HER3-addicted tumors: how biotechs are closing in - ElieDolgin
HER3, like other members of the ‘HER’ protein family, plays critical roles in tumor progression and drug resistance. But HER3 stands apart from its more famous kin—the well-known anticancer targets epidermal growth factor receptor and HER2—in lacking any tyrosine kinase activity of its own. Instead, for its oncogenic functions, HER3 relies on its ability to form dimers with other receptors to induce downstream signaling events.
Former front-runners in the HER3-targeting race, drugs such as elgemtumab from Novartis and duligotuzumab from Roche, all targeted the extracellular domain where the receptor binds NRG1. This interaction shut down ligand-dependent signaling cascades. But as cancer biologist Mark Moasser and his colleagues at the University of California, San Francisco,earlier this year, that domain is not needed for HER3–partner dimerization.
Seribantumab, too, has had a roundabout clinical trajectory. Developed initially by Merrimack Pharmaceuticals of Cambridge, Massachusetts, the IgG2 mAb reached phase 2 testing in breast, lung and ovarian cancers, but ultimately proved to have little therapeutic value in those settings. Merrimack suspended further development and, in 2019, sold the drug’s rights to Elevation, a New York–based company founded by CEO Shawn Leland.
A handful of other HER3-targeted mAbs and bispecifics remain in early-stage trials, mostly in China. Like other antibody-based candidates before them, these agents generally target the extracellular region of HER3. This is also the case with HMBD-001 from Hummingbird Bioscience of Singapore.designed
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