On April 7, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and Werewolf Therapeutics, Inc. (Nasdaq: HOWL) reported that the companies have entered into a licensing agreement under which Jazz has acquired exclusive global development and commercialization rights to Werewolf’s investigational WTX-613, a differentiated, conditionally-activated interferon alpha (IFNα) INDUKINE molecule (Press release, Jazz Pharmaceuticals, APR 7, 2022, View Source [SID1234611640]).

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"We believe WTX-613 has the potential to minimize the toxicity associated with systemic IFNα therapy, preferentially delivering IFNα to tumors, and thereby expanding its clinical utility in treating cancer. We are excited about the potential of WTX-613 based on compelling proof-of-concept data, recently presented at ASH (Free ASH Whitepaper), where a WTX-613 surrogate molecule demonstrated anti-tumor activity in preclinical models," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "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. We will continue to identify and advance promising treatments and novel combinations as we aim to deliver at least five additional novel therapies to patients by the end of the decade as part of our Vision 2025."

WTX-613 is currently in preclinical development. Jazz expects to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for WTX-613 in 2023.

"We are thrilled to join forces with Jazz to advance WTX-613 on behalf of patients," said Daniel J. Hicklin, Ph.D., president and chief executive officer of Werewolf. "This partnership comes at an exciting time for Werewolf and enables WTX-613 to rapidly move toward the clinic, while we continue to advance our lead programs, WTX-124 and WTX-330, through expected IND filings this year."

WTX-613 is an engineered IFN⍺2b cytokine pro-drug that is activated specifically within the tumor microenvironment where it can stimulate IFNα receptors on cancer-fighting immune effector cells. The aim of WTX-613 is to minimize the severe toxicities that have been observed with systemically active recombinant IFNα therapy and maximize clinical benefit when administered as monotherapy or in combination with other agents. Type 1 interferon signal transduction by IFNα agonism is a clinically validated mechanism of action, and IFNα has been shown to work synergistically in combination with other proven therapies including immune checkpoint inhibitors, targeted therapies and chemotherapy. This allows for potential application of WTX-613 across a wide range of cancer types, combination regimens and lines of therapy. WTX-613 was created leveraging Werewolf’s proprietary PREDATOR protein engineering technology, which integrates specialized protein design elements to enhance activity, stability and tumor selectivity within a single molecule, called INDUKINE molecules.

At the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021, Werewolf presented data from a surrogate WTX-613 INDUKINE molecule that demonstrated tumor stasis lasting beyond the treatment phase, efficiently blocked tumor growth, activated NK and CD8+ cell responses and induced antigen-presenting cell and effector cell markers in preclinical models.

Transaction Details
Under the terms of the transaction, Jazz has secured exclusive global rights to WTX-613. Jazz will make an upfront payment of $15 million to Werewolf, and Werewolf is eligible to receive development, regulatory and commercial milestone payments of up to $1.26 billion. Pending approval, Werewolf is eligible to receive a tiered, mid-single-digit percentage royalty on net sales of WTX-613.