Medigene Presents Efficient 6-Day TCR-T Therapy Production Process with High Stemness

Planegg/Martinsried, June 27, 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, today provides a detailed overview of its lead candidate MDG1015, a first-in-class 3rd generation T cell receptor engineered T cell (TCR-T) therapy, at the 7th Cell and Gene Therapy In-Depth Focus Summit from June 27-28, 2024, in Beijing, China. MDG1015 advances towards the clinic and targets the cancer-testisantigens (CTA) NY-ESO-1 / LAGE-1a (New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a) and is armored and enhanced by the Company’s PD1-41BB costimulatory switch protein (CSP).

The presentation with the title “MDG1015: a 3rd Generation TCR-T Therapy Incorporating the PD1-41BB Costimulatory Switch Protein, Advancing to the Clinic” is available on Medigene’s website: https://medigene.com/science/abstracts/

“Targeting tumors expressing CTAs has shown promising clinical benefits, yet there remains a need to enhance efficacy, safety, and response durability not only in orphan indications but also in more common solid tumor types. We tackle these issues with a comprehensive strategy, starting with the development of a best-in-class TCR that is sensitive, specific, and safe (3S TCR). Further, our innovative approach not only armors and enhances the TCR-T cell functionality by combining our 3S TCRs with the PD1-41BB CSP but also places a significant emphasis on the drug product (DP) manufacturing process. This process is vital for producing effective, safe, and durable TCR-T therapies” stated Kirsty Crame, MD, VP Clinical Strategy & Development.

“Our focus on optimizing the DP composition is intended to shorten the ex-vivo manufacturing time, thereby reducing the overall vein-to-vein duration for patients. This will be achieved while upholding the highest standards of safety, efficacy, and durability.”

A benefit of adding the PD1-41BB CSP to the Company´s 3S TCRs has been shown in multiple in vitro assays displaying elevated TCR-T cell proliferation, superior TCR-T cell functionality as well as quick and consistent elimination of tumor cells when compared to TCR-T cells lacking the CSP. It has been demonstrated this effect is “”gated” in that the enhancement occurs only after the 3S TCR binds to its specific target antigen.  This is an important safety feature of Medigene’s 3^rd generation TCR-T programs.In addition, Medigene devised an efficient 6-day manufacturing process that emphasizes enriching CD8+ T cells while preserving their stem-like properties. Research studies indicates that DPs with more stem-like characteristics demonstrate increased effectiveness and longer-lasting responses. By incorporating the PD1-41BB CSP, the necessity for CD4+ T cells within the DP is eliminated, allowing CD8+ T cells to independently produce the necessary cytokines that would have been provided by the CD4+ cells. This approach mitigates potential risks associated with CD4+ T cells, potentially enhancing both the safety and therapeutic benefits of the treatment.

Medigene’s lead TCR-T program, MDG1015, is scheduled for IND submission in the third quarter of 2024 and CTA submission in the fourth quarter of 2024. MDG1015’s clinical indications were selected due to significant unmet medical needs, the presence of the target antigen, and/or PD-L1 expression. This decision resulted in the initial focus on evaluating gastric cancer, ovarian cancer, myxoid/round cell liposarcoma, and synovial sarcoma. Subject to additional financing, the first patient enrollment is anticipated by the end of 2024. Based on this timeline, the Company aims to unveil early data from the dose escalation phase in the fourth quarter of 2025.

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About 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. The End-to-End Platform provides product candidates for both its own therapeutics pipeline and partnering. Medigene’s lead TCR-T program MDG1015 is on track for IND filing in Q3 2024 and CTA filing in Q4 2024. For more information, please visit https://medigene.com/

About Medigene’s MDG1015 Program

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 contains our optimal affinity 3S (sensitive, specific and safe) NY-ESO-1 /LAGE-1a TCR combined with our proprietary PD1-41BB costimulatory switch protein that blocks the PD1/PD-L1 inhibitory axis while simultaneously activating the T cell through the well described -41BB pathway further enhancing the activity and persistence of the TCR-T cell in the hostile tumor microenvironment (TME). MDG1015 is currently undergoing IND/CTA enabling studies with IND approval expected in Q3 2024 and CTA approval in Q4 2024.

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, 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.

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

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