Hoth Therapeutics Announces Its Precision Antisense Oligonucleotide HT-KIT Receives FDA Orphan Drug Designation And New Preclinical Data Show HT-KIT Achieves Over 80% Suppression Of Kit Expression And Significant Tumor-Volume Reduction By Day 8 In Systemic Mastocytosis And GIST Models

Author: Benzinga Newsdesk | October 21, 2025 07:26am
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

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):

• 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.
  
  
  
   
• 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.
  
  
  
   
• Favorable tolerability in early studies: No dose-limiting toxicities observed in the reported preclinical work to date.
  
  
  
   
• 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.

• 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):

• Complete GLP toxicology and CMC packages; submit IND.
  
  
  
   
• 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).
  
  
  
   
• 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."

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