Immatics N.V 6-K, filed May 2, 2023
Immatics N.V. (IMTX)
About this 6-K
Immatics N.V filed this 6-K on May 2, 2023.
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
May 2, 2023
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 |
☐ | |
INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K
On May 2, 2023, Immatics N.V. (the “Company,” “Immatics,” “we,” or similar terms) announced an interim clinical data update for 11 patients with recurrent and/or refractory solid cancers treated with ACTengine® IMA203 TCR-T monotherapy in the ongoing Phase 1b dose expansion Cohort A. IMA203 TCR-T cells are directed against an HLA-A*02-presented peptide derived from PRAME, a broadly expressed solid cancer target with clinical proof-of-concept for IMA203 demonstrated by Immatics in 2022. Overall, IMA203 showed a high rate of deep and durable objective responses, with a confirmed objective response rate of 67% (6/9), across multiple tumor types, including two confirmed partial responses (cPR) ongoing at more than 9 months after treatment and three additional partial responses ongoing at data cut-off. IMA203 monotherapy continues to be well tolerated in heavily pre-treated patients at doses of up to approximately 9 billion CD8+ TCR-T cells. No high-grade cytokine release syndrome (CRS) and no immune effector cell associated neurotoxicity syndrome (ICANS) were observed in Cohort A at cut-off.
Safety data for IMA203 TCR-T monotherapy in Phase 1b Cohort A: Treatment with IMA203 monotherapy continues to show manageable tolerability at doses as high as ~9x109 TCR-T cells.
| · | At data cut-off on April 4, 2023, 11 PRAME-positive patients were infused with IMA203 TCR-T cells at dose level (DL) 4 or DL5 with a mean total infused dose of 3.67x109 TCR-T cells (range 1.30-8.84x109 TCR-T cells). |
| · | Based on data review of 6 patients in the exploratory highest DL5, this DL was cleared for safety by the DSMB (Data and Safety Monitoring Board), and the updated provisional recommended Phase 2 dose (RP2D) now includes DL4 and DL5. The final RP2D will be defined prior to starting Phase 2. |
| · | Most frequent treatment-emergent adverse events (TEAEs) were as expected for cell therapies. |
| · | All 11 patients experienced expected cytopenia (Grade 1-4) associated with lymphodepletion. 10 patients (91%) had a low to moderate (Grade 1-2) cytokine release syndrome (CRS), of which 5 patients (45%) had Grade 1, and 5 patients (45%) had Grade 2 CRS. No high-grade (Grade 3 or higher) CRS and no immune effector cell associated neurotoxicity syndrome (ICANS) were observed in any of these 11 patients. No dose-dependent increase of CRS was observed across Phase 1a and Phase 1b Cohort A (N=38 patients infused with IMA203 in total). |
| · | No additional dose limiting toxicities (DLT) were observed in Cohort A since the initial Phase 1a dose escalation. |
Grade ≥3 TEAEs Observed Regardless of Relatedness to Study Treatment
All treatment-emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment that occurred in at least 1 patient (except for CRS and ICANS, where only Grade 1-2 occurred; listed for completeness due to being adverse events 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 (04-Apr-2023). 1 ICANS: Immune effector cell-associated neurotoxicity syndrome.
Clinical activity for IMA203 TCR-T monotherapy in Phase 1b Cohort A: IMA203 monotherapy demonstrates a high rate of deep objective responses with ongoing durability of more than 9 months after treatment in some patients.
| · | At data cut-off on April 4, 2023, 11 patients were infused with IMA203 TCR-T cells and evaluable for at least one tumor response assessment post treatment. |
| · | Objective responses were observed in last-line solid cancer patients including cutaneous melanoma, ovarian cancer, uveal melanoma, head and neck cancer, synovial sarcoma |
| · | Patients were heavily pre-treated with a mean of ~4 lines of prior systemic treatments and had exhausted all available standard of care treatments. |
| · | All cutaneous melanoma patients were checkpoint inhibitor-refractory, all ovarian cancer patients were platinum-resistant. |
| · | Initial objective response rate (ORR) of 64% (7/11) was observed at ~week 6 (partial responses, PR, according to RECIST 1.1). |
| · | Confirmed ORR of 67% (6/9) was observed at ~month 3; initial responses at week 6 were confirmed for all 6 responders with available subsequent 3-month scan. |
| · | Median duration of response1 was not reached (min 1.3+ months, max 8.8+ months) at a median follow-up2 of 8.5 months. |
| · | At data cut-off, 5 of 7 responses remain ongoing: |
| o | 2 cPRs (cut. & uveal melanoma) ongoing at 9+ months |
| o | 1 cPR (cut. melanoma) ongoing at 6+ months |
| o | 1 cPR (ovarian cancer) ongoing at ~3 months |
| o | 1 PR (synovial sarcoma) ongoing at 6+ weeks |
| · | Objective responses were observed in patients independent of tumor type at all PRAME expression levels above Immatics’ mass spectrometry-guided RNA threshold including expression levels at or just above this threshold. |
| · | IMA203 T cells were found in all evaluable tumor tissues and the level of tumor infiltration was associated with objective responses |
| 1 | Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut-off. Median DOR is analyzed by using the Kaplan-Meier method. |
| 2 | Median follow-up is analyzed by using the reverse Kaplan-Meier method. |
Best Overall Response – Phase 1b Cohort A
1 Ovarian cancer patient A-DL5-04 erroneously received one dose of nivolumab and is part of intent-to-treat population (shown here) but not per-protocol population; NET: Neuroendocrine Tumor; PD: Progressive disease; SD: Stable disease; PR: Partial response; cPR: Confirmed partial response; BL: Baseline; BOR: Best Overall Response
Response over Time – Phase 1b Cohort A
PRAME Prevalence across Different Tumor Types and PRAME Expression in IMA203 TCR-T Responders
PRAME target expression distribution (blue histogram) based on TCGA RNAseq data, patient data (black dots) based on IMADetect® qPCR testing of screening biopsies; 1 PRAME target prevalence is based on TCGA RNAseq data combined with a proprietary MS-guided RNA expression threshold; 2 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% compared to prevalence based on TCGA data of 50%, 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; MS: Mass spectrometry.
Manufacturing of IMA203 TCR-T cells
| · | Immatics’ proprietary manufacturing process has a manufacturing time of 7 days (+7-day expedited release testing), with a success rate of 94% in achieving the provisional RP2D. |
| · | Manufacturing improvements (including monocyte depletion) and higher applied cell doses implemented for the Phase 1b part of the trial led to significantly increased levels of IMA203 T cells in the blood of patients in Phase 1b Cohort A compared to patients in the Phase 1a dose escalation. |
| · | Immatics is currently building a state-of-the-art facility designed to manufacture ACTengine® IMA203 TCR-T products, as well as other cell therapy candidates for registration-directed trials and initial commercial supply. Built with flexibility and cost-efficiency in mind, the facility is designed to be scalable via a modular design to accommodate manufacturing demands. The facility is expected to be operational in 2024. |
Development strategy to realize the multi-cancer opportunity PRAME
Immatics believes, the results presented today further validate PRAME as one of the most promising solid tumor targets for TCR-based therapies. Immatics’ IMA203 development strategy is based on two pillars aimed initially at a (1) fast-to-market approach and, later at a (2) broad development.
The first objective is to deliver the PRAME-targeted TCR-T cell therapy in 1-2 last-line solid cancer types as fast as possible with a focus on indications with PRAME prevalence above 80% and where clinical proof-of-concept has been demonstrated, such as cutaneous melanoma (potentially bundled with uveal melanoma) and/or ovarian cancer. The buildout of the manufacturing facility will support Immatics’ efforts to maximize speed to market. Immatics plans to start a first Phase 2 trial in 1H 2024, which is intended be to designed as a registration-directed trial.
As a second step, Immatics plans to also expand development to other cancer types, such as uterine cancer, lung cancer, breast cancer, head and neck cancer and other tumor types having a broad patient reach.
An update on all three IMA203 Phase 1b Cohorts and clinical development path for PRAME TCR-T monotherapy towards registration-directed trials and potential commercialization is planned for 4Q 2023.
In addition to ACTengine® TCR-T, Immatics is addressing PRAME-positive cancers with a second therapeutic modality, TCR Bispecifics (TCER®), to leverage the full potential of the multi-cancer opportunity PRAME. Immatics’ TCER® IMA402 is a next-generation, half-life extended TCR Bispecific for which Immatics submitted a clinical trial application (CTA) to the Paul-Ehrlich-Institute (PEI) on April 14, 2023 to initiate the Phase 1/2 trial. The trial is expected to commence in 2H 2023 with first clinical data planned in 2024.
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 will continue to evaluate which of these therapeutic modalities (ACTengine® vs. TCER® or both) is best suited for each cancer type.
The Company is well capitalized with cash position3 of $386m at YE 2022 and protected reach into 2025 to leverage multi-cancer PRAME opportunity.
***
In connection with the foregoing clinical data update, the Company issued a press release, a copy of which is attached hereto as Exhibit 99.1, made available a presentation, a copy of which is attached hereto as Exhibit 99.2, and made available an updated investor presentation on its website, a copy of which is attached hereto as Exhibit 99.3.
Certain statements in this Report on Form 6-K 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
| 3 | Cash position includes cash and cash equivalents as well as other financial assets and was €362.2 million as of December 31, 2022 ($386.3 million using the exchange rate published by the European Central Bank in effect as of December 31, 2022 (1 EUR = 1,0666 USD). |
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 Report on Form 6-K 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 Report on Form 6-K 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.
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. 333-240260 and 333-258351) 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 May 2, 2023 |
| 99.2 | Presentation dated May 2, 2023 |
| 99.3 | Presentation dated May 2, 2023 |
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: May 2, 2023 | ||
| By: | /s/ Harpreet Singh | |
| Name: | Harpreet Singh | |
| Title: | Chief Executive Officer | |
Exhibit 99.1
PRESS RELEASE
Immatics
Reports Interim Clinical Data from Ongoing Phase 1b Cohort A
Monotherapy with ACTengine® IMA203 TCR-T Targeting PRAME
Company to host conference call today, May 2, at 8:30 am EDT / 2:30 pm CEST
| · | Update covers data from 11 heavily pre-treated, last-line patients in Phase 1b dose expansion Cohort A treated with IMA203 TCR-T monotherapy against PRAME |
| · | Objective response rate (ORR): 64% (7/11) initial ORR at week 6 and 67% (6/9) confirmed ORR at month 3 |
| · | Median duration of response not reached at median follow-up time of 8.5 months at data cut-off |
| · | Objective responses independent of solid tumor type at low, medium and high PRAME expression levels in checkpoint-refractory cutaneous melanoma, platinum-resistant ovarian cancer, uveal melanoma, head and neck cancer and synovial sarcoma |
| · | Cohort A IMA203 monotherapy TCR-T treatment continues to show manageable tolerability with no high-grade CRS and no ICANS; no dose dependent increase of CRS observed |
| · | Proprietary rapid manufacturing process with 7 days of manufacturing time; manufacturing success rate of 94% to reach current recommended Phase 2 dose |
| · | Next data update and pathway towards registration-directed trials planned to be set out in 4Q 2023 |
| · | Company well capitalized with cash position1 of $386m at YE 2022 and reach into 2025 to leverage multi-cancer PRAME opportunity |
Houston, Texas and Tuebingen, Germany, May 2, 2023 – 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 an interim clinical data update for 11 patients with recurrent and/or refractory solid cancers treated with ACTengine® IMA203 TCR-T monotherapy in the ongoing Phase 1b dose expansion Cohort A. IMA203 TCR-T cells are directed against an HLA-A*02-presented peptide derived from PRAME, a broadly expressed solid cancer target with clinical proof-of-concept for IMA203 demonstrated by
| 1 | Cash position includes cash and cash equivalents as well as other financial assets and was €362.2 million as of December 31, 2022 ($386.3 million using the exchange rate published by the European Central Bank in effect as of December 31, 2022 (1 EUR = 1,0666 USD). |
| Immatics Press Release May 2, 2023 | 1 | 9 |
Immatics in 2022. Overall, IMA203 showed a high rate of deep and durable objective responses, with a confirmed objective response rate of 67% (6/9), across multiple tumor types, including two confirmed partial responses (cPR) ongoing at more than 9 months after treatment and three additional partial responses ongoing at data cut-off. IMA203 monotherapy continues to be well tolerated in heavily pre-treated patients at doses of up to approximately 9 billion CD8+ TCR-T cells. No high-grade cytokine release syndrome (CRS) and no immune effector cell associated neurotoxicity syndrome (ICANS) were observed in Cohort A at data cut-off.
The data will be presented by Martin Wermke, MD, Professor at the University Hospital Dresden and Coordinating Investigator of the ACTengine® IMA203 TCR-T trial during a conference call today, May 2, at 8:30 am EDT / 2:30 pm CEST.
“The treatment of solid cancer patients who have exhausted all available standard of care options remains a significant challenge. These patients typically show fast progressing disease with very poor prognosis,” said Martin Wermke, MD, Coordinating Investigator of the ACTengine® IMA203 TCR-T trial. “It is therefore very encouraging to see that IMA203 is able to provide durable, clinically relevant responses in a variety of solid cancer patients.”
“Today marks a significant step in our efforts towards bringing our ACTengine® IMA203 monotherapy to patients with solid tumors, as we present for the first time longer-term clinical data demonstrating deep and durable responses, some of them ongoing beyond 9 months after treatment,” commented Cedrik Britten, MD, Chief Medical Officer at Immatics. “Furthermore, we show that these responses are agnostic of tumor type and that ACTengine® IMA203 achieved objective responses at widely differing PRAME expression levels. These data further increase our confidence in the success and broad potential of targeting PRAME, and our product candidate IMA203. We continue executing and anticipate announcing a potential fast-to-market pathway for the first 1-2 indications by the end of the year.”
Safety data for IMA203 TCR-T monotherapy in Phase 1b Cohort A: Treatment with IMA203 monotherapy continues to show manageable tolerability at doses as high as ~9x109 TCR-T cells.
| · | At data cut-off on April 4, 2023, 11 PRAME-positive patients were infused with IMA203 TCR-T cells at dose level (DL) 4 or DL5 with a mean total infused dose of 3.67x109 TCR-T cells (range 1.30-8.84x109 TCR-T cells). |
| · | Based on data review of 6 patients in the exploratory highest DL5, this DL was cleared by the DSMB (Data and Safety Monitoring Board) for safety, and the updated provisional recommended Phase 2 dose (RP2D) now includes DL4 and DL5. The final RP2D will be defined prior to starting Phase 2. |
| Immatics Press Release May 2, 2023 | 2 | 9 |
| · | Most frequent treatment-emergent adverse events (TEAEs) were as expected for cell therapies. |
| · | All 11 patients experienced expected cytopenia (Grade 1-4) associated with lymphodepletion. 10 patients (91%) had a low to moderate (Grade 1-2) cytokine release syndrome (CRS), of which 5 patients (45%) had Grade 1, and 5 patients (45%) had Grade 2 CRS. No high-grade (Grade 3 or higher) CRS and no immune effector cell associated neurotoxicity syndrome (ICANS) were observed in any of these 11 patients. No dose-dependent increase of CRS was observed across Phase 1a and Phase 1b Cohort A (N=38 patients infused with IMA203 in total). |
| · | No additional dose limiting toxicities (DLT) were observed in Cohort A since the initial Phase 1a dose escalation. |
Clinical activity for IMA203 TCR-T monotherapy in Phase 1b Cohort A: IMA203 monotherapy demonstrates a high rate of deep objective responses with ongoing durability of more than 9 months after treatment in some patients.
| · | At data cut-off on April 4, 2023, 11 patients were infused with IMA203 TCR-T cells and evaluable for at least one tumor response assessment post treatment. |
| · | Objective responses were observed in last-line solid cancer patients including cutaneous melanoma, ovarian cancer, uveal melanoma, head and neck cancer, synovial sarcoma. |
| · | Patients were heavily pre-treated with a mean of ~4 lines of prior systemic treatments and had exhausted all available standard of care treatments. |
| · | All cutaneous melanoma patients were checkpoint inhibitor-refractory, all ovarian cancer patients were platinum-resistant. |
| · | Initial objective response rate (ORR) of 64% (7/11) was observed at ~week 6 (partial responses, PR, according to RECIST 1.1). |
| · | Confirmed ORR of 67% (6/9) was observed at ~month 3; initial responses at week 6 were confirmed for all 6 responders with available subsequent 3-month scan. |
| · | Median duration of response2 was not reached (min 1.3+ months, max 8.8+ months) at a median follow-up3 of 8.5 months. |
| · | At data cut-off, 5 of 7 responses remain ongoing: |
| o | 2 cPRs (cut. & uveal melanoma) ongoing at 9+ months |
| o | 1 cPR (cut. melanoma) ongoing at 6+ months |
| o | 1 cPR (ovarian cancer) ongoing at ~3 months |
| 2 | Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut-off. Median DOR is analyzed by using the Kaplan-Meier method. |
| 3 | Median follow-up is analyzed by using the reverse Kaplan-Meier method. |
| Immatics Press Release May 2, 2023 | 3 | 9 |
| o | 1 PR (synovial sarcoma) ongoing at 6+ weeks |
| · | Objective responses were observed in patients independent of tumor type at all PRAME expression levels above Immatics’ mass spectrometry-guided RNA threshold including expression levels at or just above this threshold. |
| · | IMA203 T cells were found in all evaluable tumor tissues and the level of tumor infiltration was associated with objective responses. |
Best Overall Response – Phase 1b Cohort A
1 Ovarian cancer patient A-DL5-04 erroneously received one dose of nivolumab and is part of intent-to-treat population (shown here) but not per-protocol population; NET: Neuroendocrine Tumor; PD: Progressive disease; SD: Stable disease; PR: Partial response; cPR: Confirmed partial response; BL: Baseline; BOR: Best Overall Response
Response over Time – Phase 1b Cohort A
| Immatics Press Release May 2, 2023 | 4 | 9 |
Manufacturing of IMA203 TCR-T cells
| · | Immatics’ proprietary manufacturing process has a manufacturing time of 7 days (+7-day expedited release testing), with a success rate of 94% in achieving the provisional RP2D. |
| · | Manufacturing improvements (including monocyte depletion) and higher applied cell doses implemented for the Phase 1b part of the trial led to significantly increased levels of IMA203 T cells in the blood of patients in Phase 1b Cohort A compared to patients in the Phase 1a dose escalation. |
| · | Immatics is currently building a state-of-the-art facility designed to manufacture ACTengine® IMA203 TCR-T products, as well as other cell therapy candidates, for registration-directed trials and initial commercial supply. Built with flexibility and cost-efficiency in mind, the facility is designed to be scalable via a modular design to accommodate manufacturing demands. The facility is expected to be operational in 2024. |
| Immatics Press Release May 2, 2023 | 5 | 9 |
Development strategy to realize the multi-cancer opportunity PRAME
Immatics believes, the results presented today further validate PRAME as one of the most promising solid tumor targets for TCR-based therapies. Immatics’ IMA203 development strategy is based on two pillars aimed initially at a (1) fast-to-market approach and, later at a (2) broad development.
The first objective is to deliver the PRAME-targeted TCR-T cell therapy in 1-2 last-line solid cancer types as fast as possible with a focus on indications with PRAME prevalence above 80% and where clinical proof-of-concept has been demonstrated, such as cutaneous melanoma (potentially bundled with uveal melanoma) and/or ovarian cancer. The buildout of the manufacturing facility will support Immatics’ efforts to maximize speed to market. Immatics plans to start a first Phase 2 trial in 1H 2024, which is intended to be designed as a registration-directed trial.
As a second step, Immatics plans to also expand development to other cancer types, such as uterine cancer, lung cancer, breast cancer, head and neck cancer and other tumor types having a broad patient reach.
An update on all three IMA203 Phase 1b Cohorts and clinical development path for PRAME TCR-T monotherapy towards registration-directed trials and potential commercialization is planned for 4Q 2023.
In addition to ACTengine® TCR-T, Immatics is addressing PRAME-positive cancers with a second therapeutic modality, TCR Bispecifics (TCER®), to leverage the full potential of the multi-cancer opportunity PRAME. Immatics’ TCER® IMA402 is a next-generation, half-life extended TCR Bispecific for which Immatics submitted a clinical trial application (CTA4) to the Paul-Ehrlich-Institute (PEI) on April 14, 2023, to initiate the Phase 1/2 trial. The trial is expected to commence in 2H 2023 with first clinical data planned in 2024.
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 will continue to evaluate which of these therapeutic modalities (ACTengine® vs. TCER® or both) is best suited for each cancer type.
| 4 | Clinical Trial Application (CTA) is the European equivalent of an Investigational New Drug (IND) application. |
| Immatics Press Release May 2, 2023 | 6 | 9 |
Immatics conference call
Immatics will host a conference call today, May 2nd, 2023, at 8:30 am EDT / 2:30 pm CEST to discuss the clinical data. The webcast and presentation can be accessed directly through this link. Participants may also access the slides presented in 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 Immatics website for at least 90 days.
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 program’s 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.
ACTengine® IMA203 TCR-T is currently being evaluated in three ongoing Phase 1b dose expansion cohorts in last-line patients: Cohort A IMA203 TCR-T monotherapy, Cohort B IMA203 in combination with an immune checkpoint inhibitor; Cohort B is focused on generating safety data for potential further investigation of a combination approach as a front-line therapy, and Cohort C IMA203CD8 TCR-T monotherapy, where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor. IMA203CD8 is currently being explored in DL4a (up to 0.8x109 TCR-T cells/m2 BSA).
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).
| Immatics Press Release May 2, 2023 | 7 | 9 |
- END -
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.
Immatics intends to use its website www.immatics.com as a means of disclosing material non-public information. For regular updates you can also follow us on Twitter, Instagram and LinkedIn.
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 press release 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.
| Immatics Press Release May 2, 2023 | 8 | 9 |
For more information, please contact:
| Media and Investor Relations Contact |
| Eva Mulder or Charlotte Spitz |
| Trophic Communications |
| Phone: +31 65 2331 579 |
| immatics@trophic.eu |
| Immatics N.V. | |
| Anja Heuer | Jordan Silverstein |
| Senior 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 May 2, 2023 | 9 | 9 |
Exhibit 99.2
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. ACTengine® IMA203 TCR - T Monotherapy Targeting PRAME – Phase 1b Cohort A Interim Data Update Martin Wermke , Professor at the University Hospital Dresden and Coordinating Investigator of the ACTengine® IMA203 TCR - T trial Cedrik Britten , Chief Medical Officer, Immatics Harpreet Singh , Chief Executive Officer, Immatics May 02, 2023
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
Update on IMA203 TCR - T Monotherapy – Phase 1b Cohort A Delivering a Meaningful Benefit to Patients with an Unmet Need 3 Martin Wermke, MD Professor at the University Hospital Dresden, Coordinating Investigator of the ACTengine® IMA203 TCR - T trial Cedrik M. Britten, MD Chief Medical Officer Immatics Harpreet Singh, PhD Chief Executive Officer Immatics
The Multi - Cancer Opportunity of PRAME One of the Most Promising Solid Tumor Targets for TCR - based Therapies Known To Date 4 High prevalence High target density Homogeneous expression “Clean” expression profile Clinical proof - of - concept s q N S C L C Ovarian Cancer PRAME fulfills all properties of an ideal target for TCR - based therapies TUMOR CELL T CELL H LA - A * 02 : 01 PRAME TCR PRAME Pep ೦ de PRAME RNA detection in tumor samples (ISH) ISH: in situ hybridization, sqNSCLC: squamous non - small cell lung cancer
Unlocking Novel Treatments for Patients with Solid Cancers Key Pillars of Developing a Successful TCR - T Product Candidate 5 S a f e ty Anti - Tumor Activity Durability Product Quality Broad Reach
Key Pillars of Developing a Successful TCR - T Product Candidate Summary of Today’s Update on IMA203 TCR - T Phase 1b Cohort A S a f e ty Anti - Tumor Activity Durability Product Quality Broad Reach Manageable tolerability at doses as high as ~9x10 9 TCR - T cells High rate of objective responses: 64% (7/11) ORR 1 67% (6/9) cORR 2 Ongoing durable responses at 9+ months mDOR: Not reached min 1.3+, max 8.8+ mFU: 8.5 months Rapid manufacturing time of 7 days (+ 7 - day release testing), manufacturing success rate of 94% Confirmed objective responses in broad range of solid cancer types at low, medium and high PRAME levels above threshold 1 Initial ORR: Objective response rate according to RECIST 1.1 at first scan post infusion at ~week 6; 2 Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with available second scan post infusion at ~month 3 or patients with progressive disease (PD) at any timepoint before this scan; mDOR: median duration of response; mFU: median follow - up D ata c u t - o f f A p r 04 , 202 3 6
ACTengine® IMA203 TCR - T Phase 1 Design Focus on IMA203 TCR - T Monotherapy Investigated in Cohort A 7 Cohort C Phase 1b Cohort A Interim Update on 11 patients 1 Updated target dose (provisional recommended Phase 2 dose, RP2D) determined at DL4+DL5 for Cohort A and B, for Cohort C treatment of n=3 patients at DL3 completed, enrollment at DL4a ongoing before continuation at DL4b and potentially DL5; 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 Demonstrated to be important for long - term remission: Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances; 5 IMA203CD8 Dose Level 4a: 0.481 - 0.8x10 9 transduced viable CD8 T cells/m 2 BSA » Focus on generation of safety data » Further investigation of a IMA203 plus CPI combination as a front - line therapy being considered Adding functional CD4 T cells 4 nd I M A 203C D8 2 G en Phase 1b Dose Expansion 1 Phase 1a Dose Escalation Cohort A IMA203 Monotherapy (N=11) Increasing T cell:Tumor cell Ratio 2 IMA203 Monotherapy in Basket Trial (N=27) » 2 nd Gen potency - enhanced monotherapy product version » Currently being explored in dose finding at DL4a 5 Cohort B IMA203 plus Checkpoint Inhibitor 3 Blocking PD - 1/PD - L1 pathway Data cut - off Apr 04, 2023
ACTengine® IMA203 TCR - T Monotherapy – Patient Flow 8 HLA - A*02 Testing Blood sample; Central lab Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase Manufacturing by Immatics Infusion of ACTengine® IMA203 TCR - T Product Lymphodepletion * Target Profiling Fresh Tumor Biopsy; IMADetect® Low dose IL - 2 ** Safety and efficacy monitoring for 12 months Leukapheresis x x E xpr e ss i on Antigen 1 2 3 * 30 mg/m 2 Fludarabine and 500 mg/m 2 Cyclophosphamide for 4 days; ** 1m IU daily days 1 - 5 and twice daily days 6 - 10 Short process time of 14 days 7 - day rapid manufacturing process 7 - day expedited QC release testing Monocyte depletion process implemented in Phase 1b
N =11 ACTengine® IMA203 TCR - T Monotherapy – Phase 1b Cohort A Patient and Product Characteristics D ata c u t - o f f A p r 04 , 202 3 9 Heavily pre - treated, metastatic last - line patients that have exhausted all available standard of care treatments 1 Including ovarian cancer patient A - DL5 - 04 who erroneously received one dose of nivolumab and is part of intent - to - treat (shown here) but not per - protocol population; 2 Transduced viable CD8 T cells; ULN: Upper limit of normal; LDH: Lactate dehydrogenase; BSA: Body surface area; RP2D: Recommended Phase 2 Dose DL5 cleared for safety, updated provisional RP2D comprises DL4 + DL5 : 0.2 - 4.7 x 10 9 TCR - T cells/m 2 BSA Patients in Phase 1b Cohort A (N=11) 1 Age Mean (min, max) 55.4 (31, 79) Gender Male / Female [% of patients] 45.5 / 54.5 Prior lines of treatment Mean (min, max) 3.7 (1, 10) LDH at baseline >1 x ULN [% of patients] 54.5 Baseline tumor burden Mean target lesion sum of diameter [mm] (min, max) 73.8 (21.0, 207.3) Total infused dose Mean TCR - T cells 2 infused [x10 9 ] (min, max) 3.67 (1.30, 8.84)
Most Frequent Adverse Events – Phase 1b Cohort A (N=11) Manageable Treatment - emergent Adverse Events (TEAEs) CRS and ICANS graded by CARTOX criteria (Neelapu et al ., 2018); 1 ICANS: Immune Effector Cell - Associated Neurotoxicity Syndrome • Expected cytopenia (Grade 1 - 4) associated with lymphodepletion in all patients • Low - moderate cytokine release syndrome (CRS) in 91% (10/11) of patients • 45% (5/11) of patients had Grade 1 CRS (3 in DL4, 2 in DL5) • 45% (5/11) of patients had Grade 2 CRS (2 in DL4, 3 in DL5) • No dose - dependent increase of CRS • No ICANS 1 • No Dose - limiting toxicity • For IMA203 TCR - T monotherapy tolerability profile including Phase 1a dose escalation, see appendix IMA203 TCR - T monotherapy shows managable tolerability at total doses as high as ~9x10 9 TCR - T cells Data cut - off Apr 04, 2023 10
Best Overall Response – Phase 1b Cohort A Deep Objective Responses Independent of Tumor Type 1 Ovarian cancer patient A - DL5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population; 2 Initial ORR: Objective response rate according to RECIST 1.1 at first scan post infusion at ~week 6; 3 Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with available second scan post infusion at ~month 3 or patients with progressive disease (PD) at any timepoint before this scan; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BL: Baseline; BOR: Best Overall Response; NET: Neuroendocrine Tumor; CPI: Checkpoint Inhibitor ORR (at ~week 6) 2 64% (7/11) cORR (at ~month 3) 3 67% (6/9) Deep objective responses observed across multiple, heavily pre - treated tumor types • Responses observed in cutaneous and uveal melanoma, synovial sarcoma, head and neck cancer, and ovarian cancer • Initial responses at week 6 were confirmed in all 6 responders with available subsequent 3 - month scan • All cut. melanoma patients were CPI - refractory • All ovarian cancer patients were platinum - resistant Data cut - off Apr 04, 2023 11 1
Response over Time – Phase 1b Cohort A Durable Partial Responses 9+ Months after IMA203 TCR - T Treatment **Ovarian cancer patient A - DL 5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population ; 1 Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death . Patients with ongoing response will be censored at date of data cut - off . Median DOR is analyzed by using the Kaplan - Meier method ; 2 Median Follow - up is analyzed by using the reverse Kaplan - Meier method ; PD : Progressive Disease ; SD : Stable Disease ; PR : Partial Response ; cPR : Confirmed Partial Response ; BL : Baseline Median time from IMA203 TCR - T infusion to onset of response was 1.4 months Ongoing responses in 5 of 7 responders: • 2 cPRs (cut. & uveal melanoma) ongoing at 9+ months • 1 cPR (cut. melanoma) ongoing at 6+ months • 1 cPR (ovarian cancer) ongoing at ~3 months • 1 PR (synovial sarcoma) ongoing at 6+ weeks Median DOR 1 , min, max DOR Not reached, 1.3+, 8.8+ months Median Follow - up 2 8.5 months * ** * Ongoing Response until 5.7 months post infusion, target lesion response assessment not available (external assessment) Scans at approximately week 6, month 3 and then every 3 months Data cut - off Apr 04, 2023 12
Deep & Durable Responses in Heavily Pre - Treated Patients – Phase 1b Cohort A Patient ID Indication No of prior treatment lines Prior treatments Total infused dose TCR - T cells 1 [x10 9 ] BOR BOR (Max % change of target lesions) Comment A - DL5 - 01 Uveal Melanoma 1 ARRY614/Nivolumab 4.16 cPR - 60.3 Ongoing response 10.1 months post infusion A - DL4 - 03 Cut. Melanoma 7 Dabrafenib/Trametinib, Pembrolizumab, Dabrafenib/Trametinib, Vemurafenib/Cobimetinib, Dabrafenib/Trametinib, IMCgp - 100, Encorafenib/Binimetinib 1.30 cPR - 73.9 Ongoing response 9.9 months post infusion A - DL5 - 03 Cut. Melanoma 3 Interferon, Pembrolizumab, Nivolumab/Ipilimumab 5.12 cPR - 60.5 Ongoing response 6.2 months post infusion A - DL4 - 01 Head & Neck Cancer 1 Carboplatin/Paclitaxel 1.92 cPR - 33.3 Response until 5.7 months post infusion A - DL4 - 02 Ovarian Cancer 10 Carboplatin/Taxol, Taxol, Ge m ci t abine /C arbopla t in , Olaparib, Letrozole, Rucaparib, UPCC 03118 (CAR - T cell directed folate receptor), Bevacizumab/Cyclophosphamide, Carboplatin, Doxorubicin 1.97 cPR - 41.0 Response until 3.8 months post infusion A - DL5 - 05 Ovarian Cancer 3 Adriamycin/Cytotaxan/Taxol, Carboplatin/Taxol, Carboplatin/Doxil 8.84 cPR - 61.7 Ongoing response 2.5 months post infusion A - DL5 - 06 Synovial Sarcoma 1 Adriamycin/Ifosfamide/Mesna 3.94 PR - 74.8 Initial PR at week 6, 3 - month scan pending A - DL4 - 04 Melanoma (Unk. Primary) 2 Nivolumab/Ipilimumab, Nivolumab 1.73 SD 0.0 Disease stabilization until 5.7 months post infusion A - DL4 - 05 Cut. Melanoma 5 Nivolumab, Nivolumab (re - exposure), Nivolumab/Ipilimumab, Dabrafenib/Trametinib, Nivolumab 1.63 SD 11.4 Ongoing disease stabilization 2.1 months post infusion A - DL5 - 02 Pancreatic Neuroendocrine Tumor 3 Lanreotid, Streptozocin/5 - Fluorouracil, Everolismus 5.12 SD - 21.8 Disease stabilization until 2.3 months post infusion A - DL5 - 04* Ovarian Cancer 5 P acli t axel /C arbopla t in , Niraparib, Doxorubicin/Liposomal/Carpoplatin, 2020 - 0808 ZN - C3/Gemcitabine, 2020 - 0755 COM 701/BMS - 986207/Nivolumab 4.68 PD 50.8 Progressive disease at 1.2 months post infusion 1 Transduced viable CD8 T cells; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BL: Baseline; BOR: Best Overall Response *Ovarian cancer patient A - DL5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population. Data cut - off Apr 04, 2023 13
Biological Data Consistent with Clinical Data IMA203 TCR - T Levels and Tumor Infiltration across Patients in Phase 1a and Phase 1b Cohort A IMA203 T cells found in all evaluable tumor tissues, level of infiltration associated with objective responses 1 Increased levels of IMA203 T cells in the blood of patients in Cohort A following increase of cell dose and switch to monocyte depletion process Data cut - off Apr 04, 2023 14 Mann - Whitney U test; 1 T cell infiltration for 21 patients (10 non - responder, 11 responder) with 6 - week post infusion biopsy available (1 patient with ~4 - week, 2 patients with ~13 - week post infusion biopsy); PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response 1 î 10 0 1 î 10 1 1 î 10 2 1 î 10 3 1 î 10 4 1 î 10 5 1 î 10 6 IMA203 T cell infiltration [vector copies/µg gDNA] PD / S D (n=10) P R / cPR (n=11) P D /SD PR cPR 0. 0003 N = 2 1 p =0 . 0003 0 5 î 10 5 1 î 10 6 1.5 î 10 6 2 î 10 6 ) x a m C ( n o si n DNA] a exp g g k μ ea es / P i l p el co c [ T 3 20 MA I PD / SD PR cPR <0. 0 0 01 Cohort A (n=11) Phase 1a (n=27) Vector copies/µg gDNA p <0 . 0001 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 0 4 8 12 16 20 40 60 80 100 200 400 600 800 Days post infusion Vector copies/μg gDNA N = 3 8 Phase 1A Cohort A Persistence over time Peak persistence N =38
Responses above Immatics’ PRAME RNA Threshold Independent of Tumor Type Highlighting Tumor Types (left) and Type of Best Overall Response (right) – Phase 1b Cohort A PRAME RNA expression in pre - treatment biopsies relative to threshold IMA203 achieved objective responses at all expression levels above Immatics’ mass spectrometry - guided RNA threshold A - DL 5 - 01 A - DL 4 - 04 A - DL 4 - 05 A - DL 5 - 02 A - DL 5 - 04 A - DL 4 - 03 A - DL 5 - 05 A - DL 4 - 01 A - DL 5 - 03 A - DL 4 - 02 A - DL 5 - 06 IMA203 has the potential to provide clinical benefit for all PRAME biomarker - positive cancer patients Mann - Whitney U test, p=0.23; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; NET: Neuroendocrine Tumor Data cut - off Apr 04, 2023 15 T hreshold T hreshold
Potential of IMA203 in Additional Solid Cancer Indications Based on PRAME Expression in IMA203 TCR - T Responders – Phase 1b Cohort A Immatics’ proprietary mass spectrometry - guided mRNA threshold 100% 100% 95% 100% 50% (90% 2 ) 80% 60% 65% 25% % PRAME - positive patients 1 PRAME target expression distribution (blue histogram) based on TCGA RNAseq data, patient data (black dots) based on IMADetect® qPCR testing of screening biopsies; 1 PRAME target prevalence is based on TCGA RNAseq data combined with a proprietary MS - guided RNA expression threshold; 2 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% compared to prevalence based on TCGA data of 50%, 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; MS: mass spectrometry PRAME mRNA expression in Phase 1b Cohort A responders Data cut - off Apr 04, 2023 16 Selected indications A - DL4 - 03 A - DL5 - 03 A - DL5 - 06 A - DL5 - 01 A - DL4 - 02 A - DL5 - 05 A - DL4 - 01
ACTengine® IMA203 TCR - T Monotherapy Targeting PRAME Summary of Phase 1b Cohort A Interim Data Update • Manageable tolerability with no high - grade CRS, no ICANS in 11 patients in Cohort A 1 • Objective responses observed in heavily pre - treated last - line solid cancer patients including checkpoint - refractory cutaneous melanoma, platinum - resistant ovarian cancer, uveal melanoma, head and neck cancer, synovial sarcoma • High objective response rate (ORR): • 64% (7/11) ORR (at ~week 6) • 67% (6/9) cORR (at ~month 3) • Ongoing durable responses: • Median duration of response not reached at a median follow - up time of 8.5 months • Ongoing PRs 9+ months after IMA203 TCR - T treatment • Objective responses independent of tumor type at low, medium and high PRAME levels above threshold • Manufacturing success rate of 94% to reach current RP2D, rapid 7 - day manufacturing process (+7 - day release testing) Increased confidence in the success and broad potential of targeting PRAME and our product candidate IMA203 TCR - T 1 For IMA203 TCR - T monotherapy tolerability profile including Phase 1a dose escalation, see appendix; CRS: Cytokine Release Syndrome; ICANS: Immune effector cell - associated neurotoxicity syndrome; RP2D: provisional recommended Phase 2 dose Data cut - off Apr 04, 2023 17
Immatics’ ACTengine® IMA203 TCR - T Development Strategy Two Pillared Strategy 18 Objective: Deliver best - in - class therapy in 1 - 2 last - line solid cancer types as fast as possible • Focus on indications with PRAME prevalence above 80% with available clinical PoC, such as cut. melanoma (potentially bundled with uveal melanoma) and ovarian cancer • Highly modular and scalable manufacturing facility expected to be operational in 2024 to support efforts to maximize speed to market • Planned start of a first Phase 2 trial in 1H 2024 – targeted to be already registration - directed Objective: Expand development to other cancer types • Signal finding in other cancer types with a broad patient reach, such as uterine cancer, lung cancer, breast cancer, head and neck cancer FAST & F O C US E D GO BROAD Update on all three IMA203 Phase 1b cohorts and clinical development path towards registration - directed trials and potential commercialization for PRAME TCR - T monotherapy is planned for 4Q 2023
Realizing the Full Multi - Cancer Opportunity of PRAME ACTengine® IMA203 (TCR - T) and TCER® IMA402 (TCR Bispecific) 19 Indication % PRAME positive patients 1 Uterine Carcinoma Uterine Carcinosarcoma Sarcoma Subtypes Cut. Melanoma Uveal Melanoma 2 Ovarian Carcinoma Squamous NSCLC T N BC Small Cell Lung Cancer Kidney Carcinoma C h ola n g io c a r c i n oma Adeno NSCLC Breast Carcinoma H NS CC Esophageal Carcinoma HCC Bladder Carcinoma 100% 100% up to 100% 95% 90% 80% 65% 60% 55% up to 45% 35% 25% 25% 25% 20% 20% 20% TCER® IMA402 (TCR Bispecific) A C T eng i ne® IMA203 (TCR - T) Cancer Cell Death PRAME is one of the most promising and most prevalent, clinically validated solid tumor targets known to date Leverage the full potential of targeting PRAME by continued evaluation of the best suited therapeutic modality (ACTengine® vs. TCER® or both) for each cancer type x CTA submitted x Start of clinical trial planned in 2H 2023 x First clinical data 2024 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 Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=21); NSCLC: Non - small cell lung cancer, TNBC: Triple - negative breast cancer, HNSCC: Head and neck squamous cell carcinoma; HCC: Hepatocellular carcinoma
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. A. Jazaeri 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. Reshef 20 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 Appendix
ACTengine® IMA203 TCR - T 1 st Gen Monotherapy Tolerability Data • IMA203 was well tolerated • No Adverse Event ≥Grade 3 was observed with a frequency ≥10% when excluding expected cytopenias associated with lymphodepletion • No IMA203 - related Grade 5 Adverse Events 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 ( 04 - Apr - 2023 ) ; 1 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, Cytokine release syndrome, Diarrhoea, Hypokalaemia, Proteinuria ; Second patient : Humerus fracture, Muscle spasms, Neutropenia, Thrombocytopenia ; 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 were not considered related to any study drug ; 5 Patient died from sepsis of unknown origin and did not receive IMA 203 TCR - T cells . Data cut - off Apr 04, 2023 22 Adverse event ( System organ class , Preferred term) No. % Adverse event ( System organ class , Preferred term) ≥ Grade 3 ≥ Grade 3 No. % Phase 1a and Phase 1b Cohort A – All ≥Grade 3 Adverse Events (N=39) TEAEs by maximum severity for all patients in Ph1a dose escalation and Ph1b Cohort A dose expansion (N=39) 1 Patients with any adverse event 39 100.0 table continued… Adverse Events of Special Interest General disorders and administration site conditions Cytokine release syndrome 2 5.1 ICANS 2 0 0.0 Condition aggravated 4 1 2.6 Fatigue 1 2.6 Pyrexia 1 2.6 Swelling face 1 2.6 Blood and lymphatic system disorders Neutropenia 32 82.1 Lymphopenia 24 61.5 Leukopenia 22 56.4 Anaemia 20 51.3 Thrombocytopenia 15 38.5 Cytopenia 1 2.6 Leukocytosis 1 2.6 Lymphocytosis 1 2.6 Vascular disorders Hypertension 3 7.7 Hypotension 1 2.6 Metabolism and nutrition disorders Hypokalaemia 2 5.1 Failure to thrive 1 2.6 Infections and infestations Injury, poisoning and procedural complications Appendicitis 1 2.6 COVID - 19 1 2.6 Enterococcal infection 1 2.6 Infection 1 2.6 Orchitis 1 2.6 Sepsis 4,5 1 2.6 Septic shock 4 1 2.6 Humerus fracture 1 2.6 Infusion related reaction 1 2.6 Renal and urinary disorders Acute kidney injury 1 2.6 Proteinuria 1 2.6 Cardiac disorders Atrial fibrillation 3 1 2.6 Respiratory, thoracic and mediastinal disorders Endocrine disorders Hypoxia 2 5.1 Bronchial obstruction 1 2.6 Laryngeal inflammation 1 2.6 Pleural effusion 1 2.6 Respiratory failure 1 2.6 Inappropriate antidiuretic hormone secretion 1 2.6 Eye disorders Ulcerative keratitis 1 2.6 Hepatobiliary disorders Investigations Cholangitis 1 2.6 Immune system disorders Alanine aminotransferase increased 1 2.6 Aspartate aminotransferase increased 1 2.6 Blood alkaline phosphatase increased 1 2.6 Blood creatinine increased 1 2.6 Blood fibrinogen decreased 1 2.6 Contrast media allergy 1 2.6 Musculoskeletal and connective tissue disorders Muscle spasms 1 2.6 Nervous system disorders Gastrointestinal disorders Headache 1 2.6 Abdominal pain 1 2.6 Diarrhoea 1 2.6 Ileus 1 2.6 Vomiting 1 2.6 Reproductive system and breast disorders Vaginal haemorrhage 1 2.6 Skin and subcutaneous tissue disorders Rash maculo - papular 1 2.6
ACTengine® IMA203 TCR - T 1 st Gen Monotherapy Tolerability Data Focus on IMA203 Phase 1b Cohort A – All ≥Grade 3 Adverse Events (N=11) • IMA203 was well tolerated • No Adverse Event ≥Grade 3 was observed with a frequency ≥10% when excluding expected cytopenias associated with lymphodepletion • No IMA203 - related Grade 5 Adverse Events All treatment - emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment that occurred in at least 1 patient (except for CRS and ICANS, where only Grade 1 - 2 occurred ; listed for completeness due to being adverse events 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 ( 04 - Apr - 2023 ) . 1 ICANS : Immune effector cell - associated neurotoxicity syndrome . Data cut - off Apr 04, 2023 23 Adverse event ( System organ class , Preferred term) ≥ Grade 3 No. % Adverse event ( System organ class , Preferred term) ≥ Grade 3 No. % TEAEs by maximum severity for all patients in Ph1b Cohort A dose expansion (N=11) Patients with any adverse event 11 100.0 table continued… Adverse Events of Special Interest Investigations Cytokine release syndrome 0 0.0 ICANS 1 0 0.0 Alanine aminotransferase increased 1 9.1 Aspartate aminotransferase increased 1 9.1 Blood alkaline phosphatase increased 1 9.1 Blood and lymphatic system disorders Neutropenia 10 90.9 Lymphopenia 6 54.5 Leukopenia 5 45.5 Anaemia 5 45.5 Thrombocytopenia 4 36.4 Leukocytosis 1 9.1 Lymphocytosis 1 9.1 Eye disorders Ulcerative keratitis 1 9.1 Gastrointestinal disorders Ileus 1 9.1 Infections and infestations Infection 1 9.1 Nervous system disorders Headache 1 9.1 Respiratory, thoracic and mediastinal disorders Laryngeal inflammation 1 9.1
0 2 î 10 5 4 î 10 5 6 î 10 5 8 î 10 5 0. 0025 Favorable TCR - T Product Characteristics and High TCR - T Levels in Patients Manufacturing Improvements Implemented in Phase 1b Enhance Key Features of the Cell Product Manufacturing success rate of 94% to reach provisional RP2D ** Mean cell dose infused in 11 patients in Phase 1b Cohort A was 3.67x10 9 TCR - T cells Manufacturing process (infused products) MD pr o cess (n=12) Prior v e r s i o n s (n=26) Prior MD versions process (n=26) (n=12) MD process: Monocyte depletion process; * Unpaired t test; # Mann - Whitney U test; ** Updated provisional RP2D comprises DL4 + DL5: 0.2 - 4.7x10 9 transduced viable CD8 T cells/m 2 BSA; Increased peak TCR - T levels in patients Improved TCR - T product features 0 5 î 10 5 1 î 10 6 1.5 î 10 6 2 î 10 6 < 0 . 00 0 1 IMA203 T cell peak frequency [vector copies/µg gDNA] MD pr o cess (n=12) Prior v e r s i o n s (n=26) MD pr o cess (n=5) Prior v e r s i o n s (n=7) p<0.0001 # p=0.0025 # DL4 only, normalized to cell dose 0 20 40 60 80 100 % CD3+CD8+ Cells (of viable cells) 0 20 40 60 80 100 %Dextramer (of CD3+CD8+ Cells) Normalized peak frequency [vector copies per µg gDNA/10 9 TCR - T cells] Data cut - off Apr 04, 2023 24 p=0.0032 * p<0.0001 *
Focus on Melanoma Patients Phase 1a (DL4 only) and Phase 1b Cohort A Patient Characteristics (n=10) Prior lines of treatment Mean (min, max) 4.5 (1, 7) Previous lines of CPI Mean (Min, Max) 2.6 (1, 4) LDH at baseline >1 x ULN [% of patients] 60.0 Baseline tumor burden Mean target lesion sum of diameter [mm] (min, max) 66.9 (21.0, 178.7) Total infused dose Mean TCR - T cells 1 infused [x10 9 ] (min, max) 2.12 (1.07, 5.12) No. of Target - & Non - Target Lesions 60.0% with >3 lesions 40.0% with liver/brain lesions ORR 2 = 70% (7/10) cORR 3 = 56% (5/9) Median DOR 4 , min, max DOR Not reached, 2.4, 8.8+ months Median Follow - up 5 8.5 months * Maximum change of target lesions and RECIST 1 . 1 at different timepoints . 1 Transduced viable CD 8 T cells ; 2 Initial ORR : Objective response rate according to RECIST 1 . 1 at first scan post infusion at ~week 6 ; 3 Confirmed ORR (cORR) : Confirmed objective response rate according to RECIST 1 . 1 for patients with available second scan post infusion at ~ 3 months or patients with progressive disease (PD) at any timepoint before this scan ; 4 Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death . Patients with ongoing response will be censored at date of data cut - off . Median DOR is analyzed by using the Kaplan - Meier method ; 5 Median Follow - up is analyzed by using the reverse Kaplan - Meier method ; PD : Progressive Disease ; SD : Stable Disease ; PR : Partial Response ; cPR : Confirmed Partial Response ; BOR : Best Overall Response ; BL : Baseline ; CPI : Checkpoint inhibitor ; LDH : Lactate dehydrogenase Data cut - off Apr 04, 2023 25 • Heavily pre - treated melanoma patients after 1 - 4 lines of CPI: Cutaneous (N=8), uveal (N=1) and melanoma of unk. primary (N=1) • Phase 1a (N=5): previous manufacturing process • Phase 1b Cohort A (N=5): new monocyte depletion process, higher dose Phase 1a Phase 1b Cohort A Continuous Improvement from Phase 1a to Phase 1b Cohort A Best Overall Response Response over Time Phase 1a Phase 1b Cohort A
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
Exhibit 99.3
Delivering the Power of T cells to Cancer Patients © Immatics. Not for further reproduction or distribution. Immatics Corporate Presentation May 2, 2023
Forward - Looking Statement This presentation (“Presentation”) is provided by Immatics N . V . (“Immatics” or the “Company”) for informational purposes only . The information contained herein does not purport to be all - inclusive and none of Immatics, any of its affiliates, any of its or their respective control persons, officers, directors, employees or representatives makes any representation or warranty, express or implied, as to the accuracy, completeness or reliability of the information contained in this Presentation . Forward - Looking Statements . Certain statements in this presentation may be considered forward - looking statements . Forward - looking statements generally relate to future events or the Company’s future financial or operating performance . For example, statements concerning timing of data read - outs for product candidates, the timing of IND or CTA filing for pre - clinical stage product candidates, the Company’s focus on partnerships to advance its strategy, and other metrics are forward - looking statements . In some cases, you can identify forward - looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology . Such forward - looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements . These forward - looking statements are based upon estimates and assumptions that, while considered reasonable, Immatics and its management, are inherently uncertain . New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties . Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in the Company’s Annual report on Form 20 - F and other filings with the Securities and Exchange Commission (SEC) . Nothing in this presentation should be regarded as a representation by any person that the forward - looking statements set forth herein will be achieved or that any of the contemplated results of such forward - looking statements will be achieved . You should not place undue reliance on forward - looking statements, which speak only as of the date they are made . The Company undertakes no duty to update these forward - looking statements . No Offer or Solicitation . This communication is for informational purposes only and does not constitute, or form a part of, an offer to sell or the solicitation of an offer to sell or an offer to buy or the solicitation of an offer to buy any securities, and there shall be no sale of securities, in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction . No offer of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933 , as amended, or in an offering exempt from registration . Certain information contained in this Presentation relates to or is based on studies, publications, surveys and the Company’s own internal estimates and research . In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions . Finally, while the Company believes its internal research is reliable, such research has not been verified by any independent source . All the scientific and clinical data presented within this presentation are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification . 2
Therapeutic O pp o rtun i t y Potential for addressing large patient populations with high prevalence targets in solid tumors Two Clinical - Stage Modalities Pipeline of TCR - T and TCR Bispecific product candidates in clinical & preclinical development Building a Leading TCR Therapeutics Company 3 I n t r o Di f f e r e n t i a t ed Platforms Unique technologies to identify true cancer targets and right TCRs Clinical PoC for Cell Therapy Anti - tumor activity and durability of response across multiple solid tumors in early TCR - T clinical development
4 • IMA203 monotherapy • Checkpoint combo • IMA203CD8 monotherapy Next update on all three IMA203 cohorts and clinical development path for PRAME TCR - T monotherapy towards registration - directed trials is planned for 4Q 2023 ACTengine® IMA203 (PRAME) Three IMA203 Ph1b cohorts Establish clinical PoC TCER® IMA401 (MAGEA4/8) Advance ongoing Phase 1 clinical trial Start of Phase 1/2 clinical trial planned in 2H 2023 First clinical data planned in 2024 TCER® IMA402 (PRAME) CTA 1 application submitted on April 14, 2023 I n t r o Solid cash runway into 2025 to reach multiple value inflections points across our portfolio Our Near - Term Focus – Clinical Development of Our Lead Assets from Our Autologous TCR - T (ACTengine®) and TCR Bispecifics (TCER®) Pipeline 1 Clinical Trial Application (CTA) is the European equivalent of an Investigational New Drug (IND) application
Our TCR - based Approaches Leverage the Full Target Space beyond the Cancer Cell Surface 5 I n t r o
Two Distinct TCR - based Therapeutic Modalities in Clinical Development 6 Differentiated positioning of ACTengine® vs. TCER® based on patient population and medical need I n t r o 1 Interim data update from the ACTengine® IMA203 TCR - T Phase 1 trial with a 50% (6/12) confirmed ORR target dose or above with at least 1 billion infused TCR - T cells across several solid tumor indications, 80% (4/5) confirmed ORR in Phase 1b patients only; 2 Initial manufacturing may provide sufficient quantity for potential repeat dosing. TCR Bispecifics (TCER®) Autologous TCR - T (ACTengine®) • Strong clinical activity in patients with high tumor burden 1 • Single dose 2 • Proprietary manufacturing process for enhanced potency of T cells • Specialized medical centers • Target requirements: stringent tumor selectivity, low, medium, high copy numbers • Off - the - shelf biologic for immediate treatment • Repeat dosing • All hospitals and out - patient, opportunity for larger patient reach • Favorable commercial characteristics • Target requirements: strong tumor association, median to high copy numbers
Our Pipeline of TCR - based Adoptive Cell Therapies and Bispecifics 7 I n t r o 1 Phase 1a: Dose escalation, Phase 1b: Dose expansion; 2 Opdivo® (nivolumab): programmed death - 1 (PD - 1) immune checkpoint inhibitor; * Immatics proprietary ACTallo® platform utilizing Editas’ CRISPR gene editing technology Modality Product Candidate Target Preclinical Phase 1a 1 Phase 1b 1 Phase 2 Phase 3 Autologous ACT ACTengine ® IMA203 PRAME + C heckpoint Inhibito r 2 ACTengine® IMA203CD8 PRAME ACTengine® IMA204 COL6A3 Multiple programs Undisclosed Allogeneic ACT γδ T cells ACTallo® IMA30x Undisclosed * Multiple programs Undisclosed Bispecifics TCER® IMA401 MAGEA4/8 TCER® IMA402 PRAME TCER® IMA403 Undisclosed Multiple programs Undisclosed
Strategic Collaborations Synergistic Expertise that Can Foster Transformative Innovations for ACT and Bispecifics Research collaboration to develop bispecific immunotherapies 2 Immatics targets $54 M upfront Co - promotion option Broadening the clinical framework beyond our pipeline Research collaboration to develop TCR - T therapies 4 Immatics targets (3 in 2019 + 1 in 2022) $75 M (2019) + $20 M (2022) upfront; Opt - in right for 1 st program exercised by BMS in 2Q 2023 for $15 M option exercise fee Co - development/Co - fund option Research collaboration to develop off - the - shelf allogeneic γδ - based TCR - T/ CAR - T programs $60 M upfront Clinical co - development collaboration to develop Immatics’ TCR Bispecific program TCER® IMA401 $150 M upfront Co - promotion option in the US 2022 2021 2018 2019 Each of our 9 partnered programs may be eligible for • >$500 million aggregated milestone payments • Tiered royalties 8
Potential for Large Patient Populations across Multiple Solid Cancers 9 Uterine Carcinoma – 100% Sarcoma Subtypes – up to 100% Cut. Melanoma – 95% Uveal Melanoma 1 – 90% Ovarian Carcinoma – 80% Squamous NSCLC – 65% TNBC – 60% Small Cell Lung Cancel – 55% Kidney Carcinoma – up to 45% Cholangiocarcinoma – 35% Adeno NSCLC – 25% Breast Carcinoma – 25% HNSCC – 25% Esophageal Carcinoma – 20% HCC – 20% Bladder Carcinoma – 20% Sarcoma Subtypes – up to 80% Squamous NSCLC – 50% HNSCC – 35% Bladder Carcinoma – 30% Esophageal Carcinoma – 25% Uterine Carcinosarcoma – 25% Ovarian Carcinoma – 20% Melanoma – 20% IMA203 / IMA402 PRAME IMA401 M A G E A4/ 8 IMA204 COL6A3 Exon 6 I n t r o 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% ACTengine® and TCER® targets demonstrate high prevalence in multiple solid cancers Target prevalence for selected solid cancer indications are based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; 1 Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=21)
Realizing the Full Multi - Cancer Opportunity of PRAME ACTengine® IMA203 (TCR - T) and TCER® IMA402 (TCR Bispecific) 10 Indication % PRAME positive patients 1 Uterine Carcinoma Uterine Carcinosarcoma Sarcoma Subtypes Cut. Melanoma Uveal Melanoma 2 Ovarian Carcinoma Squamous NSCLC T N BC Small Cell Lung Cancer Kidney Carcinoma C h ola n g io c a r c i n oma Adeno NSCLC Breast Carcinoma H NS CC Esophageal Carcinoma HCC Bladder Carcinoma 100% 100% up to 100% 95% 90% 80% 65% 60% 55% up to 45% 35% 25% 25% 25% 20% 20% 20% TCER® IMA402 (TCR Bispecific) A C T eng i ne® IMA203 (TCR - T) Cancer Cell Death PRAME is one of the most promising and most prevalent, clinically validated solid tumor targets known to date Leverage the full potential of targeting PRAME by continued evaluation of the best suited therapeutic modality (ACTengine® vs. TCER® or both) for each cancer type x CTA submitted x Start of clinical trial planned in 2H 2023 x First clinical data 2024 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 Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=21); NSCLC: Non - small cell lung cancer, TNBC: Triple - negative breast cancer, HNSCC: Head and neck squamous cell carcinoma; HCC: Hepatocellular carcinoma I n t r o
ACTengine® IMA203 – TCR - T Targeting PRAME 11
ACTengine® IMA203 Targeting PRAME – Mechanism of Action Immatics’ Leading TCR - T Approach 12 I M A 203
Key Pillars of Developing a Successful TCR - T Product Candidate Summary of Interim Update on IMA203 TCR - T Phase 1b Cohort A as of April 2023 S a f e ty Anti - Tumor Activity Durability Product Quality Broad Reach Manageable tolerability at doses as high as ~9x10 9 TCR - T cells High rate of objective responses: 64% (7/11) ORR 1 67% (6/9) cORR 2 Ongoing durable responses at 9+ months mDOR: Not reached min 1.3+, max 8.8+ mFU: 8.5 months Rapid manufacturing time of 7 days (+ 7 - day release testing), manufacturing success rate of 94% Confirmed objective responses in broad range of solid cancer types at low, medium and high PRAME levels above threshold 1 Initial ORR: Objective response rate according to RECIST 1.1 at first scan post infusion at ~week 6; 2 Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with available second scan post infusion at ~month 3 or patients with progressive disease (PD) at any timepoint before this scan; mDOR: median duration of response; mFU: median follow - up Data cut - off Apr 04, 2023 13 I M A 203
The Multi - Cancer Opportunity of PRAME One of the Most Promising Solid Tumor Targets for TCR - based Therapies Known To Date 14 High prevalence High target density Homogeneous expression “Clean” expression profile Clinical proof - of - concept s q N S C L C Ovarian Cancer PRAME fulfills all properties of an ideal target for TCR - based therapies TUMOR CELL T CELL H LA - A * 02 : 01 PRAME TCR PRAME Pep ೦ de PRAME RNA detection in tumor samples (ISH) ISH: in situ hybridization, sqNSCLC: squamous non - small cell lung cancer I M A 203
ACTengine® IMA203 TCR - T Monotherapy – Patient Flow 15 HLA - A*02 Testing Blood sample; Central lab Treatment & Observation Phase Long Term Follow - up Screening & Manufacturing Phase Manufacturing by Immatics Infusion of ACTengine® IMA203 TCR - T Product Lymphodepletion * Target Profiling Fresh Tumor Biopsy; IMADetect® Low dose IL - 2 ** Safety and efficacy monitoring for 12 months Leukapheresis x x E xpr e ss i on Antigen 1 2 3 * 30 mg/m 2 Fludarabine and 500 mg/m 2 Cyclophosphamide for 4 days; ** 1m IU daily days 1 - 5 and twice daily days 6 - 10 Short process time of 14 days 7 - day rapid manufacturing process 7 - day expedited QC release testing Monocyte depletion process implemented in Phase 1b I M A 203
ACTengine® IMA203 TCR - T Phase 1 Design Focus on IMA203 TCR - T Monotherapy Investigated in Cohort A 16 Phase 1b Cohort A Interim Update on 11 patients 1 Updated target dose (provisional recommended Phase 2 dose, RP2D) determined at DL4+DL5 for Cohort A and B, for Cohort C treatment of n=3 patients at DL3 completed, enrollment at DL4a ongoing before continuation at DL4b and potentially DL5; 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 Demonstrated to be important for long - term remission: Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances; 5 IMA203CD8 Dose Level 4a: 0.481 - 0.8x10 9 transduced viable CD8 T cells/m 2 BSA » Focus on generation of safety data » Further investigation of a IMA203 plus CPI combination as a front - line therapy being considered Phase 1b Dose Expansion 1 Phase 1a Dose Escalation Cohort A IMA203 Monotherapy (N=11) Increasing T cell:Tumor cell Ratio 2 IMA203 Monotherapy in Basket Trial (N=27) » 2 nd Gen potency - enhanced monotherapy product version » Currently being explored in dose finding at DL4a 5 Data cut - off Apr 04, 2023 Cohort B IMA203 at Target Dose plus Checkpoint Inhibitor 3 Blocking PD - 1/PD - L1 pathway IMA203CD8 2nd Gen at Target Dose (plus DL5) 4 Adding functional CD4 T cells 5 Cohort C I M A 203
N =11 ACTengine® IMA203 TCR - T Monotherapy – Phase 1b Cohort A Patient and Product Characteristics Data cut - off Apr 04, 2023 17 Heavily pre - treated, metastatic last - line patients that have exhausted all available standard of care treatments 1 Including ovarian cancer patient A - DL5 - 04 who erroneously received one dose of nivolumab and is part of intent - to - treat (shown here) but not per - protocol population; 2 Transduced viable CD8 T cells; ULN: Upper limit of normal; LDH: Lactate dehydrogenase; BSA: Body surface area; RP2D: Recommended Phase 2 Dose DL5 cleared for safety, updated provisional RP2D comprises DL4 + DL5 : 0.2 - 4.7 x 10 9 TCR - T cells/m 2 BSA Patients in Phase 1b Cohort A (N=11) 1 Age Mean (min, max) 55.4 (31, 79) Gender Male / Female [% of patients] 45.5 / 54.5 Prior lines of treatment Mean (min, max) 3.7 (1, 10) LDH at baseline >1 x ULN [% of patients] 54.5 Baseline tumor burden Mean target lesion sum of diameter [mm] (min, max) 73.8 (21.0, 207.3) Total infused dose Mean TCR - T cells 2 infused [x10 9 ] (min, max) 3.67 (1.30, 8.84) I M A 203
Most Frequent Adverse Events – Phase 1b Cohort A (N=11) Manageable Treatment - emergent Adverse Events (TEAEs) CRS and ICANS graded by CARTOX criteria (Neelapu et al ., 2018); 1 ICANS: Immune Effector Cell - Associated Neurotoxicity Syndrome • Expected cytopenia (Grade 1 - 4) associated with lymphodepletion in all patients • Low - moderate cytokine release syndrome (CRS) in 91% (10/11) of patients • 45% (5/11) of patients had Grade 1 CRS (3 in DL4, 2 in DL5) • 45% (5/11) of patients had Grade 2 CRS (2 in DL4, 3 in DL5) • No dose - dependent increase of CRS • No ICANS 1 • No Dose - limiting toxicity • For IMA203 TCR - T monotherapy tolerability profile including Phase 1a dose escalation, see appendix IMA203 TCR - T monotherapy shows managable tolerability at total doses as high as ~9x10 9 TCR - T cells Data cut - off Apr 04, 2023 18 I M A 203
Best Overall Response – Phase 1b Cohort A Deep Objective Responses Independent of Tumor Type 1 Ovarian cancer patient A - DL5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population; 2 Initial ORR: Objective response rate according to RECIST 1.1 at first scan post infusion at ~week 6; 3 Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with available second scan post infusion at ~month 3 or patients with progressive disease (PD) at any timepoint before this scan; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BL: Baseline; BOR: Best Overall Response; NET: Neuroendocrine Tumor; CPI: Checkpoint Inhibitor ORR (at ~week 6) 2 64% (7/11) cORR (at ~month 3) 3 67% (6/9) Deep objective responses observed across multiple, heavily pre - treated tumor types • Responses observed in cutaneous and uveal melanoma, synovial sarcoma, head and neck cancer, and ovarian cancer • Initial responses at week 6 were confirmed in all 6 responders with available subsequent 3 - month scan • All cut. melanoma patients were CPI - refractory • All ovarian cancer patients were platinum - resistant Data cut - off Apr 04, 2023 19 1 I M A 203
Response over Time – Phase 1b Cohort A Durable Partial Responses 9+ Months after IMA203 TCR - T Treatment **Ovarian cancer patient A - DL 5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population ; 1 Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death . Patients with ongoing response will be censored at date of data cut - off . Median DOR is analyzed by using the Kaplan - Meier method ; 2 Median Follow - up is analyzed by using the reverse Kaplan - Meier method ; PD : Progressive Disease ; SD : Stable Disease ; PR : Partial Response ; cPR : Confirmed Partial Response ; BL : Baseline Median time from IMA203 TCR - T infusion to onset of response was 1.4 months Ongoing responses in 5 of 7 responders: • 2 cPRs (cut. & uveal melanoma) ongoing at 9+ months • 1 cPR (cut. melanoma) ongoing at 6+ months • 1 cPR (ovarian cancer) ongoing at ~3 months • 1 PR (synovial sarcoma) ongoing at 6+ weeks Median DOR 1 , min, max DOR Not reached, 1.3+, 8.8+ months Median Follow - up 2 8.5 months * ** * Ongoing Response until 5.7 months post infusion, target lesion response assessment not available (external assessment) Scans at approximately week 6, month 3 and then every 3 months Data cut - off Apr 04, 2023 20 I M A 203
Biological Data Consistent with Clinical Data IMA203 TCR - T Levels and Tumor Infiltration across Patients in Phase 1a and Phase 1b Cohort A IMA203 T cells found in all evaluable tumor tissues, level of infiltration associated with objective responses 1 Increased levels of IMA203 T cells in the blood of patients in Cohort A following increase of cell dose and switch to monocyte depletion process Data cut - off Apr 04, 2023 21 Mann - Whitney U test; 1 T cell infiltration for 21 patients (10 non - responder, 11 responder) with 6 - week post infusion biopsy available (1 patient with ~4 - week, 2 patients with ~13 - week post infusion biopsy); PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response 1 î 10 0 1 î 10 1 1 î 10 2 1 î 10 3 1 î 10 4 1 î 10 5 1 î 10 6 IMA203 T cell infiltration [vector copies/µg gDNA] PD / S D (n=10) P R / cPR (n=11) P D /SD PR cPR 0. 0003 N = 2 1 p =0 . 0003 0 5 î 10 5 1 î 10 6 1.5 î 10 6 2 î 10 6 ) x a m C ( n o si n DNA] a exp g g k μ ea es / P i l p el co c [ T 3 20 MA I PD / SD PR cPR <0. 0 0 01 Cohort A (n=11) Phase 1a (n=27) Vector copies/µg gDNA p <0 . 0001 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 0 4 8 12 16 20 40 60 80 100 200 400 600 800 Days post infusion Vector copies/μg gDNA N = 3 8 Phase 1A Cohort A Persistence over time Peak persistence N =38 I M A 203
0 2 î 10 5 4 î 10 5 6 î 10 5 8 î 10 5 0. 0025 Favorable TCR - T Product Characteristics and High TCR - T Levels in Patients Manufacturing Improvements Implemented in Phase 1b Enhance Key Features of the Cell Product Manufacturing success rate of 94% to reach provisional RP2D ** Mean cell dose infused in 11 patients in Phase 1b Cohort A was 3.67x10 9 TCR - T cells Manufacturing process (infused products) MD pr o cess (n=12) Prior v e r s i o n s (n=26) Prior MD versions process (n=26) (n=12) MD process: Monocyte depletion process; * Unpaired t test; # Mann - Whitney U test; ** Updated provisional RP2D comprises DL4 + DL5: 0.2 - 4.7x10 9 transduced viable CD8 T cells/m 2 BSA; Increased peak TCR - T levels in patients Improved TCR - T product features 0 5 î 10 5 1 î 10 6 1.5 î 10 6 2 î 10 6 < 0 . 00 0 1 IMA203 T cell peak frequency [vector copies/µg gDNA] MD pr o cess (n=12) Prior v e r s i o n s (n=26) MD pr o cess (n=5) Prior v e r s i o n s (n=7) p<0.0001 # p=0.0025 # DL4 only, normalized to cell dose 0 20 40 60 80 100 % CD3+CD8+ Cells (of viable cells) 0 20 40 60 80 100 %Dextramer (of CD3+CD8+ Cells) Normalized peak frequency [vector copies per µg gDNA/10 9 TCR - T cells] Data cut - off Apr 04, 2023 22 p=0.0032 * p<0.0001 * I M A 203
Responses above Immatics’ PRAME RNA Threshold Independent of Tumor Type Highlighting Tumor Types (left) and Type of Best Overall Response (right) – Phase 1b Cohort A PRAME RNA expression in pre - treatment biopsies relative to threshold IMA203 achieved objective responses at all expression levels above Immatics’ mass spectrometry - guided RNA threshold A - DL 5 - 01 A - DL 4 - 04 A - DL 4 - 05 A - DL 5 - 02 A - DL 5 - 04 A - DL 4 - 03 A - DL 5 - 05 A - DL 4 - 01 A - DL 5 - 03 A - DL 4 - 02 A - DL 5 - 06 IMA203 has the potential to provide clinical benefit for all PRAME biomarker - positive cancer patients Mann - Whitney U test, p=0.23; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; NET: Neuroendocrine Tumor Data cut - off Apr 04, 2023 23 T hreshold T hreshold I M A 203
Potential of IMA203 in Additional Solid Cancer Indications Based on PRAME Expression in IMA203 TCR - T Responders – Phase 1b Cohort A 24 Immatics’ proprietary mass spectrometry - guided mRNA threshold 100% 100% 95% 100% 50% (90% 2 ) 80% 60% 65% 25% % PRAME - positive patients 1 PRAME target expression distribution (blue histogram) based on TCGA RNAseq data, patient data (black dots) based on IMADetect® qPCR testing of screening biopsies; 1 PRAME target prevalence is based on TCGA RNAseq data combined with a proprietary MS - guided RNA expression threshold; 2 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% compared to prevalence based on TCGA data of 50%, 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; MS: mass spectrometry PRAME mRNA expression in Phase 1b Cohort A responders Data cut - off Apr 04, 2023 Selected indications A - DL4 - 03 A - DL5 - 03 A - DL5 - 06 A - DL5 - 01 A - DL4 - 02 A - DL5 - 05 A - DL4 - 01 I M A 203
ACTengine® IMA203 TCR - T Monotherapy Targeting PRAME Summary of Phase 1b Cohort A Interim Data Update • Manageable tolerability with no high - grade CRS, no ICANS in 11 patients in Cohort A 1 • Objective responses observed in heavily pre - treated last - line solid cancer patients including checkpoint - refractory cutaneous melanoma, platinum - resistant ovarian cancer, uveal melanoma, head and neck cancer, synovial sarcoma • High objective response rate (ORR): • 64% (7/11) ORR (at ~week 6) • 67% (6/9) cORR (at ~month 3) • Ongoing durable responses: • Median duration of response not reached at a median follow - up time of 8.5 months • Ongoing PRs 9+ months after IMA203 TCR - T treatment • Objective responses independent of tumor type at low, medium and high PRAME levels above threshold • Manufacturing success rate of 94% to reach current RP2D, rapid 7 - day manufacturing process (+7 - day release testing) Increased confidence in the success and broad potential of targeting PRAME and our product candidate IMA203 TCR - T 1 For IMA203 TCR - T monotherapy tolerability profile including Phase 1a dose escalation, see appendix; CRS: Cytokine Release Syndrome; ICANS: Immune effector cell - associated neurotoxicity syndrome; RP2D: provisional recommended Phase 2 dose Data cut - off Apr 04, 2023 25 I M A 203
Immatics’ ACTengine® IMA203 TCR - T Development Strategy Two Pillared Strategy 26 Objective: Deliver best - in - class therapy in 1 - 2 last - line solid cancer types as fast as possible • Focus on indications with PRAME prevalence above 80% with available clinical PoC, such as cut. melanoma (potentially bundled with uveal melanoma) and ovarian cancer • Highly modular and scalable manufacturing facility expected to be operational in 2024 to support efforts to maximize speed to market • Planned start of a first Phase 2 trial in 1H 2024 – targeted to be already registration - directed Objective: Expand development to other cancer types • Signal finding in other cancer types with a broad patient reach, such as uterine cancer, lung cancer, breast cancer, head and neck cancer FAST & F O C US E D GO BROAD Update on all three IMA203 Phase 1b cohorts and clinical development path towards registration - directed trials and potential commercialization for PRAME TCR - T monotherapy is planned for 4Q 2023 I M A 203
ACTengine® IMA203 TCR - T Product Manufacturing Enhancing Manufacturing Process and Capabilities Leukapheresis Rapid Manufacturing Process 1 week Expedited QC Release Testing 1 week I nf usio n - r e a d y Manufacturing of ACTengine® IMA203 TCR - T & other future autologous /allogeneic candidates Early - stage and registration - directed clinical trials as well as initial commercial supply Approx. 100,000 sq ft in Houston area, TX – modular and flexible design Expected to be operational in 2024 State - of - the - art research & GMP manufacturing facility Short manufacturing turnaround time 27 I M A 203
Selected Indications Incidence R/R Incidence PRAME Positive Patient Population Based on R/R Incidence; PRAME and HLA - A*02:01+ Cut. Melanoma 99,800 7,700 95% 2,999 Uveal Melanoma 1,500 800 90% 295 Ovarian Carcinoma 19,900 12,800 80% 4,198 Uterine Carcinoma 62,700 10,700 100% 4,387 Uterine Carcinosarcoma 3,300 1,900 100% 779 Squamous NSCLC 57,000 34,600 65% 9,221 Small Cell Lung Cancer 31,900 19,400 55% 4,375 Adeno NSCLC 91,200 55,300 25% 5,668 H N S CC 66,500 15,100 25% 1,548 Breast Carcinoma 290,600 43,800 25% TNBC: 60% 4,490 Synovial Sarcoma 1,000 400 100% 164 Cho l a n g io c a r c i no m a 8,000 7,000 35% 1,005 IMA203 TCR - T Has the Potential to Reach a Large Patient Population ~39,000 Patients per Year in the US only 28 Incidences based on public estimates and Immatics internal model; Relapsed/refractory (R/R) or last - line patient population approximated by annual mortality; Estimated 41% HLA - A*02:01 positive population in the US; PRAME target prevalence is based on TCGA (for SCLC: in - house) RNAseq data combined with a proprietary mass spec - guided RNA expression threshold; Uveal melanoma target prevalence is based on IMADetect® qPCR testing of screening biopsies from clinical trial patients (n=21) Multiple opportunities to broaden patient reach and patient benefit: » Expand beyond US population » Expand into other indications such as kidney, esophageal, bladder, liver cancer, other sarcoma subtypes through indication - specific or indication - agonistic label expansion » Move into earlier lines of therapy (R/R Incidence Incidence) » Inclusion of patients with lower PRAME - threshold TOTAL ~39,000 annually in the US I M A 203
ACTengine® IMA203CD8 – Next - generation TCR - T Building on First - Gen IMA203 Success to Further Improve Anti - Tumor Activity • Engagement of CD4 T cells by CD8 co - transduction reported to boost anti - tumor activity in TCR - T trials • Recent data from leukaemia patients treated with CAR - T suggest a relevant role of engineered CD4 T cells in maintaining durable tumor responses over a long period of time 1 • Functional superiority of the CD8αβ construct over multiple other CD8 constructs in preclinical experiments • Proprietary 4 - in - 1 lentiviral vector to engineer CD4 and CD8 T cells with the PRAME - specific IMA203 TCR and CD8αβ construct (IMA203CD8) TUMOR CELL DEATH CD4 T CELL Cy t o t o x ic Activity CD8 T CELL T cell Help Cy t o t o x ic Activity 29 1 Melenhorst et al. 2022 Nature, Bai et al. 2022 Science Advances IMA203CD8
ACTengine® IMA203CD8 – Preclinical Assessment of Anti - Tumor Efficacy Functional CD4 T cells Mediate Longer Anti - Tumor Activity than CD8 T cells in vitro 30 0 .0 0 .5 1 .0 1 .5 2 .0 CD8 0 50 100 150 200 250 300 350 400 450 Hours after Coculture Tumor fold growth 0 .0 0 .5 1.0 1 .5 2 .0 CD4 0 50 100 150 200 250 300 350 400 450 Hours after Coculture Tumor fold growth 2 nd addition of tumor cells 3 rd 4 th 5 th 6 th 2 nd addition of tumor cells 3 rd 4 th 5 th 6 th IMA203CD8 Engagement of CD4 T cells may enhance depth and durability of anti - tumor response and clinical outcome of TCR - T in solid cancer patients
ACTengine® IMA204 – TCR - T Targeting COL6A3 Exon 6 31
ACTengine® IMA204 First - in - Class TCR - T Targeting Tumor Stroma Key Features 32 HLA - A*02 - presented peptide derived from COL6A3 exon 6 Naturally and specifically presented on tumors at high target density 1 : 100 - 700 copies/cell Novel tumor stroma target identified and validated by XPRESIDENT® quant. mass spectrometry platform High - affinity, specific TCR targeting COL6A3 exon 6 Affinity - maturated, CD8 - independent TCR High functional avidity 2 : ~0.01ng/ml Identified and characterized by XCEPTOR® TCR discovery and engineering platform CD8 - independent, next - generation TCR engages both, CD8 and CD4 T cells In vitro anti - tumor activity against target - positive cell lines in CD8 and CD4 T cells Complete tumor eradication in in vivo mouse models Pancreatic Carcinoma – 80% Breast Carcinoma – 75% Stomach Carcinoma – 65% Sarcoma – 65% Esophageal Carcinoma – 60% Squamous NSCLC – 55% Adeno NSCLC – 55% HNSCC – 55% Uterine Carcinosarcoma – 55% Colorectal Carcinoma – 45% Mesothelioma – 45% Cholangiocarcinoma – 40% Ovarian Carcinoma – 40% Melanoma – 35% Bladder Carcinoma – 35% 1 Target density: peptide copy number per tumor cell, approximate range representing the majority of tumor samples analyzed; 2 Functional avidity: EC50 half maximal effective concentration; 3 Solid cancer indications with 20% or more target expression, Target prevalence for selected cancer indications based on mRNA expression (TCGA and Immatics inhouse data) T A R GET T CR PRECLINICAL DATA PATIENT POPULATION 3 IMA204 provides a promising therapeutic opportunity for a broad patient population as monotherapy or in combination with TCR - T cells directed against tumor targets I M A 204
ACTengine® IMA204 – High Affinity, CD8 - independent TCR Complete Tumor Eradication in vitro & in vivo 1 by Affinity - enhanced IMA204 TCR CD8 - independent TCR leads to tumor eradication in all mice treated 33 W Si Do ild t ngl ub l ype e e m muta n u t a n t t T u N mo o n - t r c ra n ells o s duc nl y ed Control IMA204 TCR D7 D 16 D 22 D 29 Affinity maturated CD8 - independent, next - generation TCR engages both CD4 and CD8 T cells without the need of CD8 co - transduction S tr o ma cells T u m or cells Stroma Target (COL6A3 exon 6) in Ovarian Cancer sample Example of a Tumor Target in same Ovarian Cancer sample 1 In vivo data in collaboration with Jim Riley, University of Pennsylvania, control: non - transduced T cells. TCR avidity and specificity data not shown, available in IMA204 presentation on Immatics website. COL6A3 exon 6 prevalently expressed at high target density in tumor stroma across many solid cancers I M A 204
ACTallo® – Our Next - generation Off - the - shelf TCR - T 34
ACTallo® – Immatics’ Allogeneic Cell Therapy Approach • Off - the - shelf cell therapy , no need for personalized manufacturing reduced logistics and time to application • Potential for hundreds of doses from one single donor leukapheresis lower cost of goods • Use of healthy donor material provides standardized quality and quantity of starting material • Strategic collaborations combining Immatics’ proprietary ACTallo® platform with Bristol Myers Squibb’s next - gen technologies and Editas Medicine’s CRISPR gene editing technology to develop next - gen allogeneic γδ TCR - T/CAR - T programs 35 A C T a llo® γδ T cell Cell Engineering (gene editing & armoring) γδ T cell Collection from Healthy Donor Expansion O f f - t he - she l f Products Patient T r e a t me n t
Why γδ T cells? γδ T cells Are Well Suited for an Off - the - shelf Cell Therapy Approach 36 γδ T cells x are abundant in the peripheral blood x show intrinsic anti - tumor activity x naturally infiltrate solid tumors & correlate with favorable prognosis x are HLA - independent, thus do not cause graft - vs - host disease in allogeneic setting x can be expanded to high numbers in a cGMP - compatible manner x can be effectively redirected using αβ TCR or CAR constructs In vitro anti - tumor activity 0 48 14 4 19 2 0 5 10 15 96 H o u rs ) P + F R - 2 0 S U ( h t o w r G d o l F T u m o r c e lls o n ly T ce lls ( N T ) T c e lls ( N T ) T c e lls IM A 2 0 3 TC R + T ce lls IM A 2 0 3 T C R + γδ T cells (control) + tumor cells tumor cells only αβ T cells (control) + tumor cells γδ T cells TCR + + tumor cells αβ T cells TCR + + tumor cells A C T a llo® 0 . 00 1 0 . 0 1 0 . 1 1 1 0 100 100 0 1000 0 100000 100000 0 0 5 10 15 20 25 Day Fold expansion of T cells Expansion Fold - growth (target - positive tumor cells)
TCER® – TCR Bispecifics 37
TCER® – Immatics’ Next - generation, Half - Life Extended Bispecifics Proprietary TCER® Format Consisting of Three Distinct Elements 38 High - affinity TCR domains targeting XPRESIDENT® - selected tumor - specific peptide - HLA molecules L o w - a ff i n i t y T cell recruiter against CD3/TCR Fc part for half - life extension, favorable stability and m a nu f a c t u r a b ili t y Next - gen, half - life extended TCER® format designed to safely apply high drug doses for activity in a broad range of tumors achieve optimized scheduling 2 1 3 C y t o t o xic lytic granules Tumor cell killing Activated T cell T CE R ®
TCER® – Immatics’ Next - generation, Half - Life Extended Bispecifics 39 pHLA targeting TCR x High - affinity (single digit nM) TCR targeting XPRESIDENT® - selected tumor - specific peptide - HLA molecules 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 (triple digit nM) T cell recruiter against both TCR & CD3 x Optimized biodistribution aiming for enrichment at tumor site and prevention of CRS 2 x Superior anti - tumor activity in mouse models as compared to widely used CD3 recruiters Next - generation TCER® format x Off - the - shelf biologic with antibody - like manufacturability 3 and low cost of goods x Superior anti - tumor activity 4 compared to six alternative bispecific formats x Half - life of several days expected in humans Our TCER® format is designed to maximize efficacy while minimizing toxicities in patients 1 As compared to natural TCR; 2 Based on literature data for other low - affinity recruiters (e.g. Harber et al ., 2021, Nature; Trinklein et al ., 2019, mAbs); 3 Production in mammalian cells (CHO cells); 4 Based on preclinical testing T CE R ® 1 2 3
Potency of Our Proprietary TCR Bispecific Format TCER® 40 • Seven different TCR Bispecific formats were evaluated with a pHLA targeting TCR and the identical T cell recruiting antibody • TCER® format had higher combination of potency and specificity 1 than six alternative TCR Bispecific format designs evaluated Flexible Plug - and - play platform: TCER® format successfully validated for different TCRs & different T cell recruiting antibodies T CE R ® T CE R® 2+1 TCR bispecific format: High potency was linked to a significantly reduced specificity profile Killing of target - positive cells by different TCR Bispecifics 1 Preclinical data on specificty not shown
TCER® Format Is Designed for Optimized Efficacy and Safety Superior Tumor Control Using a Novel, Low - Affinity Recruiter 41 n = 6 mice/treatment group, n = 10 mice in vehicle group, 2 donors/group Dose : 0 . 025 mg/kg Proprietary, low - affinity T cell recruiting region demonstrates superior tumor control compared to analogous TCER® molecules designed with higher - affinity variants of a widely used recruiter Widely used T cell recruiting Ab (3 variants) medium to high affinity (single to double digit nM) Immatics’ T cell recruiting Ab low affinity (triple digit nM) T CE R ® Tumor Model in Mice 1 1 Hs695T xenograft model in NOG mice, tumor volume of group means shown
TCER® Format Is Designed for Optimized Efficacy and Safety Reduced Target - Unrelated Recruiter - Mediated Cytokine Release using a Low - Affinity Recruiter 42 T CE R ® Whole blood cytokine release assay N=3 HLA - A*02 - positive donors N=16 cytokines tested, 4 exemplary cytokines shown
Our TCER® Portfolio Broad Pipeline of Next - Gen Half - Life Extended TCR Bispecifics 43 T CE R ® • PRAME peptide presented by HLA - A*02:01 • Start of clinical trial planned for 2H 2023, first clinical data in 2024 IM A 402 • Undisclosed peptide presented by HLA - A*02:01 • Preclinical PoC studies ongoing IM A 403 Potential for addressing different indications and large patient populations with novel, off - the - shelf TCR Bispecifics • MAGEA4/8 peptide presented by HLA - A*02:01 • Start of clinical trial in May 2022, dose escalation ongoing IM A 401 • Undisclosed peptides presented by HLA - A*02:01 and other HLA - types • TCER® engineering and preclinical testing ongoing IMA40x Several innovative programs
TCER® IMA402 Targeting PRAME – Efficacy Assessment in vitro Tumor Cell Killing at Low Physiological PRAME Peptide Levels 44 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] ~50 PRAME CpCs 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] Cytotoxicity [%] Target - negative 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] ~110 PRAME CpCs 0 140 120 100 80 60 40 20 0 10 - 1 10 0 10 1 10 2 10 3 10 4 10 5 IMA402 [pM] ~250 PRAME CpCs 0 • TCER® IMA402 induces killing of tumor cells with PRAME target copies as low as 50 CpCs • Physiological PRAME levels detected in majority of cancer tissues from patients are 100 – 1000 CpCs • Preclinical activity profile enables targeting of a broad variety of tumor indications, such as lung cancer, breast cancer, ovarian cancer, uterine cancer, melanoma and others I M A 402 CpC: Target peptide copy numbers per tumor cell
TCER® IMA402 Achieves Durable Tumor Control of Large Tumors in vivo 45 - 2 9 0 50 0 100 0 150 0 200 0 250 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 Study day Median tumor volume [mm 3 ] Vehicle IMA402 [0.01 mg/kg] IMA402 [0.05 mg/kg] IMA402 [0.25 mg/kg] • Dose - dependent efficacy of IMA402 in cell line - derived in vivo mouse model • Durable shrinkage of large tumors including complete responses over prolonged period • Sufficiently high drug doses are key to achieving desired anti - tumor effect I M A 402
Half - life Extended Format of IMA402 Confers Terminal Half - life of >1 Week 46 pHLA – aFc Assay pHLA – aV L Assay • IMA402 shows a terminal serum half - life of ≈ 8 days in mice • IMA402 will be initially dosed weekly in the clinical trial • Dosing frequency may be adapted based on clinical data I M A 402
Upcoming activities • Start of patient treatment planned for 2H 2023 • First clinical data planned in 2024 Advancing TCER® IMA402 Towards Clinical Development Recent and Upcoming Activities 47 IMA402 TCER® Ph1/2 clinical trial in patients with solid tumors Recent activities x Completion of IND - enabling data package x Manufacturing of GMP batch completed with high titer (>3.5 g/L) and high yield x Scientific advice with regulatory authorities x CTA 1 submitted in April 2023 I M A 402 1 Clinical Trial Application (CTA) is the European equivalent of an Investigational New Drug (IND) application
TCER® IMA402 Phase 1/2 Clinical Trial to Start in 2023 48 MABEL: minimum anticipated biological effect level Phase 1: Dose Escalation Phase 2a: Dose Expansion Basket trial with focus indications Adaptive design aimed at accelerating dose escalation • Specific indications plus ongoing basket • Combination therapies • Optional dose/application optimization Expansion cohort Expansion cohort Expansion cohort Trial Overview Phase 1/2 clinical trial to evaluate safety, tolerability and anti - tumor activity of IMA402 HLA - A*02:01 - positive patients with PRAME - expressing recurrent and/or refractory solid tumors M TD/ RP2D I M A 402
Accelerated Development of TCER® IMA402 TCER® IMA402 Phase 1/2 Clinical Trial Design Targeting enhanced treatment convenience • Initially weekly i.v. infusions, potential for early optimization of scheduling based on half - life extended TCER® format • Exploring s.c. application 49 I M A 402 MABEL: minimum anticipated biological effect level; DLT period: Evaluation period for potential dose limiting toxicities (DLT) in a patient Flexible trial design for fast clinical execution • Adaptive design with flexible dose cohorts, initially only 1 - 3 patients per dose level, optimized MABEL approach with elevated starting dose, short DLT period of 2 weeks • Basket trial in focus indications for accelerated signal finding, multiple options for expansion cohorts • Extension from phase 1/2 to pivotal possible Optimized patient selection to leverage the broad PRAME potential Assuring sufficient PRAME target expression using our IMADetect® qRT - PCR assay (mass spectrometry - guided RNA threshold) » No pretesting for indications with very high PRAME prevalence, e.g. melanoma, uterine & ovarian cancer, synovial sarcoma » Prospective target testing for indications with PRAME prevalence <80%, e.g. lung cancer, breast cancer, head and neck cancer 1 2 3
Immatics’ Proprietary Target and TCR Discovery Platforms 50
True Cancer Targets & Matching Right TCRs Goal to Maximize Anti - Tumor Activity and Minimize Safety Risks of TCR - based Immunotherapies 51 True Targets via XPRESIDENT® technology platform • are naturally presented on tumor tissues as identified by mass - spec • are absent or presented at only low levels on normal tissues • are presented at high copy numbers to trigger a pharmacological response + T e chn olo g y Right TCRs via XCEPTOR® technology platform • recognize the target peptide with high affinity and specificity • show selective killing of tumor cells • are developed to be suitable for two different therapeutic modalities, Cell Therapies and TCR Bispecifics
T e chn olo g y Pool of 200 Prioritized Targets as Foundation for Future Value Generation 52 200 Prioritized Targets Grouped in 3 Target Classes: 1. Well known and characterized parent protein (20%) e.g. MAGE family cancer testis antigens 2. Unknown or poorly characterized parent protein (60%) e.g. stroma target COL6A3 exon 6 3. Crypto - targets/Neoantigens (20%) Novel target class which includes RNA - edited peptides & non - classical neoantigens ~50% of our prioritized targets are non - HLA - A*02 restricted, substantially broadening the potential patient reach >2,500 cancer & normal tissues analyzed by Quantitative, Ultra - Sensitive Mass Spectrometry pHLA Database based on primary tissues >200 p ri o ri t i z e d targets
Immatics’ Unique Capability – Identification of the most Relevant Target Example of MAGEA4/8 Peptide Target 53 1 Copy number per tumor cell (CpC) measured on a paired - sample basis by AbsQuant®, i.e. comparing MAGEA4 vs. MAGEA4/A8 peptide presentation on same sample, 2 Students paired T test p<0.001 2 T e chn olo g y MAGEA4/8 target is presented at >5 - fold higher target density 1 than a commonly used MAGEA4 target peptide XPRESIDENT® quantitative information on target density 1 between peptides originating from the same source protein Ranking of pHLA targets
Development of the Right TCR – XCEPTOR® Technology TCR Discovery and Engineering for ACT and TCR Bispecifics 54 TCR Bispecifics T cell engaging receptor (TCER®) Adoptive Cell Therapy A C T e n g i n e® ACTallo® • Fast, efficient and highly sensitive discovery of highly specific, natural TCRs • Protein engineering capabilities to design and maturate TCRs with increased affinity while retaining specificity • Early de - selection of cross - reactive TCRs by the unique interplay between Immatics’ target and TCR discovery platforms XPRESIDENT® and XCEPTOR® during TCR discovery 1 and TCR maturation 2 Micromolar affinity Nanomolar affinity T e chn olo g y 1 XPRESIDENT® - guided off - target toxicity screening; 2 XPRESIDENT® - guided similar peptide counterselection
Optimal Target Selection & TCR Specificity for Minimizing Safety Risks Unique Interplay between Technology Platforms Allows Early De - risking for Clinical Development 55 Target peptide presented on tumor cells Selective killing of tumor cells Target peptide presented on normal cells Of f - t a r ge t toxicity On - target (off - tumor) toxicity A different HLA is recognized on normal cells Alloreactivity Similar peptide presented on normal cells 1 XPRESIDENT® - guided screening for on - and off - target toxicities of TCRs based on the extensive database of peptides presented on normal tissues T e chn olo g y 1 Clinical fatalities have occurred in TCR - T trials using a titin cross - reactive TCR (Cameron et al ., Sci Transl Med)
Robust IP Portfolio Immatics’ Patent Estate – Territorial Coverage 56 Cancer targets, TCRs and technology protected by: • 5 , 800 applications and patents filed in all major countries and regions • >115 patent families • >2,400 granted patents, thereof >550 granted patents in the US T e chn olo g y
Corporate Information & Milestones 57
Harpreet Singh Chief Executive Officer Co - Founder >20 yrs biotech experience Arnd Christ Chief Financial Officer >20 yrs biotech experience (InflaRx, Medigene, NovImmune, Probiodrug) Carsten Reinhardt Chief Development Officer >20 yrs pharma & biotech experience (Micromet, Roche, Fresenius) Cedrik Britten Chief Medical Officer 15 yrs pharma & biotech experience (GSK, BioNTech) Rainer Kramer Chief Business Officer 25 yrs pharma & biotech experience (Amgen, MorphoSys, Jerini, Shire, Signature Dx) Steffen Walter Chief Operating Officer Co - Founder Immatics US >15 yrs biotech experience Edward Sturchio General Counsel >15 yrs pharma & biotech experience (Abeona Therapeutics, AAA, Novartis, Merck, Schering) Jordan Silverstein Head of Strategy >10 yrs biotech experience (InflaRx, AAA) Toni Weinschenk Chief Innovation Officer Co - Founder >15 yrs biotech experience Experienced Global Leadership Team Across Europe and the US Corporate
Strong, Focused and Highly Integrated Trans - Atlantic Organization 59 Houston, Texas ~150 FTEs Cell therapy development & manufacturing Munich, Germany ~65 FTEs Various operating functions Tübingen, Germany ~215 FTEs Target & TCR discovery and TCR Bispecifics d ev e l o p me nt Corporate FTE status as of December 2022
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 Appendix
ACTengine® IMA203 TCR - T 1 st Gen Monotherapy Tolerability Data Focus on IMA203 Phase 1b Cohort A – All ≥Grade 3 Adverse Events (N=11) • IMA203 was well tolerated • No Adverse Event ≥Grade 3 was observed with a frequency ≥10% when excluding expected cytopenias associated with lymphodepletion • No IMA203 - related Grade 5 Adverse Events All treatment - emergent adverse events (TEAEs) with ≥ Grade 3 regardless of relatedness to study treatment that occurred in at least 1 patient (except for CRS and ICANS, where only Grade 1 - 2 occurred ; listed for completeness due to being adverse events 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 ( 04 - Apr - 2023 ) . 1 ICANS : Immune effector cell - associated neurotoxicity syndrome . Data cut - off Apr 04, 2023 61 Adverse event ( System organ class , Preferred term) ≥ Grade 3 No. % Adverse event ( System organ class , Preferred term) ≥ Grade 3 No. % TEAEs by maximum severity for all patients in Ph1b Cohort A dose expansion (N=11) Patients with any adverse event 11 100.0 table continued… Adverse Events of Special Interest Investigations Cytokine release syndrome 0 0.0 ICANS 1 0 0.0 Alanine aminotransferase increased 1 9.1 Aspartate aminotransferase increased 1 9.1 Blood alkaline phosphatase increased 1 9.1 Blood and lymphatic system disorders Neutropenia 10 90.9 Lymphopenia 6 54.5 Leukopenia 5 45.5 Anaemia 5 45.5 Thrombocytopenia 4 36.4 Leukocytosis 1 9.1 Lymphocytosis 1 9.1 Eye disorders Ulcerative keratitis 1 9.1 Gastrointestinal disorders Ileus 1 9.1 Infections and infestations Infection 1 9.1 Nervous system disorders Headache 1 9.1 Respiratory, thoracic and mediastinal disorders Laryngeal inflammation 1 9.1 I M A 203
Deep & Durable Responses in Heavily Pre - Treated Patients – Phase 1b Cohort A Patient ID Indication No of prior treatment lines Prior treatments Total infused dose TCR - T cells 1 [x10 9 ] BOR BOR (Max % change of target lesions) Comment A - DL5 - 01 Uveal Melanoma 1 ARRY614/Nivolumab 4.16 cPR - 60.3 Ongoing response 10.1 months post infusion A - DL4 - 03 Cut. Melanoma 7 Dabrafenib/Trametinib, Pembrolizumab, Dabrafenib/Trametinib, Vemurafenib/Cobimetinib, Dabrafenib/Trametinib, IMCgp - 100, Encorafenib/Binimetinib 1.30 cPR - 73.9 Ongoing response 9.9 months post infusion A - DL5 - 03 Cut. Melanoma 3 Interferon, Pembrolizumab, Nivolumab/Ipilimumab 5.12 cPR - 60.5 Ongoing response 6.2 months post infusion A - DL4 - 01 Head & Neck Cancer 1 Carboplatin/Paclitaxel 1.92 cPR - 33.3 Response until 5.7 months post infusion A - DL4 - 02 Ovarian Cancer 10 Carboplatin/Taxol, Taxol, Ge m ci t abine /C arbopla t in , Olaparib, Letrozole, Rucaparib, UPCC 03118 (CAR - T cell directed folate receptor), Bevacizumab/Cyclophosphamide, Carboplatin, Doxorubicin 1.97 cPR - 41.0 Response until 3.8 months post infusion A - DL5 - 05 Ovarian Cancer 3 Adriamycin/Cytotaxan/Taxol, Carboplatin/Taxol, Carboplatin/Doxil 8.84 cPR - 61.7 Ongoing response 2.5 months post infusion A - DL5 - 06 Synovial Sarcoma 1 Adriamycin/Ifosfamide/Mesna 3.94 PR - 74.8 Initial PR at week 6, 3 - month scan pending A - DL4 - 04 Melanoma (Unk. Primary) 2 Nivolumab/Ipilimumab, Nivolumab 1.73 SD 0.0 Disease stabilization until 5.7 months post infusion A - DL4 - 05 Cut. Melanoma 5 Nivolumab, Nivolumab (re - exposure), Nivolumab/Ipilimumab, Dabrafenib/Trametinib, Nivolumab 1.63 SD 11.4 Ongoing disease stabilization 2.1 months post infusion A - DL5 - 02 Pancreatic Neuroendocrine Tumor 3 Lanreotid, Streptozocin/5 - Fluorouracil, Everolismus 5.12 SD - 21.8 Disease stabilization until 2.3 months post infusion A - DL5 - 04* Ovarian Cancer 5 P acli t axel /C arbopla t in , Niraparib, Doxorubicin/Liposomal/Carpoplatin, 2020 - 0808 ZN - C3/Gemcitabine, 2020 - 0755 COM 701/BMS - 986207/Nivolumab 4.68 PD 50.8 Progressive disease at 1.2 months post infusion 1 Transduced viable CD8 T cells; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BL: Baseline; BOR: Best Overall Response *Ovarian cancer patient A - DL5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population. Data cut - off Apr 04, 2023 62 I M A 203
ACTengine® IMA203 TCR - T 1 st Gen Monotherapy Tolerability Data • IMA203 was well tolerated • No Adverse Event ≥Grade 3 was observed with a frequency ≥10% when excluding expected cytopenias associated with lymphodepletion • No IMA203 - related Grade 5 Adverse Events 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 ( 04 - Apr - 2023 ) ; 1 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, Cytokine release syndrome, Diarrhoea, Hypokalaemia, Proteinuria ; Second patient : Humerus fracture, Muscle spasms, Neutropenia, Thrombocytopenia ; 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 were not considered related to any study drug ; 5 Patient died from sepsis of unknown origin and did not receive IMA 203 TCR - T cells . Data cut - off Apr 04, 2023 63 Adverse event ( System organ class , Preferred term) No. % Adverse event ( System organ class , Preferred term) ≥ Grade 3 ≥ Grade 3 No. % Phase 1a and Phase 1b Cohort A – All ≥Grade 3 Adverse Events (N=39) TEAEs by maximum severity for all patients in Ph1a dose escalation and Ph1b Cohort A dose expansion (N=39) 1 Patients with any adverse event 39 100.0 table continued… Adverse Events of Special Interest General disorders and administration site conditions Cytokine release syndrome 2 5.1 ICANS 2 0 0.0 Condition aggravated 4 1 2.6 Fatigue 1 2.6 Pyrexia 1 2.6 Swelling face 1 2.6 Blood and lymphatic system disorders Neutropenia 32 82.1 Lymphopenia 24 61.5 Leukopenia 22 56.4 Anaemia 20 51.3 Thrombocytopenia 15 38.5 Cytopenia 1 2.6 Leukocytosis 1 2.6 Lymphocytosis 1 2.6 Vascular disorders Hypertension 3 7.7 Hypotension 1 2.6 Metabolism and nutrition disorders Hypokalaemia 2 5.1 Failure to thrive 1 2.6 Infections and infestations Injury, poisoning and procedural complications Appendicitis 1 2.6 COVID - 19 1 2.6 Enterococcal infection 1 2.6 Infection 1 2.6 Orchitis 1 2.6 Sepsis 4,5 1 2.6 Septic shock 4 1 2.6 Humerus fracture 1 2.6 Infusion related reaction 1 2.6 Renal and urinary disorders Acute kidney injury 1 2.6 Proteinuria 1 2.6 Cardiac disorders Atrial fibrillation 3 1 2.6 Respiratory, thoracic and mediastinal disorders Endocrine disorders Hypoxia 2 5.1 Bronchial obstruction 1 2.6 Laryngeal inflammation 1 2.6 Pleural effusion 1 2.6 Respiratory failure 1 2.6 Inappropriate antidiuretic hormone secretion 1 2.6 Eye disorders Ulcerative keratitis 1 2.6 Hepatobiliary disorders Investigations Cholangitis 1 2.6 Immune system disorders Alanine aminotransferase increased 1 2.6 Aspartate aminotransferase increased 1 2.6 Blood alkaline phosphatase increased 1 2.6 Blood creatinine increased 1 2.6 Blood fibrinogen decreased 1 2.6 Contrast media allergy 1 2.6 Musculoskeletal and connective tissue disorders Muscle spasms 1 2.6 Nervous system disorders Gastrointestinal disorders Headache 1 2.6 Abdominal pain 1 2.6 Diarrhoea 1 2.6 Ileus 1 2.6 Vomiting 1 2.6 Reproductive system and breast disorders Vaginal haemorrhage 1 2.6 Skin and subcutaneous tissue disorders Rash maculo - papular 1 2.6 I M A 203
Phase 1a and Phase 1b Cohort A – Best Overall Response 64 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; 1 Indication was updated to cutaneous melanoma post data cut - off; PD: Progressive disease; SD: Stable disease; PR: Partial response; cPR: Confirmed partial response; BL: Baseline Phase 1a (Dose Escalation) Phase 1b (Cohort A) I M A 203 N=27 # N= 1 1 Data cut - off Sept 06, 2022 – presented in Oct 2022 Data cut - off Apr 04, 2023 – presented in May 2023 1
Phase 1a and Phase 1b Cohort A – Responses over Time Improved Durability at Higher Dose and in Phase 1b Patients 65 Phase 1a (Dose Escalation) N=27 # Phase 1b (Cohort A) N=5 Best overall resp o nse (RE C I S T 1.1) I M A 203 # Synovial sarcoma patient (DL3) PD at week 6 not shown as target lesions were not evaluable; 1 Ovarian cancer patient A - DL5 - 04 erroneously received one dose of nivolumab and is part of intent - to - treat population (shown here) but not per - protocol population; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BL: Baseline Ongoing * 1 * Response until 5.7 months post infusion, target lesion response assessment not available (external assessment) Scans at approximately week 6, month 3 and then every 3 months Data cut - off Sept 06, 2022 – presented in Oct 2022 Data cut - off Apr 04, 2023 – presented in May 2023
Focus on Melanoma Patients Phase 1a (DL4 only) and Phase 1b Cohort A Patient Characteristics (n=10) Prior lines of treatment Mean (min, max) 4.5 (1, 7) Previous lines of CPI Mean (Min, Max) 2.6 (1, 4) LDH at baseline >1 x ULN [% of patients] 60.0 Baseline tumor burden Mean target lesion sum of diameter [mm] (min, max) 66.9 (21.0, 178.7) Total infused dose Mean TCR - T cells 1 infused [x10 9 ] (min, max) 2.12 (1.07, 5.12) No. of Target - & Non - Target Lesions 60.0% with >3 lesions 40.0% with liver/brain lesions ORR 2 = 70% (7/10) cORR 3 = 56% (5/9) Median DOR 4 , min, max DOR Not reached, 2.4, 8.8+ months Median Follow - up 5 8.5 months * Maximum change of target lesions and RECIST 1.1 at different timepoints. 1 Transduced viable CD8 T cells; 2 Initial ORR: Objective response rate according to RECIST 1.1 at first scan post infusion at ~week 6; 3 Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with available second scan post infusion at ~3 months or patients with progressive disease (PD) at any timepoint before this scan; 4 Duration of response (DOR) in confirmed responders is defined as time Data cut - off Apr 04, 2023 66 • Heavily pre - treated melanoma patients after 1 - 4 lines of CPI: Cutaneous (N=8), uveal (N=1) and melanoma of unk. primary (N=1) • Phase 1a (N=5): previous manufacturing process • Phase 1b Cohort A (N=5): new monocyte depletion process, higher dose Phase 1a Phase 1b Cohort A Continuous Improvement from Phase 1a to Phase 1b Cohort A Best Overall Response Response over Time Phase 1a Phase 1b Cohort A IMA203 from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut - off. Median DOR is analyzed by using the Kaplan - Meier method; 5 Median Follow - up is analyzed by using the reverse Kaplan - Meier method; PD: Progressive Disease; SD: Stable Disease; PR: Partial Response; cPR: Confirmed Partial Response; BOR: Best Overall Response; BL: Baseline; CPI: Checkpoint inhibitor; LDH: Lactate dehydrogenase
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