Atlas-backed Kymera grabs $102M as its protein degradation technology heads into clinic
When Bruce Booth and Nello Mainolfi started planning a protein degradation company, the field was open and sparse, dotted with a couple of hopeful startups and larger players making exploratory forays. Booth called it a “broad new modality with plenty of freedom to operate across potentially every therapeutic area and disease state.”
Four years later, Kymera Therapeutics is looking to become one of the first of what will likely be many protein degradation companies to enter the clinic. The company announced $102 million in Series C funding and a plan to bring its lead drug targeting IRAK4 into the first trials by next year. Biotechnology Value Fund and Redmile Group led the round.
“We are at the cusp of transitioning from a research to a development organization — or, I should say, to a research and development organization,” Mainolfi, now the CEO, told Endpoints News. “This financing really allows to build toward the concept of building a fully integrated biotech company around protein degradation, which I think is probably one of the most transformative modalities.”
As of today, Kymera would likely be the second biotech to bring a protein degrader into the clinic. A year ago, Arvinas – whose founder Craig Crews published some of the first work showing how protein degradation could be drugged — brought what it believes to be the first protein degrader into human testing, an androgen receptor-targeting drug for prostate cancer. C4 Therapeutics, the other major startup that existed when Kymera launched, has partnerships with Biogen, Roche, and Dana-Farber, but no therapies in the clinic.
The protein is a kinase implicated in several cancers. Small molecules can inhibit IRAK4’s properties as a kinase, but the protein also functions as a scaffolding protein that helps build the myddosome protein complex. The complex is supposed to be activated to respond to infection but can sometimes activate aberrantly, leading to inflammatory or autoimmune disease.
The idea behind protein degradation is that instead of sending a molecule to block the protein’s kinase binding site — and leaving the rest of the protein intact and functioning — researchers can remove the protein entirely. They do this by hijacking the body’s internal system to remove proteins that are misfolded or are in overabundance. Enzymes called E3 ligases tag unwanted proteins with a protein called ubiquitin, like a general picking targets for an air raid. Those tagged proteins are then targeted by proteases and unfolded in the body’s multi-step garbage disposal system.
Kymera uses small molecules to drag E3 ligases to the protein it wants to eliminate. Their preclinical research suggests removing IRAK4 in this way will help treat a rare inflammatory skin condition called hidradenitis suppurativa and B-cell lymphomas, among other diseases. They also have programs targeting the transcription factor STAT3, which is part of the JAK pathway.
Mainolfi said the general concept had been apparent for years, but advancements around 2016 made it look feasible.
“This is technology that has fascinated me for years, but what was lacking were really the chemical tools,” Mainolfi said.
Since then, Kymera has built up a platform they say differentiates them from some of their competitors by using informatics to identify new E3 ligases and the best drugs in immunology and oncology. And last year they signed a $70 million collaboration with Vertex. Mainolfi, who stepped into the CEO job in November after Laurent Audoly’s departure, said it helps them apply their technology in indications beyond the two they’ve focused on to date.
Eventually, he said, protein degradation is going to be everywhere.
“When I look at protein degradation, I look at a field just like antibody or RNA therapeutics 20 years ago,” Mainolfi said. “It is a field that will transform medicine.”
