COL6A3

ACTengine® IMA203 TCR-T monotherapy against PRAME showed 50% confirmed objective response rate (cORR) at or above target dose in different solid cancers in an interim clinical update in Phase 1a and Phase 1b in October 2022 ACTengine® IMA203 TCR-T clinical data update on all three ongoing IMA203 Phase 1b cohorts (Cohort A: 1st-gen monotherapy, Cohort B: combination with a checkpoint inhibitor, Cohort C: 2nd-gen monotherapy), and identification of most promising cohort to advance towards pivotal trials is planned for 2H 2023; prioritization of patient treatment with 1st and 2nd-generation monotherapy Expansion of cell therapy manufacturing capabilities with construction of an in-house GMP manufacturing facility for registration-directed and commercial production of ACTengine® TCR-T products expected to be operational in 2024 Phase 1 clinical trial for first TCR Bispecific candidate, TCER® IMA401 targeting MAGEA4/8 developed in collaboration with Bristol Myers Squibb commenced in May 2022; TCER® IMA402 targeting PRAME on track for CTA1 submission in 2Q 2023 Strategic collaboration with Bristol Myers Squibb has been expanded in June 2022 to develop allogeneic and autologous cell therapy programs; Immatics received $80 million upfront payment and is eligible for milestone payments as well as tiered royalties $110 million underwritten offering successfully completed in October 2022 Cash and cash equivalents as well as other financial assets amount to $386.3 million2 (€362.2 million) as of December 31, 2022, and projects cash runway into 2025 Tuebingen, Germany and Houston, TX, March21, 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 provided a business update and reported financial results for the quarter and full year ended December 31, 2022. Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics commented, “Our ACTengine® IMA203 clinical trial has gained significant traction over the past year with promising data for our monotherapy candidate targeting PRAME. As we continue demonstrating the potential of our first- and second-generation product candidates in patients, we have commenced establishing our in-house GMP cell therapy manufacturing facility in Houston, TX. This positions us to scale our cell therapies for registration-directed trials and commercial supply. In addition, we have significantly advanced our clinical TCR Bispecifics pipeline with one TCER® program targeting MAGEA4/8 now in the clinic and a second TCER® program targeting PRAME commencing clinical studies this year. We demonstrated our ability to execute and deliver on our goals in 2022 and look forward to continuing on this path in 2023.” Full Year 2022 and Subsequent Company Progress Adoptive Cell Therapy Programs ACTengine® IMA203(PRAME) – Immatics is investigating IMA203 TCR-T in a Phase 1b trial including three ongoing dose expansion cohorts. Immatics’ focus for 2023 is to advance its monotherapy product candidates, 1st-generation IMA203 TCR-T (Cohort A) and 2nd-generation IMA203CD8 TCR-T (Cohort C) in the last-line therapy setting. Data generated throughout 2023 with longer follow-up to assess durability of response is intended to identify the most promising cohort to advance towards pivotal trials and potential commercialization. The clinical data update on all three cohorts is planned for 2H 2023. IMA203TCR-T monotherapy (Cohort A): In October 2022, Immatics provided an interim update on the ongoing IMA203 TCR-T monotherapy trial covering data from 27 patients in the completed Phase 1a dose escalation and the first 5 patients in the Phase 1b dose expansion trial. Treatment with IMA203 continued to show a manageable tolerability pro a heavily pre-treated patient population. A confirmed objective response rate (cORR) of 50% (6/12) was observed at target dose or above across Phase 1a and Phase 1b. Confirmed responses were observed in 4/5 (80%) patients in the Phase 1b trial alone with early signs of prolonged durability at 12 weeks of follow-up with all responses ongoing at data cut-off. Manufacturing enhancements implemented in Phase 1b (including monocyte depletion) resulted in higher infused T cell doses and significantly higher T cell peak expansion and persistence. Confirmed responses were observed across different solid tumor types: cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcoma. IMA203 TCR-T in combination with nivolumab (Cohort B): In May 2022, the first patient was treated with IMA203 in combination with the PD-1 immune checkpoint inhibitor nivolumab at the provisional recommended Phase 2 dose (RP2D). Immatics is currently prioritizing patient treatment with IMA203 and IMA203CD8 TCR-T monotherapy in a last-line therapy setting but is considering further investigation of a combination with nivolumab as a front-line therapy. IMA203CD8 2nd-generation TCR-T monotherapy (Cohort C): IMA203CD8 is Immatics’ 2nd-generation monotherapy product candidate directed against PRAME in which IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor that engages functional CD4 and CD8 T cells. The first patient was treated in August 2022. As IMA203CD8 is a novel product candidate under a new IND amendment, a staggered enrollment was implemented; the treatment of three patients at dose level 3 (DL3) has been completed. Patients are currently being treated at DL4a (up to 0.8x109 TCR-T cells/m2 body surface area). Cell Therapy Manufacturing – Immatics is further enhancing its cell therapy manufacturing process and capabilities. Immatics proprietary manufacturing process is designed to produce T cells within one week, followed by a recently implemented one-week quality control release testing (previously two weeks). This allows Immatics to shorten the turnaround time and to provide the cell therapy product candidate to patients faster. Immatics is building a state-of-the-art 100,000 square foot research and commercial GMP manufacturing facility in the metropolitan area of Houston, Texas. The facility is intended to manufacture Immatics’ ACTengine® IMA203 products as well as other future autologous and allogeneic cell therapy product candidates for early-stage and registration-directed clinical trials as well as for initial commercial supply. The facility is designed for flexibility and can be expanded in a modular fashion. The GMP manufacturing facility is expected to be operational in 2024. ACTengine® IMA201 (MAGEA4/8)– The Phase 1a dose escalation cohort at target dose is ongoing. Immatics plans to discontinue this program after treatment of the remaining patients already enrolled in the clinical trial in order to focus on its TCR Bispecific program TCER® IMA401 addressing the identical target peptide derived from MAGEA4/8 as IMA201. ACTengine® IMA204 (COL6A3 exon 6) – Immatics and the University of Pennsylvania co-authored a research paperpublished in the peer-reviewed journal, Science Translational Medicine highlighting the identification of a novel proprietary HLA-A*02:01-presented target, collagen type VI alpha-3 (COL6A3) using Immatics’ proprietary discovery platforms, XPRESIDENT® and XCEPTOR®. COL6A3 is expressed at high target density across multiple solid cancer indications and specific to the tumor stroma. Targeting tumor stroma provides an innovative therapeutic opportunity to disrupt the tumor microenvironment. The COL6A3-directed TCR-T candidate ACTengine® IMA204, developed by Immatics, was able to eliminate tumor cells at physiological target levels in in vitro studies and in vivo mouse models. The company has delayed the IND submission for IMA204 to consolidate its clinical resources on accelerating the clinical development of its PRAME-directed product candidates. ACTallo®pipeline – In June 2022, Immatics entered into two strategic collaborations with the goal of developing transformative next-generation allogeneic gamma delta TCR-T/CAR-T programs with enhanced persistence, safety and potency, by combining Immatics’ proprietary ACTallo® platform with Bristol Myers Squibb’s next-generation technologies and Editas Medicine’s CRISPR gene editing technology. Immatics entered into anew multi-program collaboration with Bristol Myers Squibb to develop allogeneic TCR-T/CAR-T programs using Immatics’ proprietary ACTallo® platform and Bristol Myers Squibb’s technologies. Immatics received $60 million upfront payment and is eligible for up to $700 million per program in milestone payments as well as tiered royalties. Immatics may also develop its own ACTallo®-based programs outside of the collaboration. The strategic research collaboration and licensing agreement with Editas Medicine, Inc., combines Immatics’ ACTallo® platform with Editas Medicine’s CRISPR gene editing technology. Autologous TCR-T pipeline Immatics and Bristol Myers Squibb expanded their autologous T cell receptor-based therapy (TCR-T) collaboration signed in 2019 by including one additional TCR-T target discovered by Immatics. Immatics received an upfront payment of $20 million and is eligible for milestone payments as well as royalties. In October 2022, GSK provided Immatics with notice of its decision to terminate their collaboration. Initially announced on February 20, 2020, the terms of the agreement included a €45 million (~$50 million) upfront payment to Immatics and the potential for additional milestone and royalty payments in return for access to two of Immatics’ TCR-T programs. As communicated to Immatics, GSK’s decision was made unrelated to the programs and the progress achieved in the collaboration to date. The termination was effective on December 26, 2022. GSK transferred the rights for both TCR-T programs back to Immatics. TCR Bispecifics Programs Immatics’ TCER® candidates are next-generation, half-life extended TCR Bispecific molecules designed to maximize efficacy while minimizing toxicities in patients through its proprietary format using a low-affinity T cell recruiter and a high-affinity TCR domain. TCER® IMA401 (MAGEA4/8) – Immatics initiated a Phase 1 trial in May, to evaluate safety, tolerability and initial anti-tumor activity of its T cell engaging receptor (TCER®) IMA401 for patients with recurrent and/or refractory solid tumors. IMA401 is being developed in collaboration with Bristol Myers Squibb. TCER® IMA402 (PRAME) – A comprehensive preclinical data set was presented at the European Society for Medical Oncology(ESMO) congress in September 2022. The TCER® candidate IMA402 showed potent and selective activity against PRAME-positive tumor cell lines in vitro, high anti-tumor activity in in vivo mouse models, low target-independent T cell engager-associated cytokine release and favorable pharmacodynamic characteristics. The submission of the CTA1 application for the Phase 1/2 trial is on track for 2Q 2023. Immatics plans to start the trial in 2H 2023 with a flexible dose escalation scheme for accelerated clinical development. TCER® IMA403 and TCER® IMA40x – Immatics continues to develop several innovative preclinical TCER® product candidates against so far undisclosed targets for their proprietary and/or partnered pipeline. IMA403 is in advanced preclinical development with proof-of-concept studies ongoing. Additionally, TCER® engineering and preclinical testing is ongoing for further TCER® candidates, IMA40x, targeting peptides presented by HLA-A*02:01 and other HLA-types. Corporate Development Immatics successfully completed an underwritten public offering in October 2022, raising approximately $110 million before deducting underwriting discount and offering expenses. The offering included participation from investors including Armistice Capital Master Fund Ltd., Dellora Investments, EcoR1 Capital, Nantahala Capital, Perceptive Advisors, Rock Springs Capital, RTW Investments, LP, Samsara BioCapital, SilverArc Capital, Sofinnova Investments, Wellington Management, 683 Capital and other specialist biotech investors. Pursuant to Dievini Hopp Biotech Holding’s rights under the business combination in 2020, dievini has designated Mathias Hothum, Ph.D., for election as a director at the 2023 annual general meeting of the shareholders in June 2023, as successor to Friedrich von Bohlen und Halbach, Ph.D. Dr. Hothum has been the Managing Director of dievini Hopp Biotech Holding, which manages the life science activities and investments of Dietmar Hopp and his family. He is also the Managing Director of several investment and consulting companies. Dr. Hothum holds a Ph.D. in Pharmaceutical Economics and Medical Sociology from the University of Magdeburg, Germany. Full Year 2022 Financial Results Cash Position: Cash and cash equivalents as well as other financial assets total €362.2 million ($386.3 million2) as of December 31, 2022 compared to €145.1 million ($154.8 million2) as of December 31, 2021. The increase is mainly due to our public offering and upfront payments for collaborations, partly offset by our ongoing research and development activities. The Company projects a cash runway into 2025. Revenue: Total revenue, consisting of revenue from collaboration agreements, was €172.8 million ($184.3 million2) for the year ended December 31, 2022, compared to €34.8 million ($37.1 million2) for the year ended December 31, 2021. Research and Development Expenses: R&D expenses were €106.8 million ($113.9 million2) for the year ended December 31, 2022, compared to €87.6 million ($93.4 million2) for the year ended December 31, 2021. The increase mainly resulted from higher costs associated with the advancement of the clinical and pre-IND pipeline of ACTengine® and TCER® candidates. General and Administrative Expenses: G&A expenses were €36.1 million ($38.5 million2) for the year ended December 31, 2022, compared to €33.8 million ($36.1 million2) for the year ended December 31, 2021. Net Profit and Loss: Net profit was €37.5 million ($40.0 million2) for the year ended December 31, 2022, compared to a net loss of €93.3 million ($99.5 million2) for the year ended December 31, 2021. The improvement resulted mainly from the one-time license fee income in connection with the IMA401 collaboration with Bristol Myers Squibb, as well as the recognition of remaining deferred revenue in connection with the termination of the GSK collaboration. Full financial statements can be found in the Annual Report on Form 20-F filed with the Securities and Exchange Commission (SEC) and published on the SEC website under . 2 All amounts translated using the exchange rate published by the European Central Bank in effect as of December 31, 2022 (1 EUR = 1,0666 USD). Upcoming Investor Conferences Kempen Life Sciences Conference, Amsterdam – April 25-26, 2023 Bank of America Health Care Conference, Las Vegas (NV) – May 9-11, 2023 Jefferies Global Healthcare Conference, New York (NY) – June 7-9, 2023 To see the full list of events and presentations, visit . 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 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 presentation should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. Immatics undertakes no duty to update these forward-looking statements. For more information, please contact: Media and Investor Relations Contact Jacob Verghese or Eva Mulder Trophic Communications Phone: +49 151 7441 6179 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 N.V. and subsidiaries Condensed Consolidated Statement of Profit/(Loss) of Immatics N.V. Year ended December 31, 2022 2021 2020 (Euros in thousands, except share and per share data) Revenue from collaboration agreements 172,831 34,763 31,253 Research and development expenses (106,779) (87,574) (67,085) General and administrative expenses (36,124) (33,808) (34,186) Other income 26 325 303 Operating result 29,954 (86,294) (69,715) Change in fair value of liabilities for warrants 10,945 (10,990) 17,775 Share listing expense — — (152,787) Other financial income 9,416 5,675 2,949 Other financial expenses (8,279) (1,726) (10,063) Financial result 12,082 (7,041) (142,126) Profit/(loss) before taxes 42,036 (93,335) (211,841) Taxes on income (4,552) — — Net profit/(loss) 37,514 (93,335) (211,841) Attributable to: Equity holders of the parent 37,514 (93,335) (211,284 ) Non-controlling interest — (557) Net profit/(loss) per share: Basic 0.56 (1.48) (4.40) Diluted 0.55 (1.48) (4.40) Immatics N.V. and subsidiaries Condensed Consolidated Statement of Comprehensive Income/(Loss) of Immatics N.V. Year ended December 31, 2022 2021 2020 (Euros in thousands) Net profit/(loss) 37,514 (93,335) (211,841) Other comprehensive income/(loss) Items that may be reclassified subsequently to profit or loss Currency translation differences from foreign operations 2,464 3,514 (6,689 ) Total comprehensive income/(loss) for the year 39,978 (89,821) (218,530) Attributable to: Equity holders of the parent 39,978 (89,821) (217,973 ) Non-controlling interest — — (557) Immatics N.V. and subsidiaries Condensed Consolidated Statement of Financial Position of Immatics N.V. As of December 31, 2022 December 31, 2021 (Euros in thousands) Assets Current assets Cash and cash equivalents 148,519 132,994 Other financial assets 213,686 12,123 Accounts receivables 1,111 682 Other current assets 13,838 6,408 Total current assets 377,154 152,207 Non-current assets Property, plant and equipment 13,456 10,506 Intangible assets 1,632 1,315 Right-of-use assets 13,033 9,982 Other non-current assets 2,545 636 Total non-current assets 30,666 22,439 Total assets 407,820 174,646 Liabilities and shareholders’ equity Current liabilities Accounts payables 13,056 11,624 Deferred revenue 64,957 50,402 Liabilities for warrants 16,914 27,859 Lease liabilities 2,159 2,711 Other current liabilities 9,366 2,552 Total current liabilities 106,242 95,148 Non-current liabilities Deferred revenue 75,759 48,225 Lease liabilities 12,403 7,142 Other non-current liabilities 42 68 Total non-current liabilities 88,204 55,435 Shareholders’ equity Share capital 767 629 Share premium 714,177 565,192 Accumulated deficit (500,299) (537,813) Other reserves (1,481) (3,945) Total shareholders’ equity 213,164 24,063 Total liabilities and shareholders’ equity 407,820 174,646 Immatics N.V. and subsidiaries Condensed Consolidated Statement of Cash Flows of Immatics N.V. Year ended December 31, 2022 2021 2020 (Euros in thousands) Cash flows from operating activities Net profit/(loss) 37,514 (93,335) (211,841) Taxes on income 4,522 — — Profit/(loss) before tax 42,340 (93,335) (211,841) Adjustments for: Interest income (2,476) (133) (850) Depreciation and amortization 6,967 5,260 4,424 Interest expenses 1,038 566 289 Share listing expense — — 152,787 Equity settled share-based payment 22,570 26,403 22,908 MD Anderson compensation expense — — 45 (Decrease) Increase in other liabilities resulting from share appreciation rights — — (2,036) Payment related to share-based compensation awards previously classified as equity-settled — — (4,322) Net foreign exchange differences and expected credit losses 2,953 (2,408) 437 Change in fair value of liabilities for warrants (10,945) 10,990 (17,775) Changes in: (Increase)/decrease in accounts receivables (429) 569 (294) (Increase) in other assets (7,872) (483) (1,600) Increase/(decrease) in deferred revenue, accounts payables and other liabilities 45,559 (31,784) (23,387) Interest received 1,649 175 808 Interest paid (695) (566) (289) Income tax paid (224) — — Net cash provided by/(used in) operating activities 100,131 (84,746) (80,696) Cash flows from investing activities Payments for property, plant and equipment (5,738) (5,106) (7,420) Payments for investments classified in Other financial assets (216,323) (11,298) (58,087) Proceeds from maturity of investments classified in Other financial assets 12,695 24,448 49,662 Payments for intangible assets (477) (551) (104) Proceeds from disposal of property, plant and equipment 52 — — Net cash (used in)/provided by investing activities (209,791) 7,493 (15,949) Cash flows from financing activities Proceeds from issuance of shares to equity holders 134,484 94 217,918 Transaction costs deducted from equity (7,931) — (7,939) Repayment of lease liabilities (2,843) (2,707) (2,096) Net cash provided by/(used in) financing activities 123,710 (2,613) 207,883 Net increase/(decrease) in cash and cash equivalents 14,050 (79,866) 111,238 Cash and cash equivalents at beginning of the year 132,994 207,530 103,353 Effects of exchange rate changes on cash and cash equivalents and expected credit losses 1,475 5,330 (7,061) Cash and cash equivalents at end of the year 148,519 132,994 207,530 Immatics N.V. and subsidiaries Condensed Consolidated Statement of Changes in Shareholders’ equity (deficit) of Immatics N.V. (Euros in thousands) Share capital Share premium Accumulated deficit Other reserves Total equity (deficit) attributable to shareholders of the parent Non- controlling interest Total share- holders’ equity (deficit) Balance as of January 1, 2020 1,164 190,945 (233,194) (770) (41,855) 1,020 (40,835) Other comprehensive loss — — — (6,689) (6,689) — (6,689) Net loss — — (211,284) — (211,284) (557) (211,841) Comprehensive loss for the year — — (211,284) (6,689) (217,973) (557) (218,530) Reorganization (833) 833 — — — — — Issue of share capital MD Anderson Share Exchange 7 501 — — 508 (508) — PIPE Financing, net of transaction costs 104 89,973 — — 90,077 — 90,077 ARYA Merger, net of transaction costs 180 237,864 — — 238,044 — 238,044 SAR conversion 7 (7) — — — — — Total issuance of share capital 298 328,331 — — 328,629 (508) 328,121 Equity-settled share-based compensation — 22,908 — — 22,908 — 22,908 Payments related to share-based compensation awards previously classified as equity-settled — (4,322) — — (4,322) — (4,322) MD Anderson milestone compensation expense — — — — — 45 45 Balance as of December 31, 2020 629 538,695 (444,478) (7,459) 87,387 — 87,387 Balance as of January 1, 2021 629 538,695 (444,478) (7,459) 87,387 — 87,387 Other comprehensive income — — — 3,514 3,514 — 3,514 Net loss — — (93,335) — (93,335) — (93,335) Comprehensive loss for the year — — (93,335) 3,514 (89,821) — (89,821) Equity-settled share-based compensation — 26,403 — — 26,403 — 26,403 Share options exercised — 94 — — 94 — 94 Balance as of December 31, 2021 629 565,192 (537,813) (3,945) 24,063 — 24,063 Balance as of January 1, 2022 629 565,192 (537,813) (3,945) 24,063 — 24,063 Other comprehensive income — — — 2,464 2,464 — 2,464 Net profit — — 37,514 — 37,514 — 37,514 Comprehensive income for the year — — 37,514 2,464 39,978 — 39,978 Equity-settled share-based compensation — 22,570 — — 22,570 — 22,570 Share options exercised — 311 — — 311 — 311 Issue of share capital – net of transaction costs 138 126,104 — — 126,242 — 126,242 Balance as of December 31, 2022 767 714,177 (500,299) (1,481) 213,164 — 213,164 1 Clinical Trial Application (CTA) is the European equivalent of an Investigational New Drug (IND) application 2 All amounts translated using the exchange rate published by the European Central Bank in effect as of December 31, 2022 (1 EUR = 1,0666 USD). 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▎药明康德内容团队编辑本期看点[1] 涵盖115个来自不同疾病领域，具转化潜力的潜在创新靶点[2] 详细介绍15个癌症、代谢疾病、中枢神经疾病等相关靶点[3] 提供完整115个靶点列表下载地址，扫描下图二维码或点击文末“阅读原文/Read more”即可访问《自然》子刊Nature Reviews Drug Discovery曾指出，每个“first-in-class”药物的上市多有赖于创新药物靶点的发现，靶点的重要性不言可喻！在2022年，全球科研人员们在创新靶点的探索和开发上做出了诸多突破：这些靶点有的是创新癌症免疫疗法诞生的契机，有的有望提升T细胞疗法的活性，有的则有可能变革阿尔茨海默病、帕金森病、非酒精性脂肪性肝炎（NASH）等重大疾病的治疗格局……图片来源：药明康德内容团队制图药明康德内容团队盘点了在2022发布于国际知名科研期刊当中的潜力靶点，以供各位医药界的朋友们作为参考。在这篇文章中，我们优选15个值得关注的靶点做详细报道。扫描下图二维码或点击文末“阅读原文/Read more”，即可下载完整115个靶点列表。▲长按扫描二维码或点击文末“阅读原文/Read more”，即可下载完整115个靶点列表。靶点统计的详细方法请参见文末。癌症免疫疗法潜在靶点靶点：ZBP1应用：增加肿瘤免疫原性期刊 / PMID：《自然》 / 35614224发现：在癌症免疫治疗中，仅有一小部分病患会对免疫检查点抑制剂（ICB）单药疗法产生长期缓解。近期RNA编辑酶ADAR1被发现与免疫检查点抑制剂疗法抗性相关。ADAR1可通过抑制具免疫原性双链RNA（dsRNA）的产生，进而避免肿瘤对免疫检查点抑制剂产生应答。在此篇论文中，科学家发现ADAR1的突变或删除会造成Z型dsRNA（Z-RNA）的累积，进而活化Z-RNA感应蛋白ZBP1，并最终导致细胞发生RIPK3介导的坏死性凋亡（necroptosis）。由于临床上目前仍不存在ADAR1抑制剂，科学家找到了一种不受ADAR1影响而直接活化ZBP1的化合物CBL0137。通过引发细胞内生成Z-RNA，CBL0137可而有效地活化ZBP1。CBL0137可在肿瘤相关成纤维细胞（CAF）内引发ZBP1依赖性坏死性凋亡，并在黑色素瘤小鼠模型中逆转肿瘤对免疫检查点抑制剂的抗性。这些结果显示即便癌症对免疫检查点抑制剂已有耐药性，通过靶向活化ZBP1依旧可引发癌细胞的坏死性凋亡，恢复对免疫疗法的应答。靶点：COL6A3应用：不限癌种T细胞疗法靶点期刊 / PMID：Science Translational Medicine / 36044599发现：T细胞受体疗法靶向细胞内外抗原，但此抗原肽片段须在肿瘤细胞上，通过与特定人类白细胞抗原（HLA）分子结合，成为peptide-HLA（pHLA）复合体呈现，才能为T细胞所识别。因此识别在肿瘤中高度表达但在健康组织内罕见、具高度TCR亲和力的pHLA复合体为TCR疗法成功的关键之一。研究人员对约1500个肿瘤与健康组织样本（包含11种不同实体瘤）进行测试，并通过量化质谱法来分析、比较组织内pHLA复合体。在使用人工智能量化分析每个细胞中含有各种pHLA复合体拷贝数后，研究人员发现一种由HLA-A*02:01所呈现的肿瘤特异性肽片段。此片段来自编码6型胶原蛋白的COL6A3基因，其第六外显子（exon 6）因选择性剪接而产生。这种选择性剪接出现在多种实体瘤基质中，但在健康组织内却十分罕见。而根据此所识别出的pHLA复合体所设计出的TCR疗法，在带有人类肿瘤细胞的小鼠当中展现良好疗效。实验结果显示，接受此项TCR疗法小鼠的肿瘤不但生长速度减缓，且有肿瘤缩小的情形。重要的是，此疗法的耐受性良好，研究人员并未观察到此疗法对正常细胞的任何毒性。因此COL6A3选择性剪接具潜力被开发成为治疗不同种类实体瘤的T细胞疗法。靶点：MC5R应用：降低肿瘤免疫抑制期刊 / PMID：《科学》/ 35926007发现：下丘脑-垂体（hypothalamic–pituitary）能够分泌多种激素调控免疫反应，而其中有部分激素或效应分子在癌症病患中有增加的情形。研究人员发现，下丘脑-垂体能够促进髓系造血（myelopoiesis）与免疫抑制作用，进而促进肿瘤的生长。皮下肿瘤的植入会引发小鼠下丘脑活化，以及促进垂体分泌α-黑素细胞刺激素（α-MSH）。α-MSH通过作用于髓系祖细胞上的黑素皮质素受体5（MC5R）而促进髓系造血、髓系细胞累积、免疫抑制与肿瘤生长等作用。靶向MC5R的拮抗肽能够提升抗肿瘤免疫反应，以及靶向PD-1免疫疗法的疗效。值得一提的是，研究人员亦发现癌症患者血清中的α-MSH水平上升，并且与患者体内循环的髓系抑制细胞量呈正相关。这些发现显示神经内分泌通路可能参与抑制肿瘤免疫反应，以及MC5R为癌症免疫疗法的潜力靶点。图片来源：药明康德内容团队制图提升T细胞疗法抗肿瘤能力靶点：PARP11应用：增强CAR-T细胞疗法抗实体瘤效力期刊 / PMID：Nature Cancer / 35637402发现：免疫抑制性的肿瘤微环境（TME）帮助实体瘤逃避抗肿瘤免疫反应并对免疫疗法产生抗性。科学家们发现包含调节性T细胞与腺苷在内的TME因子，会下调在CD8+细胞毒性T淋巴细胞（CTL）上1型干扰素受体IFNAR1的表达，而此过程与肿瘤中CTL内所诱发表达的多腺苷二磷酸核糖聚合酶11（PARP11）有关。PARP11是产生免疫抑制性TME的调节物之一。基因敲除PARP11则可避免CTL上IFNAR1的丧失，进而增加CTL的肿瘤毒杀活性并引起IFNAR1依赖性的肿瘤生长抑制。因此通过遗传学工具调控或药物来抑制PARP11，有潜力增加嵌合抗原受体（CAR）-T细胞疗法的疗效。而通过工程化造成PARP11失活的CAR-CTL则可能增加其抗实体瘤的效力。这些发现显示PARP11在具免疫抑制性的TME中所扮演的关键角色，并概念性验证靶向此信号通路以提升免疫疗法效力的可能。靶点：cBAF应用：增强T细胞疗法抗实体瘤效力期刊 / PMID：《自然》/ 35732731发现：识别能够提升记忆T（Tmem）细胞生成的机制，对于癌症疫苗的发展与抗肿瘤免疫疗法的开发是至关重要的。研究人员通过CRISPR基因编辑技术筛选体内Tmem细胞的负调节因子时发现，许多哺乳类动物典型的BRG1/BRM相关因子（cBAF）组成扮演关键角色。这些cBAF复合体的组成对于活化的CD8+ T细胞分化成效应T（Teff）细胞是必须的，而这些Teff细胞的丧失则促使Tmem细胞在体内形成。有趣的是，研究人员发现，活化的CD8+ T细胞在进行分裂时，当子细胞同时具有高度MYC与cBAF表达时，细胞较有可能分化成Teff细胞；反之，当子细胞的MYC与cBAF表达量皆低时则细胞倾向分化成Tmem细胞。关键的是，当研究人员在初始CD8+ T细胞活化的48小时内以可能的cBAF抑制剂对小鼠进行治疗时，可以促进Tmem细胞生成，并改善T细胞输入疗法治疗小鼠结直肠癌与黑色素瘤的效果。此研究显示在T细胞分化早期调控cBAF，有潜力改善实体瘤癌症免疫疗法的效果。靶点：RASA2应用：增加T细胞疗法持续性期刊 / PMID：《自然》/ 36002574发现：由于外在抑制因子与内部抑制检查点的作用，过继性T细胞疗法在癌症治疗上的效用受到局限，而靶标基因编辑可能是克服这些限制、加强T细胞疗法的关键。通过在不同免疫抑制情形下进行CRISPR基因敲除的筛选过程，研究人员识别出能够避免T细胞功能障碍的基因。不同的筛选过程皆发现RasGTP酶激活蛋白（RasGAP）RASA2是人类T细胞内的信息检查点，其表达量会在T细胞受体经急性刺激后下降，也会随着T细胞在慢性抗原暴露下逐渐升高。基因敲除RASA2会增强MAPK信号以及CAR-T细胞面对靶标抗原时的细胞溶解能力。体外实验显示，缺乏RASA2的T细胞在经过反复肿瘤抗原刺激后，与野生组细胞相比，其活化程度、细胞因子生产量与代谢活性皆较高，并展现持续的癌细胞毒杀能力。此外，RASA2基因敲除CAR-T细胞在血癌小鼠模型的骨髓中，也较具适应优势。重要的是，在许多临床前T细胞受体（TCR）疗法与CAR-T疗法中，去除RASA2能够延长异种移植的血液与实体瘤小鼠的生存期。因此RASA2可能是增加现有T细胞疗法持续性与功能性的关键靶点。其他癌症治疗潜在靶点靶点：PKMYT1疾病：CCNE1扩增肿瘤期刊 / PMID：《自然》/ 35444283发现：细胞周期蛋白E1（CCNE1）基因的扩增常见于许多类型的肿瘤，尤其是在高分化浆液性卵巢癌、子宫癌与胃食管癌，在这些癌症中细胞周期蛋白E1的高度表达与基因组不稳定性、对靶向药物具抗性相关。科学家为找出CCNE1扩增肿瘤的治疗靶标，以基于CRISPR-Cas9的技术进行基因组的合成致死配对筛选。科学家们发现，当细胞CCNE1的表达量增加，其对PKMYT1激酶的抑制变得更为敏感。PKMYT1为周期蛋白依赖性激酶1（CDK1）的负调节物。当与吉西他滨（gemcitabine）组合使用时，针对PKMYT1所开发的口服、选择性抑制剂RP-6306可以造成CCNE1扩增肿瘤缩小。因此靶向PKMYT1为CCNE1扩增肿瘤的潜在靶点。靶点：ENDOD1疾病：同源重组缺陷&TP53突变肿瘤期刊 / PMID：Nature Communications / 35606358发现：研究人员发现非典型核酸酶ENDOD1在DNA修复机制中未曾被发现的功能。当细胞内ENDOD1基因被敲除时，ENDOD1功能的丧失会使具同源重组缺陷的细胞累积大量DNA双链断裂，引起合成致死效应。有趣的是，研究人员亦同时发现在TP53突变的肿瘤细胞中敲低ENDOD1，或在ENDOD1敲除细胞中进一步敲低p53时，皆会造成细胞内单链DNA快速累积而引起细胞死亡，因此ENDOD1与p53之间亦存在合成致死关系。而这也在动物实验中获得证实，小鼠对系统性EndoD1基因敲低具良好耐受性，然而对异种移植小鼠施以全身性靶向ENDOD1的siRNA时却会抑制其身上带有TP53突变的人类肿瘤进展。这些数据显示ENDOD1有潜力作为具癌症专一性的合成致死药物靶点。靶点：LCOR疾病：三阴性乳腺癌（TNBC）期刊 / PMID：Nature Cancer / 35301507发现：配体依赖辅阻遏物（LCOR）蛋白介导了正常与肿瘤乳腺癌干细胞的分化。虽然肿瘤干细胞（CSC）造成肿瘤异质性（heterogeneity）以及肿瘤治疗抗性，但其在免疫疗法当中所扮演的角色却鲜为人知。研究人员发现以免疫检查点抑制剂治疗TNBC会筛选出具低LCOR表达量的CSC，这些CSC的抗原呈递机制（APM）蛋白表达下降，因此会使得肿瘤对免疫攻击与免疫检查点抑制剂疗法不产生应答。科学家们发现LCOR是APM基因的转录激活蛋白，能以独立于干扰素（IFN）信息的方式与IFN刺激反应元素基序（ISRE）结合。LCOR的表达可增强肿瘤的免疫原性与对免疫检查点抑制剂的应答性。重要的是，LCOR的表达亦与TNBC患者对免疫检查点抑制剂的临床应答相关。当通过外泌体（EV）递送LCOR的mRNA并同时施以PD-L1抗体治疗时，可克服小鼠TNBC细胞对免疫检查点抑制剂的抗性并消除乳腺癌细胞的转移。这些结果显示LCOR可通过提升肿瘤APM表达，加强免疫检查点抑制剂对TNBC的疗效，是一款有力的潜在靶点。代谢相关疾病潜在靶点靶点：ASGR1疾病：高胆固醇期刊 / PMID：《自然》/ 35922515发现：高胆固醇是造成心血管疾病的重大风险之一。直至目前为止，尚无通过促进胆固醇排泄以降低胆固醇水平的药物上市。过去遗传学研究曾发现去唾液酸糖蛋白受体1（ASGR1）变异所导致的功能失去突变与低胆固醇水平和心血管疾病风险降低有关。ASGR1仅表达于肝脏内，其可介导血液中去唾液酸糖蛋白内化与在溶酶体中的降解。在此篇论文中，科学家们发现小鼠内Asgr1的缺失会稳定肝X受体α（LXRα），进而造成血清与肝脏内脂肪水平的下降——这可能是因为LXRα上调转运蛋白ABCA1与ABCG5/G8，进而促进胆固醇运输至高密度脂蛋白并分别排泄至胆汁与粪便中。重要的是，当施以小鼠靶向ASGR1中和抗体时能够促进胆固醇排泄并降低脂质水平，且与atorvastatin和ezetimibe这两个广为使用的降胆固醇药物产生协同作用。因此ASGR1为促进胆固醇排泄与降低脂质水平的潜在靶点。靶点：CD47-SIRPα疾病：NASH期刊 / PMID：Science Translational Medicine / 36417485发现：坏死性凋亡是造成肝细胞在NASH疾病死亡的机制之一，然而科学家们对于这些坏死性凋亡肝细胞（necHCs）在NASH中所扮演的角色却不清楚。研究人员发现，在患有NASH的人类与小鼠肝脏中necHCs的累积，与在necHCs表面所表达的“别吃我”CD47配体相关。此外，在肝脏巨噬细胞表面亦发现CD47受体SIRPα的表达量增加，这与所观察到巨噬细胞介导的necHCs清除受损现象一致。重要的是，当科学家以靶向CD47、SIRPα抗体治疗，或以腺相关病毒递送shCD47以沉默CD47在肝细胞的表达时，在两个由饮食引起的NASH小鼠模型上皆发现肝脏巨噬细胞增加对necHCs的清除，以及肝纤维化与肝脏星状细胞（HSC）活化的生物标志物降低。HSC活化是导致肝脏纤维化的原因之一。此外，以SIRPα抗体治疗亦可避免小鼠因CD47抗体治疗而产生的贫血副作用。这些发现显示阻断CD47-SIRPα信息通路可避免necHCs在肝脏的累积以及肝纤维化进展，是治疗NASH的潜在靶点。靶点：FLCN疾病：非酒精性脂肪性肝病（NAFLD）、NASH期刊 / PMID：《科学》/ 35420934发现：NAFLD和NASH目前为止都尚未存在有效的治疗方法，虽然mTORC1通路为潜在的靶向疗法，但对于mTORC1如何控制脂质代谢却存在着争议性的解读。研究人员发现，当通过删除RagC/D鸟苷三磷酸酶激活蛋白FLCN（即卵泡素，folliculin）来选择性地抑制小鼠内的mTORC1通路时，可以在不影响其他mTORC1靶标蛋白的情况下，促进肝脏转录因子E3（TFE3）的活化。TFE3可通过诱发脂质消耗与抑制脂肪生成，保护肝脏免于NAFLD与NASH的疾病进展。这些结果对以往看似相冲突的研究做出了解释，并识别如FLCN等mTORC1通路蛋白为潜在的NAFLD与NASH治疗靶点。图片来源：药明康德内容团队制图神经系统相关疾病潜在靶点靶点：USP11疾病：阿尔茨海默病期刊 / PMID：《细胞》/ 36198316发现：与男性相较，女性具有显著较高的tau蛋白含量，也易罹患阿尔茨海默病，但造成此现象的机制尚仍不清楚。科学家在此篇论文中揭示，X连锁泛素特异性肽酶11（USP11）能够对tau蛋白进行去泛素化，进而使tau蛋白的相关位点发生乙酰化，造成tau蛋白聚集扩大的病理现象。乙酰化的tau蛋白是阿尔茨海默病患脑部内的病理特征之一。研究人员并证实，通过遗传学删除具有tau病变小鼠模型内的usp11表达时，可以选择性地保护母鼠，减少乙酰化tau蛋白的累积、tau相关病变以及认知损害。因此抑制由USP11介导的tau蛋白去泛素化可能降低女性罹患阿尔茨海默病与tau蛋白病变的风险。靶点：GPNMB疾病：帕金森病期刊 / PMID：《科学》/ 35981040发现：通过全基因组关联分析（GWAS）相关研究，许多与帕金森病相关的基因位点已被识别，然而治疗帕金森病的靶点基因与机制仍多属未知。研究人员通过GWAS数据，以及对帕金森病风险讯号与位点特征表达定量（expression quantitative trait locus）的共定位分析发现，帕金森病相关的染色体7位点（包含rs199347）与非转移性黑色素瘤糖蛋白b（GPNMB）基因相关联。研究人员发现，在细胞内，GPNMB蛋白与α突触核蛋白（α-synuclein，aSyn）存在共定位与免疫共沉淀关系。在源自诱导多能干细胞的神经元模型中，GPNMB的丧失使得细胞无法内化aSyn原纤维，进而避免产生aSyn相关的病理现象。值得一提的是，在对731位帕金森病患者与59位对照组样本的分析后发现，帕金森患者血浆中GPNMB表达量升高，且其表达量与患者疾病严重程度相关。因此GPNMB为帕金森病的风险基因，且为开发生物标志物与疾病治疗的潜在靶点。靶点：CLEC7A疾病：阿尔茨海默病期刊 / PMID：《细胞》/ 36306735发现：遗传学研究显示小胶质细胞在阿尔茨海默病中扮演关键角色，其中小胶质细胞内TREM2-SYK信号异常与疾病发展相关。TREM2 R47H蛋白的变异与罹患阿尔茨海默病的高风险相关，这些变异的蛋白无法通过SYK激酶来活化小胶质细胞。研究人员发现，缺失SYK的小胶质细胞由于无法对Aβ斑块进行包覆，会加速小鼠大脑病变与行为障碍。CLEC7A受体可直接活化SYK激酶。当系统性递送靶向CLEC7A抗体至小鼠体内时，可活化TREM2 R47H蛋白变异小鼠内的SYK激酶，进而促进小胶质细胞活化，因此CLEC7A有可能成为阿尔茨海默病免疫疗法的新治疗选择。期待这些创新靶点的发现能够促进更多创新疗法的开发，带进临床治疗的突破，造福更多受不同疾病所苦的患者。为了方便读者朋友们了解更多信息，扫描下图二维码或点击文末“阅读原文/Read more”，即可下载完整115个靶点列表。▲长按扫描二维码或点击文末“阅读原文/Read more”，即可下载完整115个靶点列表。靶点统计的详细方法请参见文末。▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放*药明康德统计于2022年1月至11月底，发布于《自然》、《科学》、《细胞》、Cancer Cell、Nature Cancer、Nature Communications、Science Translational Medicine、Science Advances等众知名期刊，具有哺乳动物实验支持，具研究新颖性，且尚未进入临床2期（或以上）试验的创新靶点。若不符合筛选标准的潜在靶点则未纳入统计之中。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Interim clinical update on ACTengine® IMA203 TCR-T monotherapy targeting PRAME demonstrated high confirmed objective response rate (cORR) of 50% (6/12) at or above target dose across Phase 1a and Phase 1b; confirmed responses seen across different solid tumor types: cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcomaFirst patient treated with IMA203CD8, a 2nd generation ACTengine® TCR-T monotherapy product candidate targeting PRAME in Phase 1b expansion cohort C; patient treatment ongoing in all three Phase 1b expansion cohortsNext-generation TCR Bispecific, TCER® IMA402 targeting PRAME showed high anti-tumor activity in vivo, low T cell engager-associated toxicities and favorable pharmacodynamic characteristics in preclinical studies; Phase 1/2 clinical trial on track to start in 2023Joint publication with University of Pennsylvania in Science Translational Medicine on Immatics’ novel proprietary target COL6A3 exon 6$110 million underwritten offering of 10,905,000 ordinary shares successfully completed on Oct 12, 2022Cash and cash equivalents as well as other financial assets of $301.5 million1 (€309.3 million) as of September 30, 2022. Additional cash from the recent public offering in October 2022 funds company operations into 2025 Tuebingen, Germany and Houston, Texas, November 17, 2022 – Immatics N.V. (NASDAQ: IMTX, “Immatics”), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today provided a business update and reported financial results for the quarter ended September 30, 2022. “The initial results from our Phase 1a and Phase 1b cohort A showed a highly encouraging confirmed objective response rate of 50% for patients treated at or above target dose. Early data from cohort A alone have shown a confirmed objective response rate of 80%. With these encouraging results, we have built momentum for our multi-cohort strategy designed to leverage the full clinical potential of targeting PRAME,” commented Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. “We look forward to sharing the next data readouts from all three Phase 1b expansion cohorts in 2023, as well as initiating the Phase 1/2 clinical trial of our TCR Bispecific candidate, TCER® IMA402, targeting PRAME. With the recent addition of new capital, we have the resources to deliver on our corporate objectives for 2023 and to fund operations into 2025.” Third Quarter 2022 and Subsequent Company Progress Adoptive Cell Therapy Programs ACTengine® IMA203 (PRAME) – In October, Immatics provided an interim update from the ongoing IMA203 TCR-T monotherapy. The update covered data from 27 patients in the completed Phase 1a dose escalation and first 5 patients in the Phase 1b dose expansion (cohort A) treated with IMA203 monotherapy. Treatment with IMA203 continues to show manageable tolerability.Confirmed objective response rate (cORR): 50% (6/12) at target dose or above with at least 1 billion infused TCR-T cells across Phase 1a and 1b; thereof 80% cORR (4/5) in Phase 1b patients alone with all responses ongoing at data cut-off.Confirmed responses observed across different solid tumor types: cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcoma.Immatics has introduced improvements that may influence clinical outcomes, including higher cell doses, optimizing the cell product through manufacturing enhancements and working with disease area experts to gradually reduce the patient fraction that are very heavily pre-treated with extreme tumor burden. Immatics continues to implement such improvements to the IMA203 trial. ACTengine® IMA203 is currently being evaluated in three ongoing Phase 1b dose expansion cohorts: Cohort A - IMA203 monotherapy interim analysis demonstrated cORR in 4 of 5 patients (80%) with early signs of prolonged durability at 12 weeks of follow-up. All responses were ongoing at data cut-off. Patients are treated at provisional recommended phase 2 dose (RP2D) and dose level (DL) 5.Cohort B – The first patient in the Phase 1b expansion cohort B was treated with IMA203 in combination with the PD-1 immune checkpoint inhibitor nivolumab in May 2022. Patients will be treated at RP2D.Cohort C – The first patient was treated in August 2022 with IMA203CD8, Immatics’ 2nd -generation monotherapy product candidate in which IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor that engages functional CD4 and CD8 T cells directed against PRAME. As IMA203CD8 is a novel product candidate under a new IND2 amendment, a staggered enrollment is being implemented with the first three patients being treated at DL3. Following the initial DL3, patients will be treated at DL4 and DL5. Further data read-outs on all three individual cohorts are planned throughout 2023. 2) IND = Investigational New Drug ACTengine® IMA204 (COL6A3 exon 6) – Immatics and the University of Pennsylvania co-authored a research paper published in the peer-reviewed journal, Science Translational Medicine, that highlighted Immatics’ differentiated approach to develop TCR-based therapies through its proprietary discovery platforms, XPRESIDENT® and XCEPTOR®. With this approach, Immatics identified a novel proprietary HLA-A*02:01-presented target generated by a tumor-specific alternative splicing event in the abundantly expressed protein collagen type VI alpha-3 (COL6A3). This target is expressed at high target density across multiple solid cancer indications and specific to the tumor stroma. Targeting tumor stroma provides an innovative therapeutic opportunity to disrupt the tumor microenvironment. Immatics has engineered target-specific, affinity-enhanced proprietary TCRs, one of them being CD8-independent and thus facilitating targeting of COL6A3 exon 6 positive cells by both CD4 and CD8 T cells. The TCR-T candidate, IMA204 was able to eliminate tumor cells at physiological target levels in in vitro studies and in vivo mouse models. Due to Immatics focusing its clinical resources on the three IMA203 Phase 1b cohorts as well as accelerating the clinical development for the PRAME TCER® IMA402, the company has delayed the IND submission for an ACTengine® candidate directed against COL6A3 exon 6. TCR Bispecifics Programs TCER® IMA401 (MAGEA4/8) – IMA401 is being developed in collaboration with Bristol Myers Squibb; 9 centers in Germany have been activated and are enrolling patients. TCER® IMA402 (PRAME) – In preclinical data presented at the European Society for Medical Oncology (ESMO) Congress in September 2022, TCER® IMA402 showed potent and selective activity against PRAME-positive tumor cell lines in vitro. In vivo studies in mice demonstrated dose-dependent anti-tumor activity confirming that sufficiently high drug doses are key to achieving the desired anti-tumor effects over a prolonged time period. Pharmacokinetic characteristics of the half-life extended IMA402 suggest the potential for a favorable dosing regimen in patients with prolonged drug exposure at therapeutic levels. Immatics has completed the manufacturing process development for IMA402, and manufacturing of the clinical batch is on track for 2H 2022 with a planned start of the Phase 1/2 trial in 2023. The submission of the CTA/IND3 application is planned for 2Q 2023. 3) Clinical Trial Application (CTA) is the equivalent of an Investigational New Drug (IND) application in Europe TCER® Platform – In November, Immatics presented preclinical data of its next-generation, half-life extended TCR Bispecific format which showed higher potency in vitro than multiple other established formats, at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The proprietary TCER® format consists of three distinct elements designed for optimal efficacy and minimal toxicity risk in patients: 1) high affinity TCR domains targeting tumor-specific peptide HLA molecules 2) low affinity T cell recruiter against CD3/TCR, and 3) a human IgG Fc region (silenced) for half-life extension, favorable stability and manufacturability. The poster can be accessed on Immatics’ website here.PRAME Target (IMA203, IMA402) – In November, Immatics presented comprehensive target characterization and validation data at the SITC Annual Meeting. The data support PRAME as a highly relevant target for Immatics’ TCR-based therapies, ACTengine® IMA203 and TCER® IMA402. These therapies have the potential to address a wide variety of cancer indications such as cutaneous melanoma, ovarian cancer, uterine cancer, non-small cell lung cancer, triple-negative breast cancer, head and neck cancer and uveal melanoma, among others. The poster can be accessed on Immatics’ website here. Corporate Developments In October 2022, Immatics successfully completed the underwritten public offering of 10,905,000 ordinary shares at a price of $10.09 per ordinary share, raising approximately $110 million before deducting underwriting discount and offering expenses. The offering included participation from investors including Armistice Capital Master Fund Ltd., Dellora Investments, EcoR1 Capital, Nantahala Capital, Perceptive Advisors, Rock Springs Capital, RTW Investments, LP, Samsara BioCapital, SilverArc Capital, Sofinnova Investments, Wellington Management, 683 Capital and other specialist biotech investors. On October 24, 2022, GSK provided Immatics with notice of its decision to terminate their collaboration. Initially announced on February 20, 2020, the terms of the agreement included a €45 Million (~$50 Million) upfront payment to Immatics and the potential for additional milestone and royalty payments in return for access to two of Immatics’ TCR-T programs. As communicated to Immatics, GSK’s decision was made unrelated to the programs and the progress achieved in the collaboration to date. The termination will be effective on December 26, 2022. Third Quarter 2022 Financial Results Cash Position: Cash and cash equivalents as well as other financial assets total €309.3 million ($301.5 million1) as of September 30, 2022 compared to €324.4 million ($316.2 million1) as of June 30, 2022. The decrease is mainly due to our ongoing research and development activities. This does not include $110 million gross proceeds from our public offering in October 2022. Adding those proceeds, the Company projects a cash runway into 2025.Revenue: Total revenue, consisting of revenue from collaboration agreements, was €15.1 million ($14.7 million1) for the three months ended September 30, 2022, compared to €6.4 million ($6.2 million1) for the three months ended September 30, 2021. The increase is mainly related to the increased recognition of revenue for the multiple ongoing collaboration agreements.Research and Development Expenses: R&D expenses were €28.6 million ($27.9 million1) for the three months ended September 30, 2022, compared to €21.2 million ($20.7 million1) for the three months ended September 30, 2021. The increase is mainly related to increased expenses for clinical trials.General and Administrative Expenses: G&A expenses were €8.4 million ($8.2 million1) for the three months ended September 30, 2022, compared to €8.3 million ($8.1 million1) for the three months ended September 30, 2021. Net Income/Loss: Net loss was €20.9 million ($20.4 million1) for the three months ended September 30, 2022, compared to a net loss of €27.2 million ($26.5 million1) for the three months ended September 30, 2021. The decrease was primarily the result of the increased revenue from multiple collaboration agreements. Full financial statements can be found in the current report on Form 6-K filed with the Securities and Exchange Commission (SEC) and published on the SEC website under www.sec.gov. 1 All amounts translated using the exchange rate published by the European Central Bank in effect as of September 30, 2022 (1 EUR = 0.9748 USD). To see the full list of events and presentations, visit https://investors.immatics.com/events-presentations – END – About ImmaticsImmatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer. For regular updates about Immatics, visit www.immatics.com. You can also follow us on Instagram, Twitter 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 presentation should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. Immatics undertakes no duty to update these forward-looking statements. All the scientific and clinical data presented within this press release are – by definition prior to completion of the clinical trial and a clinical study report – preliminary in nature and subject to further quality checks including customary source data verification. For more information, please contact: Media and Investor Relations Contact Jacob Verghese or Eva Mulder Trophic Communications Phone: +49 89 2070 89831 or +31 6 52 33 1579 immatics@trophic.eu Immatics N.V. Anja Heuer Jordan Silverstein Director, Corporate Communications Head of Strategy Phone: +49 89 540415-606 Phone: +1 281 810 7545 media@immatics.com InvestorRelations@immatics.com Unaudited Condensed Consolidated Statement of Financial Position of Immatics N.V. As of September 30, 2022 December 31, 2021 (Euros in thousands) Assets Current assets Cash and cash equivalents 178,047 132,994 Other financial assets 131,287 12,123 Accounts receivable 1,139 682 Other current assets 11,838 6,408 Total current assets 322,311 152,207 Non-current assets Property, plant and equipment 11,737 10,506 Intangible assets 1,542 1,315 Right-of-use assets 14,688 9,982 Other non-current assets 4,015 636 Total non-current assets 31,982 22,439 Total assets 354,293 174,646 Liabilities and shareholders’ equity Current liabilities Provisions 4,372 51 Accounts payable 12,828 11,624 Deferred revenue 80,150 50,402 Other financial liabilities 19,982 27,859 Lease liabilities 2,424 2,711 Other current liabilities 4,366 2,501 Total current liabilities 124,122 95,148 Non-current liabilities Deferred revenue 103,215 48,225 Lease liabilities 13,857 7,142 Other non-current liabilities 55 68 Total non-current liabilities 117,127 55,435 Shareholders’ equity Share capital 657 629 Share premium 602,272 565,192 Accumulated deficit (487,067) (537,813) Other reserves (2,818) (3,945) Total shareholders’ equity 113,044 24,063 Total liabilities and shareholders’ equity 354,293 174,646 Unaudited Condensed Consolidated Statement of Profit/(Loss) of Immatics N.V. Three months ended September 30, Nine months ended September 30, 2022 2021 2022 2021 (Euros in thousands, exceptshare and per share data) (Euros in thousands, exceptshare and per share data) Revenue from collaboration agreements 15,060 6,443 135,183 19,036 Research and development expenses (28,572) (21,225) (78,933) (64,613) General and administrative expenses (8,422) (8,266) (26,383) (24,968) Other income 9 47 42 311 Operating result (21,925) (23,001) 29,909 (70,234) Financial income 7,839 1,421 16,613 4,474 Financial expenses (426) (171) (1,950) (1,400) Change in fair value of warrant liabilities (5,865) (5,452) 7,877 (9,388) Financial result 1,548 (4,202) 22,540 (6,314) Profit/(loss) before taxes (20,377) (27,203) 52,449 (76,548) Taxes on income (558) — (1,703) — Net profit/(loss) (20,935) (27,203) 50,746 (76,548) Net profit/(loss) per share: Basic (0.32) (0.43) 0.79 (1.22) Diluted (0.32) (0.43) 0.78 (1.22) Weighted average shares outstanding: Basic 65,634,347 62,911,465 64,508,091 62,909,797 Diluted 65,634,347 62,911,465 65,239,279 62,909,797 Unaudited Condensed Consolidated Statement of Comprehensive Income/(Loss) of Immatics N.V. Three months ended September 30, Nine months ended September 30, 2022 2021 2022 2021 (Euros in thousands) (Euros in thousands) Net profit/(loss) (20,935) (27,203) 50,746 (76,548) Other comprehensive income/(loss) Items that may be reclassified subsequently to profit or loss, net of tax Currency translation differences from foreign operations (211) 1,252 1,127 2,576 Total comprehensive income/(loss) for the period (21,146) (25,951) 51,873 (73,972) Unaudited Condensed Consolidated Statement of Cash Flows of Immatics N.V. Nine months ended September 30, 2022 2021 (Euros in thousands) Cash flows from operating activities Net profit/(loss) 50,746 (76,548) Adjustments for: Interest income (606) (102) Depreciation and amortization 5,218 3,967 Interest expense 748 213 Equity settled share-based payment 16,725 21,671 Net foreign exchange differences* (11,974) (3,905) Change in fair value of warrant liabilities (7,877) 9,388 Changes in: (Increase)/decrease in accounts receivable (457) 525 (Increase) in other assets (6,523) (390) Increase/(decrease) in accounts payable and other liabilities 85,888 (14,233) Interest received 213 144 Interest paid (521) (213) Net cash provided by/(used in) operating activities* 131,580 (59,483) Cash flows from investing activities Payments for property, plant and equipment (3,390) (3,277) Cash paid for investments classified in Other financial assets (128,726) (11,362) Cash received from maturity of investments classified in Other financial assets 12,695 24,447 Payments for intangible assets (220) (487) Proceeds from disposal of property, plant and equipment 52 — Net cash (used in)/provided by investing activities (119,588) 9,321 Cash flows from financing activities Proceeds from issuance of shares to equity holders 21,009 75 Transaction costs deducted from equity (626) — Payments for leases (2,162) (2,102) Net cash provided by/(used in) financing activities 18,221 (2,027) Net increase/(decrease) in cash and cash equivalents* 30,213 (52,189) Cash and cash equivalents at beginning of period 132,994 207,530 Effects of exchange rate changes on cash and cash equivalents* 14,840 5,953 Cash and cash equivalents at end of period 178,047 161,294 Unaudited Condensed Consolidated Statement of Changes in Shareholders’ equity of Immatics N.V. (Euros in thousands) Sharecapital Sharepremium Accumulateddeficit Otherreserves Totalshare-holders’equity Balance as of January 1, 2021 629 538,695 (444,478) (7,459) 87,387 Other comprehensive income — — — 2,576 2,576 Net loss — — (76,548) — (76,548) Comprehensive income/(loss) for the year — — (76,548) 2,576 (73,972) Equity-settled share-based compensation — 21,671 — — 21,671 Share options exercised — 75 — — 75 Balance as of September 30, 2021 629 560,441 (521,026) (4,883) 35,161 Balance as of January 1, 2022 629 565,192 (537,813) (3,945) 24,063 Other comprehensive income — — — 1,127 1,127 Net profit — — 50,746 — 50,746 Comprehensive income for the year — — 50,746 1,127 51,873 Equity-settled share-based compensation — 16,725 — — 16,725 Share options exercised — 202 — — 202 Issue of share capital – net of transaction costs 28 20,153 — — 20,181 Balance as of September 30, 2022 657 602,272 (487,067) (2,818) 113,044 Attachment PDF Version