Medigene AG: Medigene presents streamlined 6-day, high stemness TCR-T therapy production process

Planegg/Martinsried (pta032/25.04.2024/15:00 UTC+2)

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 presents a comprehensive overview of its lead candidate MDG1015, a first-in-class 3rd generation T cell receptor engineered T cell (TCR-T) therapy, at CHI's 8th Annual Immuno-Oncology Summit Europe from April 23-25, 2024, in London. MDG1015, which is advancing towards the clinic, targets NY-ESO-1 / LAGE-1a (New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a) and is armored and enhanced by the PD1-41BB costimulatory switch protein

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 cancer-testis antigens (CTAs) shows promising clinical benefits. However, improving efficacy, safety, and ensuring a sustained response are areas needing improvement. Medigene tackles these challenges with a comprehensive approach, which starts with the development of a potential best-in-class, 3S (sensitive, specific, and safe) TCR. Next, the 3S TCR is enhanced with the Company's exclusive PD1-41BB costimulatory switch protein (CSP) on the engineered TCR-T cells. Finally, Medigene generates a meticulously customized drug product (DP) composition.

"At Medigene, our innovative approach not only enhances TCR-T cell functionality by combining our 3S TCRs with the PD1-41BB costimulatory switch protein but also places a significant emphasis on the DP manufacturing process. This process is vital for producing effective, safe, and durable TCR-T therapies," stated Kirsty Crame, MD, VP Clinical Strategy & Development. "With our focus on the DP composition, we aim to reduce the time required to manufacture DP ex-vivo and hence reduce the overall vein-to-vein timeframe for patients, while maintaining the highest standards of safety, efficacy and durability."

Medigene has developed a streamlined 6-day manufacturing process that focuses on the enrichment of CD8+ T cells whilst simultaneously maintaining a high degree of stemness. This allows for creating highly effective DPs, as the field has shown that more stem-like DPs exhibit greater potency and durability of response. The inclusion of the PD1-41BB CSP eliminates the need for CD4+ T cells within the DP, as CD8+ T cells are empowered to autonomously produce supporting cytokines. By doing so, the potential risks posed by CD4+ T cells can be circumvented and therefore potentially enhance both clinical safety and therapeutic efficacy.

Multiple in vitro studies for MDG1015 have clearly demonstrated enhanced anti-tumor immune responses for MDG1015 in comparison to TCRs without the CSP. This enhancement is evidenced by increased TCR-T cell proliferation and marked augmentation of Interferon γ (IFNγ) release, serving as a reliable indicator of superior TCR-T cell functionality. Furthermore, MDG1015 showed elevated polyfunctionality and clear durability of effect, with rapid and sustained tumor cell eradication upon multiple serial rechallenges of CTA / PD-L1 positive cells.

IND/CTA approval for MDG1015 is expected in the second half of 2024. Clinical indications for MDG1015 were primarily chosen based on the high unmet medical need, expression of the target antigen and/or PD-L1. This led to the selection of gastric cancer, ovarian cancer, myxoid/round cell liposarcoma, and synovial sarcoma as the initial focus areas for clinical evaluation. First patient enrolment will follow by the end of 2024, subject to financing. Based on this, the Company expects to present 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 expected to receive IND/CTA approval in the second half of 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 4-1BB 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/CTA approval expected in the second half of 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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Emitter:	Medigene AG Lochhamer Straße 11 82152 Planegg/Martinsried Germany
Contact Person:	Medigene PR/IR
Phone:	+49 89 2000 3333 01
E-Mail:	investor@medigene.com
Website:	www.medigene.com
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