HMBD-001 is a unique, highly-specific, anti-HER3 neutralizing antibody with a novel mechanism of action to treat HER3-activated tumors and prevent drug resistance.
HER3 is a member of the EGFR tyrosine kinase receptor family and plays a role is the MAP/PI3K signaling pathway that promotes cancer cell division and growth. HER3 is activated by the binding of neuregulin (NRG1), which stabilizes a transient open conformation to allow it to form heterodimers with HER2/EGFR. In the presence of abundant HER2/EGFR, heterodimers can form without NRG1.
Previous attempts to block the HER3 receptor have not proven to be efficacious as they bind to regions of the HER3 protein that do not necessarily prevent heterodimerization.
HMBD-001 Unique Binding Site
Directly Blocks Dimerization
Competition
Antibodies bind immunodominant but non-critical regions of HER3, leading to sub-optimal effect.
Hummingbird
Antibody blocks critical dimerization interface, leading to effective inhibition of HER3 function.
Competition
Antibodies bind immunodominant but non-critical regions of HER3, leading to sub-optimal effect.
Hummingbird
Antibody blocks critical dimerization interface, leading to effective inhibition of HER3 function.
Ligand
Binding Region
Dimerization
Interface
Preclinical models have shown that HMBD-001 is uniquely able to bind to a critical region on HER3, effectively blocking the heterodimerization of HER3 with HER2/EGFR independent of NRG1 binding.
This potently inhibits the activation of the signaling pathway – and consequently, tumor growth.
Learn more about HMBD-001 mechanism of action
References:
Kelley LA et al. Nature Protocols 10, 845-858 (2015)
Publications
Thakkar, D. Sancenon, V., Taguiam, M., Guan, S. Wu, Z., Ng, E., Paszkiewicz, K.H., Ingram, P.J., Boyd-Kirkup, J.D., 10D1F, an Anti-HER3 antibody that uniquely blocks the receptor heterodimerization interface, potently inhibits tumor growth across a broad panel of tumor models. Mol Cancer Ther. Epub 7 Jan 2020.
https://mct.aacrjournals.org/content/19/2/490
Thakkar, D., Taguiam, M., Sancenon, V., Guan, S., Paszkiewicz, K., Ingram, P., Boyd-Kirkup, J. HMBD-001-10D1,
A novel humanized anti-HER3 antibody with a unique mechanism of action, demonstrates superior tumor inhibition in multiple tumor models compared to other EGFR family therapies. 87 EJC Vol 103 S1, Nov 2018
Boyd-Kirkup, J. D., Thakkar, D., & Ingram, P. J. (2017). Abstract 24: HMBD-001, a novel anti-ErbB3 antibody with a unique mechanism of action, effectively inhibits tumor growth in pre-clinical models of ErbB3+ solid tumors. Cancer Research, 77(13 Supplement), 24-24.
https://doi.org/10.1158/1538-7445.AM2017-24
Learn more about HMBD-001 mechanism of action
References:
Kelley LA et al. Nature Protocols 10, 845-858 (2015)
References:
Kelley LA et al. Nature Protocols 10, 845-858 (2015)