Medigene AG: Medigene presents new data on reproducible production of TCR-T cells from MDG1011 program

Planegg/Martinsried (pta022/08.11.2022/15:00 UTC+1)

Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology company focusing on the development of differentiated TCR-T therapies for cancers, today presents new data on reproducible production of TCR-T cells from elderly hematologically-challenged patients with blood cancers at the Cell UK Conference taking place November 7-8, 2022 in London. The presentation can be found on Medigene´s website: https://www.medigene.com/technologies/abstracts

MDG1011 is an autologous TCR-T therapy specific for a peptide fragment of PRAME (PReferentially expressed Antigen in MElanoma), a tumor antigen presented on cancer cells by human leukocyte antigen HLA-A2. Generation of MDG1011 in the phase I dose escalation trial (NCT03503968) was complicated by numerous factors impacting the potential quality of T cells, including that patients suffered from blood cancers, were heavily pretreated, and were mostly elderly. Leukemia blasts were detected at high levels in the blood of several patients during the leukapheresis process performed to obtain the starting patient-specific T cells for MDG1011 manufacture, which had the potential to hinder the production and the final purity of MDG1011 drug products. Despite this, a success rate of 92% was achieved in production of TCR-T cells for twelve of thirteen patients using a semi-automated modular manufacturing process. Assessment of immune reactivity demonstrated high antitumor activities for all final MDG1011 products, as potential markers of potency.

Generation of MDG1011 and functional activity

Patients underwent leukapheresis and CD8-positive T cells were enriched and cryopreserved for use in generation of MDG1011 drug products. Following thawing and activation, the PRAME-specific T cell receptor was introduced into CD8-positive T cells via retroviral gene transfer. TCR-T cells were expanded and cryopreserved for later shipment to the clinical centers for thawing and application to the patients as a single infusion. The GMP processes of drug product manufacture and quality control, with subsequent immune assessments of thawed MDG1011 products demonstrated:

• Generation of highly-enriched CD8-positive TCR-T cells was successful, despite high variability in the patient leukapheresis starting materials, with no detection of residual blood cancer cells in final MDG1011 products
• TCR-T cells expressing the PRAME-specific TCR were produced in the required numbers needed for a dose escalation phase I study of MDG1011
• MDG1011 showed high viability through all steps of the process, including before and after cryopreservation
• Poly-functional cytokine secretion and killing capacity for tumor cell lines was seen with all MDG1011 products upon antigen-specific stimulation in vitro directly after thawing
• Diverse subsets of T cells were retained during the manufacturing process of MDG1011 products, including stem cell memory T cells, central memory T cells and other effector memory T cells

Overall, highly successful generation of MDG1011 was feasible for hematologically-challenged patients. The TCR-T cells displayed excellent viability after thawing and antigen-specific poly-functional cytokine secretion was observed for all MDG1011 products manufactured from such patients.

Prof. Dolores Schendel, Chief Scientific Officer at Medigene: "The production of functionally potent MDG1011 product is critical to achieve tangible clinical benefit in patient treatment. We are pleased by this achievement with a very high success rate for MDG1011 products developed for elderly patients with relapsed or refractory blood cancers. This robust process yielded high purity, high quality poly-functional CD8-positive TCR-T cells and the lessons learned here with liquid tumors provide important insights as we develop novel TCR-T therapies for patients with solid cancers."

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About Medigene

Medigene (FSE: MDG1) is a late pre-clinical stage immuno-oncology company, focusing on discovering and developing differentiated, breakthrough cellular therapies to improve the lives of cancer patients. With an end-to-end technology platform built on multiple proprietary and exclusive product enhancement and product development technologies, Medigene aims to create best-in-class T cell receptor-modified T cell (TCR-T) therapies that are optimized for both safety and efficacy. Medigene's strategy is to develop product candidates both for its in-house therapeutics pipeline and for partnering. For more information, please visit www.medigene.com

About Medigene's TCR-Ts

T cells are at the center of Medigene's therapeutic approaches. With the aid of Medigene's immunotherapies the patient's own defense mechanisms are activated, and T cells harnessed in the battle against cancer. Medigene's therapies arm the patient's own T cells with tumor-specific T cell receptors (TCRs). The resulting TCR-Ts should thereby be able to detect and efficiently kill cancer cells.

This approach to immunotherapy aims to overcome the patient's tolerance to cancer cells and tumor-induced immunosuppression by activating the patient's T cells outside the body, genetically modifying them with tumor-specific TCRs and finally multiplying them. In this way, large numbers of specific T cells are made available to patients to fight the cancer within a short period of time.

About PRAME

PRAME (PReferentially expressed Antigen in MElanoma) is a tumor antigen of the cancer-testis-antigen family which is over-expressed in various solid tumors. Expression in healthy tissue is limited to the testis, which itself is an immuno-privileged tissue that usually cannot be attacked by the body's own immune cells. This makes PRAME very suitable as a target antigen for TCR-T therapies.

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.

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