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Wnt is back in drugmakers' sights, but is it druggable?

Nature Biotechnology volume 36, pages 1028–1029 (2018)Cite this article

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A pathway largely abandoned by industry was recently thrust back into the limelight when Samumed raised $440 million in a private funding round to progress a clinical pipeline of Wnt signaling modulators across several indications. It's the most optimistic sign yet that addressing Wnt biology could still unlock therapeutic benefits for patients, despite a lengthy catalog of failures over the past decade. For competitive reasons, Samumed has yet to disclose the precise identity of the targets with which it is working, but it plans to do so over the next 12 to 18 months as its development programs mature and its need to educate the medical and scientific community increases. “We are hopefully two to three years away from our first set of approvals,” says company founder and CEO Osman Kibar. It would not be the first biotech firm to make such a claim. But Samumed's confidence is backed by a reported $12 billion valuation. There is a lot riding on its success, therefore—and a failure could have a chilling effect on further investment into Wnt-directed drug discovery.

Despite the lack of clear-cut success in the clinic to date, academic interest in Wnt signaling has remained high since Harold Varmus and Roland Nusse identified the first mammalian Wnt proto-oncogene in 1982 (EMBO J. 31, 2670–2684, 2012). It is a key developmental pathway during embryogenesis, and it plays a central role in regulating the growth and maintenance of myriad tissues thereafter. Wnt signaling, which is highly conserved in the animal kingdom, is extraordinarily complex. It is mediated through nineteen different secreted Wnt proteins, which interact with ten different Frizzled (FZD) cell-membrane receptors that resemble—but behave differently from—classical G-protein-coupled receptors. “In some ways it defies simple description,” says Michael Kahn, professor of molecular medicine at Beckman Research Institute at City of Hope. “It controls stem cell biology in every tissue from head to toe throughout the lifespan of the organism.”

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Change history

  • 30 November 2018

    In the version of this article initially published, Table 1 listed SM04554 as a Wnt pathway inhibitor; in fact, it is a Wnt pathway activator. The error has been corrected in the HTML and PDF versions of the article.

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    Cormac Sheridan

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Sheridan, C. Wnt is back in drugmakers' sights, but is it druggable?. Nat Biotechnol 36, 1028–1029 (2018). https://doi.org/10.1038/nbt1118-1028

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