Medigene AG provided 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). 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.

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, innovative approach not only armors and enhances the TCR-T cell functionality by combining 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.

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 3rd 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.

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 Third Quarter 2024 and CTA approval in Fourth Quarter 2024.