Synthekine nabs megaround in bid to edge out Merck, Sanofi in IL-2 sprint
Nine months after launching out of Stanford with $82 million and a portfolio of engineered cytokines, Synthekine has landed a $107.5 million Series B from Deerfield Management and others to push their two lead cancer programs into the clinic.
Like a smattering of rivals, Synthekine is trying to reimagine one of the most notorious cancer drugs in history: IL-2, a synthetic version of an immune messenger molecule that proved too potent for most patients to tolerate, even though it could be highly effective at amping the immune system to attack tumors. The industry-wide hope is that new approaches to protein engineering, along with some creative thinking, could allow developers to distill the tumor-shrinking power, without all the toxicities.
IL-2 is toxic in part because it has a three-pronged receptor that binds to and activates all types of T cells; the goal is to build one that only activates tumor-killing T cells. Most companies, including Sanofi and Merck, have tried to get at the problem by building artificial proteins that don’t have the prong, called alpha, that activates so-called regulatory T cells. That leaves only the two prongs, called beta and gamma, that activate the killers.
Synthekine will use their new pot of gold to get an alternative path. They argue that alpha is abundant on the best T cells: T cells that are already programmed to attack the tumor, AKA antigen-specific killer T cells. So they’ve acquired an IL-2 that, with a mixture of specially modified alpha and beta prongs, bonds virtually only to those cells.
“We had a different biological thesis,” he told Endpoints News. “In these experiments, our molecule has looked universally better.”
Synthekine will look to file an IND for their IL-2 toward the end of this year. A few months later, they also plan to file an IND on their second program, where they’ll look to use a different custom-built IL-2 as an on/off switch for CAR-T. Using a form of the protein that only binds to a specific pocket they’ve engineered onto their CAR-T cells, they hope to use the IL-2 to help the cells proliferate whenever needed.
Ideally, Ray said, that will allow doctors to give lower doses of cells early on and then modulate the amount of IL-2 over the ensuing months and years to ensure that a patient’s response lasts as long as possible.
The round, co-led by Janus Henderson Investments, will also allow the California biotech to continue their early-stage discovery work on a handful of follow-up molecules, both for cancer and autoimmune diseases. They’ve already licensed three in April from the lab of their founder, Chris Garcia: IL-10, IL-12 and IL-22.
But Ray is particularly excited about their namesake, what they call the “synthekine platform.” The company, he said, is working on a class of molecules that are designed entirely synthetically, rather than by relying on the natural protein. That could open up the potential for new types of therapies, untethered by the structure millions of years of evolution have hammered in.
“We think that could be truly revolutionary to the field,” he said.