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STEAP2

CompoundAZD8359

Area under investigation

Metastatic prostate cancer

Scientific PillarT-cell Engager

Target Overview

STEAP2 is a 6‑transmembrane receptor that is a member of the STEAP family of metalloreductases. STEAP2 has been found to be highly overexpressed across all stages of prostate adenocarcinoma1 and its role in promoting aggressive cancer traits2, its relatively homogeneous cell surface expression in prostate cancer and limited expression in normal tissue1 make STEAP2 an attractive therapeutic target for a T cell engager.

Compound Overview

AZD8359 is a trispecific T cell engager, which incorporates 2 Fab binding domains to STEAP2, one VHH binding domain to TCR and one VHH binding domain to CD8. The CD8 and TCR domains enable preferential engagement of CD8+ T cells, with the potential to give a broad therapeutic index by reducing CD4+ T cell-associated cytokine release.3

Mechanism of Action

  • Mechanism of Action

References

1. Zanvit P, van DykD, Fazenbaker C, et al. J Clin Invest. 2023;133(22):e169655.  2. Burnell SEA, Spencer-Harty S, Howarth S, et al. Sci Rep. 2018;8(1):6252. 3. Sitnikova S, et al. Cancer Res. 2026;86(8_Suppl):Abs no ND02.

Target Overview

STEAP2 is a 6‑transmembrane receptor that is a member of the STEAP family of metalloreductases. STEAP2 has been found to be highly overexpressed across all stages of prostate adenocarcinoma1 and its role in promoting aggressive cancer traits2, its relatively homogeneous cell surface expression in prostate cancer and limited expression in normal tissue1 make STEAP2 an attractive therapeutic target for a T cell engager.

Compound Overview

AZD8359 is a trispecific T cell engager, which incorporates 2 Fab binding domains to STEAP2, one VHH binding domain to TCR and one VHH binding domain to CD8. The CD8 and TCR domains enable preferential engagement of CD8+ T cells, with the potential to give a broad therapeutic index by reducing CD4+ T cell-associated cytokine release.3

Mechanism of Action

  • Mechanism of Action

References

1. Zanvit P, van DykD, Fazenbaker C, et al. J Clin Invest. 2023;133(22):e169655.  2. Burnell SEA, Spencer-Harty S, Howarth S, et al. Sci Rep. 2018;8(1):6252. 3. Sitnikova S, et al. Cancer Res. 2026;86(8_Suppl):Abs no ND02.

Clinical trial information


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CRIUS-1 trial overview

Tumor

Adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer

Trial Identifier

NCT07529717

Phase

I/II

Regimen

AZD8359

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Abbreviations

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  • CD4

    cluster of differentiation 4

  • CD8

    cluster of differentiation 8

  • STEAP2

    six transmembrane epithelial antigen of prostate-2

  • TCR

    T-cell receptor

  • VHH

    variable domain of the heavy-chain

Some compounds herein refer to selected AstraZeneca pipeline products still under development. AstraZeneca pipeline products are investigational products and, as such, are not approved by the US Food & Drug Administration (FDA), the European Medicines Agency (EMA) or any other regulatory agency for the uses under investigation. Information regarding these investigational products should, under no circumstances, be regarded as a recommendation for their use or of their safety or efficacy.

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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