Incyte Corporation (NASDAQ:INCY) on Sunday revealed new clinical data from two Phase 1 studies of INCA033989 for mutCALR-expressing myeloproliferative neoplasms (MPNs) at the 2025 American Society of Hematology (ASH) Annual Meeting.
The preliminary analysis (data cut off September 25, 2025) evaluated the safety and efficacy of INCA033989 in myelofibrosis (MF) patients with as measured by spleen volume reduction ≥25% (SVR25) and ≥35% (SVR35), change in MPN-Symptom Assessment Form (SAF), total symptom score (TSS), anemia response and mutCALR variant allele frequency (VAF) reduction.
Exploratory analyses from the clinical studies of INCA033989 demonstrate the potential for disease-modifying activity in MF patients with a CALR mutation, the company said in a press release.
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Monotherapy Arm of the Trials
In the monotherapy arms, patients treated with INCA033989 experienced rapid and robust spleen and anemia responses and symptom improvements.
At Week 24, 41.7% of all evaluable patients achieved SVR25, and 33.3% (12/36) achieved SVR35.
Among patients not previously treated with a JAK inhibitor, 71.4% (5/7) achieved SVR25, and 57.1% (4/7) achieved SVR35.
Among those resistant or intolerant to JAK inhibitor treatment, 34.5% (10/29) and 27.6% (8/29) achieved SVR25 and SVR35 at Week 24, respectively.
Anemia response occurred in more than half (56%; 14/25) of evaluable anemic patients, with 40% (10/25) of patients achieving a major response with INCA033989 treatment.
Nearly all patients treated with INCA033989 (93.3%) experienced improved symptoms, with 60% (27/45) achieving a ≥50% reduction in TSS (TSS50) as best response. At Week 24, 39.4% (13/33) of patients achieved a TSS50.
Most patients (89.4%; 42/47) with ≥1 post-baseline VAF measurement experienced a reduction in mutCALR VAF, and 10.6% (5/47) achieved a ≥25% best reduction in VAF.
Most patients (76.5%) in the studies had co-occurring mutations. Of those, 40.5% of response-eligible patients achieved SVR35 or an anemia response. Single-cell analyses in MF patients with high clonal complexity showed consistent reductions in all CALR-mutant clones, regardless of the presence of co-occurring variants.
Ruxolitinib Combination Arm of the Trials
In the INCA033989 and ruxolitinib combination arms, most MF patients experienced spleen volume reductions and symptom improvements.
At Week 24, half (50%; 6/12) of all evaluable MF patients achieved SVR25, and 25% (3/12) achieved SVR35.
Among the 14 evaluable patients, 86% had stable anemia, and one patient with non-transfusion dependent anemia had a major anemia response.
The majority of patients (81.3%; 13/16) treated with INCA033989 in combination with ruxolitinib experienced symptom improvement, and 33.3% (3/9) achieved TSS50 at Week 24.
INCA033989 was well-tolerated, both as a monotherapy and in combination with ruxolitinib
In addition to myelofibrosis (MF), INCA033989 is also being evaluated in Phase 1 studies for the treatment of patients with essential thrombocythemia (ET).
The company plans to initiate a registrational program evaluating INCA033989 for ET patients harboring a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy in 2026.
INCY Price Action: Incyte shares were down 2.46% at $99.99 during premarket trading on Monday, according to Benzinga Pro data.
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