Jazz Howls at Immuno-Oncology Success with Werewolf Alliance (UPDATED)

Here's more about the immuno-oncology success of Jazz Pharmaceuticals. Michael Vi/Shutterstock 

Jazz Pharmaceuticals continues to advance its efforts toward becoming a leading oncology company via a key licensing deal with Werewolf Therapeutics for WTX-613, an engineered IFN⍺2b cytokine pro-drug, which is currently in preclinical development. The deal marks the first immuno-oncology program for Jazz Pharma.

Rob Iannone, global head of research and development at Jazz, expressed excitement about the potential of the Werewolf cancer asset. He told BioSpace that it has the potential to complement, rather than compete with, a broad range of currently utilized oncology treatments.

“WTX-613 is an immuno-oncology agent being developed to minimize the severe toxicities that have been observed with systemically delivered recombinant IFNα therapy and maximize clinical benefit when administered as monotherapy or in combination with other agents,” Iannone said.

He pointed to compelling proof-of-concept data Werewolf presented at the American Society of Hematology meeting last year that showed how a surrogate WTX-613 molecule demonstrated anti-tumor activity in preclinical models. Those WTX-613 molecules were also well-tolerated, according to Werewolf’s own announcement.

How was Immuno-Oncology Created?

WTX-613 immuno-oncology was created leveraging Werewolf's proprietary PREDATOR protein engineering technology. Type 1 interferon signal transduction by IFNα agonism is a clinically validated mechanism of action. Jazz noted in its announcement that IFNα has been shown to “work synergistically in combination with other proven therapies,” which includes immune checkpoint inhibitors, targeted therapies and chemotherapy. Because of this synergy, the company believes WTX-613 has applications across a wide range of cancer types, combination regimens and lines of therapy. Jazz anticipates seeking approval from the U.S. Food and Drug Administration for in-human studies next year.

Initially, Iannone said Jazz intends to explore WTX-613 in monotherapy trials and, eventually, as part of combination regimens where anti-PD-1 agents may be a potential combination partner. The company will explore other tumor types and/or combinations based on where it observes activity, Iannone said.

Additionally, Iannone said the company believes that WTX-613 immuno-oncology has the potential to minimize the toxicity currently associated with systemic IFNα therapy, something that has plagued developmental assets across the oncology space. WTX-613 is designed to specifically activate within the tumor microenvironment where it can then stimulate IFNα receptors on cancer-fighting immune effector cells.

"We are excited about the potential of WTX-613, Iannone said. “WTX-613 is aligned with our objective to explore areas where we have unique insights, there are critical unmet patient needs, and we can commercialize efficiently.”

Daniel Hicklin, president and chief executive officer of Werewolf Therapeutics, echoed Iannone’s thoughts on WTX-613. He expressed excitement about the partnership with Jazz, noting that through the collaboration, Jazz will drive WTX-613 into the clinic, which provides his company more space to advance their lead programs, WTX-124, which introduces a conditionally activated IL-2 INDUKINE molecule, and WTX-330, an IL-12 INDUKINE molecule, through expected Investigational New Drug application filings later this year.

“Jazz understands the mechanism of action for -613 very well and is the perfect partner to develop it,” Hicklin told BioSpace Thursday morning.

He noted that Jazz had become interested in WTX-613 immuno-oncology and the company’s conditionally activated INDUKINE products based on Werewolf’s efforts with its wild-type cytokines that are designed to unleash an immune response only at the site of the target and not negatively impact healthy cells. Werewolf’s INDUKINE molecules contain four components: a cytokine, an inactivation domain, a half-life extension domain and a proprietary protease-cleavable linker. 

Under terms of the deal, Werewolf will receive an upfront payment of $15 million. As WTX-613 progresses through the clinic, the value of the licensing deal could grow to $1.26 billion. If commercialized, Werewolf would then be eligible for royalties as well.

Jazz’s momentum into immuno-oncology continues following the 2021 approval of Rylaze, a new leukemia drug aimed at patients who have developed hypersensitivity to E. coli-derived asparaginase, an enzyme that is a common component of the chemotherapy regimen used with leukemia patients.

Last month, the company enrolled the first patient in its EMERGE 201 study, which will assess Zepzecala (lurbinectedin) as a monotherapy in various solid tumors. Zepzecala was approved in 2020 under the accelerated approval program for small cell lung cancer. Jazz hopes that Zepzecala, an alkylating drug that binds guanine residues within DNA, will prove to be safe and effective in different solid tumor types, including urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and homologous recombination deficient tumors

At the American Association of Cancer Research (AACR) meeting this week, Jazz will present data from the pan-RAF inhibitor JZP815 development program that will form the basis of an IND application later this year.

Iannone said the company will continue to identify and advance promising treatments and novel combinations in order to deliver at least five additional novel therapies to patients by the end of the decade as part of the company’s Vision 2025, which was announced earlier this year. Under this new image, Jazz Pharmaceuticals sees itself as a company that has expertise in neuroscience, which includes sleep and movement disorders, as well as immuno-oncology.

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