HMBD-001 is our flagship precision therapy program that targets HER3, a potent driver of tumor growth and resistance against cancer drugs.
A member of the EGFR family of receptors, HER3 activation is driven by the dimerization with HER2 or EGFR, triggering the MAPK/PI3K signaling pathway that promotes cancer cell division and growth. Dimerization is favored in the presence of the ligand, neuregulin 1 (NRG1) or HER2/EGFR overexpression. HER3 has received attention in recent years as it has been implicated in a significant number of cancers and in acquired resistance to other therapies. Moreover, a subpopulation of cancer patients has been identified with NRG1 fusions in their tumors; that is, the hybridization of the NRG1 gene with another gene to produce NRG1 fusion proteins that potently activate HER3.
Though a highly promising target, HER3 has proved difficult to drug effectively. Previous attempts to block the HER3 receptor have not proven to be efficacious, likely due to the inability of these antibodies to completely prevent dimerization of HER3, since dimerization is not fully dependent on NRG1 binding.
Engineer with Precision
Developed with our Rational Antibody Discovery platform, HMBD-001 is a unique antibody engineered to bind strongly and specifically to the dimerization interface of HER3, thereby interfering with HER3’s ability to dimerize and fully blocking its activation, regardless of NRG1 binding.
This gives HMBD-001 a novel mechanism of action for inhibiting tumor growth and drug resistance in HER3-driven cancers. Preclinical models have shown that HMBD-001 potently inhibits the activation of the MAPK/PI3K signaling pathway – and consequently, prevents tumor growth and drug resistance.
Develop with Precision
HMBD-001 has broad potential across multiple tumor types, however, optimal clinical development requires a “stepping-stone” strategy to demonstrate benefit and ensure efficient deployment of resources.
Through integrative AI-powered analyses of robust datasets, we have identified biomarkers indicative of certain patient populations who may benefit most from HMBD-001, for example, patients with functional NRG1-fusions in their tumors.
We aim to evaluate HMBD-001 for the treatment of patients with cancers expressing NRG1 fusions, as well as other priority patient populations for precision oncology, with our partner, Cancer Research UK (CRUK).
Molecular Cancer Therapeutics, AACR Journals: 10D1F, an Anti-HER3 Antibody that Uniquely Blocks the Receptor Heterodimerization Interface, Potently Inhibits Tumor Growth Across a Broad Panel of Tumor Models
European Journal of Cancer: 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.
Cancer Research, Volume 77, Issue 13 Supplement, AACR Journals: 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.
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