Planegg/Martinsried, April 25, 2024. (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 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. 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 time 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. — end of press release —