Medigene Shares Preclinical Data on Optimal Affinity TCRs Targeting Neoantigen Mutant KRAS

Planegg/Martinsried, May 15, 2024. Medigene AG, an immuno-oncology company focused on T cell immunotherapies for solid tumors, showcased its proprietary T cell receptor (TCR) discovery process at the 21st Association for Cancer Immunotherapy (CIMT) Annual Meeting in Mainz, held from May 15-17, 2024. The company's advanced approach yields optimal 3S TCRs (sensitive, specific, and safe) for targeting solid tumors, and integrates the PD1-41BB costimulatory switch protein (CSP) to further bolster TCR-T cell effectiveness in immunosuppressive tumor environments.

Medigene's presentation included a poster titled “Selection of Superior KRAS G12V Mutation-Specific T Cell Receptors with Unique Characteristics for 3rd Generation Armored and Enhanced T Cell Therapy,” which was made available online following the presentation.

Dr. Selwyn Ho, CEO of Medigene, emphasized the importance of discovering unique TCR sequences as the foundational step in creating TCR-T cells that exhibit optimal safety, efficacy, and durability. Utilizing a high-throughput process within their End-To-End (E2E) Platform, Medigene identifies TCR sequences with distinct specificity, sensitivity, and safety profiles. These 3S TCRs show promise for various therapeutic applications, including TCR-T therapies, T cell engagers, and TCR natural killer cell therapies.

Dr. Ho highlighted that these TCRs can be further enhanced within the E2E Platform through the incorporation of technologies like the PD1-41BB CSP. This enhancement significantly improves TCR-T cell functionality, persistence, and proliferation, indicating the potential for highly effective and durable TCR-T therapies.

Data presented at the meeting demonstrated the specificity and sensitivity of TCR-T cells co-expressing the PD1-41BB CSP along with one of three distinct 3S TCRs targeting the mKRAS G12V neoantigen. These TCR-T cells exhibited a substantial increase in interferon gamma (IFNγ) secretion when stimulated with mKRAS G12V-positive tumor cells, contrasting with no IFNγ secretion in response to cells expressing the wild-type KRAS protein.

All three 3S TCRs showed high sensitivity to the mKRAS G12V neoantigen, responding to minimal levels of the mKRAS-G12V peptide. The concurrent expression of the PD1-41BB CSP notably enhanced TCR-T cell functionality, enabling continued cytotoxicity against 3D tumor spheroids across multiple tumor exposure cycles, illustrating the robust anti-cancer efficacy of the TCR-T cells.

From a safety perspective, the 3S TCRs combined with the PD1-41BB CSP exhibited favorable profiles. They did not secrete IFNγ or exhibit cytotoxicity when exposed to healthy cells from major tissues or organs, confirming their selective toxicity towards cancer cells while sparing healthy tissue.

Medigene AG is committed to developing distinct T cell therapies for treating solid tumors. Its E2E Platform leverages proprietary technologies to generate optimal T cell receptors against cancer antigens and neoantigens, enhancing these TCR-engineered T cells to create superior TCR-T therapies. The platform supports both the company's therapeutic pipeline and potential partnerships. Medigene's lead TCR-T program, MDG1015, is expected to file for IND in Q3 2024 and CTA in Q4 2024.

Medigene's immunotherapies are designed to activate the patient's own T cells, equipping them with tumor-specific TCRs to efficiently target and eliminate cancer cells. Their approach aims to overcome cancer cell tolerance and tumor-induced immunosuppression by genetically modifying and expanding TCR-T cells outside the body before administering them to patients.

Additionally, Medigene's PD1-41BB CSP transforms the tumor's defense mechanism into an activating signal for TCR-T cells, enhancing their proliferation and tumor-killing capabilities in the presence of PD-L1-positive tumor cells. This innovation supports TCR-T cell function even under the challenging conditions of the tumor microenvironment.

KRAS, a protein that regulates cell proliferation and survival, often mutates in various deadly cancers, leading to uncontrolled cell growth. These mutations create neoantigens unique to cancer cells, making KRAS an attractive target for TCR-T therapies. Unlike CAR-T cells, which target surface antigens, TCR-T cells can recognize a broader range of targets, including intracellular proteins like neoantigens, making them particularly effective against KRAS mutations and other challenging cancer targets.