ASIP

MediGene AG (Medigene or the “Company”, FSE: MDG1, Prime Standard) is an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors. Prof. Dolores Schendel, Medigene‘s Chief Scientific Officer, has been invited to present at the 8th CAR-TCR Summit in Boston on August 30, 2023. The title of the presentation is “Improving TCR-T Therapeutic Persistence and Efficacy with Switch Receptors.” Professor Dolores Schendel’s presentation established the clear ethos behind Medigene’s approach to the development of best-in-class T cell receptor engineered T cell (TCR-T) therapies through its end-to-end (E2E) technology platform, comprising multiple, combinable, exclusive and proprietary technologies. The E2E platform includes multiple development optimization technologies, such as Allogeneic-HLA (Allo-HLA) TCR Priming to generate optimal specific, sensitive and potentially safer 3S TCRs, which are then combined with product enhancement technologies, such as our PD1-41BB and CD40L-CD28 costimulatory switch proteins, to overcome the immunosuppressive effects of the tumor microenvironment. “Medigene is committed to creating best-in-class, differentiated TCR-T therapies for multiple solid tumor indications that are optimized for both safety and efficacy. By combining our 3S TCRs with our expanding portfolio of costimulatory switch proteins, we are able to enhance penetration, proliferation, persistence and cytotoxicity of our TCR-T cells in solid tumors, with the aim of addressing the unmet needs of patients with solid tumors,” said Dolores Schendel Chief Scientific Officer at Medigene. “Our portfolio of emerging TCR-T therapies all share this same approach, with our lead candidate MDG1015, a first-in-class, 3rd generation NY-ESO-1/ LAGE-1a targeted TCR-T therapy, that combines an optimal 3S TCR with our PD1-41BB costimulatory switch protein as well as our growing KRAS library of 3S TCRs, with MDG2011 as our lead program targeting KRAS G12V-A11.” As a continued frontrunner in the continously advancing and evolving design of TCR-T therapies, Medigene applies innovative tools and technologies available within its E2E platform, which allows the Company to overcome the multiple challenges of treating solid tumors. For more details, please find the presentation on Medigene’s website: --- end of press release --- About Medigene AG Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell therapies to effectively eliminate cancer. Its end-to-end technology platform, built on multiple proprietary and exclusive product development and product enhancement technologies, allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit About Medigene’s TCR-T Cells T cells are at the center of Medigene’s therapeutic approaches. Medigene’s immunotherapies help activate the patient’s own defense mechanisms, and harness T cells in the battle against cancer. Medigene’s therapies arm the patient’s own T cells with tumor-specific T cell receptors (TCRs) creating TCR-modified T cells with enhanced potential to detect and efficiently kill cancer cells. Medigene’s approach to immunotherapy is designed to overcome the patient’s tolerance of cancer cells and tumor-induced immunosuppression. By activating the patient’s T cells outside the body, genetically modifying them with tumor-specific TCRs and expanding the resultant activated TCR-T cells, patients can rapidly be given significant numbers of tumor-specific T cells to fight their cancer. About Medigene’s End-to-End Platform    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 TCR-T therapies. The platform includes multiple product enhancement technologies, (e.g., PD1-41BB switch protein, CD40L-CD28 switch protein, Precision Pairing) and development optimization technologies (e.g., Allogeneic-HLA (Allo-HLA) TCR Priming) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform’s assets & technologies.  About Medigene’s PD1-41BB Costimulatory Switch Protein Checkpoint inhibition via PD-1/PD-L1 pathway: 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. The expression of PD-L1 is an adaptive immune resistance mechanism for tumors that can help them survive and grow. The 4-1BB (CD137) costimulatory signaling pathway: 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. 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. 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, these 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. About Medigene’s CD40L-CD28 Costimulatory Switch Protein  The CD40L/CD40 pathway plays a major role in immune regulation and homeostasis. The CD40L (ligand) is a member of the tumor necrosis family and primarily expressed on activated T cells:  CD4+ T cells, where its primary function is in the T cell-mediated activation of dendritic cells (DCs) and monocytes.  CD8+ T cells thus promoting their expansion and differentiation through DCs.  CD40 is also present on B cells and expressed on dendritic cells (DCs), monocytes and macrophages as well as by non-hematopoietic cells such as epithelial and endothelial cells.  Expression of CD40 has been confirmed in a wide variety of solid tumors like melanoma, prostate, and lung cancers, as well as in carcinomas of the nasopharynx, bladder, cervix, and ovary.  CD28 is expressed on T cells providing costimulatory signals required for T cell activation and survival. Thus, the CD40L/CD40 pathway plays a crucial role in activation of T cells.  Medigene´s CD40L-CD28 costimulatory switch protein may contribute to an enhancement of cellular immune responses in several ways: CD40L expressed on activated T cells and CD40 expressed on DC transmits a signal to the antigen presenting cells that results in upregulation of costimulatory molecules and further stimulation of optimal T cell responses.  CD40-expressing tumor cells can be subject to apoptosis by direct interaction with CD40L-CD28-engineered T cells independent of MHC/peptide-specific targeting. CD40 is found in the TME of the tumor endothelium, where engagement with CD40L-CD28-engineered T cells enables upregulation of adhesion molecules, thereby improving T cell infiltration into tumors.  Thus, the CD40L-CD28 costimulatory switch protein acts via DCs and other non-tumor cells and may provide complementary effects to other switch receptors that exert their effects mainly via PD-1 expressing T cells.  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 Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com LifeSci Advisors Sandya von der Weid Phone: +41 78 680 05 38 E-mail: svonderweid@lifesciadvisors.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.

A team of researchers has discovered new insights into the evolution of color patterns in frogs and toads -- collectively known as anurans. Animal color patterns can help them camouflage with their surroundings and avoid detection from preys or predators. Many anurans have a light stripe along their back, which, when observed from above, creates the optical illusion that the animal is split in two halves and confuses visually-oriented predators. Although this color pattern is widespread in frogs around the world, little is known regarding its evolution or genetic origin. A team of researchers from NYU Abu Dhabi (NYUAD) has discovered new insights into the evolution of color patterns in frogs and toads -- collectively known as anurans. Animal color patterns can help them camouflage with their surroundings and avoid detection from preys or predators. Many anurans have a light stripe along their back, which, when observed from above, creates the optical illusion that the animal is split in two halves and confuses visually-oriented predators. Although this color pattern is widespread in frogs around the world, little is known regarding its evolution or genetic origin. In their paper published in the journal Molecular Biology and Evolution, the researchers of the Evolutionary Genomics Lab at NYUAD completed a broad-scale comparative analysis, which included over 2,700 species of anurans, to further the understanding of the evolutionary history of the vertebral stripe. They found that the vertebral stripe has evolved hundreds of times and is selected for in terrestrial habitats where visual predators coming directly from above -- such as mammals or birds -- are more prevalent. In contrast, the pattern was lost significantly more often in arboreal lineages -- those living in trees -- than in other habitats. While beneficial to frogs living on the ground, this color pattern may thus be disadvantageous to frogs living in trees. To understand the genetic basis of the pattern, the researchers focused on the Ethiopian grass frog species Ptychadena robeensis, which is polymorphic -- meaning that it presents the vertebral stripe trait in multiple forms -- wide, thin or absent. They found that the gene ASIP is linked to the stripe pattern in that species. This genetic variation affects the level of expression of ASIP in the different morphs, a higher expression leading to a wide stripe and a lower expression leading to a thin stripe. They also compared the genes of closely-related species of frogs and found that, while they present the same stripe patterns, they do not share the genetic variation found in P. robeensis. This led the researchers to the conclusion that the stripe alleles found in P. robeensis evolved recently. The researchers further conclude that the vertebral stripe evolves rapidly in anurans, which may allow species to adapt to environmental changes or variable conditions. This study is the first large-scale study of the adaptive value of the anuran vertebral stripe, whose evolutionary history has, until now, not been well understood. This study also establishes a link between the ASIP gene and a color pattern in anurans for the first time. ASIP is a well-studied gene in mammals, known to be linked to melanin production and color variation. The fact that it is linked to color patterns in frogs opens new research avenues on anuran color patterns and comparative studies across vertebrates. "Our findings establish that the vertebral stripe in frogs and toads holds a great potential in the field of evolutionary biology as it represents a clear example of repeated evolution. Studying this color pattern in other species can thus help us understand to which extent evolution predictably employs the same molecular paths when identical phenotypes evolve under similar selection pressures," said Sandra Goutte, PhD, a research associate at the Evolutionary Genomics Lab at NYUAD. "The identification of ASIP's role in the coloration of anurans by our team can also guide future comparative studies across vertebrates."