Incyte Announces New Positive Data for INCA033989, its First-In-Class mutCALR-Targeted Monoclonal Antibody, in Patients with Myelofibrosis Presented at ASH 2025

Core Insights - Incyte announced new clinical data from two Phase 1 studies on INCA033989, a first-in-class monoclonal antibody targeting mutant calreticulin (mutCALR) for patients with myeloproliferative neoplasms (MPNs) [1][2] - The studies evaluated INCA033989 as a monotherapy and in combination with ruxolitinib for patients with myelofibrosis (MF) who are resistant or intolerant to JAK inhibitors [1][2] - Preliminary results showed promising efficacy and safety profiles, with plans for a registrational program in 2026 [2][8] Study Results - In the monotherapy arm, 41.7% of evaluable MF patients achieved a spleen volume reduction of 25% (SVR25) and 33.3% achieved a 35% reduction (SVR35) at Week 24 [5] - Among patients not previously treated with JAK inhibitors, 71.4% achieved SVR25 and 57.1% achieved SVR35 [5] - In the combination therapy arm, 81.3% of patients experienced symptom improvement, with 33.3% achieving a 50% reduction in total symptom score (TSS50) [5] Safety and Tolerability - INCA033989 was well-tolerated, with no dose-limiting toxicities reported in both monotherapy and combination therapy arms [4][6] - The most common treatment-emergent adverse events (TEAEs) were anemia, fatigue, and thrombocytopenia, primarily Grade 1 [13] - Only two patients discontinued treatment due to TEAEs, indicating a favorable safety profile [13] Future Plans - Incyte plans to initiate a registrational program for INCA033989 in MF in 2026, building on the positive results observed [2][8] - The drug is also being evaluated for essential thrombocythemia (ET), with Breakthrough Therapy designation granted by the FDA for patients with Type 1 CALR mutations [8][11] Industry Context - Myelofibrosis (MF) is considered one of the most aggressive types of MPNs, characterized by bone marrow fibrosis and debilitating symptoms [7] - The development of targeted therapies like INCA033989 represents a significant advancement in the treatment landscape for MPNs, particularly for patients who are resistant or intolerant to existing therapies [10][11]