Incyte Corporation, based in Wilmington, Delaware, announced promising early-stage clinical results for its experimental precision antibody, INCA033989, which has demonstrated a significant reduction in disease markers for patients suffering from essential thrombocythemia. This rare blood cancer presents limited treatment options, making these findings particularly encouraging. Updated data from two Phase 1 studies revealed that nearly 90 percent of patients receiving higher doses of INCA033989 achieved a hematologic response, with over 83 percent reaching a complete response characterized by normalized platelet and white blood cell counts. The results were shared during oral presentations at the American Society of Hematology’s 2025 annual meeting.
INCA033989 is a first-in-class monoclonal antibody designed to specifically target the mutant calreticulin (CALR) gene mutation, which is present in approximately one-quarter to one-third of essential thrombocythemia cases. Patients with this mutation often experience aggressive disease progression and derive limited benefit from standard therapies that generally suppress blood cell production instead of addressing the genetic roots of the disease.
The study not only highlighted improvements in blood counts but also indicated rapid and durable molecular responses. Almost all patients with follow-up measurements exhibited reductions in mutant CALR variant allele frequency, a critical marker of disease burden. Notably, around half of the participants achieved reductions of at least 25 percent, while nearly one-third experienced decreases of 50 percent or more. Responses appeared to be deeper and more consistent at higher doses.
Exploratory analyses suggested that INCA033989 could directly affect disease biology. Researchers documented reductions in mutant stem and progenitor cells, along with enhancements in abnormal bone marrow cell growth. These findings hint at the potential for disease-modifying activity rather than mere symptom management.
Safety data from the trials were also encouraging. No dose-limiting toxicities were reported, and the maximum tolerated dose was not reached. Most adverse events were classified as mild to moderate, with fatigue, headache, upper respiratory infections, and anemia being the most prevalent. Only one participant discontinued treatment due to side effects.
The U.S. Food and Drug Administration has granted Breakthrough Therapy designation to INCA033989 for patients with Type 1 CALR-mutated essential thrombocythemia who are resistant or intolerant to previous cytoreductive therapies. This designation may expedite the drug’s development and review process. Incyte plans to move forward with a registrational program that will encompass both Type 1 and non-Type 1 CALR mutations, potentially paving the way for mutation-specific treatments in myeloproliferative neoplasms.
For investors, these results bolster Incyte’s pipeline narrative by showcasing a novel, targeted approach with early indicators of durable efficacy and manageable risk. This combination is increasingly sought after in the realms of oncology and rare disease drug development. As the landscape of treatment options continues to evolve, Incyte’s advancements offer hope to patients facing this challenging condition.
