Incyte (INCY) Earnings Call Presentation

INCA033989 Clinical Trial Results and Safety - INCA033989 demonstrated a favorable safety profile in ET patients, with only 1 out of 49 patients discontinuing therapy due to treatment-emergent adverse events [101, 135] - INCA033989 led to rapid and sustained normalization of platelet counts in previously treated ET patients [105, 135] - Hematologic responses were achieved early and sustained, with 86% of patients receiving ≥400 mg achieving a response [113, 115] - A reduction in peripheral blood mutCALR VAF was observed in 89% (34/38) of evaluable patients, correlating with hematologic responses [119, 120, 135] - Biomarker analysis supports a reduction in mutCALR stem/progenitor cells and megakaryocytes in patients achieving a hematologic response [121, 127, 135] INCA033989 Mechanism and Preclinical Data - INCA033989 is a high-affinity mutant CALR selective monoclonal antibody that selectively inhibits constitutive JAK/STAT signaling induced by mutCALR [94] - INCA033989 directly inhibits mutCALR+ CD34+ HSPCs and megakaryocytes, without affecting non-mutated, healthy cells [94] - In a mutCALR conditional knock-in mouse model of established MPN, INCA033989 treatment led to platelet normalization, reversal of anemia, and elimination of megakaryocyte hyperplasia in the bone marrow [90, 94] Essential Thrombocythemia (ET) and Unmet Needs - CALR mutations account for 25% of Essential Thrombocythemia cases [19] - Current ET treatments aim to reduce disease-associated risks but do not impact the natural history [26] - There is an unmet need for disease-modifying therapies in ET [25, 43] Future Development Plans - A registrational trial in ET is planned to be initiated by early 2026 [137]