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 11, 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 10, 2022, Immatics N.V. (the “Company”, “Immatics”, “we”) announced a clinical data update for the ACTengine IMA203 TCR-T monotherapy targeting an HLA-A*02-presented peptide derived from the tumor antigen PRAME covering:
| · | The completed Phase 1a dose escalation part of the clinical trial, during which we treated 27 patients, including 7 patients at the provisional recommended Phase 2 dose (“RP2D”) (being dose level 4). The Phase 1a patients were heavily pre-treated, had a particularly high baseline tumor burden and an average of 4.2 prior lines of treatment, and patients treated at the RP2D had an average of 4.6 prior lines of treatment. |
| · | Initial data from the first 5 patients in the ongoing Phase 1b dose expansion cohort A (monotherapy). These Phase 1b patients were heavily pre-treated, had high to moderate baseline tumor burden and an average of 4.0 prior lines of treatment. |
The cutoff date for clinical data update is September 6, 2022.
Moving from Phase 1a to Phase 1b, we are continuing to introduce planned improvements that may influence clinical outcomes including (1) applying higher cell doses (DL4 and exploratory DL5), (2) optimizing the cell product through manufacturing enhancements, and (3) working with disease area experts to gradually reduce the fraction of very heavily pre-treated patients with extreme tumor burden who have exhausted standard of care and have undergone multiple clinical trials. In addition, the focus in Phase 1b is also shifting from initial ORR determined at ~6-week scan to confirmed ORR determined at the ~12-week scan.
We observed a higher overall response rate (“ORR”) and confirmed ORR (“cORR”) in patients who received doses above 1 billion TCR-T cells, being dose levels 4 and 5. The table below sets forth the observed overall response rates, as measured by RECIST v1.1:
| Phase 1a | Phase 1a + Phase 1b | Phase 1b only | ||
| All pts (DL1-4) | DL4 pts only1 | DL4/DL5 pts only1 | All pts (DL4/DL5)1 | |
| Patients Treated | 27 | 7 | 12 | 5 |
| ORR (~week 6) | 48% (13/27) | 57% (4/7) | 67% (8/12) | 80% (4/5) |
| cORR (~week 12)2 | 19% (5/27) | 29% (2/7) | 50% (6/12)* | 80% (4/5)* |
1 All patients received >1 billion total TCR-T cells; 2 confirmed ORR (cORR), * 1 patient with SD at ~6-week scan with pending ~12-week scan considered as non-responder for cORR; DL – dose level.
We observed confirmed objective responses in patients with a broad spectrum of different tumor types, including cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma and synovial sarcoma. The graphs below show the best percentage change in target lesions:
* Maximum change of target lesions and RECIST 1.1 BOR response at different time points; #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
In addition, we observed encouraging early signs of improved durability at higher doses and in Phase 1b patients. The graphs below show the change in sum of longest diameter of lesions over time:
# Synovial sarcoma patient (DL3) PD at week 6 not shown 12 as target lesions were not evaluable; PD: Progressive disease; SD: Stable disease; PR: Partial response; cPR: Confirmed partial response; BL: Baseline
Translational data obtained during the Phase 1a and Phase 1b cohort A trial further provide clinical validation of PRAME as a highly promising T cell target for solid cancers. Confirmed clinical responses were observed at high and low PRAME-expression levels above threshold, as shown in the following graph, indicating IMA203’s potential to provide clinical benefit for all PRAME biomarker-positive cancer patients.
The predicted high PRAME prevalence across key indications has so far been supported by prevalence rates obtained during the clinical screening of patients. Biological data including T cell engraftment, persistence and tumor infiltration were consistent with clinical outcomes, as shown in the following graphs, and support the proposed mechanism of action for IMA203.
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)
The most frequent treatment-emergent adverse events (“TEAEs”) were as expected for cell therapies, and we believe that IMA203 demonstrated a favorable tolerability profile. Specifically, we observed that:
| · | All 32 infused patients experienced cytopenia (Grade 1-4) associated with lymphodepletion; |
| · | 31 patients (97%) experienced cytokine release syndrome (“CRS”) of any grade: |
| o | 29 patients had low to moderate CRS (Grade 1-2) |
| o | 2 patients had Grade 3 CRS that occurred in Phase 1a, with both patients having recovered to Grade ≤ 2 after three and four days, respectively; |
| · | 5 patients (16%) experienced a low to moderate (Grade 1-2) immune effector cell associated neurotoxicity syndrome (ICANS); |
| · | No dose-dependent increase of CRS and ICANS was observed; |
| · | No additional dose limiting toxicities (“DLT”) were observed since the initial data release in March 2021; |
| · | No IMA203-related Grade 5 adverse events. |
The tables below show the Grade ≥3 TEAEs observed regardless of relatedness to study treatment:
1 All treatment-emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment that occurred in at least 1 patient (except for ICANS, where only Grade 1-2 occurred; listed for completeness due to being an adverse event of special interest) are presented. 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, version 5.0. Grades for CRS and ICANS were determined according to CARTOX criteria (Neelapu et al., 2018). Patients are counted only once per adverse event and severity classification. Based on interim data extracted from open clinical database (06-Sep-2022); 2 ICANS: Immune effector cell-associated neurotoxicity syndrome; 3 DLT: Dose limiting toxicity in phase 1a at DL2 reported on March 17, 2021; 4 Fatal Adverse events in N=3 patients were not considered related to any study drug; 5 Patient did not receive IMA203 TCR-T cells; * Two patients with disease progression after first IMA203 infusion received exploratory second IMA203 infusion. They had these ≥ Grade 3 TEAEs only after second infusion, which are included in the table: First patient: Abdominal pain, Diarrhoea, Cytokine release syndrome, Hypokalaemia, Proteinuria; Second patient: Fracture, Muscle spasms, Neutropenia, Thrombocytopenia.
IMA203 is currently being evaluated in an ongoing Phase 1b trial including three expansion cohorts: (A) IMA203 as a monotherapy, (B) IMA203 in combination with an immune checkpoint inhibitor and (C) IMA203CD8, a next-generation cell therapy where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor. We expect further data read-outs on the individual cohorts in the IMA203 trial throughout 2023.
In addition to the ACTengine IMA203 programs, we are addressing PRAME-positive cancers with a second therapeutic modality: TCR Bispecifics. Our TCER IMA402 is a next-generation, half-life extended TCR Bispecific which is expected enter the clinic in 2023. Both approaches, ACTengine and TCER, are distinct therapeutic modalities that have the potential to provide innovative treatment options for a variety of cancer patient populations with different medical needs.
In connection with the foregoing, the Company issued a press release, a copy of which is attached hereto as Exhibit 99.1, and made available a presentation, a copy of which is attached hereto as Exhibit 99.2.
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.
EXHIBIT INDEX
| Exhibit No. | Description |
| 99.1 | Press release dated October 10, 2022 |
| 99.2 | Presentation dated October 10, 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 11, 2022 | ||
| By: | /s/ Harpreet Singh | |
| Name: | Harpreet Singh | |
| Title: | Chief Executive Officer | |
Exhibit 99.1
PRESS RELEASE
Immatics Reports Interim Clinical Data Update on ACTengine® IMA203 TCR-T Monotherapy Targeting PRAME
Company to host conference call today, October 10, at 8:30 am EDT / 2:30 pm CEST
| · | Clinical validation of PRAME as multi-tumor target with large potential for TCR-based therapies: confirmed responses in different solid cancers, in patients with high and low PRAME expression |
| · | Update covers data from 27 patients in completed Phase 1a dose escalation and first 5 patients in Phase 1b dose expansion (cohort A) treated with IMA203 monotherapy |
| · | Confirmed objective response rate (cORR): 50% (6/12) at target dose or above with at least 1 billion infused TCR-T cells across Phase 1a and 1b; thereof 80% cORR (4/5) in Phase 1b patients alone with all responses ongoing at data cut-off |
| · | Confirmed responses across different solid tumor types: cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcoma |
| · | Treatment with IMA203 continues to show manageable tolerability; biological data including T cell engraftment, persistence and tumor infiltration consistent with clinical data |
| · | IMA203 TCR-T is part of Immatics’ strategy to leverage the full clinical potential of targeting PRAME; next data read-outs on IMA203 monotherapy, IMA203 in combination with a checkpoint inhibitor and 2nd generation IMA203CD8 planned during 2023 |
Houston, Texas and Tuebingen, Germany, October 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 a clinical data update for the IMA203 monotherapy covering the completed Phase 1a dose escalation part of the trial and initial data from the first 5 patients in the ongoing Phase 1b dose expansion cohort A (monotherapy). In the Phase 1 trial with ACTengine® IMA203, Immatics is treating recurrent and/or refractory solid cancer patients utilizing TCR-T cells directed against an HLA-A*02-presented peptide derived from PRAME, which is frequently expressed across several solid cancer indications. Overall, IMA203 continues to be well tolerated and achieved confirmed
| Immatics Press Release October 10, 2022 | 1 | 6 |
objective responses across multiple solid cancers such as cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcoma. Encouraging early signs of improved durability were seen with a 50% (6/12) confirmed objective response rate, when patients were infused at the target dose or above with more than 1 billion TCR-T cells.
Key clinical findings from IMA203 TCR-T monotherapy
The data obtained during the Phase 1a and Phase 1b cohort A trial provide clinical validation of PRAME as a highly promising T cell target for solid cancers. Confirmed clinical responses were observed at high and low PRAME-expression levels above threshold, indicating IMA203’s potential to provide clinical benefit for all PRAME biomarker-positive cancer patients. The predicted high PRAME prevalence across key indications has so far been supported by prevalence rates obtained during the clinical screening of patients.
Moving from Phase 1a to Phase 1b, Immatics has continued to introduce planned improvements that may influence clinical outcomes including (1) applying higher cell doses (DL4 and exploratory DL5), (2) optimizing the cell product through manufacturing enhancements and (3) working with disease area experts to gradually reduce the fraction of very heavily pre-treated patients with extreme tumor burden who have exhausted standard of care and have undergone multiple clinical trials. In addition, the focus in Phase 1b is also shifting from initial objective response rate (ORR) determined at the ~6-week scan to confirmed ORR determined at the ~12-week scan.
Preliminary Objective Response Rates (ORR; RECIST 1.1) in Phase 1a and Phase 1b Cohort A
| Phase 1a | Phase 1a + Phase 1b | Phase 1b only | ||
| All pts (DL1-4) | DL4 pts only 1 | DL4/DL5 pts only1 | All pts (DL4/DL5)1 | |
| Patients Treated | 27 | 7 | 12 | 5 |
| ORR (~week 6) | 48% (13/27) | 57% (4/7) | 67% (8/12) | 80% (4/5) |
| cORR (~week 12)2 | 19% (5/27) | 29% (2/7) | 50% (6/12)* | 80% (4/5)* |
1 All patients received >1 billion total TCR-T cells; 2 confirmed ORR (cORR), * 1 patient with SD at ~6-week scan with pending ~12-week scan considered as non-responder for cORR; DL – dose level
Positively evolving durability profile for IMA203 was observed at higher doses: 6 of 12 patients (50%) treated with more than 1 billion infused TCR-T cells (DL4 and DL5) in the Phase 1a and Phase 1b cohort A part of the trial experienced a confirmed objective response (partial response according to RECIST 1.1). In the Phase 1b part of the trial alone, 4 of 5 patients (80%) had a confirmed objective response which were all ongoing at the timepoint of data cut-off.
| Immatics Press Release October 10, 2022 | 2 | 6 |
“The data presented today highlight the clinical potential of PRAME as one of the most promising multi-tumor targets to achieve meaningful benefits for a large cancer patient population,” commented Cedrik Britten, MD, Chief Medical Officer at Immatics. “In addition to this first data from IMA203 monotherapy today, we are awaiting data from two additional dose expansion cohorts: IMA203 together with an immune checkpoint inhibitor and our 2nd generation product candidate IMA203CD8. As we continue to shift our focus from Phase 1a to Phase 1b, we look forward to reporting meaningful data throughout 2023, including safety and response rates, as well as durability of response with a longer follow-up time. In addition, we are excited to start a first-in-human trial with our half-life extended Bispecific against PRAME, TCER® IMA402, also in 2023.”
Safety data for IMA203 monotherapy across Phase 1a and Phase 1b: Treatment with IMA203 continues to show manageable tolerability profile.
| · | At data cut-off on September 6, 2022, 32 patients were infused with IMA203 TCR-T cells. |
| · | Most frequent treatment-emergent adverse events (TEAEs) were as expected for cell therapies. |
| · | All patients experienced expected cytopenia (Grade 1-4) associated with lymphodepletion. 31 patients (97%) experienced cytokine release syndrome (CRS) of any grade: 29 patients had low to moderate (Grade 1-2), and 2 patients had Grade 3 CRS that occurred in Phase 1a; both recovered to Grade ≤2 after 3 and 4 days. 5 patients (16%) experienced a low to moderate (Grade 1-2) immune effector cell associated neurotoxicity syndrome (ICANS). No dose-dependent increase of CRS and ICANS was observed. |
| · | No additional dose limiting toxicities (DLT) were observed since the initial data release in March 2021. |
Phase 1a - Clinical activity: IMA203 demonstrated a high initial objective response rate in several solid tumor types.
| · | At data cut-off on September 6, 2022, a total of 27 patients received IMA203 monotherapy in the Phase 1a dose escalation trial: |
| o | High initial objective response rate (ORR; partial responses according to RECIST 1.1) of 48% (13/27) was observed at the first CT scan post infusion at ~week 6, and a confirmed ORR of 19% (5/27) the second CT scan at ~week 12. |
| o | 7 out of 27 patients received doses above 1 billion TCR-T cells (DL4); initial ORR was 57% (4/7) and confirmed ORR was 29% (2/7) in these patients. |
| · | Patients were heavily pre-treated with a mean of 4.2 lines of prior systemic treatment and a particularly high baseline tumor burden. |
| Immatics Press Release October 10, 2022 | 3 | 6 |
| · | The provisional recommended Phase 2 dose (RP2D) for Phase 1b dose expansion was determined to be DL4. |
Phase 1b Cohort A - Clinical activity: IMA203 monotherapy demonstrates high confirmed objective response rate of 80% with early signs of prolonged durability.
| · | At data cut-off on September 6, 2022, 5 patients received IMA203 monotherapy at DL4 and DL5 in the Phase 1b cohort A dose expansion trial: |
| o | 4 out of 5 patients (80%) experienced an initial objective response at ~week 6 (PR according to RECIST 1.1). |
| o | In all 4 patients, objective responses were confirmed at ~week 12 and were ongoing at data cut-off: confirmed ORR was 80% (4/5). |
| o | All 4 responses were observed in different solid tumor types: cutaneous melanoma, ovarian cancer, uveal melanoma and head and neck cancer. |
| · | Patients were heavily pre-treated with a mean of 4.0 lines of prior systemic treatment and high to moderate baseline tumor burden. |
ACTengine® IMA203 is currently being evaluated in an ongoing Phase 1b study including three expansion cohorts: (A) IMA203 as a monotherapy, (B) IMA203 in combination with an immune checkpoint inhibitor and (C) IMA203CD8, a next-generation cell therapy where IMA203 engineered T cells are co-transduced with a CD8ab co-receptor. Further data read-outs on the individual cohorts are planned throughout 2023. In addition to the ACTengine® programs, Immatics is addressing PRAME-positive cancers with a second therapeutic modality: TCR Bispecifics. The company’s TCER® IMA402 is a next-generation, half-life extended TCR Bispecific which will enter the clinic in 2023. Both approaches, ACTengine® and TCER®, are distinct therapeutic modalities that have the potential to provide innovative treatment options for a variety of cancer patient populations with different medical needs.
Immatics conference call
Immatics will host a conference call today, October 10, 2022, at 8:30 am EDT / 2:30pm CEST to discuss these clinical data. The webcast and presentation can be accessed directly through this link. Participants may also access the slides and the webcast on the Immatics website in the Investors section under “Presentations” at www.investors.immatics.com/events-presentations. A replay of the webcast will be made available shortly after the conclusion of the call and archived on the Company’s website for at least 90 days.
| Immatics Press Release October 10, 2022 | 4 | 6 |
About IMA203 and target PRAME
ACTengine® IMA203 T cells are directed against an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers, thereby supporting the programs’ potential to address a broad cancer patient population. Immatics’ PRAME peptide is present at a high copy number per tumor cell and is homogenously and specifically expressed in tumor tissue. The peptide has been identified and characterized by Immatics’ proprietary mass spectrometry-based target discovery platform XPRESIDENT®. Through its proprietary TCR discovery and engineering platform XCEPTOR®, Immatics has generated a highly specific T cell receptor (TCR) against this target for its TCR-based cell therapy approach, ACTengine® IMA203.
About ACTengine®
ACTengine® is a personalized cell therapy approach for patients with advanced solid tumors. The patient’s own T cells are genetically engineered to express a novel, proprietary TCR directed against a defined cancer target. The modified T cells are then reinfused into the patient to attack the tumor. The approach is also known as TCR-engineered cell therapy (TCR-T). All Immatics’ ACTengine® product candidates can be rapidly manufactured utilizing a proprietary manufacturing process designed to enhance T cell engraftment and persistence in vivo.
The ACTengine® T cell products are manufactured at the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory in collaboration with UTHealth. The ACTengine® Programs are co-funded by the Cancer Prevention and Research Institute of Texas (CPRIT).
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About Immatics
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 and LinkedIn.
| Immatics Press Release October 10, 2022 | 5 | 6 |
Forward-Looking Statements:
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 Eva Mulder
Trophic Communications
Phone: +49 89 2070 89831 or +31 65 2331 579
immatics@trophic.eu
| Immatics N.V. | |
| Anja Heuer | Jordan Silverstein |
| Director, Corporate Communications | Head of Strategy |
| Phone: +49 89 540415-606 | Phone: +1 281 810 7545 |
| media@immatics.com | InvestorRelations@immatics.com |
| Immatics Press Release October 10, 2022 | 6 | 6 |
Exhibit 99.2
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. ACTengine® IMA203 TCR - T Targeting PRAME Cedrik Britten, Chief Medical Officer Harpreet Singh, Chief Executive Officer October 10, 2022 – Monotherapy Interim Data Update
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
Multi - Tumor Target PRAME Promising Opportunity for TCR - based Therapies 3 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:
IMA203 TCR - T Phase 1 Design Three Phase 1b Expansion Cohorts to Establish Durable Objective Responses 4 Each expansion cohort is designed to establish safety, evaluate the observed objective response rate, demonstrate durability & provide the trigger for registration trials 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; 4 Treatment of n=3 patients in DL3 prior to patient treatment at provisional RP2D (DL4); 5 Demonstrated to be important for long - term remission: Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances 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 4 Adding functional CD4 T cells 5 IMA203 Monotherapy in Basket Trial Completed & provisional RP2D 1 determined in March 2022 First pt treated March 2022 First pt treated May 2022 First pt treated Aug 2022
IMA203 TCR - T Phase 1 Design Interim Clinical Data Update Focused on Phase 1a and Expansion Cohort A 5 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 First pt treated March 2022 Cohort B IMA203 at Target Dose plus Checkpoint Inhibitor 3 Blocking PD - 1/PD - L1 pathway First pt treated May 2022 Cohort C IMA203CD8 2nd Gen 4 Adding functional CD4 T cells 5 First pt treated Aug 2022 IMA203 Monotherapy in Basket Trial Completed & provisional RP2D 1 determined in March 2022 Today’s Update 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; 4 Treatment of n=3 patients in DL3 prior to patient treatment at provisional RP2D (DL4); 5 Demonstrated to be important for long - term remission: Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances Data cut - off – 06 - Sept - 2022
Moving from Phase 1a to Phase 1b Continuous Improvement of Key Aspects that May Influence Clinical Outcome 6 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
7 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), 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
ACTengine® IMA203 Monotherapy – Patient and Product Characteristics 8 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
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 9 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
Frequency of Observed Objective Responses Improved ORR and Confirmed ORR at Higher Dose and in Phase 1b Cohort A 10 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
Best Overall Response IMA203 Continues to Deliver Objective Responses in Major Solid Tumor Types 11 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
Responses over Time Encouraging Early Signs for Improved Durability at Higher Dose and in Phase 1b Patients 12 # 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
Translational Data Consistent with Clinical Outcomes Supporting Proposed Mechanism of Action for IMA203 13 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
PRAME Expression in Tumors from Screened Patients Clinical Validation of Immatics’ Mass Spectrometry - guided RNA Threshold for PRAME 14 Mann - Whitney U test, p=0.076 IMA203 achieved objective responses at all expression levels above threshold 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 N =3 2
Moving from Phase 1a to Phase 1b 15 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 4. Transition to indication - specific development strategy: Based on PRAME prevalence, patient population size and observed responses
IMA203 TCR - T Has the Potential to Reach a Large Patient Population ~39,000 Patients per Year in the US only 16 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 spectrometry - 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
IMA203 Monotherapy – Conclusions ACTengine® IMA203 Targeting PRAME Offers a Unique Opportunity for Solid Cancer Patients 17 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
Comprehensive PRAME Strategy To Deliver Meaningful Clinical Benefit to Patients with PRAME - positive Cancers 18 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 4 Adding functional CD4 T cells 5 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 First pt treated Aug 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; 4 Treatment of n=3 patients in DL3 prior to patient treatment at provisional RP2D (DL4); 5 Demonstrated to be important for long - term remission: Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances
University Hospital Dresden University Hospital Bonn University Hospital Würzburg Columbia University University of Pittsburgh MD Anderson Cancer Center University Hospital Hamburg Dr. D. Araujo Dr. A. Tsimberidou Dr. W. Alsdorf Dr. T. Holderried Dr. M. Chatterjee Dr. J. Luke Ge rma n y United States Dr. M. Wermke … and the Investigators at the Clinical Sites Dr. R. Carvajal Dr. R. Reshef 19 We are Immensely Grateful to the Patients, Their Families …
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. ww w .i mm a ti c s . c o m
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]
IMA203 Tolerability Profile – All ≥Grade 3 Adverse Events Adverse event ≥ Grade 3 No. % TEAEs by maximum severity (N=33) 1* ≥ Grade 3 No. % Adverse event Patients with any adverse event 33 100.0 table continued… Adverse Events of Special Interest Investigations Cytokine release syndrome 2 6.1 ICANS 2 0 0.0 Blood alkaline phosphatase increased 1 3.0 Blood creatinine increased 1 3.0 Blood fibrinogen decreased 1 3.0 Blood and lymphatic system disorders Neutropenia 27 81.8 Lymphopenia 22 66.7 Leukopenia 20 60.6 Anaemia 17 51.5 Thrombocytopenia 13 39.4 Cytopenia 1 3.0 Leukocytosis 1 3.0 Lymphocytosis 1 3.0 Metabolism and nutrition disorders Hypokalaemia 2 6.1 Failure to thrive 1 3.0 Vascular disorders Hypertension 2 6.1 Hypotension 1 3.0 Injury, poisoning and procedural complications Fracture 1 3.0 Infusion related reaction 1 3.0 Infections and infestations Appendicitis 1 3.0 COVID - 19 1 3.0 Enterococcal infection 1 3.0 Orchitis 1 3.0 Sepsis 4,5 1 3.0 Septic shock 4 1 3.0 Renal and urinary disorders Acute kidney injury 1 3.0 Proteinuria 1 3.0 Cardiac disorders Atrial fibrillation 3 1 3.0 Respiratory, thoracic and mediastinal disorders Endocrine disorders Hypoxia 2 6.1 Bronchial obstruction 1 3.0 Laryngeal inflammation 1 3.0 Pleural effusion 1 3.0 Respiratory failure 1 3.0 Inappropriate antidiuretic hormone secretion 1 3.0 Eye disorders Ulcerative keratitis 1 3.0 Hepatobiliary disorders Cholangitis 1 3.0 General disorders and administration site conditions Immune system disorders Condition aggravated 4 1 3.0 Fatigue 1 3.0 Pyrexia 1 3.0 Swelling face 1 3.0 Contrast media allergy 1 3.0 Musculoskeletal and connective tissue disorders Muscle spasms 1 3.0 Reproductive system and breast disorders Gastrointestinal disorders Abdominal pain 1 3.0 Diarrhoea 1 3.0 Vomiting 1 3.0 Vaginal haemorrhage 1 3.0 Skin and subcutaneous tissue disorders Rash maculo - papular 1 3.0 1 All treatment - emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment that occurred in at least 1 patient (except for ICANS, where only Grade 1 - 2 occurred ; listed for completeness due to being an adverse event of special interest) are presented . 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, version 5 . 0 . Grades for CRS and ICANS were determined according to CARTOX criteria (Neelapu et al . , 2018 ) . Patients are counted only once per adverse event and severity classification . Based on interim data extracted from open clinical database ( 06 - Sep - 2022 ) ; 2 ICANS : Immune effector cell - associated neurotoxicity syndrome ; 3 DLT : Dose limiting toxicity in phase 1 a at DL 2 reported on March 17 , 2021 ; 4 Fatal Adverse events in N= 3 patients were not considered related to any study drug ; 5 Patient did not receive IMA 203 TCR - T cells ; * Two patients with disease progression after first IMA 203 infusion received exploratory second IMA 203 infusion . They had these ≥ Grade 3 TEAEs only after second infusion, which are included in the table : First patient : Abdominal pain, Diarrhoea, Cytokine release syndrome, Hypokalaemia, Proteinuria ; Second patient : Fracture, Muscle spasms, Neutropenia, Thrombocytopenia . 22 • IMA203 was well tolerated • No ≥Grade 3 Adverse Events in ≥ 10% of patients except for expected events associated with lymphodepletion • No IMA203 - related Grade 5 Adverse Events
Focus on Melanoma Patients High ORR and cORR in Heavily Pre - Treated Patients with High Tumor Burden 23 Melanoma Subtype ORR (~6 weeks) 1 cORR (~12 weeks) 2 Melanoma (DL4/DL5) 3 6/8 (75%) 4/8 (50%) # Melanoma (all DL) 10/13 (77%) 5/13 (38%) # Cutaneous Melanoma 7/8 (88%) 2/8 (25%) Uveal Melanoma 2/3 (67%) 2/3 (67%) Unknown Primary 1/2 (50%) 1/2 (50%) # Data cut - off – 06 - Sept - 2022 * Maximum change of target lesions and RECIST1.1 response at different timepoints; 1 ORR: Objective response rate (partial responses) according to RECIST 1.1 at first scan post infusion (~6 weeks); 2 Confirmed ORR (cORR): Confirmed objective response rate (confirmed partial responses) according to RECIST 1.1 at second scan post infusion (~12 weeks); 3 All patients received >1x10 9 total transduced viable CD8 T cells; # 1 patient with SD at ~ 6 - week scan with pending ~12 - week scan considered as non - responder for cORR; CPI: checkpoint inhibitor Patient Characteristics (n=13) Prior lines of treatment Mean (min, max) 4.5 (1, 7) Previous lines of CPI Mean (Min, Max) 2.5 (1, 4) LDH at baseline >1 x ULN [% of patients] 69% Particular hard - to - treat patient population enrolled so far
PRAME Expression in Tumors from Screened Patients Highlighting Type of Best Overall Response (left) and Study Cohort (right) 24 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 N =3 2 N =3 2 p= 0.076 IMA203 achieved objective responses at all expression levels above Immatics’ mass spectrometry - guided RNA threshold
PRAME Expression – RNAseq Data Combined with Immatics’ Mass Spectrometry - guided RNA Threshold for Prevalence Prediction 25 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