HT-KIT Shows Activity in Rare KIT-Driven Cancers, Preclinical Data Finds

Preclinical data suggest HT-KIT may offer a safer, targeted option for rare KIT-driven cancers like GIST and leukemia by silencing the KIT gene.

Preclinical data has shown compelling findings for HT-KIT, a proprietary antisense oligonucleotide therapy designed to silence aberrant KIT gene expression, among patients with rare and aggressive KIT-driven cancers, according to a news release from Hoth Therapeutics, Inc.

The investigational agent has demonstrated potent tumor downregulation of oncogenic KIT mutations in preclinical models of gastrointestinal stromal tumors (GIST) and systemic mastocytosis — two rare and aggressive cancers. In vitro studies showed over 80% reduction in KIT expression using cancer cell lines with these mutations. Moreover, among animal models, significant inhibition of tumor growth was recorded in GIST following systemic administration of HT-KIT

HT-KIT achieved these effects without observable systemic toxicity, with no observable off-target toxicity noted in the liver, kidney or bone marrow, indicating a favorable preclinical safety profile.

"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," Robb Knie, CEO of Hoth Therapeutics, said in the news release. "The strength of our preclinical data positions HT-KIT as a powerful candidate for precision oncology. We are moving rapidly toward investigational new drug [application] submission and are eager to begin human trials.”

What is HT-KIT?

HT-KIT is a synthetic antisense oligonucleotide and was developed using proprietary gene-silencing technology which was licensed exclusively by Hoth Therapeutics. It is specifically designed to bind selectively to mutant KIT mRNA transcripts, blocking their translation and thereby inhibiting production of the KIT protein — a key driver of tumor growth in malignancies such as GIST, systemic mastocytosis and certain forms of acute leukemia.

GISTs, according to the Mayo Clinic website, begins in the digestive system and is a type of cancer that happens most often in the stomach and small intestine. Systemic mastocytosis, on the other hand, is caused by too many mast cells (a type of white blood cell) building up in your body and is a rare disorder. Finally, types of acute leukemia ranges, but are all forms of cancer of the blood.

By directly targeting KIT gene expression, HT-KIT offers a novel therapeutic approach with the potential to overcome resistance observed in patients previously treated with tyrosine kinase inhibitors (TKIs), as demonstrated in preclinical studies.

Preclinical Milestones and Next Steps

Current treatment strategies for KIT-driven cancers — such as GIST, systemic mastocytosis and certain leukemias — primarily involve TKIs. Although initially effective, these small-molecule therapies can often lead to drug resistance or systemic side effects. HT-KIT is therefore aiming to fill this unmet need within the treatment space, and addressing these needs by offering a highly targeted alternative.

HT-KIT attacks the disease at the mRNA level, upstream of protein expression. This upstream intervention may reduce the likelihood of resistance development and limit systemic side effects associated with traditional TKIs.

Hoth Therapeutics is advancing HT-KIT toward clinical evaluation, with plans to submit an investigational new drug application to the United States Food and Drug Administration (FDA) in early 2026. An investigational new drug application, according to the National Institute of Health website, is an authorization request from the FDA for the administration of an investigational drug or biological product to patients. Moreover, according to the website, the investigation drug must be authorized prior to administration of any new drug or biological product that is not yet approved through a new drug application or biologics/product license application.

A phase 1 first-in-human clinical trial is anticipated to follow shortly after regulatory clearance.

To support this transition, the company is actively collaborating with regulatory consultants and contract research organizations to accelerate clinical development.

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