Reuse and recycle is more than an environmental slogan. It’s also a succinct description of how cells deal with old or damaged proteins. Kymera Therapeutics is developing drugs that use this cyclical cellular process to treat disease, and it has raised $102 million to move into clinical testing next year.
The Series C round of funding was led by Biotechnology Value Fund and Redmile Group.
The cellular process of breaking down proteins for reuse is called protein degradation. This system works by affixing an old or damaged protein with a tag, so it’s recognized by the proteasome, the cell’s recycling machinery. Cambridge, MA-based Kymera’s drugs are small molecules that bind specifically to disease-causing proteins, says CEO Nello Mainolfi (pictured above). Those molecules then bring the disease-causing protein to E3 ligase, the tag that marks proteins for recycling. Mainolfi says this approach offers a way to target disease-causing proteins that had previously been deemed “undruggable” by small molecule inhibitors or antibodies.
“You can do it with a small molecule, a pill once or twice a day,” Mainolfi says. “You can go after proteins that are disease causing, and conceptually, can’t be targeted with other drug modalities.”
In preclinical research, Mainolfi says the company’s molecules degraded proteins in relevant tissues and cells. The research also helped the company understand how much of a target protein needs to be degraded in order to have an effect on a disease.
Kymera’s approach has already attracted interest from larger pharmaceutical companies looking to add protein degradation to their pipelines. A partnership with GlaxoSmithKline (NYSE: [[ticker:GSK]]) gives the pharmaceutical giant access to Kymera’s technology for screening small molecules. Last May, Vertex Pharmaceuticals (NASDAQ: [[ticker:VRTX]]) paid Kymera $70 million—a combination of cash and equity in the startup—in an alliance aiming to discover protein degrading drugs that Vertex will advance into clinical testing. Mainolfi won’t say which diseases that partnership is targeting, but he adds that the research does not conflict with Kymera’s focus on oncology and autoimmune diseases.
Kymera’s lead program targets IRAK4, a protein with a validated role in inflammation and cancer that has not yet been successfully hit by drug hunters. A second Kymera program targets STAT3, an undrugged protein that plays a role in inflammation, cancer, and fibrosis. Mainolfi says the new financing positions Kymera to discover, develop, and potentially commercialize new drugs. The company aims to bring up to three programs into human testing in the next 12 to 16 months.
Bruce Jacobs, Kymera’s chief financial officer, says the fresh cash will support the company well into 2022. The Series C round included “crossover investors,” firms that back both private and public companies. Investment from such firms is viewed as a sign a company is preparing to go public. Asked whether the company is considering an IPO, Jacobs demurred, saying only that the company will continue to assess its financial needs. “We have plenty of resources to execute on Nello’s and the scientific team’s goals,” he says.
Protein-degrading drugs represent a new, but growing area of research. Other companies in the field include Cambridge-based Cedilla Therapeutics and C4 Therapeutics of Watertown, MA. Nurix Therapeutics of San Francisco has partnerships with Gilead Sciences (NASDAQ: [[ticker:GILD]]) and Bristol Myers Squibb (NYSE: [[ticker:BMY]]) subsidiary Celgene. (On Thursday, Nurix announced a $120 million round of funding to advance its protein-degradation drugs to clinical testing.)
Arvinas (NASDAQ: [[ticker:ARVN]]) has already advanced into early-stage testing with a protein-degrading drug for prostate cancer. The New Haven, CT-based biotech has research partnerships with Roche subsidiary Genentech and Pfizer (NYSE: [[ticker:PFE]]). Through an alliance with Bayer, Arvinas is researching protein degradation drugs for cancer, cardiovascular diseases, and women’s health.
“This field is exploding,” Mainolfi says. “We hope many companies will be successful. We hope to be successful in the targets we have chosen and in the pathways we’ve chosen, to unlock new biology in new areas that are not well served by existing drug programs.”
In total, Kymera has raised $250M in capital, Jacobs says. The company last raised money in 2018, a $65 million Series B round. The other disclosed investors in Kymera’s latest financing include Wellington Management Company, Bain Capital Life Sciences, funds managed by Janus Henderson Investors and BlackRock, and Rock Springs Capital. The company says earlier investors, including Vertex, also participated in the Series C round. Kymera’s financing haul includes a strategic investment from The Leukemia & Lymphoma Society’s Therapy Acceleration Program, which supports the company’s work to treat blood-based cancers.
Photo by Kymera Therapeutics