Incyte Sets Mid-Year Phase 3 Trial for CALR Antibody 989 as Pipeline Updates Roll Out

Key Points

• Incyte plans to start a Phase 3 trial of mutant CALR antibody 989 in essential thrombocythemia around mid-year, after productive FDA discussions and with breakthrough therapy designation in hand. The study will test 989 against best available therapy and uses a 24-week endpoint aimed at faster readout.
• Myelofibrosis remains a more complicated path because there is no quick biomarker like platelet counts in ET, so Incyte is weighing endpoints such as spleen reduction, symptoms, VAF, and anemia response. The company expects more regulatory clarity after mid-year and may discuss a composite endpoint with the FDA.
• Incyte is also pushing a subcutaneous version of 989 even though registration studies will begin with IV dosing. The company sees this as important for long-term patient convenience, especially in ET, and hopes to bridge to a subcutaneous launch shortly after the initial IV rollout.

Incyte NASDAQ: INCY Chief Medical Officer Steven Stein outlined the company’s development priorities across hematology, oncology and immunology, with a particular focus on its mutant CALR antibody 989, during a company news event.

Stein said myeloproliferative neoplasms remain “front and center” for Incyte’s hematology strategy, describing mutation-specific therapies as the next step beyond broader JAK-STAT inhibition. The company’s first program in that area is 989, which is being developed initially in essential thrombocythemia, or ET, and myelofibrosis, or MF.

989 Phase 3 ET Trial Set to Begin Mid-Year

Stein said Incyte plans to begin a Phase 3 trial of 989 in ET around mid-year following discussions with the U.S. Food and Drug Administration. He characterized the company’s interactions with the agency as highly collaborative and noted that 989 has breakthrough therapy designation.

In ET, Stein said mutant CALR accounts for about 25% of all cases, and the setting provides a “clean environment” for study because platelet levels serve as a sensitive pharmacodynamic marker. He said that feature helped Incyte secure an abbreviated endpoint timeline in its Phase 3 design.

The planned study will enroll all comers with mutant CALR ET rather than separating patients by mutation subtype at the site level. Patients will begin at 750 mg, and those who have not reached a platelet threshold of 400 or below by cycle two, day one, will escalate to 2,500 mg. Stein said Incyte expects most type 1 mutation patients to remain controlled at 750 mg, while a larger share of non-type 1 patients may require escalation.

The primary endpoint will be complete hematologic control for at least 12 weeks, measured at 24 weeks rather than the 52-week timeframe used in some other programs. Stein said the endpoint includes platelets below 400, white blood cells below 11,000, and no thrombosis or bleeding. The study will compare 989 against best available therapy, which Stein said may include hydroxyurea, anagrelide and interferons.

Stein also said the FDA encouraged Incyte to include variant allele frequency, or VAF, as a secondary endpoint, given the potential for disease modification. He said Incyte plans to show data at the European Hematology Association meeting correlating VAF reductions of at least 25% with hematologic response.

Myelofibrosis Path Forward Remains Under Discussion

For myelofibrosis, Stein said the regulatory path is more complex because there is no similarly rapid biomarker like platelets in ET. Instead, the company is evaluating spleen volume reduction, symptom control, VAF reduction and anemia response.

At EHA, Stein said Incyte expects to present data on about 80 MF patients, with a substantial portion having 24 weeks of follow-up in the second-line setting. He said the abstract showed a 58% anemia response rate, which he described as supporting potential disease-modifying activity.

Stein said the company’s immediate assumption is that a registration study could use established endpoints such as spleen volume reduction of at least 35% and symptom measures. However, he said Incyte would like to discuss a composite endpoint with the FDA, citing work from the European Leukemia Network suggesting that measures involving hemoglobin, blast count, platelets and spleen may correlate more directly with overall survival and leukemia-free survival.

He said the company hopes to have regulatory clarity sometime after mid-year and to update investors on its third-quarter call. The likely second-line MF control arm would be best available therapy, potentially including ruxolitinib, fedratinib, momelotinib, pacritinib, hydroxyurea, danazol and lenalidomide.

Subcutaneous Formulation Remains a Strategic Goal

Stein said 989 will start in registration studies as an intravenous therapy, but developing a subcutaneous formulation is important, particularly for ET patients who may otherwise face years of clinic or infusion center visits.

Incyte has completed a healthy volunteer study to assess bioavailability and is moving into patients for additional evaluation. Stein said the company is working with the FDA-approved enFuse device, which can hold up to 25 mL and may allow administration over roughly 10 to 20 minutes depending on volume.

He said the company is comfortable that it can fit the intended top dose into a single device, though likely toward the upper end of the device’s volume capacity. Stein said the second-line ET registration study is expected to be intravenous, with a potential launch in 2029, and that Incyte has an agreement with the FDA to conduct bridging work that could allow a subcutaneous version within six months of launch. He said a first-line MF study is intended to use subcutaneous 989 from the start.

Updates on JAKAFI XR, Tafasitamab and Other Pipeline Programs

Stein also discussed Jakafi XR, saying Incyte has launched the extended-release version at price parity with the immediate-release formulation. He said payer formulary coverage is the key near-term focus, with the company aiming to reach 50% to 70% coverage as quickly as possible.

He said 2026 could represent the first full year with adequate formulary coverage, with a potential $100 million sales year, while a longer-term conversion rate around 20% could support a $500 million to $700 million product. Stein cautioned that the company needs to advance beyond reliance on Jakafi XR by that time.

In oncology, Stein highlighted positive Phase 3 data for tafasitamab in first-line diffuse large B-cell lymphoma. He said the study, which will be presented in plenary sessions at ASCO and EHA, showed a hazard ratio of 0.75 and a P value of 0.019. He described it as the second positive study in first-line diffuse large B-cell lymphoma in 25 years.

Stein said investors should focus on additional endpoints, cell-of-origin data and two-year progression-free and event-free survival results. He said Incyte sees tafasitamab adding to its existing business in the $300 million to $400 million range, while noting the company has been measured in its expectations given the broader competitive landscape.

Immunology Opportunities Include Povo and OPZELURA

Stein said Incyte sees a substantial opportunity for povorcitinib, referred to as “povo,” in hidradenitis suppurativa, or HS. He said longer-term data at 54 weeks looked stronger than the 12-week endpoint previously presented, with HiSCR rates “where biologics are,” strong pain control and encouraging draining tunnel data.

He estimated about 300,000 HS patients, with roughly 200,000 treated, and said Incyte hopes to launch early next year and have a full year in 2027. Stein said the company wants to use povo in both pre-biologic and post-biologic settings and believes around $500 million in sales is achievable in HS. If vitiligo and prurigo nodularis are added, he said the opportunity could exceed $1 billion.

For OPZELURA in mild HS, Stein said enrollment has been strong enough that adding 100 patients to each study did not affect timelines. He said the expansion was intended to help control for placebo response. Stein described OPZELURA as a potential topical option for mild HS, with povo positioned for moderate and more severe disease.

About Incyte NASDAQ: INCY

Incyte Corporation is a Wilmington, Delaware–based biopharmaceutical company focused on the discovery, development and commercialization of novel therapies in oncology and inflammation. Since its founding in 2002, Incyte has grown from a small research organization into a global enterprise, advancing a portfolio of internally developed and partnered assets. The company's research and development efforts center on small-molecule drugs and biologics that modulate critical signaling pathways implicated in cancer, autoimmune disorders and rare diseases.

The company's flagship product is Jakafi® (ruxolitinib), a Janus kinase (JAK) inhibitor approved for the treatment of myelofibrosis and polycythemia vera.

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