On November 4, 2025 Prelude Therapeutics Incorporated (Nasdaq:PRLD), a clinical-stage precision oncology company, reported an exclusive option agreement with Incyte (Nasdaq:INCY) focused on Prelude’s previously undisclosed mutant selective JAK2V617F JH2 inhibitor program in development for patients with myeloproliferative neoplasms (MPNs). Per the agreement, Incyte secures an exclusive option to acquire the JAK2V617F program in exchange for an upfront payment and a strategic equity investment in Prelude, plus potential downstream milestones and royalties.

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Kris Vaddi, Ph.D., Chief Executive Officer of Prelude stated, "We’re pleased to put this agreement in place with Incyte, recognized global leaders in the MPN field. Prelude and Incyte both aim to deliver transformational treatments to improve upon the standard of care established with first generation JAK2 JH1 inhibitors like Jakafi (ruxolitinib). Our research team made significant progress discovering the first known inhibitors that bind into the JAK2 JH2 ‘deep pocket’ where the V617F mutation resides. These potent and orally bioavailable compounds demonstrate mutant specific inhibition and the potential for disease modification in multiple preclinical models of MPNs. Today’s agreement with Incyte provides us with the capital needed to advance further our JAK2V617F program, while also allowing us to advance the development of our other pipeline programs."

"The agreement with Prelude provides an opportunity to enhance our robust portfolio of clinical and preclinical JAK2V617F candidates for patients with MPNs," said Bill Meury, President and Chief Executive Officer of Incyte. "This transaction aligns with our strategy to develop new and innovative therapies poised to make a meaningful difference for patients."

Terms of the Agreement
Under the terms of the Transaction Agreement, Incyte secures an exclusive option to acquire Prelude’s mutant selective JAK2V617F JH2 inhibitor program, including Prelude’s library of preclinical candidates. Prelude will receive $60 million in capital, comprised of an upfront payment of $35 million, plus a $25 million equity investment by Incyte in Prelude. Incyte will purchase 6.25 million shares of Prelude non-voting common stock at a price of $4.00 per share at deal close. Prelude intends to apply the upfront payment and net proceeds from the sale of the purchased shares to advance the JAK2V617F program and other pipeline assets, and for working capital and general corporate purposes.

Prelude expects to advance the JAK2V617F program to pre-defined milestones. Incyte may elect to exercise its exclusive option during the option period to acquire the program and associated assets from Prelude for $100 million. As the JAK2V617F program candidates advance in the clinic, Prelude would be eligible to receive up to $775 million in additional clinical and regulatory milestones, and single digit royalties on global net sales. Combined, total potential cash payments from the transaction, excluding royalties, could reach up to $910 million.

If Incyte elects to not exercise its option to acquire the program, all JAK2V617F global program rights and interests would remain in the sole ownership and control of Prelude.

Prelude Therapeutics was advised on the transaction by Morgan Lewis & Bockius LLP as legal counsel.

Mutant selective JAK2V617F JH2 inhibitor program
JAK2V617F is the primary driver mutation responsible for disease progression in the majority of patients living with myeloproliferative neoplasms (MPNs). The mutation impacts approximately 95% of patients with polycythemia vera (PV), 60% of patients with essential thrombocythemia (ET) and 55% of patients with myelofibrosis (MF). Identifying JAK2 JH2 inhibitors that selectively target V617F+ cells has long been a shared goal and challenge for industry. If successful, this approach has potential to reduce mutant allele burden, modify disease progression, and transform treatment outcomes for MPN patients. Prelude has discovered novel allosteric inhibitors that bind into the JAK2 JH2 "deep pocket" where the V617F mutation resides. These candidates demonstrate mutant specific inhibition in multiple preclinical models of MPNs. The first disclosure of program data was accepted for oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 67th Annual Meeting taking place in Orlando, FL December 6-9, 2025. The abstract can be found on the ASH (Free ASH Whitepaper) 2025 website ASH (Free ASH Whitepaper) Annual Meeting & Exposition – Hematology.org.

(Press release, Prelude Therapeutics, NOV 4, 2025, View Source [SID1234659368])