>80% KIT knock-down and significant tumor-volume reduction in systemic mastocytosis and GIST models; GLP-validated bio analytics complete; Japan Patent protects through 2039 as IND work advances.
Planned Next Steps (Near-Term):
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Complete GLP toxicology and CMC packages; submit IND.
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Initiate Phase 1/2 dose-escalation/expansion study in advanced systemic mastocytosis and other KIT-driven tumors with translational biomarkers of target engagement (KIT knock-down, tryptase/MRK signaling) and early efficacy readouts (ORR, DCR, PFS signals).
NEW YORK, Oct. 21, 2025 — Hoth Therapeutics, Inc. (NASDAQ: HOTH) today highlighted FDA Orphan Drug Designation for HT-KIT and new preclinical data demonstrating >80% suppression of KIT expression and significant tumor-volume reduction by Day 8 in systemic mastocytosis and GIST models. HT-KIT, a precision antisense oligonucleotide (ASO) targeting KIT mRNA, also completed GLP-validated bioanalytical methods supporting IND-enabling studies; Japan Patent No. 7677628 extends platform protection to 2039.
Preclinical Summary (2025):
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Potent gene-level target suppression: HT-KIT achieved >80% reduction of KIT mRNA/protein across in-vitro systems and in vivo models of systemic mastocytosis and GIST.
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Rapid anti-tumor activity: In xenograft models, statistically significant tumor-volume reduction by Day 8 was observed, accompanied by apoptotic signaling consistent with KIT pathway knock-down.
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Favorable tolerability in early studies: No dose-limiting toxicities observed in the reported preclinical work to date.
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Bioanalytical readiness: GLP-validated bioanalytical methods completed to support pharmacokinetic, biodistribution, and exposure-response analyses for IND.
Mechanistic Rationale:
Unlike small-molecule TKIs that inhibit kinase activity, HT-KIT operates upstream at the transcript level, silencing both mutant and wild-type KIT. This mechanism is designed to bypass resistance pathways (secondary mutations, compensatory signaling) and reduce off-target liabilities, potentially improving durability and tolerability in KIT-driven diseases such as aggressive systemic mastocytosis (ASM), SM-AHN, mast cell leukemia (MCL), GIST, and select leukemias.
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Orphan Drug Designation (U.S.) supports development in a rare disease with incentives including potential exclusivity upon approval, tax credits, and fee waivers.
Planned Next Steps (Near-Term):
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Complete GLP toxicology and CMC packages; submit IND.
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Initiate Phase 1/2 dose-escalation/expansion study in advanced systemic mastocytosis and other KIT-driven tumors with translational biomarkers of target engagement (KIT knock-down, tryptase/MRK signaling) and early efficacy readouts (ORR, DCR, PFS signals).
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Continue regional IP expansion and evaluate strategic partnerships for development and commercialization.
“HT-KIT’s transcript-level suppression of KIT has now produced consistent anti-tumor performance across models, with a clean preclinical tolerability profile and GLP-ready analytics,” said Robb Knie, Chief Executive Officer. “With Orphan Drug Designation secured and an IND-enabling package progressing, we are preparing for a disciplined entry into first-in-human evaluation.”
About HT-KIT:
HT-KIT is a precision ASO designed to silence KIT at the mRNA level, aiming to overcome resistance and off-target toxicity seen with kinase inhibitors in systemic mastocytosis, GIST, and select leukemias.
About Hoth Therapeutics, Inc.
Hoth Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative, impactful, and ground-breaking treatments with a goal to improve patient quality of life. We are a catalyst in early-stage pharmaceutical research and development, elevating drugs from the bench to pre-clinical and clinical testing. Utilizing a patient-centric approach, we collaborate and partner with a team of scientists, clinicians, and key opinion leaders to seek out and investigate therapeutics that hold immense potential to create breakthroughs and diversify treatment options. To learn more, please visit https://ir.hoththerapeutics.com/.