Planegg/Martinsried, March 6, 2024. Medigene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, will present a poster at the American Association for Cancer Research Annual Meeting (AACR) 2024 taking place from April 5-10, 2024 in San Diego, USA as well as an oral presentation at the ELRIG-Forum 2024 to be held in Darmstadt, Germany on March 7, 2024.

Planegg/Martinsried，2024年3月6日。Medigene AG（Medigene或“公司”，FSE:MDG1，Prime Standard）是一家专注于实体瘤T细胞免疫疗法的发现和开发的免疫肿瘤学平台公司，将于2024年4月5日至10日在圣地亚哥举行的2024年美国癌症研究协会年会（AACR）上发布海报，以及将于2024年3月7日在德国达姆施塔特举行的2024年ELRIG论坛上的口头演讲。

Poster presentation:

海报展示：

AACR 2024

AACR 2024

https://www.aacr.org/meeting/aacr-annual-meeting-2024/

https://www.aacr.org/meeting/aacr-annual-meeting-2024/

Location: San Diego Convention Center, San Diego

地点：圣地亚哥会议中心，圣地亚哥

Date: April 5-10, 2024

日期：2024年4月5日至10日

Details on the poster presentation are as follows:

海报展示详情如下：

Abstract title: TCR-gated control of costimulatory switch protein (CSP) activation in rTCR-T cells expressing PD1-41BB

摘要标题：TCR门控控制表达PD1-41BB的rTCR-T细胞中共刺激开关蛋白（CSP）的激活

Maja Buerdek, Petra U. Prinz, Kathrin Mutze, Andrea Coluccio, Stefanie Tippmer, Miriam Bosch, Giulia Longinotti, Mario Catarinella, Kathrin Davari, Christiane Geiger, Barbara Loesch, Kristy Crame, Dolores J. Schendel.

Maja Buerdek、Petra U.Prinz、Kathrin Mutze、Andrea Coluccio、Stefanie Tipper、Miriam Bosch、Giulia Longinotti、Mario Catarinella、Kathrine Davari、Christiane Geiger、Barbara Loesch、Kristy Crame、Dolores J.Schendel。

Session details: PO.IM01.13 - Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T, Sunday, April 7, 1:30 PM - 5:00 PM local time

会话详细信息：PO。IM01.13-过继细胞疗法1：肿瘤抗原特异性T细胞和TCR-T，当地时间4月7日星期日下午1:30-下午5:00

The work to be presented shows that recombinant T cell receptor engineered T cells (rTCR-T cells), when armored and enhanced by the PD1-41BB CSP, exhibit superior TCR-T cell functionality and safety as well as a favorable safety profile, revealing the strong potential for improving treatment of cancer patients suffering from advanced solid tumor malignancies.

将要介绍的工作表明，重组T细胞受体工程化T细胞（rTCR-T细胞）在被PD1-41BB CSP包裹和增强时，表现出优异的TCR-T细胞功能和安全性以及良好的安全性，揭示了改善晚期实体瘤恶性肿瘤癌症患者治疗的巨大潜力。

The abstract for this research has been published online at https://www.abstractsonline.com/pp8/#!/20272/presentation/6084 and the poster will be available online after the conference at https://medigene.com/science/abstracts/.

这项研究的摘要已在网上发表https://www.abstractsonline.com/pp8/#哦/20272/presentation/6084和海报将在会议结束后在线提供https://medigene.com/science/abstracts/.

The Company is planning a first-in-human trial for MDG1015, a TCR-T therapy incorporating the CSP in gastric cancer, ovarian cancer, myxoid/round cell liposarcoma and synovial sarcoma with IND/CTA filing targeted for 2H 2024. MDG1015 is a first-in-class, third generation TCR-T therapy targeting NY-ESO-1/ LAGE-1a, armored and enhanced by the PD1-41BB CSP.

该公司计划对MDG1015进行首次人体试验，MDG1015是一种TCR-T疗法，将CSP纳入胃癌，卵巢癌，粘液样/圆形细胞脂肪肉瘤和滑膜肉瘤，IND/CTA归档目标为2024年下半年。MDG1015是针对NY-ESO-1/LAGE-1a的一流的第三代TCR-T疗法，由PD1-41BB CSP进行装甲和增强。

Oral presentation:

口头陈述：

ELRIG-Forum 2024

ELRIG论坛2024

https://www.elrig.de/index.php/elrig-foren/elrig-forum-2024

https://www.elrig.de/index.php/elrig-foren/elrig-forum-2024

Location: Darmstadtium Convention Centre, Darmstadt

地点：达姆施塔特达姆施塔迪姆会议中心

Date and time: March 7, 2024, 11:10 – 11:30am local time

日期和时间：2024年3月7日，当地时间上午11:10–11:30

Presenter: Dr. Barbara Lösch, Head, Technology & Innovation

主持人：Barbara Lösch博士，技术与创新主管

Title: Evolution by Innovation: Connecting the Dots of TCR-T Therapies

标题：通过创新进化：连接TCR-T疗法的各个点

Dr. Lösch will provide an overview on the Company’s proprietary End-to-End (E2E) Platform and highlight various tools within the E2E Platform that can enhance TCR-T cell functionality, safety and efficacy for generation of best-in-class, differentiated TCR-T therapies.

Lösch博士将概述该公司专有的端到端（E2E）平台，并重点介绍E2E平台内的各种工具，这些工具可以增强TCR-T细胞的功能，安全性和有效性，从而产生同类最佳的差异化TCR-T疗法。

This presentation will available on Medigene’s website on March 7, 2024: https://medigene.com/science/abstracts/

本演示文稿将于2024年3月7日在Medigene网站上发布：https://medigene.com/science/abstracts/

About Medigene AG

Medigene AG

Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing differentiated T cell therapies for treatment of solid tumors. Its End-to-End Platform is built on multiple proprietary and exclusive technologies that enable the Company to generate optimal T cell receptors against both cancer testis antigens and neoantigens, armor and enhance these T cell receptor engineered (TCR) -T cells to create best-in-class, differentiated TCR-T therapies, and optimize the drug product composition for safety, efficacy and durability.

Medigene AG（FSE:MDG1）是一家免疫肿瘤学平台公司，致力于开发用于治疗实体瘤的分化T细胞疗法。其端到端平台基于多种专有和独家技术，使该公司能够产生针对癌症睾丸抗原和新抗原的最佳T细胞受体，保护和增强这些T细胞受体工程（TCR）-T细胞，以创造一流的分化TCR-T疗法，并优化药物产品组成以实现安全性，有效性和耐久性。

The End-to-End Platform provides product candidates for both its own therapeutics pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is expected to receive IND/CTA approval in the second half of 2024.

端到端平台为其自身的治疗管道和合作提供了候选产品。Medigene的主要TCR-T计划MDG1015预计将于2024年下半年获得IND/CTA批准。

About Medigene’s End-to-End Platform

关于Medigene的端到端平台

Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s End-to-End Platform combines multiple exclusive and proprietary technologies to create best-in-class, differentiated TCR-T therapies. The platform includes multiple TCR generation and optimization technologies (e.g., Allogeneic-HLA (Allo-HLA) TCR Priming), as well as product enhancement technologies (e.g., PD1-41BB and CD40L-CD28 Costimulatory Switch Proteins, Precision Pairing) to address challenges in developing effective, durable and safe TCR-T therapies.

Medigene的免疫疗法通过利用T细胞对抗癌症，帮助激活患者自身的防御机制。Medigene的端到端平台结合了多种专有技术，创造了一流的差异化TCR-T疗法。该平台包括多种TCR生成和优化技术（例如同种异体HLA（Allo-HLA）TCR引发），以及产品增强技术（例如PD1-41BB和CD40L-CD28共刺激开关蛋白，精确配对），以应对开发有效，持久和安全TCR-T疗法的挑战。

Partnerships with multiple companies including BioNTech and 2seventy bio, continue to validate the platform’s assets and technologies.

与包括BioNTech和2seventy bio在内的多家公司合作，继续验证平台的资产和技术。

About Medigene’s PD1-41BB Costimulatory Switch Protein

关于Medigene的PD1-41BB共刺激开关蛋白

Checkpoint inhibition via PD-1/PD-L1 pathway:

通过PD-1/PD-L1途径抑制检查点：

Cells of solid tumors are sensitive to killing by activated T cells but can escape this killing activity by producing inhibitory molecules known as ‘checkpoint proteins’, such as the Programmed Death Ligand 1 (PD-L1), on their surface. When this occurs, activated T cells which express PD-1, the natural receptor for PD-L1, are inactivated.

实体瘤细胞对活化的T细胞的杀伤敏感，但可以通过在其表面产生称为“检查点蛋白”的抑制性分子（例如程序性死亡配体1（PD-L1））来逃避这种杀伤活性。当这种情况发生时，表达PD-1（PD-L1的天然受体）的活化T细胞被灭活。

The expression of PD-L1 is an adaptive immune resistance mechanism for tumors that can help them survive and grow.

PD-L1的表达是肿瘤的适应性免疫抵抗机制，可以帮助它们存活和生长。

The 4-1BB (CD137) costimulatory signaling pathway:

4-1BB（CD137）共刺激信号通路：

Effective T cell immune responses to antigens typically require both a primary antigenic stimulation via the T cell receptor (TCR) and costimulatory signals. The intracellular signaling domains of the 4-1BB protein offer a well-characterized pathway to costimulation and enhanced T cell responses.

对抗原的有效T细胞免疫应答通常需要通过T细胞受体（TCR）进行初级抗原刺激和共刺激信号。4-1BB蛋白的细胞内信号传导结构域为共刺激和增强的T细胞应答提供了良好表征的途径。

Medigene’s PD1-41BB switch receptor turns the tumor’s attempted self-defense mechanism against the tumor by substituting the inhibitory signaling domain of PD-1 with the activating signaling domain of 4-1BB. Therefore, instead of inactivating T cells, the switch receptor delivers an activating signal to TCR-T cells.

Medigene的PD1-41BB开关受体通过将PD-1的抑制性信号传导结构域替换为4-1BB的激活信号传导结构域，从而改变了肿瘤试图针对肿瘤的自卫机制。因此，开关受体不是使T细胞失活，而是向TCR-T细胞传递激活信号。

PD1-41BB-modified TCR-T cells proliferate strongly in the presence of PD-L1-positive tumor cells and kill more tumor cells upon repeated exposure. Additionally, switch receptor signals enable TCR-T cells to function better with low levels of glucose or high levels of TGFß, two conditions characteristic of strongly hostile tumor microenvironments.

PD1-41BB修饰的TCR-T细胞在PD-L1阳性肿瘤细胞存在下强烈增殖，并在反复暴露时杀死更多的肿瘤细胞。此外，开关受体信号使TCR-T细胞能够在低水平葡萄糖或高水平TGFβ的情况下更好地发挥作用，这是强烈敌对的肿瘤微环境的两种特征。