Found 1 Presentation For Request "753P"

Investigational immunotherapy

753P - Targeting solid tumors with IMA402, a next-generation bispecific T cell engaging receptor against PRAME

Presentation Number
753P
Speakers
  • Sarah Missel (Munich, Germany)
Date
Mon, 12.09.2022

Abstract

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.

Legal entity responsible for the study

Immatics Biotechnologies GmbH.

Funding

Immatics Biotechnologies GmbH.

Disclosure

S. Missel: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. S. Bunk: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. M. Hofmann: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. G. Pszolla: Financial Interests, Full or part-time Employment: Bayer AG. M. Hutt: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. F. Schwoebel: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. F. Unverdorben: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. C. Wagner: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. M. Jaworski: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. H. Schuster: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. F. Schwoerer: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. C. Schraeder: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. O. Schoor: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. T. Weinschenk: Financial Interests, Full or part-time Employment: Immatics N.V.. D. Maurer: Financial Interests, Full or part-time Employment: Immatics Biotechnologies GmbH. C. Reinhardt: Financial Interests, Full or part-time Employment: Immatics N.V.; Other, Member of the Board of Directors: Revitope Oncology Inc., Theolytics.

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