Jazz Pharmaceuticals’ pipeline has oncology bets sprinkled throughout, but nothing in cancer immunotherapy. The company is turning to Werewolf Therapeutics to fill that gap, striking a deal to get a cytokine therapy that’s on the path to clinical testing.
According to financial terms announced Thursday, Dublin-based Jazz is paying $15 million up front for global rights to Werewolf drug WTX-613. Milestone payments could bring Werewolf, based in Cambridge, Massachusetts, up to $1.26 billion. If Jazz is able to commercialize its new asset, it would pay Werewolf royalties on the drug’s sales.
Cytokines are signaling proteins that can spark an immune response. Engineered versions of these proteins have been used for decades as cancer treatments. However, as these drugs circulate through the body, they spark an immune response that goes beyond cancer cells—a toxic effect that limits their use. Cytokine therapies also don’t have a long-lasting therapeutic effect. Werewolf and other biotech companies have been engineering a new generation of cytokine therapies intended to provide a safer and more effective immune response.
The Werewolf platform technology, called Predator, engineers a cytokine in a way that shields it from binding to anything until it reaches a tumor. The therapy is also designed to have a longer half-life, overcoming the durability issues of earlier cytokine therapies. WTX-613 is an engineered version of a cytokine called interferon alpha.
Last December, Werewolf presented promising preclinical data for its version of interferon alpha during the annual meeting of the American Society of Hematology. In a mouse model for blood cancer, Werewolf reported that its drug stopped tumor growth and activated responses from two types of immune cells, natural killer cells and CD8+ cells. The company also reported that the drug showed an extended half-life compared to native interferon alpha.
With the encouraging preclinical data in hand, Werewolf planned to submit an investigational new drug application with the FDA in 2023. That timeline is still intact, but Jazz now plans to make that FDA filing.
“This transaction underscores our commitment to enhancing our pipeline to deliver novel oncology therapies to patients, and also provides us with an opportunity to expand into immuno-oncology,” Rob Iannone, executive vice president, global head of research and development of Jazz Pharmaceuticals said in a prepared statement.
For Werewolf, the Jazz deal means the biotech can keep its focus on its lead programs. WTX-124 is an engineered version of a cytokine called interleukin-2, while WTX-330 is Werewolf’s version of interleukin-12. The biotech said it expects to file investigational new drug applications for both programs later this year.
There’s plenty of cytokine competition facing both Jazz and Werewolf. Last November, the FDA approved Besremi, an interferon alpha drug that PharmaEssentia drug developed for polycythemia, a rare blood cancer. Asher Bio emerged from stealth last year with technology for engineering a better, potentially more targeted version of IL-2. Xilio Therapeutics aims to improve on cytokine safety with a “mask” that stays on the therapy until it reaches the tumor microenvironment. That company’s IL-2 program is on track for an investigational new drug application this year.
Meanwhile, Avenge Bio is taking a cell therapy approach to cytokines. The company contends that human IL-2 could have advantages over engineered versions. Its approach employs immune cells engineered to produce IL-2. Those cells are implanted at the tumor site to localize the immunotherapy’s effect.
Photo by Flickr user Five Furlongs via a Creative Commons license
