A year after coming out of the shadows, Werewolf Therapeutics is kicking it up a notch. With $72 million in new financing, the company will push two shape-shifting cytokine drugs into the clinic and ramp up its discovery and preclinical work.
Werewolf is working on a pipeline that delivers the promise of cytokines without their nasty side effects. Known as Indukines, Werewolf’s candidates are “switched off” when they’re given to patients and activate only when they arrive in cancer cells.
RELATED: Sanofi inks $2.5B Synthorx takeover to gain IL-2 cancer drug
Since raising a $56 million series A round in November 2019, the company has brought forward three programs based on the cytokines interferon alpha, interleukin-2 and interleukin-12. The series B round, drawn from a laundry list of old and new backers—including RA Capital Management, Deerfield Management, MPM Capital and Longwood Fund—will get the latter two programs through phase 1 trials and propel other preclinical-stage prospects toward the clinic.
Cytokines, such as interleukin-2, emerged decades ago as promising cancer treatments. But they evolved as signaling molecules and not as drugs, so it’s no surprise that they’re missing some key pharmaceutical features that would make them good drugs.
“These mechanisms are a very powerful way to stimulate the immune system to attack tumors, but unfortunately, a number of cytokines can activate the immune system in an adverse way where it can attack normal tissues,” Werewolf CEO Daniel Hicklin, Ph.D., said. Werewolf’s protein engineering technology is designed to limit its drugs’ effects on healthy tissues.
The company isn’t sharing yet which cancer types it’s looking at—just that its lead programs, WTX-124 and WTX-330, are based on interleukin-2 and interleukin-12, respectively. It’s developing its programs for use on their own as well as in combination with other cancer treatments such as checkpoint inhibitors, in the hopes of making such treatments accessible to more patients.
RELATED: Synthekine debuts with $82M, Stanford tech to create a new generation of cytokine therapies
Now that it’s landed on its first development candidates, Werewolf is ready to rev up its discovery engine.
“There are over a dozen pro-inflammatory cytokines that have some level of validation around them in terms of antitumor activity. Now that we’re able to establish proof of concept for the platform, we are certainly interested in exploring some of those additional mechanisms,” Hicklin said. “Our goal is to establish a number of programs that cover a diversity of immune stimulatory mechanisms because we don’t feel that any one mechanism will address all of the unmet need."
Other players hoping to make better cytokines for cancer treatment include Synthekine, which launched in September with $82 million, and Bright Peak Therapeutics, which debuted in July with $35 million. And Sanofi bet big on the approach in December 2019, when it inked a $2.5 billion deal to acquire Synthorx.