics’ Proprietary Target and TCR Discovery Platforms 42
True Cancer Targets & Matching Right TCRs Goal to Maximize Anti - Tumor Activity and Minimize Safety Risks of TCR - based Immunotherapies 43 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 + Technology 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 44 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<0.001 2 Technology 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
Technology Pool of 200 Prioritized Targets as Foundation for Future Value Generation 45 200 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 a nalyzed by Quantitative, Ultra - Sensitive Mass Spectrometry pHLA Database based on primary tissues >200 prioritized targets
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics 46 TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy ACTengine® ACTallo ® • Fast, efficient and highly sensitive discovery of highly specific, natural TCRs • Protein engineering capabilities to design and maturate TCRs with increased affinity while retaining specificity • Early de - selection of cross - reactive TCRs by the u nique interplay between Immatics’ target and TCR discovery platforms XPRESIDENT® and XCEPTOR® during TCR discovery 1 and TCR maturation 2 Micromolar affinity Nanomolar affinity Technology 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 47 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Off - target 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 Technology 1 Clinical fatalities have occurred in TCR - T trials using a titin cross - reactive TCR (Cameron et al ., Sci Transl Med)
Corporate Information & Milestones 48
Experienced Global Leadership Team Across Europe and the US 49 Harpreet Singh Chief Executive Officer Co - Founder >20 yrs biotech experience Carsten Reinhardt Chief Development Officer >20 yrs pharma & biotech experience ( Micromet , Roche, Fresenius) 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 Arnd Christ Chief Financial Officer >20 yrs biotech experience ( Probiodrug , NovImmune , Medigene , InflaRx ) Toni Weinschenk Chief Innovation Officer Co - Founder >15 yrs biotech experience Jordan Silverstein Head of Strategy >10 yrs biotech experience (Advanced Accelerator Applications, InflaRx ) Edward Sturchio General Counsel >15 yrs pharma & biotech experience (Schering, Merck, Novartis, Advanced Accelerator Applications, Abeona Therapeutics) Cedrik Britten Chief Medical Officer >10 yrs pharma & biotech experience ( BioNTech , GSK) Corporate
Strong, Focused and Highly Integrated Trans - Atlantic Organization 50 Senior Leadership, Business Development, Clinical Operations, Intellectual Property, Regulatory Affairs, Communications Senior Leadership, Research and Development (Adoptive Cell Therapy), CMC, Clinical Operations, Regulatory Affairs, QA/QC, HR, Investor Relations Munich, Germany, ~45 FTEs Tübingen, Germany, ~175 FTEs Houston, Texas , ~ 125 FTEs Senior Leadership, Research and Development (XPRESIDENT®, XCEPTOR®, TCER®), Translational Development, Clinical Operations, Finance, HR, IT, QM Corporate FTE status as of 31 December 2021
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 51 Cancer targets, TCRs and technology protected by: • 5,800 applications and patents filed in all major countries and regions • >120 patent families • >2,000 granted patents, thereof >490 granted patents in the US Corporate
Near - Term Value Drivers and Development Milestones Clinical Expansion of TCR Bispecifics and the Next - generation of TCR - T 52 Leverage full potential of targeting PRAME • Focused & accelerated development of IMA203 expansion cohorts • Develop IMA402, an off - the - shelf TCER® Advance clinical development of ACTengine® candidates • Initiation of multiple IMA203 Ph1b expansion cohorts ongoing: Monotherapy, checkpoint combination, 2nd - gen approach IMA203CD8 • Next IMA203 monotherapy data read - out in 2H 2022 • Initial data read - out for checkpoint combination, IMA203CD8 YE 2022 • Advance IMA204 to the clinic, submission of IND application YE 2022 Further clinical development of TCER® candidates • Start of Ph1 trial for IMA401 (MAGEA4/8) in May 2022 • Manufacturing of IMA402 clinical batch in 2H 2022, clinical trial in 2023 • Innovative TCER® program(s) IMA40X in preclinical development Corporate
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