On December 10, 2021 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of highly differentiated immuno-oncology therapeutics for patients, reported the presentation of new preclinical data for its anti-TIGIT monoclonal antibody, EOS-448, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition and the TIGIT Therapies Digital Summit 2021 (Press release, iTeos Therapeutics, DEC 10, 2021, View Source [SID1234596766]).

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"The data we presented this week at the TIGIT Therapies Digital Summit provide further evidence of the multifaceted mechanism of our high affinity, potent anti-TIGIT monoclonal antibody, EOS-448. We presented preclinical data showing activation of immune stimulatory cells is dependent on activating via FcγR, and also show clinically that this activation is translating to depletion of immunosuppressive cells. Furthermore, the upcoming data presentations at ASH (Free ASH Whitepaper) demonstrate the synergistic effect of combining an FcγR active anti-TIGIT antibody with an IMiD in a preclinical model of multiple myeloma and provide strong rationale for our ongoing Phase 1/2 trial in this difficult to treat cancer," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "These results underscore our enthusiasm for EOS-448 as a potential therapy capable of harnessing the immune system to help improve outcomes for patients with advanced, aggressive cancers. We look forward to progressing our clinical development plan in 2022 in both multiple myeloma and solid tumors with several combinations."

ASH 2021:

The Combination of Anti-Tigit and Lenalidomide Promotes Synergistic Myeloma-Specific Immunity after ASCT
Presented by: Simone A. Minnie, Ph.D., Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Abstract #: 154087

Preclinical data demonstrating the efficacy of a mouse surrogate EOS-448 as a single agent and in combination with an immunomodulatory imide drug (IMiD) in a preclinical model of multiple myeloma was presented by our collaborator at the Fred Hutchinson Cancer Research Center. The Fc-enabled anti-TIGIT monoclonal antibody elicited effective control of multiple myeloma disease progression, while an Fc-disabled version was inactive, indicating the importance of engaging the FcγR. Furthermore, the Fc-enabled anti-TIGIT antibody demonstrated synergistic activity when combined with an IMiD, a class of drugs that has previously shown clinical activity in multiple myeloma.

TIG-007: Study of EOS884448/GSK4428859A Alone, and in Combination with Iberdomide with or without Dexamethasone, in Participants with Relapsed or Refractory Multiple Myeloma
Presented by: Philippe Moreau, M.D., Hematology Department, Nantes University Hospital, Nantes, France
Abstract #: 152395

The presentation highlighted TIG-007, an ongoing open-label, multicenter, dose-escalation/expansion Phase 1/2 trial evaluating the safety, tolerability, and preliminary activity of EOS-448 as monotherapy and in combination with Bristol Myers Squibb’s IMiD, iberdomide, with or without dexamethasone, in adults with relapsed or refractory multiple myeloma. The preclinical data presented from the preclinical model of multiple myeloma provide a strong rationale for combining TIGIT inhibition with immunomodulatory drugs to prevent the progression of myeloma, and previous studies have shown notable clinical activity and acceptable tolerability with iberdomide in combination with dexamethasone or other antimyeloma agents in heavily pre-treated patients with relapsed or refractory multiple myeloma. The study aims to assess the therapeutic opportunity of EOS-448 alone or in combination with iberdomide, with or without dexamethasone to amplify myeloma-specific T cell anti-tumor responses in patients with difficult-to-treat relapsed or refractory multiple myeloma.

TIGIT Therapies Digital Summit 2021:

Targeting TIGIT: Which cell populations are modulated by FcγR engagement?
Presented by: Gregory Driessens, Ph.D., Senior Director, Project Head, iTeos Therapeutics

The presentation featured both preclinical and clinical evidence for the multifaceted mechanism of action of EOS-448, including activation of T cells, modulation of antigen-presenting cells and depletion of regulatory T cells (Tregs) and terminally exhausted T cells. Preclinical data demonstrated that FcγR engagement activated professional antigen-presenting cells either alone or synergistically with anti-PD1, both in the tumor and within the tumor draining lymph node. This effect was only evident when using a fully functional anti-TIGIT antibody, providing support for the design of EOS-448 as an IgG1 antibody. An update on the pharmacodynamic effect of EOS-448 in the blood of treated patients from the Phase 1 trial showed strong depletion of Tregs, an increase in the CD8/Treg ratio and a transient increase in proliferation (as assessed by the Ki67 marker), in line with previous observations with pembrolizumab.