Medigene AG presented novel preclinical data of their MDG 2011 program lead candidates which are optimal affinity Kirsten rat sarcoma viral oncogene homologue mutation (mKRAS)-specific T cell receptors (TCRs) targeting human leukocyte antigens (HLA) A*11, in combination with a PD1-41BB costimulatory switch protein (CSP) at the Society for Immunotherapy of Cancer (SITC) 2023 November 1-5, 2023, in San Diego, USA. To date, 21 so-called missense mutations (in which single amino acids are exchanged) have been identified in the KRAS gene, with G12D, G12V and G12C being the most common. Given the high prevalence of various mutations within the KRAS gene and the limitations of current therapeutic approaches, there is an unmet need to further improve targeted therapies.

The presented data demonstrate, utilizing a high-throughput approach, the generation of optimal affinity TCRs targeting the mKRAS G12V neoantigen presented by multiple HLA-A*11 subtypes through use of the Company's unique E2E Platform and shows further in vitro characterization with regards to specificity, sensitivity, and safety (3S), of the multiple TCR candidates in combination with the PD1-41BB-CSP. Robust co-expression of the recombinant TCRs (rTCRs) and the PD1-41BB CSP was demonstrated for the three TCR candidates. The TCRs showed excellent specificity for the mKRAS G12 V target, verified by release of interferon-gamma (IFN) only detected after stimulation with mKRAS G12V targets but not after stimulation with naturally occurring wild-type KRAS.

None of the TCRs recognized HLA allotypes other than HLA-A11 in a panel of cell lines expressing globally common HLA allotypes. Most importantly, healthy cells representing major tissues or organs did not trigger IFN release upon exposure to the TCR candidates, approving that cytotoxicity is restricted to cancer cells with no signs of toxicity to healthy tissue.