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

Planegg/Martinsried, June 27, 2024 - Medigene AG, an immuno-oncology company specializing in T cell immunotherapies for solid tumors, presented comprehensive details on its leading candidate MDG1015 at the 7th Cell and Gene Therapy In-Depth Focus Summit in Beijing, China. MDG1015 is a pioneering 3rd generation T cell receptor engineered T cell (TCR-T) therapy aimed at combating cancer-testis antigens (CTA) NY-ESO-1 / LAGE-1a and is enhanced by Medigene’s PD1-41BB costimulatory switch protein (CSP).

MDG1015 is designed to enter clinical trials shortly, targeting NY-ESO-1 / LAGE-1a antigens known for their presence in various tumors. The therapy incorporates Medigene’s PD1-41BB CSP to elevate T cell function and persistence. The presentation, titled “MDG1015: a 3rd Generation TCR-T Therapy Incorporating the PD1-41BB Costimulatory Switch Protein, Advancing to the Clinic,” is available on Medigene’s website.

Medigene’s approach addresses the need for greater efficacy, safety, and response durability in treating tumors expressing CTAs. The company developed a sensitive, specific, and safe TCR (3S TCR) and combined it with the PD1-41BB CSP to improve TCR-T cell functionality. A significant component of this strategy is optimizing the drug product (DP) manufacturing process to ensure the production of effective and safe TCR-T therapies.

Dr. Kirsty Crame, VP Clinical Strategy & Development, emphasized that the focus on optimizing DP composition aims to reduce ex-vivo manufacturing time, thereby shortening the vein-to-vein duration for patients while maintaining high standards of safety, efficacy, and durability.

The addition of the PD1-41BB CSP has shown promising results in multiple in vitro assays, demonstrating enhanced TCR-T cell proliferation and functionality compared to TCR-T cells without the CSP. This enhancement is gated, meaning it occurs only when the 3S TCR binds to its specific target antigen, adding an essential safety feature to Medigene’s 3rd generation TCR-T programs.

Medigene has developed a six-day manufacturing process that enriches CD8+ T cells while preserving their stem-like properties, which research indicates can lead to more effective and longer-lasting TCR-T therapies. By incorporating the PD1-41BB CSP, the process eliminates the need for CD4+ T cells, allowing CD8+ T cells to independently produce necessary cytokines, potentially reducing risks and enhancing the therapy's safety and benefits.

MDG1015 is slated for an Investigational New Drug (IND) application in the third quarter of 2024, followed by a Clinical Trial Application (CTA) in the fourth quarter of 2024. The candidate targets indications with significant unmet medical needs, focusing initially on gastric cancer, ovarian cancer, myxoid/round cell liposarcoma, and synovial sarcoma. Pending additional financing, patient enrollment could begin by the end of 2024, with early data from the dose-escalation phase expected by the fourth quarter of 2025.

Medigene’s comprehensive T cell engineering platform is dedicated to developing therapies for solid tumors, leveraging proprietary technologies to generate optimal T cell receptors and enhance their effectiveness. The company's lead program, MDG1015, is on track for regulatory submissions and aims to address critical gaps in cancer treatment by providing advanced T cell therapies.