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Saturday, 09/10/2022 10:41:56 PM

Saturday, September 10, 2022 10:41:56 PM

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Interesting news on a Saturday - ESMO 2022 related

ESMO Presentation


T cell engaging bispecifics redirecting T cells towards human leukocyte antigen (HLA)-presented peptides are emerging as promising treatment modality for patients with solid tumors. We have developed bispecific T cell engaging receptor (TCER®) molecules, which consist of an affinity maturated TCR, a humanized T cell-recruiting antibody and an Fc-part conferring half-life extension and favorable stability characteristics. Our TCER® candidate IMA402 targets an HLA-A*02-presented peptide derived from PRAME, which is highly prevalent across multiple solid tumors incl. melanoma, gynecological cancers, lung cancer, sarcoma and others.


After systematic evaluation, a TCR with high avidity and specificity towards the PRAME target peptide was selected for affinity maturation via yeast surface display resulting in more than 1,000-fold increased binding affinity while retaining specificity. The maturated TCR was then incorporated into our TCER® format.


IMA402 showed in vitro anti-tumor activity at picomolar concentrations against tumor cells with naturally occurring PRAME target peptide levels and demonstrated absence of reactivity towards normal tissue cells at relevant concentration, suggesting a broad therapeutic window. In preclinical xenograft mouse models, IMA402 led to consistent tumor regression including complete remissions and showed a serum half-life of several days. In these models, low affinity T cell recruiting domain demonstrated superior tumor control compared to analogous TCER® molecules with widely used higher-affinity T cell recruiters. Distinct affinities of the TCR (high) and T cell recruiter (low) are designed to optimize biodistribution and activation of T cells at the tumor site, aiming to reduce occurrence of immune-related toxicities like cytokine release syndrome, while achieving relevant doses in tumor tissue.


Upon preclinical proof-of-concept for the novel bispecific T cell engager IMA402 GMP manufacturing was initiated and is currently ongoing. IMA402 directed against PRAME will be the second TCER® entering clinical development with start of the phase 1 basket trial in several solid tumor indications planned for 2023.

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