Cogent Biosciences has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for bezuclastinib in patients with nonadvanced systemic mastocytosis (SM), the company shared in a recent press release.
The submission comes following positive results from the SUMMIT clinical trial, which met all of its primary and secondary endpoints. The study found that bezuclastinib significantly reduced serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. levels and 11 different patient-reported symptoms compared with a placebo. These benefits extended through 48 weeks, with favorable safety and tolerability profiles.
What is the difference between advanced and nonadvanced SMNonadvanced SM In these subtypes of SM, mast cells accumulate in the body but do not usually cause severe organ damage. Nonadvanced SM includes the subtypes indolent SM and smoldering SM.?
Nonadvanced SM comprises the indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases. and smoldering SMSmoldering SM A subtype of nonadvanced SM, with a higher mast cell burden than the indolent subtype. Smoldering SM has a higher likelihood of progressing to an advanced form. subtypes. Advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. includes aggressive SMAggressive SM A subtype of advanced SM marked by a high mast cell burden that leads to organ damage. Aggressive SM accounts for less than 10% of SM cases., SM with an associated hematologic neoplasm and mast cell leukemiaMast cell leukemia The most severe subtype of SM, caused by the rapid buildup of immature mast cells in the bone marrow and blood. Mast cell leukemia accounts for less than 5% of SM cases and has a poor prognosis..
“Building on the exceptional results from the SUMMIT trial, this filing moves us closer to delivering an important disease-modifying therapy to patients with [non-advanced SM],” said Andrew Robbins, president and chief executive officer at Cogent Biosciences. If approved, Cogent will be permitted to sell and market the drug in the U.S.
Read more about SM therapies
In October 2025, bezuclastinib received Breakthrough Therapy Designation from the FDA for patients with nonadvanced SM who previously received avapritinib and patients with smoldering SM. The designation helps accelerate the development and review processes for therapies aimed to treat serious or life-threatening diseases.
Cogent Biosciences also plans to submit New Drug Applications for bezuclastinib in gastrointestinal stromal tumor and advanced SM during the first half of 2026. The company reported promising clinical trial results for bezuclastinib in both of these diseases in late 2025.
A targeted tyrosine kinase inhibitorTyrosine kinase inhibitor Targeted therapies designed to block the KIT D816V mutation that drives most cases of SM. Includes avapritinib, midostaurin and imatinib., bezuclastinib is an oral pill that works by blocking mutations in the KIT gene, including the KIT D816V mutation. By doing so, the drug aims to prevent the accumulation of mast cells throughout the body and associated symptoms.
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