Werewolf Therapeutics uncloaks with $56M and shape-shifting cancer meds

Werewolf is using its aptly named PREDATOR protein engineering technology to create this new class of drugs that are "switched off” until they reach their destination, where they switch on. (Werewolf Therapeutics)

It’s a full moon for Werewolf Therapeutics as the company comes out of stealth with $56 million and an approach it believes can cut through the toxic effects that have limited the use of certain cancer-killing agents.  

The series A, led by MPM Capital and Longwood, will allow Werewolf to bring two programs into the clinic, though the Cambridge, Massachusetts-based biotech says it’s too early to say which kinds of cancer it’s aiming at. Taiho Ventures, Arkin Bio Ventures, UPMC Enterprises and DC Investment Partners also chipped into the round. 

“We are working with a number of mechanisms that have been either preclinically or clinically validated to some extent, such as pro-inflammatory cytokines or immune receptor agonists,” the company’s founder and CEO Daniel Hicklin, Ph.D., told FierceBiotech. 

Drugs that dial up these mechanisms call forth a “very potent immune responses against tumor tissue,” Hicklin said, but they can also harm healthy tissue, especially if they’re given to patients systemically. Werewolf is working on medicines that are delivered systemically, but—thanks to their structural design—stay inactive within the body until they reach a tumor. There, the drugs will shape-shift into active versions of themselves and provoke an immune response to attack the tumor. 

That’s where the company’s name comes from: “The whole idea was to try and capture the imagery of an agent that is masked in normal life, but exposes its predatory and destructive power, but only in a selective moment in time,” said Luke Evnin, Ph.D., Werewolf chairman and co-founder and managing director at MPM Capital. 

It’s been difficult to develop drugs that “step on the gas” of the immune system rather than “braking” it as checkpoint inhibitors do, Evnin said. 

One of the reasons is that drugs tend to stimulate the immune system in a broad, nonspecific way, provoking a response that could harm normal tissues, Hicklin said. 

Werewolf is using its aptly named PREDATOR protein engineering technology to create this new class of drugs that are "switched off” until they reach their destination, where they switch on. The company is “taking great pains” not to compromise potency when making them conditionally active, Hicklin said. 

Its first focus will be to create what it calls Indukines, or cytokines that activate only in the tumor microenvironment. The company aims to select two programs to move into the clinic in the next six months, Hicklin said. 

He won’t be doing it alone. The former CEO of Potenza Therapeutics has brought along several of his old colleagues after the company’s $165 million sale to Astellas last December. They include Chief Scientific Officer Cynthia Seidel-Dugan and Chief Operating Officer Reid Leonard—both of whom are reprising the roles they held at Potenza—and Bill Winston, Ph.D., and Andres Salmeron, Ph.D., who came along as vice president of research and VP of immunology, respectively. 

“The immuno-oncology space is pretty young and it started out as just a handful of people, so there are not many teams that have had repeat successes in the space,” Evnin said. “The team at Werewolf today is one of those very rare teams.”

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