Patients facing systemic mastocytosis (SM) and other KIT-driven cancers may soon gain a new treatment option, as Hoth Therapeutics reported in a recent press release that its experimental antisense drug HT-KIT sharply reduced tumor growth and mutant KIT protein production in preclinical studies.
These data suggest the therapy could bypass resistance and side effects linked to current tyrosine kinase inhibitors, potentially giving people with advanced SM longer control of their disease and a better quality of life.
“We believe HT-KIT represents a first-in-class approach to treating KIT-mutated cancers at the genetic level, offering hope for patients who have exhausted traditional therapies,” said Robb Knie, CEO of Hoth Therapeutics. “The strength of our preclinical data positions HT-KIT as a powerful candidate for precision oncology.”
Researchers showed that HT-KIT lowered KIT expression by more than 80% in cell cultures bearing activating KIT mutations, the genetic engine behind SM, gastrointestinal stromal tumors and some leukemias. When the synthetic oligonucleotide was injected into animal models of gastrointestinal stromal tumors and mast-cell tumors, it produced “significant” tumor inhibition, according to the company. Just as important for patients, investigators detected no off-target damage in liver, kidney or bone marrow tissue — organs often stressed by existing therapies.
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SM arises when mutated KIT signals mast cells to multiply uncontrollably, leading to bone pain, anaphylaxis, organ dysfunction and, in aggressive forms, shortened survival. Standard tyrosine kinase inhibitors can slow the disorder, but many patients develop drug resistance or experience fatigue, edema and other systemic toxicities.
HT-KIT works farther upstream by binding mutant KIT messenger RNA and preventing production of the faulty protein, a strategy that may limit resistance pathways and spare healthy cells.
Hoth’s leadership stated that the company plans to submit an Investigational New Drug application in early 2026, clearing the way for Phase 1 trials soon afterward. The company is already consulting regulatory experts and contract research organizations to keep that timeline on track.
For people living with SM, an approved antisense therapy could translate into fewer infusions, milder side effects and extended periods without disease progression. While those benefits remain to be proven in humans, the preclinical results give patients and caregivers new hope that the next wave of targeted treatments is on the horizon.
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