GSK and iTeos Therapeutics Forge $2 Billion+ Collaboration to Advance Next-Generation Anti-TIGIT Antibody EOS-448 in Immuno-Oncology

Today, GlaxoSmithKline (GSK) and iTeos Therapeutics jointly announced that they will co-develop and commercialize EOS-448, an anti-TIGIT antibody in Phase 1 clinical development. GSK's press release noted that this collaboration provides GSK with investigational antibody therapies targeting three distinct targets associated with the CD226 immune checkpoint pathway (TIGIT, CD96, and PVRIG). These therapies have the potential to exert synergistic effects, enhancing the efficacy of cancer immunotherapy.

CD226 is a costimulatory receptor expressed on the surface of T lymphocytes and natural killer (NK) cells. Its binding to CD155 and CD112 expressed on the surface of tumor cells can activate T/NK lymphocytes. However, other immune checkpoint proteins are also expressed on the surface of T/NK cells, including CD96, TIGIT, and PVRIG, in addition to the well-known PD-1. By binding to CD155 and CD112, these immune checkpoint proteins block their binding to CD226, thereby inhibiting the activation of T/NK cells.

GSK's preclinical research has validated the critical role of the CD226 signaling pathway in oncology. Consequently, the company has advanced its pipeline to develop the CD96-targeting antibody therapy GSK'608 and the PVRIG-targeting antibody therapy GSK'562. When used in combination with the company's recently approved PD-1 inhibitor Jemperli (dostarlimab), these next-generation immune checkpoint inhibitors hold the potential to transform the treatment landscape for multiple cancer types.

▲GSK's R&D Pipeline Targeting the CD226 Signaling Pathway (Image source: Reference [2])

EOS-448, developed by iTeos Therapeutics, is an anti-TIGIT monoclonal antibody with multiple mechanisms of action. Through the collaboration with iTeos Therapeutics, GSK’s R&D pipeline will include investigational antibody therapies targeting CD96, TIGIT, and PVRIG, providing a more diverse toolkit for further developing combination cancer immunotherapies.

▲EOS-448 Features Multiple Mechanisms of Action (Image Source: Reference [3])

Under the agreement, iTeos will receive a $625 million upfront payment, plus up to $1.45 billion in additional potential milestone payments. GSK and iTeos will jointly share the development costs and responsibilities for EOS-448.

Note: The original text has been abridged.

References:

[1] GSK and iTeos Therapeutics announce development and commercialisation collaboration for EOS-448, an anti-TIGIT monoclonal antibody, enabling novel next-generation immuno-oncology combinations. Retrieved June 14, 2021, from https://www.gsk.com/en-gb/media/press-releases/gsk-and-iteos-therapeutics-announce-development/

[2] JP Morgan Healthcare Conference. Retrieved June 14, 2021, from https://www.gsk.com/media/6528/gsk_jpm_2021_final_12012021.pdf

[3] Preliminary data from Phase I first-in-human study of EOS884448, a novel potent anti-TIGIT antibody, monotherapy shows favorable tolerability profile and early signs of clinical activity in immune-resistant advanced cancers. Retrieved June 14, 2021, from https://www.iteostherapeutics.com/sites/default/files/2021-04/TIGIT%20poster%20AACR%202021_final%20210325.pdf

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