Hoth Therapeutics Reports FDA Orphan Drug Designation and Strong Preclinical Data for HT-KIT in Rare c-KIT-Driven Cancers

Rhea-AI Summary

Hoth Therapeutics (NASDAQ: HOTH) announced FDA Orphan Drug Designation for HT-KIT and presented preclinical results showing >80% KIT mRNA/protein suppression and statistically significant tumor-volume reduction by Day 8 in systemic mastocytosis and GIST models. GLP-validated bioanalytical methods are complete to support IND-enabling studies, and Japan Patent No. 7677628 protects the platform through 2039. Reported tolerability showed no dose-limiting toxicities in the described preclinical work. Near-term plans include completing GLP toxicology and CMC packages, submitting an IND, and initiating a Phase 1/2 dose-escalation/expansion study with translational biomarkers and early efficacy readouts.

Positive

• Orphan Drug Designation granted by FDA (U.S.)
• >80% KIT mRNA/protein suppression in preclinical models
• Statistically significant tumor-volume reduction by Day 8
• GLP-validated bioanalytical methods completed for IND support
• Japan Patent No. 7677628 protecting platform through 2039

Negative

• Program remains preclinical; no human clinical data yet
• IND submission still pending pending completion of GLP toxicology and CMC
• Clinical efficacy and safety in humans are unproven despite preclinical signals

>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):

• 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).

NEW YORK, Oct. 21, 2025 /PRNewswire/ -- 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."

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/.

Forward-Looking Statement

This press release includes forward-looking statements based upon Hoth's current expectations, which may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws, and are subject to substantial risks, uncertainties, and assumptions. These statements concern Hoth's business strategies; the timing of regulatory submissions; the ability to obtain and maintain regulatory approval of existing product candidates and any other product candidates we may develop, and the labeling under any approval we may obtain; the timing and costs of clinical trials, and the timing and costs of other expenses; market acceptance of our products; the ultimate impact of the current coronavirus pandemic, or any other health epidemic, on our business, our clinical trials, our research programs, healthcare systems, or the global economy as a whole; our intellectual property; our reliance on third-party organizations; our competitive position; our industry environment; our anticipated financial and operating results, including anticipated sources of revenues; our assumptions regarding the size of the available market, benefits of our products, product pricing, and timing of product launches; management's expectation with respect to future acquisitions; statements regarding our goals, intentions, plans, and expectations, including the introduction of new products and markets; and our cash needs and financing plans. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. You should not place reliance on these forward-looking statements, which include words such as "could," "believe," "anticipate," "intend," "estimate," "expect," "may," "continue," "predict," "potential," "project" or similar terms, variations of such terms, or the negative of those terms. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee such outcomes. Hoth may not realize its expectations, and its beliefs may not prove correct. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described in the section titled "Risk Factors" in Hoth's most recent Annual Report on Form 10-K and Hoth's other filings made with the U. S. Securities and Exchange Commission. All such statements speak only as of the date made. Consequently, forward-looking statements should be regarded solely as Hoth's current plans, estimates, and beliefs. Investors should not place undue reliance on forward-looking statements. Hoth cannot guarantee future results, events, levels of activity, performance, or achievements. Hoth does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events, or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law.

Investor Contact:
LR Advisors LLC 
Email: investorrelations@hoththerapeutics.com
www.hoththerapeutics.com
Phone: (678) 570-6791

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SOURCE Hoth Therapeutics, Inc.

FAQ

What did Hoth (HOTH) announce on October 21, 2025 about HT-KIT?

Hoth announced FDA Orphan Drug Designation for HT-KIT and preclinical data showing >80% KIT suppression and tumor reduction by Day 8.

How strong were HT-KIT preclinical results reported by Hoth (HOTH)?

HT-KIT achieved >80% reduction of KIT mRNA/protein and showed statistically significant tumor-volume reduction in xenograft models by Day 8.

What regulatory and IP milestones does Hoth (HOTH) report for HT-KIT?

Hoth secured FDA Orphan Drug Designation in the U.S. and a Japan patent (No. 7677628) extending platform protection to 2039.

What are Hoth's near-term clinical plans for HT-KIT (HOTH)?

Hoth plans to complete GLP toxicology and CMC packages, submit an IND, and initiate a Phase 1/2 dose-escalation/expansion study in KIT-driven tumors.

Does HT-KIT have human safety or efficacy data yet for Hoth (HOTH)?

No; the announcement describes only preclinical tolerability with no dose-limiting toxicities observed to date and no human clinical data.