Planegg/Martinsried, August 23, 2023. 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, today announces the expansion of the IP license for its PD1-41BB and CD40L-CD28 costimulatory switch proteins, enabling their application to additional cell types and for use in Chimeric Antigen Receptor T cell (CAR-T) therapies (patent number WO2017/162797A1). Medigene's PD1-41BB and CD40L-CD28 costimulatory switch protein technologies were developed by its partner Helmholtz Munich and are exclusively licensed to Medigene.

With the expansion of the IP license to include various cell types beyond T cell receptor engineered T cells (TCR-T), Medigene significantly enhances the potential use of both costimulatory switch proteins, which are currently combined with the Company’s  specific, sensitive and safe T cell receptors (TCRs), across various cell types beyond T cells. This provides an opportunity to leverage the advantages of other immune cells and enhance the tumor cell killing activity, proliferation and persistence of its TCR-based therapies.

In addition, this IP license expansion enables Medigene to potentially enhance the efficacy of CAR-T therapies in patients who relapse and do not respond adequately to earlier lines of therapy due to the upregulation of PD-L1 in certain cancers.

“We are very pleased to continue our excellent collaboration with Helmholtz Munich and expand our IP license, enabling us to extend the anti-tumor enhancements of our PD1-41BB and CD40L-CD28 costimulatory switch proteins, in additional cell types beyond TCR-T therapies,” said Dr. Selwyn Ho, Chief Executive Officer at Medigene. “Further, the expansion of this IP license fits well with our mid to long term strategy of focusing on the treatment of solid tumors. We also aim to selectively partner this technology with companies with demonstrated CAR-T expertise to further develop this novel therapeutic approach. This may open up opportunities for new treatment modalities that could help address current unmet needs in difficult-to-treat malignancies.”

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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 www.medigene.com

About Helmholtz Munich

Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, and with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en     

About Medigene’s PD1-41BB Costimulatory Switch Receptor

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. 

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 CAR-T cells

CAR-T cells are a type of immunotherapy where T cells are genetically engineered to express chimeric antigen receptors (CARs) which are tumor reactive antibodies fused to signaling domains of  αβT cells. This process provides both antigen-binding and T cell activating functions against fixed surface antigens on tumor cells. Multiple clinical trials have shown the therapeutic potential of this approach, leading to several approved products for various indications. Improving existing CAR-T therapies may be beneficial for novel therapeutic approaches, specifically in relapsed and/or non-B cell or non-plasma cell diseases where there is significant unmet need for additional treatment options.

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

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