Volume 95 Issue 44 | p. 13 | News of The Week
Issue Date: November 6, 2017 | Web Date: November 1, 2017

Kymera launches with $30 million to tackle targeted protein degradation

Backed by Atlas Venture, the firm hopes to put its first compound in the clinic by 2020
Department: Business
Keywords: Start-ups, Kymera, protein degradation, Arvinas
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TAGGED FOR TRASH
Kymera's small molecules bind to both proteins and the ubiquitin E3 ligase, allowing them to be tagged for disposal by the proteosome.
Credit: Kymera
Graphic depicting a bifunctional small molecule bound to its protein target and a ubiquitin ligand.
 
TAGGED FOR TRASH
Kymera's small molecules bind to both proteins and the ubiquitin E3 ligase, allowing them to be tagged for disposal by the proteosome.
Credit: Kymera

Kymera Therapeutics has launched with $30 million in funding from Atlas Venture, Lilly Ventures, and Amgen Ventures. The firm intends to develop bifunctional small molecules that can tackle disease-causing proteins that have long stymied drug developers.

Kymera is the latest biotech company working on targeted protein degradation, a way of tagging troublesome proteins for the cellular trash bin.

Traditionally, small-molecule drugs work by blocking the activity of errant proteins. But that approach has limited drug developers to a small fraction of the thousands of proteins made by humans.

Kymera and other protein degradation firms want to use small molecules to coax the body into getting rid of troublesome proteins altogether—a strategy more often associated with RNA-based drugs.

To do that, they are taking advantage of the body’s own protein disposal system. When a protein’s time has come, it is tagged with ubiquitin so that it is recognized by the proteasome—the trash compactor of the cell—for removal. Kymera is designing small molecules that feature a protein-binding domain linked to a ubiquitin ligase-binding domain. Forcing the protein and ligase to nestle together causes the protein to be tagged for breakdown. The drug is then released to repeat the process.

Several well-funded biotech firms have emerged to exploit targeted protein degradation, including Arvinas, founded by Yale University chemist Craig Crews, and C4 Therapeutics, spun out of Dana-Farber Cancer Institute.

Most drug discovery efforts have relied on E3 ubiquitin ligases identified by Crews and the Dana-Farber team. “These two are the front runner ligases for various reasons, so the challenge in the field is, ‘Can we now expand this to other ligases?’” says University of Dundee chemist Alessio Ciulli, whose lab is working on protein degradation with Boehringer Ingelheim.

While Kymera isn’t dismissing the existing ligase toolbox, “we are going beyond those that are out there,” says its co-founder and chief technology officer, Nello Mainolfi. The biotech firm further distinguishes itself by using informatics to find the right protein target-ligase pairs and strong medicinal chemistry skills to design molecules, Mainolfi says.

Kymera will focus on immuno- oncology, autoimmune diseases, and fibrosis.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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