Hoth Therapeutics has announced compelling preclinical results for HT-KIT, an antisense oligonucleotide designed to silence mutant KIT mRNA in KIT-driven cancers. The precision therapy demonstrated rapid tumor kill and achieved over 80% knockdown of KIT expression in vitro, positioning it as a potential first-in-class treatment for gastrointestinal stromal tumors (GIST), systemic mastocytosis, and certain leukemias.
Rapid Anti-Tumor Activity and Strong KIT Suppression
HT-KIT triggered significant tumor cell death in preclinical models of GIST and systemic mastocytosis as early as 24 hours post-treatment, with statistically significant tumor shrinkage observed by day 8. The therapy achieved over 80% knockdown of KIT expression in vitro, targeting the oncogenic driver responsible for multiple aggressive cancers.
"These results combine a rare and powerful story — tumor kill within 24 hours, clean safety across all systems, and GLP-validated reproducibility beyond regulatory standards," said Robb Knie, CEO of Hoth Therapeutics. "We believe HT-KIT has the potential to transform outcomes in KIT-driven cancers, and these milestones accelerate our path toward IND submission and first-in-human trials."
Clean Safety Profile Across Multiple Organ Systems
Multi-dose in vivo studies confirmed no off-target toxicity across critical organs including liver, kidneys, spleen, bone marrow, and thymus. A preclinical safety study demonstrated proportional liver engagement with an increase from 1.11g to 1.32g at 3.0 mg/kg dosing, while showing zero gross pathology at any organ site.
GLP-Validated Bioanalytical Excellence
The bioanalytical study, conducted by Altasciences Company Inc. under OECD, FDA, and EMA GLP standards, demonstrated that HT-KIT meets or exceeds strict regulatory benchmarks. All calibration curve, quality control, and dilution integrity requirements passed with high reproducibility, while 90.5% of Incurred Sample Reanalysis (ISR) values fell within ±30%, well above the 66.7% regulatory minimum.
HT-KIT remained stable in serum for 37 days at -80°C, surpassing the validated 28-day stability period, with further studies ongoing. The study showed flawless compliance with no protocol or SOP deviations impacting study reliability.
Market Opportunity and Development Timeline
The global systemic mastocytosis market is valued at $269.9 million in 2024 and is expected to reach $489.0 million by 2035. Current therapies like AYVAKIT and QINLOCK face challenges including resistance and limited patient access. HT-KIT's upstream targeting of KIT mRNA offers a differentiated approach that potentially circumvents these limitations.
The antisense and RNAi therapeutics market is projected to grow at a 13.1% CAGR from $1.93 billion in 2025 to $3.18 billion by 2029. Hoth Therapeutics plans to submit an IND application in early 2026 and initiate Phase 1 trials shortly thereafter.
Mechanism and Competitive Positioning
HT-KIT is designed to silence mutant KIT mRNA at the genetic level, seeking to overcome resistance to tyrosine kinase inhibitors while minimizing systemic side effects. By targeting KIT expression upstream, the therapy addresses a key limitation in current KIT-driven cancer treatments where resistance mechanisms often develop.
The company expects to integrate the bioanalytical data into its formal GLP toxicology package as it prepares for IND submission. The preclinical data from 2023 to 2025 demonstrate the therapy's ability to achieve significant tumor downregulation in animal models with no observable off-target toxicity.
