Pipeline – TAK-186

Overview^1-3

TAK-186 is a COnditional Bispecific Redirected Activation (COBRA) T-cell engager designed to bind to EGFR.

Mechanism of Action^1-3

- The intact prodrug molecule is activated preferentially by tumor associated proteases after it binds EGFR expressed on cells in the tumor microenvironment.

- Once activated, TAK-186 engages and activates CD3+ T cells. Activated T cells interacting with tumor cells release cytolytic granules which drives tumor cell death.

CD3, cluster of differentiation 3; COBRA^TM, COnditional Bispecific Redirected Activation; EGFR, epidermal growth factor receptor

Takeda's COBRA molecules are investigational. The mechanism of action is based on preclinical data. Clinical efficacy and safety have not been determined.

B7-H3, B7 homolog 3 protein; COBRA, COnditional Bispecific Redirected Activation; EGFR, epidermal growth factor receptor; MMP, matrix metalloproteinases; TME, tumor microenvironment.
1. Krakow J, et al. Antib Ther. 2022;5:1-10; 2. Panchal A, et al. MAbs. 2020;12:1792130; 3. Dettling DE, et al. J Immunother Cancer. 2022;10:e004336; 4. Waldman AD, et al. Nat Rev Immunol. 2020;20:651-668; 5. Huehls AM, et al. Immunol Cell Biol. 2015;93:290-296; 6. Kamakura D, et al. Pharmaceuticals (Basel). 2021;14:1172.

Clinical Trials

Study Name

A Phase 1/2, First-in-Human, Open Label, Dose Escalation Study of MVC-101, An EGFR x CD3 COnditional Bispecific Redirected Activation (COBRA) Protein in Patients With Unresectable Locally Advanced or Metastatic Cancer

References

1. Panchal A, Seto P, Wall R, et al. COBRA™: a highly potent conditionally active T cell engager engineered for the treatment of solid tumors. MAbs. 2020;12(1):1792130. doi:10.1080/19420862.2020.1792130

2. Dettling DE, Kwok E, Quach L, et al. Regression of EGFR positive established solid tumors in mice with the conditionally active T cell engager TAK-186. J Immunother Cancer. 2022;10(6):e004336. doi:10.1136/jitc-2021-004336

3. Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651-668. doi:10.1038/s41577-020-0306-5