MDG-1015

Planegg/Martinsried, November 11, 2024. Medigene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, presented latest updates on its End-to-End (E2E) Platform technology - the UniTope and TraCR technology, a universal detection system for tagging and tracking recombinant TCRs (rTCRs), at the Protein & Antibody Engineering Summit (PEGS) in Barcelona from November 5-7, 2024, and the Society of Immunotherapy of Cancer (SITC) 2024 conference in Houston, TX, USA from November 6-10, 2024. The presentation ”Seamless Integration of a Universal Epitope into Recombinant TCRs for Tagging and Tracking of TCR-T Cells Expressing 3S TCRs” and the poster “UniTope & TraCR – A universal tagging and tracking system for TCR-T cells directly integrated in recombinant TCRs” are available on the Medigene website: https://medigene.com/science/abstracts/ “Precise tracking of T cells engineered to express rTCRs is essential for thoroughly vetting rTCR candidates to identify optimal 3S (specific, sensitive and safe) lead candidates, assess specific rTCR sequences during drug product development, and provide consistent monitoring of TCR-T cells throughout Good Manufacturing Practice production,” said Dolores Schendel, CSO of Medigene AG. “At Medigene, we are constantly aiming to expand our End-to-End (E2E) Platform by integrating new proprietary technologies such as the UniTope & TraCR system to optimize our discovery process for selection of 3S rTCRs. With UniTope & TraCR, rTCR sequences of any specificity can also be precisely identified during drug product manufacture through accurate assessment of rTCR expression and frequency of rTCR-T cells. During the clinical phases of development, these technologies support robust quality control processes for drug product release, facilitates precise dosing calculations for therapeutic administration and provides a simple methodology for assessing the pharmacokinetics and pharmacodynamics of TCR-T cells post-infusion in patients, all of which contribute to optimizing patient safety.”The data presented at both conferences showcased Medigene's novel UniTope and TraCR System for universal identification of rTCRs in TCR-T therapies. This system enables standardized tagging, enrichment and tracking of rTCRs by use of simple flow cytometry-based technologies with a single detection reagent. Bioinformatic studies were used to identify a unique, six-amino-acid peptide, designated as UniTope, with predicted low immunogenicity. This sequence is absent in all natural TCR chains, enabling rTCRs to be earmarked with a unique identifier through seamless integration of UniTope directly in the rTCR sequence of either chain of any TCR heterodimer. A corresponding antibody, designated TraCR, was developed that specifically binds to UniTope-modified rTCRs, but not to any natural TCR sequence, enabling precise identification of tagged rTCRs. Comprehensive studies compared UniTope-modified rTCRs with unmodified rTCRs for 3S attributes of specificity, sensitivity and safety. In vitro tests showed that integrating UniTope in rTCRs expressed by TCR-T cells targeting the neoantigen mKRAS G12V or the cancer-testis antigens NY-ESO-1 and PRAME preserved TCR expression as well as function, confirming that UniTope-modification had no impact on the rTCRs structural and functional attributes. Safety assessments further validated TCR-T cells with UniTope-modified rTCRs maintained a high safety profile with no signals for unintended recognition of cells originating from primary healthy tissues. Overall, equivalent specificity, safety, and functionality of UniTope-modified rTCRs, compared with unmodified rTCRs, demonstrates the versatility of the UniTope & TraCR System as a high precision technology that facilitates optimized development of TCR-T therapies. --- end of press release --- About Medigene AG Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell receptor (TCR)-guided therapies to effectively eliminate cancer. Its End-to-End Platform generates optimal 3S (sensitive, specific and safe) T cell receptors with unique and distinctive attributes that are utilized in multiple therapeutic modalities, such as T cell receptor engineered T cell (TCR-T) therapies, TCR-guided T cell engager therapies and TCR-natural killer cell therapies for both its in-house product pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is a potential best-in-class, TCR-T therapy to treat multiple solid tumor indications. The End-to-End Platform technologies enable armoring and enhancing of these T cells to overcome the immunosuppressive tumor microenvironment (TME) and ensure the T cell drug product composition maximizes safety, efficacy and durability of response. Medigene’s MDG1015 received IND approval in Q3 2024 and is filing for CTA in Q4 2024. For more information, please visit https://medigene.com/ About Medigene’s End-to-End Platform Medigene’s approach to immunotherapy harnesses the immense power of natural T cell receptors. By combining these TCRs with different components of the immune system such as T cells, natural killer (NK) cells or a CD3 complex (TCE, T cell engager), highly specific, sensitive and safe modalities are formed to either complement and/or activate the body’s defense systems against cancer. Medigene’s comprehensive End-to-End (E2E) Platform is built on a foundation of proprietary and cutting-edge technologies, driving the development of highly specific TCR-guided therapies, including the latest advancements in TCR-T, TCR-NK and TCR-TCE drug products. The E2E Platform incorporates sophisticated TCR generation and optimization techniques, such as Allogeneic-HLA TCR Priming, and integrates advanced product armoring and enhancement features like PD1-41BB and CD40L-CD28 Costimulatory Switch Proteins, and iM-TCR. In addition, the E2E Platform offers solutions to developing optimal cell therapy drug products for improved safety, efficacy and durability. Collaborations with partners like BioNTech, Regeneron and WuXi Biologics further underscore the platform’s capabilities and its potential to revolutionize cancer treatment. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. Medigene AG Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com In case you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.

Members of Medigene management as expert speakers, Prof. Dolores Schendel, Chief Scientific Officer and Kirsty Crame, MD, Vice President, Clinical Strategy & DevelopmentPresentations and seminars highlighted Medigene’s proprietary End-to-End Platform for generation of extraordinary T cell receptors for application in various modalities and overview of the lead TCR-T therapy program MDG1015 Planegg/Martinsried, November 8, 2024. Medigene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, highlighted recent advances in its proprietary End-to-End Platform to create optimal safe, sensitive, and specific (3S) T cell receptors that can be applied in various modalities, including therapies utilizing T cell receptor engineered T (TCR-T) cells, TCR-guided T cell engagers (TCR-TCEs) and TCR-natural killer cell therapies (TCR-NK) at the Cell 2024 Conference by Oxford Global taking place in London, UK from November 6-8, 2024. Data presented and discussed included Kirsty Crame, MD, participated in the panel “Exploring Autologous vs. Allogeneic Therapies.” which covered clinical insights, patient considerations, key immunological factors, and manufacturing challenges associated with each therapeutic approach.Kirsty Crame, MD, held the keynote address “Making the Ordinary Extraordinary: MDG1015 A Clinic Ready 3rd Generation TCR-T Therapy” providing a comprehensive overview of MDG1015. MDG1015 is a first-in-class, 3rd generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1 / LAGE-1a, a well-recognized and validated cancer-testis antigen, which is expressed in multiple tumor types. MDG1015 received IND approval in Q3 2024 and is on track for CTA filing in Q4 2024.Prof. Dolores Schendel presented the “TCR-T Platform for Solid Tumors” covering Medigene’s End-to-End Platform offering advanced technologies for developing 3S TCRs that can be utilized across multiple modalities. Precision tools enabling selection of 3S TCRs with high specificity, sensitivity, and safety for accurate tumor targeting were presented. Additionally, armoring and enhancement technologies were showcased which empower TCR-T cells to perform optimally within the challenging microenvironments of solid tumors. Furthermore, innovative tagging and tracing tools were highlighted, enabling seamless tracking of 3S TCRs throughout all phases of research and clinical development. The presentations will be available on Medigene’s website: https://medigene.com/science/abstracts/ "Among other factors, the success of TCR-guided therapies for solid tumors hinges on several key innovations: developing optimal TCRs that are safe, sensitive, and specific; enhancing engineered cells to overcome the tumor microenvironment; and refining manufacturing strategies for optimized drug composition and timely patient delivery," said Dolores Schendel, Medigene’s Chief Scientific Officer. "Our E2E Platform addresses each of these critical areas, positioning us to deliver optimal 3S TCRs that can be utilized in multiple therapeutic modalities, such as TCR-T therapies, TCR-TCEs and TCR-NK cell therapies. This approach of developing different TCR-guided therapies enables us to provide innovative treatment options tailored to patients across various indications, disease stages, and specific individual needs.” --- end of press release --- About Medigene AG Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell receptor (TCR)-guided therapies to effectively eliminate cancer. Its End-to-End Platform generates optimal 3S (sensitive, specific and safe) T cell receptors with unique and distinctive attributes that are utilized in multiple therapeutic modalities, such as T cell receptor engineered T cell (TCR-T) therapies, TCR-guided T cell engager therapies and TCR-natural killer cell therapies for both its in-house product pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is a potential best-in-class, TCR-T therapy to treat multiple solid tumor indications. The End-to-End Platform technologies enable armoring and enhancing of these T cells to overcome the immunosuppressive tumor microenvironment (TME) and ensure the T cell drug product composition maximizes safety, efficacy and durability of response. Medigene’s MDG1015 received IND approval in Q3 2024 and is filing for CTA in Q4 2024. For more information, please visit https://medigene.com/ About Medigene’s End-to-End Platform Medigene’s approach to immunotherapy harnesses the immense power of natural T cell receptors. By combining these TCRs with different components of the immune system such as T cells, natural killer (NK) cells or a CD3 complex (TCE, T cell engager), highly specific, sensitive and safe modalities are formed to either complement and/or activate the body’s defense systems against cancer. Medigene’s comprehensive End-to-End (E2E) Platform is built on a foundation of proprietary and cutting-edge technologies, driving the development of highly specific TCR-guided therapies, including the latest advancements in TCR-T, TCR-NK and TCR-TCE drug products. The E2E Platform incorporates sophisticated TCR generation and optimization techniques, such as Allogeneic-HLA TCR Priming, and integrates advanced product armoring and enhancement features like PD1-41BB and CD40L-CD28 Costimulatory Switch Proteins, and iM-TCR. In addition, the E2E Platform offers solutions to developing optimal cell therapy drug products for improved safety, efficacy and durability. Collaborations with partners like BioNTech, Regeneron and WuXi Biologics further underscore the platform’s capabilities and its potential to revolutionize cancer treatment. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. Medigene AG Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com In case you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.