Incyte Corporation ( INCY ) on Sunday revealed the first clinical data from two studies evaluating the safety, tolerability, and efficacy of INCA033989 for mutant calreticulin (mutCALR)-expressing myeloproliferative neoplasms (MPNs).

MPNs are a group of rare blood cancers where the bone marrow produces too many blood cells (red blood cells, white blood cells, or platelets).

These data, featured at the European Hematology Association 2025 (EHA2025), focus on the dose escalation portion of the studies in patients with high risk essential thrombocythemia (ET) who are resistant/intolerant to prior cytoreductive therapy.

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The studies evaluated the safety and efficacy of INCA033989 in patients with ET as measured by hematologic response and reduction in mutCALR variant allele frequency (VAF).

As of April 4, 2025, results showed rapid and durable normalization of platelet counts across all dose levels, with a trend toward improved responses in higher doses (>400 mg) in patients with ET treated with INCA033989.

Eighty-six percent of patients at doses 400 mg and above achieved a complete or partial hematologic response, with the majority (82%) achieving a complete response.

Eighty-nine percent of evaluable patients (34/38) showed a reduction in mutCALR VAF from baseline. A partial molecular response (>50% VAF reduction) was observed in 21% of evaluable patients (8/38) after only three cycles of treatment.

An exploratory study using single-cell DNA (scDNA) sequencing showed that INCA033989 directly targets and reduces cells carrying mutCALR. This reduction was seen in early blood-forming (CD34-positive) cells and cells in the myeloid-erythroid (ME) lineage.

At the same time, there was an increase in healthy (wild-type CALR) cells, suggesting that the treatment supports the return of normal blood production.

Bone marrow biopsies further confirmed these effects, showing fewer megakaryocytes with mutCALR protein and a notable increase in megakaryocytes without mutCALR protein.

The results (N=49) showed that INCA033989 was well tolerated across all dose cohorts (24 to 2,500 mg), with no dose-limiting toxicities observed.

Additional data from the INCA033989 study in patients with myelofibrosis will be submitted for presentation at a future medical meeting. Discussions with regulatory authorities are planned with the goal to initiate a Phase 3 study by early 2026.

William Blair views the INCA33989 update as promising, with strong initial efficacy reported. However, some questions remain around dosing differences between type 1 and type 2 mutCALR patients and the best setting for the therapy in ET patients (post-hydroxyurea, in combination, or head-to-head).

Analyst Matt Phipps noted that investors have debated the read-through of the ET data to the potential of INCA33989 in MF, where results as a monotherapy and in combination with Jakafi are expected later this year. The VAF reductions are encouraging and likely to have read-through to additional indications, he mentioned in a report.

Price Action: INCY stock is trading higher by 6.82% to $72.37 premarket at last check Monday.

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