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Drug-induced protein degradation heats up

    Two more companies have launched into the red-hot targeted protein degrader space. This trendy modality opens up new therapeutic avenues by targeting specific proteins for degradation, rather than for classical protein inhibition. Typically target degradation agents consist of bifunctional small molecules that bind a target with one arm and an E3 ubiquitin ligase with another, resulting in the target being tagged for destruction by the proteasome.

    The newest entrants have disclosed few details of their approaches, as yet. Orionis Biosciences, which broke public ground in March, has been operating in stealth mode since 2015. One of the platforms they have developed is their Allo-Glues, small molecules that bind targets at allosteric sites to alter their form and function. At launch, Orionis disclosed that it is partnering with Novartis in a four-year deal to use this platform to find protein degraders and other drugs across therapeutic areas.

    Amphista Therapeutics made its debut in April with the completion of a $7.5-million series A funding round. Amphista’s platform operates “independent of traditional E3 ubiquitin ligases,” the company has said. It is on the hunt for cancer drugs.

    More established targeted protein degrader players are also continuing to attract attention, as well as funding. Kymera Therapeutics closed on another $102 million in March and plans to advance candidates into the clinic by next year. Nurix Therapeutics also raised another $120 million in March and expects to file an Investigational New Drug application with the US Food and Drug Administration by the end of the year.

    Last year Arvinas became the first company to advance a targeted protein degrader into the clinic. Yale University’s Craig Crews, who kick-started the targeted degrader field with his seminal work on PROTACs (proteolysis-targeting chimeras), founded Arvinas in 2013. Before the COVID-19 shutdown, Arvinas had expected phase 1 dose-escalation data for their first-in-modality program in the second quarter of 2020.

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    Drug-induced protein degradation heats up. Nat Biotechnol 38, 514 (2020). https://doi.org/10.1038/s41587-020-0529-9

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