Medigene Presents Preclinical Data on Optimal Affinity TCRs Targeting the Neoantigen Mutant KRAS

Planegg/Martinsried, May 15, 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, today presents the company’s proprietary T cell receptor (TCR) discovery process to obtain optimal affinity 3S (sensitive, specific and safe) TCRs at the 21^th Association for Cancer Immunotherapy (CIMT) Annual Meeting in Mainz from May 15 - 17, 2024. Data presented also shows the clear benefit of adding the PD1-41BB costimulatory switch protein (CSP) to further armor and enhance these 3S TCR-T cells, which enables them to overcome the immunosuppressive tumor microenvironment.

The poster with the title “Selection of superior KRAS G12V mutation-specific T cell receptors with unique characteristics for 3rd generation armored and enhanced T cell therapy” will be available on Wednesday, May 15, 2024, following the presentation on Medigene’s website: https://medigene.com/science/abstracts/

“The discovery process of unique TCR sequences is the first key step to generate TCR-T cells with optimal safety, efficacy and durability,” said Dr. Selwyn Ho, Chief Executive Officer at Medigene. “Employing a high-throughput process as part of our End-To-End (E2E) Platform enabled us to discover unique TCR sequences with distinct features with respect to specificity, sensitivity and safety (3S). These potential best-in-class 3S TCRs hold promise for utilization across diverse modalities, here focusing on T cell receptor engineered T cell (TCR-T) therapies, but also for use in T cell engagers and TCR natural killer cell therapies. “

He continued: “Our TCRs can undergo further enhancement through integration of various technologies within our E2E Platform such as with our exclusive PD1-41BB CSP, which significantly enhances TCR-T cell functionality, persistence and proliferation and offers the promise of highly effective and durable TCR-T therapies in patients.”

The presented data highlighted the specificity and sensitivity of TCR-T cells co-expressing the PD1-41BB CSP alongside one of three distinct 3S TCRs targeting the mKRAS G12V neoantigen. These TCR-T cells displayed markedly increased secretion of interferon gamma (IFNγ) observed upon TCR-T cell stimulation with mKRAS G12V-positive tumor cells, contrasting with the absence of IFN γ secretion upon stimulation with any tumor or healthy cell expressing naturally occurring wild-type KRAS protein.

All three 3S TCRs also demonstrated high sensitivity to the mKRAS G12V neoantigen, as demonstrated by their activation in response to extremely low levels of mKRAS-G12V peptide. Concurrent expression of the PD1-41BB CSP significantly augmented TCR-T cell functionality, enabling sustained cytotoxicity targeting 3D tumor spheroids across multiple rounds of tumor exposure. This underscores the potent anti-cancer efficacy of the TCR-T cells.

From a safety perspective, all three 3S TCRs combined with the PD1-41BB CSP demonstrated favorable safety profiles, with no IFNγ secretion or cytotoxicity when exposed to healthy cells from major tissues or organs, affirming their selective cytotoxicity towards cancer cells while sparing healthy tissue from toxicity.