Incyte presented updated Phase 1 data for its first‑in‑class mutant‑calreticulin (mutCALR) antibody, INCA033989, at the American Society of Hematology (ASH) Annual Meeting in Orlando on December 8, 2025. The presentation covered dose‑escalation cohorts of 55 patients with essential thrombocythemia (ET) and 36 patients with myelofibrosis (MF). In the ET cohort, 90 % of patients achieved a hematologic response and 83.3 % achieved a complete hematologic response, while in the MF cohort 41.7 % of patients achieved a ≥25 % spleen volume reduction and 33.3 % achieved a ≥35 % reduction; 56 % of anemic MF patients experienced an anemia response.
The high response rates and the observed reduction in peripheral blood mutCALR variant allele frequency (VAF) suggest that INCA033989 may exert disease‑modifying effects beyond symptom control. In ET patients, 96.2 % showed a VAF reduction from baseline, with roughly half achieving at least a 25 % decrease, indicating a durable molecular response. In MF patients, the VAF decline was also significant, reinforcing the antibody’s potential to alter the underlying clonal driver of the disease.
Safety data were encouraging, with no dose‑limiting toxicities reported and only one patient discontinuing due to a treatment‑emergent adverse event. This safety profile aligns with earlier interim analyses and supports the feasibility of advancing to a larger Phase 3 program. The data also reinforce the FDA’s Breakthrough Therapy designation granted for INCA033989 in ET patients with type 1 CALR mutations, a regulatory milestone that can accelerate development and approval pathways.
Strategically, the results position INCA033989 as a disease‑modifying therapy that diversifies Incyte’s portfolio beyond its flagship JAK1/JAK2 inhibitor, Jakafi. The company plans to launch a Phase 3 program in mid‑2026 for both ET and MF indications, leveraging the strong early clinical signals and the Breakthrough designation to secure regulatory and payer momentum.
Management emphasized the significance of the findings, noting that “the compelling efficacy and safety data presented today at ASH 2025 provide additional evidence of INCA033989’s potential to deliver disease modification for high‑risk ET patients harboring a CALR mutation.” The company’s leadership views the data as a critical step toward expanding treatment options for patients with mutCALR‑positive myeloproliferative neoplasms.
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