Using protein degradation against targets in oncology, immunology and inflammation.
Founder, president and chief scientific officer: Nello Mainolfi, Ph.D.
Based: Cambridge, Massachusetts
Clinical focus: Creating small-molecule drugs that exploit the body’s protein degradation machinery—the ubiquitin-proteasome system—to knock down disease-causing proteins
The scoop: Kymera is looking to expand the pool of druggable proteins by harnessing the body’s own process for dealing with unwanted molecules: protein degradation. To that end, it has raised more than $150 million from investors and through partnerships with the likes of GlaxoSmithKline and Vertex, and is working on a pipeline of small molecules led by a program targeting IRAK4, a protein involved in disease signaling pathways.
What makes Kymera fierce: Kymera was founded in 2016 to bridge a gap: “There were a lot of really cool targets in the space with a high degree of validation but had not been drugged because of a lack of the right modality,” President and Chief Scientific Officer Nello Mainolfi, Ph.D., said.
If you think about it, Mainolfi said, antibodies, RNAi therapies and CRISPR-based treatments—the key new technologies of the past 20 years—have expanded the field of druggable proteins. But in spite of these advances, a vast number of proteins are still out of reach. Using targeted protein degradation, Kymera wants to attack everything that hasn’t been addressed by those other approaches, Mainolfi said. He reckons that could cover more than half of the remaining “undruggable” proteome.
“Our mission was to take all the data that has been generated in the past 20 to 30 years since the genome was sequenced and use protein degradation to provide a first-in-class or best-in-class solution to underserved patients,” he said.
Kymera isn’t alone in the protein-degradation space: Celgene, C4 Therapeutics, Arvinas and Cedilla Therapeutics are all pursuing therapies in this area. What sets it apart, Mainolfi said, are its technology, its can-do attitude and the team of drug hunters it’s assembled.
The company has built a “disease-agnostic” platform dubbed Pegasus to identify, target and degrade “the most intractable of proteins,” Mainolfi said. It uses predictive modeling to understand the mechanism of protein degradation and dissect all the different biological steps that form this process. And Kymera has been building a toolbox of E3 ligases, the enzymes that drive recognition of protein targets.
“What we did very early on was to go beyond existing tools for engaging E3 ligases and expand the world of potential E3 ligases to use in protein degradation,” he said.
Kymera isn’t a company that built a platform and then cast about for disease areas it might be useful in, stressed Mainolfi and Jared Gollob, M.D., the company’s chief medical officer.
“You can have a fancy technology, but if you’re not aiming at the right disease, not committed to getting into the clinic and to patients as soon as practicable, you can’t really be fierce,” Gollob said.
The company has disclosed two targets: scaffolding kinase IRAK4 and transcription factor STAT3.
It’s developing its lead program, KYM-001, for an aggressive type of B-cell lymphoma. By going after patients with a mutation in IRAK4, Kymera believes it can select the patients most likely to benefit from treatment and boost the probability of success in the clinic.
“We are well on track to be in the clinic in these patients by the second half of next year,” Gollob said. At the same time, Kymera is developing KYM-001 for inflammatory diseases.
The company is in a similar spot with its STAT3 program. The target has been linked to inflammatory and autoimmune diseases, as well as numerous cancers, and Kymera has found it can attack the root cause of disease in patients with rare but aggressive T cell-based blood cancers by degrading STAT3.
“We are building more and more preclinical and clinical data in more indications,” Gollob said. “We’ve made a lot of progress and are attracting support from experts in the area. We are on track for being in the clinic next year.”
While Kymera works on its own cancer and immunology programs, it's applying its technology to other areas in its collaborations. It teamed up with GSK in April 2018 and with Vertex last May, but it's keeping most of the details of that deal under wraps.
“[With Vertex], we are working on diseases that I cannot talk about but are well beyond immunology and oncology that we have been working on in our internal programs,” Mainolfi said.
Vertex ponied up $70 million to secure the partnership but promised more than $1 billion in milestone payments tied to the success of six programs.
Mainolfi and Bruce Booth, D.Phil, a partner at Atlas Venture, founded Kymera and signed on Laurent Audoly, Ph.D. as the company's first CEO. An industry veteran who had served in various roles at Pierre Fabre, Pfizer, Merck, MedImmune and Pieris, Audoly left the company two months after Kymera teamed up with Vertex. The search for a new CEO is ongoing.
The company has about 36 people at the moment, with 17 new staffers joining in the last eight months, said Stephanie Moore, VP of human resources. Kymera plans to add another 27 employees “in short order,” but has had a plan since day 1 to preserve its culture.
“We’ve brought over $150 million of capital into the company in the form of financing and alliances, and it’s a reflection from both investors and collaborators that this truly is a unique platform technology and has the opportunity to be a very exciting and productive new modality,” said Kymera CFO Bruce Jacobs. “That interest remains very strong both from future potential collaborators and future investors.”
Investors: 6 Dimensions Capital, Aju IB Investment, Atlas Venture, Amgen Ventures, Bessemer Venture Partners, Hatteras Venture Partners, Lilly Ventures, MRL Ventures Fund, Pfizer Ventures, Sanofi Ventures
Editor's note: This story was updated to include more details on Kymera's pipeline and to clarify that Laurent Audoly was the company's first CEO, but not its founding CEO.