Immatics NV (IMTX)

[FACT-MASTER]

Interesting news on a Saturday - ESMO 2022 related

https://ih.advfn.com/stock-market/NASDAQ/immatics-nv-IMTX/stock-news/89032003/immatics-presents-comprehensive-preclinical-data-s

ESMO Presentation

https://oncologypro.esmo.org/meeting-resources/esmo-congress/targeting-solid-tumors-with-ima402-a-next-generation-bispecific-t-cell-engaging-receptor-against-prame

Background

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.

Methods

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.

Results

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.

Conclusions

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.