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Drug Development

Vertex and Kymera explore new protein-degradation targets

The deal expands Kymera’s scope beyond oncology and immunology

by Lisa M. Jarvis
May 16, 2019 | APPEARED IN VOLUME 97, ISSUE 20

 

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Credit: Kymera Therapeutics
Protein degraders work by tethering a disease-causing protein to an E3 ubiquitin ligase (1), recruiting an E2 protein and tagging the protein for ubiquitination (2) and subsequent breakdown into amino acids in the proteasome (3). The molecules then move on to repeat that process.

Vertex Pharmaceuticals is buying into the burgeoning field of protein degradation through a 4-year pact with fellow Cambridge, Massachusetts–based biotech firm Kymera Therapeutics. Kymera will receive $70 million, including an equity investment, from Vertex, which will get an exclusive option to license any drugs that emerge from the deal.

The partners will develop protein degraders for a set of undisclosed drug targets. While conventional small-molecule drugs typically turn off a protein’s activity, protein degraders get rid of bad-acting proteins altogether. These complex molecules feature two ends: one side binds to a protein of interest, and the other tethers to an E3 ubiquitin ligase, a protein that helps tag the target for the cell’s trash compactor, the proteasome. The drug then moves on to break down more proteins.

Formed in late 2015, Kymera—one of C&EN’s 2018 10 Start-Ups to Watch—has raised $95 million in venture capital to support development of its protein-degrader technology. In the past year, it has had discussions with many potential partners, but Vertex stood out as a match, says Nello Mainolfi, Kymera’s founder and chief scientific officer.

For each target it pursues, Vertex expects a deep understanding of human biology and an “exceptionally clear” hypothesis for how to design a drug for it, Mainolfi says. That approach resonated with Kymera, which wants to work on only highly validated drug targets as it wades into a new therapeutic modality. “We’re taking the technology risk, but not the biology risk,” he says.

The companies are not disclosing which targets they will pursue, but Mainolfi says the pact will allow Kymera to expand its therapeutic focus beyond oncology and immunology.

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