Halozyme and Incyte will advance subcutaneous INCA033989 for mutCALR-positive MPNs, with the aim of improving treatment delivery while supporting targeted clinical development.
Halozyme Therapeutics has entered a global
Drug: INCA033989, mutCALR-targeted monoclonal antibody
Indication: mutCALR-expressing MPNs (ET, myelofibrosis)
Technology: Enhanze (rHuPH20), subcutaneous delivery
Deal: Halozyme licenses Enhanze to Incyte
Terms: Upfront payment, milestones, and royalties
Status: INCA033989 in phase 1; subcutaneous formulation now in development
"This collaboration with Incyte underscores the continued momentum and broad applicability of our [Enhanze] technology across high-value therapeutic areas," said
Under the agreement, Halozyme will receive an upfront payment from Incyte and is eligible for additional payments tied to development, regulatory, and commercial milestones, along with royalties on net sales of any commercialized medicines using Enhanze. The dollar value of the upfront payment or potential milestone payments was not disclosed.
INCA033989 is designed to selectively target mutCALR, a driver mutation present in an estimated 20% to 30% of patients with MPNs, a group of clonal blood cancers that includes essential thrombocythemia (ET) and myelofibrosis (MF).2 Despite mutCALR's prevalence, the MPN treatment landscape has historically lacked an agent that selectively targets the mutation itself, with most available options acting downstream through JAK inhibition or nonspecific cytoreduction.2
INCA033989 functions as an antagonist that blocks mutCALR-driven activation of the thrombopoietin receptor (TPO-R). Preclinical data describe this mechanism as capable of normalizing TPO-R signaling without affecting normal hematopoiesis.2 In phase 1 data presented at the American Society of Hematology's 2025 annual meeting, Incyte reported that INCA033989 monotherapy and combination treatment with ruxolitinib (Jakafi) produced reductions in spleen volume and symptom burden, along with improvements in anemia, in patients with mutCALR-positive myelofibrosis (dose range 24 mg to 2,500 mg), with a safety profile the company described as favorable.3 Incyte has said it plans to initiate a registrational program evaluating INCA033989 in ET in 2026.3
Enhanze, the technology at the center of the new agreement, pairs Halozyme's proprietary recombinant human hyaluronidase enzyme (rHuPH20) with a partner's biologic to enable subcutaneous rather than intravenous administration. The technology has been used in 10 commercialized products across more than 100 global markets, touching more than 1 million patient lives, and is licensed to companies including Roche, Takeda, Pfizer, Janssen, AbbVie, Eli Lilly and Company, Bristol-Myers Squibb, argenx, ViiV Healthcare, Chugai Pharmaceutical, Acumen Pharmaceuticals, Merus, Skye Bioscience, and GSK.1
The agreement extends a pattern of Enhanze licensing deals Halozyme has signed in 2026, including prior collaborations with GSK, Takeda, and Skye Bioscience. Because INCA033989 remains in early-stage clinical development, Enhanze's application in this Incyte collaboration is preparatory rather than tied to an approved or late-stage product
The company’s announcement does not specify a timeline for when a subcutaneous formulation of INCA033989 might enter clinical testing, nor does it detail which additional targets Incyte may nominate under the agreement's option. INCA033989 itself remains investigational, with registrational studies in ET not yet initiated as of the companies' most recent public disclosures.1,3
