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]

Core Insights - Incyte (INCY) shares increased by 5.1% following a global partnership with QIAGEN N.V. to develop a diagnostic panel for myeloproliferative neoplasms (MPNs), which account for approximately 40% of hematological malignancies [1][4] Partnership Details - The collaboration focuses on INCA033989, Incyte's investigational monoclonal antibody targeting mutant calreticulin (mutCALR), currently in early-stage development for myelofibrosis (MF) and essential thrombocythemia (ET) [2] - QIAGEN will create a multimodal panel using next-generation sequencing (NGS) technology to identify key gene alterations in MPNs, initially concentrating on mutCALR, the second most common driver of MPNs [2][5] - The panel will be validated on the Illumina NextSeq 550Dx platform for whole blood samples, with QIAGEN assisting in regulatory submissions and market access in the U.S., EU, and certain Asia-Pacific regions [3][6] Benefits of the Collaboration - The partnership enhances Incyte's precision medicine efforts by facilitating the identification of genetic mutations like CALR, which is crucial for treatment decisions in rare blood cancers [5] - It allows for widespread CALR testing, improving patient selection for Incyte's therapies and increasing the likelihood of better treatment outcomes [6] - The collaboration strengthens Incyte's position in personalized medicine and accelerates regulatory and market access for its mutCALR-targeted treatment [6][7] Clinical Data and Future Prospects - Incyte reported positive data from two Phase I studies of INCA033989, showing rapid and lasting platelet normalization in ET patients, with 86% achieving a complete/partial hematologic response at doses above 400 mg [11][12] - The candidate demonstrated selective targeting of mutCALR cells while sparing healthy cells, indicating potential for disease modification [12] - Incyte plans to advance INCA033989 into late-stage development for MPN indications in 2026 after discussions with regulatory authorities [13]