iTeos Presents New Data for Anti-TIGIT Antibody, EOS-448/GSK4428859A, at the AACR Annual Meeting 2022
- Treatment with EOS-448 results in a decrease of TIGIT-positive cells in tumor biopsies, the first evidence of a treatment effect in the tumors of patients treated with an anti-TIGIT antibody
- In preclinical studies and in blood samples from patients with advanced cancers, treatment with EOS-448 results in a reduction in suppressive and exhausted immune cell populations, indicating engagement of FcγR, an essential component in many immune system effector functions
WATERTOWN, Mass. and GOSSELIES, Belgium, April 08, 2022 (GLOBE NEWSWIRE) — iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of potentially differentiated immuno-oncology therapeutics for patients, today announced a presentation featuring preclinical and clinical analyses supporting the multifaceted mechanism of action of its anti-TIGIT antibody, EOS-448/GSK4428859A, which is being developed in collaboration with GSK, at the American Association of Cancer Research (AACR) Annual Meeting 2022, taking place April 8-13, 2022 in New Orleans, Louisiana.
“We are excited to share new data in support of the multifaceted mechanism of our high affinity, potent anti-TIGIT antibody, EOS-448, that we believe support the important role of FcγR engagement in strategies targeting TIGIT for the treatment of cancer,” said Yvonne McGrath, Ph.D., chief scientific officer of iTeos Therapeutics. “We’re also encouraged by the evidence of TIGIT engagement in patient tumor biopsies, supporting our excitement for EOS-448 as a potentially important advancement in immuno-oncology. We look forward to continuing our assessment of EOS-448 in multiple late-stage clinical trials with the goal of providing a more effective treatment for people with advanced cancers.”
The presentation featured both preclinical and clinical evidence for the multifaceted mechanism of action of EOS-448, including activation of effector T cells, modulation of antigen-presenting cells and depletion of immunosuppressive regulatory T cells (Tregs) and terminally exhausted T cells which express TIGIT. Cell-based assays demonstrate higher potency with EOS-448 compared to other anti-TIGIT monoclonal antibodies in clinical development and provided the basis for its selection as a therapeutic candidate. Depletion of Tregs and exhausted CD8 T cells in patients with advanced cancers who were treated with EOS-448 demonstrate target engagement, providing additional evidence of potency.
Preclinical analyses of different anti-TIGIT antibody isotypes in combination with an anti-PD1 antibody in a murine cancer model demonstrate differences in anti-tumor activity depending on the anti-TIGIT isotype tested. Only the FcγR-engaging isotype induces a strong anti-tumor effect, which correlates with Treg depletion and activation of effector CD8 T cells in the tumor microenvironment. In addition, ex vivo analysis of human peripheral blood mononuclear cells demonstrates that EOS-448 preferentially depletes Tregs and progenitors of exhausted T cells, but not stem-like memory T cells. Pharmacodynamic analyses in the blood of patients treated across multiple dose levels of EOS-448 show sustained depletion of Tregs and terminally exhausted CD8 T cells with high TIGIT expression, resulting in an increased effector CD8 T cell/Treg ratio. In patient tumor biopsies, treatment with EOS-448 results in a decrease of TIGIT-expressing cells in the tumor; EOS-448 is the first anti-TIGIT antibody to demonstrate target engagement in patient tumors. These results are consistent with previously reported data providing evidence of FcγR engagement with EOS-448 and demonstrating initial clinical activity for EOS-448 as a monotherapy.
The abstract can be accessed on the AACR conference website. The abstract details are as follows:
Title: Pharmacodynamic assessment of a-TIGIT mAb EOS-448 highlights multiple FcγR-mediated mode-of-actions in blood and tumor of patients with advanced solid tumors
Session Title: Late Breaking Research: Experimental and Molecular Therapeutics 2
Abstract Number: LB189 / Section 16
Authors: Julia Cuende, et al.
About iTeos Therapeutics, Inc.
iTeos Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of highly differentiated immuno-oncology therapeutics for patients. iTeos Therapeutics leverages its deep understanding of tumor immunology and immunosuppressive pathways to design novel product candidates with the potential to restore the immune response against cancer. The Company’s innovative pipeline includes two clinical-stage programs targeting novel, validated immuno-oncology pathways designed with optimized pharmacologic properties with the goal of improving clinical outcomes. The first antibody product candidate, EOS-448, is a high affinity, potent, anti-TIGIT antibody with a functional Fc domain, designed to enhance the anti-tumor response through a multifaceted immune modulatory mechanism, currently progressing in multiple indications in collaboration with GSK. The Company is also advancing inupadenant, a next-generation adenosine A2A receptor antagonist tailored to overcome cancer immunosuppression into proof-of concept trials in several indications following encouraging single-agent activity in Phase 1. iTeos Therapeutics is headquartered in Watertown, MA with a research center in Gosselies, Belgium.
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