On 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, reported 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 (Press release, MediGene, JUN 27, 2024, View Source [SID1234644580]). 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).
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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: View Source
"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 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.