For 30 years, scientists have been trying to unleash the promise of Interleukin-2 (IL-2), a powerful protein that fights cancer but is highly toxic. Researchers at the University of Washington may finally have done it, and they’re launching a startup to make a commercial version.
The breakthrough is described in a paper published in the journal Nature by researchers at the Institute for Protein Design at the UW and their co-authors.
“Interleukin-2 is one of the master mediators of the immune system,” Daniel-Adriano Silva, a lead author of the paper, said in an interview. Unfortunately, toxic side effects have severely limited the use of this protein powerhouse to fight disease. Currently, IL-2 is approved for the treatment of melanoma and renal cell carcinoma, where it cures 5 to 10 percent of patients.
“The problem is that it comes with such acute toxicity that the patients have to be treated in the intensive care unit,” said Silva.
Silva and his collaborators set out to create a manmade version of IL-2 that could do the job of stimulating T-cells to attack tumors without the toxic side effects. They used a protein design program called Rosetta to make a molecule that bound to the two receptors on T-cells but lacked a third, which is thought to cause the harm.
The result of their efforts, called Neo-2/15, successfully stimulated cancer-fighting T-cells in animals without the nasty side effects. “That was a very exciting moment,” said Silva.
Following the discovery, the team filed a patent and formed Neoleukin Therapeutics, a startup that will pursue a commercial version of the science. Its co-founders are Silva, co-authors Umut Ulge, Alfredo Quijano Rubio and Carl Walkey, as well as David Baker, director of the Institute for Protein Design and leader of the research. The new company’s CEO is Jonathan Drachman, who spent 14 years at Seattle Genetics where he was chief medical officer and head of R&D.
“It’s an incredible achievement to design a completely de novo protein that is not just biologically active but better than what nature evolved,” said Drachman. “This seems like the kind of thing that could overcome the problems of IL-2.”
The company formed with the help of UW’s CoMotion, which offers support to early-stage companies and has launched more than two dozen startups in the past two years. Other biotech startups from CoMotion include PvP Biologics, which is developing a therapy for celiac disease, and Cyrus Biotechnology, a software-as-a-service company for protein design.
Neoleukin plans to develop the protein further with the aim of creating a biopharmaceutical and has secured an exclusive license on the intellectual property that came out of the research. One of the first major goals is to see if Neo-2/15, the synthetic protein, can beat IL-2 in the treatment of melanoma and renal cell carcinoma.
If successful, Neo-2/15 could be “like stepping on the gas” in treating certain cancers, providing a significant boost to a patient’s immune system, Drachman said. “The long-term opportunity is to grow a company that is a leader in de novo protein therapeutics.”
